Compound based on oxo-isoindolinyl substituted tetrahydropyrimidinedione and application thereof

Abstract

The present disclosure relates to compounds of Formula (I) and Formula (II) or salts, enantiomers, stereoisomers, solvates, isotope enriched analogs, prodrugs or polymorphs thereof, and uses thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds of formula (I) or salts, enantiomers, stereoisomers, solvates, isotope enriched analogs, prodrugs or polymorphs thereof as active ingredients and uses thereof. # imgabs0 #

Description

Compounds based on oxoisoindolinyl-substituted tetrahydropyrimidinedione and their applications Technical Field

[0001] The present disclosure relates to compounds of formula (I), cereblon (CRBN) E3 ubiquitin ligase ligand compounds of formula (II), and their uses. The CRBN E3 ubiquitin ligase ligand compounds of formula (II) can bind to CRBN E3 ligase and are used to prepare compounds of formula (I). Compounds of formula (I) of the present disclosure designed based on compounds of formula (II) and various target protein ligands can exhibit a wide range of pharmacological activities by degrading / inhibiting various pathogenic protein classes or families. Background Art

[0002] Bifunctional protein degradation targeted drugs consist of three components: a ligand warhead that binds to a specific target protein at one end and a small molecule ligand for the E3 ubiquitin ligase at the other. These two components are connected by a linker unit of varying lengths and types. Bifunctional protein degradation small molecules leverage the binding of the ligands at both ends to simultaneously bind to both the target protein and the E3 ubiquitin ligase, thereby recruiting the E3 ubiquitin ligase to the vicinity of the target protein and allowing it to ubiquitinate the target protein. The polyubiquitinated target protein is then recognized and degraded by the proteasome in the body. Compared to traditional small molecule inhibitors, protein degradation targeted drugs significantly differ in that they mobilize the entire cell as a drug response unit. This mode of action requires only a brief binding of the small molecule to the target protein, marking it for removal. Therefore, low drug concentrations can be sufficient, significantly reducing the risk of off-target effects and potentially eliminating tumor progression caused by aberrant driver gene expression and drug resistance due to acquired driver gene mutations.

[0003] The E3 ubiquitin ligases involved in the design of targeted protein degradation drugs include more than 600 different proteins, and only a few have been successfully applied to the research of degraders. Among them, Cereblon (CRBN) E3 ubiquitin ligase is one of the most widely used E3 ubiquitin ligases. Currently known CRBN-type E3 ubiquitin ligase ligands (i.e., CRBN ligands) include thalidomide and its analogs lenalidomide and pomalidomide, all of which have a phthalimide backbone. Several bifunctional protein degraders currently in clinical trials, such as ARV-110 targeting AR, ARV-471 targeting ER, NX-2127 targeting BTK, and FHD-609 targeting BRD9, are all designed using phthalimide-type CRBN ligands containing a phthalimide backbone.

[0004] After binding to CRBN, doxorubicin-like CRBN E3 ubiquitin ligase ligands themselves can act as molecular glues, inducing CRBN to recognize new substrate proteins for ubiquitination and degradation, thereby exerting pharmacological effects including anti-tumor and immunomodulatory effects. Molecular glue degraders offer potential advantages, such as targeting undruggable targets, by directly targeting and degrading target proteins. Furthermore, due to their typically small molecular weight and good drugability, the development of this class of drugs has attracted significant attention. In addition to the marketed doxorubicin-like drugs, a series of molecular glue compounds based on CRBN E3 ubiquitin ligases have been developed, including CC-122, CC-220, CC-90009, CC-99282, and CC-92480 from Bristol-Myers Squibb (BMS), DKY709 from Novartis, and CFT7455 from C4 Therapeutics, all currently undergoing clinical trials. The scope of degradation substrates of these molecular glues is also expanding, from the initially discovered transcription factors IKZF1 / 3 to casein kinase 1α (CK1α), zinc finger protein 91 (ZFP91), and translation factor GSPT1. The degradation of these substrate proteins enables molecular glues to exert pharmacological activities such as immunomodulation, anti-inflammatory, and anti-tumor in different indications.

[0005] In summary, CRBN ligands can be used as part of a bifunctional protein degrader to effectively degrade specific pathogenic proteins, while also acting as molecular glue degraders to induce degradation of diverse substrate proteins. Therefore, the diversification of scaffold design, the development of more novel druggable CRBN ligands, and their application in the development of bifunctional protein degraders have become research hotspots in this field.

[0006] Despite this, there are still some challenges for this phthalimide-based CRBN E3 ubiquitin ligase ligand, especially poor solubility and weak CRBN binding. In addition, this phthalimide-based CRBN ligand compound usually contains a piperidine-2,6-dione-substituted isoindolinone structure (i.e. Wherein A represents CO or CH2), the structure contains a chiral center, which exists in R and S configurations. In order to obtain a single chiral compound, it is often necessary to use expensive asymmetric synthesis, enzyme catalysis or chiral resolution methods.

[0007] Therefore, there is an urgent need to develop a series of novel CRBN ligands with high CRBN binding affinity and drugability to design and synthesize corresponding bifunctional protein degraders for different targets to treat and / or prevent diseases or conditions mediated by or related to the target protein.

[0008] SUMMARY OF THE INVENTION

[0009] In view of the above, the purpose of the present disclosure is to provide novel small molecule ligands for E3 ubiquitin ligases, protein degradation molecules designed based on novel small molecule ligands for E3 ubiquitin ligases and various target protein ligands, their uses, and methods of use. The E3 ligands provided herein have stronger CRBN binding affinity and drugability, and their activity as molecular glues to induce substrate protein degradation is stronger and / or more selective; based on the E3 ligands provided herein, bifunctional degraders designed for different targets have stronger degradation / inhibition effects on various pathogenic protein classes or families, good pharmacokinetic properties, and thus produce a wide range of pharmacological activities.

[0010] To achieve the above-mentioned and other related objectives, the present disclosure provides, in one aspect, small molecule ligands for CRBN E3 ubiquitin ligases that can act as molecular glues to bind to CRBN E3 ligases. The isoindolinyl-substituted tetrahydropyrimidinedione backbone designed in the present invention addresses the chirality issues of existing piperidine-2,6-dione-substituted isoindolinone structures, exhibits CRBN binding, and exhibits excellent pharmacokinetic properties or anti-tumor activity. Furthermore, it can be applied to bifunctional protein-degrading small molecule drugs.

[0011] In some embodiments, the small molecule ligand of the E3 ubiquitin ligase of the present disclosure can be a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph thereof:

[0012] in

[0013] A represents CO, CH2 or CD2;

[0014] R a1 、R a2 、R a3 and R a4 The same or different and each independently represents hydrogen, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0015] (R a5 ) m represents that the isoindoline ring connected thereto is optionally replaced by m R a5 Replace, each R a5 The same or different and each independently represents halogen, hydroxyl, mercapto, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1- 6 alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 Alkynyl;

[0016] m represents an integer 0, 1, 2, 3 or 4;

[0017] R w represents O, S, S(O), S(O)2, alkenylene, alkynylene or N(R a6 ), where R a6 Indicates H or C 1-3 Alkyl, or R w represents a key; or

[0018] R w express:

[0019] Among them, each ring A 1 are the same or different and each independently represent a nitrogen-containing heterocyclic group, an arylene group or a heteroarylene group, y1 represents an integer of 1 or 2, (R y1 ) a1 Represents each ring A 1 Each independently optionally represented by a1 R y1 Group substitution, each R y1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a1 represents an integer of 0-20;

[0020] Each ring A 2 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group or a heteroarylene group, y2 represents an integer of 0 or 1, (R y2 ) a2 Represents each ring A 2 independently optionally by a2 R y2 Group substitution, each R y2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2- 6 alkenyl, and a2 represents an integer of 0-20; and

[0021] R w1 represents a bond, or represents an optionally substituted straight or branched C 1-20 Alkylene, wherein the linear or branched C 1-20 Any one or more methylene groups of the main carbon chain skeleton of the alkylene group may be optionally replaced by one or more groups selected from the following: a 、R b and any combination thereof, each group R a Each independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each R a7 Each independently represents H or C 1-3 Alkyl, and when the linear or branched C 1-20 One or more adjacent methylene groups of the main carbon chain skeleton of the alkylene group are replaced by one or more groups R a When substituted, each group R a Not directly connected to each other; each group R b are each independently selected from optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene, alkynylene, alkenylene, and any combination thereof; and

[0022] R w3 represents hydrogen, deuterium, a leaving group, a hydroxyl group, a halogen, COOH, NH2, N3, CHO, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group or a p-toluenesulfonyloxy group.

[0023] On the other hand, the protein degradation molecules designed based on the small molecule ligands of E3 ubiquitin ligase and various target protein ligands disclosed herein can be compounds of formula (I) or salts, stereoisomers (including enantiomers), solvates, isotopically enriched analogs, prodrugs or polymorphs thereof:

[0024] PBM-LIN-ULM

[0025] Formula (I)

[0026] Wherein PBM represents a targeting moiety capable of binding to a protein, and PBM is covalently linked to ULM via the group LIN;

[0027] ULM represents a ligand moiety capable of binding to an E3 ubiquitin ligase and represents a structure of the following formula (ULM):

[0028] in

[0029] A represents CO, CH2 or CD2;

[0030] R a1 、R a2 、R a3 and R a4 The same or different and each independently represents hydrogen, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0031] (R a5 ) m represents that the isoindoline ring connected thereto is optionally replaced by m R a5 Replace, each R a5 The same or different and each independently represents halogen, hydroxyl, mercapto, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1- 6 alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 Alkynyl;

[0032] m represents an integer 0, 1, 2, 3 or 4;

[0033] R w represents O, S, S(O), S(O)2, alkenylene, alkynylene or N(R a6 ), where R a6 Indicates H or C 1-3 Alkyl, or R w represents a key; or

[0034] R w express:

[0035] Among them, each ring A 1 are the same or different and each independently represent a nitrogen-containing heterocyclic group, an arylene group or a heteroarylene group, y1 represents an integer of 1 or 2, (R y1 ) a1 Represents each ring A 1 Each independently optionally represented by a1 R y1 Group substitution, each R y1 Deuterium, C1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a1 represents an integer of 0-20;

[0036] Each ring A 2 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group or a heteroarylene group, y2 represents an integer of 0 or 1, (R y2 ) a2 Represents each ring A 2 independently optionally by a2 R y2 Group substitution, each R y2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2- 6 alkenyl, and a2 represents an integer of 0-20; and

[0037] LIN means:

[0038] where R w2 Connect PBM, R w1 Connect R w ;

[0039] R w2 represents a bond, C(O), C(O)NH, or NHC(O);

[0040] Each ring A 3 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, y3 represents an integer of 0, 1, 2 or 3, (R y3 ) a3 Represents each ring A 3 Independently optionally a3 R y3 Group substitution, each R y3 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a3 represents an integer of 0-10;

[0041] Each ring A4 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, y4 represents an integer of 0, 1, 2 or 3, (R y4 ) a4 Represents each ring A 4 Independently optionally by a4 R y4 Group substitution, each R y4 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a4 represents an integer of 0-10;

[0042] Each ring A 5 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, y5 represents an integer of 0, 1, 2 or 3, (R y5 ) a5 Represents each ring A 5 Independently optionally a5 R y5 Group substitution, each R y5 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a5 represents an integer of 0-10;

[0043] R w1 represents a bond, or represents an optionally substituted straight or branched C 1-20 Alkylene, wherein the linear or branched C 1-20 Any one or more methylene groups of the main carbon chain skeleton of the alkylene group may be optionally replaced by one or more groups selected from the following: a 、R b and any combination thereof, each group R a Each independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each Ra7 Each independently represents H or C 1-3 Alkyl, and when the linear or branched C 1-20 One or more adjacent methylene groups of the main carbon chain skeleton of the alkylene group are replaced by one or more groups R a When substituted, each group R a Not directly connected to each other; each group R b Each is independently selected from optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene, alkynylene, alkenylene, and any combination thereof.

[0044] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph thereof, and at least one pharmaceutically acceptable carrier.

[0045] In another aspect, the present disclosure also provides a pharmaceutical kit or a test kit comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same.

[0046] In another aspect, the present disclosure provides a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use as a medicament.

[0047] On the other hand, the compound of formula (I) provided by the present disclosure or its salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph or pharmaceutical composition comprising the same as an active ingredient can be used to treat and / or prevent a disease or condition selected from the following: tumor or cancer, autoinflammatory disease, inflammatory disease, autoimmune disease, neurological disease, respiratory disease, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin disease, functional uterine bleeding, anemia, pediatric aplastic anemia, endometriosis, polycystic ovary syndrome and thyroid disease.

[0048] On the other hand, the present disclosure also provides the use of the compound of formula (I) or its pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph, or the pharmaceutical composition of the present disclosure, wherein the use is for preparing a medicament for treating or preventing a disease or condition selected from the following: tumor or cancer, autoinflammatory disease, inflammatory disease, autoimmune disease, neurological disease, respiratory disease, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin disease, functional uterine bleeding, anemia, pediatric aplastic anemia, endometriosis, polycystic ovary syndrome and thyroid disease.

[0049] In another aspect, the present disclosure also provides a method for treating or preventing a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, or a pharmaceutical composition comprising the same, wherein the disease or condition comprises tumors or cancer, autoinflammatory diseases, inflammatory diseases, autoimmune diseases, neurological diseases, respiratory diseases, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin diseases, functional uterine bleeding, anemia, pediatric aplastic anemia, endometriosis, polycystic ovary syndrome and thyroid disease.

[0050] In another aspect, the present disclosure provides the use of a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph thereof for preparing a compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof of the present disclosure.

[0051] In another aspect, the present disclosure also provides a method for preparing a compound of formula (I) of the present disclosure or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof using a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph thereof.

[0052] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph thereof, and at least one pharmaceutically acceptable carrier.

[0053] In another aspect, the present disclosure also provides a pharmaceutical kit or a test kit comprising a compound of formula (II) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising the same.

[0054] In another aspect, the present disclosure provides a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use as a medicament.

[0055] In another aspect, the compound of formula (II) provided herein, or its salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, prodrug or polymorph, or a pharmaceutical composition comprising the same as an active ingredient, can be used to treat and / or prevent diseases or conditions associated with cereblon protein.

[0056] In another aspect, the present disclosure further provides the use of the compound of formula (II) or its pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph, or the pharmaceutical composition of the present disclosure, for preparing a medicament for treating or preventing a disease or condition associated with the cereblon protein.

[0057] In another aspect, the present disclosure also provides a method for treating or preventing a disease or condition associated with cereblon protein in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, or a pharmaceutical composition comprising the same.

[0058] The diseases or conditions associated with cereblon protein include tumors or cancer, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure or diabetes. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] FIG1 shows the Western Blot experimental results of the compounds of the present invention on the degradation of target substrate proteins in cells.

[0060] Detailed Description of the Invention

[0061] The following detailed description is provided as an exemplary embodiment to help those skilled in the art understand and implement the present disclosure. However, it should be understood that such description is not intended to limit the scope of the present disclosure. Without departing from the spirit and scope of the present disclosure, the specific embodiments described in the present disclosure may be subjected to various modifications and changes, and these changes and improvements all fall within the scope of the present disclosure as claimed.

[0062] I. Compounds

[0063] Compound of formula (I)

[0064] The compounds of formula (I) disclosed herein, or their salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, prodrugs, or polymorphs, can bind to target proteins, recruiting them to E3 ubiquitin ligases for ubiquitination and degradation. The compounds of formula (I) disclosed herein can specifically target specific target protein classes or families, exhibiting a wide range of pharmacological activities by degrading / inhibiting a variety of target protein classes or families.

[0065] PBM-LIN-ULM

[0066] Formula (I)

[0067] wherein PBM, LIN and ULM are as defined above in the compound of formula (I).

[0068] In some embodiments, PBMs can be small molecule ligands that bind to specific target proteins, including but not limited to epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 / 6 (CDK4 / 6), anaplastic lymphoma kinase (ALK), activin receptor-like kinase 2 (ALK2), fibroblast growth factor receptors (FGFRs), proto-oncogene tyrosine-protein kinase receptor RET (RET), focal adhesion kinase (FAK), breakpoint cluster region (BCR)-Abelson leukemia virus (ABL) (BCR-ABL) tyrosine kinase, Bruton tyrosine kinase (BTK), and androgen receptor (AR). receptor (AR), estrogen receptor (ER), bromodomain and extra-terminal domain protein (BET), interleukin-1 receptor-associated kinase 4 (IRAK4), cyclin-dependent kinase 9 (CDK9), cyclin-dependent kinase 2 (CDK2), serine / threonine protein kinase (AKT), microtubule-associated protein tau, histone-lysine N-methyltransferase EZH2 (EZH2), neurotrophic receptor tyrosine kinase (NTK), leukocyte antigen 2 (LEC), leukocyte antigen 2 (LEC), leukocyte antigen 2 (LEC), thym ...The proteins involved include NTRK, Src homology 2 domain containing protein tyrosine phosphatase (SHP2), poly (ADP-ribose) polymerase (PARP), signal transducers and activators of transcription 3 (STAT3), FMS-like tyrosine kinase 3 (FLT3), BCL-2 (B cell lymphoma-2) family proteins, SOS Ras / Rac guanine nucleotide exchange factor 1 (SOS1) or GTPase Kras (KRAS), SWI / SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 / 4; SMARCA2 / 4) and ribosomal protein S6 kinase (RSK).

[0069] In some embodiments, the PBM comprises a structure selected from the following formulae:

[0070] in

[0071] (R 1a ) p1a Indicates that the benzene ring to which it is connected is surrounded by p1a R 1a Replace, each R 1a The same or different and each independently represents deuterium, halogen, hydroxyl, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, NO2, NH2 or cyano;

[0072] p1a represents an integer 0, 1, 2, 3, 4, or 5;

[0073] R1b represents substituted or unsubstituted C 3-15 cycloalkyl groups, such as cyclopentyl;

[0074] R in formula (PBM-2) 2a Indicates C 6-10 aryl or 5- to 20-membered heteroaryl, the C 6-10 Aryl and 5- to 20-membered heteroaryl are each independently optionally substituted by one or more (e.g., 1-10, 1-8, 2-6, 1-5, 1-4, 1-3 or 2-5) groups each independently selected from deuterium, halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or any combination thereof;

[0075] R 2b Indicates C 6-10 aryl or 5- to 20-membered heteroaryl (e.g., 5- to 20-membered heteroaryl comprising 1 or 2 5- to 7-membered rings and 1 to 4 heteroatoms selected from N, O, and S), wherein the C 6-10 The aryl group and the 5- to 20-membered heteroaryl group are each independently optionally substituted by one or more (e.g., 1-10, 1-8, 2-6, 1-5, 1-4, 1-3 or 2-5) R 2d Replace, and each R 2d The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0076] (R 2c ) p2a The isoindoline ring in formula (PBM-2) is optionally replaced by p2a R 2c Replace, each R 2c The same or different and each independently represents deuterium, halogen, hydroxyl, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, NO2, NH2, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or cyano;

[0077] p2a represents an integer 0, 1, 2, or 3;

[0078] R in formula (PBM-3) 3a Represents hydrogen, C 1-10 Alkyl (e.g. ), deuterated C 1-10 Alkyl or halogenated C 1-10 alkyl;

[0079] R 3b express or a 4- to 12-membered nitrogen-containing heterocyclic group, wherein the 4- to 12-membered nitrogen-containing heterocyclic group is optionally substituted by one or more (e.g., 1-10, 1-8, 2-6, 1-5, 1-4, 1-3 or 2-5) groups independently selected from deuterium, halogen, hydroxyl, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, NO2, NH2, cyano or any combination thereof;

[0080] Ring A in formula (PBM-4) represents C 6-10 aryl or 5- to 20-membered heteroaryl (e.g., 5- to 20-membered heteroaryl comprising 1 or 2 5- to 7-membered rings and 1-4 heteroatoms selected from N, O, and S), wherein the ring A is optionally substituted by one or more (e.g., 1-10, 1-8, 2-6, 1-5, 1-4, 1-3, or 2-5) R 4a Replace, and each R 4a The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 Alkynyl;

[0081] Ring B in formula (PBM-4) represents C 3-15 Cycloalkyl or 4- to 20-membered heterocyclyl (e.g., 4- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from N, O and S), wherein the ring B is optionally substituted by one or more (e.g., 1-10, 1-8, 2-6, 1-5, 1-4, 1-3 or 2-5) R 4b Replace, and each R 4b The same or different and each independently is deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0082] Ring C in formula (PBM-4) represents a 5- to 20-membered heteroaryl group (e.g., a 5- to 20-membered monocyclic or bicyclic heteroaryl group containing 1-4 heteroatoms selected from N, O and S), which is optionally substituted by one or more (e.g., 1-10, 1-8, 2-6, 1-5, 1-4, 1-3 or 2-5) R 4c Replace, and each R 4c The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0083] X1 in formula (PBM-5) represents N or CR 5f , where R 5f represents hydrogen, deuterium or amino, X2 represents N or CR 5g , where R 5g represents hydrogen or represents R c , and X3 represents CH or N;

[0084] R 5a and R 5b Each independently represents hydrogen or represents R c ;

[0085] (R 5c ) p5a Indicates that the benzene ring connected to it is p5a R 5c Replace, each R 5c The same or different and each independently represents -O-aryl, -O-heteroaryl, 4- to 20-membered heterocyclic group, -C 1-3 Alkylene-NHC(O)-heteroaryl, -C 1-3 Alkylene-C(O)NH-heteroaryl, C 1-6 Alkyl, deuterium, deuterated C 1-6 Alkyl, halogen, or halogenated C 1-6 The 4- to 20-membered heterocyclyl, aryl and heteroaryl groups are each independently optionally substituted by one or more (e.g., 1-10, 1-8, 2-6, 1-5, 1-4, 1-3 or 2-5) R 5h Replace, and each R 5h The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0086] p5a represents an integer 1, 2, 3, or 4;

[0087] R 5d Represents R c , hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy;

[0088] R 5e Represents hydrogen, halogen, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl or amino;

[0089] where R 5g 、R 5a 、R 5b and R 5d are not hydrogen at the same time, and R 5g 、R 5a 、R 5b and R 5d There is only one representation R c ,in

[0090] When R 5a Represents R c When X2 represents CH or N, and R 5b is hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy;

[0091] When X2 represents CR 5g , where R 5g Represents R c When R 5a and R 5b are hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy;

[0092] When R 5bRepresents R c When X2 represents N or CH, and R 5a is hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy; and

[0093] When R 5d Represents R c When X2 represents N or CH, and R 5a and R 5b All are hydrogen;

[0094] X4 in the formula (PBM-6) represents CR 6e or fragment The symbol # represents the connection point of N adjacent to X4, the symbol ## represents the connection point with X5, and each R 6e Each independently represents deuterium, hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-deuterated C 1-6 Alkyl or -C(O)NR 6f R 6g , where R 6f 、R 6g are the same or different and each independently represent hydrogen, C 1-6 Alkyl or deuterated C 1-6 alkyl;

[0095] X5 in formula (PBM-6) represents N or CR 6h , where R 6h Represents hydrogen, deuterium, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl;

[0096] X6 and X7 each independently represent CH or N;

[0097] R 6a represents a bond or an optionally substituted heteroarylene (e.g., a halogen- or deuterium-substituted heteroarylene);

[0098] R 6b Represents hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, or optionally substituted C 3-12 Cycloalkyl;

[0099] (R 6c ) p6a Indicates that the pyridine ring connected thereto is optionally replaced by p6a R 6c Replace, each R 6c The same or different and each independently represents deuterium, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 Alkyl, p6a represents an integer of 0, 1, 2 or 3;

[0100] (R 6d ) p6b represents a bicyclic nitrogen-containing heteroaromatic ring connected thereto which is optionally replaced by p6b R 6d Replace, each R 6d The same or different and each independently represents deuterium, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 Alkyl, p6b represents an integer of 0 or 1;

[0101] (R 7a ) p7a Indicates that the benzene ring connected thereto is optionally replaced by p7a R 7a Replace, each R 7a The same or different and each independently represents deuterium, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, or deuterated C 1-6 Alkyl, p7a represents an integer of 0, 1, 2 or 3;

[0102] (R 7b ) p7b Indicates that the benzene ring connected thereto may be optionally replaced by p7b R 7b Replace, each R 7b The same or different and each independently represents deuterium, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, or deuterated C 1-6 Alkyl, p7b represents an integer of 0, 1, 2, 3 or 4;

[0103] Each R 7cand R 7d The same or different and each independently is deuterium, C 1-6 Alkyl, halogen, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0104] X8, X9, X in formula (PBM-8) 10 、X 11 and X 12 are the same or different and each independently represent N or CH;

[0105] R 8a represents a bond or an optionally substituted methylene group (e.g., a halogen-substituted methylene group);

[0106] R 8b Represents -C(O)N(R 8f )R 8e 、-N(R 8f )C(O)R 8e 、-S(O)2N(R 8f )R 8e 、-N(R 8f )S(O)2R 8e 、-S(O)2R 8e or -P(O)(R 8e )2, where each R 8e The same or different and each independently represents C 1-6 Alkyl or deuterated C 1-6 Alkyl, R 8f Represents hydrogen or C 1-6 alkyl;

[0107] (R 8c ) p8a Indicates that it is connected to X9 and X 10 The six-membered ring is optionally replaced by p8a R 8c Replace, each R 8c The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0108] p8a represents an integer 0, 1, 2, 3, or 4;

[0109] R 8d Denotes deuterium, halogen, hydroxyl, amino, cyano, C 1-6Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0110] R in formula (PBM-9) 9a represents -NHC(O)- or -C(O)NH-;

[0111] R 9b Indicates -NH-, -N(C 1-6 alkyl)- or ethynylene;

[0112] Ring D in formula (PBM-9) represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S, (R 9c ) p9a Indicates that the ring D is optionally replaced by p9a R 9c Replace, and each R 9c The same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0113] p9a represents an integer 0, 1, 2, or 3;

[0114] Each (R 9d ) p9b Each independently represents that the benzene ring connected thereto is each independently optionally replaced by p9b R 9d Replace, each R 9d The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0115] Each p9b is the same or different and independently represents an integer of 0, 1, 2, 3 or 4;

[0116] R in formula (PBM-10) 10d represents O, S or CH2;

[0117] (R 10c ) p10a The expression (PBM-10) contains R 10dThe benzo-fused six-membered ring is optionally replaced by p10a R 10c Replace, each R 10c The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0118] p10a represents an integer 0, 1, 2, 3, or 4;

[0119] R 10a and R 10b There is only one representation R c , and the other represents hydrogen, halogen, hydroxy, cyano, amino, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0120] Ring E in formula (PBM-11) represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O and S;

[0121] R 11b represents an optionally substituted 5- to 15-membered heteroaryl, an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0122] R 11a Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0123] R in formula (PBM-12) 12a represents an optionally substituted 5- to 15-membered heterocyclic group, an optionally substituted 5- to 15-membered heteroaryl group, deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0124] R 12b represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1-4 heteroatoms selected from N, O and S, wherein the heteroaryl group is optionally substituted by one or more (e.g. 1-10, 1-8, 2-6, 1-5, 1-4, 1-3 or 2-5) groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or any combination thereof;

[0125] R in formula (PBM-13) 13g Indicates N or CR 13h , where R 13h represents hydrogen or halogen, R 13i Indicates N or CR 13j , where R 13j represents hydrogen or halogen;

[0126] R 13f represents a bond, -C(O)NH-, -NHC(O)-, -S(O)2NH- or -NHS(O)2-;

[0127] (R 13a ) p13a In the expression (PBM-13), R 13g and R 13i The six-membered ring is optionally replaced by p13a R 13a Replace, each R 13a The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0128] p13a represents an integer 0, 1, or 2;

[0129] R 13b Represents hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl or -C 1-3 Alkylene-C 3-6 Cycloalkyl;

[0130] R 13c Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6Alkyl or halogenated C 1-6 alkyl; or

[0131] R 13b and R 13c together with the corresponding nitrogen and carbon atoms to which they are respectively attached, form an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring;

[0132] R 13d Represents hydrogen or R c , R 13e Represents hydrogen or R c , where R 13d and R 13e are not hydrogen at the same time, and R 13d and R 13e There is only one representation R c , another represents hydrogen;

[0133] R in formula (PBM-14) 14a Indicates key, C 1-3 Alkylene or halogenated C 1-3 alkylene;

[0134] R 14b represents an optionally substituted halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, or optionally substituted C 1-6 Alkyl (eg, C optionally substituted with optionally substituted aryl) 1-6 alkyl);

[0135] (R 14c ) p14a The benzene ring in the formula (PBM-14) is optionally replaced by p14a R 14c Replace, each R 14c The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0136] p14a represents an integer 0, 1, 2, 3, or 4;

[0137] R in formula (PBM-15) 15a Indicates C 1-3 Alkylene or halogenated C 1-3 alkylene;

[0138] R 15b Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, or optionally substituted C 3-6 Cycloalkyl;

[0139] R 15c and R 15d Each independently represents S or O;

[0140] R in formula (PBM-16) 16a Indicates -S- or fragment When R 16a When -S- is represented, the formula (PBM-16) contains R 16a and the nitrogen atom is a thiazolyl group, and when R 16a Representation fragment When the formula (PBM-16) contains R 16a and the heteroaryl group of the nitrogen atom is pyridyl;

[0141] R 16b Indicates N or CH;

[0142] R 16c represents hydrogen or optionally substituted C 1-10 alkyl;

[0143] R 16d Represents hydrogen, -C 1-3 Alkylene-optionally substituted 4- to 10-membered heterocyclyl, or optionally substituted 4- to 10-membered heterocyclyl;

[0144] R 16e Represents hydroxyl, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0145] R in formula (PBM-17) 17a Indicates C(O)NH, NHC(O), (CH2) 1-2 C(O)NH, (CH2) 1-2 NHC(O), S(O)2NH or NHS(O)2;

[0146] R 17b Represents hydrogen, hydroxyl, halogen, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C1-6 alkyl;

[0147] R 17c Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; or

[0148] R 17b and R 17c Together with the carbon atom and nitrogen atom to which they are attached and the carbon atom of the benzene ring to which the nitrogen atom is attached, they form an optionally substituted 4- to 6-membered heteroaryl ring or an optionally substituted 4- to 6-membered heterocyclic ring;

[0149] R 17d represents an optionally substituted C 3-6 Cycloalkyl, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 alkyl or an optionally substituted 4- to 20-membered heterocyclic group;

[0150] (R 17e ) p17a Indicates that the pyridin-2(1H)-one ring connected to it is replaced by p17a R 17e Replace, each R 17e The same or different and each independently represents hydroxyl, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0151] p17a represents an integer 0, 1, 2, or 3;

[0152] Ring F in formula (PBM-17) represents an arylene group or a 5- to 20-membered monocyclic or bicyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O and S; (R 17f ) p17b Indicates that the ring F is optionally replaced by p17b R 17f Replace, and each R 17f The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0153] p17b represents an integer 0, 1, 2, 3, or 4;

[0154] R in formula (PBM-18)18f 、R 18g and R 18h Each independently represents CH or N;

[0155] R 18a represents a bond, S or NH;

[0156] R 18b Represents R c , an optionally substituted cycloalkyl group or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclic group;

[0157] R 18c Represents R c , halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, halogenated C 1-6 an alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclic group;

[0158] where R 18b and R 18c R c , and R 18b and R 18c There is only one representation R c (ie R 18b and R 18c One of them represents R c , the other one is not R c );

[0159] (R 18d ) p18a The six-membered ring connected thereto may be optionally 18a R 18d Replace, each R 18d The same or different and each independently represents hydroxyl, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0160] p18a represents an integer 0, 1, 2, 3, or 4;

[0161] (R 18e ) p18b represents a nitrogen-containing six-membered heteroaromatic ring connected thereto which is optionally replaced by p18b R 18e Replace, each R 18e The same or different and each independently represents hydroxyl, amino, cyano, halogen, C 1-6 Alkyl, C1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0162] p18b represents an integer 0, 1, or 2;

[0163] R in formula (PBM-19) 19a 、R 19b 、R 19c Each independently represents CH or N;

[0164] R 19d Represents -C(O)NHR 19h 、-NHC(O)R 19h 、-S(O)2NHR 19h 、-NHS(O)2R 19h 、-S(O)2R 19h or -P(O)(R 19h )2, where each R 19h The same or different and each independently represents C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0165] (R 19e ) p19a Indicates p19a substituent R 19e , each R 19e The same or different and each independently represents halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0166] p19a represents an integer 0, 1, 2, 3, or 4;

[0167] (R 19f ) p19b Indicates p19b substituent R 19f , each R 19f The same or different and each independently represents halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0168] p19b represents an integer 0, 1, or 2;

[0169] (R 19g ) p19c The benzene ring connected thereto may be optionally replaced by p19c R 19g Replace, and each R 19g Each independently represents halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy;

[0170] p19c represents an integer 0, 1, 2, 3, or 4;

[0171] R in formula (PBM-20) c1 Indicates a key, or R c1 Indicates -NH-R c2 -C(O)-***, where the symbol *** represents the c The connection point, and R c2 represents an optionally substituted C 3-15 Cycloalkyl;

[0172] (R 20a ) p20a The 1H-pyrrolo[2,3-b]pyridine ring connected thereto is optionally replaced by p20a R 20a Replace, and each R 20a are independently cyano, halogen, hydroxy, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p20a represents an integer of 0, 1, 2, 3, 4 or 5;

[0173] (R 20b ) p20b Indicates that the pyridine ring connected thereto is optionally replaced by p20b R 20b Replace, and each R 20b are independently cyano, halogen, hydroxyl, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 Alkoxy or NR 20c R 20d , where R 20c 、R 20d are the same or different and each independently represent hydrogen, C 1-6 Alkyl, deuterated C1-6 Alkyl, halogenated C 1-6 Alkyl, optionally substituted C 3-15 cycloalkyl or an optionally substituted 4- to 15-membered heterocyclyl, and p20b represents an integer of 0, 1, 2 or 3;

[0174] R in formula (PBM-21) 21a represents NHC(O), C(O)NH, NHS(O)2 or S(O)2NH;

[0175] (R 21b ) p21a The benzene ring connected thereto may be optionally replaced by p21a R 21b Replace, and each R 21b are independently halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p21a represents an integer of 0, 1, 2, 3, 4 or 5;

[0176] (R 21c ) p21b Indicates that the 1H-pyrazole ring connected thereto is optionally replaced by p21b R 21c Replace, and each R 21c are independently halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p21b represents an integer of 0, 1 or 2;

[0177] R in formula (PBM-22) 22a Indicates N or CH, R 22b represents O, S, NH, CH2, CH(F) or C(F)2;

[0178] R 22c represents a bond or an optionally substituted methylene group (e.g., a halogen-substituted methylene group);

[0179] Ring G represents C 6-15 aryl, 4- to 15-membered heterocyclic group or 5- to 15-membered heteroaryl, (R 22d ) p22a Indicates that the ring G connected thereto is optionally replaced by p22a R 22d Replace, and each R 22d The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, oxo, C1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p22a represents an integer of 0, 1, 2, 3 or 4;

[0180] (R 22e ) p22b Indicates that it contains R 22a The six-membered nitrogen-containing heteroaromatic ring is optionally replaced by p22b R 22e Replace, each R 22e Each independently represents deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl, and p22b represents an integer of 0, 1 or 2;

[0181] (R 22f ) p22c The benzene ring connected thereto may be optionally replaced by p22c R 22f Replace, each R 22f The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl, and p22c represents an integer of 0, 1, 2, 3 or 4;

[0182] R in formula (PBM-23) 23a Indicates N or CH;

[0183] R 23b represents NHC(O), C(O)NH, NHS(O)2 or S(O)2NH;

[0184] (R 23c ) p23a Indicates R-containing 23a The six-membered ring is optionally replaced by p23a R 23c Replace, each R 23c The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6alkoxy, and p23a represents an integer of 0, 1, 2, 3 or 4;

[0185] Ring H represents a 5- to 15-membered heteroarylene group, (R 23d ) p23b Indicates that the ring H connected thereto is optionally replaced by p23b R 23d Replace, each R 23d The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1- 6 alkyl, hydroxy substituted C 1-6 Alkyl, amino substituted C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or optionally substituted C 3-15 cycloalkyl, and p23b represents an integer of 0, 1, 2 or 3;

[0186] The dashed lines in Formula (PBM-24) indicate the optional presence of a double bond (i.e., represents a single bond or a double bond);

[0187] (R 24a ) p24a The six-membered cycloalkyl group connected thereto is optionally replaced by p24a R 24a Replace, each R 24a The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24a represents an integer of 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0188] (R 24b ) p24b Indicates that the benzene ring connected thereto may be optionally replaced by p24b R 24b Replace, each R 24b The same or different and each independently represents deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24b represents an integer of 0, 1, 2, 3, 4 or 5;

[0189] (R 24c )p24c represents a six-membered cycloalkyl group connected thereto which is optionally replaced by p24c R 24c Replace, each R 24c The same or different and each independently represents halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24c represents an integer of 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0190] (R 24d ) p24d The benzene ring connected thereto is optionally replaced by p24d R 24d Replace, each R 24d The same or different and each independently represents halogen, hydroxyl, mercapto, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or and p24d represents an integer 0, 1, or 2;

[0191] (R 24e ) p24e Indicates that the benzene ring connected thereto may be optionally replaced by p24e R 24e Replace, each R 24e The same or different and each independently represents deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, -SO2CF3, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24e represents an integer of 0, 1, 2, 3 or 4;

[0192] R 24f represents hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or Where y represents an integer 1, 2 or 3;

[0193] (R 25a ) p25a Indicates p25a substituents R 25a , each R25a The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p25a represents an integer of 0, 1, 2, 3, 4 or 5;

[0194] (R 25b ) p25b Indicates that the benzene ring connected thereto is optionally replaced by p25b R 25b Replace, each R 25b The same or different and each independently represents deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p25b represents an integer of 0, 1, 2, 3 or 4; and

[0195] R 25c Indicates C 1-6 Alkylene or halogenated C 1-6 alkylene;

[0196] (R 26a ) p26a Indicates that the benzene ring connected thereto may be optionally replaced by p26a R 26a Replace, each R 26a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0197] p26a represents an integer 0, 1, 2, 3, or 4;

[0198] (R 26b ) p26b Indicates that the 4-oxo-3,4-dihydroquinazoline ring connected to it is replaced by p26b R 26b Replace, each R 26b The same or different and each independently represents halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6alkyl;

[0199] p26b represents the integer 1, 2, 3, or 4;

[0200] (R 27a ) p27a Indicates that it contains R 27d The six-membered ring is optionally replaced by p27a R 27a Replace, each R 27a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0201] p27a represents an integer 0, 1, 2, or 3;

[0202] (R 27b ) p27b Indicates p27b R 27b Substituents, each R 27b The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 alkyl or an optionally substituted 5- to 15-membered aryl group;

[0203] p27b represents an integer 0, 1, 2, or 3;

[0204] R 27c and R 27d Each independently represents N or CH;

[0205] R 27e represents hydrogen or the structure of the following formula (III):

[0206] Among them (R 27g ) p27c The benzene ring connected thereto may be optionally replaced by p27c R 27g Replace, each R 27g The same or different and each independently represents hydrogen, deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0207] p27c represents an integer 0, 1, 2, 3, or 4;

[0208] n represents an integer 1, 2, 3, 4 or 5;

[0209] (R 27h ) p27d Indicates p27d R 27h Substituents, each R 27h The same or different and each independently represents hydrogen, deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0210] p27d represents an integer 0, 1, 2, 3, 4, 5, 6, or 7; and

[0211] The symbol * indicates the connection point with LIN;

[0212] R 27f Represents hydrogen or R c ;

[0213] When R 27e When it represents hydrogen, R 27f Represents R c ; When R 27f When it represents hydrogen, R 27e represents the structure of formula (III);

[0214] R 28a represents O, S or NH;

[0215] (R 28b ) p28a Indicates that the nitrogen-containing five-membered ring connected thereto is optionally replaced by p28a R 28b Substituent substitution, each R 28b The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0216] p28a represents an integer 0, 1, or 2;

[0217] (R 28c ) p28b Indicates that the benzene ring connected thereto may be optionally replaced by p28b R 28c Substituent substitution, each R 28cThe same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl;

[0218] p28b represents an integer 0, 1, 2, 3, or 4;

[0219] (R 28d ) p28c Indicates that the benzene ring connected thereto is optionally replaced by p28c R 28d Substituent substitution, each R 28d The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl or optionally substituted C 3-15 Cycloalkyl;

[0220] p28c represents an integer 0, 1, 2, 3, 4, or 5;

[0221] R 29a represents S(O)2 or represents a bond;

[0222] R 29b represents NH, NHC(O) or C(O)NH;

[0223] R 29c Indicates CH or N;

[0224] R 29d Indicates N(R 29h ), where R 29h represents H, -C(O)-optionally substituted aryl or -C(O)-optionally substituted heteroaryl; or

[0225] R 29d Representation fragment The symbol ** represents the connection point with the adjacent N atom, the symbol ### represents the connection point with the adjacent C atom, and R 29i Deuterium, hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl;

[0226] (R 29e ) p29a Indicates that the benzene ring connected thereto may be optionally replaced by p29a R 29eSubstituent substitution, each R 29e The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl;

[0227] p29a represents an integer 0, 1, 2, 3, or 4;

[0228] (R 29f ) p29b Indicates that the nitrogen-containing ring connected to it is p29b R 29f Substituent substitution, each R 29f The same or different and each independently represents deuterium, amino, halogen, hydroxyl, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 alkyl, -NH-optionally substituted aryl, or -NH-optionally substituted heteroaryl;

[0229] p29b represents an integer 1 or 2;

[0230] (R 30a ) p30a Indicates that the three rings connected thereto are optionally connected by p30a R 30a Substituent substitution, each R 30a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0231] p30a represents an integer 0, 1, 2, 3, 4, 5, or 6;

[0232] In formula (PBM-30) represents a single bond or a double bond;

[0233] The fragment of the tricyclic ring in formula (PBM-30) express where R 30f Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0234] When the fragment express Time, fragment express

[0235] When the fragment express Time, fragment express

[0236] R 30d and R 30e are the same or different and each independently represent N or CH;

[0237] R in formula (PBM-31) 31a represents O, S or NH;

[0238] (R 31b ) p31a Indicates R-containing 31a The five-membered ring is optionally replaced by p31a R 31b Substituent substitution, each R 31b The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0239] p31a represents an integer 0, 1, 2, or 3;

[0240] (R 31c ) p31b Indicates that the diazacyclic ring connected thereto is optionally replaced by p31b R 31c Substituent substitution, each R 31c The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0241] p31b represents the integer 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

[0242] Z1 represents an integer 1, 2, or 3;

[0243] Z2 represents an integer 1, 2, 3, 4, 5 or 6;

[0244] R in formula (PBM-32)32a represents O, S or NH;

[0245] R 32b Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0246] Z3 represents an integer 1, 2, or 3;

[0247] (R 32c ) p32a Indicates that the benzene ring connected thereto may be optionally replaced by p32a R 32c Substituent substitution, each R 32c The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl;

[0248] p32a represents the integer 0, 1, 2, 3, 4, or 5;

[0249] (R 32d ) p32b Indicates R-containing 32a The five-membered ring is optionally replaced by p32b R 32d Substituent substitution, each R 32d The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0250] p32b represents the integer 0, 1 or 2;

[0251] (R 32e ) p32c Indicates that the pyrazole ring connected thereto is optionally replaced by p32c R 32e Substituent substitution, each R 32e The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0252] p32c represents the integer 0, 1, or 2;

[0253] (R 33a ) p33a Indicates that the benzene ring connected thereto may be optionally replaced by p33a R 33a Substituent substitution, each R 33a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl;

[0254] p33a represents an integer 0, 1, 2, 3, 4, or 5;

[0255] R in formula (PBM-33) 33b 、R 33c 、R 33d 、R 33e 、R 33f 、R 33g and R 33h The same or different and each independently represents hydrogen, deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 Alkyl; and

[0256] R in each general formula c Each independently represents a bond, -O-, -N(R d )-, -NHC(O)-*, -C(O)NH-*, -N(R d )-R f -N(R e )-*、-R f -C(O)NH-*、-R f -NHC(O)-*、-R f -C(O)O-*、-R f -OC(O)-*, -C(O)O-*, -OC(O)-*, -R f -、-R f -N(R d )-*、-OR f -N(R d )-*、

[0257] Among them, each ring W 1 are the same or different and each independently represent a nitrogen-containing heterocyclic group, t1 represents an integer of 1 or 2, (Rc1 ) m2 Indicates each ring W 1 Each independently optionally represented by m1 R c1 Group substitution, each R c1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c4 -R c3 -, where R c3 is an optional substituted C 1-6 Alkylene or optionally substituted C 2-6 Alkenylene, R c4 Represents halogen, R c5 R c6 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c5 and R c6 The same or different and each independently represents hydrogen or C 1-3 alkyl, and m1 represents an integer of 0-20;

[0258] Each ring W 2 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, t2 represents an integer of 0 or 1, (R c2 ) m3 Indicates each ring W 2 Independently optionally m2 R c2 Group substitution, each R c2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c8 -R c7 -, where R c7 is an optional substituted C 1-6 Alkylene or optionally substituted C 2- 6-alkenylene, R c8 Represents halogen, R c9 R c10 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c9 and R c10The same or different and each independently represents hydrogen or C 1-3 alkyl, and m2 represents an integer of 0-20; and

[0259] R d and R e Each independently represents hydrogen or C 1-6 Alkyl, R f and R g Each independently represents an optionally substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene, and the symbol * indicates the point of attachment to LIN.

[0260] In various embodiments of the present disclosure, the number of substituents is in principle not subject to any limitation, either automatically limited by the size of the building block (ie, the total number of replaceable hydrogen atoms of the building block), or as explicitly defined herein.

[0261] In some embodiments, the PBM represents a small molecule ligand for EGFR.

[0262] In some embodiments, PBM represents the structure of the following formula (PBM-1):

[0263] in,

[0264] (R 1a ) p1a Indicates that the benzene ring to which it is connected is surrounded by p1a R 1a Replace, each R 1a The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, C 1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), NO2, NH2 or cyano;

[0265] p1a represents an integer 0, 1, 2, 3, 4, or 5;

[0266] R 1b represents substituted or unsubstituted C 3-15 Cycloalkyl (e.g. substituted or unsubstituted C 3-10 Cycloalkyl or C 3-6 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl). In some embodiments, the C 3-15 The cycloalkyl group may be substituted by one or more (eg 1-3, 1, 2 or 3) groups selected from deuterium, hydroxy, amino, mercapto, nitro, halogen (eg fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally halogenated C 3-6 Cycloalkyl, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-6 Alkyl-NHC(O)-, C 1-6The group consisting of: -C(O)NH- and -C(O)NH- is substituted with any combination thereof.

[0267] In some embodiments, PBM represents the structure of the following formula (PBM-1-1):

[0268] In some embodiments, PBM represents the following structure of Formula (PBM-2-1A), Formula (PBM-2-1B), Formula (PBM-2-1C), or Formula (PBM-2-1D) (which are non-limiting examples of structures of Formula (PBM-2)):

[0269] Wherein, in formula (PBM-2-1A), formula (PBM-2-1B), formula (PBM-2-1C) and formula (PBM-2-1D),

[0270] R 2a Indicates C 6-10 aryl or 5- to 20-membered heteroaryl (e.g., 5- to 20-membered heteroaryl containing 1 or 2 5- to 7-membered rings and 1 to 4 heteroatoms selected from N, O and S), wherein C 6-10 Aryl and 5- to 20-membered heteroaryl are each independently optionally substituted by one or more (e.g., 1-6, such as 1, 2, 3, 4, 5 or 6) groups each independently selected from deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-6 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-5 Alkoxy or C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof;

[0271] R 2b Indicates C 6-10 aryl or 5- to 20-membered heteroaryl (e.g., 5- to 20-membered heteroaryl containing 1 or 2 5- to 7-membered rings and 1 to 4 heteroatoms selected from N, O and S), wherein C 6-10 Aryl and 5- to 20-membered heteroaryl are each independently optionally substituted by one or more (e.g., 1-6, such as 1, 2, 3, 4, 5 or 6) groups each independently selected from deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy) and halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) 2d Replacement; and

[0272] (R 2c ) p2a Indicates that the isoindoline ring connected thereto is optionally replaced by p2a R2c Replace, each R 2c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halo 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), NO2, NH2, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-), or cyano; and

[0273] p2a represents an integer 0, 1, 2, or 3.

[0274] In some embodiments, R 2a Indicates C 6-10 Aryl, such as but not limited to phenyl or naphthyl, phenyl or naphthyl each optionally substituted by one or more (e.g. 1-6, such as 1, 2, 3, 4, 5 or 6) independently selected from deuterium, halogen (e.g. fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0275] In some embodiments, R 2a represents a 5- to 20-membered heteroaryl group, for example a 5- to 20-membered heteroaryl group comprising 1 or 2 5- to 7-membered rings and 1 to 4 heteroatoms selected from N, O and S. In one subembodiment, R 2arepresents a 5- to 14-membered monocyclic or bicyclic aromatic ring group containing one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. In one embodiment, examples of heteroaryl include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, Benzo[1,2,3]thiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, imidazo[1,2-b]pyridazinyl or 6,7-dihydro-5H-pyrrolo[1,2-c]imidazolyl. The heteroaryl group may be optionally substituted by one or more (e.g. 1-6, e.g. 1, 2, 3, 4, 5 or 6) groups independently selected from deuterium, halogen (e.g. fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1- 4 alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0276] In some embodiments, R 2b Indicates C 6-10 Aryl, such as but not limited to phenyl or naphthyl, each of which is optionally substituted with one or more (e.g. 1-6, such as 1, 2, 3, 4, 5 or 6) R as defined above 2d replace.

[0277] In some embodiments, R 2b represents a heteroaryl group comprising 1 or 2 5- to 7-membered rings and 1 to 4 heteroatoms selected from N, O and S. In one subembodiment, R 2b represents a 5- to 14-membered monocyclic or bicyclic aromatic ring group containing one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. In one embodiment, examples of heteroaryl include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]oxadiazolyl] ... or imidazo[1,2-b]pyridazine. The heteroaryl group is optionally substituted with one or more (e.g., 1 to 6, e.g., 1, 2, 3, 4, 5, or 6) R as defined above. 2d replace.

[0278] In some embodiments, PBM represents the structure of Formula (PBM-2-1), Formula (PBM-2-2), Formula (PBM-2-3), Formula (PBM-2-4), or Formula (PBM-2-5):

[0279] In some embodiments, PBM represents the structure of the following formula (PBM-3):

[0280] in

[0281] R 3a Represents hydrogen, C 1-10 Alkyl (e.g. C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl groups, such as methyl, ethyl, propyl, isopropyl butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., perdeuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-10 Alkyl (e.g. halo-C 1-8 Alkyl or halogenated C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-); and

[0282] R 3b express or a 4- to 12-membered nitrogen-containing heterocyclic group, wherein the 4- to 12-membered nitrogen-containing heterocyclic group is optionally substituted by one or more independently selected from deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-5 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkoxy (e.g., perdeuterated C 1-4 alkyl, such as CD3-O-, CD3CD2-O-, or CD3CD2CD2-O-), NO2, NH2, cyano, or any combination thereof. In some subembodiments, examples of 4- to 12-membered nitrogen-containing heterocyclic groups include, but are not limited to, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azepanyl, diazepanyl (e.g., 1,4-diazacycloheptane-1-yl), azocanyl, diazacyclooctanyl, azabicyclo[3.1.1]heptanyl, azabicyclo[2. 2.1]heptyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[3.1.1]heptyl, diazabicyclo[2.2.1]heptyl, diazabicyclo[3.2.1]octanyl (e.g. 3,8-diazabicyclo[3.2.1]octan-3-yl), diazabicyclo[2.2.2]octanyl (e.g. 2,5-diazabicyclo[2.2.2]octan-2-yl).

[0283] In some embodiments, PBM represents the structure of the following Formula (PBM-3-1) or Formula (PBM-3-2):

[0284] In some embodiments, PBM represents the structure of the following formula (PBM-19):

[0285] in

[0286] R 19a 、R 19b 、R 19c Each independently represents CH or N;

[0287] R 19d Represents -C(O)NHR 19h 、-NHC(O)R 19h 、-S(O)2NHR 19h 、-NHS(O)2R 19h 、-S(O)2R19h or -P(O)(R 19h )2, where each R 19h The same or different and each independently represents C 1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or perdeuterated C 1-3 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-5 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0288] (R 19e ) p19a Indicates p19a substituent R 19e , each R 19e The same or different and each independently represents halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or perdeuterated C 1-3 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-5 Alkoxy, C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as trifluoromethoxy);

[0289] p19a represents an integer 0, 1, 2, 3, or 4;

[0290] (R 19f ) p19b Indicates p19b substituent R 19f , each R 19f The same or different and each independently represents halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or perdeuterated C 1-3 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-5 Alkoxy, C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as trifluoromethoxy);

[0291] p19b represents an integer 0, 1, or 2;

[0292] (R 19g ) p19c The benzene ring connected thereto may be optionally replaced by p19c R 19g Replace, and each R 19g Each independently represents halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or perdeuterated C 1-3 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-5 Alkoxy, C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as trifluoromethoxy); and

[0293] p19c represents an integer 0, 1, 2, 3, or 4.

[0294] In some embodiments, R 19a and R 19b Each independently represents CH or N. In some subembodiments, R 19a Indicates CH, R 19b represents N. In some sub-embodiments, R 19a Indicates CH, R 19b In some subembodiments, R 19a Indicates N, R 19b In some subembodiments, R 19a Indicates N, R 19b Indicates N.

[0295] In some embodiments, R 19c represents CH or N. In some subembodiments, R 19c represents N. In some sub-embodiments, R 19c Indicates CH.

[0296] In some embodiments, R 19d Represents -C(O)NHR 19h 、-NHC(O)R 19h 、-S(O)2NHR 19h 、-NHS(O)2R 19h 、-S(O)2R 19h or -P(O)(R 19h )2, where each R 19h The same or different and each independently represents C1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or perdeuterated C 1-3 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-5 Alkyl or halogenated C 1-3 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-). In some subembodiments, R 19d Represents -P(O)(R 19h )2, where each R 19h The same or different and each independently represents C 1-6 Alkyl (e.g. C 1-4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or perdeuterated C 1-3 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-5 Alkyl or halogenated C 1-3 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-). In some subembodiments, R 19d It represents -P(O)(CH3)2.

[0297] In some embodiments, p19c represents the integer 0, 1, 2, 3, or 4. In some subembodiments, p19c represents the integer 2.

[0298] In some embodiments, PBM represents the following structure of Formula (PBM-19-1), Formula (PBM-19-2), Formula (PBM-19-3), Formula (PBM-19-4), or Formula (PBM-19-5):

[0299] In some embodiments, PBM represents a small molecule ligand for AR.

[0300] In some embodiments, PBM represents the structure of the following formula (PBM-4):

[0301] in

[0302] Ring A represents C 6-10 aryl (e.g. phenyl or naphthyl) or 5- to 20-membered heteroaryl (e.g. 5- to 20-membered heteroaryl comprising 1 or 2 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S), ring A is optionally substituted by one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) R 4a Replace, and each R 4a are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 2-6 alkenyl (e.g., ethenyl, propenyl, or butenyl), or C 2-6 Alkynyl (e.g., ethynyl, propynyl, or butynyl);

[0303] Ring B represents C 3-15cycloalkyl or 4- to 20-membered heterocyclyl (e.g., 4- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from N, O, and S), wherein Ring B is optionally substituted by one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) R 4b Replace, and each R 4b are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), C 1- 6 alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-); and

[0304] Ring C represents a 5- to 20-membered heteroaryl group (e.g. a 5- to 20-membered monocyclic or bicyclic heteroaryl group containing 1-4 heteroatoms selected from N, O and S), wherein Ring C is optionally substituted by one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) R 4c Replace, and each R 4c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0305] In some embodiments, PBM represents the structure of the following formula (PBM-4-1A):

[0306] in

[0307] The benzene ring in formula (PBM-4-1A) is optionally replaced by one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) R 4a Replace, and each R 4a are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 2-6 alkenyl (e.g., ethenyl, propenyl, or butenyl), or C 2-6 Alkynyl (e.g., ethynyl, propynyl, or butynyl);

[0308] Ring B represents C 3-15 cycloalkyl or 4- to 20-membered heterocyclyl (e.g., 4- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from N, O, and S), wherein Ring B is optionally substituted by one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) R 4b Replace, and each R 4b are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), C 1- 6 alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-);

[0309] Q1 represents N or CH; and

[0310] The heteroaryl group containing Q1 and a nitrogen atom in formula (PBM-4-1A) is optionally replaced by one or more (eg, 1-3, such as 1, 2 or 3) R 4c Replace, and each R 4c are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0311] In some embodiments, Ring B in Formula (PBM-4) and Formula (PBM-4-1A) each independently represents C 3-15 Cycloalkyl or 4- to 20-membered heterocyclic group (eg, 4- to 20-membered heterocyclic group containing 1 to 4 heteroatoms selected from N, O and S). 3-15 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, 2,3-dihydro-1H-indenyl, spirocyclyl (e.g., C 5-15 Spirocyclyl), adamantyl, noradamantyl and norbornyl. C 3-15 Optional substituents of the cycloalkyl group are optionally selected from halogen (eg, fluorine, chlorine, bromine or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), and halo-C 1-6 Alkoxy (e.g., halo-C 1-4Examples of the 4- to 20-membered heterocyclic radical include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, azepanyl, diazepanyl (e.g., 1,4-diazepan-1-yl), azocanyl, diazacyclooctanyl, azabicyclo[3.1.1]heptane-1-yl, alkyl, azabicyclo[2.2.1]heptyl, azabicyclo[3.2.1]octyl, azabicyclo[2.2.2]octyl, diazabicyclo[3.1.1]heptyl, diazabicyclo[2.2.1]heptyl, diazabicyclo[3.2.1]octyl (e.g. 3,8-diazabicyclo[3.2.1]octane-3-yl), diazabicyclo[2.2.2]octane (e.g. 2,5-diazabicyclo[2.2.2]octane-2-yl). Optional substituents of the 4- to 20-membered heterocyclyl group are optionally selected from halogen (e.g. fluorine, chlorine, bromine or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), and halo-C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0312] In some embodiments, PBM represents the structure of Formula (PBM-4-1), Formula (PBM-4-2), Formula (PBM-4-3), or Formula (PBM-4-4):

[0313] In some embodiments, PBM represents the structure of the following formula (PBM-27):

[0314] in

[0315] (R 27a ) p27a Indicates that it contains R 27d The six-membered ring is optionally replaced by p27a R 27a Replace, each R 27a The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0316] p27a represents an integer 0, 1, 2, or 3;

[0317] (R 27b ) p27b Indicates p27b R 27b Substituents, each R 27b The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or an optionally substituted C 6-10 aryl;

[0318] p27b represents an integer 0, 1, 2, or 3;

[0319] R 27c and R 27d Each independently represents N or CH;

[0320] R 27erepresents hydrogen or the structure of the following formula (III):

[0321] Among them (R 27g ) p27c The benzene ring connected thereto may be optionally replaced by p27c R 27g Replace, each R 27g The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0322] p27c represents an integer 0, 1, 2, 3, or 4;

[0323] n represents an integer 1, 2, 3, 4 or 5;

[0324] (R 27h ) p27d Indicates p27d R 27h Substituents, each R 27h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0325] p27d represents an integer 0, 1, 2, 3, 4, 5, 6, or 7; and

[0326] The symbol * indicates the connection point with LIN;

[0327] R 27f Represents hydrogen or R c ;

[0328] When R 27e When it represents hydrogen, R 27f Represents R c ; When R 27f When it represents hydrogen, R 27e The structure of formula (III) is shown.

[0329] In some embodiments, R 27e represents hydrogen, and R 27f Represents R c .

[0330] In some embodiments, R 27f represents hydrogen, and R 27e The structure of formula (III) is:

[0331] Among them (R 27g ) p27c The benzene ring connected thereto may be optionally replaced by p27c R 27g Replace, each R 27g The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0332] p27c represents an integer 0, 1, 2, 3, or 4;

[0333] n represents an integer 1, 2, 3, 4 or 5;

[0334] (R 27h ) p27d represents that the cycloalkyl group to which it is attached is optionally replaced by p27d R 27h Substituent substitution, each R 27h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0335] p27d represents an integer 0, 1, 2, 3, 4, 5, 6, or 7; and

[0336] The symbol * indicates the connection point to LIN.

[0337] In some embodiments, PBM represents a structure of the following formula (PBM-27-A):

[0338] in

[0339] (R 27a ) p27a Indicates that it contains R 27d The six-membered ring is optionally replaced by p27a R 27a Replace, each R 27a The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0340] p27a represents an integer 0, 1, 2, or 3;

[0341] (R 27b ) p27b Indicates p27b R 27b Substituents, each R 27b The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or an optionally substituted C 6-10 aryl;

[0342] p27b represents the integer 0, 1, 2, or 3; and

[0343] R 27c and R 27d Each independently represents N or CH.

[0344] In some embodiments, R in Formula (PBM-27) and Formula (PBM-27-A) 27b Each independently represents C 6-10 Aryl, such as but not limited to phenyl or naphthyl, phenyl or naphthyl each optionally substituted by one or more (e.g. 1-6, such as 1, 2, 3, 4, 5 or 6) independently selected from deuterium, halogen (e.g. fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4The alkoxy group is substituted with a substituent such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0345] In some embodiments, R in formula (PBM-27-A) 27c and R 27d Indicates CH.

[0346] In some embodiments, PBM represents a structure of the following formula (PBM-27-1):

[0347] In some embodiments, PBM represents the structure of the following formula (PBM-28):

[0348] in

[0349] R in formula (PBM-28) 28a represents O, S or NH;

[0350] (R 28b ) p28a Indicates that the nitrogen-containing five-membered ring connected thereto is optionally replaced by p28a R 28b Substituent substitution, each R 28b The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0351] p28a represents an integer 0, 1, or 2;

[0352] (R 28c ) p28b Indicates that the benzene ring connected thereto may be optionally replaced by p28b R 28c Substituent substitution, each R 28c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0353] p28b represents an integer 0, 1, 2, 3, or 4;

[0354] (R 28d ) p28cIndicates that the benzene ring connected thereto is optionally replaced by p28c R 28d Substituent substitution, each R 28d The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or an optionally substituted C 3-15 cycloalkyl; and

[0355] p28c represents the integer 0, 1, 2, 3, 4, or 5.

[0356] In some embodiments, R in formula (PBM-28) 28d Each independently represents C 3-15 Cycloalkyl. C 3-15 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, 2,3-dihydro-1H-indenyl, spirocyclyl (e.g., C 5-15 Spirocyclyl), adamantyl, noradamantyl and norbornyl. C 3-15Optional substituents of the cycloalkyl group are optionally selected from halogen (eg, fluorine, chlorine, bromine or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), and halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0357] In some embodiments, R in formula (PBM-28) 28a Indicates O.

[0358] In some embodiments, PBM represents the structure of the following formula (PBM-28-1):

[0359] In some embodiments, the PBM represents a small molecule ligand of AKT.

[0360] In some embodiments, PBM represents a structure of the following formula (PBM-27-B):

[0361] in

[0362] (R 27a ) p27a Indicates that it contains R 27d The six-membered ring is optionally replaced by p27a R27a Replace, each R 27a The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0363] p27a represents an integer 0, 1, 2, or 3;

[0364] (R 27b ) p27b Indicates p27b R 27b Substituents, each R 27b The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or an optionally substituted C 6-10 aryl;

[0365] p27b represents an integer 0, 1, 2, or 3;

[0366] R 27c and R 27d Each independently represents N or CH;

[0367] (R 27g ) p27c The benzene ring connected thereto may be optionally replaced by p27c R 27g Replace, each R 27g The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0368] p27c represents an integer 0, 1, 2, 3, or 4;

[0369] n represents an integer 1, 2, 3, 4 or 5;

[0370] (R 27h ) p27d Indicates p27d R 27h Substituents, each R 27h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-); and

[0371] p27d represents an integer 0, 1, 2, 3, 4, 5, 6, or 7.

[0372] In some embodiments, R in formula (PBM-27-B) 27c and R 27d Indicates N.

[0373] In some embodiments, PBM represents the structure of the following formula (PBM-27-2):

[0374] In some embodiments, PBM represents the structure of the following formula (PBM-32):

[0375] in

[0376] R in formula (PBM-32) 32a represents O, S or NH;

[0377] R 32b Represents hydrogen, C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0378] Z3 represents an integer 1, 2, or 3;

[0379] (R 32c ) p32a represents a benzene ring optionally replaced by p32a R 32c Substituent substitution, each R 32cThe same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0380] p32a represents the integer 0, 1, 2, 3, 4, or 5;

[0381] (R 32d ) p32b Indicates containing R 32a The five-membered ring is optionally replaced by p32b R 32d Substituent substitution, each R 32d The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0382] p32b represents the integer 0, 1 or 2;

[0383] (R 32e ) p32c indicates that the pyrazole ring is optionally replaced by p32c R 32e Substituent substitution, each R 32e The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-); and

[0384] p32c represents the integer 0, 1, or 2.

[0385] In some embodiments, PBM represents the structure of the following Formula (PBM-32-1) or Formula (PBM-32-2):

[0386] In some embodiments, PBM represents a small molecule ligand of BTK.

[0387] In some embodiments, PBM represents the structure of the following formula (PBM-5):

[0388] in

[0389] X1 in formula (PBM-5) represents N or CR 5f , where R 5f represents hydrogen, deuterium or amino, X2 represents N or CR 5g , where R 5g represents hydrogen or represents R c , and X3 represents CH or N;

[0390] R 5a and R 5b Each independently represents hydrogen or represents R c ;

[0391] (R 5c ) p5a Indicates that the benzene ring connected to it is p5a R 5c Replace, each R 5c The same or different and each independently represents -O-aryl, -O-heteroaryl, 4- to 20-membered heterocyclic group, -C 1-3 Alkylene-NHC(O)-heteroaryl, -C 1-3 Alkylene-C(O)NH-heteroaryl, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterium, deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogen (such as fluorine, chlorine, bromine or iodine), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), the 4- to 20-membered heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more (e.g., 1-5, e.g., 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-);

[0392] p5a represents an integer 1, 2, 3, or 4;

[0393] R 5d Represents R c , hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), or C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy);

[0394] R 5e represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or amino;

[0395] where R 5g 、R 5a 、R 5b and R 5d are not hydrogen at the same time, and R 5g 、R 5a 、R 5b and R 5d There is only one representation R c ,in

[0396] When R 5a Represents R c When X2 represents CH or N, and R 5b is hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy;

[0397] When X2 represents CR 5g , where R 5g Represents R c When R 5a and R 5b are hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy;

[0398] When R 5b Represents R c When X2 represents N or CH, and R 5a is hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy; or

[0399] When R 5dRepresents R c When X2 represents N or CH, and R 5a and R 5b All are hydrogen.

[0400] In this article, R in formula (PBM-5) 5g 、R 5a 、R 5b and R 5d One of them represents R c , and the rest are not R c .

[0401] In some embodiments, R in formula (PBM-5) 5c represents -O-aryl, -O-heteroaryl, -C 1-3 Alkylene-NHC(O)-heteroaryl, or -C 1-3 Alkylene-C(O)NH-heteroaryl, wherein the aryl group may be optionally substituted C 6-10 Aryl, including but not limited to phenyl or naphthyl, heteroaryl can be an optionally substituted 5- to 14-membered monocyclic or bicyclic or polycyclic aromatic ring group containing 1 or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen and sulfur. In one embodiment, R 5c represents -O-phenyl or -O-naphthyl, phenyl or naphthyl optionally substituted by one or more (eg 1-5, such as 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy or halogenated C 1-3 Alkoxy, for example, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-). In one subembodiment, R 5c represents -O-heteroaryl, -C 1-3 Alkylene-NHC(O)-heteroaryl, or -C 1-3 Alkylene-C(O)NH-heteroaryl, heteroaryl is optionally substituted by one or more (eg 1-5, such as 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy or halogenated C 1-3Alkoxy groups, for example, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-). In one subembodiment, examples of heteroaryl include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3] oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl.

[0402] In some embodiments, R in formula (PBM-5) 5c represents a 4- to 20-membered (e.g., 4- to 15-membered, 4- to 12-membered, 4- to 10-membered, 4- to 7-membered, or 4- to 6-membered) monocyclic or bicyclic or polycyclic heterocyclic group, wherein the 4- to 20-membered monocyclic or bicyclic or polycyclic heterocyclic group may be optionally substituted. In one subembodiment, R 5c represents a 4- to 20-membered monocyclic or bicyclic or polycyclic heterocyclic group, which is optionally substituted by one or more (e.g. 1-5, e.g. 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy or halogenated C 1-3 In one embodiment, examples of 4- to 20-membered monocyclic or bicyclic or polycyclic heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, azepanyl, diazepanyl (e.g., 1,4-diazepan-1-yl), azocanyl, diazacyclooctanyl, azabicyclo [3.1.1]heptyl, azabicyclo[2.2.1]heptyl, azabicyclo[3.2.1]octyl, azabicyclo[2.2.2]octyl, diazabicyclo[3.1.1]heptyl, diazabicyclo[2.2.1]heptyl, diazabicyclo[3.2.1]octyl (e.g., 3,8-diazabicyclo[3.2.1]octane-3-yl), diazabicyclo[2.2.2]octane (e.g., 2,5-diazabicyclo[2.2.2]octane-2-yl).

[0403] In some embodiments, R 5b Represents R c , R 5a is hydrogen, X2 represents N or CH, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C1-6 Alkoxy.

[0404] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 Alkoxy, and X2 represents N, X1 represents CR 5f , where R 5f is hydrogen or represents amino, and X3 represents N.

[0405] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 Alkoxy, and X2 represents N, X1 represents CR 5f , where R 5f is hydrogen or represents amino, and X3 represents CH.

[0406] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy, and X2 represents N, X1 represents N, and X3 represents CH.

[0407] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy, and X2 represents N, X1 represents N, and X3 represents N.

[0408] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 Alkoxy, and X2 represents CH, X1 represents CR 5f , where R 5f is hydrogen or represents amino, and X3 represents N.

[0409] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 Alkoxy, and X2 represents CH, X1 represents CR 5f , where R 5f is hydrogen or represents amino, and X3 represents CH.

[0410] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy, and X2 represents CH, X1 represents N, and X3 represents CH.

[0411] In some embodiments, R 5b Represents R c , R 5a is hydrogen, R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy, and X2 represents CH, X1 represents N, and X3 represents N.

[0412] In some embodiments, PBM represents a structure of the following formula (PBM-5-1A):

[0413] in

[0414] X1 in formula (PBM-5-1A) represents N or CR 5f , where R 5f is hydrogen or represents amino, X2 represents N or CH, and X3 represents CH or N;

[0415] (R 5c ) p5a Indicates that the benzene ring connected to it is p5a R 5c Replace, each R 5c The same or different and each independently represents -O-aryl, -O-heteroaryl, 4- to 20-membered heterocyclic group, -C 1-3 Alkylene-NHC(O)-heteroaryl, or -C 1-3 Alkylene-C(O)NH-heteroaryl, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterium, deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogen (such as fluorine, chlorine, bromine or iodine), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), wherein the 4- to 20-membered heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more (e.g., 1-5, e.g., 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy or halogenated C 1-3 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-);

[0416] p5a represents an integer 1, 2, 3, or 4;

[0417] R 5d represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), or C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy); for example R 5d represents hydrogen or methyl; and

[0418] R 5e represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or amino.

[0419] In some embodiments, R of formula (PBM-5-1A) 5c represents -O-aryl, -O-heteroaryl, -C 1-3 Alkylene-NHC(O)-heteroaryl, or -C 1-3 Alkylene-C(O)NH-heteroaryl, wherein the aryl group may be optionally substituted C 6-10 Aryl, including but not limited to phenyl or naphthyl, heteroaryl can be an optionally substituted 5- to 14-membered monocyclic or bicyclic aromatic ring group containing 1 or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen and sulfur. In one embodiment, R 5c represents -O-phenyl or -O-naphthyl, phenyl or naphthyl optionally substituted by one or more (eg 1-5, such as 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy or halogenated C 1-3 Alkoxy, for example, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-). In one subembodiment, R 5c represents -O-heteroaryl, -C 1-3 Alkylene-NHC(O)-heteroaryl, or -C 1-3 Alkylene-C(O)NH-heteroaryl, heteroaryl is optionally substituted by one or more (eg 1-5, such as 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy or halogenated C 1-3 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-). In one subembodiment, examples of heteroaryl include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3] oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl.

[0420] In some embodiments, R in formula (PBM-5-1A) 5c represents a 4- to 20-membered (e.g., 4- to 15-membered, 4- to 12-membered, 4- to 10-membered, 4- to 7-membered, or 4- to 6-membered) monocyclic or bicyclic or polycyclic heterocyclic group, wherein the 4- to 20-membered monocyclic or bicyclic or polycyclic heterocyclic group may be optionally substituted. In one subembodiment, R 5crepresents a 4- to 20-membered monocyclic or bicyclic or polycyclic heterocyclic group, which is optionally substituted by one or more (e.g. 1-5, e.g. 1, 2, 3, 4 or 5) R 5h Replace, and each R 5h The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy or C 1-3 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy or halogenated C 1-3In one embodiment, examples of 4- to 20-membered monocyclic or bicyclic or polycyclic heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, azepanyl, diazepanyl (e.g., 1,4-diazepan-1-yl), azocanyl, diazacyclooctanyl, azabicyclo [3.1.1]heptyl, azabicyclo[2.2.1]heptyl, azabicyclo[3.2.1]octyl, azabicyclo[2.2.2]octyl, diazabicyclo[3.1.1]heptyl, diazabicyclo[2.2.1]heptyl, diazabicyclo[3.2.1]octyl (e.g., 3,8-diazabicyclo[3.2.1]octane-3-yl), diazabicyclo[2.2.2]octane (e.g., 2,5-diazabicyclo[2.2.2]octane-2-yl).

[0421] In some embodiments, X1 of formula (PBM-5-1A) represents N, X2 represents N, and X3 represents CH.

[0422] In some embodiments, X1 of formula (PBM-5-1A) represents N, X2 represents N, and X3 represents N.

[0423] In some embodiments, X1 of formula (PBM-5-1A) represents N, X2 represents CH, and X3 represents CH.

[0424] In some embodiments, X1 of formula (PBM-5-1A) represents N, X2 represents CH, and X3 represents N.

[0425] In some embodiments, X1 of formula (PBM-5-1A) represents CR 5f , where R 5f is hydrogen or represents amino, X2 represents N, and X3 represents N.

[0426] In some embodiments, X1 of formula (PBM-5-1A) represents CR 5f , where R 5f is hydrogen or represents amino, X2 represents N, and X3 represents CH.

[0427] In some embodiments, X1 of formula (PBM-5-1A) represents CR5f , where R 5f is hydrogen or represents amino, X2 represents CH, and X3 represents N.

[0428] In some embodiments, X1 of formula (PBM-5-1A) represents CR 5f , where R 5f is hydrogen or represents amino, X2 represents CH, and X3 represents CH.

[0429] In some embodiments, PBM represents the structure of the following formula (PBM-5-1):

[0430] In some embodiments, the PBM represents a small molecule ligand for CDK4 / 6.

[0431] In some embodiments, PBM represents the structure of Formula (PBM-6-1A), Formula (PBM-6-1B), Formula (PBM-6-1C), or Formula (PBM-6-1D):

[0432] in

[0433] Each R 6e Each independently represents deuterium, hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), -C(O)-C 1-6 Alkyl (e.g. -C(O)-C 1-5 Alkyl or -C(O)-C 1-3 Alkyl, such as -C(O)-CH3, -C(O)-CH2CH3), -C(O)-deuterated C 1-6 Alkyl (e.g. -C(O)-deuterated C 1-5 Alkyl or -C(O)-deuterated C1-3 Alkyl, such as -C(O)-CD3) or -C(O)NR 6f R 6g , where R 6f 、R 6g are the same or different and each independently represent hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), and R 6f 、R 6g Not simultaneously hydrogen;

[0434] Each X5 independently represents N or CR 6h , where R 6h represents hydrogen, deuterium, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0435] X6 and X7 each independently represent CH or N;

[0436] R in formula (PBM-6-1B) and formula (PBM-6-1D) 6aEach independently represents an optionally substituted heteroarylene group (e.g., an optionally substituted 5- to 20-membered monocyclic or bicyclic or polycyclic aromatic ring group containing 1 or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen and sulfur), wherein the heteroarylene group is optionally substituted by 1-2 groups each independently selected from halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof;

[0437] Each R 6b Each independently represents hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or optionally substituted C 3-12 Cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl or cycloheptyl, which may be optionally substituted, for example, with halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 substituted with a substituent on the alkyl group);

[0438] Each (R 6c ) p6a Each independently represents the pyridine ring connected thereto which is optionally replaced by p6a R 6c Replace, each R 6c are the same or different and each independently represent deuterium, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), p6a represents an integer 0, 1, 2 or 3; and

[0439] Each (R 6d )p6b Each independently represents a bicyclic nitrogen-containing heteroaromatic ring connected thereto which is optionally replaced by p6b R 6d Replace, each R 6d are the same or different and each independently represent deuterium, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), p6b represents an integer of 0 or 1.

[0440] In some embodiments, R in Formula (PBM-6-1B) and Formula (PBM-6-1D) 6aEach independently represents an optionally substituted heteroarylene, such as an optionally substituted 5- to 14-membered monocyclic or bicyclic or polycyclic heteroarylene containing 1 or more (e.g. 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen and sulfur. Examples of heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, Benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, 4H-fluoro[3,2-b]pyrroleylene, pyrrolo[2,1-b]thiazolylene and imidazo[2,1-b]thiazolylene. The heteroarylene group is optionally substituted with one or more (e.g., 1-4, such as 1, 2, 3, or 4) substituents selected from halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0441] In some embodiments, PBM represents the structure of Formula (PBM-6-1), Formula (PBM-6-2), or Formula (PBM-6-3):

[0442] In some embodiments, the PBM represents a small molecule ligand for ALK.

[0443] In some embodiments, PBM represents the structure of the following formula (PBM-7):

[0444] in

[0445] (R 7a ) p7a Indicates that the benzene ring connected thereto is optionally replaced by p7a R 7a Replace, each R 7a Each independently represents deuterium, cyano, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), p7a represents an integer 0, 1, 2 or 3; and

[0446] (R 7b ) p7b Indicates that the benzene ring connected thereto may be optionally replaced by p7b R 7b Replace, each R 7b Each independently represents deuterium, cyano, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), p7b represents an integer 0, 1, 2, 3 or 4; and

[0447] Each R 7c and R 7d The same or different and each independently is deuterium, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogen (such as fluorine, chlorine, bromine or iodine), halo-C 1-6 Alkyl (such as fluorine, chlorine, bromine or iodine), deuterated C1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0448] In some embodiments, PBM represents the structure of the following formula (PBM-7-1):

[0449] In some embodiments, PBM represents the structure of the following formula (PBM-8):

[0450] in

[0451] X8, X9, X in formula (PBM-8) 10 、X 11 and X 12 are the same or different and each independently represent N or CH;

[0452] R 8a represents a bond or an optionally substituted methylene group (e.g., a halogen-substituted methylene group);

[0453] R 8b Represents -C(O)N(R 8f )R 8e 、-N(R 8f )C(O)R 8e 、-S(O)2N(R 8f )R 8e 、-N(R 8f )S(O)2R 8e 、-S(O)2R 8e or -P(O)(R 8e )2, where each R 8e The same or different and each independently represents C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), R 8f Represents hydrogen or C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl);

[0454] (R 8c ) p8a Indicates that it is connected to X9 and X 10 The six-membered ring is optionally replaced by p8a R 8c Replace, each R 8c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0455] p8a represents the integer 0, 1, 2, 3, or 4; and

[0456] R 8d represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0457] In some embodiments, R in formula (PBM-8) 8a In other words, the X in formula (PBM-8) 11 and X 12 The six-membered ring is directly connected to -NH-.

[0458] In some embodiments, R in formula (PBM-8) 8a represents an optionally substituted methylene group (eg, a halogen-substituted methylene group).

[0459] In some embodiments, PBM represents the structure of the following formula (PBM-8-1A):

[0460] in

[0461] X8, X9 and X 10 are the same or different and each independently represent N or CH;

[0462] R 8b Represents -C(O)N(R 8f )R 8e 、-N(R 8f )C(O)R 8e 、-S(O)2N(R 8f )R 8e 、-N(R 8f )S(O)2R 8e 、-S(O)2R 8e or -P(O)(R 8e )2, where each R 8e The same or different and each independently represents C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), R 8f Represents hydrogen or C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl);

[0463] (R 8c ) p8a Indicates that it is connected to X9 and X 10 The six-membered ring is optionally replaced by p8a R 8c Replace, each R 8c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0464] p8a represents the integer 0, 1, 2, 3, or 4; and

[0465] R 8d represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0466] In some embodiments, PBM represents a structure of the following formula (PBM-8-1B):

[0467] in

[0468] X9 and X 10 are the same or different and each independently represent N or CH;

[0469] R 8b Represents -C(O)N(R 8f )R 8e 、-N(R 8f )C(O)R 8e 、-S(O)2N(R 8f )R 8e 、-N(R 8f )S(O)2R 8e 、-S(O)2R 8e or -P(O)(R 8e )2, where each R 8e The same or different and each independently represents C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), R 8f Represents hydrogen or C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl);

[0470] (R 8c ) p8a Indicates that it is connected to X9 and X 10 The six-membered ring is optionally replaced by p8a R 8c Replace, each R8c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-); and

[0471] p8a represents an integer 0, 1, 2, 3, or 4.

[0472] In some embodiments, PBM represents the structure of the following Formula (PBM-8-1) or Formula (PBM-8-2):

[0473] In some embodiments, the PBM represents a small molecule ligand for BCR-ABL.

[0474] In some embodiments, the PBM represents the structure of formula (PBM-9):

[0475] in

[0476] R 9a represents -NHC(O)- or -C(O)NH-;

[0477] R 9b Indicates -NH-, -N(C1-6 alkyl)- or ethynylene;

[0478] Ring D represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S, (R 9c ) p9a Indicates that the ring D is optionally replaced by p9a R 9c Replace, and each R 9c The same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1- 3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-);

[0479] p9a represents an integer 0, 1, 2, or 3;

[0480] Each (R 9d ) p9b Each independently represents that the benzene ring connected thereto is each independently optionally replaced by p9b R 9d Replace, each R 9d The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-); and

[0481] Each p9b is the same or different and independently represents an integer of 0, 1, 2, 3 or 4.

[0482] In some embodiments, ring D in formula (PBM-9) represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1-4 heteroatoms selected from N, O, and S. In one subembodiment, examples of 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl groups include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3 ]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. The heteroaryl group is optionally replaced by p9a R 9c substituted, p9a represents an integer of 0, 1, 2, or 3, and each R 9c The same or different and each independently represent: optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0483] In some embodiments, R in formula (PBM-9) 9c represents an optionally substituted 5- to 15-membered heteroaryl. In some embodiments, the 5- to 15-membered heteroaryl is a 5- to 14-membered monocyclic or bicyclic aromatic ring group containing 1 or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some subembodiments, examples of heteroaryl include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo The heteroaryl group is optionally substituted with one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents, wherein the substituents are optionally selected from: halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, cyano, amino, C- pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, or imidazo[1,2-b]pyridazinyl. 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0484] In some embodiments, R in formula (PBM-9) 9b It represents -NH-.

[0485] In some embodiments, R in formula (PBM-9) 9b It represents an ethynylene group.

[0486] In some embodiments, PBM represents the structure of the following formula (PBM-9-1A):

[0487] in

[0488] R 9a represents -NHC(O)- or -C(O)NH-;

[0489] Ring D represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S, (R 9c ) p9a Indicates that the ring D is optionally replaced by p9a R 9c Replace, and each R 9c The same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1- 3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-);

[0490] p9a represents an integer 0, 1, 2, or 3;

[0491] Each (R 9d ) p9b Each independently represents that the benzene ring connected thereto is each independently optionally replaced by p9b R 9d Replace, each R 9d The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-); and

[0492] Each p9b is the same or different and independently represents an integer of 0, 1, 2, 3 or 4.

[0493] In some embodiments, ring D in formula (PBM-9-1A) represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1-4 heteroatoms selected from N, O, and S. In one subembodiment, examples of 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl groups include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3 ]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. The heteroaryl group is optionally replaced by p9a R 9c substituted, p9a represents an integer of 0, 1, 2, or 3, and each R 9c The same or different and each independently represent: optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0494] In some embodiments, R in formula (PBM-9-1A) 9c represents an optionally substituted 5- to 15-membered heteroaryl. In some embodiments, the 5- to 15-membered heteroaryl is a 5- to 14-membered monocyclic, bicyclic, or polycyclic aromatic ring group containing 1 or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some subembodiments, examples of heteroaryl include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo The heteroaryl group is optionally substituted with one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents, wherein the substituents are optionally selected from: halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, cyano, amino, C- pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, or imidazo[1,2-b]pyridazinyl. 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0495] In some embodiments, PBM represents the structure of the following formula (PBM-9-1):

[0496] In some embodiments, PBM represents the structure of the following formula (PBM-21):

[0497] in

[0498] R in formula (PBM-21) 21a represents NHC(O), C(O)NH, NHS(O)2 or S(O)2NH;

[0499] (R 21b ) p21a The benzene ring connected thereto may be optionally replaced by p21a R 21b Replace, and each R 21b are each independently halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy) or halogenated C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), and p21a represents an integer 0, 1, 2, 3, 4 or 5; and

[0500] (R 21c ) p21b Indicates that the 1H-pyrazole ring connected thereto is optionally replaced by p21b R 21c Replace, and each R 21c are each independently halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy) or halogenated C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), and p21b represents an integer 0, 1 or 2.

[0501] In some embodiments, p21a in Formula (PBM-21) represents an integer of 1, and R 21b is halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy) or halogenated C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example, F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-). In some embodiments, R 21b It is F2ClC-O-.

[0502] In some embodiments, R 21a In some embodiments, R 21aIt represents C(O)NH.

[0503] In some embodiments, p21b represents the integer 0.

[0504] In some embodiments, PBM represents the structure of the following formula (PBM-21-1):

[0505] In some embodiments, the PBM represents a small molecule ligand for FAK.

[0506] In some embodiments, PBM represents a structure of the following formula (PBM-8-1C):

[0507] in

[0508] X8, X in formula (PBM-8-1C) 11 and X 12 are the same or different and each independently represent N or CH;

[0509] R 8a represents a bond or an optionally substituted methylene group (e.g., a halogen-substituted methylene group);

[0510] R 8b Represents -C(O)N(R 8f )R 8e 、-N(R 8f )C(O)R 8e 、-S(O)2N(R 8f )R 8e 、-N(R 8f )S(O)2R 8e 、-S(O)2R 8e or -P(O)(R 8e )2, where each R 8e The same or different and each independently represents C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), R 8f Represents hydrogen or C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl);

[0511] (R 8c ) p8a Indicates that the benzene ring connected thereto may be optionally replaced by p8a R 8c Replace, each R 8c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0512] p8a represents the integer 0, 1, 2, 3, or 4; and

[0513] R 8d represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy groups such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0514] In some embodiments, R in formula (PBM-8-1C) 8a In other words, the X-containing 11 and X 12 The six-membered ring is directly connected to -NH-.

[0515] In some embodiments, R in formula (PBM-8-1C) 8a represents an optionally substituted methylene group (eg, a halogen-substituted methylene group).

[0516] In some embodiments, PBM represents the structure of the following formula (PBM-8-1D) or formula (PBM-8-1E):

[0517] in

[0518] X8, X 11 and X 12 are the same or different and each independently represent N or CH;

[0519] Each R 8g are the same or different and each independently represent hydrogen or halogen;

[0520] R 8b Represents -C(O)N(R 8f )R 8e 、-N(R8f )C(O)R 8e 、-S(O)2N(R 8f )R 8e 、-N(R 8f )S(O)2R 8e 、-S(O)2R 8e or -P(O)(R 8e )2, where each R 8e The same or different and each independently represents C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), R 8f Represents hydrogen or C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl);

[0521] (R 8c ) p8a Indicates that the benzene ring connected thereto may be optionally replaced by p8a R 8c Replace, each R 8c The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0522] p8a represents the integer 0, 1, 2, 3, or 4; and

[0523] R 8d represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, amino, cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0524] In some embodiments, PBM represents the structure of Formula (PBM-8-3), Formula (PBM-8-4), Formula (PBM-8-5), Formula (PBM-8-6), Formula (PBM-8-7), or Formula (PBM-8-8):

[0525] In some embodiments, PBM represents the structure of the following formula (PBM-22):

[0526] where R 22a Indicates N or CH;

[0527] R 22b represents O, S, NH, CH2, CH(F) or C(F)2;

[0528] R 22c represents a bond or an optionally substituted methylene group (e.g., a halogen-substituted methylene group);

[0529] Ring G represents C 6-15 aryl, 4- to 15-membered heterocyclic group or 5- to 15-membered heteroaryl, (R 22d ) p22a Indicates that the ring G connected thereto is optionally replaced by p22a R 22d Replace, and each R 22d are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, oxo, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), and p22a represents an integer 0, 1, 2, 3 or 4;

[0530] (R 22e ) p22b Indicates that it contains R 22a The six-membered nitrogen-containing heteroaromatic ring is optionally replaced by p22b R 22e Replace, each R 22e represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), and p22b represents an integer 0, 1 or 2;

[0531] (R 22f ) p22c The benzene ring connected thereto may be optionally replaced by p22c R 22f Replace, each R 22fThe same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups such as F3C-O-, FCH2-O-, F2CH-O-, F2ClC-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 p22c represents an integer of 0, 1, 2, 3 or 4.

[0532] In some embodiments, R 22a Indicates N.

[0533] In some embodiments, R 22a Indicates CH.

[0534] In some embodiments, R 22c Indicates a key.

[0535] In some embodiments, R 22c represents an optionally substituted methylene group (eg a methylene group optionally substituted with halogen such as fluorine, chlorine, bromine or iodine).

[0536] In some embodiments, ring G represents C 6-15 Aryl, 4 to 15-membered heterocyclyl or 5 to 15-membered heteroaryl. 6-15Examples of aryl groups include, but are not limited to, phenyl and naphthyl. Examples of 4- to 15-membered heterocyclic groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, azepanyl, diazepanyl (e.g., 1,4-diazacycloheptane-1-yl), azocanyl, diazacyclooctanyl, azabicyclo[3.1.1]heptanyl , azabicyclo[2.2.1]heptyl, azabicyclo[3.2.1]octyl, azabicyclo[2.2.2]octyl, diazabicyclo[3.1.1]heptyl, diazabicyclo[2.2.1]heptyl, diazabicyclo[3.2.1]octyl (e.g., 3,8-diazabicyclo[3.2.1]octane-3-yl), diazabicyclo[2.2.2]octane (e.g., 2,5-diazabicyclo[2.2.2]octane-2-yl). Examples of 5- to 15-membered heteroaryl groups include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, isoindolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, 4H-fluoro[3,2-b]pyrrolyl, pyrrolo[2,1-b]thiazolyl, and imidazo[2,1-b]thiazolyl.

[0537] In some embodiments, (R 22d ) p22a Indicates that the ring G is optionally replaced by p22a R 22d Replace, and each R 22d are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, oxo, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), and p22a represents an integer 0, 1, 2, 3 or 4.

[0538] In some embodiments, ring G represents isoindolinyl, which may be further optionally substituted with p22a R 22d Replace, and each R 22d are the same or different and are each independently deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, oxo, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C1-6 Alkoxy (e.g., halo-C 1-4 In some embodiments, ring G represents an isoindolinyl group, which may be further substituted with halogen (e.g., fluorine, chlorine, bromine or iodine), oxo and C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl).

[0539] In some embodiments, (R 22e ) p22b Indicates that it contains R 22a The six-membered nitrogen-containing heteroaromatic ring is optionally replaced by p22b R 22e Replace, each R 22e represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy (e.g. C 1- 4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), and p22b represents an integer 0, 1, or 2. In some embodiments, each R 22e Each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 Alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), and p22b represents an integer of 0, 1 or 2.

[0540] In some embodiments, (R 22f ) p22c The benzene ring connected thereto may be optionally replaced by p22c R 22f Replace, each R 22f The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), and p22c represents an integer 0, 1, 2, 3, or 4. In some embodiments, each R 22f Each independently represents a halogen (such as fluorine, chlorine, bromine or iodine) or C 1-6 Alkoxy (e.g. C 1- p22c represents an integer of 0, 1, 2, 3 or 4.

[0541] In some embodiments, PBM represents the structure of Formula (PBM-22-1A), Formula (PBM-22-1B), Formula (PBM-22-1C), Formula (PBM-22-2A), Formula (PBM-22-2B), or Formula (PBM-22-2C):

[0542] Among them, R 22a 、R 22c 、(R 22d ) p22a 、(R 22e ) p22b and (R 22f ) p22c As defined in each embodiment of Formula (PBM-22) and each subembodiment thereof.

[0543] In some embodiments, PBM represents the following structure of Formula (PBM-22-1), Formula (PBM-22-2), Formula (PBM-22-3), or Formula (PBM-22-4):

[0544] In some embodiments, PBM represents a small molecule ligand of ER.

[0545] In some embodiments, PBM represents the following structure of Formula (PBM-10-1A) or Formula (PBM-10-1B) (which are non-limiting examples of structures of Formula (PBM-10)):

[0546] in

[0547] Each R 10d Each independently represents O, S or CH2;

[0548] (R 10c ) p10a Indicates containing R10d The benzo-fused six-membered ring is optionally replaced by p10a R 10c Replace, each R 10c The same or different and each independently represents hydrogen, hydroxy, halogen (such as fluorine, chlorine, bromine or iodine), hydroxy, cyano, amino, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0549] p10a represents an integer 0, 1, 2, 3, or 4; and

[0550] R 10a and R 10b Each independently represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0551] In some embodiments, PBM represents the structure of Formula (PBM-10-1), Formula (PBM-10-2), Formula (PBM-10-3), Formula (PBM-10-4), Formula (PBM-10-5), Formula (PBM-10-6), Formula (PBM-10-7), Formula (PBM-10-8), Formula (PBM-10-9), Formula (PBM-10-10), Formula (PBM-10-11), or Formula (PBM-10-12):

[0552] In some embodiments, the PBM represents a small molecule ligand of IRAK4.

[0553] In some embodiments, PBM represents the structure of the following formula (PBM-11):

[0554] in

[0555] Ring E in formula (PBM-11) represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O and S;

[0556] R 11b represents an optionally substituted 5- to 15-membered heteroaryl, an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-);

[0557] R 11a represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0558] In some embodiments, ring E in formula (PBM-11) represents a 5- to 20-membered monocyclic, bicyclic, or polycyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O, and S. In some embodiments, the 5- to 20-membered monocyclic, bicyclic, or polycyclic heteroarylene group is a 5- to 14-membered monocyclic, bicyclic, or polycyclic divalent aromatic ring group containing 1 to 4 (e.g., 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some subembodiments, examples of 5- to 20-membered monocyclic or bicyclic or polycyclic heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo [2,1,3]oxadiazole group, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylene, imidazo[2,1-b]thiazolylene or imidazo[1,2-b]pyridazinylene. The 5- to 20-membered monocyclic or bicyclic or polycyclic heteroarylene group is optionally further substituted by one or more (eg, 1-3, such as 1, 2, or 3) substituents R 11b Replace, each R 11b Each independently represents an optionally substituted 5- to 15-membered heteroaryl, an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 The alkylene group is substituted with alkoxy, for example, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0559] In some embodiments, R in formula (PBM-11) 11brepresents an optionally substituted 5- to 15-membered heteroaryl. In some embodiments, the 5- to 15-membered heteroaryl is a 5- to 15-membered monocyclic, bicyclic, or polycyclic aromatic ring group containing 1-4 (e.g., 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some subembodiments, examples of heteroaryl include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo R is benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. 11b The heteroaryl represented by is optionally further substituted by one or more (eg, 1-3, such as 1, 2, or 3) substituents, wherein the substituents are optionally selected from: -N(R 11c )-C 1-6 Alkylene-optionally substituted C 3-8 Cycloalkyl, -N(R 11c )-optionally halogenated C 1-6 Alkyl, halogen (such as fluorine, chlorine, bromine or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof, wherein each R 11c independently represents hydrogen or C 1-3 In some embodiments, R 11b The substituent of the heteroaryl represented by 11c )-C 1-6 Alkylene-optionally substituted C 3-8 Cycloalkyl, where R 11c Represents hydrogen or C 1-3 In some embodiments, C 1-6 Examples of alkylene groups include, but are not limited to, C 1- In some embodiments, C 3-8 Examples of cycloalkyl groups include, but are not limited to, C 3-6 In some embodiments, C 3-8 Representative examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. 3-8 The cycloalkyl group may be further substituted by one or more (eg 1-3, such as 1, 2, or 3) groups selected from C1-C3 alkyl, C 3- 6 cycloalkyl, hydroxyl, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino substituted C 1- 3 alkylene, cyano or any combination thereof. In some embodiments, R 11b The substituent of the heteroaryl represented by 11c )-optionally halogenated C 1-6 Alkyl, where R 11c Represents hydrogen or C 1-3 In some embodiments, the alkyl group is optionally halogenated. 1-6 Examples of alkyl groups include, but are not limited to, optionally halogenated C 1-4 Alkyl, optionally halogenated C 1-3 Alkyl and optionally halogenated C 1-2 In some embodiments, the alkyl group may be optionally halogenated. 1-6 Representative examples of alkyl groups include, but are not limited to, -CH2-CF3.

[0560] In some embodiments, R in formula (PBM-11) 11b Represents an optionally substituted 5- to 15-membered heterocyclic radical. In some sub-embodiments, "5- to 15-membered heterocyclic radical" refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not completely conjugated) cycloalkyl group containing one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) 5 to 15-membered monocyclic, bicyclic, or tricyclic heteroatoms independently selected from sulfur, oxygen, and nitrogen. In some sub-embodiments, the example of heterocyclic radical includes but is not limited to azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazacycloheptane-1-yl) and diazepanyl. The heterocyclic group may be optionally substituted with one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2 or 1) selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, halogenated C 1-6 The alkyl group is substituted with an alkoxy group or any combination thereof.

[0561] In some embodiments, PBM represents the structure of Formula (PBM-11-1), Formula (PBM-11-2), Formula (PBM-11-3), or Formula (PBM-11-4):

[0562] In some embodiments, PBM represents the structure of the following formula (PBM-12):

[0563] in

[0564] R in formula (PBM-12) 12a represents an optionally substituted 5- to 15-membered heterocyclyl, an optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-); and

[0565] R 12b represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1-4 heteroatoms selected from N, O and S, which is optionally substituted by one or more (e.g. 1-6, such as 1, 2, 3, 4, 5 or 6) selected from deuterium, halogen (e.g. fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0566] In some embodiments, R in formula (PBM-12) 12a Represents an optionally substituted 5- to 15-membered heterocyclic radical. In some sub-embodiments, "5- to 15-membered heterocyclic radical" refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not completely conjugated) cycloalkyl group containing one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) 5 to 15-membered monocyclic, bicyclic, or tricyclic heteroatoms independently selected from sulfur, oxygen, and nitrogen. In some sub-embodiments, the example of heterocyclic radical includes but is not limited to azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazacycloheptane-1-yl) and diazepanyl. The heterocyclic group may be optionally substituted with one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2 or 1) selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 3-6 Cycloalkyl, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0567] In some embodiments, R in formula (PBM-12) 12b represents an optionally substituted 5- to 20-membered (e.g., 5- to 15-membered, 5- to 10-membered, or 5- to 6-membered) monocyclic or bicyclic or polycyclic heteroaryl group containing 1-4 heteroatoms selected from N, O, and S. In some subembodiments, examples of heteroaryl groups include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]oxadiazolyl] ...], benzo[2,1,3]oxadiazolyl], benzo[2,1,3]oxadiazolyl], benzo[2,1,3]ox The heteroaryl group is optionally substituted with one or more (e.g., 1-3, e.g., 1, 2, or 3) substituents, wherein the substituents are optionally selected from: halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C- pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0568] In some embodiments, PBM represents the structure of Formula (PBM-12-1), Formula (PBM-12-2), or Formula (PBM-12-3):

[0569] In some embodiments, PBM represents the structure of the following formula (PBM-20):

[0570] in

[0571] R in formula (PBM-20) x1 Indicates a bond or C(O), or R x1 Represents -C(O)NH-R x2 -C(O)-***, where the symbol *** represents the c The connection point, and R x2 represents an optionally substituted C 3-15 Cycloalkyl;

[0572] (R 20a ) p20a The 1H-pyrrolo[2,3-b]pyridine ring connected thereto is optionally replaced by p20a R 20a Replace, and each R 20a are each independently cyano, halogen (such as fluorine, chlorine, bromine or iodine), hydroxy, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), and p20a represents an integer 0, 1, 2, 3, 4 or 5;

[0573] (R 20b ) p20b Indicates that the pyridine ring connected thereto is optionally replaced by p20b R 20b Replace, and each R 20b are each independently cyano, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or NR 20c R 20d , where R 20c 、R 20d are the same or different and each independently represent hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally substituted C 3-15 p20b represents an integer of 0, 1, 2 or 3; p20c represents an optionally substituted 4- to 15-membered heterocyclic group; and p20d represents an integer of 0, 1, 2 or 3.

[0574] In some embodiments, R in formula (PBM-20) x1 Indicates a key.

[0575] In some embodiments, R in formula (PBM-20) x1 Represents C(O).

[0576] In some embodiments, R in formula (PBM-20) x1 Represents -C(O)NH-R x2 -C(O)-***, where the symbol *** represents the c The connection point, and R x2 represents an optionally substituted C 3-15 In some subembodiments, the optionally substituted C 3-15Examples of cycloalkyl groups include, but are not limited to, optionally substituted C 3-11 Cycloalkyl and optionally substituted C 3-8 Cycloalkyl, such as optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, optionally substituted cyclohexyl, optionally substituted cycloheptyl, or optionally substituted cyclooctyl. 3-15 The cycloalkyl group is optionally substituted with one or more (e.g., 1-3, 1, 2, or 3) substituents selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0577] In some embodiments, (R 20a ) p20a The 1H-pyrrolo[2,3-b]pyridine ring in the formula (PBM-20) is optionally replaced by p20a R 20a Replace, and each R 20a are each independently cyano, halogen (such as fluorine, chlorine, bromine or iodine), hydroxy, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), and p20a represents an integer 0, 1, 2, 3, 4 or 5.

[0578] In some embodiments, (R 20a ) p20a In the formula (PBM-20), the 1H-pyrrolo[2,3-b]pyridine ring connected to it is replaced by p20a R 20a substituted, wherein p20a represents the integer 1, and R 20a It's cyano.

[0579] In some embodiments, (R 20b ) p20b Indicates that the pyridine ring connected thereto is optionally replaced by p20b R 20b Replace, and each R 20b are each independently cyano, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or NR 20c R 20d , where R 20c 、R 20d are the same or different and each independently represent hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally substituted C 3-15 Cycloalkyl (eg, optionally substituted C 3-12 Cycloalkyl and optionally substituted C 3-8cycloalkyl) or an optionally substituted 4- to 15-membered heterocyclyl (e.g., an optionally substituted 4- to 12-membered heterocyclyl or an optionally substituted 4- to 10-membered heterocyclyl), and p20b represents an integer 0, 1, 2, or 3. In some subembodiments, the optionally substituted C 3-15 Examples of cycloalkyl include, but are not limited to, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, optionally substituted cyclohexyl, optionally substituted cycloheptyl, or optionally substituted cyclooctyl. In some subembodiments, examples of optionally substituted 4- to 15-membered heterocyclyl include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azepanyl, diazepanyl, azooctanyl, or diazaoctanyl. In some subembodiments, optionally substituted C 3-15 The substituents of the cycloalkyl and optionally substituted 4- to 15-membered heterocyclyl are optionally selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0580] In some embodiments, (R 20b ) p20b Indicates that the pyridine ring connected to it is p20b R 20b Substitution, wherein p20b represents the integer 1, and R 20b It is NR 20c R 20d , where R 20c represents hydrogen, and R 20d Indicates C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl).

[0581] In some embodiments, PBM represents the following structure of Formula (PBM-20-1), Formula (PBM-20-2), Formula (PBM-20-3), or Formula (PBM-20-4):

[0582] In some embodiments, PBM represents the structure of the following formula (PBM-23):

[0583] in

[0584] R in formula (PBM-23) 23a Indicates N or CH;

[0585] R 23b represents NHC(O), C(O)NH, NHS(O)2 or S(O)2NH;

[0586] (R 23c ) p23a Indicates R-containing 23a The six-membered ring is optionally replaced by p23a R 23c Replace, each R 23c The same or different and each independently represents halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1- 4 alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1- 6 alkyl (such as halogenated C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), and p23a represents an integer 0, 1, 2, 3 or 4; and

[0587] Ring H represents a 5- to 15-membered heteroarylene group, (R 23d ) p23b Indicates that the ring H connected thereto is optionally replaced by p23b R 23d Replace, each R 23d The same or different and each independently represents halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), hydroxyl-substituted C 1-6 Alkyl, amino substituted C 1-6 Alkyl, C1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or an optionally substituted C 3-15 cycloalkyl, and p23b represents an integer of 0, 1, 2 or 3.

[0588] In some embodiments, R 23a represents N. In some embodiments, R 23a Indicates CH.

[0589] In some embodiments, (R 23c ) p23a Indicates R-containing 23a The six-membered ring is optionally replaced by p23a R 23c Replace, each R 23c The same or different and each independently represents halogen (such as fluorine, chlorine, bromine, iodine), hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g. deuterated C 1-3 Alkyl, such as CD3), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), p23a represents an integer of 0, 1, 2, 3 or 4, and contains R 23a The aromatic ring is a pyridine ring or a benzene ring. 23a The aromatic ring is a pyridine ring, R 23c represents F3C-, and p23a represents the integer 1.

[0590] In some embodiments, ring H represents a 5- to 15-membered heteroarylene group, such as a 5- to 12-membered heteroarylene group, or a 5- to 10-membered heteroarylene group. In some embodiments, examples of ring H include, but are not limited to, benzimidazolylene, benzothiazolylene, 2H-indazoleylidene, benzoxazolylene, isoindolylene, benzofurylene, isobenzofurylene, benzothiophenylene, benzisoxazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolin ... quinolinylene, quinolinylene, quinolinylene, quinolinylene, quinolinylene, quinolinylene, quinolinylene, quinolinylene, quinolin Quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, imidazo[1,2-b]pyridazinyl or 6,7-dihydro-5H-pyrrolo[1,2-c]imidazolyl. Ring H is optionally replaced by p23b R 23d Replace, each R 23d The same or different and each independently represents halogen (such as fluorine, chlorine, bromine, iodine), hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g. deuterated C 1-3Alkyl, such as CD3), hydroxy substituted C 1-6 Alkyl (e.g. hydroxy substituted C 1-4 Alkyl, such as hydroxypropyl, hydroxyisopropyl), amino-substituted C 1-6 Alkyl (e.g. amino substituted C 1-4 Alkyl, such as aminopropyl, aminoisopropyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, F2ClC-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or an optionally substituted C 3-15 cycloalkyl, and p23b represents an integer of 0, 1, 2 or 3. In some embodiments, R 23d represents hydroxypropyl or hydroxyisopropyl, and p23b represents the integer 1. In some embodiments, R 23d represents an optionally substituted C 3-15 Cycloalkyl. C 3-15 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, 2,3-dihydro-1H-indenyl, spirocyclyl (e.g., C 5-15 Spirocyclyl), adamantyl, noradamantyl and norbornyl. C 3-15 Optional substituents of the cycloalkyl group are optionally selected from halogen (eg, fluorine, chlorine, bromine or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), and halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0591] In some embodiments, PBM represents the structure of Formula (PBM-23-1), Formula (PBM-23-2), Formula (PBM-23-3), Formula (PBM-23-4), Formula (PBM-23-5), Formula (PBM-23-6), Formula (PBM-23-7), Formula (PBM-23-8), Formula (PBM-23-9), Formula (PBM-23-10), Formula (PBM-23-11), Formula (PBM-23-12), or Formula (PBM-23-13):

[0592] In some embodiments, the PBM represents a small molecule ligand for CDK9.

[0593] In some embodiments, PBM represents the structure of the following formula (PBM-13):

[0594] in

[0595] R in formula (PBM-13) 13g Indicates N or CR 13h , where R 13h represents hydrogen or halogen (such as fluorine, chlorine, bromine or iodine), R 13i Indicates N or CR 13j , where R 13j represents hydrogen or a halogen (for example, fluorine, chlorine, bromine or iodine);

[0596] R 13f represents a bond, -C(O)NH-, -NHC(O)-, -S(O)2NH- or -NHS(O)2-;

[0597] (R 13a ) p13a In the expression (PBM-13), R 13g and R 13iThe six-membered ring is optionally replaced by p13a R 13a Replace, each R 13a The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), and halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-);

[0598] p13a represents an integer 0, 1, or 2;

[0599] R 13b represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or -C 1-3 Alkylene-C 3-6 Cycloalkyl;

[0600] R 13c Represents hydrogen, C 1-6 Alkyl (e.g. C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl or halogenated C 1-3 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); or

[0601] R 13b and R 13c together with the corresponding nitrogen and carbon atoms to which they are respectively attached, form an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring;

[0602] R 13d Represents hydrogen or R c , R 13e Represents hydrogen or R c , where R 13d and R 13e are not hydrogen at the same time, and R 13d and R 13e There is only one representation R c , and the other represents hydrogen. (In other words, R 13d and R 13e One of them represents R c , and the other represents hydrogen).

[0603] In some embodiments, R in formula (PBM-13) 13f Indicates a key.

[0604] In some embodiments, R in formula (PBM-13) 13fIt represents -C(O)NH-, -NHC(O)-, -S(O)2NH- or -NHS(O)2-.

[0605] In some embodiments, R in formula (PBM-13) 13b represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or -C 1-3 Alkylene-C 3-6 Cycloalkyl (e.g., methylene-cyclopropyl); and / or

[0606] R 13c Represents hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0607] In some embodiments, R in formula (PBM-13) 13b and R 13cTogether with the corresponding nitrogen atoms and carbon atoms to which they are each connected, an optionally substituted 5- to 7-membered nitrogen-containing heterocycle is formed. In some embodiments, the 5- to 7-membered nitrogen-containing heterocycle includes, but is not limited to, for example, a 5- to 7-membered (e.g., 5 to 6-membered, 5-membered) heterocycle containing a nitrogen atom and optionally containing a heteroatom selected from nitrogen, oxygen, and sulfur. The 5- to 7-membered nitrogen-containing heterocycle is fused with the pyrazole ring in formula (PBM-13) to form a fused ring, such as, but not limited to, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole ring. The 5- to 7-membered nitrogen-containing heterocycle is optionally substituted by one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, 1 to 3, or 2) substituents selected from the following: halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, amino, cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1- 5-alkyl or fully deuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.).

[0608] In some embodiments, R 13b and R 13c The 5- to 7-membered nitrogen-containing heterocyclic ring formed together with the corresponding nitrogen atom and carbon atom to which they are attached is fused with the adjacent pyrazole ring to form the following group:

[0609] In some embodiments, PBM represents a structure of the following formula (PBM-13-1A):

[0610] in

[0611] R 13g Indicates N or CR 13h , where R 13h represents hydrogen or halogen, R 13i Indicates N or CR 13j , where R 13j represents hydrogen or halogen;

[0612] R 13frepresents a bond, -C(O)NH-, -NHC(O)-, -S(O)2NH- or -NHS(O)2-;

[0613] (R 13a ) p13a Indicates R-containing 13g and R 13i The six-membered ring is optionally replaced by p13a R 13a Replace, each R 13a represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0614] p13a represents an integer 0, 1, or 2;

[0615] R 13b represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or -C 1-3 Alkylene-C 3-6 cycloalkyl (e.g., -methylene-cyclopropyl);

[0616] R 13c Represents hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); or

[0617] R 13b and R 13c Together with the corresponding nitrogen atom and carbon atom to which they are respectively attached, they form an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring.

[0618] In some embodiments, PBM represents a structure of the following formula (PBM-13-1B):

[0619] in

[0620] R 13g Indicates N or CR 13h , where R 13h represents hydrogen or halogen, R 13i Indicates N or CR 13j , where R 13j represents hydrogen or halogen;

[0621] (R13a ) p13a Indicates R-containing 13g and R 13i The six-membered ring is optionally replaced by p13a R 13a Replace, each R 13a represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0622] p13a represents an integer 0, 1, or 2;

[0623] R 13b represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or -C 1-3 Alkylene-C 3-6 cycloalkyl (e.g., -methylene-cyclopropyl);

[0624] R 13c Represents hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); or

[0625] R 13b and R 13c Together with the corresponding nitrogen atom and carbon atom to which they are respectively attached, they form an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring.

[0626] In some embodiments, R in Formula (PBM-13-1A) and Formula (PBM-13-1B) 13b Each independently represents hydrogen, halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-) or -C 1-3 Alkylene-C 3-6 Cycloalkyl (eg, -methylene-cyclopropyl).

[0627] In some embodiments, R in Formula (PBM-13-1A) and Formula (PBM-13-1B) 13c Each independently represents hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0628] In some embodiments, R in formula (PBM-13-1A) 13b and R 13c Each independently represents hydrogen.

[0629] In some embodiments, R in formula (PBM-13-1B) 13b represents -methylene-cyclopropyl, R 13c Represents a methyl group.

[0630] In some embodiments of Formula (PBM-13-1A) and Formula (PBM-13-1B), the pyrazole ring is connected to the ring consisting of R 13b and R 13c The nitrogen-containing heterocyclic rings, together with the corresponding nitrogen and carbon atoms to which they are attached, are fused to form the following groups:

[0631] In some embodiments, PBM represents the structure of the following Formula (PBM-13-1) or Formula (PBM-13-2):

[0632] In some embodiments, PBM represents the structure of the following formula (PBM-14):

[0633] in

[0634] R 14a Indicates key, C 1-3 Alkylene (e.g. methylene, ethylene or propylene) or halogenated C 1-3 an alkylene group (e.g., a halomethylene group, a haloethylene group, or a halopropylene group);

[0635] R 14b represents halogen (e.g., fluorine, chlorine, bromine or iodine), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), optionally substituted C 3-15 Cycloalkyl (eg, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, or optionally substituted cyclohexyl; or, for example, haloC 3-6 cycloalkyl, such as halocyclopropyl, halocyclobutyl, halocyclopentyl or halocyclohexyl), or an optionally substituted C 1-6 Alkyl (eg, optionally substituted C 1-5 Alkyl, optionally substituted C 1-4 Alkyl or optionally substituted C 1-3 alkyl);

[0636] (R 14c ) p14a The benzene ring in the formula (PBM-14) is optionally replaced by p14a R 14c Replace, each R 14c The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; and

[0637] p14a represents an integer 0, 1, 2, 3, or 4.

[0638] In some embodiments, R in formula (PBM-14) 14a Indicates a key.

[0639] In some embodiments, R in formula (PBM-14) 14a Indicates C 1-3 Alkylene (e.g. methylene, ethylene or propylene) or halogenated C 1-3 Alkylene (eg, halomethylene, haloethylene, or halopropylene).

[0640] In some embodiments, R in formula (PBM-14) 14b represents an optionally substituted C 3-15 Cycloalkyl, such as optionally substituted C 3-8 Cycloalkyl, such as optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl or optionally substituted cyclohexyl. 3-15 The cycloalkyl group is optionally substituted with one or more (e.g., 1-3, 1, 2, or 3) substituents selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 3-6 Cycloalkyl, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0641] In some embodiments, R in formula (PBM-14) 14b Represents cyclobutyl.

[0642] In some embodiments, PBM represents the structure of the following formula (PBM-14-1):

[0643] In some embodiments, PBM represents the structure of the following formula (PBM-15):

[0644] in

[0645] R in formula (PBM-15) 15a Indicates C 1-3 Alkylene (e.g. methylene, ethylene or propylene) or halogenated C 1-3 an alkylene group (e.g., a halomethylene group, a haloethylene group, or a halopropylene group); and

[0646] R 15b Deuterium, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or optionally substituted C 3-6 cycloalkyl; and

[0647] R 15c and R 15d Each independently represents S or O.

[0648] In some embodiments, R in formula (PBM-15)15b represents an optionally substituted C 3-6 Cycloalkyl, such as optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl or optionally substituted cyclohexyl. 3-6 The cycloalkyl group is optionally substituted with one or more (e.g., 1-3, 1, 2, or 3) substituents selected from the group consisting of deuterium, hydroxyl, amino, mercapto, nitro, cyano, halogen (e.g., fluorine, chlorine, bromine, iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally perdeuterated cyclopropyl, optionally perdeuterated cyclobutyl, optionally perdeuterated cyclopentyl, or optionally perdeuterated cyclohexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-) or any combination thereof.

[0649] In some embodiments, PBM represents a structure of the following formula (PBM-15-1):

[0650] In some embodiments, PBM represents the structure of the following formula (PBM-16):

[0651] in

[0652] R in formula (PBM-16) 16a Indicates -S- or fragment When R 16a When -S- is represented, the formula (PBM-16) contains R 16a and the nitrogen atom is a thiazolyl group, and when R 16a Representation fragment When the formula (PBM-16) contains R 16a and the heteroaryl group of the nitrogen atom is pyridyl;

[0653] R 16b Indicates N or CH;

[0654] R 16c represents hydrogen or optionally substituted C 1-10 alkyl;

[0655] R 16d Represents hydrogen, -C 1-3 alkylene-optionally substituted 4- to 10-membered heterocyclyl, or optionally substituted 4- to 10-membered heterocyclyl; and

[0656] R 16e represents a hydroxyl group, a halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0657] In some embodiments, R in formula (PBM-16) 16a represents -S-, and the formula (PBM-16) contains R 16a and the nitrogen atom is a heteroaryl group and a thiazolyl group.

[0658] In some embodiments, R in formula (PBM-16) 16a Representation fragment When the formula (PBM-16) contains R 16a and the nitrogen atom is a pyridyl group.

[0659] In some embodiments, R in formula (PBM-16) 16c represents hydrogen or optionally substituted C 1-10 In some embodiments, the optionally substituted C 1-10 Examples of alkyl groups include, but are not limited to, optionally substituted C 1-8 Alkyl, optionally substituted C 1-6 Alkyl, or optionally substituted C 1-4 In some embodiments, C 1-10 The alkyl group may be optionally substituted with one or more (e.g., 1-3, 1, 2, or 3) groups selected from deuterium, hydroxy, amino, thiol, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 3-6 The cycloalkyl group or any combination thereof is substituted.

[0660] In some embodiments, R in formula (PBM-16) 16d Represents hydrogen, -C 1-3 Alkylene - optionally substituted 4- to 10-membered heterocyclyl, or optionally substituted 4- to 10-membered heterocyclyl. In some embodiments, each optionally substituted 4- to 10-membered heterocyclyl is, for example, a 4- to 10-membered (e.g., 4-9, 4-8, 5-7, or 4-6-membered) monocyclic or bicyclic heterocyclyl containing one or more, for example, 1-4 or 1, 2, 3, or 4, heteroatoms selected from nitrogen, oxygen, and sulfur, including but not limited to azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azepanyl, diazepanyl,

[0015] In some embodiments, the present invention includes but is not limited to 1,4-diazacycloheptan-1-yl, ... In some embodiments, the 4- to 10-membered heterocyclyl is optionally selected from deuterium, hydroxy, amino, thiol, nitro, halogen (eg, fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 3-6 The cycloalkyl group or any combination thereof is substituted.

[0661] In some embodiments, PBM represents the structure of the following Formula (PBM-16-1A) or Formula (PBM-16-1B):

[0662] in

[0663] R 16b Indicates N or CH;

[0664] R 16c represents hydrogen or optionally substituted C 1-10 alkyl;

[0665] R 16d Represents hydrogen, -C 1-3 alkylene-optionally substituted 4- to 10-membered heterocyclyl, or optionally substituted 4- to 10-membered heterocyclyl; and

[0666] R 16e represents a hydroxyl group, a halogen (such as fluorine, chlorine, bromine or iodine), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0667] In some embodiments, each R in Formula (PBM-16-1A) and Formula (PBM-16-1B) 16c Each independently represents hydrogen or an optionally substituted C 1-10 In some embodiments, the optionally substituted C 1-10 Examples of alkyl groups include, but are not limited to, optionally substituted C 1-8 Alkyl, optionally substituted C 1-6 Alkyl, or optionally substituted C 1-4 In some embodiments, C 1-10 The alkyl group may be optionally substituted with one or more (e.g., 1-3, 1, 2, or 3) groups selected from deuterium, hydroxy, amino, thiol, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 3-6 The cycloalkyl group or any combination thereof is substituted.

[0668] In some embodiments, each R in Formula (PBM-16-1A) and Formula (PBM-16-1B) 16d Each independently represents hydrogen, -C 1-3 Alkylene - optionally substituted 4- to 10-membered heterocyclyl, or optionally substituted 4- to 10-membered heterocyclyl. In some embodiments, each optionally substituted 4- to 10-membered heterocyclyl is, for example, a 4- to 10-membered (e.g., 4-9, 4-8, 5-7, or 4 to 6-membered) monocyclic or bicyclic or polycyclic heterocyclyl containing one or more, for example, 1-4 or 1, 2, 3, or 4, heteroatoms selected from nitrogen, oxygen, and sulfur, including but not limited to azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azepanyl, diazepine Cycloheptyl (e.g., 1,4-diazacycloheptan-1-yl), azacyclooctanyl, diazacyclooctanyl, azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl (e.g., 3,8-diazabicyclo[3.2.1]octan-3-yl), and diazabicyclo[2.2.2]octan-2-yl (e.g., 2,5-diazabicyclo[2.2.2]octan-2-yl). In some embodiments, the 4- to 10-membered heterocyclyl is optionally selected from deuterium, hydroxy, amino, thiol, nitro, halogen (eg, fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 3-6 The cycloalkyl group or any combination thereof is substituted.

[0669] In some embodiments, PBM represents the structure of the following Formula (PBM-16-1) or Formula (PBM-16-2):

[0670] In some embodiments, the PBM represents a small molecule ligand for EZH2.

[0671] In some embodiments, PBM represents the structure of the following formula (PBM-17):

[0672] in

[0673] R in formula (PBM-17) 17a Indicates C(O)NH, NHC(O), (CH2) 1-2 C(O)NH, (CH2) 1-2 NHC(O), C(O)NH(CH2) 1-2 、NHC(O)(CH2) 1-2 , S(O)2NH or NHS(O)2;

[0674] R 17b represents hydrogen, hydroxy, halogen (such as fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-5 Alkoxy, C 1-4 Alkoxy or C 1-3 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0675] R 17c Represents hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); or

[0676] R 17b and R 17cTogether with the carbon atom and nitrogen atom to which they are attached and the carbon atom of the benzene ring to which the nitrogen atom is attached, they form an optionally substituted 4- to 6-membered heteroaryl ring or an optionally substituted 4- to 6-membered heterocyclic ring;

[0677] R 17d represents an optionally substituted C 3-6 Cycloalkyl (eg, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl or optionally substituted cyclohexyl), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or an optionally substituted 4- to 20-membered heterocyclyl;

[0678] (R 17e ) p17a Indicates that the pyridin-2(1H)-one ring connected to it is replaced by p17a R 17e Replace, each R 17e The same or different and each independently represents a hydroxyl group, a halogen (such as fluorine, chlorine, bromine or iodine), a cyano group, a C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0679] p17a represents an integer 0, 1, 2, or 3;

[0680] Ring F in formula (PBM-17) represents an arylene group or a 5- to 20-membered monocyclic or bicyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O and S; (R 17f ) p17b Indicates that the ring F is optionally replaced by p17b R 17f Replace, and each R 17f The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-); and

[0681] p17b represents an integer 0, 1, 2, 3, or 4.

[0682] In some embodiments, R in formula (PBM-17) 17a represents C(O)NH, NHC(O), CH2C(O)NH, CH2CH2C(O)NH, CH2NHC(O), CH2CH2NHC(O), C(O)NHCH2, C(O)NHCH2CH2, NHC(O)CH2, NHC(O)CH2CH2, S(O)2NH or NHS(O)2.

[0683] In some embodiments, R in formula (PBM-17) 17b represents hydrogen, hydroxy, halogen (such as fluorine, chlorine, bromine or iodine), cyano, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0684] In some embodiments, R in formula (PBM-17) 17c Represents hydrogen, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0685] In some embodiments, R in formula (PBM-17) 17b and R 17c Together with the carbon atoms and nitrogen atoms to which they are attached and the carbon atoms on the benzene ring attached to the nitrogen atom, form an optionally substituted 4- to 6-membered heteroaromatic ring (e.g., an optionally substituted 4- to 6-membered nitrogen-containing heteroaromatic ring) or an optionally substituted 4- to 6-membered heterocyclic ring (e.g., an optionally substituted 4- to 6-membered nitrogen-containing heterocyclic ring). In some embodiments, R in formula (PBM-17) 17b and R 17c Together they represent the following fragments: -CH2-, -CH=CH-, -CH=N-, -N=CH-, -N=N-, -CH2-CH2-, -NH-CH2-, or -CH2-CH2-CH2-. In some embodiments, the 4- to 6-membered nitrogen-containing heterocycle includes, but is not limited to, for example, a 4- to 6-membered (e.g., 4-, 5-, 6-membered) heterocycle containing one nitrogen atom and optionally containing a heteroatom selected from nitrogen, oxygen, and sulfur. The 4- to 6-membered nitrogen-containing heterocycle is fused with the benzene ring in formula (PBM-17) to form a fused ring. The 4- to 6-membered nitrogen-containing heterocycle is optionally substituted by one or more (e.g., 1 to 4, 1 to 3, or 2) substituents selected from the following: halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxyl, amino, cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.).

[0686] In some embodiments, R in formula (PBM-17) 17d represents an optionally substituted C 3-6 Cycloalkyl (eg, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl or optionally substituted cyclohexyl), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or an optionally substituted 4- to 20-membered heterocyclyl.

[0687] In some embodiments, R in formula (PBM-17) 17d represents an optionally substituted C 3-6 Cycloalkyl, such as optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl or optionally substituted cyclohexyl. 3-6 The cycloalkyl group is optionally substituted with one or more (e.g., 1-3, 1, 2, or 3) substituents selected from the group consisting of deuterium, hydroxy, amino, thiol, nitro, halogen, cyano, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, halogenated C 1-6alkoxy or any combination thereof.

[0688] In some embodiments, R in formula (PBM-17) 17d Represents an optionally substituted 4- to 20-membered heterocyclyl. An optionally substituted 4- to 20-membered heterocyclyl is, for example, an optionally substituted 4- to 20-membered (e.g., 4-15, 4-9, 4-8, 5-7, or 4 to 6-membered) monocyclic or bicyclic or polycyclic heterocyclyl containing one or more, for example, 1-4 or 1, 2, 3, or 4, heteroatoms selected from nitrogen, oxygen, and sulfur, including, but not limited to, the following optionally substituted groups: azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azepanyl, In some embodiments, the 4- to 20-membered heterocyclic radical is optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, halogenated C 1-6 The alkyl group is substituted with an alkoxy group or any combination thereof.

[0689] In some embodiments, ring F in formula (PBM-17) represents an arylene group (eg, C 5-20 Arylene, C 5-15 Arylene, C 5-10 Arylene, or C 5-6The term "arylene" refers to a 5- to 20-membered (e.g., 5- to 15-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, or 6-membered) monocyclic or bicyclic heteroarylene group containing 1-4 (e.g., 1 to 3, or 1 to 2) heteroatoms selected from N, O, and S. Examples of arylene groups include, but are not limited to, phenylene and naphthylene. Examples of heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, Benzo[2,1,3]thiadiazolylidene, benzo[1,2,3]thiadiazolylidene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, 4H-fluoro[3,2-b]pyrroleylene, pyrrolo[2,1-b]thiazolylidene and imidazo[2,1-b]thiazolylidene. In some embodiments, the ring F is optionally replaced by p17b R 17f Replace, and each R 17f The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1- 3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-); and p17b represents an integer 0, 1, 2, 3 or 4.

[0690] In some embodiments, PBM represents the structure of Formula (PBM-17-1A), Formula (PBM-17-1B), Formula (PBM-17-1C), Formula (PBM-17-1D), Formula (PBM-17-1E), Formula (PBM-17-1F), Formula (PBM-17-1G), Formula (PBM-17-1H), Formula (PBM-17-1I), Formula (PBM-17-1J), or Formula (PBM-17-1K):

[0691] in

[0692] Various R 17d Each independently represents an optionally substituted C 3-6 Cycloalkyl (eg, optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl or optionally substituted cyclohexyl), C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or an optionally substituted 4- to 10-membered heterocyclyl;

[0693] Various (R 17e ) p17a Each independently represents the pyridin-2(1H)-one ring of each formula being replaced by p17a R17e Replace, each R 17e The same or different and each independently represents a hydroxyl group, a halogen (such as fluorine, chlorine, bromine or iodine), a cyano group, a C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-);

[0694] p17a in each formula independently represents an integer of 0, 1, 2 or 3;

[0695] Ring F in each formula independently represents an arylene group or a 5- to 20-membered monocyclic or bicyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O and S; (R 17f ) p17b Indicates that the ring F is optionally replaced by p17b R 17f Replace, and each R 17f The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-); and

[0696] p17b in each formula independently represents an integer of 0, 1, 2, 3 or 4.

[0697] In some embodiments, each R in Formula (PBM-17-1A), Formula (PBM-17-1B), Formula (PBM-17-1C), Formula (PBM-17-1D), Formula (PBM-17-1E), Formula (PBM-17-1F), Formula (PBM-17-1G), Formula (PBM-17-1H), Formula (PBM-17-1I), Formula (PBM-17-1J), and Formula (PBM-17-1K) 17d Each independently represents an optionally substituted C 3-6 Cycloalkyl, such as optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl or optionally substituted cyclohexyl. 3-6 The cycloalkyl group is optionally substituted with one or more (e.g., 1-3, 1, 2, or 3) substituents selected from the group consisting of deuterium, hydroxy, amino, thiol, nitro, halogen, cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 3-6 cycloalkyl or any combination thereof.

[0698] In some embodiments, each R in Formula (PBM-17-1A), Formula (PBM-17-1B), Formula (PBM-17-1C), Formula (PBM-17-1D), Formula (PBM-17-1E), Formula (PBM-17-1F), Formula (PBM-17-1G), Formula (PBM-17-1H), Formula (PBM-17-1I), Formula (PBM-17-1J), and Formula (PBM-17-1K) 17dEach independently represents an optionally substituted 4- to 20-membered heterocyclic group. The optionally substituted 4- to 20-membered heterocyclic group is, for example, an optionally substituted 4- to 20-membered (e.g., 4-15, 4-12, 4-9, 4-8, 5-7, or 4 to 6-membered) monocyclic or bicyclic or polycyclic heterocyclic group containing one or more, for example, 1-4 or 1, 2, 3 or 4, heteroatoms selected from nitrogen, oxygen and sulfur, including but not limited to the following optionally substituted groups: azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxane, azacyclohexane 1 ,4-diazacycloheptane-1-yl), azacyclooctane, diazacyclooctane, azabicyclo[3.1.1]heptane, azabicyclo[2.2.1]heptane, azabicyclo[3.2.1]octane, azabicyclo[2.2.2]octane, diazabicyclo[3.1.1]heptane, diazabicyclo[2.2.1]heptane, diazabicyclo[3.2.1]octane (e.g. 3,8-diazabicyclo[3.2.1]octane-3-yl), and diazabicyclo[2.2.2]octane (e.g. 2,5-diazabicyclo[2.2.2]octane-2-yl). In some embodiments, the 4- to 20-membered heterocyclic radical is optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1- 6-alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 3-6 The cycloalkyl group or any combination thereof is substituted.

[0699] In some embodiments, each ring F in Formula (PBM-17-1A), Formula (PBM-17-1B), Formula (PBM-17-1C), Formula (PBM-17-1D), Formula (PBM-17-1E), Formula (PBM-17-1F), Formula (PBM-17-1G), Formula (PBM-17-1H), Formula (PBM-17-1I), Formula (PBM-17-1J), and Formula (PBM-17-1K) independently represents an arylene group (e.g., C 5-20 Arylene, C 5-15 Arylene, C 5-10 Arylene, or C 5-6 The term "arylene" refers to a 5- to 20-membered (e.g., 5- to 15-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, or 6-membered) monocyclic or bicyclic heteroarylene group containing 1-4 (e.g., 1 to 3, or 1 to 2) heteroatoms selected from N, O, and S. Examples of arylene groups include, but are not limited to, phenylene and naphthylene. Examples of heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, Benzo[2,1,3]thiadiazolylidene, benzo[1,2,3]thiadiazolylidene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, 4H-fluoro[3,2-b]pyrroleylene, pyrrolo[2,1-b]thiazolylidene and imidazo[2,1-b]thiazolylidene. In some embodiments, the ring F is optionally replaced by p17b R 17f Replace, and each R 17fThe same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, cyano, amino, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-...

Claims

1. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof: PBM-LIN-ULM Formula (I) Wherein PBM represents a targeting moiety capable of binding to a protein, and PBM is covalently linked to ULM via the group LIN; ULM represents a ligand moiety capable of binding to an E3 ubiquitin ligase and represents a structure of the following formula (ULM): in A represents CO, CH2 or CD2; R a1 、R a2 、R a3 and R a4 The same or different and each independently represents hydrogen, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy or halogenated C 1-6 alkoxy; (R a5 ) m represents that the isoindoline ring connected thereto is optionally replaced by m R a5 Replace, each R a5 The same or different and each independently represents halogen, hydroxyl, mercapto, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1- 6 alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 Alkynyl; m represents an integer 0, 1, 2, 3 or 4; R w represents O, S, S(O), S(O)2, alkenylene, alkynylene or N(R a6 ), where R a6 Indicates H or C 1-3 Alkyl, or R w represents a key; or R w express: Among them, each ring A 1 are the same or different and each independently represent a nitrogen-containing heterocyclic group, an arylene group or a heteroarylene group, y1 represents an integer of 1 or 2, (R y1 ) a1 Represents each ring A 1 Each independently optionally represented by a1 R y1 Group substitution, each R y1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a1 represents an integer of 0-20; Each ring A 2 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group or a heteroarylene group, y2 represents an integer of 0 or 1, (R y2 ) a2 Represents each ring A 2 independently optionally by a2 R y2 Group substitution, each R y2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2- 6 alkenyl, and a2 represents an integer of 0-20; and LIN means: where R w2 Connect PBM, R w1 Connect R w ; R w2 represents a bond, C(O), C(O)NH, or NHC(O); Each ring A 3 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, y3 represents an integer of 0, 1, 2 or 3, (R y3 ) a3 Represents each ring A 3 Independently optionally a3 R y3 Group substitution, each R y3 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a3 represents an integer of 0-10; Each ring A 4 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, y4 represents an integer of 0, 1, 2 or 3, (R y4 ) a4 Represents each ring A 4 Independently optionally by a4 R y4 Group substitution, each R y4 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a4 represents an integer of 0-10; Each ring A 5 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, y5 represents an integer of 0, 1, 2 or 3, (R y5 ) a5 Represents each ring A 5 Independently optionally a5 R y5 Group substitution, each R y5 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a5 represents an integer of 0-10; R w1 represents a bond, or represents an optionally substituted straight or branched C 1-20 Alkylene, wherein the linear or branched C 1-20 Any one or more methylene groups of the main carbon chain skeleton of the alkylene group may be optionally replaced by one or more groups selected from the following: a 、R b and any combination thereof, each group R a Each independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each R a7 Each independently represents H or C 1-3 Alkyl, and when the linear or branched C 1-20 Any two or more methylene groups of the main carbon chain skeleton of the alkylene group are replaced by two or more groups R a When substituted, each group R a Not directly connected to each other; each group R b Each is independently selected from optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene, alkynylene, alkenylene, and any combination thereof.

2. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1, wherein the PBM represents a small molecule ligand that binds to the following proteins: epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 / 6 (CDK4 / 6), anaplastic lymphoma kinase (ALK), focal adhesion kinase (FAK), breakpoint cluster region (BCR)-Abelson leukemia virus (ABL) (BCR-ABL) tyrosine kinase, Bruton tyrosine kinase (BTK), androgen receptor (AR), estrogen receptor (ER), bromodomain and extra-terminal domain protein (BTRK), androgen receptor (AR). The proteins involved in the expression of the following proteins are: BET protein, interleukin-1 receptor-associated kinase 4 (IRAK4), cyclin-dependent kinase 9 (CDK9), histone-lysine N-methyltransferase EZH2 (EZH2), BCL-2 (B cell lymphoma-2) family proteins, cyclin-dependent kinase 2 (CDK2), poly(ADP-ribose) polymerase (PARP), serine / threonine protein kinase (AKT), microtubule-associated protein tau, SWI / SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 2 / 4;SMARCA2 / 4) or ribosomal protein S6 kinase (RSK).

3. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1, wherein the PBM comprises a structure selected from the following formula: in (R 1a ) p1a Indicates that the benzene ring to which it is connected is surrounded by p1a R 1a Replace, each R 1a The same or different and each independently represents deuterium, halogen, hydroxyl, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, NO2, NH2 or cyano; p1a represents an integer 0, 1, 2, 3, 4, or 5; R 1b represents substituted or unsubstituted C 3-15 cycloalkyl groups, such as cyclopentyl; R in formula (PBM-2) 2a Indicates C 6-10 aryl or 5- to 20-membered heteroaryl, the C 6-10 Aryl and 5- to 20-membered heteroaryl are each independently optionally substituted by one or more groups each independently selected from deuterium, halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or any combination thereof; R 2b Indicates C 6-10 aryl or 5- to 20-membered heteroaryl (e.g., 5- to 20-membered heteroaryl comprising 1 or 2 5- to 7-membered rings and 1 to 4 heteroatoms selected from N, O, and S), wherein the C 6-10 Aryl and the 5- to 20-membered heteroaryl are each independently optionally substituted by one or more R 2d Replace, and each R 2d The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; (R 2c ) p2a The isoindoline ring in formula (PBM-2) is optionally replaced by p2a R 2c Replace, each R 2c The same or different and each independently represents deuterium, halogen, hydroxyl, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, NO2, NH2, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or cyano; p2a represents an integer 0, 1, 2, or 3; R in formula (PBM-3) 3a Represents hydrogen, C 1-10 Alkyl (e.g. ), deuterated C 1-10 Alkyl or halogenated C 1-10 alkyl; R 3b express or a 4- to 12-membered nitrogen-containing heterocyclic group, wherein the 4- to 12-membered nitrogen-containing heterocyclic group is optionally substituted by one or more independently selected from deuterium, halogen, hydroxyl, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, NO2, NH2, cyano or any combination thereof; Ring A in formula (PBM-4) represents C 6-10 aryl or 5- to 20-membered heteroaryl (e.g., 5- to 20-membered heteroaryl comprising 1 or 2 5- to 7-membered rings and 1-4 heteroatoms selected from N, O, and S), wherein the ring A is optionally substituted by one or more R 4a Replace, and each R 4a The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 Alkynyl; Ring B in formula (PBM-4) represents C 3-15 Cycloalkyl or 4- to 20-membered heterocyclyl (e.g., 4- to 20-membered heterocyclyl containing 1 to 4 heteroatoms selected from N, O, and S), wherein the ring B is optionally substituted by one or more R 4b Replace, and each R 4b The same or different and each independently is deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; Ring C in formula (PBM-4) represents a 5- to 20-membered heteroaryl group (e.g., a 5- to 20-membered monocyclic or bicyclic heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S), and the ring C is optionally substituted by one or more R 4c Replace, and each R 4c The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; X1 in formula (PBM-5) represents N or CR 5f , where R 5f represents hydrogen, deuterium or amino, X2 represents N or CR 5g , where R 5g represents hydrogen or represents R c , and X3 represents CH or N; R 5a and R 5b Each independently represents hydrogen or represents R c ; (R 5c ) p5a Indicates that the benzene ring connected to it is p5a R 5c Replace, each R 5c The same or different and each independently represents -O-aryl, -O-heteroaryl, 4- to 20-membered heterocyclic group, -C 1-3 Alkylene-NHC(O)-heteroaryl, -C 1-3 Alkylene-C(O)NH-heteroaryl, C 1-6 Alkyl, deuterium, deuterated C 1-6 Alkyl, halogen, or halogenated C 1-6 alkyl, the 4- to 20-membered heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 5h Replace, and each R 5h The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; p5a represents an integer 1, 2, 3, or 4; R 5d Represents R c , hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy; R 5e Represents hydrogen, halogen, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl or amino; where R 5g 、R 5a 、R 5b and R 5d are not hydrogen at the same time, and R 5g 、R 5a 、R 5b and R 5d There is only one representation R c ,in When R 5a Represents R c When X2 represents CH or N, and R 5b is hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy; When X2 represents CR 5g , where R 5g Represents R c When R 5a and R 5b are hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy; When R 5b Represents R c When X2 represents N or CH, and R 5a is hydrogen, and R 5d Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, or C 1-6 alkoxy; and When R 5d Represents R c When X2 represents N or CH, and R 5a and R 5b All are hydrogen; X4 in the formula (PBM-6) represents CR 6e or fragment The symbol # represents the connection point of N adjacent to X4, the symbol ## represents the connection point with X5, and each R 6e Each independently represents deuterium, hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-deuterated C 1-6 Alkyl or -C(O)NR 6f R 6g , where R 6f 、R 6g are the same or different and each independently represent hydrogen, C 1-6 Alkyl or deuterated C 1-6 alkyl; X5 in formula (PBM-6) represents N or CR 6h , where R 6h Represents hydrogen, deuterium, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl; X6 and X7 each independently represent CH or N; R 6a represents a bond or an optionally substituted heteroarylene (e.g., a halogen- or deuterium-substituted heteroarylene); R 6b Represents hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, or optionally substituted C 3-12 Cycloalkyl; (R 6c ) p6a Indicates that the pyridine ring connected thereto is optionally replaced by p6a R 6c Replace, each R 6c The same or different and each independently represents deuterium, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 Alkyl, p6a represents an integer of 0, 1, 2 or 3; (R 6d ) p6b represents a nitrogen-containing bicyclic heteroaromatic ring connected thereto which is optionally replaced by p6b R 6d Replace, each R 6d The same or different and each independently represents deuterium, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 Alkyl, p6b represents an integer of 0 or 1; (R 7a ) p7a Indicates that the benzene ring connected thereto is optionally replaced by p7a R 7a Replace, each R 7a are the same or different and each independently represent deuterium, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, or deuterated C 1-6 Alkyl, p7a represents an integer of 0, 1, 2 or 3; (R 7b ) p7b Indicates that the benzene ring connected thereto may be optionally replaced by p7b R 7b Replace, each R 7b are the same or different and each independently represent deuterium, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, or deuterated C 1-6 Alkyl, p7b represents an integer of 0, 1, 2, 3 or 4; Each R 7c and R 7d The same or different and each independently is deuterium, C 1-6 Alkyl, halogen, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; X8, X9, X in formula (PBM-8) 10 、X 11 and X 12 are the same or different and each independently represent N or CH; R 8a represents a bond or an optionally substituted methylene group (e.g., a halogen-substituted methylene group); R 8b Represents -C(O)N(R 8f )R 8e 、-N(R 8f )C(O)R 8e 、-S(O)2N(R 8f )R 8e 、-N(R 8f )S(O)2R 8e 、-S(O)2R 8e or -P(O)(R 8e )2, where each R 8e The same or different and each independently represents C 1-6 Alkyl or deuterated C 1-6 Alkyl, R 8f Represents hydrogen or C 1-6 alkyl; (R 8c ) p8a Indicates that it is connected to X9 and X 10 The six-membered ring is optionally replaced by p8a R 8c Replace, each R 8c The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p8a represents an integer 0, 1, 2, 3, or 4; R 8d Denotes deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; R in formula (PBM-9) 9a represents -NHC(O)- or -C(O)NH-; R 9b Indicates -NH-, -N(C 1-6 alkyl)- or ethynylene; Ring D in formula (PBM-9) represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S, (R 9c ) p9a Indicates that the ring D is optionally replaced by p9a R 9c Replace, and each R 9c The same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; p9a represents an integer 0, 1, 2, or 3; Each (R 9d ) p9b Each independently represents that the benzene ring connected thereto is each independently optionally replaced by p9b R 9d Replace, each R 9d The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; Each p9b is the same or different and independently represents an integer of 0, 1, 2, 3 or 4; R in formula (PBM-10) 10d represents O, S or CH2; (R 10c ) p10a The expression (PBM-10) contains R 10d The benzo-fused six-membered ring is optionally replaced by p10a R 10c Replace, each R 10c The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p10a represents an integer 0, 1, 2, 3, or 4; R 10a and R 10b There is only one representation R c , and the other represents hydrogen, halogen, hydroxy, cyano, amino, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; Ring E in formula (PBM-11) represents a 5- to 20-membered monocyclic, bicyclic, or polycyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O, and S; R 11b represents an optionally substituted 5- to 15-membered heteroaryl, an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; R 11a Represents hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; R in formula (PBM-12) 12a represents an optionally substituted 5- to 15-membered heterocyclic group, an optionally substituted 5- to 15-membered heteroaryl group, deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; R 12b represents a 5- to 20-membered monocyclic or bicyclic or polycyclic heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S, said heteroaryl group being optionally substituted by one or more radicals selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or any combination thereof; R in formula (PBM-13) 13g Indicates N or CR 13h , where R 13h represents hydrogen or halogen, R 13i Indicates N or CR 13j , where R 13j represents hydrogen or halogen; R 13f represents a bond, -C(O)NH-, -NHC(O)-, -S(O)2NH- or -NHS(O)2-; (R 13a ) p13a In the expression (PBM-13), R 13g and R 13i The six-membered ring is optionally replaced by p13a R 13a Replace, each R 13a The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p13a represents an integer 0, 1, or 2; R 13b Represents hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl or -C 1-3 Alkylene-C 3-6 Cycloalkyl; R 13c Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; or R 13b and R 13c together with the corresponding nitrogen and carbon atoms to which they are respectively attached, form an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring; R 13d Represents hydrogen or R c , R 13e Represents hydrogen or R c , where R 13d and R 13e are not hydrogen at the same time, and R 13d and R 13e There is only one representation R c ; R in formula (PBM-14) 14a Indicates key, C 1-3 Alkylene or halogenated C 1-3 alkylene; R 14b represents halogen, optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, or optionally substituted C 3-15 Cycloalkyl; (R 14c ) p14a The benzene ring in the formula (PBM-14) is optionally replaced by p14a R 14c Replace, each R 14c The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p14a represents an integer 0, 1, 2, 3, or 4; R in formula (PBM-15) 15a Indicates C 1-3 Alkylene or halogenated C 1-3 alkylene; R 15b Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, or optionally substituted C 3-6 Cycloalkyl; R 15c and R 15d Each independently represents S or O; R in formula (PBM-16) 16a Indicates -S- or fragment When R 16a When -S- is represented, the formula (PBM-16) contains R 16a and the nitrogen atom is a thiazolyl group, and when R 16a Representation fragment When the formula (PBM-16) contains R 16a and the heteroaryl group of the nitrogen atom is pyridyl; R 16b Indicates N or CH; R 16c represents hydrogen or optionally substituted C 1-10 alkyl; R 16d Represents hydrogen, -C 1-3 Alkylene-optionally substituted 4- to 10-membered heterocyclyl, or optionally substituted 4- to 10-membered heterocyclyl; R 16e Represents hydroxyl, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; R in formula (PBM-17) 17a Indicates C(O)NH, NHC(O), (CH2) 1-2 C(O)NH, (CH2) 1-2 NHC(O), C(O)NH(CH2) 1-2 、NHC(O)(CH2) 1-2 , S(O)2NH or NHS(O)2; R 17b Represents hydrogen, hydroxyl, halogen, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; R 17c Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; or R 17b and R 17c Together with the carbon atom and nitrogen atom to which they are attached and the carbon atom of the benzene ring to which the nitrogen atom is attached, they form an optionally substituted 4- to 6-membered heteroaryl ring or an optionally substituted 4- to 6-membered heterocyclic ring; R 17d represents an optionally substituted C 3-6 Cycloalkyl, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 alkyl or an optionally substituted 4- to 20-membered heterocyclic group; (R 17e ) p17a Indicates that the pyridin-2(1H)-one ring connected to it is replaced by p17a R 17e Replace, each R 17e The same or different and each independently represents hydroxyl, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p17a represents an integer 0, 1, 2, or 3; Ring F in formula (PBM-17) represents an arylene group or a 5- to 20-membered monocyclic or bicyclic heteroarylene group containing 1 to 4 heteroatoms selected from N, O and S; (R 17f ) p17b Indicates that the ring F is optionally replaced by p17b R 17f Replace, and each R 17f The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; p17b represents an integer 0, 1, 2, 3, or 4; R in formula (PBM-18) 18f 、R 18g and R 18h Each independently represents CH or N; R 18a represents a bond, S or NH; R 18b Represents R c , an optionally substituted cycloalkyl group or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclic group; R 18c Represents R c , halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, halogenated C 1-6 an alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclic group; where R 18b and R 18c R c , and R 18b and R 18c There is only one representation R c ; (R 18d ) p18a Indicates that the six-membered ring connected thereto is optionally substituted by p18a R 18d Replace, each R 18d The same or different and each independently represents hydroxyl, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p18a represents an integer 0, 1, 2, 3, or 4; (R 18e ) p18b represents a nitrogen-containing six-membered heteroaromatic ring connected thereto which is optionally replaced by p18b R 18e Replace, each R 18e The same or different and each independently represents hydroxyl, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p18b represents an integer 0, 1, or 2; R in formula (PBM-19) 19a 、R 19b 、R 19c Each independently represents CH or N; R 19d Represents -C(O)NHR 19h 、-NHC(O)R 19h 、-S(O)2NHR 19h 、-NHS(O)2R 19h 、-S(O)2R 19h or -P(O)(R 19h )2, where each R 19h The same or different and each independently represents C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; (R 19e ) p19a Indicates p19a substituent R 19e , each R 19e The same or different and each independently represents halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; p19a represents an integer 0, 1, 2, 3, or 4; (R 19f ) p19b Indicates p19b substituent R 19f , each R 19f The same or different and each independently represents halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; p19b represents an integer 0, 1, or 2; (R 19g ) p19c The benzene ring connected thereto may be optionally replaced by p19c R 19g Replace, and each R 19g Each independently represents halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy; p19c represents an integer 0, 1, 2, 3, or 4; R in formula (PBM-20) x1 Indicates a bond or C(O), or R x1 Represents -C(O)NH-R x2 -C(O)-***, where the symbol *** represents the c The connection point, and R x2 represents an optionally substituted C 3-15 Cycloalkyl; (R 20a ) p20a The 1H-pyrrolo[2,3-b]pyridine ring connected thereto is optionally replaced by p20a R 20a Replace, and each R 20a are independently cyano, halogen, hydroxy, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p20a represents an integer of 0, 1, 2, 3, 4 or 5; (R 20b ) p20b Indicates that the pyridine ring connected thereto is optionally replaced by p20b R 20b Replace, and each R 20b are independently cyano, halogen, hydroxyl, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 Alkoxy or NR 20c R 20d , where R 20c 、R 20d are the same or different and each independently represent hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally substituted C 3-15 cycloalkyl or an optionally substituted 4- to 15-membered heterocyclyl, and p20b represents an integer of 0, 1, 2 or 3; R in formula (PBM-21) 21a represents NHC(O), C(O)NH, NHS(O)2 or S(O)2NH; (R 21b ) p21a The benzene ring connected thereto may be optionally replaced by p21a R 21b Replace, and each R 21b are independently halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p21a represents an integer of 0, 1, 2, 3, 4 or 5; (R 21c ) p21b Indicates that the 1H-pyrazole ring connected thereto is optionally replaced by p21b R 21c Replace, and each R 21c are independently halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p21b represents an integer of 0, 1 or 2; R in formula (PBM-22) 22a Indicates N or CH, R 22b represents O, S, NH, CH2, CH(F) or C(F)2; R 22c represents a bond or an optionally substituted methylene group (e.g., a halogen-substituted methylene group); Ring G represents C 6-15 aryl, 4- to 15-membered heterocyclic group or 5- to 15-membered heteroaryl, (R 22d ) p22a Indicates that the ring G connected thereto is optionally replaced by p22a R 22d Replace, and each R 22d The same or different and each independently is deuterium, halogen, hydroxyl, cyano, amino, nitro, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p22a represents an integer of 0, 1, 2, 3 or 4; (R 22e ) p22b Indicates that it contains R 22a The six-membered nitrogen-containing heteroaromatic ring is optionally replaced by p22b R 22e Replace, each R 22e Each independently represents deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl, and p22b represents an integer of 0, 1 or 2; (R 22f ) p22c The benzene ring connected thereto may be optionally replaced by p22c R 22f Replace, each R 22f The same or different and each independently represents deuterium, halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl, and p22c represents an integer of 0, 1, 2, 3 or 4; R in formula (PBM-23) 23a Indicates N or CH; R 23b represents NHC(O), C(O)NH, NHS(O)2 or S(O)2NH; (R 23c ) p23a Indicates R-containing 23a The six-membered ring is replaced by p23a R 23c Replace, each R 23c The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p23a represents an integer of 0, 1, 2, 3 or 4; Ring H represents a 5- to 15-membered heteroarylene group, (R 23d ) p23b Indicates that the ring H connected thereto is optionally replaced by p23b R 23d Replace, each R 23d The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1- 6 alkyl, hydroxy substituted C 1-6 Alkyl, amino substituted C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or optionally substituted C 3-15 cycloalkyl, and p23b represents an integer of 0, 1, 2 or 3; The dashed line in formula (PBM-24) indicates the optional presence of a double bond; (R 24a ) p24a The six-membered cycloalkyl group connected thereto is optionally replaced by p24a R 24a Replace, each R 24a The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24a represents an integer of 0, 1, 2, 3, 4, 5, 6, 7 or 8; (R 24b ) p24b Indicates that the benzene ring connected thereto may be optionally replaced by p24b R 24b Replace, each R 24b The same or different and each independently represents deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24b represents an integer of 0, 1, 2, 3, 4 or 5; (R 24c ) p24c It means that the piperazinyl group connected thereto is optionally replaced by p24c R 24c Replace, each R 24c The same or different and each independently represents halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24c represents an integer of 0, 1, 2, 3, 4, 5, 6, 7 or 8; (R 24d ) p24d The benzene ring connected thereto is optionally replaced by p24d R 24d Replace, each R 24d The same or different and each independently represents halogen, hydroxyl, mercapto, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or and p24d represents an integer 0, 1, or 2; (R 24e ) p24e Indicates that the benzene ring connected thereto may be optionally replaced by p24e R 24e Replace, each R 24e The same or different and each independently represents deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, -SO2CF3, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p24e represents an integer of 0, 1, 2, 3 or 4; R 24f represents hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy or Where y represents an integer 1, 2 or 3; (R 25a ) p25a Indicates p25a substituents R 25a , each R 25a The same or different and each independently represents halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p25a represents an integer of 0, 1, 2, 3, 4 or 5; (R 25b ) p25b Indicates that the benzene ring connected thereto is optionally replaced by p25b R 25b Replace, each R 25b The same or different and each independently represents deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 alkoxy, and p25b represents an integer of 0, 1, 2, 3 or 4; and R 25c Indicates C 1-6 Alkylene or halogenated C 1-6 alkylene; (R 26a ) p26a The benzene ring connected thereto may be optionally replaced by p26a R 26a Replace, each R 26a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p26a represents an integer 0, 1, 2, 3, or 4; (R 26b ) p26b Indicates that the 4-oxo-3,4-dihydroquinazoline ring connected to it is replaced by p26b R 26b Replace, each R 26b The same or different and each independently represents halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p26b represents the integer 1, 2, 3, or 4; (R 27a ) p27a Indicates that it contains R 27d The six-membered ring is optionally replaced by p27a R 27a Replace, each R 27a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p27a represents an integer 0, 1, 2, or 3; (R 27b ) p27b Indicates p27b R 27b Substituents, each R 27b The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl or optionally substituted C 6-10 aryl; p27b represents an integer 0, 1, 2, or 3; R 27c and R 27d Each independently represents N or CH; R 27e represents hydrogen or the structure of the following formula (III): Among them (R 27g ) p27c The benzene ring connected thereto may be optionally replaced by p27c R 27g Replace, each R 27g The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p27c represents an integer 0, 1, 2, 3, or 4; n represents an integer 1, 2, 3, 4 or 5; (R 27h ) p27d Indicates p27d R 27h Substituents, each R 27h The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p27d represents an integer 0, 1, 2, 3, 4, 5, 6, or 7; and The symbol * indicates the connection point with LIN; R 27f Represents hydrogen or R c ; When R 27e When it represents hydrogen, R 27f Represents R c When R 27f When it represents hydrogen, R 27e represents the structure of formula (III); R 28a represents O, S or NH; (R 28b ) p28a Indicates that the nitrogen-containing five-membered ring connected thereto is optionally replaced by p28a R 28b Substituent substitution, each R 28b The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p28a represents an integer 0, 1, or 2; (R 28c ) p28b Indicates that the benzene ring connected thereto may be optionally replaced by p28b R 28c Substituent substitution, each R 28c The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl; p28b represents an integer 0, 1, 2, 3, or 4; (R 28d ) p28c Indicates that the benzene ring connected thereto is optionally replaced by p28c R 28d Substituent substitution, each R 28d The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl or optionally substituted C 3-15 Cycloalkyl; p28c represents an integer 0, 1, 2, 3, 4, or 5; R 29a represents S(O)2 or represents a bond; R 29b represents NH, NHC(O) or C(O)NH; R 29c Indicates CH or N; R 29d N(R 29h ), where R 29h represents H, -C(O)-optionally substituted aryl or -C(O)-optionally substituted heteroaryl; or R 29d Representation fragment The symbol ** represents the connection point with the adjacent N atom, the symbol ### represents the connection point with the adjacent C atom, and R 29i Deuterium, hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl; (R 29e ) p29a Indicates that the benzene ring connected thereto may be optionally replaced by p29a R 29e Substituent substitution, each R 29e The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl; p29a represents an integer 0, 1, 2, 3, or 4; (R 29f ) p29b Indicates that the nitrogen-containing ring connected to it is p29b R 29f Substituent substitution, each R 29f The same or different and each independently represents deuterium, amino, halogen, hydroxyl, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 alkyl, -NH-optionally substituted aryl, or -NH-optionally substituted heteroaryl; p29b represents an integer 1 or 2; (R 30a ) p30a Indicates that the three rings connected thereto are optionally connected by p30a R 30a Substituent substitution, each R 30a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 Alkyl; p30a represents an integer of 0, 1, 2, 3, 4, 5 or 6; In formula (PBM-30) represents a single bond or a double bond; The fragment of the tricyclic ring in formula (PBM-30) express where R 30f Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; Among them, when the fragment express Time, fragment express When the fragment express Time, fragment express R 30d and R 30e are the same or different and each independently represent N or CH; R in formula (PBM-31) 31a represents O, S or NH; (R 31b ) p31a Indicates R 31a The five-membered ring is optionally replaced by p31a R 31b Substituent substitution, each R 31b The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl; p31a represents an integer 0, 1, 2, or 3; (R 31c ) p31b represents a diazacyclic ring optionally replaced by p31b R 31c Substituent substitution, each R 31c The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p31b represents the integer 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Z1 represents an integer 1, 2, or 3; Z2 represents an integer 1, 2, 3, 4, 5 or 6; R in formula (PBM-32) 32a represents O, S or NH; R 32b Represents hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; Z3 represents an integer 1, 2, or 3; (R 32c ) p32a Indicates that the benzene ring connected thereto may be optionally replaced by p32a R 32c Substituent substitution, each R 32c The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl; p32a represents the integer 0, 1, 2, 3, 4, or 5; (R 32d ) p32b Indicates R-containing 32a The five-membered ring is optionally replaced by p32b R 32d Substituent substitution, each R 32d The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p32b represents the integer 0, 1 or 2; (R 32e ) p32c Indicates that the pyrazole ring connected thereto is optionally replaced by p32c R 32e Substituent substitution, each R 32e The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl; p32c represents the integer 0, 1, or 2; (R 33a ) p33a Indicates that the benzene ring connected thereto may be optionally replaced by p33a R 33a Substituent substitution, each R 33a The same or different and each independently represents deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1- 6-alkyl; p33a represents an integer 0, 1, 2, 3, 4, or 5; R in formula (PBM-33) 33b 、R 33c 、R 33d 、R 33e 、R 33f 、R 33g and R 33h The same or different and each independently represents hydrogen, deuterium, halogen, hydroxyl, amino, cyano, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 Alkyl; and R in each general formula c Each independently represents a bond, -O-, -N(R d )-, -NHC(O)-*, -C(O)NH-*, -N(R d )-R f -N(R e )-*、-R f -C(O)NH-*、-R f -NHC(O)-*、-R f -C(O)O-*、-R f -OC(O)-*, -C(O)O-*, -OC(O)-*, -R f -、-R f -N(R d )-*、-OR f -N(R d )-*、 Among them, each ring W 1 are the same or different and each independently represent a nitrogen-containing heterocyclic group, t1 represents an integer of 1 or 2, (R c1 ) m1 Indicates each ring W 1 Each independently optionally represented by m1 R c1 Group substitution, each R c1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c4 -R c3 -, where R c3 is an optional substituted C 1-6 Alkylene or optionally substituted C 2-6 Alkenylene, R c4 Represents halogen, R c5 R c6 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c5 and R c6 The same or different and each independently represents hydrogen or C 1-3 alkyl, and m1 represents an integer of 0-20; Each ring W 2 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group, or a heteroarylene group, t2 represents an integer of 0 or 1, (R c2 ) m2 Indicates each ring W 2 Independently optionally m2 R c2 Group substitution, each R c2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c8 -R c7 -, where R c7 is an optional substituted C 1-6 Alkylene or optionally substituted C 2- 6-alkenylene, R c8 Represents halogen, R c9 R c10 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c9 and R c10 The same or different and each independently represents hydrogen or C 1-3 alkyl, and m2 represents an integer of 0-20; and R d and R e Each independently represents hydrogen or C 1-6 Alkyl, R f and R g Each independently represents an optionally substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene, and the symbol * indicates the point of attachment to LIN.

4. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 3, wherein the PBM represents a structure of the following formula: where R c As defined in claim 3.

5. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph as claimed in claim 3, wherein The R c represents a bond, -O-, -NHC(O)-*, -C(O)NH-*, -C(O)O-*, -OC(O)-*, or -NH-, or R c Represents the following structure: -N(R d )-、-N(R d )-R f -N(R e )-*、-R f -C(O)NH-*、-R f -NHC(O)-*、-R f -C(O)O-*、-R f -OC(O)-*、-R f -、-R f -N(R d )-*、-O-R f -N(R d )-*、 Among them, each ring W 1 are the same or different and each independently represent a 4- to 20-membered nitrogen-containing heterocyclic group, t1 represents an integer of 1 or 2, (R c1 ) m1 Indicates each ring W 1 Each independently optionally represented by m1 R c1 Group substitution, each R c1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c4 -R c3 -, where R c3 is an optional substituted C 1- 6 alkylene or optionally substituted C 2-6 Alkenylene, R c4 Represents halogen, R c5 R c6 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c5 and R c6 The same or different and each independently represents hydrogen or C 1-3 alkyl, and m1 represents an integer of 0-20; Each ring W 2 are the same or different and each independently represent a 4- to 20-membered heterocyclylene group, C 3-20 Cycloalkylene, C 5-20 arylene, or 5- to 20-membered heteroarylene, t2 represents an integer of 0 or 1, (R c2 ) m2 Indicates each ring W 2 Independently optionally m2 R c2 Group substitution, each R c2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c8 -R c7 -, where R c7 is an optional substituted C 1-6 Alkylene or optionally substituted C 2-6 Alkenylene, R c8 Represents halogen, R c9 R c10 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c9 and R c10 The same or different and each independently represents hydrogen or C 1- 3 alkyl, and m2 represents an integer from 0 to 20; and R d and R e Each independently represents hydrogen or C 1-6 Alkyl, R f and R g Each independently represents an optionally substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene; The C 1-6 Alkylene and C 2-6 Each alkenylene group is independently optionally substituted with one or more radicals selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 Substitution of the alkoxy group by a substituent; and The symbol * indicates the connection point to LIN.

6. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in any one of claims 3 to 5, wherein Each ring W 1 are the same or different and each independently represent a 4- to 15-membered nitrogen-containing heterocyclic group, for example piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazepanylene, azaocinylene, diazaocinylene, azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo [3.2.1] octanediyl, diazabicyclo [2.2.2] octanediyl, 3-azaspiro [5.5] undecanediyl, 8-azaspiro [4.5] decanediyl, 2-oxa-8-azaspiro [4.5] decanediyl, or 3-methyl-2-oxa-8-azaspiro [4.5] decanediyl, or Among them, each ring W 1 Each independently optionally represented by m1 R c1 Group substitution, each R c1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c4 -R c3 -, where R c3 is an optional substituted C 1-6 Alkylene or optionally substituted C 2-6 Alkenylene, R c4 Represents halogen, R c5 R c6 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c5 and R c6 The same or different and each independently represents hydrogen or C 1-3 Alkyl, and the C 1-6 The alkylene group and the C 2-6 Each alkenylene group is independently optionally substituted with one or more radicals selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 The alkoxy group is substituted by a substituent, and m1 represents an integer of 0-20; and / or Each ring W 2 are the same or different and each independently represent a 4- to 15-membered nitrogen-containing heterocyclic group, C 3-15 Cycloalkylene, 6- to 15-membered arylene, or 5- to 15-membered heteroarylene, for example, piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazepanylene, azaoctinylene, diazaoctinylene, azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene, diazabicyclo[2.2.2]octanylene , 3-azaspiro[5.5]undecanylidene, 8-azaspiro[4.5]decanylidene, 2-oxa-8-azaspiro[4.5]decanylidene, 3-methyl-2-oxa-8-azaspiro[4.5]decanylidene, cyclopropylene, cyclobutylene, cyclopentylidene, cyclopentenylidene, cyclohexylidene, cyclohexenylidene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylidene, octahydro-1H-indenylidene, 2,3-dihydro-1H-indenylidene, spirocyclylene, adamantylene, noradamantylene, norbornylene, phenylene, naphthylene, furylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thienylene oxazolyl, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothiophenylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolelene, benzo[2,1,3]oxadiazolelene, benzo[2,1,3]thiadiazolylene , benzo[1,2,3]thiadiazolylidene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylidene, or imidazo[2,1-b]thiazolylidene, or Among them, each ring W 2 Independently optionally m2 R c2 Group substitution, each R c2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R c8 -R c7 -, where R c7 is an optional substituted C 1- 6 alkylene or optionally substituted C 2-6 Alkenylene, R c8 Represents halogen, R c9 R c10 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c9 and R c10 The same or different and each independently represents hydrogen or C 1-3 Alkyl, and the C 1-6 The alkylene group and the C 2-6 Each alkenylene group is independently optionally substituted with one or more deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 The substituent of the alkoxy group is substituted, and m2 represents an integer of 0-20.

7. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in any one of claims 3 to 6, wherein R c Parts of the general formulas Represents the following groups: wherein said groups are each independently optionally further substituted with one or more deuterated C 1-6 Alkyl, optionally halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, R c12 -R c11 , or any combination thereof, wherein R c11 is an optional substituted C 1-6 Alkylene or optionally substituted C 2-6 Alkenylene, R c12 Represents halogen, R c13 R c14 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c13 and R c14 The same or different and each independently represents hydrogen or C 1-3 Alkyl, the C 1-6 Alkylene and C 2-6 Each alkenylene group is independently optionally substituted with one or more radicals selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1- 6 alkyl, C 1-6 Alkoxy or halogenated C 1-6 The substituents of the alkoxy group are substituted.

8. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in any one of claims 3 to 6, wherein R c Represents the following groups: a key, -O-, -NHC(O)-*, -C(O)NH-*, -C(O)O-*, -OC(O)-*, -CH2C(O)O-*, -CH2OC(O)-*, -NH-, -N(CH3)-, -N(CH3)-(CH2)2-N(CH3)-*, -N(CH3)-(CH2)3-N(CH3)-*, -NH-(CH2)2-N(CH3)-*, -N(CH3)-(CH2)3-NH-*, -CH2-NHC(O)-*, -CH2-C(O)NH-*, -CH2-NH-*, -O-(CH2)2-N(CH3)-*, -O-(CH2)2-NH-*, or -CH2-N(CH3)-*, or wherein said groups are each independently optionally further substituted with one or more selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, R c12 -R c11 -, or any combination thereof, wherein R c11 is an optional substituted C 1-6 Alkylene or optionally substituted C 2-6 Alkenylene, R c12 Represents halogen, R c13 R c14 N-, hydroxy, carboxyl, ethynyl, or vinyl, where R c13 and R c14 The same or different and each independently represents hydrogen or C 1-3 Alkyl, the C 1-6 Alkylene and C 2-6 Each alkenylene group is independently optionally substituted with one or more radicals selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1- 6 alkoxy substituents are substituted; and the symbol * indicates the point of attachment to LIN.

9. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1, wherein the ULM represents the structure of the following Formula (ULM-1-1), Formula (ULM-1-2), Formula (ULM-1-3) or Formula (ULM-1-4): in A represents CO, CH2 or CD2; R a1 、R a2 、R a3 and R a4 The same or different and each independently represents hydrogen, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy or halogenated C 1-6 alkoxy; (R a5 ) m represents that the isoindoline ring connected thereto is optionally replaced by m R a5 Replace, each R a5 The same or different and each independently represents halogen, hydroxyl, mercapto, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1- 6 alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 Alkynyl; m represents an integer 0, 1, 2, 3 or 4; R w represents O, S, S(O), S(O)2, alkenylene, alkynylene or N(R a6 ), where R a6 Indicates H or C 1-3 Alkyl, or R w represents a key; or R w express: Among them, each ring A 1 are the same or different and each independently represent a nitrogen-containing heterocyclic group, an arylene group or a heteroarylene group, y1 represents an integer of 1 or 2, (R y1 ) a1 Represents each ring A 1 Each independently optionally represented by a1 R y1 Group substitution, each R y1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a1 represents an integer of 0-20; Each ring A 2 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group or a heteroarylene group, y2 represents an integer of 0 or 1, (R y2 ) a2 Represents each ring A 2 independently optionally by a2 R y2 Group substitution, each R y2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2- 6 alkenyl, and a2 represents an integer of 0-20.

10. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1 or 9, wherein the ULM represents the structure of the following Formula (ULM-2-1), Formula (ULM-2-2), Formula (ULM-2-3) or Formula (ULM-2-4): Among them, A, (R a5 ) m and R w As defined in claim 1 or 9.

11. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1, wherein (i) Each ring A 1 Each independently represents a 4- to 20-membered nitrogen-containing heterocyclic group, C 5-20 arylene or 5- to 20-membered heteroarylene; preferably each ring A 1 Each independently represents: piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazepanylene, azaoctinylene, diazaoctinylene, azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene alkylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene, diazabicyclo[2.2.2]octanylene, 3-azaspiro[5.5]undecylene, 8-azaspiro[4.5]decylene, 2-oxa-8-azaspiro[4.5]decylene, 3-methyl-2-oxa-8-azaspiro[4.5]decylene, phenylene, naphthylene, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, phenylene Thiazolyl, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothiophenylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolelene, benzo[2,1,3]oxadiazolelene, benzo[2,1,3]thiadiazolylene , benzo[1,2,3]thiadiazolylidene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylidene, or imidazo[2,1-b]thiazolylidene, or Each ring A 1 Each independently optionally represented by a1 R y1 Group substitution, each R y1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl; a1 represents an integer from 0 to 20; and / or (ii) Each ring A 2 Each independently represents a 4- to 20-membered heterocyclylene group, C 3-20 Cycloalkylene, C 5-20 arylene or 5- to 20-membered heteroarylene; preferably each ring A 2 Each independently represents: Azolidinyl, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azepanylene, dioxanylene, azepanylene, azepanylene, diazepanylene, diazepanylene, diazacycloheptanediylene, diazacyclooctanylene, 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6 -diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, 5- to 20-membered azaspirocyclic group, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C 5-15 spirocyclylene, adamantylene, noradamantylene, norbornylene, phenylene, naphthylene, furylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzo isoxazoleylidene, benzothiazolylidene, benzisothiazolylidene, benzotriazoleylidene, benzo[2,1,3]oxadiazoleylidene, benzo[2,1,3]thiadiazolylidene, benzo[1,2,3]thiadiazolylidene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylidene, or imidazo[2,1-b]thiazolylidene, or Each ring A 2 independently optionally by a2 R y2 Group substitution, each R y2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl; and a2 represents an integer from 0 to 20.

12. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1 or 9, wherein R w express: wherein the above groups are optionally selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 The substituents of the alkenyl group are substituted.

13. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in any one of claims 1 to 12, wherein Each ring A 3 are the same or different and each independently represent a 4- to 20-membered heterocyclylene group, C 3-20 Cycloalkylene, C 5-20 Arylene, or 5- to 20-membered heteroarylene, preferably each ring A 3 Each independently represents: Azolidinyl, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azepanylene, dioxanylene, azepanylene, azepanylene, diazepanylene, diazepanylene, diazacycloheptanediylene, diazacyclooctanylene, 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6 -diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, 5- to 20-membered azaspirocyclic group, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C 5-15 spirocyclylene, adamantylene, noradamantylene, norbornylene, phenylene, naphthylene, furylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene yl, benzo[2,1,3]oxadiazoleylidene, benzo[2,1,3]thiadiazolylidene, benzo[1,2,3]thiadiazolylidene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylidene, or imidazo[2,1-b]thiazolylidene, or y3 represents an integer of 0, 1, 2 or 3, (R y3 ) a3 Represents each ring A 3 Independently optionally a3 R y3 Group substitution, each R y3 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a3 represents an integer of 0-10; and / or Each ring A 4 are the same or different and each independently represent a 4- to 20-membered heterocyclylene group, C 3-20 Cycloalkylene, C 5-20 Arylene, or 5- to 20-membered heteroarylene, preferably each ring A 4 Each independently represents: Azolidinyl, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azepanylene, dioxanylene, azepanylene, azepanylene, diazepanylene, diazepanylene, diazacycloheptanediylene, diazacyclooctanylene, 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6 -diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, 5- to 20-membered azaspirocyclic group, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C 5-15 Spirocyclylene, adamantylene, noradamantylene, norbornylene, phenylene, naphthylene, furylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene yl, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothiophenylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolelene, benzo[2,1,3]oxadiazolelene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolelene oxazolidinyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl, or y4 represents an integer of 0, 1, 2 or 3, (R y4 ) a4 Represents each ring A 4 Independently optionally by a4 R y4 Group substitution, each R y4 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a4 represents an integer of 0-10; and / or Each ring A 5 are the same or different and each independently represent a 4- to 20-membered heterocyclylene group, C 3-20 Cycloalkylene, C 5-20 Arylene, or 5- to 20-membered heteroarylene, preferably each ring A 5 Each independently represents: Azolidinyl, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azepanylene, dioxanylene, azepanylene, azepanylene, diazepanylene, diazepanylene, diazacycloheptanediylene, diazacyclooctanylene, 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6 -diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, 5- to 20-membered azaspirocyclic group, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C 5-15 spirocyclylene, adamantylene, noradamantylene, norbornylene, phenylene, naphthylene, furylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene yl, benzo[2,1,3]oxadiazoleylidene, benzo[2,1,3]thiadiazolylidene, benzo[1,2,3]thiadiazolylidene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylidene, or imidazo[2,1-b]thiazolylidene, or y5 represents an integer of 0, 1, 2 or 3, (R y5 ) a5 Represents each ring A 5 Independently optionally a5 R y5 Group substitution, each R y5 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a5 represents an integer of 0-10; and / or R w1 represents a bond, or represents an optionally substituted straight or branched C 1-20 Alkylene, wherein the linear or branched C 1-20 Any one or more methylene groups of the main carbon chain skeleton of the alkylene group may be optionally replaced by one or more groups selected from the following: a 、R b and any combination thereof, each group R a Each independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each R a7 Each independently represents H or C 1-3 Alkyl, and when the linear or branched C 1-20 Any two or more methylene groups of the main carbon chain skeleton of the alkylene group are replaced by two or more groups R a When substituted, each group R a Not directly connected to each other; each group R b are each independently selected from optionally substituted cycloalkylene (eg, optionally substituted C 3-20 cycloalkylene), optionally substituted arylene (e.g., optionally substituted C 5-20 arylene), optionally substituted heterocyclylene (e.g., optionally substituted 4- to 20-membered heterocyclylene), optionally substituted heteroarylene (e.g., optionally substituted 5- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 Alkyne), alkenylene (e.g. C 2-6 and any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene and the heteroarylene are each independently optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 cycloalkyl, 4- to 10-membered heterocyclic group and any combination thereof, and wherein the linear or branched C 1-20 One or more hydrogen atoms of the alkylene group may be selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, haloC 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 The substituents are substituted by cycloalkyl, 4- to 10-membered heterocyclyl, and any combination thereof.

14. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in any one of claims 1 to 13, wherein the part in the general formula of LIN is express: wherein the above groups are optionally selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 Substitution of the alkenyl group by a substituent; and / or R w1 represents a key, or R w1 express: -C 1-15 Alkylene-; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -(R a (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -(R a (C(R a12 )(R a13 )) n3 ) m4 -(R a (C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -((C(R a12 )(R a13 )) n3 R a ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -((C(R a12 )(R a13 )) n3 R a ) m4 -((C(R a14 )(R a15 )) n4 R a ) m5 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -(R b (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -(R b (C(R a12 )(R a13 )) n3 ) m4 -(R b (C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -((C(R a12 )(R a13 )) n3 R b ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -((C(R a12 )(R a13 )) n3 R b ) m4 -((C(R a14 )(R a15 )) n4 R b ) m5 -; -(C(R a8 )(R a9 )) n1 -(R a -R b -(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -(R b (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(R b -R a -(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -(R a (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -R a -R b ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -((C(R a12 )(R a13 )) n3 R b ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -R b -R a ) m3 -;or -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -((C(R a12 )(R a13 )) n3 R a ) m4 -; in, Each group R a independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each R a7 Each independently represents H or C 1-3 Alkyl; each group R b are independently selected from optionally substituted cycloalkylene (eg, optionally substituted C 3-20 cycloalkylene), optionally substituted arylene (e.g., optionally substituted C 5-20 arylene), an optionally substituted heterocyclylene (e.g., an optionally substituted 4- to 20-membered heterocyclylene), Optionally substituted heteroarylene (e.g., 5- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 Alkyne), alkenylene (e.g. C 2-6 and any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene and the heteroarylene are each independently optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 substituted by cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof; R a8 、R a9 、R a10 、R a11 、R a12 、R a13 、R a14 and R a15 Each independently represents H, deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, halo 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 Cycloalkyl, 4- to 10-membered heterocyclyl, and any combination thereof; and n1, n2, n3, n4, m3, m4, m5 are each independently selected from the integers 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and The C 1-15 Any one or more hydrogen atoms of the main carbon chain of the alkylene group may be optionally replaced by a substituent selected from the group consisting of deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof.

15. A compound of formula (I) according to any one of claims 1 to 13, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein R w1 Represents the following structure: -(C(R a8 )(R a9 )) n1 -(O(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(O(C(R a10 )(R a11 )) n2 ) m3 -(O(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(O(C(R a10 )(R a11 )) n2 ) m3 -(O(C(R a12 )(R a13 )) n3 ) m4 -(O(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 O) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 O) m3 -((C(R a12 )(R a13 )) n3 O) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 O) m3 -((C(R a12 )(R a13 )) n3 O) m4 -((C(R a14 )(R a15 )) n4 O) m5 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )(C(R a10 )(R a11 )) n2 ) m3 -(N(R a7 )(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )(C(R a10 )(R a11 )) n2 ) m3 -(N(R a7 )(C(R a12 )(R a13 )) n3 ) m4 -(N(R a7 )(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 N(R a7 )) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 N(R a7 )) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 N(R a7 )) m4 -((C(R a14 )(R a15 )) n4 N(R a7 )) m5 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -(C(O)N(R a7 )-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -(C(O)N(R a7 )-(C(R a12 )(R a13 )) n3 ) m4 -(C(O)N(R a7 )-(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 -C(O)N(R a7 )) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 -C(O)N(R a7 )) m4 -((C(R a14 )(R a15 )) n4 -C(O)N(R a7 )) m5 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -(O-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 -(O(C(R a12 )(R a13 )) n3 ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 O) m4 -; -(C(R a8 )(R a9 )) n1 -(C(R a10 )(R a11 )) n2 -C(O)N(R a7 )-((C(R a12 )(R a13 )) n3 O) m3 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 ) m3 -(O-(C(R a12 )(R a13 ))) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 ) m3 -(O-(C(R a12 )(R a13 )) n3 ) m4 -(O-(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 -(O(C(R a12 )(R a13 )) n3 ) m3 -; -(C(R a8 )(R a9 )) n1 -N(R a7 )C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -N(R a7 )C(O)) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -N(R a7 )C(O)) m3 -((C(R a12 )(R a13 ))) n3 -O) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -N(R a7 )C(O)) m3 -((C(R a12 )(R a13 )) n3 O) m4 -((C(R a14 )(R a15 )) n4 O) m5 -; -(C(R a8 )(R a9 )) n1 -(C(R a10 )(R a11 )) n2 -N(R a7 )C(O)-((C(R a12 )(R a13 )) n3 O) m3 -; -(C(R a8 )(R a9 )) n1 -(arylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(arylene-(C(R a10 )(R a11 )) n2 ) m3 -arylene-(C(R a12 )(R a13 )) n3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -arylene) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -arylene) m3 -(C(R a12 )(R a13 )) n3 -arylene-; -(C(R a8 )(R a9 )) n1 -(Heterocyclylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(Heterocyclylene-(C(R a10 )(R a11 )) n2 ) m3 -(Heterocyclylene-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heterocyclylene) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heterocyclylene) m3 -((C(R a12 )(R a13 )) n3 -heterocyclylene) m4 -; -(C(R a8 )(R a9 )) n1 -(heteroarylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(heteroarylene-(C(R a10 )(R a11 )) n2 ) m3 -(heteroarylene-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heteroarylene) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heteroarylene) m3 -((C(R a12 )(R a13 )) n3 -heteroarylene) m4 -; -(C(R a8 )(R a9 )) n1 -(cycloalkylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(cycloalkylene-(C(R a10 )(R a11 )) n2 ) m3 -(cycloalkylene-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -cycloalkylene) m3 -;or -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -cycloalkylene) m3 -((C(R a12 )(R a13 )) n3 -cycloalkylene) m4 -; Among them, each R a7 independently represents H or C 1-3 alkyl; The cycloalkylene group (eg C 3-20 Cycloalkylene), the arylene group (such as C 5-20 arylene), the heterocyclylene (e.g., 4- to 20-membered heterocyclylene) and the heteroarylene (e.g., 5- to 20-membered heteroarylene) are each independently optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 substituted by cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof; R a8 、R a9 、R a10 、R a11 、R a12 、R a13 、R a14 and R a15 Each independently represents H, deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, halo C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 Cycloalkyl, 4- to 10-membered heterocyclyl, and any combination thereof; and n1, n2, n3, n4, m3, m4, m5 are each independently selected from integers 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

16. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1, wherein R w1 express: -CH2-、-(CH2)2-、-(CH2)3-、-(CH2)4-、-(CH2)5-、-(CH2)6-、-(CH2)7-、-(CH2)8-、-(CH2)9-、-(CH2) 10 -、-(CH2) 11 -、-(CH2) 12 -、-(CH2) 13 -、-(CH2) 14 -、-(CH2) 15 -;-O-CH2-、-O-(CH2)2-、-O-(CH2)3-、-O-(CH2)4-、-O-(CH2)5-、-O-(CH2)6-、-O-(CH2)7-、-O-(CH2)8-、-O-(CH2)9-、-O-(CH2) 10 -、-(CH2)1-O-、-(CH2)2-O-、-(CH2)3-O-、-(CH2)4-O-、-(CH2)5-O-、-(CH2)6-O-、-(CH2)7-O-、-(CH2)8-O-、-(CH2)9-O-、-(CH2) 10 -O-、-CH2-O-CH2-、-CH2-O-(CH2)2-、-(CH2)1-O-(CH2)3-、-(CH2)1-O-(CH2)4-、-(CH2)1-O-(CH2)5-、-(CH2)1-O-(CH2)6-、-(CH2)1-O-(CH2)7-、-(CH2)1-O-(CH2)8-、-(CH2)1-O-(CH2)9-、-(CH2)1-O-(CH2) 10 -、-(CH2)2-O-(CH2)1-、-(CH2)2-O-(CH2)2-、-(CH2)2-O-(CH2)3-、-(CH2)2-O-(CH2)4-、-(CH2)2-O-(CH2)5-、-(CH2)2-O-(CH2)6-、-(CH2)2-O-(CH2)7-、-(CH2)2-O-(CH2)8-、-(CH2)2-O-(CH2)9-、-(CH2)2-O-(CH2) 10 -、-(CH2)3-O-(CH2)1-、-(CH2)3-O-(CH2)2-、-(CH2)3-O-(CH2)3-、-(CH2)3-O-(CH2)4-、-(CH2)3-O-(CH2)5-、-(CH2)3-O-(CH2)6-、-(CH2)3-O-(CH2)7-、-(CH2)4-O-(CH2)1-、-(CH2)4-O-(CH2)2-、-(CH 2)4-O-(CH2)3-、-(CH2)4-O-(CH2)4-、-(CH2)4-O-(CH2)5-、-(CH2)4-O-(CH2)6-、-(CH2)5-O-(CH2)1-、-(CH2)5-O-(CH2)2-、-(CH2)5-O-(CH2)3-、-(CH2)5-O-(CH2)4-、-(CH2)5-O-(CH2)5-、-(CH2)6-O-( CH2)1-、-(CH2)6-O-(CH2)2-、-(CH2)6-O-(CH2)3-、-(CH2)6-O-(CH2)4-、-(CH2)7-O-(CH2)1-、-(CH2)7-O-(CH2)2-、-(CH2)7-O-(CH2)3-、-(CH2)8-O-(CH2)1-、-(CH2)8-O-(CH2)2-、-CH(CH3)-O-(CH2)1- 、-CH(CH3)-O-(CH2)2-、-CH(CH3)-O-(CH2)3-、-CH(CH3)-O-(CH2)4-、-CH(CH3)-O-(CH2)5-、-CH(CH3)-O-(CH2)6-、-CH(CH3)-O-(CH2)7-、-CH(CH3)-O-(CH2)8-、-CH(CH3)-O-(CH2)9-、-CH(CH3)-O-(CH2) 10 -、-(O(CH2)2)2-、-(O(CH2)2)3-、-(O(CH2)2)4-、-(O(CH2)2)5-、-(O(CH2)2)6-、-(O(CH2)2)7-、-CH2-(O(CH2)2)2-、-CH2-(O(CH2)2)3-、-CH2-(O(CH2 )2)4-、-CH2-(O(CH2)2)5-、-CH2-(O(CH2)2)6-、-CH2-(O(CH2)2)7-、-CH2- (O(CH2)2)1-OCH2-、-CH2-(O(CH2)2)2-OCH2-、-CH2-(O(CH2)2)3-OCH2-、-C H2-(O(CH2)2)4-OCH2-、-CH2-(O(CH2)2)5-OCH2-、-(CH2)2-(O(CH2)2)2-、 -(CH2)2-(O(CH2)2)3-、-(CH2)2-(O(CH2)2)4-、-(CH2)2-(O(CH2)2)5-、-(C H2)2-(O(CH2)2)6-、-(CH2)3-(O(CH2)2)2-、-(CH2)3-(O(CH2)2)3-、-(CH2 )3-(O(CH2)2)4-、-(CH2)3-(O(CH2)2)5-、-(CH2)4-(O(CH2)2)2-、-(CH2)4- (O(CH2)2)3-、-(CH2)4-(O(CH2)2)4-、-(CH2)4-(O(CH2)2)5-、-CH2-(O(CH2)3)2-、-CH2-(O(CH2)3)3-、-CH2-(O(CH2)3)4-、-(CH2)2-(O(CH2)3)2-、-( CH2)2-(O(CH2)3)3-、-(CH2)2-(O(CH2)3)4-、-(CH2)3-(O(CH2)3)2-、-(CH2)3-(O(CH2)3)3-、-(CH2)3-(O(CH2)3)4-、-CH2-O-(CH2)2-O-(CH2)3-、-CH2-(O(CH2)2)2-(O(CH2)3)2-、(CH2)2-O-(CH2)2-O-(CH2)3-、-(CH2)2-(O(CH2)3)2-、-(CH2)3-O-(CH2)2-O-(CH2)3-、-(CH2)3-(O(CH2)2 )2-(O(CH2)3)2-、-CH2-O-(CH2)3-O-(CH2)2-、-CH2-(O(CH2)3)2-(O(CH2)2)2-、-(CH2)2-O-(CH2)3-O-(CH2)2-、-(CH2)2-(O(CH2)3)2-(O(CH2)2)2-、-(CH2)3-O-(CH2)3-O-(CH2)2-、-(CH2)3-(O(CH2)3)2-(O(CH2)2)2-、-CH2-O-(CH2)2-O-CH2-、-(CH2)2-O-(CH2)2-O-CH2-、-(CH2)2-(O(CH2)2)2-O-(CH2)3 -、-(CH2)2-(O(CH2)2)3-O-(CH2)3-、-(CH2)2-(O(CH2)2)4-O-(CH2)3-、-(CH2)5-(O(CH2)2)2-O-(CH2)5-、-(CH2)5-(O(CH2)2)2-O-(CH2)6-、-(CH2)1-N(R、 a7 )- (CH2)1-、-(CH2)1-N(R a7 )-(CH2)2-、-(CH2)1-N(R a7 )-(CH2)3-、-(CH2)1-N(R a7 )-(CH2)4-、-(CH2)1-N(R a7 )-(CH2)5-、-(CH2)1-N(R a7 )-(CH2)6-、-(CH2)1-N(R a7 )-(CH2)7-、-(CH2)1-N(R a7 )-(CH2)8-、-(CH2)1-N(R a7 )-(CH2)9-、-(CH2)1-N(R a7 )-(CH2) 10 -、-N(R a7 )-(CH2)1-、-N(R a7 )-(CH2)2-、-N(R a7 )-(CH2)3-、-N(R a7 )-(CH2)4-、-N(R a7 )-(CH2)5-、-N(R a7 )-(CH2)6-、-N(R a7 )-(CH2)7-、-N(R a7 )-(CH2)8-、-N(R a7 )-(CH2)9-、-N(R a7 )-(CH2) 10 -、-(CH2)2-N(R a7 )-(CH2)1-、-(CH2)2-N(R a7 )-(CH2)2-、-(CH2)2-N(R a7 )-(CH2)3-、-(CH2)2-N(R a7 )-(CH2)4-、-(CH2)2-N(R a7 )-(CH2)5-、-(CH2)2-N(R a7 )-(CH2)6-、-(CH2)2-N(R a7 )-(CH2)7-、-(CH2)2-N(R a7 )-(CH2)8-、-(CH2)2-N(R a7 )-(CH2)9-、-(CH2)2-N(R a7 )-(CH2) 10 -、-(CH2)3-N(R a7 )-(CH2)1-、-(CH2)3-N(R a7 )-(CH2)2-、-(CH2)3-N(R a7 )-(CH2)3-、-(CH2)4-N(R a7 )-(CH2)1-、-(CH2)4-N(R a7 )-(CH2)2-、-(CH2)4-N(R a7 )-(CH2)3-、-(CH2)4-N(R a7 )-(CH2)4-、-(CH2)5-N(R a7 )-(CH2)1-、-(CH2)5-N(R a7 )-(CH2)2-、-(CH2)5-N(R a7 )-(CH2)3-、-(CH2)5-N(R a7 )-(CH2)4-、-(CH2)5-N(R a7 )-(CH2)5-、-(CH2)6-N(R a7 )-(CH2)1-、-(CH2)6-N(R a7 )-(CH2)2-、-(CH2)6-N(R a7 )-(CH2)3-、-(CH2)7-N(R a7 )-(CH2)1-、-(CH2)7-N(R a7 )-(CH2)2-、-(CH2)7-N(R a7 )-(CH2)3-、-(CH2)8-N(R a7 )-(CH2)1-、-(CH2)8-N(R a7 )-(CH2)2-、-(CH2)8-N(R a7 )-(CH2)3-、-CH(CH3)-N(R a7 )-(CH2)1-、-CH(CH3)-N(R a7 )-(CH2)2-、-CH(CH3)-N(R a7 )-(CH2)3-、-CH(CH3)-N(R a7 )-(CH2)4-、-CH(CH3)-N(R a7 )-(CH2)5-、-CH(CH3)-N(R a7 )-(CH2)6-、-CH(CH3)-N(R a7 )-(CH2)7-、-CH(CH3)-N(R a7 )-(CH2)8-、-CH(CH3)-N(R a7 )-(CH2)9-、-CH(CH3)-N(R a7 )-(CH2) 10 -, -C(O)NHCH2-, -C(O)NH(CH2)2-, -C(O)NH(CH2)3-, -C(O)NH(CH2)4-, -C(O)NH(CH2)5-, -CH2C(O)NHCH2-, -(CH2)2C(O)NH(CH2)2-, -(CH2)2C(O)NH (CH2)3-, -(CH2)2C(O)NH(CH2)4-, -(CH2)2C(O)NH(CH2)5-, -(CH2)3C(O)NH(CH2)3-, -(CH2)3C(O)NH(CH2)4-, -(CH2)4C(O)NH(CH2)4-, -(CH2)5C(O) NH(CH2)5-, -(CH2)6C(O)NH(CH2)7-, -(CH2)6C(O)NH(CH2)6-, -(CH2)7C(O)NH(CH2)7-, -(CH2)2C(O)NH(CH2)2-O-(CH2)2-, -NHC(O)CH2-, -NHC(O)(C H2)2-, -NHC(O)(CH2)3-, -NHC(O)(CH2)4-, -NHC(O)(CH2)5-, -CH2NHC(O)CH2-, -(CH2)2NHC(O)(CH2)2-, -(CH2)2NHC(O)(CH2)3-, -(CH2)2NHC(O)(CH 2)4-, -(CH2)2NHC(O)(CH2)5-, -(CH2)3NHC(O)(CH2)3-, -(CH2)3NHC(O)(CH2)4-, -(CH2)4NHC(O)(CH2)4-, -(CH2)5NHC(O)(CH2)5-, -(CH2)6NHC(O)( CH2)7-, -(CH2)6NHC(O)(CH2)6-, -(CH2)7NHC(O)(CH2)7-, -(CH2)4NHC(O)(CH2)8-, -(CH2)2NHC(O)(CH2)2-O-(CH2)2-, -(CH2)4NHC(O)CH2-, -phenylene-C H2-, -phenylene-(CH2)2-, -phenylene-(CH2)3-, -phenylene-(CH2)4-, -phenylene-(CH2)5-, -phenylene-(CH2)6-, -phenylene-(CH2)7-, -phenylene-(CH2)8-, -CH2-phenylene-CH2-, -CH2-phenylene-(CH2)2-, -CH2-phenylene-(CH2)3-, -CH2-phenylene-(CH2)4-, -CH2-phenylene-(CH2)5-, -CH2-phenylene-(CH2)6-, -CH2-phenylene-(CH2)7-, -CH2-phenylene-(CH2)8-, -(CH2)2-phenylene-(CH2)1-,-(CH2)2-phenylene-(CH2)2-, -(CH2)2-phenylene-(CH2)3-, -(CH2)2-phenylene-(CH2)4-, -(CH2)2-phenylene-(CH2)5-, -(CH2)2-phenylene-(CH2)6-, -(CH2)2-phenylene-(CH2)7-, -(CH2)2-phenylene-(CH2)8-, -(CH2)3-phenylene-CH2-, -(CH2)3-phenylene Phenyl-(CH2)2-, -(CH2)3-phenylene-(CH2)3-, -(CH2)3-phenylene-(CH2)4-, -(CH2)3-phenylene-(CH2)5-, -(CH2)3-phenylene-(CH2)6-, -(CH2)3-phenylene-(CH2)7-, -(CH2)3-phenylene-(CH2)8-, -(CH2)4-phenylene-CH2-, -(CH2)4-phenylene-(CH2)2- , -(CH2)4-phenylene-(CH2)3-, -(CH2)4-phenylene-(CH2)4-, -(CH2)4-phenylene-(CH2)5-, -(CH2)4-phenylene-(CH2)6-, -(CH2)4-phenylene-(CH2)7-, -(CH2)4-phenylene-(CH2)8-, -(CH2)5-phenylene-(CH2)1-, -(CH2)5-phenylene-(CH2)2-, -(CH2) 5-phenylene-(CH2)3-, -(CH2)5-phenylene-(CH2)4-, -(CH2)5-phenylene-(CH2)5-, -(CH2)5-phenylene-(CH2)6-, -(CH2)5-phenylene-(CH2)7-, -(CH2)5-phenylene-(CH2)8-, -(CH2)6-phenylene-(CH2)1-, -(CH2)6-phenylene-(CH2)2-, -(CH2)6-phenylene-, (CH2)3-, -(CH2)6-phenylene-(CH2)4-, -(CH2)6-phenylene-(CH2)5-, -(CH2)6-phenylene-(CH2)6-, -(CH2)6-phenylene-(CH2)7-, -(CH2)6-phenylene-(CH2)8-, -(CH2)7-phenylene-(CH2)1-, -(CH2)7-phenylene-(CH2)2-, -(CH2)7-phenylene-(CH2)3-, -(CH2) 7-phenylene-(CH2)4-, -(CH2)7-phenylene-(CH2)8-, -(CH2)8-phenylene-CH2-, -(CH2)8-phenylene-(CH2)2-, -(CH2)8-phenylene-(CH2)3-, -(CH2)8-phenylene-(CH2)4-, -(CH2)8-phenylene-(CH2)5-, -(CH2)8-phenylene-(CH2)6-, -(CH2)8-phenylene-(CH2)7-, -N(R a7 )-CH2-phenylene-CH2-、-N(R a7 )-CH2-phenylene-(CH2)2-, -N(R a7 )-CH2-phenylene-(CH2)3-、-N(R a7 )-CH2-phenylene-(CH2)4-、-N(R a7 )-CH2-phenylene-(CH2)5-、-N(R a7 )-CH2-phenylene-(CH2)6-、-N(R a7 )-CH2-phenylene-(CH2)7-、-N(R a7 )-CH2-phenylene-(CH2)8-, -CH2-N(R a7 )-CH2-phenylene-CH2-, -CH2-N(R a7 )-CH2-phenylene-(CH2)2-, -CH2-N(R a7 )-CH2-phenylene-(CH2)3-, -CH2-N(R a7 )-CH2-phenylene-(CH2)4-, -CH2-N(R a7 )-CH2-phenylene-(CH2)5-, -CH2-N(R a7 )-CH2-phenylene-(CH2)6-, -CH2-N(R a7 )-CH2-phenylene-(CH2)7-, -CH2-N(R a7 )-CH2-phenylene-(CH2)8-, -CH2-N(R a7 )-(CH2)2-phenylene-CH2-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)2-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)3-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)4-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)5-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)6-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)7-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)8-, -(CH2)2-N(R a7 )-CH2-phenylene-CH2-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)4-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)5-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)6-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)7-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)3-N(R a7 )-CH2-phenylene-CH2-, -(CH2)3-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)3-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)3-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)4-N(R a7 )-CH2-phenylene-CH2-, -(CH2)4-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)4-N(R a7 )-CH2-phenylene-(CH2)3-、-(CH2)4-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)5-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)5-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)6-N(R a7 )-CH2-phenylene-(CH2)3-、-(CH2)6-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)7-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)8-N(R a7 )-CH2-phenylene-CH2-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)4-、-(CH2)8-N(R a7 )-CH2-phenylene-(CH2)5-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)6-, -piperidinylene-CH2-, -piperidinylene-(CH2)2-, -piperidinylene-(CH2)3-, -piperidinylene-(CH2)4-, -piperidinylene-(CH2)5-, -piperidinylene-(CH2)6-, -piperidinylene-(CH2)7-, -piperidinylene-(CH2)8-, -CH2-piperidinylene-CH2-, -CH2-piperidinylene-(CH2)2-, -CH2-piperidinylene-(CH2)3-, -CH2-piperidinylene-(CH2)4-, -CH2-piperidinylene-(CH2)5-, -CH2-piperidinylene-(CH2)6-, -CH2-piperidinylene-(CH2)7- , -(CH2)2-piperidinylene-(CH2)8-, -(CH2)2-piperidinylene-(CH2)1-, -(CH2)2-piperidinylene-(CH2)2-, -(CH2)2-piperidinylene-(CH2)3-, -(CH2)2-piperidinylene-(CH2)4-, -(CH2)2-piperidinylene-(CH2)5-, -(CH2)2-piperidinylene-(CH2)6-, -(CH2)2-piperidinylene-(CH2)7-, -(CH2)2-piperidinylene-(CH2)8-, -(CH2)3-piperidinylene-CH2-, -(CH2)3-piperidinylene-(CH2)2-, -(CH2)3-piperidinylene-(CH2)3-, -( -(CH2)3-piperidinylene-(CH2)4-, -(CH2)3-piperidinylene-(CH2)5-, -(CH2)3-piperidinylene-(CH2)6-, -(CH2)3-piperidinylene-(CH2)7-, -(CH2)3-piperidinylene-(CH2)8-, -(CH2)4-piperidinylene-CH2-, -(CH2)4-piperidinylene-(CH2)2-, -(CH2)4-piperidinylene-(CH2)3-, -(CH2)4-piperidinylene-(CH2)4-, -(CH2)4-piperidinylene-(CH2)5-, -(CH2)4-piperidinylene-(CH2)6-, -(CH2)4-piperidinylene-(CH2)7-, -(CH2)3-piperidinylene-(CH2)8-, -(CH2)4-piperidinylene-CH2-, -(CH2)4-piperidinylene-(CH2)2-, -(CH2)4-piperidinylene-(CH2)3-, -(CH2)4-piperidinylene-(CH2)4-, -(CH2)4-piperidinylene-(CH2)5-, -(CH2)4-piperidinylene-(CH2)6-, -(CH2)4-piperidinylene-(CH2)7-, -(CH2) -(CH2)4-piperidinylene-(CH2)8-, -(CH2)5-piperidinylene-(CH2)1-, -(CH2)5-piperidinylene-(CH2)2-, -(CH2)5-piperidinylene-(CH2)3-, -(CH2)5-piperidinylene-(CH2)4-, -(CH2)5-piperidinylene-(CH2)5-, -(CH2)5-piperidinylene-(CH2)6-, -(CH2)5-piperidinylene-(CH2)7-, -(CH2)5-piperidinylene-(CH2)8-, -(CH2)6-piperidinylene-(CH2)1-, -(CH2)6-piperidinylene-(CH2)2-, -(CH2)6-piperidinylene-(CH2)3-,-(CH2)6-piperidinyl-(CH2)4-、-、 (CH2)6-piperidinylene-(CH2)5-, -(CH2)6-piperidinylene-(CH2)6-, -(CH2)6-piperidinylene-(CH2)7-, -(CH2)6-piperidinylene-(CH2)8-, -(CH2)7-piperidinylene-(CH2)1-, -(CH2)7-piperidinylene-(CH2)2-, -(CH2)7-piperidinylene-(CH2)3-, -(CH2)7-piperidinylene-(CH2)4-, - (CH2)7-piperidinylene-(CH2)8-, -(CH2)8-piperidinylene-CH2-, -(CH2)8-piperidinylene-(CH2)2-, -(CH2)8-piperidinylene-(CH2)3-, -(CH2)8-piperidinylene-(CH2)4-, -(CH2)8-piperidinylene-(CH2)5-, -(CH2)8-piperidinylene-(CH2)6-, -(CH2)8-piperidinylene-(CH2)7-, -N(R a7 )-CH2-piperidinyl-CH2-、-N(R a7 )-CH2-piperidinyl-(CH2)2-、-N(R a7 )-CH2-piperidinyl-(CH2)3-、-N(R a7 )-CH2-piperidinyl-(CH2)4-、-N(R a7 )-CH2-piperidinyl-(CH2)5-、-N(R a7 )-CH2-piperidinyl-(CH2)6-、-N(R a7 )-CH2-piperidinyl-(CH2)7-、-N(R a7 )-CH2-piperidinyl-(CH2)8-, -CH2-N(R a7 )-CH2-piperidinyl-CH2-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)2-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)3-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)4-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)5-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)6-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)7-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)8-, -CH2-N(R a7 )-(CH2)2-piperidinyl-CH2-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)2-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)3-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)4-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)5-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)6-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)7-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)8-, -(CH2)2-N(R a7 )-CH2-piperidinyl-CH2-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)4-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)5-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)6-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)7-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)3-N(R a7 )-CH2-piperidinyl-CH2-, -(CH2)3-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)3-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)3-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)4-N(R a7 )-CH2-piperidinyl-CH2-, -(CH2)4-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)4-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)4-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)5-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)5-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)6-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)6-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)7-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)8-N(R a7 )-CH2-piperidinyl-CH2-, -(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)4-、-(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)5-, -(CH2)8-N(R a7 )-CH2-piperidinylene-(CH2)6-, -piperazinylene-CH2-, -piperazinylene-(CH2)2-, -piperazinylene-(CH2)3-, -piperazinylene-(CH2)4-, -piperazinylene-(CH2)5-, -piperazinylene-(CH2)6-, -piperazinylene-(CH2)7-, -piperazinylene-(CH2)8-, -CH2-piperazinylene-CH2-, -CH2-piperazinylene-(CH2)2-, -CH2-piperazinylene-(CH2)3-, -CH2-piperazinylene-(CH2)4-, -CH2-piperazinylene-(CH2)5-, -CH2-piperazinylene-(CH2)6-, -piperazinylene-(CH2)7-, -piperazinylene-(CH2)8-, -CH2-piperazinylene-CH2-, -CH2-piperazinylene-(CH2)2-, -CH2-piperazinylene-(CH2)3-, -CH2-piperazinylene-(CH2)4-, -CH2-piperazinylene-(CH2)5-, -CH2-piperazinylene-(CH2)6 -, -CH2-piperazinylene-(CH2)7-, -CH2-piperazinylene-(CH2)8-, -(CH2)2-piperazinylene-(CH2)1-, -(CH2)2-piperazinylene-(CH2)2-, -(CH2)2-piperazinylene-(CH2)3-, -(CH2)2-piperazinylene-(CH2)4-, -(CH2)2-piperazinylene-(CH2)5-, -(CH2)2-piperazinylene-(CH2)6-, -(CH2)2-piperazinylene-(CH2)7-, -(CH2)2-piperazinylene-(CH2)8-, -(CH2)3-piperazinylene-CH2-, -(CH2)3- Piperazinylene-(CH2)2-, -(CH2)3-piperazinylene-(CH2)3-, -(CH2)3-piperazinylene-(CH2)4-, -(CH2)3-piperazinylene-(CH2)5-, -(CH2)3-piperazinylene-(CH2)6-, -(CH2)3-piperazinylene-(CH2)7-, -(CH2)3-piperazinylene-(CH2)8-, -(CH2)4-piperazinylene-CH2-, -(CH2)4-piperazinylene-(CH2)2-, -(CH2)4-piperazinylene-(CH2)3-, -(CH2)4-piperazinylene-(CH2)4-, -(CH2)4-piperazinylene -(CH2)5-, -(CH2)4-piperazinylene-(CH2)6-, -(CH2)4-piperazinylene-(CH2)7-, -(CH2)4-piperazinylene-(CH2)8-, -(CH2)5-piperazinylene-(CH2)1-, -(CH2)5-piperazinylene-(CH2)2-, -(CH2)5-piperazinylene-(CH2)3-, -(CH2)5-piperazinylene-(CH2)4-, -(CH2)5-piperazinylene-(CH2)5-, -(CH2)5-piperazinylene-(CH2)6-, -(CH2)5-piperazinylene-(CH2)7-, -(CH2)5-piperazinylene- (CH2)8-, -(CH2)6-piperazinylene-(CH2)1-, -(CH2)6-piperazinylene-(CH2)2-, -(CH2)6-piperazinylene-(CH2)3-, -(CH2)6-piperazinylene-(CH2)4-, -(CH2)6-piperazinylene-(CH2)5-, -(CH2)6-piperazinylene-(CH2)6-, -(CH2)6-piperazinylene-(CH2)7-, -(CH2)6-piperazinylene-(CH2)8-, -(CH2)7-piperazinylene-(CH2) 2) 1-, -(CH2)7-piperazinylene-(CH2)2-, -(CH2)7-piperazinylene-(CH2)3-, -(CH2)7-piperazinylene-(CH2)4-, -(CH2)8-piperazinylene-CH2-, -(CH2)8-piperazinylene-(CH2)2-, -(CH2)8-piperazinylene-(CH2)3-, -(CH2)8-piperazinylene-(CH2)4-, -(CH2)8-piperazinylene-(CH2)5-, or -(CH2)8-piperazinylene-(CH2)6-; Among them, each R a7 independently represents H or C 1-3 alkyl; The phenylene, the piperazinyl and the piperidinyl are each independently selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 The substituents are substituted by cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof.

17. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 1, wherein LIN represents: a bond, C(O), C(O)NH, NHC(O), -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9-, -(CH2) 10 -, -(CH2) 11 -, -(CH2) 12 -, -(CH2) 13 -, -(CH2) 14 -, -(CH2) 15 -; -O-CH2-, -O-(CH2)2-, -O-(CH2)3-, -O-(CH2)4-, -O-(CH2)5-, -O-(CH2)6-, -O-(CH2)7-, -O-(CH2)8-, -O-(CH2)9-, -O-(CH2) 10 -, -(CH2)1-O-, -(CH2)2-O-, -(CH2)3-O-, -(CH2)4-O-, -(CH2)5-O-, -(CH2)6-O-, -(CH2)7-O-, -(CH2)8-O-, -(CH2)9-O-, -(CH2) 10 -O-、-CH2-O-CH2-、-CH2-O-(CH2)2-、-(CH2)1-O-(CH2)3-、-(CH2)1-O-(CH2)4-、-(CH2)1-O-(CH2)5-、-(CH2)1-O-(CH2)6-、-(CH2)1-O-(CH2)7-、-( CH2)1-O-(CH2)8-、-(CH2)2-O-(CH2)1-、-(CH2)2-O-(CH2)2-、-(CH2)2-O-(CH2)3-、-(CH2)2-O-(CH2)4-、-(CH2)2-O-(CH2)5-、-(CH2)2-O-(CH2)6-、-(CH2)2-O-(CH2)7-、-(CH2)2-O-(CH2)8-、-(CH2)3-O-(CH2)1-、-(CH2)3-O-(CH2)2-、-(CH2)3-O-(CH2)3-、-(CH2)3-O-(CH2)4-、-(CH2)3-O-(CH2 )5-、-(CH2)3-O-(CH2)6-、-(CH2)3-O-(CH2)7-、-(CH2)4-O-(CH2)1-、-(CH2)4-O-(CH2)2-、-(CH2)4-O-(CH2)3-、-(CH2)4-O-(CH2)4-、-(CH2)4-O-(C H2)5-、-(CH2)4-O-(CH2)6-、-(CH2)5-O-(CH2)1-、-(CH2)5-O-(CH2)2-、- (CH2)5-O-(CH2)3-、-(CH2)5-O-(CH2)4-、-(CH2)5-O-(CH2)5-、-(CH2)6-O -(CH2)1-、-(CH2)6-O-(CH2)2-、-(CH2)6-O-(CH2)3-、-(CH2)6-O-(CH2)4-、-(CH2)7-O-(CH2)1-、-(CH2)7-O-(CH2)2-、-(CH2)7-O-(CH2)3-、-(CH2)8-O-(CH2)1-、-(CH2)8-O-(CH2)2-、-CH(CH3)-O-(CH2)1-、-CH(CH3)-O-(CH2)2-、-CH(CH3)-O-(CH2)3-、-CH(CH3)-O-(CH2)4-、-CH(CH3)-O-(CH2)5 -、-CH(CH3)-O-(CH2)6-、-CH(CH3)-O-(CH2)7-、-CH(CH3)-O-(CH2)8-、-(O(CH2)2)2-、-(O(CH2)2)3-、-(O(CH2)2)4-、-(O(CH2)2)5-、-(O(CH2)2)6-、-CH2-(O(CH2)2)2-、-CH2-(O(CH2)2)3-、-CH2-(O(CH2)2)4-、-CH2-(O(CH2)2)5-、-CH2-(O(CH2)2)6-、-CH2-(O(CH2)2)1-OCH2-、-CH2-(O(CH2)2)2-OCH2-、-CH2-(O(CH2)2)3-OCH2-、-CH2-(O(CH2)2)4-OCH2-、-CH2-(O(CH2)2)5-OCH2-、-CH2-(O(CH2)2)6-OCH2-、-(CH2)2-(O(CH2)2)2-、-(CH2)2-(O(CH2)2)3-、-(CH2)2-(O(CH2)2)4-、-(CH2)2-(O(CH2)2)5-、-(CH2)2-(O(CH2)2)6-、-(CH2)3-(O(CH2)2)2-、-(CH2)3-(O(CH2)2)3-、-(CH2)3-(O(CH2)2)4-、-(CH2)3-(O(CH2)2)5-、-(CH2)4-(O(CH2)2)2-、-(CH2)4-(O(CH2)2)3-、-(CH2)4-(O(CH2)2)4-、-(CH2)4-(O(CH2)2)5-、-CH2-(O(CH2)3)2-、-CH2-(O(CH2)3)3-、-CH2-(O(CH2)3)4-、-(CH2)2-(O(CH2)3)2-、-(CH2)2-(O(CH2)3)3-、-(CH2)2-(O(CH2)3)4-、-(CH2)3-(O(CH2)3)2-、-(CH2)3-(O(CH2)3)3-、-CH2-O-(CH2)2-O-(CH2)3-、-CH2-(O(CH2)2)2-(O(CH2)3)2-、(CH2)2-O-(CH2)2-O-(CH2)3-、-(CH2)2-(O(CH2)2)2-(O(CH2)3)2-、-(CH2)3-O-(CH2)2-O-(CH2)3-、-(CH2)3-(O(CH2)2)2-(O(CH2)3)2-、-CH2-O-、 (CH2)3-O-(CH2)2-、-CH2-(O(CH2)3)2-(O(CH2)2)2-、(CH2)1-N(R a7 )-(CH2)1-、-(CH2)1-N(R a7 )-(CH2)2-、-(CH2)1-N(R a7 )-(CH2)3-、-(CH2)1-N(R a7 )-(CH2)4-、-(CH2)1-N(R a7 )-(CH2)5-、-(CH2)1-N(R a7 )-(CH2)6-、-N(R a7 )-(CH2)1-、-N(R a7 )-(CH2)2-、-N(R a7 )-(CH2)3-、-N(R a7 )-(CH2)4-、-N(R a7 )-(CH2)5-、-N(R a7 )-(CH2)6-、-(CH2)2-N(R a7 )-(CH2)1-、-(CH2)2-N(R a7 )-(CH2)2-、-(CH2)2-N(R a7 )-(CH2)3-、-(CH2)2-N(R a7 )-(CH2)4-、-(CH2)2-N(R a7 )-(CH2)5-、-(CH2)2-N(R a7 )-(CH2)6-、-(CH2)3-N(R a7 )-(CH2)1-、-(CH2)3-N(R a7 )-(CH2)2-、-(CH2)3-N(R a7 )-(CH2)3-、-(CH2)4-N(R a7 )-(CH2)1-、-(CH2)4-N(R a7 )-(CH2)2-、-(CH2)4-N(R a7 )-(CH2)3-、-(CH2)4-N(R a7 )-(CH2)4-、-(CH2)5-N(R a7 )-(CH2)1-、-(CH2)5-N(R a7 )-(CH2)2-、-(CH2)5-N(R a7 )-(CH2)3-、-(CH2)5-N(R a7 )-(CH2)4-、-(CH2)5-N(R a7 )-(CH2)5-、-(CH2)6-N(R a7 )-(CH2)1-、-(CH2)6-N(R a7 )-(CH2)2-、-(CH2)6-N(R a7 )-(CH2)3-、-(CH2)7-N(R a7 )-(CH2)1-、-(CH2)7-N(R a7 )-(CH2)2-、-(CH2)7-N(R a7 )-(CH2)3-、-(CH2)8-N(R a7 )-(CH2)1-、-(CH2)8-N(R a7 )-(CH2)2-、-(CH2)8-N(R a7 )-(CH2)3-、-CH(CH3)-N(R a7 )-(CH2)1-、-CH(CH3)-N(R a7 )-(CH2)2-、-CH(CH3)-N(R a7 )-(CH2)3-、-CH(CH3)-N(R a7 )-(CH2)4-、-CH(CH3)-N(R a7 )-(CH2)5-、-CH(CH3)-N(R a7 )-(CH2)6-, -C(O)NHCH2-, -C(O)NH(CH2)2-, -C(O)NH(CH2)3-, -C(O)NH(CH2)4-, -C(O)NH(CH2)5-, -CH2C(O)NHCH2-, -(CH2)2C(O)NH(CH2)2-, -(CH2 )2C(O)NH(CH2)3-, -(CH2)2C(O)NH(CH2)4-, -(CH2)2C(O)NH(CH2)5-, -(CH2)3C(O)NH(CH2)3-, -(CH2)3C(O)NH(CH2)4-, -(CH2)4C(O)NH(CH2)4-, -(C H2)5C(O)NH(CH2)5-, -(CH2)2C(O)NH(CH2)2-O-(CH2)2-, -NHC(O)CH2-, -NHC(O)(CH2)2-, -NHC(O)(CH2)3-, -NHC(O)(CH2)4-, -NHC(O)(CH2)5-, -CH2 NHC(O)CH2-, -(CH2)2NHC(O)(CH2)2-, -(CH2)2NHC(O)(CH2)3-, -(CH2)2NHC(O)(CH2)4-, -(CH2)2NHC(O)(CH2)5-, -(CH2)3NHC(O)(CH2)3-, -(CH2)3N HC(O)(CH2)4-, -(CH2)4NHC(O)(CH2)4-, -(CH2)5NHC(O)(CH2)5-, -(CH2)2NHC(O)(CH2)2-O-(CH2)2-, -(CH2)4NHC(O)CH2-, -CH2-phenylene-CH2-, -CH2-phenylene-(CH2)2-, -CH2-phenylene-(CH2)3-, -CH2-phenylene-(CH2)4-, -CH2-phenylene-(CH2)5-, -CH2-phenylene-(CH2)6-, -(CH2)2-phenylene-(CH2)1-, -(CH2)2-phenylene-(CH2)2-, -(CH2) 2-phenylene-(CH2)3-, -(CH2)2-phenylene-(CH2)4-, -(CH2)2-phenylene-(CH2)5-, -(CH2)3-phenylene-CH2-, -(CH2)3-phenylene-(CH2)2-, -(CH2)3-phenylene-(CH2)3-, -(CH2)3-phenylene-(CH2)4-, -(CH2)3-phenylene-(CH2)5-, -(CH2)4-phenylene-CH2-, -(CH2)4-phenylene-(CH2)2-, -(CH2)4-phenylene-(CH2)3-, -(CH2)4-phenylene-(CH2)4-, -(CH2)4-phenylene-(CH2)5-,-CH2-piperidinylene-CH2-, -CH2-piperidinylene-(CH2)2-, -CH2-piperidinylene-(CH2)3-, -CH2-piperidinylene-(CH2)4-, -CH2-piperidinylene-(CH2)5-, -CH2-piperidinylene-(CH2)6-, -(CH2)2-piperidinylene-(CH2)1-, -(CH2)2-piperidinylene-(CH2)2-, -(CH2)2-piperidinylene-(CH2)3-, -(CH2)2-piperidinylene-(CH2)4-, -(CH2)2-piperidinylene-( -(CH2)5-, -(CH2)3-piperidinylene-CH2-, -(CH2)3-piperidinylene-(CH2)2-, -(CH2)3-piperidinylene-(CH2)3-, -(CH2)3-piperidinylene-(CH2)4-, -(CH2)3-piperidinylene-(CH2)5-, -CH2-piperazinylene-CH2-, -CH2-piperazinylene-(CH2)2-, -CH2-piperazinylene-(CH2)3-, -CH2-piperazinylene-(CH2)4-, -CH2-piperazinylene-(CH2)5-, -(CH2)2 -piperazinylene-(CH2)1-, -(CH2)2-piperazinylene-(CH2)2-, -(CH2)2-piperazinylene-(CH2)3-, -(CH2)2-piperazinylene-(CH2)4-, -(CH2)2-piperazinylene-(CH2)5-, -(CH2)3-piperazinylene-CH2-, -(CH2)3-piperazinylene-(CH2)2-, -(CH2)3-piperazinylene-(CH2)3-, -(CH2)3-piperazinylene-(CH2)4-, -(CH2)3-piperazinylene-(CH2)5-, -(C H2)4-piperazinylene-CH2-, -(CH2)4-piperazinylene-(CH2)2-, -(CH2)4-piperazinylene-(CH2)3-, -(CH2)4-piperazinylene-(CH2)4-, -(CH2)4-piperazinylene-(CH2)5-, -(CH2)8-piperazinylene-CH2-, -(CH2)8-piperazinylene-(CH2)2-, -(CH2)8-piperazinylene-(CH2)3-, -(CH2)8-piperazinylene-(CH2)4-, or -(CH2)8-piperazinylene-(CH2)5-; or, LIN means: wherein the above groups are optionally selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 The substituents of the alkenyl group are substituted.

18. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph according to claim 1, which is also represented by the following formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5-1), formula (I-5-2), formula (I-5-3), formula (I-5-4), formula (I-6), formula (I-7), formula (I-8), formula (I-9), formula (I-10-1), formula (I-10-2), formula (I-11), formula (I-12), formula (I-13), formula (I-14), formula (I-15), formula (I-16), formula (I-17), formula (I-18), formula (I-19), formula (I-20), formula (I-21), formula (I-22), formula (I-23), formula (I-24), formula (I-25), formula (I-26), formula (I-27), formula (I-28), formula (I-29), formula (I-30), formula (I-31), formula (I-32), formula (I-33), formula (I-34), formula (I-35), formula (I-36), formula (I-37), formula (I-38), formula (I-39), formula (I-40), formula (I-41), formula (I-42), formula (I-43), formula (I-44), formula (I-45), formula (I-46), formula (I-47), formula (I-48), formula (I-49), formula (I-5 3-1), formula (I-13-2), formula (I-14), formula (I-15), formula (I-16), formula (I-17), formula (I-18-1), formula (I-18-2), formula (I-19), formula (I-20), formula (I-21), formula (I-22) , the structural representation of formula (I-23), formula (I-24), formula (I-25), formula (I-26), formula (I-27-1), formula (I-27-2), formula (I-28), formula (I-29), formula (I-30), formula (I-31) or formula (I-32): Where A, R a1 , R a2 , R a3 , R a4 , (R a5 ) m , R w , LIN, R c , (R 1a ) p1a , R 1b , R 2a , R 2b , (R 2c ) p2a , R 3a , R 3b , Ring A, Ring B, Ring C, R 5a , R 5b , (R 5c ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ 13e , R 13f , R 13g , R 13i , R 14a , R 14b , (R 14c ) p14a , R 15a , R 15b , R 15c , R 15d , R 16a , R 16b , R 16c , R 16d , R 16e , R 17a , R 17b , R 17c , R 17d , (R 17e ) p17a , (R 17f ) p17b , Ring F, R 18a , R 18c , (R 18d ) p18a , (R 18e ) p18b , R 18f , R 18g , R 18h , R 19a , R 19b , R 19c , R 19d , (R 19e ) p19a , (R 19f ) p19b , (R 19g ) p19c , (R 20a ) p20a , (R 20b ) p20b , R x1 , R 21a , (R 21b ) p21a , (R 21c ) p21b , R 22a , R 22b , R 22c , (R 22d ) p22a , (R 22e ) p22b , (R 22f ) p22c , Ring G, R 23a , R 23b , (R 23c ) p23a , (R 23d ) p23b , ring H, (R 24a ) p24a , (R 24b ) p24b , (R 24c ) p24c , (R 24d ) p24d , (R 24e ) p24e , R 24f , (R 25a ) p25a , (R 25b ) p25b , R 25c , (R 26a ) p26a , (R 26b ) p26b , (R 27a ) p27a , (R 27b ) p27b , R 27c , R 27d , (R 27g ) p27c , n, (R 27h ) p27d , R 28a , (R 28b ) p28a , (R 28c ) p28b , (R 28d ) p28c , R 29a , R 29b , R 29c , R 29d , (R 29e ) p29a , (R 29f ) p29b , (R 30a ) p30a , snippet snippet R 30d 、R 30e 、R 31a 、(R 31b ) p31a 、(R 31c ) p31b , Z1, Z2, R 32a 、R 32b 、(R 32c ) p32a 、(R 32d ) p32b 、(R 32e ) p32c 、Z3、(R 33a ) p33a 、R 33b 、R 33c 、R 33d 、R 33e 、R 33f 、R 33g and R 33h As defined in claim 3.

19. A compound of formula (I) according to claim 1 or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof selected from: 1-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(7-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)amino)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-((1S,4S)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-((1R,4R)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(8-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 1-(5-((4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1′-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-[1,4′-bipiperidine]-4-carboxamide; 4-(2,6-dichlorobenzamido)-N-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methoxy)phenyl)acetamide; 1-(5-((4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 4-(((4-(5-chloro-2-((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((5'-chloro-2'-((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridyl]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((5'-chloro-2'-((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-4-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridyl]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; 7-cyclopentyl-2-((5-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 1-(5-((4-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 8-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 2-((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)amino)piperidin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; N-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-fluoro-5-methoxy-4-((4-((2-methyl-3-oxoisoindolin-4-yl)oxy)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-3-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; 1-(5-((4-(4-((4-((3-(methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)-[1,4'-bipiperidinyl]-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-7-yl)-3-(trifluoromethyl)benzamide; N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; N-(5-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; N-(5-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; N-(5-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; N-(5-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; 6-(5-cyano-1H-pyrrolo[2,3-b]pyridin-1-yl)-N-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-4-(isopropylamino)nicotinamide; N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; N-(3-(difluoromethyl)-1-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)-[1,4'-bipiperidinyl]-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; N-(3-(difluoromethyl)-1-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; (R)-N-(2-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-5-(3-hydroxypyrrolidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]thiazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]oxazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; 6-(6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; 6-(6-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; 6-(6-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; (R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d8)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-3,5-dimethylpiperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-2,6-dimethylpiperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(6-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(3-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(8-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(3-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((R)-4-((1R,4R)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((R)-4-((1S,4S)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; (R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide; (R)-N-(1-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)amino)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; 1-(5-((4-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((4-(3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-[1,4'-bipiperidinyl]-1'-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3S)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-(((1S,4S)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3R)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-(((1R,4R)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((8-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((6-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(((1S,4S)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(((1R,4R)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((8-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((6-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; 5-((4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(((1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(((1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)(methyl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-(7-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)amino)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-((1S,4S)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-((1R,4R)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(8-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 5-((4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(((1-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(1-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(((1-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(1-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1′-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-[1,4′-bipiperidine]-4-carboxamide; 4-(2,6-dichlorobenzamido)-N-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide; 4-(2,6-dichlorobenzamido)-N-(1-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methoxy)phenyl)acetamide; 5-((4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(((4-(5-chloro-2-((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((5'-chloro-2'-((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridyl]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; 7-cyclopentyl-2-((5-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((1S,4S)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((1R,4R)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((8-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((6-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(((1-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(1-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 8-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 5-((4-(1-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)amino)piperidin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; N-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-fluoro-5-methoxy-4-((4-((2-methyl-3-oxoisoindolin-4-yl)oxy)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(4-((4-((3-(methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-[1,4'-bipiperidinyl]-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; 2-(2-((cyclopropylmethyl)amino)pyridin-4-yl)-N-(3-(difluoromethyl)-1-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1H-pyrazol-4-yl)oxazole-4-carboxamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-7-yl)-3-(trifluoromethyl)benzamide; N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxamide; N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxamide; N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1S,4R)-4-(((1S,4S)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1R,4R)-4-(((1R,4R)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((8-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((6-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; N-(5-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; N-(5-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; N-(5-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; N-(5-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; N-(5-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-1-((1s,4s)-4-(hydroxymethyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide; 6-(5-cyano-1H-pyrrolo[2,3-b]pyridin-1-yl)-N-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-4-(isopropylamino)nicotinamide; N-(3-(difluoromethyl)-1-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; N-(3-(difluoromethyl)-1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; N-(3-(difluoromethyl)-1-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-[1,4'-bipiperidinyl]-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxamide; (R)-N-(2-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-5-(3-hydroxypyrrolidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]thiazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]oxazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]oxazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]oxazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-[1,4'-bipiperidin]-4-yl)methyl)piperidin-4-yl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; 6-(6-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; 6-(6-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; 6-(6-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; (R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d8)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3,5-dimethylpiperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-2,6-dimethylpiperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(6-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(3-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(8-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(3-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((R)-4-((1R,4R)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((R)-4-((1S,4S)-5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((2R)-4-(5-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; (R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide; 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-(((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)amino)-3-nitrophenyl)sulfonyl)benzamide; (R)-N-(1-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)amino)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; 5-((4-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)-[1,4'-bipiperidinyl]-1'-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(3-amino-6-(5-fluoro-2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)methyl)-[1,4'-bipiperidinyl]-1'-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-(((1-(4-((9-chlorophenyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-(((1-(4-((9-chlorophenyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(1-(4-((9-chlorophenyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(1-(4-((9-chlorophenyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-(((1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-(((1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(1-(4-((5-bromo-4-((5-(dimethylphosphonyl)quinoxalin-6-yl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-(((1-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-(((1-(1-isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-((1R,4R)-5-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-(6-(4-((1R,4R)-5-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-4-fluoro-1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide; 4-(((4-(5-chloro-2-((1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((4-(5-chloro-2-((1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 5-(4-((4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(((5'-chloro-2'-((1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridyl]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((5'-chloro-2'-((1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridyl]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-(4-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)acetamide; N-(4-((4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-((4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; N-(4-(chlorodifluoromethoxy)phenyl)-6-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)-5-(1H-pyrazol-3-yl)nicotinamide; 7-Chlorophenyl-2-((5-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Chlorophenyl-2-((5-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-chlorophenyl-2-((5-(4-(((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)(methyl)amino)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-(((1-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-(((1-(6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)isoindoline-1,3-dione; 7-Chlorophenyl-2-((5-(4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Chlorophenyl-2-((5-(4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Chlorophenyl-2-((5-(4-((5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 8-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 1-(5-((4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-(((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-(((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((1S,4S)-5-((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((1R,4R)-5-((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(dimethylphosphonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; N-(3-(((2-((4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-(4-((4-((3-(methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-(4-((4-((3-(methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; N-(3-(((2-((4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; N-(3-(((2-((4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)phenyl)-N-methylmethanesulfonamide; 2-((2-((4-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 2-((2-((4-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-2-isopropoxy-5-methylphenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide; 6-(5-cyano-1H-pyrrolo[2,3-b]pyridin-1-yl)-N-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-4-(isopropylamino)nicotinamide; 6-(5-cyano-1H-pyrrolo[2,3-b]pyridin-1-yl)-N-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-4-(isopropylamino)nicotinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]thiazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]thiazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(2-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-[1,4'-bipiperidin-4-yl)methyl)piperidin-4-yl)-5-(2-hydroxypropan-2-yl)benzo[d]oxazol-6-yl)-6-(trifluoromethyl)picolinamide; N-(3-(difluoromethyl)-1-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-[1,4'-bipiperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-(1-((1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-[1,4'-bipiperidin-4-yl)methyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; (R)-N-(2-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-5-(3-hydroxypyrrolidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide; (R)-N-(2-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)-5-(3-hydroxypyrrolidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide; N-(1-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-methoxy-1H-indazol-7-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1S,4r)-4-(((1S,4S)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1R,4r)-4-(((1R,4R)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((8-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1S,4r)-4-(((1S,4S)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1R,4r)-4-(((1R,4R)-5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((8-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide; N-(2-((1r,4r)-4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,3-difluoropiperidin-4-yl)piperazin-1-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; N-(2-((1r,4r)-4-((5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)cyclohexyl)-6-methoxy-2H-indazol-5-yl)-3-(trifluoromethyl)benzamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 5-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-N-(3-(difluoromethyl)-1-((1r,4R)-4-((5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)cyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide; 6-(6-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; 6-(6-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)pyridin-3-yl)-1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-((4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-((4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)(methyl)amino)piperidin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)(methyl)amino)piperidin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4′-(4-(1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-1-yl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide; (R)-N-(1-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; (R)-N-(1-(4-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)benzyl)-1H-pyrazol-4-yl)-9-methyl-6-oxo-6,7,8,9-tetrahydropyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamide; 2-((5-bromo-2-((4-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)sulfonyl)-2-methylphenyl)amino)pyrimidin-4-yl)amino)-6-fluorobenzamide; 2-((5-bromo-2-((4-((4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)sulfonyl)-2-methylphenyl)amino)pyrimidin-4-yl)amino)-6-fluorobenzamide; 2-((5-bromo-2-((4-((4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)sulfonyl)-2-methylphenyl)amino)pyrimidin-4-yl)amino)-6-fluorobenzamide; 2-((5-bromo-2-((4-((4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)sulfonyl)-2-methylphenyl)amino)pyrimidin-4-yl)amino)-6-fluorobenzamide; 1-(5-((4-((4-((5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-((4-((5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-((4-((5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-((4-((5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-((4-((5-amino-1-(3-methylthiophene-2-carbonyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-((4-((5-amino-1-(3-methylthiophene-2-carbonyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-((4-((5-amino-1-(3-methylthiophene-2-carbonyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-((4-((5-amino-1-(3-methylthiophene-2-carbonyl)-1H-1,2,4-triazol-3-yl)amino)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazole-3-carboxamide; 4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-(4-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazole-3-carboxamide; 4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazole-3-carboxamide; 4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-(4-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazole-3-carboxamide; 1-(5-((4-(5-(5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(5-(5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(5-(5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 1-(1-oxo-5-((4-(5-(5-(2,2,2-trifluoroethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(5-(5-(2,2,2-trifluoroethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-(5-(5-(2,2,2-trifluoroethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-(5-(5-(2,2,2-trifluoroethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 1-(5-((4-(5-(5-(difluoromethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(5-(5-(difluoromethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(5-(5-(difluoromethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(5-(5-(difluoromethyl)-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)-3-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)-3-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)-3-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)-3-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)-4-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)-4-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-(5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)-4-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 1-(5-((4-(3-methyl-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(3-methyl-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-((4-(3-methyl-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-((4-(3-methyl-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione; 1-(5-((4-(3-chloro-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(3-chloro-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(3-chloro-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(3-chloro-5-(5-methyl-5H-pyrido[4,3-b]indol-7-yl)pyridin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((4-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((4-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperazin-1-yl)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((4-(1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)piperazin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-(((1-(4-(4-acetyl-1,4-diazepan-1-yl)-6-((2-(thiophen-2-yl)ethyl)amino)-1,3,5-triazin-2-yl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-(((1-(4-(4-acetyl-1,4-diazepan-1-yl)-6-((2-(thiophen-2-yl)ethyl)amino)-1,3,5-triazin-2-yl)piperidin-4-yl)(methyl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((1S,4S)-5-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((1R,4R)-5-((1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(6-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(3-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(8-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(4-((1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoroisoindoline-1,3-dione; 6-(4-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-(4-((1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(4-(4-((1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(5-((1-(Benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-chloro-2-(7-chloro-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)phenoxy)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-chloro-2-(7-chloro-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)phenoxy)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)amino)phenyl)cyclopropane-1-carbonitrile; 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((1-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)amino)phenyl)cyclopropane-1-carbonitrile; 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)phenyl)cyclopropane-1-carbonitrile; 1-(4-((5-(3,5-dimethylisoxazol-4-yl)-2-methylphenyl)((1-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)phenyl)cyclopropane-1-carbonitrile; 1-(5-((2-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-(methylsulfonyl)phenoxy)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((5-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)nicotinamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)amino)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; 1-(5-(((1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)amino)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)amino)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; 5-(((1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)amino)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)amino)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(4-((2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)amino)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; 5-(4-(((1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)amino)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)amino)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; 4-(4-(((1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)amino)methyl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)amino)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(3,4-difluorophenyl)-3-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)propan-2-yl)furan-2-carboxamide; (S)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-(1-(4-((1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)-3-(3-fluorophenyl)propan-2-yl)thiophene-2-carboxamide; 1-(5-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepanin[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(2,4-Dioxotetrahydropyrimidin-1(2H)-yl)-5-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepanin[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepanin[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(4-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepanin[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)piperidin-1-yl)isoindoline-1,3-dione; and 1-(5-((4-(1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione.

20. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, or polymorph thereof as claimed in any one of claims 1 to 19, which is a hydrohalide (including hydrochloride, hydrobromide), sulfate, citrate / citrate, maleate, methanesulfonate, lactate, lactobionate, L-tartrate, fumarate, L-malate, α-ketoglutarate, hippurate, D-glucuronate, D-glucon ... -D-Gluceptate, Glycolate, Mucate, L-Ascorbate, Orotate, Picrate, Glycinate, Alanine, Arginine, Cinnamate, Laurate, Pamoate, Sebacate, Benzenesulfonate, Methanesulfonate, Ethylate, Ethylenedisulfonate, Formate, Acetate, 2,2-Dichloroacetate, Trimethylacetate, Propionate, Valerate, Palmitate, Triphenylacetate, 2-Ethyl-Succinate, Iodate, Nicotinate, L-Pyroglutamate, L-proline, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecylenate, camphorate, camphorsulfonate, dodecylsulfonate, phosphate, thiocyanate, dihydrogenphosphate, pyrophosphate, metaphosphate, oxalate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthoate, trifluoroacetate, methanesulfonate, hippurate, glycolate, or p-toluenesulfonate.

21. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof: in A represents CO, CH2 or CD2; R a1 、R a2 、R a3 and R a4 The same or different and each independently represents hydrogen, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy or halogenated C 1-6 alkoxy; (R a5 ) m represents that the isoindoline ring connected thereto is optionally replaced by m R a5 Replace, each R a5 The same or different and each independently represents halogen, hydroxyl, mercapto, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1- 6 alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 Alkynyl; m represents an integer 0, 1, 2, 3 or 4; R w represents O, S, S(O), S(O)2, alkenylene, alkynylene or N(R a6 ), where R a6 Indicates H or C 1-3 Alkyl, or R w represents a key; or R w express: Among them, each ring A 1 are the same or different and each independently represent a nitrogen-containing heterocyclic group, an arylene group or a heteroarylene group, y1 represents an integer of 1 or 2, (R y1 ) a1 Represents each ring A 1 Each independently optionally represented by a1 R y1 Group substitution, each R y1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl, and a1 represents an integer of 0-20; Each ring A 2 are the same or different and each independently represent a heterocyclylene group, a cycloalkylene group, an arylene group or a heteroarylene group, y2 represents an integer of 0 or 1, (R y2 ) a2 Represents each ring A 2 independently optionally by a2 R y2 Group substitution, each R y2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2- 6 alkenyl, and a2 represents an integer of 0-20; and R w1 represents a bond, or represents an optionally substituted straight or branched C 1-20 Alkylene, wherein the linear or branched C 1-20 Any one or more methylene groups of the main carbon chain skeleton of the alkylene group may be optionally replaced by one or more groups selected from the following: a 、R b and any combination thereof, each group R a Each independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each R a7 Each independently represents H or C 1-3 Alkyl, and When the linear or branched C 1-20 One or more adjacent methylene groups of the main carbon chain skeleton of the alkylene group are replaced by one or more groups R a When substituted, each group R a Not directly connected to each other; each group R b are each independently selected from optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene, alkynylene, alkenylene, and any combination thereof; and R w3 represents hydrogen, deuterium, a leaving group, a hydroxyl group, a halogen, COOH, NH2, N3, CHO, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group or a p-toluenesulfonyloxy group.

22. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 21, which is also a compound of formula (II-1) or formula (II-2): Among them, A, (R a5 ) m 、R w Ring A 1 Ring A 2 ,y1,(R y1 ) a1 ,y2,(R y2 ) a2 、R w1 and R w3 As defined in claim 20.

23. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in claim 21 or 22, wherein (i) Each ring A 1 Each independently represents a 4- to 20-membered nitrogen-containing heterocyclic group, C 5-20 arylene or 5- to 20-membered heteroarylene; preferably each ring A 1 Each independently represents: piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazepanylene, azaoctinylene, diazaoctinylene, azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene alkylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene, diazabicyclo[2.2.2]octanylene, 3-azaspiro[5.5]undecylene, 8-azaspiro[4.5]decylene, 2-oxa-8-azaspiro[4.5]decylene, 3-methyl-2-oxa-8-azaspiro[4.5]decylene, phenylene, naphthylene, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, phenylene Thiazolyl, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothiophenylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolelene, benzo[2,1,3]oxadiazolelene, benzo[2,1,3]thiadiazolylene , benzo[1,2,3]thiadiazolylidene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylidene, or imidazo[2,1-b]thiazolylidene, or Each ring A 1 Each independently optionally represented by a1 R y1 Group substitution, each R y1 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl; and a1 represents an integer from 0 to 20; and / or (ii) Each ring A 2 Each independently represents a 4- to 20-membered heterocyclylene group, C 3-20 Cycloalkylene, C 5-20 arylene or 5- to 20-membered heteroarylene; preferably each ring A 2 Each independently represents: Azolidinyl, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azepanylene, dioxanylene, azepanylene, azepanylene, diazepanylene, diazepanylene, diazacycloheptanediylene, diazacyclooctanylene, 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6 -diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, 5- to 20-membered azaspirocyclic group, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C 5-15 spirocyclylene, adamantylene, noradamantylene, norbornylene, phenylene, naphthylene, furylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene yl, benzo[2,1,3]oxadiazoleylidene, benzo[2,1,3]thiadiazolylidene, benzo[1,2,3]thiadiazolylidene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylidene, or imidazo[2,1-b]thiazolylidene, or Each ring A 2 Each independently optionally represented by a2 R y2 Group substitution, each R y2 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 alkenyl; and a2 represents an integer from 0 to 20.

24. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in claim 21, wherein R w express: wherein the above groups are optionally selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxyl, C 2-6 Alkynyl or C 2-6 The substituents of the alkenyl group are substituted.

25. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 21 or 22, wherein R w1 represents a bond, or represents an optionally substituted straight or branched C 1-20 Alkylene, wherein the linear or branched C 1-20 Any one or more methylene groups of the main carbon chain skeleton of the alkylene group may be optionally replaced by one or more groups selected from the following: a 、R b and any combination thereof, each group R a Each independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each R a7 Each independently represents H or C 1-3 Alkyl, and when the linear or branched C 1-20 Any two or more methylene groups of the main carbon chain skeleton of the alkylene group are replaced by two or more groups R a When substituted, each group R a Not directly connected to each other; each group R b are each independently selected from optionally substituted cycloalkylene (eg, optionally substituted C 3-20 cycloalkylene), optionally substituted arylene (e.g., optionally substituted C 5-20 arylene), optionally substituted heterocyclylene (e.g., optionally substituted 4- to 20-membered heterocyclylene), optionally substituted heteroarylene (e.g., optionally substituted 5- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 Alkyne), alkenylene (e.g. C 2-6 and any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene and the heteroarylene are each independently optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 cycloalkyl, 4- to 10-membered heterocyclic group and any combination thereof, and wherein the linear or branched C 1-20 One or more hydrogen atoms of the alkylene group may be selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, halo, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 The substituents are substituted by cycloalkyl, 4- to 10-membered heterocyclyl, and any combination thereof.

26. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in claim 21 or 22, wherein R w1 Indicates a key, or R w1 express: -C 1-15 Alkylene-; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -(R a (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -(R a (C(R a12 )(R a13 )) n3 ) m4 -(R a (C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -((C(R a12 )(R a13 )) n3 R a ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -((C(R a12 )(R a13 )) n3 R a ) m4 -((C(R a14 )(R a15 )) n4 R a ) m5 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -(R b (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -(R b (C(R a12 )(R a13 )) n3 ) m4 -(R b (C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -((C(R a12 )(R a13 )) n3 R b ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -((C(R a12 )(R a13 )) n3 R b ) m4 -((C(R a14 )(R a15 )) n4 R b ) m5 -; -(C(R a8 )(R a9 )) n1 -(R a -R b -(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R a (C(R a10 )(R a11 )) n2 ) m3 -(R b (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(R b -R a -(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(R b (C(R a10 )(R a11 )) n2 ) m3 -(R a (C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -R a -R b ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R a ) m3 -((C(R a12 )(R a13 )) n3 R b ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -R b -R a ) m3 -;or -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 R b ) m3 -((C(R a12 )(R a13 )) n3 R a ) m4 -; in, Each group R a independently selected from O, C(O), OC(O), S, S(O), S(O)2, S(O)2N(R a7 )、N(R a7 )S(O)2、C(O)N(R a7 )、N(R a7 )C(O), N(R a7 ) and N(R a7 )C(O)N(R a7 ), where each R a7 Each independently represents H or C 1-3 Alkyl; each group R b are independently selected from optionally substituted cycloalkylene (eg, optionally substituted C 3-20 cycloalkylene), optionally substituted arylene (e.g., optionally substituted C 5-20 arylene), optionally substituted heterocyclylene (e.g., optionally substituted 4- to 20-membered heterocyclylene), optionally substituted heteroarylene (e.g., 5- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 Alkyne), alkenylene (e.g. C 2-6 and any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene and the heteroarylene are each independently optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 substituted by cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof; R a8 、R a9 、R a10 、R a11 、R a12 、R a13 、R a14 and R a15 Each independently represents H, deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, halo 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 Cycloalkyl, 4- to 10-membered heterocyclyl, and any combination thereof; and n1, n2, n3, n4, m3, m4, m5 are each independently selected from the integers 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and The C 1-15 Any one or more hydrogen atoms of the main carbon chain of the alkylene group may be optionally replaced by a substituent selected from the group consisting of deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof.

27. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in claim 21 or 22, wherein R w1 Represents the following structure: -(C(R a8 )(R a9 )) n1 -(O(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(O(C(R a10 )(R a11 )) n2 ) m3 -(O(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(O(C(R a10 )(R a11 )) n2 ) m3 -(O(C(R a12 )(R a13 )) n3 ) m4 -(O(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 O) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 O) m3 -((C(R a12 )(R a13 )) n3 O) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 O) m3 -((C(R a12 )(R a13 )) n3 O) m4 -((C(R a14 )(R a15 )) n4 O) m5 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )(C(R a10 )(R a11 )) n2 ) m3 -(N(R a7 )(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )(C(R a10 )(R a11 )) n2 ) m3 -(N(R a7 )(C(R a12 )(R a13 )) n3 ) m4 -(N(R a7 )(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 N(R a7 )) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 N(R a7 )) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 N(R a7 )) m4 -((C(R a14 )(R a15 )) n4 N(R a7 )) m5 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -(C(O)N(R a7 )-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -(C(O)N(R a7 )-(C(R a12 )(R a13 )) n3 ) m4 -(C(O)N(R a7 )-(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 -C(O)N(R a7 )) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 -C(O)N(R a7 )) m4 -((C(R a14 )(R a15 )) n4 -C(O)N(R a7 )) m5 -; -(C(R a8 )(R a9 )) n1 -(C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 ) m3 -(O-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 -(O(C(R a12 )(R a13 )) n3 ) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -C(O)N(R a7 )) m3 -((C(R a12 )(R a13 )) n3 O) m4 -; -(C(R a8 )(R a9 )) n1 -(C(R a10 )(R a11 )) n2 -C(O)N(R a7 )-((C(R a12 )(R a13 )) n3 O) m3 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 ) m3 -(O-(C(R a12 )(R a13 ))) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -(N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 ) m3 -(O-(C(R a12 )(R a13 )) n3 ) m4 -(O-(C(R a14 )(R a15 )) n4 ) m5 -; -(C(R a8 )(R a9 )) n1 -N(R a7 )C(O)-(C(R a10 )(R a11 )) n2 -(O(C(R a12 )(R a13 )) n3 ) m3 -; -(C(R a8 )(R a9 )) n1 -N(R a7 )C(O)N(R a7 )-(C(R a10 )(R a11 )) n2 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -N(R a7 )C(O)) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -N(R a7 )C(O)) m3 -((C(R a12 )(R a13 ))) n3 -O) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -N(R a7 )C(O)) m3 -((C(R a12 )(R a13 )) n3 O) m4 -((C(R a14 )(R a15 )) n4 O) m5 -; -(C(R a8 )(R a9 )) n1 -(C(R a10 )(R a11 )) n2 -N(R a7 )C(O)-((C(R a12 )(R a13 )) n3 O) m3 -; -(C(R a8 )(R a9 )) n1 -(arylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(arylene-(C(R a10 )(R a11 )) n2 ) m3 -arylene-(C(R a12 )(R a13 )) n3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -arylene) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -arylene) m3 -(C(R a12 )(R a13 )) n3 -arylene-; -(C(R a8 )(R a9 )) n1 -(Heterocyclylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(Heterocyclylene-(C(R a10 )(R a11 )) n2 ) m3 -(Heterocyclylene-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heterocyclylene) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heterocyclylene) m3 -((C(R a12 )(R a13 )) n3 -heterocyclylene) m4 -; -(C(R a8 )(R a9 )) n1 -(heteroarylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(heteroarylene-(C(R a10 )(R a11 )) n2 ) m3 -(heteroarylene-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heteroarylene) m3 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -heteroarylene) m3 -((C(R a12 )(R a13 )) n3 -heteroarylene) m4 -; -(C(R a8 )(R a9 )) n1 -(cycloalkylene-(C(R a10 )(R a11 )) n2 ) m3 -; -(C(R a8 )(R a9 )) n1 -(cycloalkylene-(C(R a10 )(R a11 )) n2 ) m3 -(cycloalkylene-(C(R a12 )(R a13 )) n3 ) m4 -; -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -cycloalkylene) m3 -;or -(C(R a8 )(R a9 )) n1 -((C(R a10 )(R a11 )) n2 -cycloalkylene) m3 -((C(R a12 )(R a13 )) n3 -cycloalkylene) m4 -; in, Each R a7 independently represents H or C 1-3 alkyl; The cycloalkylene group (eg C 3-20 Cycloalkylene), the arylene group (such as C 5-20 arylene), the heterocyclylene (e.g., 4- to 20-membered heterocyclylene) and the heteroarylene (e.g., 5- to 20-membered heteroarylene) are each independently optionally selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 substituted by cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof; R a8 、R a9 、R a10 、R a11 、R a12 、R a13 、R a14 and R a15 Each independently represents H, deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, halo 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 Cycloalkyl, 4- to 10-membered heterocyclyl, and any combination thereof; and n1, n2, n3, n4, m3, m4, m5 are each independently selected from integers 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

28. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in any one of claims 21 to 27, wherein R w1 express: -CH2-、-(CH2)2-、-(CH2)3-、-(CH2)4-、-(CH2)5-、-(CH2)6-、-(CH2)7-、-(CH2)8-、-(CH2)9-、-(CH2) 10 -、-(CH2) 11 -、-(CH2) 12 -、-(CH2) 13 -、-(CH2) 14 -、-(CH2) 15 -;-O-CH2-、-O-(CH2)2-、-O-(CH2)3-、-O-(CH2)4-、-O-(CH2)5-、-O-(CH2)6-、-O-(CH2)7-、-O-(CH2)8-、-O-(CH2)9-、-O-(CH2) 10 -、-(CH2)1-O-、-(CH2)2-O-、-(CH2)3-O-、-(CH2)4-O-、-(CH2)5-O-、-(CH2)6-O-、-(CH2)7-O-、-(CH2)8-O-、-(CH2)9-O-、-(CH2) 10 -O-、-CH2-O-CH2-、-CH2-O-(CH2)2-、-(CH2)1-O-(CH2)3-、-(CH2)1-O-(CH2)4-、-(CH2)1-O-(CH2)5-、-(CH2)1-O-(CH2)6-、-(CH2)1-O-(CH2)7-、-(CH2)1-O-(CH2)8-、-(CH2)1-O-(CH2)9-、-(CH2)1-O-(CH2) 10 -、-(CH2)2-O-(CH2)1-、-(CH2)2-O-(CH2)2-、-(CH2)2-O-(CH2)3-、-(CH2)2-O-(CH2)4-、-(CH2)2-O-(CH2)5-、-(CH2)2-O-(CH2)6-、-(CH2)2-O-(CH2)7-、-(CH2)2-O-(CH2)8-、-(CH2)2-O-(CH2)9-、-(CH2)2-O-(CH2) 10 -、-(CH2)3-O-(CH2)1-、-(CH2)3-O-(CH2)2-、-(CH2)3-O-(CH2)3-、-(CH2)3-O-(CH2)4-、-(CH2)3-O-(CH2)5-、-(CH2)3-O-(CH2)6-、-(CH2)3-O-(CH2)7-、-(CH2)4-O-(CH2)1-、-(CH2)4-O-(CH2)2-、-(CH2)4-O-(CH2)3-、-(CH2)4-O- (CH2)4-、-(CH2)4-O-(CH2)5-、-(CH2)4-O-(CH2)6-、-(CH2)5-O-(CH2)1-、-(CH2)5-O-(CH2)2-、-(CH2)5-O-(CH2)3-、-(CH2)5-O-(CH2)4-、-(CH2)5-O-(CH2)5-、-(CH2)6-O-(CH2)1-、-(CH2)6-O-(CH2)2-、-(CH2)6-O-(CH2)3-、-(CH2)6-O-(CH2)4-、-(CH2)7-O-(CH2)1-、-(CH2)7-O-(CH2)2- 、-(CH2)7-O-(CH2)3-、-(CH2)8-O-(CH2)1-、-(CH2)8-O-(CH2)2-、-CH(CH3)-O-(CH2)1-、-CH(CH3)-O-(CH2)2-、-CH(CH3)-O-(CH2)3-、-CH(CH3)-O-(CH2)4-、-CH(CH3)-O-(CH2)5-、-CH(CH3)-O-(CH2)6-、-CH(CH3)-O-(CH2)7-、-CH(CH3)-O-(CH2)8-、-CH(CH3)-O-(CH2)9-、-CH(CH3)-O-(CH2) 10 -、-(O(CH2)2)2-、-(O(CH2)2)3-、-(O(CH2)2)4-、-(O(CH2)2)5-、-(O(CH2)2)6-、-(O(CH2)2)7-、-CH2-(O(CH2)2)2-、-CH2-(O(CH2)2)3-、-CH2-(O(CH2 )2)4-、-CH2-(O(CH2)2)5-、-CH2-(O(CH2)2)6-、-CH2-(O(CH2)2)7-、-CH2- (O(CH2)2)1-OCH2-、-CH2-(O(CH2)2)2-OCH2-、-CH2-(O(CH2)2)3-OCH2-、-C H2-(O(CH2)2)4-OCH2-、-CH2-(O(CH2)2)5-OCH2-、-(CH2)2-(O(CH2)2)2-、 -(CH2)2-(O(CH2)2)3-、-(CH2)2-(O(CH2)2)4-、-(CH2)2-(O(CH2)2)5-、-(C H2)2-(O(CH2)2)6-、-(CH2)3-(O(CH2)2)2-、-(CH2)3-(O(CH2)2)3-、-(CH2 )3-(O(CH2)2)4-、-(CH2)3-(O(CH2)2)5-、-(CH2)4-(O(CH2)2)2-、-(CH2)4- (O(CH2)2)3-、-(CH2)4-(O(CH2)2)4-、-(CH2)4-(O(CH2)2)5-、-CH2-(O(CH2)3)2-、-CH2-(O(CH2)3)3-、-CH2-(O(CH2)3)4-、-(CH2)2-(O(CH2)3)2-、-( CH2)2-(O(CH2)3)3-、-(CH2)2-(O(CH2)3)4-、-(CH2)3-(O(CH2)3)2-、-(CH2)3-(O(CH2)3)3-、-(CH2)3-(O(CH2)3)4-、-CH2-O-(CH2)2-O-(CH2)3-、-CH2-(O(CH2)2)2-(O(CH2)3)2-、(CH2)2-O-(CH2)2-O-(CH2)3-、-(CH2)2-(O(CH2)3)2-、-(CH2)3-O-(CH2)2-O-(CH2)3-、-(CH2)3-(O(CH2)2 )2-(O(CH2)3)2-、-CH2-O-(CH2)3-O-(CH2)2-、-CH2-(O(CH2)3)2-(O(CH2)2)2-、-(CH2)2-O-(CH2)3-O-(CH2)2-、-(CH2)2-(O(CH2)3)2-(O(CH2)2)2-、-(CH2)3-O-(CH2)3-O-(CH2)2-、-(CH2)3-(O(CH2)3)2-(O(CH2)2)2-、-CH2-O-(CH2)2-O-CH2-、-(CH2)2-O-(CH2)2-O-CH2-、-(CH2)2-(O(CH2)2)2-O-(CH2)3-、-(CH2)2-(O(CH2)2)3-O-(CH2)3-、-(CH2)2-(O(CH2)2)4-O-(CH2)3-、-(CH2)5-(O(CH2)2)2-O-(CH2)5-、-(CH2)5-(O(CH2)2)2-O-(CH2)6-、-(CH2)1-N(R、 a7 )-(CH2)1-、-(CH2)1-N(R a7 )-(CH2)2-、-(CH2)1-N(R a7 )-(CH2)3-、-(CH2)1-N(R a7 )-(CH2)4-、-(CH2)1-N(R a7 )-(CH2)5-、-(CH2)1-N(R a7 )-(CH2)6-、-(CH2)1-N(R a7 )-(CH2)7-、-(CH2)1-N(R a7 )-(CH2)8-、-(CH2)1-N(R a7 )-(CH2)9-、-(CH2)1-N(R a7 )-(CH2) 10 -、-N(R a7 )-(CH2)1-、-N(R a7 )-(CH2)2-、-N(R a7 )-(CH2)3-、-N(R a7 )-(CH2)4-、-N(R a7 )-(CH2)5-、-N(R a7 )-(CH2)6-、-N(R a7 )-(CH2)7-、-N(R a7 )-(CH2)8-、-N(R a7 )-(CH2)9-、-N(R a7 )-(CH2) 10 -、-(CH2)2-N(R a7 )-(CH2)1-、-(CH2)2-N(R a7 )-(CH2)2-、-(CH2)2-N(R a7 )-(CH2)3-、-(CH2)2-N(R a7 )-(CH2)4-、-(CH2)2-N(R a7 )-(CH2)5-、-(CH2)2-N(R a7 )-(CH2)6-、-(CH2)2-N(R a7 )-(CH2)7-、-(CH2)2-N(R a7 )-(CH2)8-、-(CH2)2-N(R a7 )-(CH2)9-、-(CH2)2-N(R a7 )-(CH2) 10 -、-(CH2)3-N(R a7 )-(CH2)1-、-(CH2)3-N(R a7 )-(CH2)2-、-(CH2)3-N(R a7 )-(CH2)3-、-(CH2)4-N(R a7 )-(CH2)1-、-(CH2)4-N(R a7 )-(CH2)2-、-(CH2)4-N(R a7 )-(CH2)3-、-(CH2)4-N(R a7 )-(CH2)4-、-(CH2)5-N(R a7 )-(CH2)1-、-(CH2)5-N(R a7 )-(CH2)2-、-(CH2)5-N(R a7 )-(CH2)3-、-(CH2)5-N(R a7 )-(CH2)4-、-(CH2)5-N(R a7 )-(CH2)5-、-(CH2)6-N(R a7 )-(CH2)1-、-(CH2)6-N(R a7 )-(CH2)2-、-(CH2)6-N(R a7 )-(CH2)3-、-(CH2)7-N(R a7 )-(CH2)1-、-(CH2)7-N(R a7 )-(CH2)2-、-(CH2)7-N(R a7 )-(CH2)3-、-(CH2)8-N(R a7 )-(CH2)1-、-(CH2)8-N(R a7 )-(CH2)2-、-(CH2)8-N(R a7 )-(CH2)3-、-CH(CH3)-N(R a7 )-(CH2)1-、-CH(CH3)-N(R a7 )-(CH2)2-、-CH(CH3)-N(R a7 )-(CH2)3-、-CH(CH3)-N(R a7 )-(CH2)4-、-CH(CH3)-N(R a7 )-(CH2)5-、-CH(CH3)-N(R a7 )-(CH2)6-、-CH(CH3)-N(R a7 )-(CH2)7-、-CH(CH3)-N(R a7 )-(CH2)8-、-CH(CH3)-N(R a7 )-(CH2)9-、-CH(CH3)-N(R a7 )-(CH2) 10 -、-C(O)NHCH2-、-C(O)NH(CH2)2-、-C(O)NH(CH2)3-、-C(O)NH(CH2)4-、-C(O)NH(CH2)5-、-CH2C(O)NHCH2-、-(CH2)2C(O)NH(CH2)2-、-(CH2)2C(O)NH(CH2)3-、 -(CH2)2C(O)NH(CH2)4-, -(CH2)2C(O)NH(CH2)5-, -(CH2)3C(O)NH(CH2)3-, -(CH2)3C(O)NH(CH2)4-, -(CH2)4C(O)NH(CH2)4-, -(CH2)5C(O)NH(CH2)5- , -(CH2)6C(O)NH(CH2)7-, -(CH2)6C(O)NH(CH2)6-, -(CH2)7C(O)NH(CH2)7-, -(CH2)2C(O)NH(CH2)2-O-(CH2)2-, -NHC(O)CH2-, -NHC(O)(CH2)2-, -NHC (O)(CH2)3-, -NHC(O)(CH2)4-, -NHC(O)(CH2)5-, -CH2NHC(O)CH2-, -(CH2)2NHC(O)(CH2)2-, -(CH2)2NHC(O)(CH2)3-, -(CH2)2NHC(O)(CH2)4-, -(CH2) 2NHC(O)(CH2)5-, -(CH2)3NHC(O)(CH2)3-, -(CH2)3NHC(O)(CH2)4-, -(CH2)4NHC(O)(CH2)4-, -(CH2)5NHC(O)(CH2)5-, -(CH2)6NHC(O)(CH2)7-, -(CH2 )6NHC(O)(CH2)6-、-(CH2)7NHC(O)(CH2)7-、-(CH2)4NHC(O)(CH2)8-、-(CH2)2NHC(O)(CH2)2-O-(CH2)2-、-(CH2)4NHC(O)CH2-、-phenylene-CH2-、-phenylene-(CH2)2-、-phenylene-(CH2)3-、-phenylene-(CH2)4-、-phenylene-(CH2)5-、-phenylene-(CH2)6-、-phenylene-(CH2)7-、-phenylene-(CH2)8-、-CH2-phenylene-CH2-、-CH2-phenylene-(CH2)2-、-CH2-phenylene-(CH 2)3-, -CH2-phenylene-(CH2)4-, -CH2-phenylene-(CH2)5-, -CH2-phenylene-(CH2)6-, -CH2-phenylene-(CH2)7-, -CH2-phenylene-(CH2)8-, -(CH2)2-phenylene-(CH2)1-, -(CH2)2-phenylene-(CH2)2-, -(CH2)2-phenylene-(CH2)3-, -(CH2)2-phenylene-(CH2)4-, -(CH2)2-phenylene-(CH2)5-, -(CH2)2-phenylene-(CH2)6-, -(CH2)2-phenylene-(CH2)7-, -(CH2)2-phenylene-(CH2)8-,-(CH2)3-phenylene-CH2-, -(CH2)3-phenylene-(CH2)2-, -(CH2)3-phenylene-(CH2)3-, -(CH2)3-phenylene-(CH2)4-, -(CH2)3-phenylene-(CH2)5-, -(CH2)3-phenylene-(CH2)6-, -(CH2)3-phenylene-(CH2)7-, -(CH2)3-phenylene-(CH2)8-, -(CH2)4-phenylene-CH2-, -(CH2)4-phenylene-(CH2)2-, -(CH2)4-phenylene-(CH2)3-, -(CH2 )4-phenylene-(CH2)4-, -(CH2)4-phenylene-(CH2)5-, -(CH2)4-phenylene-(CH2)6-, -(CH2)4-phenylene-(CH2)7-, -(CH2)4-phenylene-(CH2)8-, -(CH2)5-phenylene-(CH2)1-, -(CH2)5-phenylene-(CH2)2-, -(CH2)5-phenylene-(CH2)3-, -(CH2)5-phenylene-(CH2)4-, -(CH2)5-phenylene-(CH2)5-, -(CH2)5-phenylene-(CH2)6-, -(CH 2)5-phenylene-(CH2)7-, -(CH2)5-phenylene-(CH2)8-, -(CH2)6-phenylene-(CH2)1-, -(CH2)6-phenylene-(CH2)2-, -(CH2)6-phenylene-(CH2)3-, -(CH2)6-phenylene-(CH2)4-, -(CH2)6-phenylene-(CH2)5-, -(CH2)6-phenylene-(CH2)6-, -(CH2)6-phenylene-(CH2)7-, -(CH2)6-phenylene-(CH2)8-, -(CH2)7-phenylene-(CH2)1-, -(CH2)6-phenylene-(CH2)2-, -(CH2)6-phenylene-(CH2)3-, -(CH2)6-phenylene-(CH2)4-, -(CH2)6-phenylene-(CH2)5-, -(CH2)6-phenylene-(CH2)6-, -(CH2)6-phenylene-(CH2)7-, -(CH2)6-phenylene-(CH2)8-, -(CH2)7-phenylene-(CH2)1-, -(CH2)6-phenylene H2)7-phenylene-(CH2)2-, -(CH2)7-phenylene-(CH2)3-, -(CH2)7-phenylene-(CH2)4-, -(CH2)7-phenylene-(CH2)8-, -(CH2)8-phenylene-CH2-, -(CH2)8-phenylene-(CH2)2-, -(CH2)8-phenylene-(CH2)3-, -(CH2)8-phenylene-(CH2)4-, -(CH2)8-phenylene-(CH2)5-, -(CH2)8-phenylene-(CH2)6-, -(CH2)8-phenylene-(CH2)7-, -N(R, a7 )-CH2-phenylene-CH2-、-N(R a7 )-CH2-phenylene-(CH2)2-, -N(R a7 )-CH2-phenylene-(CH2)3-、-N(R a7 )-CH2-phenylene-(CH2)4-、-N(R a7 )-CH2-phenylene-(CH2)5-、-N(R a7 )-CH2-phenylene-(CH2)6-、-N(R a7 )-CH2-phenylene-(CH2)7-、-N(R a7 )-CH2-phenylene-(CH2)8-, -CH2-N(R a7 )-CH2-phenylene-CH2-, -CH2-N(R a7 )-CH2-phenylene-(CH2)2-, -CH2-N(R a7 )-CH2-phenylene-(CH2)3-, -CH2-N(R a7 )-CH2-phenylene-(CH2)4-, -CH2-N(R a7 )-CH2-phenylene-(CH2)5-, -CH2-N(R a7 )-CH2-phenylene-(CH2)6-, -CH2-N(R a7 )-CH2-phenylene-(CH2)7-, -CH2-N(R a7 )-CH2-phenylene-(CH2)8-, -CH2-N(R a7 )-(CH2)2-phenylene-CH2-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)2-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)3-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)4-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)5-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)6-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)7-, -CH2-N(R a7 )-(CH2)2-phenylene-(CH2)8-, -(CH2)2-N(R a7 )-CH2-phenylene-CH2-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)4-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)5-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)6-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)7-, -(CH2)2-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)3-N(R a7 )-CH2-phenylene-CH2-, -(CH2)3-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)3-N(R a7 )-CH2-phenylene- (CH2)3-、-(CH2)3-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)4-N(R a7 )-CH2-phenylene-CH2-, -(CH2)4-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)4-N(R a7 )-CH2-phenylene-(CH2)3-、-(CH2)4-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)5-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)5-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)6-N(R a7 )-CH2-phenylene-(CH2)3-、-(CH2)6-N(R a7 )-CH2-phenylene-(CH2)8-, -(CH2)7-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)8-N(R a7 )-CH2-phenylene-CH2-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)2-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)3-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)4-、-(CH2)8-N(R a7 )-CH2-phenylene-(CH2)5-, -(CH2)8-N(R a7 )-CH2-phenylene-(CH2)6-, -piperidinylene-CH2-, -piperidinylene-(CH2)2-, -piperidinylene-(CH2)3-, -piperidinylene-(CH2)4-, -piperidinylene-(CH2)5-, -piperidinylene-(CH2)6-, -piperidinylene-(CH2)7-, -piperidinylene-(CH2)8-, -CH2-piperidinylene-CH2-, -CH2-piperidinylene-(CH2)2-, -CH2-piperidinylene-(CH2)3-, -CH2-piperidinylene-(CH2)4-, -CH2-piperidinylene-(CH2)5-, -CH2-piperidinylene-(CH2)6-, -CH2-piperidinylene-(CH2)7- , -(CH2)2-piperidinylene-(CH2)8-, -(CH2)2-piperidinylene-(CH2)1-, -(CH2)2-piperidinylene-(CH2)2-, -(CH2)2-piperidinylene-(CH2)3-, -(CH2)2-piperidinylene-(CH2)4-, -(CH2)2-piperidinylene-(CH2)5-, -(CH2)2-piperidinylene-(CH2)6-, -(CH2)2-piperidinylene-(CH2)7-, -(CH2)2-piperidinylene-(CH2)8-, -(CH2)3-piperidinylene-CH2-, -(CH2)3-piperidinylene-(CH2)2-, -(CH2)3-piperidinylene-(CH2)3-, -( -(CH2)3-piperidinylene-(CH2)4-, -(CH2)3-piperidinylene-(CH2)5-, -(CH2)3-piperidinylene-(CH2)6-, -(CH2)3-piperidinylene-(CH2)7-, -(CH2)3-piperidinylene-(CH2)8-, -(CH2)4-piperidinylene-CH2-, -(CH2)4-piperidinylene-(CH2)2-, -(CH2)4-piperidinylene-(CH2)3-, -(CH2)4-piperidinylene-(CH2)4-, -(CH2)4-piperidinylene-(CH2)5-, -(CH2)4-piperidinylene-(CH2)6-, -(CH2)4-piperidinylene-(CH2)7-, -(CH2)3-piperidinylene-(CH2)8-, -(CH2)4-piperidinylene-CH2-, -(CH2)4-piperidinylene-(CH2)2-, -(CH2)4-piperidinylene-(CH2)3-, -(CH2)4-piperidinylene-(CH2)4-, -(CH2)4-piperidinylene-(CH2)5-, -(CH2)4-piperidinylene-(CH2)6-, -(CH2)4-piperidinylene-(CH2)7-, -(CH2) -(CH2)4-piperidinylene-(CH2)8-, -(CH2)5-piperidinylene-(CH2)1-, -(CH2)5-piperidinylene-(CH2)2-, -(CH2)5-piperidinylene-(CH2)3-, -(CH2)5-piperidinylene-(CH2)4-, -(CH2)5-piperidinylene-(CH2)5-, -(CH2)5-piperidinylene-(CH2)6-, -(CH2)5-piperidinylene-(CH2)7-, -(CH2)5-piperidinylene-(CH2)8-, -(CH2)6-piperidinylene-(CH2)1-, -(CH2)6-piperidinylene-(CH2)2-, -(CH2)6-piperidinylene-(CH2)3-,-(CH2)6-piperidinylene-(CH2)4-, -(CH2)6-piperidinylene-(CH2)5-, -(CH2)6-piperidinylene-(CH2)6-, -(CH2)6-piperidinylene-(CH2)7-, -(CH2)6-piperidinylene-(CH2)8-, -(CH2)7-piperidinylene-(CH2)1-, -(CH2)7-piperidinylene-(CH2)2-, -(CH2)7-piperidinylene-(CH2)3-, -(CH2)7-piperidinylene -(CH2)4-, -(CH2)7-piperidinylene-(CH2)8-, -(CH2)8-piperidinylene-CH2-, -(CH2)8-piperidinylene-(CH2)2-, -(CH2)8-piperidinylene-(CH2)3-, -(CH2)8-piperidinylene-(CH2)4-, -(CH2)8-piperidinylene-(CH2)5-, -(CH2)8-piperidinylene-(CH2)6-, -(CH2)8-piperidinylene-(CH2)7-, -N(R, a7 )-CH2-piperidinyl-CH2-、-N(R a7 )-CH2-piperidinyl-(CH2)2-、-N(R a7 )-CH2-piperidinyl-(CH2)3-、-N(R a7 )-CH2-piperidinyl-(CH2)4-、-N(R a7 )-CH2-piperidinyl-(CH2)5-、-N(R a7 )-CH2-piperidinyl-(CH2)6-、-N(R a7 )-CH2-piperidinyl-(CH2)7-、-N(R a7 )-CH2-piperidinyl-(CH2)8-, -CH2-N(R a7 )-CH2-piperidinyl-CH2-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)2-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)3-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)4-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)5-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)6-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)7-, -CH2-N(R a7 )-CH2-piperidinyl-(CH2)8-, -CH2-N(R a7 )-(CH2)2-piperidinyl-CH2-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)2-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)3-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)4-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)5-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)6-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)7-, -CH2-N(R a7 )-(CH2)2-piperidinyl-(CH2)8-, -(CH2)2-N(R a7 )-CH2-piperidinyl-CH2-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)4-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)5-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)6-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)7-, -(CH2)2-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)3-N(R a7 )-CH2-piperidinylene- CH2-、-(CH2)3-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)3-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)3-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)4-N(R a7 )-CH2-piperidinyl-CH2-, -(CH2)4-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)4-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)4-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)5-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)5-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)6-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)6-N(R a7 )-CH2-piperidinyl-(CH2)8-, -(CH2)7-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)8-N(R a7 )-CH2-piperidinyl-CH2-, -(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)2-, -(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)3-, -(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)4-、-(CH2)8-N(R a7 )-CH2-piperidinyl-(CH2)5-, -(CH2)8-N(R a7 )-CH2-piperidinylene-(CH2)6-, -piperazinylene-CH2-, -piperazinylene-(CH2)2-, -piperazinylene-(CH2)3-, -piperazinylene-(CH2)4-, -piperazinylene-(CH2)5-, -piperazinylene-(CH2)6-, -piperazinylene-(CH2)7-, -piperazinylene-(CH2)8-, -CH2-piperazinylene-CH2-, -CH2-piperazinylene-(CH2)2-, -CH2-piperazinylene-(CH2)3-, -CH2-piperazinylene-(CH2)4-, -CH2-piperazinylene-(CH2)5-, -CH2-piperazinylene-(CH2)6-, -CH2-piperazinylene-(CH2)7-, -piperazinylene-(CH2)8-, -CH2-piperazinylene-CH2-, -CH2-piperazinylene-(CH2)2-, -CH2-piperazinylene-(CH2)3-, -CH2-piperazinylene-(CH2)4-, -CH2-piperazinylene-(CH2)5-, -CH2-piperazinylene-(CH2)6-, -CH2-piperazinylene-(CH2)7 -, -CH2-piperazinylene-(CH2)8-, -(CH2)2-piperazinylene-(CH2)1-, -(CH2)2-piperazinylene-(CH2)2-, -(CH2)2-piperazinylene-(CH2)3-, -(CH2)2-piperazinylene-(CH2)4-, -(CH2)2-piperazinylene-(CH2)5-, -(CH2)2-piperazinylene-(CH2)6-, -(CH2)2-piperazinylene-(CH2)7-, -(CH2)2-piperazinylene-(CH2)8-, -(CH2)3-piperazinylene-CH2-, -(CH2)3-piperazinylene-(CH2)2-, -(CH2)3-piperazinylene-(CH2)3-, -( -(CH2)3-piperazinylene-(CH2)4-, -(CH2)3-piperazinylene-(CH2)5-, -(CH2)3-piperazinylene-(CH2)6-, -(CH2)3-piperazinylene-(CH2)7-, -(CH2)3-piperazinylene-(CH2)8-, -(CH2)4-piperazinylene-CH2-, -(CH2)4-piperazinylene-(CH2)2-, -(CH2)4-piperazinylene-(CH2)3-, -(CH2)4-piperazinylene-(CH2)4-, -(CH2)4-piperazinylene-(CH2)5-, -(CH2)4-piperazinylene-(CH2)6-, -(CH2)4-piperazinylene-(CH2)7-, -(CH2)3-piperazinylene-(CH2)8-, -(CH2)4-piperazinylene-CH2-, -(CH2)4-piperazinylene-(CH2)2-, -(CH2)4-piperazinylene-(CH2)3-, -(CH2)4-piperazinylene-(CH2)4-, -(CH2)4-piperazinylene-(CH2)5-, -(CH2)4-piperazinylene-(CH2)6-, -(CH2)4-piperazinylene-(CH2)7-, -(CH2) -(CH2)4-piperazinylene-(CH2)8-, -(CH2)5-piperazinylene-(CH2)1-, -(CH2)5-piperazinylene-(CH2)2-, -(CH2)5-piperazinylene-(CH2)3-, -(CH2)5-piperazinylene-(CH2)4-, -(CH2)5-piperazinylene-(CH2)5-, -(CH2)5-piperazinylene-(CH2)6-, -(CH2)5-piperazinylene-(CH2)7-, -(CH2)5-piperazinylene-(CH2)8-, -(CH2)6-piperazinylene-(CH2)1-, -(CH2)6-piperazinylene-(CH2)2-, -(CH2)6-piperazinylene-(CH2)3-,-(CH2)6-piperazinylene-(CH2)4-, -(CH2)6-piperazinylene-(CH2)5-, -(CH2)6-piperazinylene-(CH2)6-, -(CH2)6-piperazinylene-(CH2)7-, -(CH2)6-piperazinylene-(CH2)8-, -(CH2)7-piperazinylene-(CH2)1-, -(CH2)7-piperazinylene-(CH2)2-, -(CH2)7-piperazinylene -(CH2)3-, -(CH2)7-piperazinylene-(CH2)4-, -(CH2)8-piperazinylene-CH2-, -(CH2)8-piperazinylene-(CH2)2-, -(CH2)8-piperazinylene-(CH2)3-, -(CH2)8-piperazinylene-(CH2)4-, -(CH2)8-piperazinylene-(CH2)5-, or -(CH2)8-piperazinylene-(CH2)6-; Among them, each R a7 independently represents H or C 1-3 alkyl; The phenylene, the piperazinyl and the piperidinyl are each independently selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl, deuterated C 3-6 The substituents are substituted by cycloalkyl, 4- to 10-membered heterocyclic group, and any combination thereof.

29. A compound of formula (I) according to claim 21 or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof selected from: 1-(1-Oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-fluoroisoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoroisoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-hydroxyisoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-hydroxyisoindoline-1,3-dione; 5-Bromo-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-Bromo-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(hydroxymethyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(hydroxymethyl)isoindoline-1,3-dione; 5-(Aminomethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(2-aminoethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(3-aminopropyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(Aminomethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(2-aminoethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(3-aminopropyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(iodomethyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(2-iodoethyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(3-iodopropyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(iodomethyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(2-iodoethyl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(3-iodopropyl)isoindoline-1,3-dione; 5-(Bromomethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(2-Bromoethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(3-Bromopropyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(Bromomethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(2-Bromoethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(3-Bromopropyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(Chloromethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(2-chloroethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(3-chloropropyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(Chloromethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(2-chloroethyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 4-(3-chloropropyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; (2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)methyl 4-methylbenzenesulfonate; 2-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)ethyl 4-methylbenzenesulfonate; 3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)propyl 4-methylbenzenesulfonate; (2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)methyl 4-methylbenzenesulfonate; 2-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)ethyl 4-methylbenzenesulfonate; 3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)propyl 4-methylbenzenesulfonate; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-5-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-fluoro-6-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-fluoro-6-(piperazin-1-yl)isoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-(4-(piperazin-1-yl)piperidin-1-yl)isoindoline-1,3-dione; 5-(3,3-difluoro-4-(piperazin-1-yl)piperidin-1-yl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-4-yl)piperidine-4-carbaldehyde; 1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbaldehyde; 1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1,3-dioxoisoindolin-5-yl)-[1,4'-bipiperidine]-4-carbaldehyde; 1-(5-Fluoro-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-Fluoro-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-Fluoro-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-Fluoro-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-Hydroxy-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-hydroxy-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-Hydroxy-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-Hydroxy-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-Bromo-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-Bromo-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-Bromo-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-Bromo-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(Hydroxymethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(Hydroxymethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(2-aminoethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3-aminopropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(2-aminoethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(3-aminopropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(iodomethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(2-iodoethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3-iodopropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(iodomethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(2-iodoethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(3-iodopropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(Bromomethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(2-bromoethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3-bromopropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(Bromomethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(2-bromoethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(3-bromopropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(Chloromethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(2-chloroethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3-chloropropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(Chloromethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(2-chloroethyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-(3-chloropropyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; (2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)methyl 4-methylbenzenesulfonate; 2-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)ethyl 4-methylbenzenesulfonate; 3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)propyl 4-methylbenzenesulfonate; (2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-4-yl)methyl 4-methylbenzenesulfonate; 2-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-4-yl)ethyl 4-methylbenzenesulfonate; 3-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-4-yl)propyl 4-methylbenzenesulfonate; 1-(1-oxo-4-(piperazin-1-yl)isoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(1-oxo-5-(piperazin-1-yl)isoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(4-Fluoro-1-oxo-5-(piperazin-1-yl)isoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-Fluoro-1-oxo-5-(piperazin-1-yl)isoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-Fluoro-1-oxo-5-(piperazin-1-yl)isoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((1R,4R)-2,5-diazabicyclo[2.2.1]heptane-2-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-((1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(1-oxo-6-(4-(piperazin-1-yl)piperidin-1-yl)isoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(3,3-difluoro-4-(piperazin-1-yl)piperidin-1-yl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-4-yl)piperidine-4-carbaldehyde; 1-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-oxoisoindolin-5-yl)piperidine-4-carbaldehyde; and 1'-(2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-3-oxoisoindolin-5-yl)-[1,4'-bipiperidine]-4-carbaldehyde.

30. A pharmaceutical composition comprising: A compound of formula (I) according to any one of claims 1 to 20, or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof; or A compound of formula (II) according to any one of claims 21 to 29, or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof; and at least one pharmaceutically acceptable carrier.

31. The pharmaceutical composition of claim 30, comprising at least one additional therapeutic agent, such as an anticancer agent.

32. A kit or test kit comprising: A compound of formula (I) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 20; or A compound of formula (II) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 21 to 29; or The pharmaceutical composition of claim 30 or 31.

33. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph as described in any one of claims 1 to 20 for use in treating and / or preventing a disease or condition selected from the group consisting of tumors and cancer, autoinflammatory diseases, inflammatory diseases, autoimmune diseases, neurological diseases, respiratory diseases, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin diseases, dysfunctional uterine bleeding, anemia, aplastic anemia in children, endometriosis, polycystic ovary syndrome and thyroid disease.

34. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in claim 33, wherein the disease or condition is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; neutropenia; leukemia, including chronic myeloid leukemia, B-cell chronic lymphocytic leukemia, anemia associated with leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), monocytic leukemia, myelomonocytic leukemia, acute lymphocytic leukemia (ALL), acute T-lymphocytic leukemia, T-lymphocytic leukemia, chronic lymphocytic leukemia (CLL); lymphoma, including diffuse large B-cell lymphoma, non- Hodgkin lymphoma, Hodgkin lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, immunoblastic T-cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin lymphoma, relapsed diffuse large B-cell lymphoma, relapsed mediastinal (thymic) large B-cell lymphoma, primary mediastinal ( Thymic large B-cell lymphoma, relapsed transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; astrocytoblastoma; glioma; Peripheral neuroepithelial tumors; ovarian cancer; bronchogenic cancer; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, ductal carcinoma, and patients with Cowden disease; pancreatic cancer; central nervous system cancers; neuroblastoma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumors; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcomas, including rhabdomyosarcoma, various adipose-derived tumors, Ewing sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; and bile duct cancer. Bone cancer; cervical cancer; skin cancer; Ongwericht syndrome; Richter syndrome (RS); sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjögren's syndrome, atopic dermatitis; keratoconjunctivitis sicca; autoinflammatory diseases, including gout; inflammatory diseases, including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, AIDS, and COVID-19 novel coronavirus infection. infection, Gram-negative infection, Gram-positive infection, tuberculosis, etc.; septic shock; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; multiple organ failure due to cachexia and septic shock; acute liver failure; dysfunctional uterine bleeding; anemia; aplastic anemia in children; endometriosis; polycystic ovary syndrome; thyroid disease; cardiovascular disease (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); skin diseases (e.g., acne); Kennedy disease; seborrheic alopecia; and hirsutism.

35. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, prodrug or polymorph thereof as claimed in any one of claims 21 to 29 for use in treating and / or preventing a disease or condition associated with the cereblon protein selected from the group consisting of:

36. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof as claimed in claim 35, wherein the disease or condition associated with the cereblon protein comprises a tumor or cancer, an infectious disease, an inflammatory disease, an autoimmune disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure or diabetes.

37. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof according to claim 35, wherein the disease or condition associated with cereblon protein is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; Neutropenia; leukemias, including chronic myeloid leukemia, B-cell chronic lymphocytic leukemia, leukemia-related anemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), monocytic leukemia, myelomonocytic leukemia, acute lymphoblastic leukemia (ALL), acute T-lymphocytic leukemia, T-lymphocytic leukemia, chronic lymphocytic leukemia (CLL); lymphomas, including diffuse large B-cell lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, anaplastic lymphoma Tumor, anaplastic large cell lymphoma, immunoblastic T-cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin's lymphoma, relapsed diffuse large B-cell lymphoma, relapsed mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, relapsed transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including adenocarcinoma and squamous cell carcinoma; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; glioma; glioblastoma; astrocytoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, ductal carcinoma, and Cowden's disease; pancreatic cancer; central nervous system cancers; neuroblastoma; glioma; Peripheral neuroepithelial tumor; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumor; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcomas, including rhabdomyosarcoma, various adipose tumors, Ewing sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; bile duct cancer; Bone cancer; cervical cancer; skin cancer; Ongwericht syndrome; Richter syndrome (RS); sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjögren's syndrome, atopic dermatitis; keratoconjunctivitis sicca; inflammatory diseases, including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, AIDS ), COVID-19 novel coronavirus infection, Gram-negative bacterial infection, Gram-positive bacterial infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular disease (such as coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure caused by cachexia and septic shock; and acute liver failure.

38. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph as claimed in any one of claims 1 to 20 for the preparation of a medicament for treating and / or preventing a disease or condition selected from the group consisting of: tumors or cancers, autoinflammatory diseases, inflammatory diseases, autoimmune diseases, neurological diseases, respiratory diseases, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin diseases, dysfunctional uterine bleeding, anemia, aplastic anemia in children, endometriosis, polycystic ovary syndrome and thyroid disease.

39. A method for treating or preventing a disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph as described in any one of claims 1 to 20, or a pharmaceutical composition as described in claim 30 or 31, wherein the disease or condition comprises a tumor or cancer, an autoinflammatory disease, an inflammatory disease, an autoimmune disease, a neurological disease, a respiratory disease, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin diseases, dysfunctional uterine bleeding, anemia, aplastic anemia in children, endometriosis, polycystic ovary syndrome and thyroid disease.

40. The use of claim 38 or the method of claim 39, wherein the disease or condition is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; neutropenia; leukemia, including chronic myeloid leukemia, B-cell chronic lymphocytic leukemia, anemia associated with leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), monocytic leukemia, myelomonocytic leukemia, acute lymphoblastic leukemia (ALL), acute T-lymphocytic leukemia, T-lymphocytic leukemia, chronic lymphocytic leukemia (CLL); lymphoma, including diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, interstitial cell carcinoma, Anaplastic lymphoma, anaplastic large cell lymphoma, immunoblastic T-cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, marginal zone lymphoma (MZL), prima...

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