E3 ubiquitin ligase ligand compounds, protein degraders developed based on said ligand compounds and their applications

Abstract

The present disclosure relates to compounds of formula (I) and formula (II) or their salts, enantiomers, stereoisomers, solvates, isotopically enriched analogs, pharmaceutical precursors or polymorphs and applications thereof. The present disclosure also relates to pharmaceutical compositions comprising compounds of formula (I) and formula (II) or their salts, enantiomers, stereoisomers, solvates, isotopically enriched analogs, pharmaceutical precursors or polymorphs as active ingredients and applications thereof. [chemical 856] JPEG2025502928001164.jpg1739 formula (I) PBM-R f -LIN-ULM formula (II)

Description

[Technical Field]

[0001] The present disclosure relates to a cereblon (CRBN) E3 ubiquitin ligase ligand compound of formula (I), a proteolytic compound of formula (II) containing the same, and applications thereof. The CRBN E3 ubiquitin ligase ligand compound can effectively treat or prevent diseases or conditions mediated by cereblon protein. The proteolytic compound of formula (II) can effectively treat or prevent diseases or conditions associated with degraded proteins. [Background technology]

[0002] Bifunctional proteolytic targeting drugs consist of three parts: one end is a ligand warhead capable of binding to a specific target protein; the other end is a small molecule ligand for E3 ubiquitin ligase; and the middle part is connected by linker units of varying lengths and types. Bifunctional proteolytic compounds can simultaneously bind to a specific target protein and an E3 ubiquitin ligase through the binding action of the ligands at both ends, recruiting the E3 ubiquitin ligase to the specific target protein and allowing it to ubiquitinate the target protein. The polyubiquitinated target protein is then recognized and degraded by proteases in the body. The biggest difference between proteolytic targeting drugs and traditional small molecule inhibitors is that they mobilize the entire cell as the drug's effective unit. In this drug action model, small molecule drugs simply bind to target proteins temporarily and tag them as requiring degradation, which allows for low drug doses to be administered, significantly reducing the risk of detargeting effects and fundamentally eliminating tumor progression caused by abnormal expression of driver genes and drug resistance caused by acquired mutations in driver genes.

[0003] E3 ubiquitin ligases, relevant for drug design targeting protein degradation, include over 500 different proteins, each with a distinct cellular expression profile. They can be classified into several categories based on the structural elements of their E3 functional activity. Currently, only a small number of ligases have been successfully applied to preclinical degraders, with Cereblon (CRBN) E3 ubiquitin ligase being one of the most widely used. Currently known CRBN-type E3 ubiquitin ligase ligands (CRBN ligands) include thalidomide and its analogs pomalidomide and lenalidomide, both of which contain a phthalimide backbone. CRBN-type E3 ubiquitin ligase ligands themselves act as molecular groups, capable of inducing the degradation of specific proteins. Cereblon (CRBN) forms a functional E3 ubiquitin ligase complex with damaged DNA-binding protein 1 (DDB1) and Cullin4A. In this complex, CRBN acts as a substrate receptor, and molecular glue degraders such as thalidomide bind to CRBN, allowing CRBN to recognize and ubiquitinate new substrate proteins, which then target CRBN for further recognition and degradation by proteases.

[0004] CRBN ligands have been widely used in protein degradation, and a series of CRBN ligand-based proteolytic small molecules have been developed that utilize the function of the CRBN E3 ubiquitin ligase complex. CRBN ligands can act as molecular glue degraders to induce the degradation of different substrate proteins and can also be used as part of bifunctional proteolytic drugs to efficiently degrade specific pathogenic proteins. However, because many existing domide compounds have unavoidable side effects and drug resistance issues, it is of great importance to design novel, optimized E3 ubiquitin ligase ligands and explore their binding ability and biological activity with CRBN, which can then be used in bifunctional proteolytic small molecule drugs.

[0005] Therefore, there is a pressing need for a series of novel CRBN ligands that can be used as efficient molecular glue degraders and further synthesize corresponding bifunctional protein degraders to be used to treat and / or prevent diseases or conditions mediated by or associated with degraded proteins. Summary of the Invention

[0006] In view of the above, the present disclosure aims to provide novel CRBN ligands, proteolytic molecules designed based on the novel CRBN ligands and various target protein ligands, their uses, and methods for using them. The advantage of the compounds provided herein is that they can have broad pharmacological activity by degrading / inhibiting a variety of different disease-causing protein types or families.

[0007] To achieve the above and other related objects, the present disclosure provides novel CRBN ligands that can bind to CRBN E3 ligase as molecular glues and induce degradation of CRBN substrate proteins (including, but not limited to, GSPT1, IKZF1, IKZF2, IKZF3 (Aiolos), and IKZF4 proteins).

[0008] In some embodiments, the novel CRBN ligands disclosed herein may be compounds of formula (I) or salts, stereoisomers (including enantiomers), solvates, isotopically enriched analogs, pharmaceutical precursors, or polymorphs thereof: [ka] where: A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent, for example, hydrogen, deuterium, halogen, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy or halogenated C 1-6 represents alkyl; (Ra ) m The benzene ring has m R a Each R represents a substitution a are the same or different and each independently have the following structure: [ka] represents; where: R is chlorine, bromine, iodine, hydroxy, a leaving group, NR7R8 or a group W 1 represents wherein R7 and R8 are the same or different and each independently represent hydrogen, C 1-6 Alkyl, C 2-6 Alkynyl-C 1-6 Alkylene-, C 2-6 Alkenyl-C 1-6 alkylene-, optionally substituted 4- to 15-membered nitrogen-containing heterocyclyl, or R 2a -R 1a - where R 1a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 represents alkenylene, and R 2a is halogen, amino, hydroxy, carboxy, C 2-6 Alkynyl, C 2-6 represents an alkenyl or leaving group; and Base W 1 is a structure of the formula: [ka] or [ka] represents; Here, the ring W 2 represents an optionally substituted nitrogen-containing heterocyclyl, and each ring W 3 are the same or different and each independently represent an optionally substituted nitrogen-containing heterocyclylene; t represents an integer of 1 or 2; and the ring W 4represents optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl; R5 and R6 are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C 2-30 alkyl, wherein the straight or branched chain C 2-30 The alkyl carbon backbone may contain one or more groups R c and / or one or more groups R d or one or more groups R c and R d and any combination of the groups R c , R d or group R c and R d The combination of R c is O, N(R e ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R e ), N(R e )C(O), or N(R e )C(O)N(R e ), wherein each R e are independently H or C 1-6 represents alkyl, and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkyl c When inserted, each group R c are not directly connected; each group R d is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, or any combination thereof; Or, R and R5 together with the carbon atom to which they are attached form a carbonyl, and R is hydrogen, optionally substituted methyl, or optionally substituted straight or branched chain C 2-30 alkyl, wherein the straight or branched chain C 2-30 The alkyl carbon backbone may contain one or more groups R c and / or one or more groups R d or one or more groups R c and R d and any combination of the groups R c , R d or group R c and R d The combination of R c is O, N(R e ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R e ), N(R e )C(O), or N(R e )C(O)N(R e ), wherein each R e are independently H or C 1-6 represents alkyl, and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkyl c When inserted, each group R c are not directly connected; each group R dis selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof; (R b ) n is a group in which the benzene ring is n-number of R b Each R represents a substitution b are the same or different and each independently represent deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, C 2-6 Alkenyl, or C 2-6 represents alkynyl; and m represents an integer of 1, 2, 3, or 4, n represents an integer of 0, 1, 2, or 3, and the sum of m and n represents an integer of 1, 2, 3, or 4; wherein, when R and R5 together with the carbon atom connected thereto form a carbonyl group and R6 represents hydrogen, m represents an integer of 1, 2 or 3, n represents an integer of 1, 2 or 3, and the sum of m and n represents an integer of 2, 3 or 4; The conditions include the following compound and a compound of formula (I'): [ka] is eliminated; and When A represents CH or C(O) and R represents an unsubstituted piperazinyl group, m represents an integer of 1 and n represents an integer of 0; A represents CH2 or C(O), and R a represents H2N-CH2-, m represents an integer of 1 and n represents an integer of 0; When A represents C(O) and R represents bromine, m represents an integer of 1 and n represents an integer of 0; and [ka] Formula (I') Here, in formula (I'), A represents CH2 or C(O), and R represents unsubstituted piperidinyl or piperidinyl substituted with methylamino.

[0009] In one aspect, the proteolytic molecule of the present disclosure is a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, PBM-R f -LIN-ULM Formula (II) Here, PBM-R f - represents a targeting moiety capable of binding to a protein, ULM represents a ligand moiety capable of binding to an E3 ubiquitin ligase, LIN is a connecting moiety, and PBM-R f is covalently linked to ULM by the group LIN; ULM has the structure of the following formula (ULM): [ka] Formula (ULM) where: A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent hydrogen, deuterium, halogen, or optionally deuterated C 1-6 Alkyl, optionally deuterated C1-6 Alkoxy or halogenated C 1-6 represents alkyl; (R b ) n The benzene ring is optionally connected to n R b Each R represents a substitution b are the same or different and each independently represent deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, C 2-6 Alkenyl, or C 2-6 represents alkynyl; n represents an integer of 0, 1, 2, or 3; LIN has the following structure: [ka] represents; wherein R5 and R6 are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C 2-30 alkyl, wherein the straight or branched chain C 2-30 The alkyl carbon backbone may contain one or more groups R c and / or one or more groups R d or one or more groups R c and R d and any combination of the groups R c , R d or group R c and R d The combination of R c is O, N(R e ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R e ), N(R e )C(O), or N(Re )C(O)N(R e ), wherein each R e are independently H or C 1-6 represents alkyl, and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkyl c When inserted, each group R c are not directly connected; each group R d is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, or any combination thereof; R f is a bond, -O-, -N(R g )-, -NHC(O)-R h -W 5 -*, -C(O)NH-R h -W 5 -*, -NHC(O)-W 5 -*, -C(O)NH-W 5 -*, -NHC(O)-*, -C(O)NH-*, -OR h -W 5 -*, -OW 5 -*, -OR h -N(R i )-*, -N(R g )-R h -N(R i )-*, -W5 -, -W 5 -N(R g )-*, -N(R g )-W 5 -*, -N(R g )-W 5 -N(R i )-*, -R h -W 5 -*, -R h -C(O)-W 5 -*, -C(O)-W 5 -*, -R h -C(O)NH-R j -W 5 -*, -R h -NHC(O)-R j -W 5 -*, -R h -C(O)NH-*, -R h -NHC(O)-*, -R h -, -R h -N(R i )-*, or [ka] represents Here, the group W 5 is a structure of the formula: [ka] represents Here, each ring W 6 are the same or different and each independently represent a nitrogen-containing heterocycline, t1 represents an integer of 1 or 2, (R a2 ) m2 is each ring W 6 There are m2 R a2 represents an alkyl group optionally substituted with a substituted aryl group, and each R a2 are independently deuterium, and optionally deuterated C 1-6 Alkyl, optionally halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6Cycloalkyl, or R 12a -R 11a -, where R 11a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene, and R 12a is halogen, R 13a R 14a N-, hydroxy, carboxy, ethynyl, or vinyl, where R 13a and R 14a are the same or different and each independently represent hydrogen or C 1-3 alkyl, and m2 represents an integer of 0-20; Each ring W 7 are the same or different and each independently represent a nitrogen-containing heterocyclylene, arylene, or heteroarylene; t2 represents an integer of 0 or 1; (R a3 ) m3 is each ring W 7 m3 R a3 represents an alkyl group optionally substituted with a substituted aryl group, and each R a3 are independently deuterium, and optionally deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R 16a -R 15a -, where R 15a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene, and R 16a is halogen, R 17a R 18a N-, hydroxy, carboxy, ethynyl, or vinyl, where R 17a and R 18a are the same or different and each independently represent hydrogen or C 1-3 represents alkyl, and m3 represents an integer from 0 to 20; and R g and R iare each independently hydrogen or C 1-6 represents alkyl, and R h and R j are each independently an optionally substituted C 1-6 Alkylene or optionally substituted C 2-6 represents alkenylene, and the symbol * represents the point of attachment to LIN; wherein PBM has the following structural formula: [ka] and together with -R f -LIN- [ka] where the symbol ** represents the connection point with the ULM. b ) n The benzene ring of formula (ULM) is one, two or three R b Each R represents a substitution b are the same or different and each independently represent deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, C 2-6 Alkenyl, or C 2-6 represents alkynyl; The conditions include the following compounds: 3-(4-((3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)pyrrolidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)azetidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; and 2-(2,6-Dioxopiperidin-3-yl)-5-((3-(4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione Except.

[0010] In another aspect, the present disclosure provides pharmaceutical compositions comprising a compound of formula (I) or a salt thereof, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph, and at least one pharmaceutically acceptable carrier.

[0011] In one aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (II) or a salt thereof, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph, and at least one pharmaceutically acceptable carrier.

[0012] In one aspect, the present disclosure also provides a method for manufacturing a semiconductor device comprising: a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the same; or Compounds of formula (II) or pharmaceutically acceptable salts thereof, or pharmaceutical compositions containing them A pharmaceutical kit or reagent kit is provided, comprising:

[0013] In one aspect, the present disclosure provides a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, or a pharmaceutical composition comprising same as an active ingredient, for use as a medicament.

[0014] In one aspect, the present disclosure further provides a pharmaceutical composition comprising, as an active ingredient, a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, for use in treating or preventing a disease or condition mediated by cereblon protein.

[0015] In some embodiments, the disease or condition mediated by cereblon protein includes, but is not limited to, a tumor, an infectious disease, an autoinflammatory disease, an inflammatory disease, an autoimmune disease, a neurological disease, a respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Unverricht syndrome, Richter syndrome (RS), acute liver failure, or diabetes.

[0016] In one aspect, the present disclosure provides a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use as a medicament.

[0017] In one aspect, the present disclosure further provides a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use in treating and / or preventing a disease or condition selected from the group consisting of tumor, infectious disease, autoinflammatory disease, inflammatory disease, autoimmune disease, neurological disease, respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, Unverricht syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin disease, cardiovascular disease, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, or thyroid disease.

[0018] In one aspect, the present disclosure provides the use of a compound of formula (I), or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, for use in the preparation of a compound of formula (II), or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, according to the present disclosure.

[0019] In one aspect, the present disclosure further provides a method of preparing a compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to the present disclosure using a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

[0020] In one aspect, the present disclosure further provides the use of a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof in the manufacture of a medicament for treating or preventing a disease or condition mediated by cereblon protein.

[0021] In one aspect, the disclosure further provides the use of a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof for use in the manufacture of a medicament for treating and / or preventing a disease or condition selected from the group consisting of a tumor, an infectious disease, an autoinflammatory disease, an inflammatory disease, an autoimmune disease, a neurological disease, a respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, Unverricht syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, a skin disease, a cardiovascular disease, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, or a thyroid disease.

[0022] In one aspect, the present disclosure further provides a method for treating or preventing a disease or condition mediated by cereblon protein 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 analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising same.

[0023] In one aspect, the present disclosure further provides a method of treating or preventing a disease or condition in a subject, wherein the disease or condition comprises a tumor, an infectious disease, an autoinflammatory disease, an inflammatory disease, an autoimmune disease, a neurological disease, a respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, Unverricht syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, a skin disease, a cardiovascular disease, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, and a thyroid disease, 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 analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising same. DETAILED DESCRIPTION OF THE INVENTION

[0024] In order to facilitate understanding and implementation of the contents of the present disclosure, the following detailed description is provided as an illustrative specific embodiment. However, such description is not intended to limit the scope of the present disclosure. The specific embodiments described in the present disclosure can be further modified and changed in various ways without departing from the spirit and scope of the present disclosure, and it should be recognized that these modifications and improvements fall within the protection scope of the present disclosure. I. Compound Compounds of formula (I)

[0025] The present disclosure relates to compounds of formula (I) or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogues, pharmaceutical precursors or polymorphs thereof: [ka] where A, R1, R2, R3, R4, (R a ) m , (R b ) n , m and n are as defined above for compounds of formula (I).

[0026] In some embodiments, R, R, R, and R of the compound of Formula (I) are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0027] In some embodiments, R 1 , R 2 , R 3 , and R 4 of the compound of Formula (I) are the same or different and each independently represent hydrogen or deuterium.

[0028] In some embodiments, R1, R2, R3, and R4 of the compound of formula (I) represent hydrogen.

[0029] In some embodiments, the compound A of formula (I) represents CO.

[0030] In some embodiments, the compound A of formula (I) represents CH2.

[0031] In some embodiments, the compound A of formula (I) represents CD2.

[0032] In some embodiments, in the compound of Formula (I), m represents an integer of 1; n represents an integer of 0, 1, 2, or 3; and the sum of m and n represents an integer of 1, 2, 3, or 4.

[0033] In some embodiments, in the compound of Formula (I), m represents an integer of 2; n represents an integer of 0, 1, or 2; and the sum of m and n represents an integer of 2, 3, or 4.

[0034] In some embodiments, when R and R5 together with the carbon atoms to which they are attached form a carbonyl group and R6 represents hydrogen, m represents an integer of 1, 2, or 3, n represents an integer of 1, 2, or 3, and the sum of m and n represents an integer of 2, 3, or 4. In some subembodiments, m represents an integer of 1, n represents an integer of 1, 2, or 3, and the sum of m and n represents an integer of 2, 3, or 4. In some subembodiments, m represents an integer of 2, n represents an integer of 1 or 2, and the sum of m and n represents an integer of 3 or 4. In some subembodiments, m represents an integer of 3 and n represents an integer of 1.

[0035] In some embodiments, R of the compound of Formula (I) represents chlorine, bromine, iodine, hydroxy, or a leaving group (e.g., —N3, chlorine, bromine, iodine, a sulfonate group such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)).

[0036] In some embodiments, R in the compound of formula (I) represents NR7R8, where R7 and R8 are the same or different and each independently represent hydrogen, C 1-6 Alkyl (e.g., C1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 2-6 Alkynyl-C 1-6 Alkylene-(e.g., C 2-6 Alkynyl-C 1-4 Alkylene- or C 2-6 Alkynyl-C 1-3 alkylene-, for example ethynyl-methylene-, ethynyl-ethylene-, ethynyl-propylene-, ethynyl-butylene-, ethynyl-pentylene-, or ethynyl-hexylene-), C 2-6 Alkenyl-C 1-6 Alkylene-(e.g., C 2-6 Alkenyl-C 1-4 Alkylene- or C 2-6 Alkenyl-C 1-3 alkylene-, for example, vinyl-methylene-, vinyl-ethylene-, vinyl-propylene-, vinyl-butylene-, vinyl-pentylene-, or vinyl-hexylene-), optionally substituted 4- to 15-membered (for example, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, or 5- to 9-membered) nitrogen-containing monocyclic heterocyclyl, optionally substituted a substituted 4- to 15-membered (e.g., 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, or 5- to 9-membered) nitrogen-containing bridged heterocyclyl, or an optionally substituted 4- to 15-membered (e.g., 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, or 5- to 9-membered) nitrogen-containing spiroheterocyclyl, or R 2a -R 1a - where R 1a is an arbitrarily substituted C 1-6 Alkylene (e.g., optionally substituted C 1-4 alkylene, e.g., optionally substituted methylene, ethylene, or propylene) or optionally substituted C 2-6 Alkenylene (e.g., optionally substituted C 2-4 alkenylene, e.g., optionally substituted vinylene, propenylene, butenylene), R 2ais halogen (e.g., fluorine, chlorine, bromine, or iodine), amino, hydroxy, carboxy, CHO, C 2-6 Alkynyl (e.g., C 2-4 alkynyl, for example, ethynyl, propynyl or butynyl), C 2-6 Alkenyl (e.g., C 2-4 alkenyl, for example, vinyl, propenyl, or butenyl) or a leaving group (for example, -N3, chlorine, bromine, iodine, a sulfonate group, for example, methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), and the 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, the 4- to 15-membered nitrogen-containing bridged heterocyclyl, and the 4- to 15-membered nitrogen-containing spiroheterocyclyl each independently represent deuterium, C 1-6 Alkyl (e.g., C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy, pentyloxy, or hexyloxy), halogen (e.g., fluorine, chlorine, bromine, or iodine), leaving groups (e.g., -N3, chlorine, bromine, iodine, sulfonate groups (e.g., methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), amino, hydroxy, carboxy, CHO, C 2-6 Alkynyl (e.g., C 2-4 alkynyl, for example, ethynyl, propynyl or butynyl), C 2-6 Alkenyl (e.g., C 2-4 alkenyl, for example, vinyl, propenyl or butenyl), R 4a -R 3a -, or any combination thereof, wherein R 3ais an arbitrarily substituted C 1-6 Alkylene (e.g., optionally substituted C 1-4 alkylene, e.g., optionally substituted methylene, ethylene, or propylene) or optionally substituted C 2-6 Alkenylene (e.g., optionally substituted C 2-4 alkenylene, e.g., optionally substituted vinylene, propenylene, butenylene), R 4a is halogen, R 5a R 6a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl, or a leaving group (e.g., -N3, chlorine, bromine, iodine, a sulfonate group such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), where R 5a and R 6a are the same or different and each independently represent hydrogen or C 1-3 represents alkyl (e.g., methyl, ethyl, or propyl). The number of substituents is not limited in principle, or is automatically limited by the size of the structural unit. For example, when the substituent is deuterium, the 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, the 4- to 15-membered nitrogen-containing bridged heterocyclyl, and the 4- to 15-membered nitrogen-containing spiroheterocyclyl are each independently optionally completely or partially deuterated.

[0037] In some subembodiments, R of the compound of Formula (I) represents NR7R8, where R7 and R8 are the same or different and each independently represent one of the following: Hydrogen, C 1-6 Alkyl, C 2-6 Alkynyl-C 1-6 Alkylene- or C 2-6 Alkenyl-C 1-6 Alkylene-; or An optionally substituted 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, an optionally substituted 4- to 15-membered nitrogen-containing bridged heterocyclyl, or an optionally substituted 4- to 15-membered nitrogen-containing spiroheterocyclyl, for example: Piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, diazacyclooctyl, azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octaniyl diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl, diazabicyclo[2.2.2]octanyl, 3-azaspiro[5.5]undecan-3-yl, 8-azaspiro[4.5]decan-4-yl, 2-oxa-8-azaspiro[4.5]decan-4-yl, or 3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl, or [ka] [ka] [ka] [ka] [ka] [ka] [ka] R 2a -R 1a -(where R 1a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 represents alkenylene, and R 2a are halogen, amino, hydroxy, carboxy, CHO, C 2-6 Alkynyl, C 2-6 alkenyl or a leaving group), represents Here, the 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, the 4- to 15-membered nitrogen-containing bridged heterocyclyl, and the 4- to 15-membered nitrogen-containing spiroheterocyclyl are each independently selected from the group consisting of deuterium, C 1-6 Alkyl, C 1-6 Alkoxy, halogen, leaving group, amino, hydroxy, carboxy, CHO, C 2-6 Alkynyl, C 2-6 Alkenyl, R 4a -R 3a -, or any combination thereof, wherein R 3a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 represents alkenylene, and R 4a is halogen, R 5a R 6a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R 5a and R 6a are the same or different and each independently represent hydrogen or C 1-3 represents alkyl. The number of substituents is not limited in principle, or is automatically limited by the size of the structural unit. For example, when the substituent is deuterium, the 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, the 4- to 15-membered nitrogen-containing bridged heterocyclyl, and the 4- to 15-membered nitrogen-containing spiroheterocyclyl are each independently optionally completely or partially deuterated.

[0038] In some embodiments, R of the compound of formula (I) is selected from the group consisting of NH, —NHCH, —NHCHCH, —N(CH), —N(CH)—CHCH, —N(CH)—CHCHBr, [ka] , [ka] , [ka] , or [ka] Represents.

[0039] In some embodiments, R of the compound of formula (I) has the structure of the following formula: [ka] Group W represented by 1 represents Here, the ring W 2 represents a 4- to 20-membered (e.g., 4- to 15-membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, or 5- to 9-membered) nitrogen-containing heterocyclyl, for example, a 4- to 20-membered (e.g., 4- to 15-membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, or 5- to 9-membered) heterocyclyl containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur; (R a1 ) m1 Ring W 2 There are m1 R a1 represents an alkyl group optionally substituted with a substituted aryl group, and each R a1 are independently deuterium, and optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, or tert-butoxy), halogen (for example, fluorine, chlorine, bromine, or iodine), leaving groups (for example, -N3, chlorine, bromine, iodine, sulfonate groups, for example, methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), amino, hydroxy, mercapto, cyano, carboxy, CHO, C 2-6 Alkynyl (e.g., C 2-4 alkynyl, for example, ethynyl, propynyl or butynyl), C 2-6 Alkenyl (e.g., C 2-4 alkenyl, for example vinyl, propenyl or butenyl), optionally deuterated C 3-6 cycloalkyl (e.g., optionally perdeuterated cyclopropyl, optionally perdeuterated cyclobutyl, optionally perdeuterated cyclopentyl, or optionally perdeuterated cyclohexyl), or R 8a -R 7a -, where R 7a is an arbitrarily substituted C 1-6 Alkylene (e.g., optionally substituted C 1-4 alkylene, e.g., optionally substituted methylene, ethylene, or propylene) or optionally substituted C 2-6 Alkenylene (e.g., optionally substituted C 2-4 alkenylene, e.g., optionally substituted vinylene, propenylene, butenylene), and R 8a is a halogen (e.g., fluorine, chlorine, bromine, or iodine), R 9a R 10a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl, or a leaving group (e.g., -N3, chlorine, bromine, iodine, a sulfonate group such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), where R 9a and R 10a are the same or different and each independently represent hydrogen or C 1-3alkyl (e.g., methyl, ethyl, or propyl); Here, m1 represents an integer of 0-20 (for example, an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 20). The quantity is not limited in principle or is automatically limited to the size of the constituent unit.

[0040] In some subembodiments, R of the compound of Formula (I) has a structure of the following formula: [ka] Group W represented by 1 represents Here, the ring W 2 is a 4- to 20-membered nitrogen-containing heterocyclyl, for example, a 4- to 20-membered (e.g., 4- to 15-membered, 4- to 12-membered, 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, or 5- to 9-membered) heterocyclyl containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur, for example, Piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, diazacyclooctyl, 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, diazabicyclo[2.2.2]octanyl, 3-azaspiro[5.5]undecanyl, 8-azaspiro[4.5]decanyl, 2-oxa-8-azaspiro[4.5]decanyl, or 3-methyl-2-oxa-8-azaspiro[4.5]decanyl, or [ka] [ka] [ka] [ka] [ka] [ka] [ka] represents; (R a1 ) m1 Ring W 2 There are m1 R a1 represents an alkyl group optionally substituted with a substituted aryl group, and each R a1 are independently deuterium, and optionally deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R 8a -R 7a -, where R 7a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene, and R 8a is halogen, R 9a R 10a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R 9a and R 10a are the same or different and each independently represent hydrogen or C 1-3 represents alkyl; Here, m1 represents an integer of 0-20 (for example, an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 20). The quantity is not limited in principle or is automatically limited to the size of the constituent unit.

[0041] In some embodiments, the ring W 2 is optionally fully deuterated or partially deuterated.

[0042] In some embodiments, R of the compound of formula (I) has the structure of the following formula: [ka] Group W represented by 1 represents Here, each ring W 3 are the same or different and each independently represent a 4- to 20-membered (e.g., 4-15-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 4-7-membered, 4-6-membered, 5-15-membered, or 5-9-membered) nitrogen-containing heterocyclylene, for example, a 4- to 20-membered (e.g., 4-15-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 4-7-membered, 4-6-membered, 5-15-membered, or 5-9-membered) heterocyclylene containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur; t represents an integer of 1 or 2, (R a2 ) m2 is each ring W 3 There are m2 R a2 represents an alkyl group optionally substituted with a substituted aryl group, and each R a2 are independently deuterium, and optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy, pentyloxy, or hexyloxy), halogen (e.g., fluorine, chlorine, bromine, or iodine), leaving groups (e.g., -N3, chlorine, bromine, iodine, sulfonate groups (e.g., methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), amino, hydroxy, mercapto, cyano, carboxy, CHO, C2-6 Alkynyl (e.g., C 2-4 alkynyl, for example, ethynyl, propynyl or butynyl), C 2-6 Alkenyl (e.g., C 2-4 alkenyl, for example vinyl, propenyl or butenyl), optionally deuterated C 3-6 cycloalkyl (e.g., optionally perdeuterated cyclopropyl, optionally perdeuterated cyclobutyl, optionally perdeuterated cyclopentyl, or optionally perdeuterated cyclohexyl), or R 12a -R 11a - where R 11a is an arbitrarily substituted C 1-6 Alkylene (e.g., optionally substituted C 1-4 alkylene, e.g., optionally substituted methylene, ethylene, or propylene) or optionally substituted C 2-6 Alkenylene (e.g., optionally substituted C 2-4 alkenylene, e.g., optionally substituted vinylene, propenylene, butenylene), and R 12a is a halogen (e.g., fluorine, chlorine, bromine, or iodine), R 13a R 14a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl, or a leaving group (e.g., -N3, chlorine, bromine, iodine, a sulfonate group such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), where R 13a and R 14a are the same or different and each independently represent hydrogen or C 1-3 alkyl (e.g., methyl, ethyl, or propyl); and Ring W 4is a 4-membered to 15-membered (e.g., 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 4-7-membered, 4-6-membered, 5-15-membered, or 5-9-membered) nitrogen-containing heterocyclyl (e.g., a 4-membered to 15-membered (e.g., 4-15-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, (4-7-membered, 4-6-membered, 5-15-membered, or 5-9-membered) heterocyclyl), 6-membered to 10-membered aryl, or 5-membered to 10-membered (e.g., 5-6-membered, or 5-9-membered) heteroaryl (e.g., 5-membered to 10-membered (e.g., 5-9-membered, 5-8-membered, 5-7-membered, or 5-6-membered) heteroaryl containing one nitrogen atom and optionally containing heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur); (R a3 ) m3 Ring W 4 There are m3 R a3 represents a group substituted with a3 are independently deuterium, and optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy, pentyloxy, or hexyloxy), halogen (e.g., fluorine, chlorine, bromine, or iodine), leaving groups (e.g., -N3, chlorine, bromine, iodine, sulfonate groups (e.g., methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), amino, hydroxy, mercapto, cyano, carboxy, CHO, C 2-6 Alkynyl (e.g., C 2-4 alkynyl, for example, ethynyl, propynyl or butynyl), C 2-6 Alkenyl (e.g., C 2-4 alkenyl, for example vinyl, propenyl or butenyl), optionally deuterated C 3-6cycloalkyl (e.g., optionally perdeuterated cyclopropyl, optionally perdeuterated cyclobutyl, optionally perdeuterated cyclopentyl, or optionally perdeuterated cyclohexyl), or R 16a -R 15a -, where R 15a is an arbitrarily substituted C 1-6 Alkylene (e.g., optionally substituted C 1-4 alkylene, e.g., optionally substituted methylene, ethylene, or propylene) or optionally substituted C 2-6 Alkenylene (e.g., optionally substituted C 2-4 alkenylene, e.g., optionally substituted vinylene, propenylene, butenylene), and R 16a is a halogen (e.g., fluorine, chlorine, bromine, or iodine), R 17a R 18a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl, or a leaving group (e.g., -N3, chlorine, bromine, iodine, a sulfonate group such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), where R 17a and R 18a are the same or different and each independently represent hydrogen or C 1-3 alkyl (e.g., methyl, ethyl, or propyl); Here, m2 and m3 each independently represent an integer of 0 to 20 (e.g., an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 20). The quantity is not limited in principle, or is automatically limited by the size of the constituent unit.

[0043] In some subembodiments, R of the compound of Formula (I) has a structure of the following formula: [ka] Group W represented by 1 represents Here, each ring W 3are the same or different and each independently represent a 4- to 20-membered nitrogen-containing heterocyclylene, for example, Piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene, diazacyclooctylene, azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo 2-azaspiro[5.5]undecanylene, 8-azaspiro[4.5]decanylene, 2-oxa-8-azaspiro[4.5]decanylene, or 3-methyl-2-oxa-8-azaspiro[4.5]decanylene, or [ka] [ka] [ka] [ka] [ka] [ka] [ka] represents t represents an integer of 1 or 2, (R a2 ) m2 is each ring W 3 There are m2 R a2 represents a group substituted with a2 are independently deuterium, and optionally deuterated C 1-6Alkyl, C 1-6 Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R 12a -R 11a -, where R 11a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene, and R 12a is halogen, R 13a R 14a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R 13a and R 14a are the same or different and each independently represent hydrogen or C 1-3 represents alkyl; and Ring W 4 is a 4- to 15-membered nitrogen-containing heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, for example: Piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, diazacyclooctyl, 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, diazabicyclo[2.2.2]octanyl, 3-azaspiro[5.5]undecanyl, 8-azaspiro[4.5]decanyl, 2-oxa-8-azaspiro[4.5]decanyl, 3-methyl-2-oxa-8-azaspiro[4.5]decanyl, phenyl, naphthyl, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, Thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, 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]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl, or [ka] [ka] [ka] [ka] [ka] [ka] [ka] represents (R a3 ) m3 is a ring W 4 There are m3 R a3 represents a group substituted with a3 are independently deuterium, and optionally deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C 2-6 Alkynyl, C 2-6 Alkenyl, optionally deuterated C 3-6 Cycloalkyl, or R 16a -R 15a -, where R 15a is an arbitrarily substituted C 1-6 Alkylene or optionally substituted C 2-6 alkenylene, and R 16a is halogen, R 17a R 18a represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R 17a and R 18a are the same or different and each independently represent hydrogen or C 1-3 represents alkyl; Here, m2 and m3 each independently represent an integer of 0 to 20 (e.g., an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 20). The quantity is not limited in principle, or is automatically limited by the size of the constituent unit.

[0044] In some subembodiments, each ring W 3 are each independently optionally fully deuterated or partially deuterated.

[0045] In some subembodiments, the ring W 4 is optionally fully deuterated or partially deuterated.

[0046] In some subembodiments, R of the compound of Formula (I) is one of the following groups: chlorine, bromine, iodine, hydroxy, -N3, sulfonate groups such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-) or p-toluenesulfonyloxy (TsO-), NH2, or [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Represents.

[0047] In some embodiments, R5 and R6 of the compound of Formula (I) are each independently: Hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C 2-30 represents alkyl, wherein the linear or branched chain C 2-30 The alkyl carbon backbone may contain one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and / or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R d , or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and R d Any combination of the groups R c , R d or group R c and R d The combination of the carbon-carbon bonds between one or more pairs (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2 pairs, or one pair) of adjacent carbon atoms in the carbon backbone is cleaved; c is O, N(R e ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R e ), N(R e )C(O), or N(R e )C(O)N(R e ), wherein each R e are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), and the linear or branched C2-30 Two or more groups R in the main carbon chain of the alkyl c When inserted, each group R c are not directly connected; each group R d is a cycloalkylene (e.g., C 3-20 cycloalkylene), arylene (e.g., C 3-20 arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 4- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 alkynylene), alkenylene (e.g., C 2-6 alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently be further selected from the group consisting of deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), cyano, or any combination thereof; and The hydrogen of the methyl and the C 2-30 One or more (e.g., 1-30, e.g., 1-25, 1-20, 1-15, 1-10, 1-5, 1-4, 1-3, 1-2, or 1) hydrogens in the CH of the alkyl may be further replaced by deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6Cycloalkyl (e.g., optionally perdeuterated cyclopropyl, optionally perdeuterated cyclobutyl, optionally perdeuterated cyclopentyl, or optionally perdeuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), or any combination thereof.

[0048] In some embodiments, R5 of the compound of formula (I) represents hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, optionally substituted methoxy, optionally substituted ethoxy, optionally substituted propoxy, optionally substituted butoxy, or optionally substituted tert-butoxy.

[0049] In some embodiments, R and R of the compound of formula (I) together with the carbon atom to which they are attached form a carbonyl. In other words, R of the compound of formula (I)a is the following group: [ka] represents where R6 is as defined above.

[0050] In some embodiments, R and R5 are as defined above in the compounds of formula (I) and any of the embodiments thereof, and R6 is Hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C 2-30 represents alkyl, wherein the linear or branched chain C 2-30 The alkyl carbon backbone may contain one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and / or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R d , or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and R d Any combination of the groups R c , R d or group R c and R d The combination of the carbon-carbon bonds between one or more pairs (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2 pairs, or one pair) of adjacent carbon atoms in the carbon backbone is cleaved; c is O, N(R e ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R e ), N(R e )C(O), or N(R e )C(O)N(R e), wherein each R e are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), and the linear or branched C 2-30 Two or more groups R in the main carbon chain of the alkyl c When inserted, each group R c are not directly connected; each group R d is a cycloalkylene (e.g., C 3-20 cycloalkylene), arylene (e.g., C 3-20 arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 4- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 alkynylene), alkenylene (e.g., C 2-6 alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; and The hydrogen of the methyl and the C 2-30 One or more (e.g., 1-30, e.g., 1-25, 1-20, 1-15, 1-10, 1-5, 1-4, 1-3, 1-2, or 1) hydrogens in the CH of the alkyl may be replaced by deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C1-4Alkyl, for example 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), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), or any combination thereof.

[0051] In some subembodiments, R6 of the compound of Formula (I) represents hydrogen, fluorine, chlorine, bromine, or iodine.

[0052] In some subembodiments, R6 of the compound of Formula (I) has the structure of the following formula: -C 1-30 アルキル; -(C(R a4 )(R a5 )) n1 -(R c -(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(R c -(C(R a6 )(R a7 )) n2 ) m4 -(R c -(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(R c -(C(R a6 )(R a7 )) n2 ) m4 -(R c -(C(R a8 )(R a9 )) n3 ) m5 -(R c -(C(R a10 )(R a11 )) n4 ) m6 -H; -(C(R a4 )(R a5 )) n1 -(R d -(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(R d -(C(R a6 )(R a7 )) n2 ) m4 -(R d-(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(R d -(C(R a6 )(R a7 )) n2 ) m4 -(R d -(C(R a8 )(R a9 )) n3 ) m5 -(R d -(C(R a10 )(R a11 )) n4 ) m6 -H; -(C(R a4 )(R a5 )) n1 -(R c -R d -(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(R c -(C(R a6 )(R a7 )) n2 ) m4 -(R d -(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(R d -R c -(C(R a6 )(R a7 )) n2 ) m4 -H; or -(C(R a4 )(R a5 )) n1 -(R d -(C(Ra6 )(R a7 )) n2 ) m4 -(R c -(C(R a8 )(R a9 )) n3 ) m5 -H represents where each group R c is O, N(R e ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R e ), N(R e )C(O), or N(R e )C(O)N(R e ), wherein each R e are independently H or C 1-6 represents alkyl; each group R d is a cycloalkylene (e.g., C 3-20 cycloalkylene), arylene (e.g., C 5-20 arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 5- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 alkynylene), alkenylene (e.g., C 2-6 alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, can further comprise deuterium (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), cyano, or any combination thereof; Said C 1-30 One or more (e.g., 1-30, e.g., 1-25, 1-20, 1-15, 1-10, 1-5, 1-4, 1-3, 1-2, or 1) hydrogens in the CH of the alkyl may be further replaced by deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example 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), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), or any combination thereof; R a4 , R a5 , R a6 , R a7 , R a8 , R a9 , R a10 and R a11 teeth、 Each independently represents H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, or optionally deuterated C. 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example 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), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), or optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4alkyl-C(O)NH-, for example, CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-; and n1, n2, n3, n4, m4, m5, and m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

[0053] In some subembodiments, R6 of the compound of Formula (I) has the structure of the following formula: -(C(R a4 )(R a5 )) n1 -(O-(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(O-(C(R a6 )(R a7 )) n2 ) m4 -(O-(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(O-(C(R a6 )(R a7 )) n2 ) m4 -(O-(C(R a8 )(R a9 )) n3 ) m5 -(O-(C(R a10 )(R a11 )) n4 ) m6 -H; -(C(R a4 )(R a5 )) n1 -(N(R e )-(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(Ra4 )(R a5 )) n1 -(N(R e )-(C(R a6 )(R a7 )) n2 ) m4 -(N(R e )-(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(N(R e )-(C(R a6 )(R a7 )) n2 ) m4 -(N(R e )-(C(R a8 )(R a9 )) n3 ) m5 -(N(R e )-(C(R a10 )(R a11 )) n4 ) m6 -H; -(C(R a4 )(R a5 )) n1 -(C(O)N(R e )-(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(C(O)N(R e )-(C(R a6 )(R a7 )) n2 ) m4 -(C(O)N(R e )-(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(C(O)N(R e )-(C(Ra6 )(R a7 )) n2 ) m4 -(C(O)N(R e )-(C(R a8 )(R a9 )) n3 ) m5 -(C(O)N(R e )-(C(R a10 )(R a11 )) n4 ) m6 -H; -(C(R a4 )(R a5 )) n1 -(C(O)N(R e )-(C(R a6 )(R a7 )) n2 ) m4 -(O-(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -C(O)N(R e )-(C(R a6 )(R a7 )) n2 -(O-(C(R a8 )(R a9 )) n3 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(N(R e )C(O)-(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(N(R e )C(O)-(C(R a6 )(R a7 )) n2 ) m4 -(O-(C(R a8 )(R a9 )) n3) m5 -H; -(C(R a4 )(R a5 )) n1 -(N(R e )C(O)-(C(R a6 )(R a7 )) n2 ) m4 -(O-(C(R a8 )(R a9 )) n3 ) m5 -(O-(C(R a10 )(R a11 )) n4 ) m6 -H; -(C(R a4 )(R a5 )) n1 -N(R e )C(O)-(C(R a6 )(R a7 )) n2 -(O-(C(R a8 )(R a9 )) n3 ) m4 -H; -(C(R a4 )(R a5 )) n1 -N(R e )C(O)N(R e )-(C(R a6 )(R a7 )) n2 -H; -(C(R a4 )(R a5 )) n1 -C(O)-(C(R a6 )(R a7 )) n2 -H; -(C(R a4 )(R a5 )) n1 -(アリーレン-(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(アリーレン-(C(R a6 )(Ra7 )) n2 ) m4 -Arylene-(C(R a8 )(R a9 )) n3 -H; -(C(R a4 )(R a5 )) n1 -(heterocyclylene-(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(heterocyclylene-(C(R a6 )(R a7 )) n2 ) m4 -(heterocyclylene-(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(heteroarylene-(C(R a6 )(R a7 )) n2 ) m4 -H; -(C(R a4 )(R a5 )) n1 -(heteroarylene-(C(R a6 )(R a7 )) n2 ) m4 -(heteroarylene-(C(R a8 )(R a9 )) n3 ) m5 -H; -(C(R a4 )(R a5 )) n1 -(cycloalkylene-(C(R a6 )(R a7 )) n2 ) m4 -H; or -(C(R a4 )(R a5 )) n1-(cycloalkylene-(C(R a6 )(R a7 )) n2 ) m4 -(cycloalkylene-(C(R a8 )(R a9 )) n3 ) m5 -H; represents Here, each R e are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; The cycloalkylene (e.g., C 3-20 Cycloalkylene, C 3-15 Cycloalkylene, C 3-10 Cycloalkylene, C 3-8 Cycloalkylene, or C 3-6 cycloalkylene), the arylene (e.g., C 5-20 Arylene, C 5-15 Arylene, C 5-10 Arylene or C 5-6 arylene), the heterocyclylene (e.g., 4- to 20-membered heterocyclylene, 4- to 15-membered heterocyclylene, 4- to 10-membered heterocyclylene, 4- to 9-membered heterocyclylene, 4- to 8-membered heterocyclylene, 5- to 7-membered heterocyclylene, or 6-membered heterocyclylene), and the heteroarylene (e.g., 5- to 20-membered heteroarylene, 5- to 15-membered heteroarylene, 5- to 10-membered heteroarylene, 5- to 9-membered heteroarylene, 5- to 8-membered heteroarylene, 5- to 7-membered heteroarylene, or 6-membered heteroarylene), each independently, further include deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 3-6Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), cyano, or any combination thereof; R a4 , R a5 , R a6 , R a7 , R a8 , R a9 , Ra10 and R a11 are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example 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), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), or optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4alkyl-C(O)NH-, for example, CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-; and n1, n2, n3, n4, m4, m5, and m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

[0054] In some subembodiments, R6 of the compound of Formula (I) is one of the following groups: H, fluorine, chlorine, bromine, iodine, -CH3, -CH2-CH3, -(CH2)2-CH3, -(CH2)3-CH3, -(CH2)4-CH3, -(CH2)5-CH3, -(CH2)6-CH3, -(CH2)7-CH3, -(CH2)8-CH3, -(CH2)9-CH3, -(CH2) 10 -CH3, -(CH2) 11 -CH3, -(CH2) 12 -CH3, -(CH2) 13 -CH3, -(CH2) 14 -CH3, -(CH2) 15 -CH3, -(CH2) 16 -CH3, -(CH2) 17 -CH3, -(CH2) 18 -CH3, -(CH2) 19 -CH3, -(CH2) 20 -CH3, -(CH2) 21 -CH3, -(CH2) 22 -CH3, -(CH2) 25 -CH3, -(CH2) 29 -CH3;-CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-O-(CH2)2-CH3, -(CH2)1-O-(CH2)3-CH3, -(CH2)1-O-(CH2)4-CH3, -(CH2)1-O-(CH2 )5-CH3, -(CH2)1-O-(CH2)6-CH3, -(CH2)1-O-(CH2)7-CH3, -(CH2)1-O-(CH2)8-CH3, -(CH2)1-O-(CH2)9-CH3, -(CH2)1-O-(CH2) 10-CH3、-(CH2)2-O-CH3、-(CH2)2-O-CH2-CH3、-(CH2)2-O-(CH2)2-CH3、-(CH2)2-O-(CH2)3-CH3、-(CH2)2-O-(CH2)4-CH3、-(CH2)2-O-(CH2)5-CH3、-(CH2)2-O-(CH2)6-CH3、-(CH2)2-O-(CH2)7-CH3、-(CH2)2-O-(CH2)8-CH3、-(CH2)2-O-(CH2)9-CH3、-(CH2)2-O-(CH2) 10 -CH3、-(CH2)2-O-(CH2) 11 -CH3、-(CH2)2-O-(CH2) 12-CH3、-(CH2)3-O-CH3、-(CH2)3-O-CH2-CH3、-(CH2)3-O-(CH2)2-CH3、-(CH2)3-O-(CH2)3-CH3、-(CH2)3-O-(CH2)4-CH3、-(CH2)3-O-(CH2)5-CH3、-(CH2)3-O-(CH2)6-CH3、-(CH2)3-O-(CH2)7-CH3、-(CH2)4-O-CH3、-(CH2)4-O-CH2-CH3、-(CH2)4-O-(CH2)2-CH3、 -(CH2)4-O-(CH2)3-CH3、-(CH2)4-O-(CH2)4-CH3、-(CH2)4-O-(CH2)5-CH3、-(CH2)4-O-(CH2)6-CH3、-(CH2)5-O-CH3、-(CH2)5-O-CH2-CH3、-(CH2)5-O-(CH2)2-CH3、-(CH2)5-O-(CH2)3-CH3、-(CH2)5-O-(CH2)4-CH3、-(CH2)5-O-(CH2)5-CH3、-(CH2)6-O-CH3、-( CH2)6-O-CH2-CH3、-(CH2)6-O-(CH2)2-CH3、-(CH2)6-O-(CH2)3-CH3、-(CH2)6-O-(CH2)4-CH3、-(CH2)7-O-CH3、-(CH2)7-O-CH2-CH3、-(CH2)7-O-(CH2)2-CH3、-(CH2)7-O-(CH2)3-CH3、-(CH2)8-O-CH3、-(CH2)8-O-CH2-CH3、-(CH2)8-O-(CH2)2-CH3、-CH(CH3)-O -CH3、-CH(CH3)-O-CH2-CH3、-CH(CH3)-O-(CH2)2-CH3、-CH(CH3)-O-(CH2)3-CH3、-CH(CH3)-O-(CH2)4-CH3、-CH(CH3)-O-(CH2)5-CH3、-CH(CH3)-O-(CH2)6-CH3、-CH(CH3)-O-(CH2)7-CH3、-CH(CH3)-O-(CH2)8-CH3、-CH(CH3)-O-(CH2)9-CH3、-CH(CH3)-O-(CH2) 10-CH3、-CH2-(O(CH2)2)1-OCH2CH3、-CH2-(O(CH2)2)2-OCH2CH3、-CH2-(O(CH2)2)3-OCH2CH3、-CH2-(O(CH2)2)4-OCH2CH3、-CH2-(O(CH2)2)5- OCH2CH3、-CH2-(O(CH2)2)6-OCH2CH3、-CH2-(O(CH2)2)7-OCH2CH3、-CH2-(O(CH2)2)8-OCH2CH3、-CH2-(O(CH2)2)9-OCH2CH3、-CH2-(O(CH2)2) 10 -OCH2CH3、-CH2-(O(CH2)2)1-OCH3、-CH2-(O(CH2)2)2-OCH3、-CH2-(O(CH2)2)3-OCH3、-CH2-(O(CH2)2)4-OCH3、-CH2-(O(CH2)2)5-OCH3、-CH2-(O(CH2)2)6-OCH3、-CH2-(O(CH2)2)7-OCH3、-CH2-(O(CH2)2)8-OCH3、-CH2-(O(CH2)2)9-OCH3、-CH2-(O(CH2)2) 10 -OCH3、-(CH2)2-(O(CH2)2)1-OCH2CH3、-(CH2)2-(O(CH2)2)2-OCH2CH3、-(CH2)2-(O(CH2)2) 3-OCH2CH3、-(CH2)2-(O(CH2)2)4-OCH2CH3、-(CH2)2-(O(CH2)2)5-OCH2CH3、-(CH2)2-(O(CH2) )2)6-OCH2CH3、-(CH2)2-(O(CH2)2)7-OCH2CH3、-(CH2)2-(O(CH2)2)8-OCH2CH3、-(CH2)2-(O(CH2)2)9-OCH2CH3、-(CH2)2-(O(CH2)2) 10-OCH2CH3、-(CH2)3-(O(CH2)2)1-OCH2CH3、-(CH2)3-(O(CH2)2)2-OCH2CH3、-(CH2)3-(O(CH2)2)3-OCH2CH3、-(CH2)3-(O(CH2)2)4-OCH2CH3、-(CH2)3-(O(CH2)2)5-OCH2CH3、-(CH2)3-(O(CH2)2)6-OCH2CH3、-(CH2)3-(O(CH2)2)7-OCH2CH3、-(CH2)3-(O(CH2)2)8-OCH2CH3、-(CH2)3-(O(CH2)2)9-OCH2CH3、-(CH2)3-(O(CH2)2) 10 -OCH2CH3、-(CH2)4-(O(CH2)2)1-OCH2CH3、-(CH2)4-(O(CH2)2)2-OCH2CH3、-(CH2)4-(O(CH2)2)3-OCH2CH3、-(CH2)4-(O(CH2)2)4-OCH2CH3、-(CH2)4-(O(CH2)2)5-OCH2CH3、-(CH2)4-(O(CH2)2)6-OCH2CH3、-(CH2)4-(O(CH2)2)7-OCH2CH3、-(CH2)4-(O(CH2)2)8-OCH2CH3、-(CH2)4-(O(CH2)2)9-OCH2CH3、-(CH2)4-(O(CH2)2) 10 -OCH2CH3、-CH2-(O(CH2)3)1-OCH2CH2CH3、-CH2-(O(CH2)3)2-OCH2CH2CH3、-CH2-(O(CH2)3)3-OCH2CH2CH3、-CH2-(O(CH2)3)4-OCH2CH2CH3、-CH2-(O(CH2)3)5-OCH2CH2CH3、-CH2-(O(CH2)3)6-OCH2CH2CH3、-CH2-(O(CH2)3)7-OCH2CH2CH3、-CH2-(O(CH2)3)8-OCH2CH2CH3、-CH2-(O(CH2)3)9-OCH2CH2CH3、-CH2-(O(CH2)3) 10-OCH2CH2CH3、-(CH2)2-(O(CH2)3)1-OCH2CH2CH3、-(CH2)2-(O(CH2)3)2-OCH2CH2CH3、-(CH2)2-(O(CH2)3)3-OCH2CH2CH3、-(CH2)2-(O(CH2)3)4-OCH2CH2CH3、-(CH2)2-(O(CH2)3)5-OCH2CH2CH3、-(CH2)2-(O(CH2)3)6-OCH2CH2CH3、-(CH2)2-(O(CH2)3)7-OCH2CH2CH3、-(CH2)2-(O(CH2)3)8-OCH2CH2CH3、-(CH2)3-(O(CH2)3)1-OCH2CH2CH3、-(CH2)3-(O(CH2)3)2-OCH2CH2CH3、-(CH2)3-(O(CH2)3)3-OCH2CH2CH3、-(CH2)3-(O(CH2)3)4-OCH2CH2CH3、-(CH2)3-(O(CH2)3)5-OCH2CH2CH3、-(CH2)3-(O(CH2)3)6-OCH2CH2CH3、-(CH2)3-(O(CH2)3)7-OCH2CH2CH3、-(CH2)3-(O(CH2)3)8-OCH2CH2CH3、-CH2-O-(CH2)2-O-(CH2)2-CH3、-CH2-(O(CH2)2)2-(O(CH2)3)1-OCH2CH2CH3、-CH2-(O(CH2)2)3-(O(CH2)3)2-OCH2CH2CH3、-CH2-(O(CH2)2)4-(O(CH2)3)3-OCH2CH2CH3、-CH2-(O(CH2)2)5-(O(CH2)3)4-OCH2CH2CH3、-(CH2)2-O-(CH2)2-O-(CH2)2CH3、-(CH2)2-(O(CH2)2)2-(O(CH2)3)1-OCH2CH2CH3、-(CH2)2-(O(CH2)2)3-(O(CH2)3)2-OCH2CH2CH3、-(CH2)2-(O(CH2)2)4-(O(CH2)3)3-OCH2CH2CH3、-(CH2)2-(O(CH2)2)5-(O(CH2)3)4-OCH2CH2CH3、-(CH2)3-O-(CH2)2-O-(CH2)2CH3、-(CH2)3-(O(CH2)2)2-(O(CH2)3)1-OCH2CH2CH3、-(CH2)3-(O(CH2)2)3-(O(CH2)3)2-OCH2CH2CH3、-(CH2)3-(O(CH2)2)4-(O(CH2)3)3-OCH2CH2CH3、-(CH2)3-(O(CH2)2)5-(O(CH2)3)4-OCH2CH2CH3、-CH2-O-(CH2)3-O-CH2CH3 、-CH2-(O(CH2)3)2-(O(CH2)2)1-O-CH2CH3、-CH2-(O(CH2)3)3-(O(CH2)2)2-O-CH2CH3、-CH2-(O(CH2)3)4-(O(CH2)2)3-O-CH、 2CH3、-CH2-(O(CH2)3)5-(O(CH2)2)4-O-CH2CH3、-(CH2)2-O-(CH2)3-O-CH2CH3、-(CH2)2-( O(CH2)3)2-(O(CH2)2)1-O-CH2CH3、-(CH2)2-(O(CH2)3)3-(O(CH2)2)2-O-CH2CH3、-(CH2)2- (O(CH2)3)4-(O(CH2)2)3-O-CH2CH3、-(CH2)2-(O(CH2)3)5-(O(CH2)2)4-O-CH2CH3、-(CH2)3 -O-(CH2)3-O-CH2CH3、-(CH2)3-(O(CH2)3)2-(O(CH2)2)1-O-CH2CH3、-(CH2)3-(O(CH2)3)3- (O(CH2)2)2-O-CH2CH3、-(CH2)3-(O(CH2)3)4-(O(CH2)2)3-O-CH2CH3、-(CH2)3-(O(CH2)3) 5-(O(CH2)2)4-O-CH2CH3、-CH2-O-(CH2)2-O-CH3、-(CH2)2-O-(CH2)2-O-CH3、-(CH2)2-(O(C H2)2)2-O-(CH2)2CH3、-(CH2)2-(O(CH2)2)3-O-(CH2)2CH3、-(CH2)2-(O(CH2)2)4-O-(CH2)2CH3、-(CH2)5-(O(CH2)2)2-O-(CH2)4CH3、-(CH2)5-(O(CH2)2)2-O-(CH2)5CH3、-(CH2)1-N(R e )-CH3、-(CH2)1-N(R e )-(CH2)1-CH3、-(CH2)1-N(R e )-(CH2)2-CH3、-(CH2)1-N(R e )-(CH2)3-CH3、-(CH2)1-N(R e)-(CH2)4-CH3、-(CH2)1-N(R e )-(CH2)5-CH3、-(CH2)1-N(R e )-(CH2)6-CH3、-(CH2)1-N(R e )-(CH2)7-CH3、-(CH2)1-N(R e )-(CH2)8-CH3、-(CH2)1-N(R e )-(CH2)9-CH3、-(CH2)2-N(R e )-CH3、-(CH2)2-N(R e )-(CH2)1-CH3、-(CH2)2-N(R e )-(CH2)2-CH3、-(CH2)2-N(R e )-(CH2)3-CH3、-(CH2)2-N(R e )-(CH2)4-CH3、-(CH2)2-N(R e )-(CH2)5-CH3、-(CH2)2-N(R e )-(CH2)6-CH3、-(CH2)2-N(R e )-(CH2)7-CH3、-(CH2)2-N(R e )-(CH2)8-CH3、-(CH2)2-N(R e )-(CH2)9-CH3、-(CH2)2-N(R e )-(CH2) 10 -CH3、-(CH2)2-N(R e )-(CH2) 11 -CH3、-(CH2)3-N(R e )-CH3、-(CH2)3-N(R e )-(CH2)1-CH3、-(CH2)3-N(R e )-(CH2)2-CH3、-(CH2)4-N(R e )-CH3、-(CH2)4-N(R e )-(CH2)1-CH3、-(CH2)4-N(R e )-(CH2)2-CH3、-(CH2)4-N(R e )-(CH2)3-CH3、-(CH2)5-N(R e )-CH3、-(CH2)5-N(R e )-(CH2)1-CH3、-(CH2)5-N(R e)-(CH2)2-CH3、-(CH2)5-N(R e )-(CH2)3-CH3、-(CH2)5-N(R e )-(CH2)4-CH3、-(CH2)6-N(R e )-CH3、-(CH2)6-N(R e )-(CH2)1-CH3、-(CH2)6-N(R e )-(CH2)2-CH3、-(CH2)7-N(R e )-CH3、-(CH2)7-N(R e )-(CH2)1-CH3、-(CH2)7-N(R e )-(CH2)2-CH3、-(CH2)8-N(R e )-CH3、-(CH2)8-N(R e )-(CH2)1-CH3、-(CH2)8-N(R e )-(CH2)2-CH3、-CH(CH3)-N(R e )-CH3、-CH(CH3)-N(R e )-(CH2)1-CH3、-CH(CH3)-N(R e )-(CH2)2-CH3、-CH(CH3)-N(R e )-(CH2)3-CH3、-CH(CH3)-N(R e )-(CH2)4-CH3、-CH(CH3)-N(R e )-(CH2)5-CH3、-CH(CH3)-N(R e )-(CH2)6-CH3、-CH(CH3)-N(R e )-(CH2)7-CH3、-CH(CH3)-N(R e )-(CH2)8-CH3、-CH(CH3)-N(R e)-(CH2)9-CH3、-CH2C(O)NHCH3、-(CH2)2C(O)NHCH2CH3、-(CH2)2C(O)NH(CH2)2-CH3、-(CH2)2C(O)NH(CH2)3-CH3、-(CH2)2C(O)NH(CH2)4-CH3、-(CH2)3C(O)NH(CH2)2-CH3、-(CH2)3C(O)NH(CH2)3-CH3、-(CH 2)4C(O)NH(CH2)3-CH3、-(CH2)5C(O)NH(CH2)4-CH3、-(CH2)6C(O)NH(CH2)6-CH3、-(CH2)6C(O)NH(CH2)5-CH3、-(CH2)7C(O)NH(CH2)6-CH3、-(CH2)8C(O)NH(CH2)7-CH3、U-(CH2)9C(O)NH(CH2)8-CH3、-(CH2) 10 C(O)NH(CH2)9-CH3、-(CH2)2C(O)NH(CH2)2-O-CH2-CH3、-CH2NHC( O)CH3、-(CH2)2NHC(O)CH2CH3、-(CH2)2NHC(O)(CH2)2-CH3、-(CH2)2NHC(O)(CH2)3-CH3、-(CH2) 2NHC(O)(CH2)4-CH3、-(CH2)3NHC(O)(CH2)2-CH3、-(CH2)3NHC(O)(CH2)3-CH3、-(CH2)4NHC(O)( CH2)3-CH3、-(CH2)5NHC(O)(CH2)4-CH3、-(CH2)6NHC(O)(CH2)6-CH3、-(CH2)6NHC(O)(CH2)5-CH 3、-(CH2)7NHC(O)(CH2)6-CH3、-(CH2)8NHC(O)(CH2)7-CH3、-(CH2)9NHC(O)(CH2)8-CH3、-(CH2) 10NHC(O)(CH2)9-CH3, -(CH2)4NHC(O)(CH2)7-CH3, -(CH2)2NHC(O)(CH2)2-O-CH2-CH3, -(CH2)4NHC(O)CH3, -CH2-piperidinylene-CH3, -CH2-piperidinylene-CH2-CH3, -CH2-piperidinylene-(CH2)2-CH3, -CH2-piperidinylene-(CH2)3-CH3, -CH2-piperidinylene-(CH2)4-CH3, -CH2-piperidinylene-(CH2)5-CH3, -CH2-piperidinylene-(CH2)6-CH3, -CH2-Piperidinylene-(CH2)7-CH3, -(CH2)2-piperidinylene-CH3, -(CH2)2-piperidinylene-CH2-CH3, -(CH2)2-piperidinylene-(CH2)2-CH3, -(CH2)2-piperidinylene-(CH2)3-CH3, -(CH2)2-piperidinylene-(CH2)4-CH3, -(CH2)2-piperidinylene-(CH2)5-CH3, -(CH2)2-piperidinylene-(CH2)6-CH3, -(CH2)2-piperidinylene-(CH2)7-CH3, -(CH2)3-piperidinylene-C H3, -(CH2)3-piperidinylene-CH2-CH3, -(CH2)3-piperidinylene-(CH2)2-CH3, -(CH2)3-piperidinylene-(CH2)3-CH3, -(CH2)3-piperidinylene-(CH2)4-CH3, -(CH2)3-piperidinylene-(CH2)5-CH3, -(CH2)3-piperidinylene-(CH2)6-CH3, -(CH2)3-piperidinylene-(CH2)7-CH3, -(CH2)4-piperidinylene-CH3, -(CH2)4-piperidinylene-CH2-CH3, -(CH2)4-piperidinylene ylene-(CH2)2-CH3, -(CH2)4-piperidinylene-(CH2)3-CH3, -(CH2)4-piperidinylene-(CH2)4-CH3, -(CH2)4-piperidinylene-(CH2)5-CH3, -(CH2)4-piperidinylene-(CH2)6-CH3, -(CH2)4-piperidinylene-(CH2)7-CH3, -(CH2)5-piperidinylene-CH3, -(CH2)5-piperidinylene-CH2-CH3, -(CH2)5-piperidinylene-(CH2)2-CH3, -(CH2)5-piperidinylene-(CH2)3-CH3,-(CH2)5-piperidinylene-(CH2)4-CH3, -(CH2)5-piperidinylene-(CH2)5-CH3, -(CH2)5-piperidinylene-(CH2)6-CH3, -(CH2)5-piperidinylene-(CH2)7-CH3, -(CH2)6-piperidinylene-CH3, -(CH2)6-piperidinylene-CH2-CH3, -(CH2)6-piperi Piperidinylene-(CH2)2-CH3, -(CH2)6-piperidinylene-(CH2)3-CH3, -(CH2)6-piperidinylene-(CH2)4-CH3, -(CH2)6-piperidinylene-(CH2)5-CH3, -(CH2)6-piperidinylene-(CH2)6-CH3, -(CH2)6-piperidinylene-(CH2)7-CH3, -(CH2)7-piperidinylene ylene-CH3, -(CH2)7-piperidinylene-CH2-CH3, -(CH2)7-piperidinylene-(CH2)2-CH3, -(CH2)7-piperidinylene-(CH2)3-CH3, -(CH2)7-piperidinylene-(CH2)7-CH3, -(CH2)8-piperidinylene-CH3, -(CH2)8-piperidinylene-CH2-CH3, -(CH2)8 -piperidinylene-(CH2)2-CH3, -(CH2)8-piperidinylene-(CH2)3-CH3, -(CH2)8-piperidinylene-(CH2)4-CH3, -(CH2)8-piperidinylene-(CH2)5-CH3, -(CH2)8-piperidinylene-(CH2)6-CH3, -(CH2)8-piperidinylene-(CH2)7-CH3, -CH2-N(R, e )-CH2-piperidinylene-CH3, -CH2-N(R e )-CH2-piperidinylene-CH3, -CH2-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -CH2-N(R e )-CH2-piperidinylene-(CH2)3-CH3, -CH2-N(R e )-CH2-piperidinylene-(CH2)4-CH3, -CH2-N(R e )-CH2-piperidinylene-(CH2)5-CH3, -CH2-N(R e )-CH2-piperidinylene-(CH2)6-CH3, -CH2-N(R e)-CH2-piperidinylene-(CH2)7-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-CH2-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-(CH2)2-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-(CH2)3-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-(CH2)4-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-(CH2)5-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-(CH2)6-CH3, -CH2-N(R e )-(CH2)2-piperidinylene-(CH2)7-CH3, -(CH2)2-N(R e )-CH2-piperidinylene-CH3, -(CH2)2-N(R e )-CH2-piperidinylene-CH2-CH3, -( CH2)2-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -(CH2)2-N(R e )-CH2-piperidinylene-(CH2)3-CH3, -(CH2)2-N(R e )-CH2-piperidinylene-(CH2)4-CH3, -(CH2)2-N(R e )-CH2-piperidinylene-(CH2)5-CH3, -(CH2)2-N(R e )-CH2-piperidinylene-(CH2)6-CH3, -(CH2)2-N(R e )-CH2-piperidinylene-(CH2)7-CH3, -(CH2)3-N(R e )-CH2-piperidinylene-CH3, -(CH2)3-N(R e )-CH2-piperidinylene-CH2-CH3, -(CH2)3-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -(CH2)3-N(R e )-CH2-piperidinylene-(CH2)7-CH3, -(CH2)4-N(Re )-CH2-piperidinylene-CH3, -(CH2)4-N(R e )-CH2-piperidinylene-CH2-CH3, -(CH2)4-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -(CH2)4-N(R e )-CH2-piperidinylene-(CH2)7-CH3, -(CH2)5-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -(CH2)5-N(R e )-CH2-piperidinylene-(CH2)7-CH3, -(CH2)6-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -(CH2)6-N(R e )-CH2-piperidinylene-(CH2)7-CH3, -(CH2)7-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -(CH2)7-N(R e )-CH2-piperidinylene-(CH2)7-CH3, -(CH2)8-N(R e )-CH2-piperidinylene-CH3, -(CH2)8-N(R e )-CH2-piperidinylene-CH2-CH3, -(CH2)8-N(R e )-CH2-piperidinylene-(CH2)2-CH3, -(CH2)8-N(R e )-CH2-piperidinylene-(CH2)3-CH3, -(CH2)8-N(R e )-CH2-piperidinylene-(CH2)4-CH3, -(CH2)8-N(R e )-CH2-piperidinylene-(CH2)5-CH3, -(CH2)8-N(R e )-CH2-piperidinylene-(CH2)6-CH3, -(CH2)8-N(R e)-CH2-piperidinylene-(CH2)7-CH3, -CH2-piperazinylene-CH3, -CH2-piperazinylene-CH2-CH3, -CH2-piperazinylene-(CH2)2-CH3, -CH2-piperazinylene-(CH2)3-CH3, -CH2-piperazinylene-(CH2)4-CH3, -CH2-piperazinylene-(CH2)5-CH3, -CH2-piperazinylene-(CH2)6-CH3, -CH2-piperazinylene-(CH2)7-CH3, -(CH2)2-piperazinylene-CH3, -(CH2)2-piperazinylene-C H2-CH3, -(CH2)2-piperazinylene-(CH2)2-CH3, -(CH2)2-piperazinylene-(CH2)3-CH3, -(CH2)2-piperazinylene-(CH2)4-CH3, -(CH2)2-piperazinylene-(CH2)5-CH3, -(CH2)2-piperazinylene-(CH2)6-CH3, -(CH2)2-piperazinylene-(CH2)7-CH3, -(CH2)3-piperazinylene-CH3, -(CH2)3-piperazinylene-CH2-CH3, -(CH2)3-piperazinylene-(CH2)2-CH3, -(CH 2) 3-piperazinylene-(CH2)3-CH3, -(CH2)3-piperazinylene-(CH2)4-CH3, -(CH2)3-piperazinylene-(CH2)5-CH3, -(CH2)3-piperazinylene-(CH2)6-CH3, -(CH2)3-piperazinylene-(CH2)7-CH3, -(CH2)4-piperazinylene-CH3, -(CH2)4-piperazinylene-CH2-CH3, -(CH2)4-piperazinylene-(CH2)2-CH3, -(CH2)4-piperazinylene-(CH2)3-CH3, -(CH2)4-piperazinylene -(CH2)4-CH3, -(CH2)4-piperazinylene-(CH2)5-CH3, -(CH2)4-piperazinylene-(CH2)6-CH3, -(CH2)4-piperazinylene-(CH2)7-CH3, -(CH2)5-piperazinylene-CH3, -(CH2)5-piperazinylene-CH2-CH3, -(CH2)5-piperazinylene-(CH2)2-CH3, -(CH2)5-piperazinylene-(CH2)3-CH3, -(CH2)5-piperazinylene-(CH2)4-CH3, -(CH2)5-piperazinylene-(CH2)5-CH3,-(CH2)5-piperazinylene-(CH2)6-CH3, -(CH2)5-piperazinylene-(CH2)7-CH3, -(CH2)6-piperazinylene-CH3, -(CH2)6-piperazinylene-CH2-CH3, -(CH2)6-piperazinylene-(CH2)2-CH3, -(CH2)6-piperazinylene-(CH2)3-CH3, -(CH2)6-piperazinylene-(CH2)4-CH3, -(CH2)6-piperazinylene-(CH2)5-CH3, -(CH2)6-piperazinylene-(CH2)6-CH3, -(CH2)6-piperazinylene-(CH2)7-CH3, -(CH2)7-piperazinylene-CH3, -(CH2)7-piperazinylene-CH 2-CH3, -(CH2)7-piperazinylene-(CH2)2-CH3, -(CH2)7-piperazinylene-(CH2)3-CH3, -(CH2)7-piperazinylene-(CH2)7-CH3, -(CH2)8-piperazinylene-CH3, -(CH2)8-piperazinylene-CH2-CH3, -(CH2)8-piperazinylene-(CH2)2-CH3, -(CH2)8-piperazinylene-(CH2)3-CH3, -(CH2)8-piperazinylene-(CH2)4-CH3, -(CH2)8-piperazinylene-(CH2)5-CH3, -(CH2)8-piperazinylene-(CH2)6-CH3, or -(CH2)8-piperazinylene-(CH2)7-CH3; wherein the piperidinylene and the piperazinylene may each independently further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), cyano, or any combination thereof; The CH hydrogen and one or more (e.g., 1-30, e.g., 1-25, 1-20, 1-15, 1-10, 1-5, 1-4, 1-3, 1-2, or 1) CH hydrogens in the group may be replaced by deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example 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), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), or any combination thereof; Each R e are independently H or C 1-6 Alkyl (e.g., C 1-4alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; and n1, n2, n3, n4, m4, m5, and m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

[0055] In some embodiments, R5 and R6 of the compound of formula (I) represent hydrogen.

[0056] In some embodiments, (R b ) n is a group in which the benzene ring is n-number of R b Each R represents a substitution b are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally substituted C 3-6 cycloalkyl (e.g., optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, or optionally substituted cyclohexyl), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6alkynyl (e.g., ethynyl, propynyl, or butynyl); where n represents an integer of 0, 1, 2, or 3. In some subembodiments, the optionally substituted C 3-6 The substituents of cycloalkyl are C1-C3 alkyl, C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkyl-NH-, halogenated C1-C3 alkyl, NH2-C 1-3 Alkylene, C 1-3 Alkyl-NHC(O)-, C 1-3 The substituents are selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof, and the number of the substituents may be one or more (for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1). The number of the substituents is not limited in principle, or is automatically limited by the size of the constitutional unit.

[0057] In some embodiments, the compound of Formula (I) is also a compound of Formula (I-1) or Formula (I-2): [ka] Here, A, R1, R2, R3, R4, (R b ) n and (R a ) m is as defined above for the compounds of formula (I) and each embodiment thereof.

[0058] In some embodiments, the compound of Formula (I) is also a compound of Formula (I-3) or Formula (I-4): [ka] where A, (R b ) n and (R a ) m is as defined above for the compounds of formula (I) and each embodiment thereof.

[0059] In some embodiments, the compound of Formula (I) is also a compound of Formula (I-5), Formula (I-6), Formula (I-7), or Formula (I-8): [ka] Here, A, R1, R2, R3, R4, (R b ) n and R a is as defined above for the compounds of formula (I) and each embodiment thereof.

[0060] In some embodiments, in the compound of Formula (I-5), Formula (I-6), Formula (I-7), or Formula (I-8), A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); (R a ) m The benzene ring has m R a Each R represents a substitution a are the same or different and each independently have the following structure: [ka] represents; where: R is chlorine, bromine, iodine, hydroxy, a leaving group (e.g., -N3, chlorine, bromine, iodine, a sulfonate group such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)), NR7R8, or a group W 1 represents wherein R7 and R8 are the same or different and each independently represent hydrogen, C 1-6 Alkyl (e.g., C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 2-6 Alkynyl-C 1-6 Alkylene-(e.g., C 2-6 Alkynyl-C 1-4 Alkylene- or C 2-6 Alkynyl-C 1-3 alkylene-, for example, ethynyl-methylene-, ethynyl-ethylene-, ethynyl-propylene-, ethynyl-butylene-, ethynyl-pentylene-, or ethynyl-hexylene-), C 2-6 Alkenyl-C 1-6 Alkylene-(e.g., C 2-6 Alkenyl-C 1-4 Alkylene- or C 2-6 Alkenyl-C 1-3 alkylene-, e.g., vinyl-methylene-, vinyl-ethylene-, vinyl-propylene-, vinyl-butylene-, vinyl-pentylene-, or vinyl-hexylene-), optionally substituted 4- to 15-membered (e.g., 4- to 11-membered, 4- to 10-membered, 4- to 9-membered, 4- to 8-membered, 4- to 7-membered, 4- to 6-membered, 5- to 15-membered, or 5- to 9-membered) nitrogen-containing heterocyclyl, or R 2a -R 1a - represents where R 1a is an arbitrarily substituted C 1-6 Alkylene (e.g., optionally substituted C 1-4 alkylene, e.g., optionally substituted methylene, ethylene, or propylene) or optionally substituted C 2-6Alkenylene (e.g., optionally substituted C 2-4 alkenylene, e.g., optionally substituted vinylene, propenylene, butenylene), R 2a is halogen (e.g., fluorine, chlorine, bromine, or iodine), amino, hydroxy, carboxy, C 2-6 Alkynyl (e.g., C 2-4 alkynyl, for example, ethynyl, propynyl or butynyl), C 2-6 Alkenyl (e.g., C 2-4 alkenyl, e.g., vinyl, propenyl, or butenyl) or a leaving group (e.g., —N3, chlorine, bromine, iodine, a sulfonate group, e.g., methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-), or p-toluenesulfonyloxy (TsO-)); and Base W 1 is a structure of the formula: [ka] or [ka] represents; Here, the ring W 2 represents an optionally substituted nitrogen-containing heterocyclyl (e.g., an optionally substituted 4- to 20-membered nitrogen-containing heterocyclyl), and each ring W 3 are the same or different and each independently represent an optionally substituted nitrogen-containing heterocyclylene (e.g., an optionally substituted 4- to 20-membered nitrogen-containing heterocyclylene), t represents an integer of 1 or 2, and the ring W 4 represents an optionally substituted aryl (e.g., an optionally substituted 6- to 10-membered aryl), an optionally substituted heteroaryl (e.g., an optionally substituted 5- to 10-membered heteroaryl), or an optionally substituted heterocyclyl (e.g., a 4- to 15-membered nitrogen-containing heterocyclyl); R5 and R6 are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C 2-30alkyl, wherein the straight or branched chain C 2-30 The alkyl carbon backbone may contain one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and / or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R d , or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and R d Any combination of the groups R c , R d or group R c and R d The combination of the carbon-carbon bonds between one or more pairs (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2 pairs, or one pair) of adjacent carbon atoms in the carbon backbone is cleaved; c is O, N(R e ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R e ), N(R e )C(O), or N(R e )C(O)N(R e ), wherein each R e are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), and the linear or branched C 2-30 Two or more groups R in the main carbon chain of the alkyl c When inserted, each group R c are not directly connected; each group R d is a cycloalkylene (e.g., C 3-20 cycloalkylene), arylene (e.g., C 3-20arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 4- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 alkynylene), alkenylene (e.g., C 2-6 alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, can further comprise deuterium (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), or any combination thereof; Or, R and R5 together with the carbon atom to which they are attached form a carbonyl, and R6 is hydrogen, optionally substituted methyl, or optionally substituted straight or branched chain C 2-30 alkyl, wherein the straight or branched chain C 2-30 The alkyl carbon backbone may contain one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and / or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R d , or one or more (e.g., 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R c and R d Any combination of the groups R c , R d or group R c and R d The combination of the carbon-carbon bonds between one or more pairs (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2 pairs, or one pair) of adjacent carbon atoms in the carbon backbone is cleaved; c is O, N(R e ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R e ), N(R e )C(O), or N(Re )C(O)N(R e ), wherein each R e are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), and the linear or branched C 2-30 Two or more groups R in the main carbon chain of the alkyl c When inserted, each group R c are not directly connected; each group R d is a cycloalkylene (e.g., C 3-20 cycloalkylene), arylene (e.g., C 3-20 arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 4- to 20-membered heteroarylene), alkynylene (e.g., C 2-6 alkynylene), alkenylene (e.g., C 2-6 alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently be further selected from the group consisting of deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH- and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and N3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and N3CH2CH2-C(O)NH-), cyano, or any combination thereof; (R b ) n is a group in which the benzene ring is n-number of R b Each R represents a substitution b are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally substituted C 3-6 cycloalkyl (e.g., optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl, or optionally substituted cyclohexyl), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 alkynyl (e.g., ethynyl, propynyl, or butynyl); and m represents an integer of 1, 2, 3, or 4, n represents an integer of 0, 1, 2, or 3, and the sum of m and n represents an integer of 1, 2, 3, or 4; where, when R and R5 together with the carbon atoms connected thereto form a carbonyl group and R6 represents hydrogen, m represents an integer of 1, 2, or 3, n represents an integer of 1, 2, or 3, and the sum of m and n represents an integer of 2, 3, or 4; The conditions are as follows: except for the following compounds and compounds of formula (I'): [ka] When A represents CH or C(O) and R represents an unsubstituted piperazinyl group, m represents an integer of 1 and n represents an integer of 0; A represents CH2 or C(O), and R a represents H2N-CH2-, m represents an integer of 1 and n represents an integer of 0; When A represents C(O) and R represents bromine, m represents an integer of 1 and n represents an integer of 0; and Compounds of formula (I'): [ka] Formula (I') Here, A represents CH2 or C(O), and R represents unsubstituted piperidinyl or piperidinyl substituted with methylamino.

[0061] In some embodiments, specific compounds of Formula (I) in Table 1 below and salts (including pharmaceutically acceptable salts, e.g., hydrochloride salts thereof), pharmaceutical precursors, solvates, isotopically enriched analogues, polycrystalline forms, stereoisomers (including enantiomers and non-enantiomers), or mixtures of stereoisomers thereof are provided. Table 1. Compounds of the present disclosure Compound of formula (II)

[0062] The present disclosure provides a compound of formula (II) or a salt (including a pharmaceutically acceptable salt), stereoisomer (including an enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof: PBM-R f -LIN-ULM Formula (II) Here, PBM, R f , LIN and ULM are as defined above for the compound of formula (II).

[0063] The compounds of formula (II) of the present disclosure are the following compounds: 3-(4-((3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl) methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)pyrrolidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)azetidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; and Not 2-(2,6-dioxopiperidin-3-yl)-5-((3-(4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione.

[0064] The compounds of formula (II) of the present disclosure, or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, pharmaceutical precursors, or polymorphs thereof, can bind to target proteins, recruit the target proteins to E3 ubiquitin ligase, ubiquitinate them, and degrade them. The compounds of formula (II) of the present disclosure can specifically target a particular target protein type or family and have broad pharmacological activity by degrading / inhibiting a variety of different target protein types or families.

[0065] In some embodiments, specific target proteins include, but are not limited to, the target proteins in Table 2 below. Table 2. Applicable specific target proteins

[0066] In some embodiments, the PBM-R f- may be a small molecule ligand bound to a specific target protein, and the target protein may be epidermal growth factor receptor (EGFR), cyclin-dependent protein 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, focal adhesion kinase (FAK), breakpoint cluster region (BCR)-Abelson leukemia virus (ABL) (BCR-ABL), Bruton tyrosine kinase (BTK), and androgen receptor (ABL). receptor (AR), estrogen receptor (ER), bromodomain and extra-terminal domain protein (BET), interleukin-1 receptor-associated kinase 4 (IRAK4), cyclin-dependent kinase 9 (CDK9), histone-lysine N-methyltransferase EZH2 (EZH2), neurotrophic receptor tyrosine kinase (NRK),These include, but are not limited to, NTRK, Src homology 2 domain-containing protein tyrosine phosphatase (SHP2), poly(ADP-ribose) polymerase 1 (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, or GTPase KRas (KRAS).

[0067] In some embodiments, the PBM has the formula: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] and where: (R 1 ) p1 is a group in which the benzene ring in formula (PBM-1) is p1 R 1 Each R represents a substitution 1 are the same or different and each independently represent halogen, hydroxy, NH2, NO2, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 represents alkoxy; (R 2 ) p2 In formula (PBM-1), the quinazoline ring is R 2 Each R represents a substitution 2 are the same or different and each independently represent a halogen, NO2, cyano, halogenated C 1-6 Alkyl, C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Alkoxy, halogenated C 1-10 alkoxy, -O-optionally substituted heterocyclyl, or -NHC(O)R 3 where R 3 is C 1-10 Alkyl, deuterated C 1-10 Alkyl or C 2-10 alkenyl, e.g., R 2 is methyl, methoxy, [ka] or [ka] , for example, [ka] represents; p1 represents an integer of 1, 2, 3, 4, or 5; p2 represents an integer of 1, 2, or 3; (R 4 ) p3 In formula (PBM-2), the benzene ring is p3 R 4 Each R represents a substitution 4 are the same or different and each independently represent a halogen, nitro, cyano, halogenated C 1-6 Alkyl, C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Alkoxy or -NHC(O)R 15a where R 15a is C 1-10 Alkyl, deuterated C 1-10 Alkyl or C 2-10 represents alkenyl, for example, R 4 is a methyl, methoxy, nitro group or [ka] represents; p3 represents an integer of 1, 2, 3, or 4; (R 5 ) p4 In formula (PBM-2), the 1H-indole ring is 5 p4 represents an integer of 0, 1, 2, or 3, and each R 5 are the same or different and each independently represent hydrogen, C 1-10 Alkyl or deuterated C 1-10 represents alkyl; R 6 is hydrogen, C 1-10 Alkyl or deuterated C 1-10 represents alkyl; (R 7 ) p5 In formula (PBM-3), the benzene ring is p5 R 7 Each R represents a substitution 7 are the same or different and each independently represent a halogen, a hydroxyl, or C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 represents an alkyl, NO2, NH2, or cyano group; p5 represents an integer of 0, 1, 2, 3, 4 or 5; R 8 is a substituted or unsubstituted C 3-15 cycloalkyl, for example, cyclopentyl; (R 9 ) p6 In formula (PBM-4), the benzene ring is p6 R 9 Each R represents a substitution 9 are the same or different and each independently represent a halogen, a hydroxyl, or C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, NO2, NH2, C 1-6 Alkoxy, halogenated C 1-6 represents an alkoxy or cyano group; p6 represents 2, 3, 4 or 5; R 10 is C 6-10 aryl, or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the C 6-10 The aryl and the heteroaryl each optionally have one or more R b1 and each R b1 are the same or different and each independently represent 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 is alkoxy; (R11 ) p7 The benzene ring and the pyridine ring in formula (PBM-5) each have p7 R 11 each p7 is the same or different and independently represents an integer of 0, 1, 2, or 3; 11 are the same or different and each independently represent hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; R 12 is hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; R in formula (PBM-6) 13 is hydrogen, C 1-10 Alkyl (e.g., [ka] ), deuterated C 1-10 Alkyl or halogenated C 1-10 represents alkyl; R 14 teeth [ka] where (R b2 ) p8 The piperidine ring is optionally selected from p8 R b2 Each R represents a substitution b2 are the same or different and each independently represent deuterium, halogen, hydroxy, 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 represents an alkoxy, NO2, NH2, or cyano group, and p8 represents an integer of 1, 2, 3, 4, or 5; Ring A in formula (PBM-7) is C 6-10aryl, or a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring A optionally contains one or more R b3 and each R b3 are the same or different and each independently represent 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, C 2-6 Alkenyl, or C 2-6 is alkynyl; Ring B in formula (PBM-7) is C 3-15 cycloalkyl, or 3-20 membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring B optionally contains one or more R b4 and each R b4 are the same or different and each independently represent 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 is alkoxy; Ring C in formula (PBM-7) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and the ring C optionally contains one or more R b5 and each R b5 are the same or different and each independently represent deuterium, halogen, hydroxy, 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 is alkoxy; R in formula (PBM-8) 15represents a 4- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein said heterocyclyl is optionally joined to one or more R b6 and each R b6 are the same or different and each independently represent 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 is alkoxy; (R 16 ) p9 The benzene ring in formula (PBM-8) has p9 R 16 Each R represents a substitution 16 are the same or different and each independently represent a halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl, and p9 represents an integer of 1, 2, 3, or 4; X1 in formula (PBM-9) is N or CR b7 where R b7 is hydrogen or represents amino, and X2 is N or CR 17 where R 17 is hydrogen or represents a bond, and X3 represents CH or N; R 18 and R 19 each independently represents hydrogen or a bond; (R 20 ) p10 In formula (PBM-9), the benzene ring is p10 R 20 Each R represents a substitution 20 are the same or different and each independently represent -O-aryl, -O-heteroaryl, -C 1-3 Alkylene-NHC(O)-heteroaryl, -C 1-3 alkylene-C(O)NH-heteroaryl or halogen, wherein the aryl and heteroaryl are each independently optionally selected from one or more R b8 and each Rb8 are the same or different and each independently represent deuterium, halogen, hydroxy, 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 is alkoxy; p10 represents an integer of 1, 2, 3 or 4; R 21 is a bond, deuterium, hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, or C 1-6 represents alkoxy; R 22 represents hydrogen, halogen, cyano, or amino; where R 17 , R 18 , R 19 and R 21 is not simultaneously hydrogen and R 17 , R 18 , R 19 and R 21 is not simultaneously a bond, and R 17 , R 18 , R 19 and R 21 where only one represents a bond, R 18 When represents a bond, R 18 The ring carbon atom connecting to R f X2 represents CH or N, and R 19 is hydrogen, and R 21 is not a bond; X2 is CR 17 where R 17 When represents a bond, R 17 The ring carbon atom connecting to R f directly connected to R 18 and R 19 are both hydrogen, and R 21 is not a bond; R 19 When represents a bond, R19 The nitrogen atom of the ring connected to f directly connected to, X2 represents N or CH, and R 18 is hydrogen, and R 21 is not a bond; and R 21 When represents a bond, R 21 The ring carbon atom connecting to R f is directly connected to, and X2 represents N or CH, and R 18 and R 19 are both hydrogen; (R 23 ) p11 is a group in which the cyclopentene ring in formula (PBM-10) is p11 R 23 Each R represents a substitution 23 are the same or different and each independently represent a halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl, and p11 represents an integer of 2, 3, or 4; (R 24 ) p12 In formula (PBM-10), the pyridine is R 24 Each R represents a substitution 24 are the same or different and each independently represent a halogen, -C 1-3 Alkylene-OH, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl, and p12 represents an integer of 1, 2, or 3; R 25 is hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; X4 in formula (PBM-11) is CR 26 or fragment [ka] where # denotes the connection point of X4 and the adjacent N, ## denotes the connection point of X5, and R26 are deuterium, hydrogen, halogens, 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 b9 R b10 where R b9 , R b10 are the same or different and each independently represent hydrogen, C 1-6 Alkyl or deuterated C 1-6 represents alkyl; X5 in formula (PBM-11) is N or CR 27 where R 27 are hydrogen, deuterium, halogens, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; X6 and X7 each independently represent CH or N; R 28 represents a bond or an optionally substituted heteroarylene (e.g., halogen-substituted heteroarylene); R 29 is hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl or optionally substituted C 3-7 represents cycloalkyl; R 30 and R 31 are the same or different and each independently represent hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R in formula (PBM-12) 32 are hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; R 33 is hydrogen, cyano, halogen, C 1-6Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; (R 34 ) p13 In formula (PBM-13), the benzene ring is p13 R 34 Each R represents a substitution 34 are the same or different and each independently represent halogen, hydroxy, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; p13 represents an integer of 1, 2, 3, 4, or 5; R 35 is NR b11 R b12 where R b11 , R b12 are the same or different and each independently represent hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; (R 36 ) p14 The benzene ring in formula (PBM-14) is optionally selected from p14 R 36 p14 represents an integer of 1, 2 or 3, and each R in formula (PBM-14) 36 are the same or different and each independently represent a halogen, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; R 37 is hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; X8, X9, and X in formula (PBM-15) 10 , X 11 and X 12 are the same or different and each independently represent N or CH; R 38represents a bond or an optionally substituted methylene (e.g., methylene substituted with a halogen); R 39 -C(O)NHR b13 , -NHC(O)-R b13 , -S(O)2NHR b13 , -N(R b14 )S(O)2R b13 , -S(O)2R b13 or -P(O)(R b13 )2, where each R b13 are the same or different and each independently: C 1-6 Alkyl or deuterated C 1-6 represents alkyl, and R b14 is hydrogen or C 1-6 represents alkyl; (R 40 ) p15 represents X and X in formula (PBM-15). 10 A six-membered ring containing p15 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p15 represents an integer of 0, 1, 2, 3 or 4; R 41 is halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; (R 42 ) p16 The benzene ring in formula (PBM-16) may be any of p16 R 42 Each R in formula (PBM-16) represents a substituent. 42 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; each p16 is the same or different and independently represents an integer of 0, 1, 2, 3, or 4; (R 43 ) p17 In formula (PBM-17), the benzene ring is p17 R 43 p17 represents an integer of 0, 1, 2, 3, or 4; and each R in formula (PBM-17) 43 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; (R 44 ) p18 The benzene ring in formula (PBM-18) may be any of p18 R 44 Each R represents a substitution 44 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p18 represents an integer of 0, 1, 2, 3 or 4; (R 45 ) p19 In formula (PBM-18), the 4-oxo-3,4-dihydroquinazoline ring is p19 R 45 Each R represents a substitution 45 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p19 represents an integer of 1, 2, 3 or 4; (R 46 ) p20 In formula (PBM-19), the benzene ring is p20 R 46 Each R represents a substitution 46 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p20 represents an integer of 1, 2, 3, 4 or 5; R 47 is halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; (R 48 ) p21 In formula (PBM-20), the quinoline ring has p21 R 48 Each R represents a substitution 48 are the same or different and each independently represent a halogen, a cyano, or C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p21 represents an integer of 1, 2, 3 or 4; (R 49 ) p22 In formula (PBM-20), the benzene ring is p22 R 49 Each R represents a substitution 49 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p22 represents an integer of 2, 3, or 4; R in formula (PBM-21) 50 represents -NHC(O)- or -C(O)NH-; R 51 represents -NH- or ethynylene; (R 52 ) p23 In formula (PBM-21), each benzene ring is arbitrarily selected from p23 R 52 Each R represents a substitution 52 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; each p23 is the same or different and independently represents an integer of 0, 1, 2, 3, or 4; Ring D in formula (PBM-21) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and (R 53 ) p24 The ring D is optionally selected from p24 R 53 and each R 53 are the same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen, hydroxy, 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 represents alkoxy; p2 represents an integer of 0, 1, 2, or 3; R in formula (PBM-22) 54 , R 55 , R 56 and R 57 where only one represents a bond, and the remaining three are the same or different and each independently represent hydrogen, halogen, or hydroxy; 54 , R 55 , R 56 and R 57 When one of them represents a bond, the benzene ring or methylene in formula (PBM-22) connected by the bond is R f directly connected to; In formula (PBM-22), the symbol " [ka] " represents a bond that may be in any spatial configuration (cis or trans, or E or Z); X in formula (PBM-23) 13 represents -O- or -CH2-; (R58 ) p25 R in formula (PBM-23) has p25 1,2,3,4-tetrahydronaphthalene rings. 58 Each R represents a substitution 58 are the same or different and each independently represent hydrogen, hydroxy, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p25 represents an integer of 1, 2, 3 or 4; R 59 and R 60 Only one of them represents a bond, and the other is hydrogen, halogen, or C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl, where R 59 and R 60 When one of them represents a bond, the ring carbon atom in formula (PBM-23) connected by said bond is R f directly connected to; Ring E in formula (PBM-24) represents a 5- to 20-membered monocyclic or bicyclic heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S; R 62 is an optionally substituted 5- to 15-membered heteroaryl, an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen, hydroxy, 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 represents alkoxy; R 61 is halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; R in formula (PBM-25) 63 is an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen, hydroxy, cyano, amino, C 1-6 Alkyl, halogenated C1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 represents alkoxy; R 64 represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and the heteroaryl is selected from the group consisting of deuterium, halogen, hydroxy, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 optionally substituted with one or more substituents selected from the group consisting of alkoxy, or any combination thereof; (R 65 ) p26 isoquinoline ring in formula (PBM-26) is p26 R 65 Each R represents a substitution 65 are the same or different and each independently represent hydrogen, hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, -C(O)NH2, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p26 represents an integer of 1, 2, 3 or 4; R 66 are the same or different and each independently represent hydrogen, hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; X in formula (PBM-27) 14 is N or CR b23 where R b23 represents hydrogen or halogen, and X 15 represents N or CH; R 67 represents a bond, —C(O)NH—, or —NHC(O)—; R 68 is halogen, C1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 69 is hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl or -C 1-3 Alkylene-C 3-6 represents cycloalkyl; R 70 is hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; or R 69 and R 70 together with the corresponding nitrogen and carbon atoms attached thereto form an optionally substituted 5- to 7-membered nitrogen-containing heterocycle; R 71 represents hydrogen or a bond, and R 72 represents hydrogen or a bond, where R 71 and R 72 is not simultaneously hydrogen and R 71 and R 72 where only one represents a bond and the other represents a hydrogen, and R 71 When represents a bond, R 71 The ring carbon atom connected to R f directly connected to R 72 When represents a bond, R 72 The ring carbon atom connected to R f directly connected to; R in formula (PBM-28) 74 is C 1-3 Alkylene or halogenated C 1-3 represents alkylene; R 73 is an arbitrarily substituted C 3-6 Cycloalkyl, halogenated C 3-6 cycloalkyl, or optionally substituted C 1-6 represents alkyl; R in formula (PBM-29) 75 is C 1-3Alkylene or halogenated C 1-3 represents alkylene; R 76 is C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl or optionally substituted C 3-6 represents cycloalkyl; R in formula (PBM-30) 77 is C 1-3 Alkylene or halogenated C 1-3 represents alkylene; R 78 is hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 79 and R 80 are the same or different and each independently represent hydrogen, optionally substituted C 1-10 Alkyl or optionally substituted C 3-6 represents cycloalkyl; R 81 are hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; X in formula (PBM-31) 16 -S- or fragment [ka] where X 16 When represents -S-, X in formula (PBM-31) 16 and heteroaryl containing a nitrogen atom is thiazolyl, and X 16 is a fragment [ka] When expressing the formula (PBM-31), X in 16 and heteroaryl containing a nitrogen atom is pyridyl; X 17 represents N or CH; R 82 represents hydrogen or optionally substituted C 1-10 represents alkyl; R 83 is hydrogen, -C 1-3 alkylene-represents an optionally substituted 4- to 10-membered heterocyclyl or an optionally substituted 4- to 10-membered heterocyclyl; R 84 is hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R in formula (PBM-32) 85 and R 86 are the same or different and each independently represent hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 87 represents -S(O)2NH2 or -C(O)NH2; R in formula (PBM-33) 88 is hydrogen, hydroxy, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 89 is C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; or R 88 and R 89 together with the corresponding carbon and nitrogen atoms attached thereto form an optionally substituted 4- to 6-membered heteroaromatic ring or an optionally substituted 4- to 6-membered heterocyclic ring; R 90 is an arbitrarily substituted C 3-6 Cycloalkyl, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6alkyl or optionally substituted 4- to 10-membered heterocyclyl; (R 91 ) p27 In formula (PBM-33), the pyridin-2(1H)-one ring has p27 R 91 Each R represents a substitution 91 are the same or different and each independently represent hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p27 represents an integer of 1, 2 or 3; Ring F in formula (PBM-33) represents arylene or a 5- to 20-membered monocyclic or bicyclic heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S; (R 92 ) p28 The ring F may be any of p28 R 92 and each R 92 are the same or different and each independently represent deuterium, halogen, hydroxy, 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 represents alkoxy; p28 represents an integer of 0, 1, 2, 3 or 4; (R 93 ) p29 R in formula (PBM-34) has p29 benzene rings 93 Each R represents a substitution 93 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p29 represents an integer of 1, 2, 3, 4 or 5; R 94 is hydrogen, hydroxy, amino, cyano, halogen, C1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 95 is NR b15 R b16 where R b15 , R b16 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 3-6 represents cycloalkyl or an optionally substituted 4- to 8-membered heterocyclyl; X in formula (PBM-35) 18 , X 19 and X 20 are the same or different and each independently represent CH or N, where X 18 , X 19 and X 20 is not simultaneously N, and X 18 , X 19 , X 20 and six-membered rings containing nitrogen atoms may further include halogen, cyano, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 optionally substituted with 1 or 2 substituents selected from the group consisting of alkyl, aryl, arylsulfonyl ... X in formula (PBM-35) 21 and X 22 are the same or different and each independently represent C or N, where X 21 and X 22 is not simultaneously N; (R 96 ) p30 R in formula (PBM-35) has p30 benzene rings 96 Each R represents a substitution 96 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C1-6 Alkyl or halogenated C 1-6 represents alkyl; p30 represents an integer of 1, 2, 3, 4 or 5; (R 97 ) p31 In formula (PBM-35), the tetrahydropyrrole ring is optionally p31 R 97 Each R represents a substitution 97 are the same or different and each independently represent hydrogen, hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p31 represents an integer of 0, 1, 2, 3, 4, 5 or 6; R 98 , R 99 , R 100 are the same or different and each independently represent hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; X in formula (PBM-36) 23 represents CH or N; R 101 represents a bond or -S-; R 102 represents a bond or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclyl; R 103 is a bond, halogen, amino, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 alkyl, or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclyl; where R 102 and R 103 is not simultaneously a bond and R 102 and R 103 where only one of the groups is a bond, and R 102 When represents a bond, R 102 The ring carbon atom connected to R f directly connected to R103 When represents a bond, R 103 The ring carbon atom connected to R f directly connected to; (R 104 ) p32 In formula (PBM-36), the six-membered ring is optionally p32 R 104 Each R represents a substitution 104 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p32 represents an integer of 0, 1, 2, 3 or 4; (R 105 ) p33 In formula (PBM-37), the benzene ring is optionally p33 R 105 Each R represents a substitution 105 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p33 represents an integer of 1, 2, 3 or 4; (R 106 ) p34 In formula (PBM-37), the phthalazinone ring is optionally selected from p34 R 106 Each R represents a substitution 106 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p34 represents an integer of 0, 1, 2, 3 or 4; (R 107 ) p35 In formula (PBM-38), the 2H-indazole ring is optionally p35 R 107 Each R represents a substitution107 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p35 represents an integer of 0, 1, 2 or 3; (R 108 ) p36 The benzene ring in formula (PBM-38) is optionally p36 R 108 Each R represents a substitution 108 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p36 represents an integer of 0, 1, 2 or 3; (R 109 ) p37 In formula (PBM-39), the 2H-indazole ring is optionally selected from p37 R 109 Each R represents a substitution 109 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p37 represents an integer of 0, 1, 2 or 3; (R 110 ) p38 In formula (PBM-39), the benzene ring is optionally p38 R 110 Each R represents a substitution 110 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p38 represents an integer of 0, 1, 2 or 3; (R 111 ) p39 The benzene ring in formula (PBM-40) is optionally p39 R 111 Each R represents a substitution 111 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p39 represents an integer of 0, 1, 2, 3 or 4; R 112 , R 113 , R 114 are the same or different and each independently represent hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R in formula (PBM-41) 115 is hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 116 , R 117 , R 118 are the same or different and each independently represent hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; (R 119 ) p40 The benzene ring in formula (PBM-41) is arbitrarily p40 R 119 Each R represents a substitution 119 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p40 represents an integer of 0, 1, 2, 3 or 4; R in formula (PBM-42)120 , R 121 are the same or different and each independently represent hydrogen, halogen, C 1-3 Alkyl or halogenated C 1-3 represents alkyl; R 122 is a bond, hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 123 is a structure of the formula: [ka] represents where R 124 represents a bond or hydrogen; (R 125 ) p41 The benzene ring is optionally divided into p41 R 125 Each R represents a substitution 125 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl, and p41 represents an integer of 0, 1, 2, 3, or 4; or R 123 is a structure of the formula: [ka] represents where (R 126 ) p42 The benzene ring is optionally p42 R 126 Each R represents a substitution 126 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl, and p42 represents an integer of 0, 1, 2, 3, 4, or 5; where R 122and R 124 is not simultaneously a bond and R 122 and R 124 where only one represents a bond, and R 122 When represents a bond, R 122 The nitrogen atom of the ring connected to R f directly connected to R 124 When represents a bond, R 124 The ring carbon atom connected to R f directly connected to; (R 127 ) p43 In formula (PBM-43), the benzene ring is optionally p43 R 127 Each R represents a substitution 127 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p43 represents an integer of 0, 1, 2, 3 or 4; R in formula (PBM-45) 131 is C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 represents alkyl or hydrogen; R 132 is C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, optionally substituted 4- to 8-membered nitrogen-containing heterocyclyl or NR b11 R b12 where R b11 , R b12 are the same or different and each independently represent hydrogen, C 1-6 Alkyl, deuterated C 1-6 alkyl or optionally substituted 4- to 8-membered heterocyclyl; (R 133 ) p46 The benzene ring in formula (PBM-45) is optionally p46 R 133Each R represents a substitution 133 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p46 represents an integer of 0, 1, 2, 3 or 4; (R 134 ) p47 The benzene ring in formula (PBM-46) is optionally p47 R 134 Each R represents a substitution 134 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p47 represents an integer of 0, 1, 2, 3 or 4; (R 135 ) p48 The benzene ring in formula (PBM-46) is optionally p48 R 135 Each R represents a substitution 135 are the same or different and each independently represent hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p48 represents an integer of 0, 1, 2, 3 or 4; Ring H in formula (PBM-48) is C 6-10 Arylene or C 6-10 represents heteroarylene, (R 137 ) p49 The ring H may be any of p49 R 137 and each R 137 are the same or different and each independently represent deuterium, halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 is alkoxy; p49 represents an integer of 0, 1, 2, 3 or 4; R 136 represents an optionally substituted 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, and is selected from the group consisting of hydroxy, amino, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkyl or halogenated C 1-6 optionally substituted with one or more substituents selected from the group consisting of alkyl; X in formula (PBM-49) 24 , X 25 , X 26 each independently represents CH or N; R 138 -C(O)NHR b19 , -NHC(O)-R b19 , -S(O)2NHR b19 , -NHS(O)2R b19 , -S(O)2R b19 or -P(O)(R b19 )2, where each R b19 are the same or different and each independently: C 1-6 Alkyl or deuterated C 1-6 represents alkyl; R 139 and R 140 are each 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 represents alkoxy; (R 141 ) p50 The benzene ring is optionally divided into p50 R 141 and each R 141 are each independently halogen, hydroxy, cyano, amino, nitro, C1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 is alkoxy; p50 represents an integer of 0, 1, 2, 3, or 4; and (R 143 ) p51 The benzene ring is optionally divided into p51 R 143 and each R 143 are each 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 is alkoxy; p51 represents an integer of 0, 1, 2, 3, 4 or 5; R 142 is H, C 1-6 Alkyl or halogenated C 1-6 represents alkyl; (R 144 ) p52 The quinazoline ring in formula (PBM-50) may be any of p52 R 144 and each R 144 Each independently represents 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 is alkoxy; and p52 represents the integer 1, 2, or 3; R in formula (PBM-51) f2 represents a bond, or R f2 Ha-NH-R f3 -C(O)-***, where *** is R f1 represents the connection point with, and R f3 is an arbitrarily substituted C 3-8 represents cycloalkyl; (R 145 ) p53 In formula (PBM-51), the 1H-pyrrolo[2,3-b]pyridine ring is optionally selected from p53 R 145 and each R 145 are each 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 p53 represents an integer of 0, 1, 2, 3, 4, or 5; (R 146 ) p54 The pyridine ring in formula (PBM-51) may be any of p54 R 146 and each R 146 are each independently cyano, halogen, hydroxy, 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 b25 R b26 where R b25 , R b26 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 3-6 cycloalkyl or optionally substituted 4- to 8-membered heterocyclyl, and p54 represents an integer of 0, 1, 2, or 3; (R 147 ) p55 The benzene ring is optionally divided into p55 R 147 and each R 147 are each independently halogen, hydroxy, cyano, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6Alkoxy or halogenated C 1-6 alkoxy, and p55 represents an integer of 0, 1, 2, 3, 4, or 5; R 148 represents NHC(O) or C(O)NH; (R 149 ) p56 In formula (PBM-52), the 1H-pyrazole ring is optionally selected from p56 R 149 and each R 149 are each 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 p56 represents an integer of 0, 1, or 2; and X in formula (PBM-53) 27 represents N or CH; R 150 represents a bond or an optionally substituted methylene (e.g., methylene substituted with a halogen); Ring I is C 6-10 (R represents arylene or 5- to 15-membered heteroarylene; 151 ) p57 The ring I may optionally contain p57 R 151 and each R 151 are the same or different and each independently represent a deuterium, a halogen, a hydroxyl, a cyano, an amino, a nitro, an oxo group, 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 p57 represents an integer of 0, 1, 2, 3, or 4; (R 152 ) p58 is the X in formula (PBM-53) 27 A six-membered ring containing any of p58 R 152 Each R represents a substitution 152 is halogen, C 1-6 Alkoxy, C1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 alkyl, and p58 represents an integer of 0, 1, or 2; (R 153 ) p59 The benzene ring in formula (PBM-53) is optionally p59 R 153 Each R represents a substitution 153 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 p15 represents an integer of 0, 1, 2, 3 or 4;

[0068] In some embodiments, the PBM-R f - represents a small molecule ligand of EGFR.

[0069] In some embodiments, the PBM has the structure of formula (PBM-1-1A), (PBM-1-1B), (PBM-1-1C), or (PBM-1-1D): [ka] represents Here, in Formula (PBM-1-1A), Formula (PBM-1-1B), Formula (PBM-1-1C) and Formula (PBM-1-1D), (R 1 ) p1 R each independently has p1 benzene rings 1 Each R represents a substitution 1 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, NH, NO, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl or fully deuterated C1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example 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-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); (R 2 ) p2 each independently represents a group in which the quinazoline ring is p2 R 2 Each R represents a substitution 2 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), NO, cyano, halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-10 Alkoxy (e.g., C 1-8 Alkoxy, C 1-6 Alkoxy or C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-10 Alkoxy (e.g., halogenated C1-4 alkoxy, e.g., trifluoromethoxy), -O-optionally substituted heterocyclyl (wherein heterocyclyl is, for example, a 4- to 20-membered monocyclic or bicyclic heterocyclyl containing one or more, e.g., 1-4 or 1, 2, 3, or 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), or -NHC(O)R 3 where R 3 is C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or C 2-10 Alkenyl (e.g., C 2-6 Alkenyl or C 2-4 alkenyl, such as vinyl, propenyl, butenyl or pentenyl), such as R 2 is methyl, methoxy, [ka] or [ka] ,for example, [ka] represents; p1 represents an integer of 1, 2, 3, 4, or 5; and p2 represents an integer of 1, 2, or 3.

[0070] In some embodiments, R 2 represents an optionally substituted heterocyclyl, wherein the heterocyclyl is 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 heterocyclyl containing one or more (e.g., 1-4 or 1, 2, 3, or 4) heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is exemplified by azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, azacyl, Examples of cyclohexyl include, but are not limited to, cycloheptyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptan-1-yl), azacyclooctyl, diazacyclooctyl, 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]octanyl (e.g., 2,5-diazabicyclo[2.2.2]octan-2-yl). In some embodiments, the heterocyclyl is selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, and optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6Alkyl-NHC(O)-, optionally deuterated C 1-6 It is optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- or any combination thereof.

[0071] In some embodiments, R 2 teeth, fluorine, chlorine, bromine or iodine; methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl; methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy; -NHC(O)-C 2-10 Alkenyl, for example, —NHC(O)-vinyl (i.e., [ka] ), -NHC(O)-propenyl or -NHC(O)-butenyl; or [ka] Represents.

[0072] In some embodiments, the PBM has the structure of formula (PBM-1-1), (PBM-1-2), (PBM-1-3), (PBM-1-4), or (PBM-1-5): [ka] Represents.

[0073] In some embodiments, the PBM has the structure of formula (PBM-2-1A), (PBM-2-1B), (PBM-2-1C), (PBM-2-1D) or (PBM-2-1E): [ka] wherein in formula (PBM-2-1A), formula (PBM-2-1B), formula (PBM-2-1C), formula (PBM-2-1D) and formula (PBM-2-1E), (R 4 ) p3 each independently represents a group in which the benzene ring is p3 R 4 Each R represents a substitution 4 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), nitro, cyano, halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-10 Alkoxy (e.g., C 1-8 Alkoxy, C 1-6 Alkoxy or C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy) or —NHC(O)R 19a where R 19a is C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or C 2-10 Alkenyl (e.g., C 2-6 Alkenyl or C 2-4 alkenyl, such as vinyl, propenyl, butenyl or pentenyl), such as R 4 is a methyl, methoxy, nitro group or [ka] represents; p3 represents an integer of 1, 2, 3, or 4; (R 5 ) p4 each independently represents a group in which the 1H-indole ring is connected to p4 R 5 Each R represents a substitution 5 are the same or different and each independently: C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl) or deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); and p4 represents an integer of 0, 1, 2 or 3.

[0074] In some embodiments, the PBM has the structure of formula (PBM-2-1) or formula (PBM-2-2): [ka] Represents.

[0075] In some embodiments, the PBM has the structure of formula (PBM-3-1A), formula (PBM-3-1B), or formula (PBM-3-1C): [ka] wherein in formula (PBM-3-1A), formula (PBM-3-1B) and formula (PBM-3-1C), (R 7 ) p5 each independently represents a group in which the benzene ring is p5 R 7 Each R represents a substitution 7 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 alkyl (e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), NO2, NH2, or cyano group; p5 represents an integer of 0, 1, 2, 3, 4 or 5; R 8 are each independently a substituted or unsubstituted C 3-15 Cycloalkyl (e.g., substituted or unsubstituted C 3-10 Cycloalkyl or C 3-6 In some embodiments, the C represents cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3-15 Cycloalkyl is a group selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, and optionally deuterated C 1-6Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 Optionally substituted with one or more (eg, 1-3, 1, 2, or 3) substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof.

[0076] In some embodiments, the PBM has the structure of the following formula (PBM-3-1): [ka] Represents.

[0077] In some embodiments, the PBM has the structure of formula (PBM-4-1A), (PBM-4-1B), (PBM-4-1C), or (PBM-4-1D): [ka] represents Here, in formula (PBM-4-1A), formula (PBM-4-1B), formula (PBM-4-1C) and formula (PBM-4-1D), (R 9 ) p6 each independently represents a group in which the benzene ring is p6 R 9 Each R represents a substitution 9 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), NO2, NH2, C 1-6 Alkoxy (e.g., C 1-5 Alkoxy or C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy (e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), or a cyano group, p6 represents 2, 3, 4 or 5; and R 10 are each independently, C 6-10 aryl, or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the C 6-10 The aryl and the heteroaryl each may have one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R b1 and each R b1 are the same or different and each independently represent 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 1-3alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-).

[0078] In some embodiments, R 10 is C 6-10 Aryl, for example, but not limited to, phenyl or naphthyl, each of which may be one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R as defined above. b1 is optionally replaced by

[0079] In some embodiments, R 10 represents a heteroaryl containing one or two 5- to 7-membered rings and 1-4 heteroatoms selected from the group consisting of N, O, and S. In one subembodiment, R 10represents 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 the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, examples of heteroaryl include furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]o Heteroaryl includes, but is not limited to, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. Heteroaryl includes one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R as defined above. b1 is optionally replaced by

[0080] In some embodiments, the PBM has the structure of formula (PBM-4-1) or formula (PBM-4-2): [ka] Represents.

[0081] In some embodiments, the PBM has the structure of formula (PBM-5-1A), (PBM-5-1B), (PBM-5-1C), or (PBM-5-1D): [ka] Represents. Here, in Formula (PBM-5-1A), Formula (PBM-5-1B), Formula (PBM-5-1C), and Formula (PBM-5-1D), (R 11 ) p7 each independently represents that the benzene ring and the pyridine ring are each optionally selected from p7 R 11 each p7 is the same or different and independently represents an integer of 0, 1, 2, or 3; 11 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1- 4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); and R 12 are independently hydrogen, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0082] In some embodiments, the PBM has the structure of the following formula (PBM-5-1): [ka] Represents.

[0083] In some embodiments, the PBM has the structure of formula (PBM-6): [ka] represents where: R 13 is hydrogen, C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example, methyl, ethyl, propyl, isopropyl ( [ka] ), butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-10 Alkyl (e.g., halogenated C 1-8 Alkyl or halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and R 14 teeth [ka] where (R b2 ) p8 The piperidine ring has p8 R b2 Each R represents a substitution b2 are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-5 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated 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-), deuterated C 1-6 Alkoxy (e.g., fully deuterated C 1-4 represents an alkoxy (for example, CD3-O-, CD3CD2-O-, or CD3CD2CD2-O-), NO2, NH2, or cyano group; and p8 represents an integer of 1, 2, 3, 4, or 5.

[0084] In some embodiments, the PBM has the structure of formula (PBM-6-1) or formula (PBM-6-2): [ka] Represents.

[0085] In some embodiments, the PBM has the structure of formula (PBM-49): [ka] represents where: X 24 , X 25 , X 26 each independently represents CH or N; R 138 -C(O)NHR b19 , -NHC(O)-R b19 , -S(O)2NHR b19 , -NHS(O)2R b19 , -S(O)2R b19 or -P(O)(R b19 )2, where each R b19 are the same or different and each independently represents C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C1-4 Alkyl or fully deuterated C 1-3 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); R 139 and R 140 are each independently halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or fully deuterated C 1-3 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), 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-butoxy or tert-butoxy), or halogenated C 1-6 alkoxy (e.g., halogenated C1-4 alkoxy, e.g., trifluoromethoxy); (R 141 ) p50 The benzene ring is optionally divided into p50 R 141 and each R 141 are each independently halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-4alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or fully deuterated C 1-3 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), 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-butoxy or tert-butoxy), or halogenated C 1-6 alkoxy (e.g., halogenated C1-4 alkoxy, e.g., trifluoromethoxy); and p50 represents an integer of 0, 1, 2, 3 or 4.

[0086] In some embodiments, the PBM has the structure of formula (PBM-49-1A), (PBM-49-1B), (PBM-49-1C), or (PBM-49-1D): [ka] [ka] represents Here, in formula (PBM-49-1A), formula (PBM-49-1B), formula (PBM-49-1C), formula (PBM-49-1D), and formula (PBM-49-1E), X 24 , X 25 , X 26 each independently represents CH or N; R 138-C(O)NHR b19 , -NHC(O)-R b19 , -S(O)2NHR b19 , -NHS(O)2R b19 , -S(O)2R b19 or -P(O)(R b19 )2, where each R b19 are the same or different and each independently represents C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or fully deuterated C 1-3 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); R 139 and R 140 are each independently halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or fully deuterated C 1-3 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-5 Alkoxy, C 1-4 Alkoxy or C 1-3Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 alkoxy (e.g., halogenated C1-4 alkoxy, e.g., trifluoromethoxy); (R 141 ) p50 The benzene ring is optionally divided into p50 R 141 and each R 141 are each independently halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or fully deuterated C 1-3 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), 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-butoxy or tert-butoxy), or halogenated C 1-6 alkoxy (e.g., halogenated C1-4 alkoxy, e.g., trifluoromethoxy); and p50 represents an integer of 0, 1, 2, 3 or 4.

[0087] In some embodiments, X 24 and X 25 each independently represents CH or N. In some subembodiments, X24 represents CH, and X 25 represents N. In some subembodiments, X 24 represents CH, and X 25 represents CH. In some subembodiments, X 24 represents N, and X 25 represents CH. In some subembodiments, X 24 represents N, and X 25 represents N.

[0088] In some embodiments, X 26 represents CH or N. In some subembodiments, X 26 represents N. In some subembodiments, X 26 represents CH.

[0089] In some embodiments, R 138 -C(O)NHR b19 , -NHC(O)-R b19 , -S(O)2NHR b19 , -NHS(O)2R b19 , -S(O)2R b19 or -P(O)(R b19 )2, where each R b19 are the same or different and each independently: C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or fully deuterated C 1-3 In some subembodiments, R represents alkyl, e.g., CD, CDCD-, CDCDCD-, etc. 138 is -P(O)(R b19 )2, where each R b19 are the same or different and each independently: C 1-6 Alkyl (e.g., C 1-4alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-5 Alkyl, fully deuterated C 1-4 Alkyl or fully deuterated C 1-3 In some subembodiments, R represents alkyl, e.g., CD, CDCD-, CDCDCD-, etc. 138 represents -P(O)(CH3)2.

[0090] In some embodiments, p50 represents the integer 0, 1, 2, 3, or 4. In some subembodiments, p50 represents the integer 2.

[0091] In some embodiments, the PBM has the structure of formula (PBM-49-1), (PBM-49-2), (PBM-49-3), (PBM-49-4), or (PBM-49-5): [ka] [ka] Represents.

[0092] In some embodiments, the PBM has the structure of formula (PBM-55): [ka] represents where: R 157 is C 6-10 aryl, or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the C 6-10 The aryl and the heteroaryl may each be selected from halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 optionally substituted with one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of alkoxy, e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-); R 158 represents a 5- to 15-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the 5- to 15-membered heteroaryl is selected from the group consisting of halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-); and (R 159 ) p61 In formula (PBM-55), the isoindolinone ring is p61 R 159 Each R represents a substitution 159 are the same or different and each independently represent halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C1-4alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-), and p61 represents an integer of 0, 1, 2 or 3.

[0093] In some embodiments, R 157 is C 6-10 aryl, including, but not limited to, phenyl or naphthyl, which may each be selected from the group consisting of halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-).

[0094] In some embodiments, R 157 represents a heteroaryl containing one or two 5- to 7-membered rings and 1-4 heteroatoms selected from the group consisting of N, O, and S. In one subembodiment, R 157represents a 5- to 15-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 the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, examples of heteroaryl include furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]o Heteroaryl includes, but is not limited to, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. Heteroaryl includes, but is not limited to, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-).

[0095] In some embodiments, R 158 represents a 5- to 15-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S. In one subembodiment, R 158represents a 5- to 15-membered monocyclic or bicyclic aromatic ring group containing 1 to 4 (e.g., 1 to 3, or 1 to 2, or 1) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, examples of heteroaryl include 6,7-dihydro-5H-pyrrolo[1,2-c]imidazolyl, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, Heteroaryl includes, but is not limited to, halogen, 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]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. Heteroaryl includes, but is not limited to, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-).

[0096] In some embodiments, the PBM has the structure of formula (PBM-55-1) or formula (PBM-55-2): [ka] Represents.

[0097] In some embodiments, the PBM-R f - represents a small molecule ligand of AR.

[0098] In some embodiments, the PBM has the structure of the following formula (PBM-7-1A): [ka] represents where: Ring A in formula (PBM-7-1A) is C 6-10 aryl, or a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S; (R b3 ) t3 is a set of rings A and R b3 and each R b3are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated 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., vinyl, propenyl, or butenyl), or C 2-6 alkynyl (e.g., ethynyl, propynyl, or butynyl); Ring B in formula (PBM-7-1A) is C 3-15 cycloalkyl or 3- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S; (R b4 ) t4 is a ring B that has any t4 R b4and each R b4 are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); Ring C in formula (PBM-7-1A) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and (R b5 ) t5 is a ring C with any t5 R b5 and each R b5 are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); t3 represents an integer of 1, 2, 3, 4, 5, or 6; t4 represents an integer of 1, 2, 3, 4, 5, or 6; and t5 represents an integer of 1 or 2.

[0099] In some embodiments, the PBM has the structure of the following formula (PBM-7-1A-1): [ka] represents where: (R b3 ) t3The benzene ring is optionally connected to t3 R b3 Each R represents a substitution b3 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated 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., vinyl, propenyl, or butenyl), or C 2-6 alkynyl (e.g., ethynyl, propynyl, or butynyl); Ring B in formula (PBM-7-1A-1) is C 3-15 cycloalkyl or 3-20 membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, where (Rb4 ) t4 The ring B is optionally selected from t4 R b4 and each R b4 are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); Q1 represents N or CH; and (R b5 ) t5 is a nitrogen-containing heteroaryl optionally followed by t5 R b5 Each R represents a substitution b5are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); t3 represents an integer of 1, 2, 3, 4, 5, or 6; t4 represents an integer of 1, 2, 3, 4, 5, or 6; and t5 represents an integer of 1 or 2.

[0100] In some embodiments, the PBM has the structure of formula (PBM-7-1), (PBM-7-2), (PBM-7-3), or (PBM-7-4): [ka] Represents.

[0101] In some embodiments, the PBM has the structure of formula (PBM-8-1A), (PBM-8-1B), (PBM-8-1C), (PBM-8-1D), or (PBM-8-1E): [ka] represents Here, in formula (PBM-8-1A), formula (PBM-8-1B), formula (PBM-8-1C), formula (PBM-8-1D), and formula (PBM-8-1E), R 15 each independently represent a 4- to 20-membered heterocyclyl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the heterocyclyl is optionally joined to one or more R b6 and each R b6 are the same or different and each independently represent halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, C 1-6 Alkyl (e.g., C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example, methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); and (R 16 ) p9 R each independently has p9 benzene rings 16 Each R represents a substitution 16 are the same or different and each independently represent a halogen, C 1-6 Alkyl (e.g., C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and p9 represents an integer of 1, 2, 3 or 4.

[0102] In some embodiments, the PBM has a structure of formula (PBM-8-1), (PBM-8-2), (PBM-8-3), or (PBM-8-4): [ka] Represents.

[0103] In some embodiments, the PBM-R f - represents a small molecule ligand of BTK.

[0104] In some embodiments, the PBM has the structure of formula (PBM-9): [ka] represents where: X1 in formula (PBM-9) is N or CR b7 where R b7 is hydrogen or represents amino, and X2 is N or CR 17 where R 17 is hydrogen or represents a bond, and X3 represents CH or N; R 18 and R 19 each independently represents hydrogen or a bond; (R 20 ) p10 In formula (PBM-9), the benzene ring is p10 R 20 Each R represents a substitution 20 are the same or different and each independently represent -O-aryl, -O-heteroaryl, -C 1-3 Alkylene-NHC(O)-heteroaryl, -C 1-3 alkylene-C(O)NH-heteroaryl or halogen (e.g., fluorine, chlorine, bromine, or iodine), wherein the aryl and heteroaryl each independently optionally have one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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 1-3alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); p10 represents an integer of 1, 2, 3 or 4; R 21 is a bond, deuterium, hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy; R 22 represents hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, or amino; where R 17 , R 18 , R 19 and R 21 is not simultaneously hydrogen and R 17 , R 18 , R 19 and R 21 is not simultaneously a bond, and R 17 , R 18 , R 19 and R 21 where only one represents a bond, R 18 When represents a bond, R 18 The ring carbon atom connected to R f X2 represents CH or N, and R 19 is hydrogen, and R 21 is not a bond; X2 is CR 17 where R 17 When represents a bond, R 17 The ring carbon atom connected to R f directly connected to R 18 and R 19 are both hydrogen, and R 21 is not a bond; R 19 When represents a bond, R 19 The nitrogen atom of the ring connected to R f directly connected to, X2 represents N or CH, and R 18 is hydrogen, and R 21 is not a bond; and R 21 When represents a bond, R 21 The ring carbon atom connected to R f is directly connected to, and X2 represents N or CH, and R 18 and R 19 are both hydrogen.

[0105] In some embodiments, R in formula (PBM-9) 20 -O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where aryl is an optionally substituted C 6-10 It may be aryl, for example, but not limited to, phenyl or naphthyl, and heteroaryl may be an optionally substituted 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 the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, R 20 represents -O-phenyl or -O-naphthyl, and the phenyl or naphthyl may optionally be joined by one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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 20 is -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where heteroaryl optionally includes one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 Alkoxy or halogenated C 1-3Alkoxy, 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 are furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzyl and imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1,3]oxadiazolyl.

[0106] In some embodiments, R 19 represents a bond, and R 18 is hydrogen and R 21 is not a bond, and X2 represents N or CH.

[0107] In some embodiments, R 19 represents a bond, and R 18 is hydrogen and R 21 is not a bond, and X2 represents N, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0108] In some embodiments, R 19 represents a bond, and R 18is hydrogen and R 21 is not a bond, and X2 represents N, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0109] In some embodiments, R 19 represents a bond, and R 18 is hydrogen and R 21 is not a bond, and X2 represents N, X1 represents N, and X3 represents CH.

[0110] In some embodiments, R 19 represents a bond, and R 18 is hydrogen and R 21 is not a bond, and X2 represents N, X1 represents N, and X3 represents N.

[0111] In some embodiments, R 19 represents a bond, and R 18 is hydrogen and R 21 is not a bond, and X2 represents CH, and X1 represents CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0112] In some embodiments, R 19 represents a bond, and R 18 is hydrogen and R 21 is not a bond, and X2 represents CH, and X1 represents CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0113] In some embodiments, R 19 represents a bond, and R 18 is hydrogen and R 21 is not a bond, and X2 represents CH, X1 represents N, and X3 represents CH.

[0114] In some embodiments, R 19 represents a bond, and R 18is hydrogen and R 21 is not a bond, and X2 represents CH, X1 represents N, and X3 represents N.

[0115] In some embodiments, R 18 When represents a bond, R 18 The ring carbon atom connected to R f X2 represents CH or N, and R 19 is hydrogen, and R 21 is not a bond.

[0116] In some embodiments, R 18 represents a bond, and R 18 represents a bond, and R 19 is hydrogen and R 21 is not a bond, and X2 represents CH, X1 represents N, and X3 represents N.

[0117] In some embodiments, R 18 represents a bond, and R 19 is hydrogen and R 21 is not a bond, and X2 represents CH, X1 represents N, and X3 represents CH.

[0118] In some embodiments, R 18 represents a bond, and R 19 is hydrogen and R 21 is not a bond, and X2 represents CH, and X1 represents CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0119] In some embodiments, R 18 represents a bond, and R 19 is hydrogen and R 21 is not a bond, and X2 represents CH, and X1 represents CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0120] In some embodiments, R 18 represents a bond, and R19 is hydrogen and R 21 is not a bond, and X2 represents N, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0121] In some embodiments, R 18 represents a bond, and R 19 is hydrogen and R 21 is not a bond, and X2 represents N, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0122] In some embodiments, R 18 represents a bond, and R 19 is hydrogen and R 21 is not a bond, and X2 represents N, X1 represents N, and X3 represents CH.

[0123] In some embodiments, R 18 represents a bond, and R 19 is hydrogen and R 21 is not a bond, and X2 represents N, X1 represents N, and X3 represents N.

[0124] In some embodiments, X2 is CR 17 where R 17 When represents a bond, R 17 The ring carbon atom connected to R f directly connected to R 18 and R 19 are both hydrogen, and R 21 is not a bond.

[0125] In some embodiments, X2 is CR 17 where R 17 When represents a bond, R 17 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and R21 is not a bond, and X1 represents N, and X3 represents CH.

[0126] In some embodiments, X2 is CR 17 where R 17 When represents a bond, R 17 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and R 21 is not a bond, and X1 represents N, and X3 represents N.

[0127] In some embodiments, X2 is CR 17 where R 17 When represents a bond, R 17 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and R 21 is not a bond, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0128] In some embodiments, X2 is CR 17 where R 17 When represents a bond, R 17 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and R 21 is not a bond, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0129] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f is directly connected to, and X2 represents N or CH, and R 18 and R19 are both hydrogen.

[0130] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and X2 represents N, X1 represents N, and X3 represents CH.

[0131] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and X2 represents N, X1 represents N, and X3 represents N.

[0132] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, X2 represents N, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0133] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, X2 represents N, and X1 is CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0134] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to Rf directly connected to R 18 and R 19 are all hydrogen, and X2 represents CH, X1 represents N, and X3 represents CH.

[0135] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and X2 represents CH, X1 represents N, and X3 represents N.

[0136] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and X2 represents CH, and X1 represents CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0137] In some embodiments, R 21 When represents a bond, R 21 The ring carbon atom connected to R f directly connected to R 18 and R 19 are all hydrogen, and X2 represents CH, and X1 represents CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0138] In some embodiments, the PBM has the structure of the following formula (PBM-9-1A): [ka] represents where: X1 in formula (PBM-9-1A) is N or CR b7 where R b7is hydrogen or represents amino, X2 represents N or CH, and X3 represents CH or N; (R 20 ) p10 is a group in which the benzene ring in formula (PBM-9-1A) is p10 R 20 Each R represents a substitution 20 are the same or different and each independently represent -O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, wherein the aryl and heteroaryl each independently represent one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C1-6 Alkoxy (e.g., halogenated 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-); R 21 is deuterium, hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), for example, R 21 represents hydrogen or methyl; and R 22 represents hydrogen, halogen (for example, fluorine, chlorine, bromine or iodine), cyano, or amino.

[0139] In some embodiments, R of formula (PBM-9-1A) 20-O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where aryl is an optionally substituted C 6-10 It may be aryl (e.g., including but not limited to, phenyl or naphthyl), and heteroaryl may be an optionally substituted 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 the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, R 20 represents -O-phenyl or -O-naphthyl, and the phenyl or naphthyl may optionally be joined by one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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 20 is -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where heteroaryl optionally includes one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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, examples of heteroaryl are furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzyl and imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1,3]oxadiazolyl.

[0140] In some embodiments, X1 of formula (PBM-9-1A) represents N, X2 represents N, and X3 represents CH.

[0141] In some embodiments, X1 represents N, X2 represents N, and X3 represents N in formula (PBM-9-1A).

[0142] In some embodiments, X1 of formula (PBM-9-1A) represents N, X2 represents CH, and X3 represents CH.

[0143] In some embodiments, X 1 represents N, X 2 represents CH, and X 3 represents N in formula (PBM-9-1A).

[0144] In some embodiments, X1 of formula (PBM-9-1A) is CR b7 where R b7 is hydrogen or represents amino, X2 represents N, and X3 represents N.

[0145] In some embodiments, X1 of formula (PBM-9-1A) is CR b7 where R b7 is hydrogen or represents amino, X2 represents N, and X3 represents CH.

[0146] In some embodiments, X1 of formula (PBM-9-1A) is CR b7 where R b7 is hydrogen or represents amino, X2 represents CH, and X3 represents N.

[0147] In some embodiments, X1 of formula (PBM-9-1A) is CR b7 where R b7 is hydrogen or represents amino, X2 represents CH, and X3 represents CH.

[0148] In some embodiments, the PBM has the structure of the following formula (PBM-9-1): [ka] Represents.

[0149] In some embodiments, the PBM has the structure of the following formula (PBM-9-1B): [ka] represents where: X1 in formula (PBM-9-1B) is N or CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH or N; (R 20 ) p10 In formula (PBM-9-1B), the benzene ring is p10 R 20 Each R represents a substitution 20 are the same or different and each independently represent -O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, wherein the aryl and heteroaryl are each independently optionally selected from one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); R 21 is deuterium, hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), for example, R 21 represents hydrogen or methyl; and R 22 represents hydrogen, halogen (for example, fluorine, chlorine, bromine or iodine), cyano, or amino.

[0150] In some embodiments, R of formula (PBM-9-1B) 20 -O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where aryl is an optionally substituted C 6-10 It may be aryl (e.g., including but not limited to, phenyl or naphthyl), and heteroaryl may be an optionally substituted 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 the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, R 20 represents -O-phenyl or -O-naphthyl, and the phenyl or naphthyl may optionally be joined by one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C1-4 Alkoxy or C 1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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 20 is -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where heteroaryl optionally includes one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R b8 and each R b8 are the same or different and each independently represent deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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, examples of heteroaryl are furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzyl and imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1,3]oxadiazolyl.

[0151] In some embodiments, X 1 of formula (PBM-9-1B) represents N and X 3 represents CH.

[0152] In some embodiments, X 1 represents N and X 3 represents N in formula (PBM-9-1B).

[0153] In some embodiments, X1 of formula (PBM-9-1B) is CR b7 where R b7 is hydrogen or represents amino, and X3 represents CH.

[0154] In some embodiments, X1 of formula (PBM-9-1B) is CR b7 where R b7 is hydrogen or represents amino, and X3 represents N.

[0155] In some embodiments, the PBM has the structure of the following formula (PBM-9-2): [ka] Represents.

[0156] In some embodiments, the PBM has the structure of formula (PBM-10-1A) or formula (PBM-10-1B): [ka] represents Here, in Formula (PBM-10-1A) and Formula (PBM-10-1B), (R 23 ) p11 R each independently represents a group having p11 cyclopentene rings. 23 Each R represents a substitution 23 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and p11 represents an integer of 2, 3, or 4; (R 24 ) p12 each independently represents that the pyridine is p R 24 Each R represents a substitution 24 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), -C 1-3 Alkylene -OH (e.g., -CH2-OH, -CH2CH2-OH, -CH2CH2CH2-OH), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), where p12 represents an integer of 1, 2, or 3; and R 25 are independently hydrogen, C 1-6 Alkyl (e.g., C 1-5Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0157] In some embodiments, the PBM has the structure of formula (PBM-10-1) or formula (PBM-10-2): [ka] Represents.

[0158] In some embodiments, the PBM has the structure of formula (PBM-46-1A), formula (PBM-46-1B), or formula (PBM-46-1C): [ka] represents Here, in formula (PBM-46-1A), formula (PBM-46-1B), and formula (PBM-46-1C), (R 134 ) p47 R independently has p47 benzene rings. 134 Each R represents a substitution 134 are the same or different and each independently represent hydroxy, amino, cyano, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p47 represents an integer of 0, 1, 2, 3 or 4; (R 135 ) p48 R independently has p48 benzene rings. 135 Each R represents a substitution 135 are the same or different and each independently represent hydroxy, amino, cyano, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy or C 1-3Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p48 represents an integer of 0, 1, 2, 3 or 4.

[0159] In some embodiments, the PBM has the structure of the following formula (PBM-46-1): [ka] Represents.

[0160] In some embodiments, the PBM has the structure of formula (PBM-45-1A), (PBM-45-1B), (PBM-45-1C), (PBM-45-1D), or (PBM-45-1E): [ka] where: R 131 is C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or R 131 represents hydrogen; R 132 represents an optionally substituted 4- to 8-membered nitrogen-containing heterocyclyl; (R 133 ) p46 The benzene ring in formula (PBM-45-1A), formula (PBM-45-1B), formula (PBM-45-1C), formula (PBM-45-1D), or formula (PBM-45-1E) is optionally substituted with p46 R 133 Each R represents a substitution 133 are the same or different and each independently represent hydroxy, amino, cyano, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), C 1-6 Alkoxy (e.g., C 1-5 Alkoxy or C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p46 represents an integer of 0, 1, 2, 3 or 4.

[0161] In some embodiments, R 131represents ethyl. In some embodiments, R 131 represents hydrogen. In some embodiments, R 132 represents an optionally substituted 4- to 8-membered heterocyclyl. In some embodiments, the optionally substituted 4- to 8-membered heterocyclyl is, for example, an optionally substituted 4- to 8-membered (e.g., 4- to 7-membered, 4- to 6-membered, 5- to 7-membered, or 5- to 6-membered) monocyclic or bicyclic heterocyclyl containing one or more, for example, 1-4 or 1, 2, 3, or 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is selected from the following optionally substituted groups: azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl. , azacycloheptyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptan-1-yl), azacyclooctyl, diazacyclooctyl, 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]octanyl (e.g., 2,5-diazabicyclo[2.2.2]octan-2-yl). In some embodiments, the 4- to 8-membered heterocyclyl is selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, and optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6In some embodiments, R is optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, 3-methyl-2-oxoimidazolidin-1-yl, or any combination thereof. 132 represents piperidinyl, wherein the piperidinyl is optionally substituted with 3-methyl-2-oxoimidazolidin-1-yl. In some embodiments, p46 represents the integer 0. In some embodiments, p46 represents 1 and R 133 represents methoxy.

[0162] In some embodiments, the PBM has the structure of formula (PBM-45-2), (PBM-45-3), or (PBM-45-4): [ka] Represents.

[0163] In some embodiments, the PBM-R f - represents a small molecule ligand of CDK4 / 6.

[0164] In some embodiments, the PBM has the structure of formula (PBM-11-1A), (PBM-11-1B), (PBM-11-1C), or (PBM-11-1D): [ka] represents where: R in Formula (PBM-11-1A), Formula (PBM-11-1B), Formula (PBM-11-1C) and Formula (PBM-11-1D) 26 are each independently deuterium, hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., 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, e.g., -C(O)-CH, -C(O)-CHCH, -C(O)-deuterated C 1-6 Alkyl (e.g., -C(O)-deuterated C 1-5 Alkyl or -C(O)-deuterated C 1-3 Alkyl, for example, —C(O)—CD3) or —C(O)NR b9 R b10 where R b9 , R b10 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R b9 , R b10 is not simultaneously hydrogen; X5 in Formula (PBM-11-1A), Formula (PBM-11-1B), Formula (PBM-11-1C), and Formula (PBM-11-1D) each independently represents N or CR 27 where R 27is hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); X6 and X7 in Formula (PBM-11-1A), Formula (PBM-11-1B), Formula (PBM-11-1C), and Formula (PBM-11-1D) each independently represent CH or N; Ring G in formula (PBM-11-1B) and formula (PBM-11-1D) each independently represents heteroarylene (e.g., an optionally substituted 5- to 20-membered monocyclic or bicyclic aromatic 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 the group consisting of nitrogen, oxygen, and sulfur); (R b19 ) t6 is a ring G with t6 R b19 Each R represents a substitution b19 are the same or different and each independently represent 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 1-3alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); (R b20 ) t7 is a ring G with t7 R b20 Each R represents a substitution b20 are the same or different and each independently represent 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); R in Formula (PBM-11-1A), Formula (PBM-11-1B), Formula (PBM-11-1C) and Formula (PBM-11-1D) 29 is hydrogen, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4alkyl, e.g., CD, CDCD-, CDCDCD-, etc.), or optionally substituted C 3-7 Cycloalkyl (e.g., halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, or cycloheptyl, optionally substituted with a substituent selected from the group consisting of: R in Formula (PBM-11-1A), Formula (PBM-11-1B), Formula (PBM-11-1C) and Formula (PBM-11-1D) 30 and R 31 are the same or different and each independently represent hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); t6 represents an integer of 0, 1, or 2; and t7 represents an integer of 0, 1, or 2.

[0165] In some embodiments, ring G represents an optionally substituted heteroarylene, e.g., an optionally substituted 5- to 14-membered monocyclic or bicyclic heteroarylene 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 the group consisting of oxygen, nitrogen, and sulfur. Examples of heteroarylenes include furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3] Heteroarylene includes, but is not limited to, oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, 4H-fluoro[3,2-b]pyrrolylene, pyrrolo[2,1-b]thiazolylene, and imidazo[2,1-b]thiazolylene. Heteroarylene is selected from the group consisting of 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-).

[0166] In some embodiments, the PBM has the structure of formula (PBM-11-1), (PBM-11-2), or (PBM-11-3): [ka] Represents.

[0167] In some embodiments, the PBM-R f - represents a small molecule ligand of ALK.

[0168] In some embodiments, the PBM has the structure of formula (PBM-12-1A), (PBM-12-1B), (PBM-12-1C), or (PBM-12-1D): [ka] represents where: R in Formula (PBM-12-1A), Formula (PBM-12-1B), Formula (PBM-12-1C) and Formula (PBM-12-1D) 32are each independently hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); and R in Formula (PBM-12-1A), Formula (PBM-12-1B), Formula (PBM-12-1C) and Formula (PBM-12-1D) 33 are each independently hydrogen, cyano, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0169] In some embodiments, the PBM has the structure of the following formula (PBM-12-1): [ka] Represents.

[0170] In some embodiments, the PBM has the structure of formula (PBM-13): [ka] where: (R 34 ) p13 In formula (PBM-13), the benzene ring is p13 R 34 Each R represents a substitution 34 are the same or different and each independently represent halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, amino, cyano, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); p13 represents an integer of 1, 2, 3, 4, or 5; or R 35 is NR b11 R b12 where R b11 , Rb12 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0171] In some embodiments, the PBM has the structure of the following formula (PBM-13-1): [ka] Represents.

[0172] In some embodiments, the PBM has the structure of formula (PBM-14), formula (PBM-14-1A), or formula (PBM-14-1B): [ka] represents where: (R 36 ) p14 The benzene ring in formula (PBM-14) is optionally selected from p14 R 36 p14 represents an integer of 1, 2 or 3, and each R 36 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), amino, cyano, C 1-6 Alkyl (e.g., C 1-5Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); and R 37 is hydrogen, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0173] In some embodiments, the PBM has the structure of the following formula (PBM-14-1): [ka] Represents.

[0174] In some embodiments, the PBM has the structure of formula (PBM-15): [ka] represents where: X8, X9, and X in formula (PBM-15) 10 , X 11 and X 12 are the same or different and each independently represent N or CH; R 38 represents a bond or an optionally substituted methylene (e.g., methylene substituted with a halogen); R 39 -C(O)NHR b13 , -NHC(O)-R b13 , -S(O)2NHR b13 , -N(R b14 )S(O)2R b13 , -S(O)2R b13 or -P(O)(R b13 )2, where each R b13 are the same or different and each independently: 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., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R b14 is hydrogen or C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; (R 40 )p15 represents X and X in formula (PBM-15). 10 A six-membered ring containing p15 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p15 represents an integer of 0, 1, 2, 3 or 4; and R 41 is a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0175] In some embodiments, R in formula (PBM-15) 38 represents a bond. In other words, X in formula (PBM-15) 11 and X 12 The six-membered ring containing is directly connected to -NH-.

[0176] In some embodiments, R in formula (PBM-15) 38 represents an optionally substituted methylene (eg, methylene substituted with a halogen).

[0177] In some embodiments, the PBM has the structure of formula (PBM-15-1A), formula (PBM-15-1B), or formula (PBM-15-1C): [ka] represents where: X8, X9 and X 10 are the same or different and each independently represent N or CH; R 39 -C(O)NHR b13 , -NHC(O)-R b13 , -S(O)2NHR b13 , -N(R b14 )S(O)2R b13 , -S(O)2R b13 or -P(O)(R b13 )2, where each R b13 are the same or different and each independently: C1-6 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., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R b14 is hydrogen or C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; (R 40 ) p15 are the X9 and X 10 A six-membered ring containing p15 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p15 represents an integer of 0, 1, 2, 3 or 4; and R 41 is a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0178] In some embodiments, the PBM has the structure of formula (PBM-15-1D), formula (PBM-15-1E), or formula (PBM-15-1F): [ka] represents where: X9 and X 10 are the same or different and each independently represent N or CH; R 39 -C(O)NHRb13 , -NHC(O)-R b13 , -S(O)2NHR b13 , -N(R b14 )S(O)2R b13 , -S(O)2R b13 or -P(O)(R b13 )2, where each R b13 are the same or different and each independently: 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., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R b14 is hydrogen or C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; (R 40 ) p15 are the X9 and X 10 A six-membered ring containing p15 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p15 represents an integer of 0, 1, 2, 3 or 4.

[0179] In some embodiments, the PBM has the structure of formula (PBM-15-1) or formula (PBM-15-2): [ka] Represents.

[0180] In some embodiments, the PBM-R f - represents a small molecule ligand of FAK.

[0181] In some embodiments, the PBM has the structure of the following formula (PBM-15-1G): [ka] represents where: X8, X in formula (PBM-15-1G) 11 and X 12 are the same or different and each independently represent N or CH; R 38 represents a bond or an optionally substituted methylene (e.g., methylene substituted with a halogen); R 39 -C(O)NHR b13 , -NHC(O)-Rb13 , -S(O)2NHR b13 , -N(R b14 )S(O)2R b13 , -S(O)2R b13 or -P(O)(R b13 )2, where each R b13 are the same or different and each independently: 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., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R b14 is hydrogen or C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; (R 40 ) p15 represents X and X in formula (PBM-15). 10 A six-membered ring containing p15 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen, C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p15 represents an integer of 0, 1, 2, 3 or 4; and R 41 is halogen, C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0182] In some embodiments, R in formula (PBM-15-1G) 38 represents a bond. In other words, X in formula (PBM-15-1G) 11 and X 12The six-membered ring containing is directly connected to -NH-.

[0183] In some embodiments, R in formula (PBM-15-1G) 38 represents an optionally substituted methylene (eg, methylene substituted with a halogen).

[0184] In some embodiments, the PBM has the structure of formula (PBM-15-1H) or formula (PBM-15-1I): [ka] represents where: X8, X 11 and X 12 are the same or different and each independently represent N or CH; Each R b21 are the same or different and each independently represent hydrogen or halogen; R 39 -C(O)NHR b13 , -NHC(O)-R b13 , -S(O)2NHR b13 , -N(R b14 )S(O)2R b13 , -S(O)2R b13 or -P(O)(R b13 )2, where each R b13 are the same or different and each independently: 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., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R b14 is hydrogen or C 1-6 Alkyl (e.g., C1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; (R 40 ) p15 represents X and X in formula (PBM-15). 10 A six-membered ring containing p15 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen, C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p15 represents an integer of 0, 1, 2, 3 or 4; and R 41 is halogen, C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0185] In some embodiments, the PBM has a structure of formula (PBM-15-6), (PBM-15-7), (PBM-15-8), (PBM-15-9), (PBM-15-10), or (PBM-15-11): [ka] [ka] Represents.

[0186] In some embodiments, the PBM has the structure of formula (PBM-53): [ka] represents where X 27 represents N or CH; R 150 represents a bond or an optionally substituted methylene (e.g., methylene substituted with a halogen); Ring I is C 6-10 aryl or 5- to 15-membered heteroaryl, (R 151 ) p57 The ring I may optionally contain p57 R 151and each R 151 are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, or oxo group, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-), and p57 represents an integer of 0, 1, 2, 3 or 4; (R 152 ) p58 is the X in formula (PBM-53) 27 A six-membered ring containing any of p58 R 152 Each R represents a substitution 152 is a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), and p58 represents an integer of 0, 1 or 2; (R 153 ) p59 The benzene ring in formula (PBM-53) is optionally p59 R 153 Each R represents a substitution 153 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), and p15 represents an integer of 0, 1, 2, 3 or 4.

[0187] In some embodiments, X 27 represents N.

[0188] In some embodiments, X 27 represents CH.

[0189] In some embodiments, R 150 represents a bond.

[0190] In some embodiments, R 150 represents an optionally substituted methylene (eg, methylene optionally substituted with a halogen (eg, fluorine, chlorine, bromine, or iodine)).

[0191] In some embodiments, Ring I is C 6-10 In some embodiments, Ring I represents C 6-10It represents aryl, or a 5- to 15-membered (e.g., 5- to 12-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, or 6-membered) monocyclic or bicyclic heteroaryl containing 1 to 4 (e.g., 1 to 3, or 1 to 2) heteroatoms selected from the group consisting of N, O, and S. Examples of aryl include, but are not limited to, phenyl and naphthyl. Examples of heteroaryl include furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, isoindolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxazolyl, and benzo[2,1,3]oxazolyl. Examples include, but are not limited to, thiadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolylene, pyrrolo[2,1-b]thiazolyl, and imidazo[2,1-b]thiazolyl.

[0192] In some embodiments, (R 151 ) p57 The ring I may optionally contain p57 R 151 and each R 151 are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, or oxo group, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-), and p57 represents an integer of 0, 1, 2, 3 or 4.

[0193] In some embodiments, Ring I represents isoindolinyl and further comprises p57 R 151 and each R 151 are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro, or oxo group, C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 and p57 represents an integer of 0, 1, 2, 3, or 4. In some embodiments, p57 represents an integer of 0, 1, 2, 3, or 4. In some embodiments, Ring I represents isoindolinyl, further comprising a halogen (e.g., fluorine, chlorine, bromine, or iodine), an oxo group, and C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 It is optionally substituted with alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0194] In some embodiments, (R 152 ) p58 is the X in formula (PBM-53) 27 A six-membered ring containing any of p58 R 152 Each R represents a substitution 152 is a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, e.g., F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), and p58 represents an integer of 0, 1, or 2. In some embodiments, each R 152 are each independently a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), and p58 represents an integer of 0, 1 or 2.

[0195] In some embodiments, (R 153 ) p59 The benzene ring in formula (PBM-53) is optionally p59 R 153 Each R represents a substitution 153are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, e.g., F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), and p15 represents an integer of 0, 1, 2, 3, or 4. In some embodiments, each R 153 are each independently a halogen (e.g., fluorine, chlorine, bromine, or iodine) or C 1-6 Alkoxy (e.g., C 1-4 alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), and p15 represents an integer of 0, 1, 2, 3 or 4.

[0196] In some embodiments, the PBM has the structure of formula (PBM-53-1A), (PBM-53-1B), (PBM-53-1C), (PBM-53-2A), (PBM-53-2B), or (PBM-53-2C): [ka] [ka] represents where X 27 , R 150 , (R 151 ) p57 , (R 152 ) p58 and (R 153 ) p59 is as defined in each embodiment of formula (PBM-53) and each subembodiment thereof.

[0197] In some embodiments, the PBM has the structure of formula (PBM-53-1), (PBM-53-2), (PBM-53-3) or (PBM-53-4): [ka] Represents.

[0198] In some embodiments, the PBM-R f - represents a small molecule ligand of RET.

[0199] In some embodiments, the PBM has the structure of formula (PBM-15-1J), formula (PBM-15-1K), or formula (PBM-15-1L): [ka] represents where: X9 and X 10 are the same or different and each independently represent N or CH; R 39 -C(O)NHR b13 , -NHC(O)-R b13 , -S(O)2NHR b13 , -N(R b14 )S(O)2R b13 , -S(O)2R b13 or -P(O)(R b13 )2, where each R b13 are the same or different and each independently: C 1-6 Alkyl (e.g., C 1-5Alkyl, 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., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R b14 is hydrogen or C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl; (R 40 ) p15 are the X9 and X 10 A six-membered ring containing p15 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p15 represents an integer of 0, 1, 2, 3 or 4.

[0200] In some embodiments, the PBM has the structure of formula (PBM-15-3), (PBM-15-4), or (PBM-15-5): [ka] Represents.

[0201] In some embodiments, the PBM has the structure of formula (PBM-16-1A), (PBM-16-1B), (PBM-16-1C), (PBM-16-1D), or (PBM-16-1E): [ka] [ka] represents where: (R 42 ) p16 each independently represents that the benzene ring is optionally connected to p16 R 42 Each R represents a substitution 42 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and Each p16 is the same or different and each independently represents an integer of 0, 1, 2, 3 or 4.

[0202] In some embodiments, the PBM has the structure of the following formula (PBM-16-1): [ka] Represents.

[0203] In some embodiments, the PBM-R f - represents a small molecule ligand of BET.

[0204] In some embodiments, the PBM has the structure of formula (PBM-17): [ka] represents where: (R 43 ) p17 In formula (PBM-17), the benzene ring is p17 R 43 Each R represents a substitution 43 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p17 represents an integer of 0, 1, 2, 3 or 4.

[0205] In some embodiments, the PBM has the structure of the following formula (PBM-17-1): [ka] Represents.

[0206] In some embodiments, the PBM has the structure of formula (PBM-18-1A), (PBM-18-1B), (PBM-18-1C), (PBM-18-1D), or (PBM-18-1E): [ka] represents where: (R 44 ) p18R each independently represents a group having p 18 benzene rings. 44 Each R represents a substitution 44 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p18 represents an integer of 0, 1, 2, 3 or 4; (R 45 ) p19 each independently represents a group in which the 4-oxo-3,4-dihydroquinazoline ring is present in p19 R 45 Each R represents a substitution 45 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p19 represents an integer of 1, 2, 3 or 4.

[0207] In some embodiments, the PBM has the structure of the following formula (PBM-18-1): [ka] Represents.

[0208] In some embodiments, the PBM-R f - represents a small molecule ligand of BCR-ABL.

[0209] In some embodiments, the PBM has the structure of formula (PBM-19-1A) or formula (PBM-19-1B): [ka] represents where: (R 46 ) p20 R each independently has p20 benzene rings 46 Each R represents a substitution 46are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p20 represents an integer of 1, 2, 3, 4, or 5; and R 47 is a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0210] In some embodiments, the PBM has the structure of the following formula (PBM-19-1): [ka] Represents.

[0211] In some embodiments, the PBM has the structure of formula (PBM-20-1A), (PBM-20-1B), (PBM-20-1C), or (PBM-20-1D): [ka] represents where: (R 48 ) p21 each independently represents a group in which the quinoline ring is p21 R 48 Each R represents a substitution 48 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p21 represents an integer of 1, 2, 3 or 4; (R 49 ) p22 R each independently has p22 benzene rings 49 Each R represents a substitution 49 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p22 represents an integer of 2, 3 or 4.

[0212] In some embodiments, the PBM has the structure of the following formula (PBM-20-1): [ka] Represents.

[0213] In some embodiments, the PBM has the structure of formula (PBM-21): [ka] represents where: R 50 represents -NHC(O)- or -C(O)NH-; R 51 represents -NH- or ethynylene; (R 52 ) p23 In formula (PBM-21), each benzene ring is arbitrarily selected from p23 R 52 Each R represents a substitution 52 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); each p23 is the same or different and independently represents an integer of 0, 1, 2, 3, or 4; Ring D in formula (PBM-21) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and (R 53 ) p24 The ring D is optionally selected from p24 R 53 and each R 53 are the same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); and p24 represents an integer of 0, 1, 2, or 3.

[0214] In some embodiments, ring D in formula (PBM-21) represents a heteroaryl containing one or two 5- to 7-membered rings and 1-4 heteroatoms selected from the group consisting of N, O, and S. In one subembodiment, ring D represents a 5- to 14-membered monocyclic or bicyclic aromatic ring group containing one or more (e.g., 1-6, or 1-5, or 1-4, or 1-3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, examples of heteroaryl are furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]o

[0033] benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. Heteroaryl is optionally substituted with one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents, where the substituents are halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or any combination thereof.

[0215] In some embodiments, R in formula (PBM-21) 53represents 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 one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. In some subembodiments, examples of heteroaryl include furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3] including, but not limited to, oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. Heteroaryl is optionally substituted with one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents, where the substituents are 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or any combination thereof.

[0216] In some embodiments, R in formula (PBM-21) 51 represents -NH-.

[0217] In some embodiments, R in formula (PBM-21) 51 represents ethynylene.

[0218] In some embodiments, the PBM has the structure of formula (PBM-21-1A), (PBM-21-1B), (PBM-21-1C), (PBM-21-1D), or (PBM-21-1E): [ka] [ka] represents where: (R 52 ) p23 each independently represents that the benzene ring is independently optionally selected from p23 R 52 Each R represents a substitution 52are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p23 represents an integer of 0, 1, 2, 3 or 4.

[0219] In some embodiments, the PBM has the structure of the following formula (PBM-21-1): [ka] Represents.

[0220] In some embodiments, the PBM has the structure of formula (PBM-21-1F), (PBM-21-1G), (PBM-21-1H), (PBM-21-1I), or (PBM-21-1J): [ka] [ka] represents where: Each (R 52 ) p23 each independently represents that the benzene ring is independently optionally selected from p23 R 52 Each R represents a substitution 52 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p23 represents an integer of 0, 1, 2, 3 or 4; Each ring D in Formulae (PBM-21-1F), (PBM-21-1G), (PBM-21-1H), (PBM-21-1I) and (PBM-21-1J) independently represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O and S, and (R 53 ) p24 The ring D is optionally selected from p24 R 53and each R 53 are the same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated 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-); and p24 represents an integer of 0, 1, 2, or 3.

[0221] In some embodiments, each Ring D in Formulae (PBM-21-1F), (PBM-21-1G), (PBM-21-1H), (PBM-21-1I), and (PBM-21-1J) each independently represents a heteroaryl containing one or two 5- to 7-membered rings and 1-4 heteroatoms selected from the group consisting of N, O, and S. In one subembodiment, Ring D independently represents a 5- to 14-membered monocyclic or bicyclic aromatic ring group containing one or more (e.g., 1-6, or 1-5, or 1-4, or 1-3) heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, examples of heteroaryl are furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]o

[0033] benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl or imidazo[1,2-b]pyridazinyl. Heteroaryl is optionally substituted with one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents, where the substituents are 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or any combination thereof.

[0222] In some embodiments, the PBM has the structure of the following formula (PBM-21-2): [ka] Represents.

[0223] In some embodiments, the PBM has the structure of formula (PBM-52): [ka] represents where: (R 147 ) p55 The benzene ring is optionally divided into p55 R 147 and each R 147 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 1-3alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy) or halogenated C 1-6 Alkoxy (e.g., halogenated 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-), and p55 represents an integer of 0, 1, 2, 3, 4 or 5; R 148 represents NHC(O) or C(O)NH; and (R 149 ) p56 In formula (PBM-52), the 1H-pyrazole ring is optionally selected from p56 R 149 and each R 149 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy) or halogenated C 1-6 Alkoxy (e.g., halogenated 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-), and p56 represents an integer of 0, 1 or 2.

[0224] In some embodiments, (R 147 ) p55 The benzene ring has p55 R 147 where p55 represents an integer of 1, and R 147 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, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy) or halogenated C 1-6 Alkoxy (e.g., halogenated 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-). 147 is F2ClC-O-.

[0225] In some embodiments, R 148 represents NHC(O). In some embodiments, R 148 represents C(O)NH.

[0226] In some e...

Claims

1. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, comprising: [Formula 1] where: A is C(O), CH ２ or CD ２ represents; R １ , R ２ , R ３ and R ４ are the same or different and each independently represent hydrogen, deuterium, halogen, or optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy or halogenated C １－６ represents alkyl; (R ａ ) ｍ is a group in which the benzene ring is m in number ａ and each R ａ are the same or different and each independently have the following structure: [chemical 2] represents; where: R is chlorine, bromine, iodine, hydroxy, a leaving group, NR ７ R ８ or base W １ represents Here, R ７ and R ８ are the same or different and each independently represent hydrogen, C １－６ Alkyl, C ２－６ Alkynyl-C １－６ Alkylene-, C ２－６ Alkenyl-C １－６ alkylene-, optionally substituted 4- to 15-membered nitrogen-containing heterocyclyl, or R ２ａ -R １ａ -, where R １ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ represents alkenylene, R ２ａis halogen, amino, hydroxy, carboxy, C ２－６ Alkynyl, C ２－６ represents an alkenyl or leaving group; and Base W １ is a structure of the formula: [C3] or [C4] represents; Here, ring W ２ represents an optionally substituted nitrogen-containing heterocyclyl, and each ring W ３ are the same or different and each independently represent an optionally substituted nitrogen-containing heterocyclylene; t represents an integer of 1 or 2; and the ring W ４ represents optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl; R ５ and R ６ are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C ２－３０ alkyl, wherein the straight or branched C ２－３０ The alkyl carbon backbone may contain one or more groups R ｃ and / or one or more groups R ｄ or one or more groups R ｃ and R ｄ and any combination of the groups R ｃ , R ｄ or group R ｃ and R ｄ The combination of R ｃ is O, N (R ｅ ), C(O), C(O)O, S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , OC(O), C(O)N(R ｅ ), N(R ｅ ) C(O), or N(R ｅ )C(O)N(R ｅ ), wherein each R ｅ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ Two or more groups R in the carbon backbone of the alkyl ｃ When inserted, each group R ｃ are not directly connected to each other; ｄ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with substituents selected from the group consisting of alkyl-C(O)NH—, or any combination thereof; Or, R and R ５ form a carbonyl together with the carbon atom attached thereto, and R ６ is hydrogen, optionally substituted methyl, or optionally substituted straight or branched chain C ２－３０ alkyl, wherein the straight or branched C ２－３０ The alkyl carbon backbone may contain one or more groups R ｃ and / or one or more groups R ｄ or one or more groups R ｃ and R ｄ and any combination of the groups R ｃ , R ｄ or group R ｃ and R ｄThe combination of R ｃ is O, N (R ｅ ), C(O), C(O)O, S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , OC(O), C(O)N(R ｅ ), N(R ｅ ) C(O), or N(R ｅ )C(O)N(R ｅ ) wherein each R ｅ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ Two or more groups R in the carbon backbone of the alkyl ｃ When inserted, each group R ｃ are not directly connected to each other; ｄ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; (R ｂ ) ｎ is a group in which the benzene ring is n R ｂ and each R ｂare the same or different and each independently represent deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, optionally substituted C ３－６ Cycloalkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; and m represents an integer of 1, 2, 3, or 4, n represents an integer of 0, 1, 2, or 3, and the sum of m and n represents an integer of 1, 2, 3, or 4; where R and R ５ form a carbonyl group together with the carbon atom attached thereto, and R ６ represents hydrogen, m represents an integer of 1, 2 or 3, n represents an integer of 1, 2 or 3, and the sum of m and n represents an integer of 2, 3 or 4; The conditions include the following compound and a compound of formula (I'): [C5] Except; and A is CH ２ or C(O), and when R represents an unsubstituted piperazinyl group, m represents an integer of 1, and n represents an integer of 0; A is CH ２ or C(O), and R ａ H ２ N-CH ２ -, m represents an integer of 1 and n represents an integer of 0; When A represents C(O) and R represents bromine, m represents an integer of 1 and n represents an integer of 0; and Compounds of formula (I'): [C6] Formula (I') In the formula (I'), A is CH ２or C(O) and R represents unsubstituted piperidinyl or methylamino substituted piperidinyl, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

2. It is also a compound of formula (I-1) or formula (I-2), [C79] Here, A and R １ , R ２ , R ３ , R ４ , R ａ , R ｂ 2. A compound of formula (I) according to claim 1, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein m, m and n are as defined in claim 1.

3. R is: chlorine, bromine, iodine, hydroxy, or a leaving group; or NR ７ R ８ , where R ７ and R ８ are the same or different and each independently represent hydrogen, C １－６ Alkyl, C ２－６ Alkynyl-C １－６ Alkylene-, C ２－６ Alkenyl-C １－６ alkylene-, optionally substituted 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, optionally substituted 4- to 15-membered nitrogen-containing bridged heterocyclyl, or optionally substituted 4- to 15-membered nitrogen-containing spiroheterocyclyl, or R ２ａ -R １ａ -, where R １ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ represents alkenylene, R ２ａ is halogen, amino, hydroxy, carboxy, CHO, C ２－６ Alkynyl, C ２－６The 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, the 4- to 15-membered nitrogen-containing bridged heterocyclyl, and the 4- to 15-membered nitrogen-containing spiroheterocyclyl each represent deuterium, C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, R ４ａ -R ３ａ -, or any combination thereof, wherein R ３ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ represents alkenylene, R ４ａ is halogen, R ５ａ R ６ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R ５ａ and R ６ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; or A group W represented by the structure １ : [C24] Here, ring W ２ represents a 4- to 20-membered nitrogen-containing heterocyclyl, and (R ａ１ ) ｍ１ Is Ring W ２ There are m R ａ１ represents that the group is optionally substituted with a group, and each R ａ１ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R ８ａ -R ７ａ -, where R ７ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R ８ａ is halogen, R ９ａ R １０ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R ９ａ and R １０ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; or [C32] represents Here, each ring W ３ are the same or different and each independently represent a 4- to 20-membered nitrogen-containing heterocyclylene, t represents an integer of 1 or 2, (R ａ２ ) ｍ２ is each ring W ３ If m2 R ａ２ represents a group substituted with ａ２ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １２ａ -R １１ａ -, where R １１ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １２ａ is halogen, R １３ａ R １４ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R １３ａ and R １４ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; and Ring W ４represents a 4- to 15-membered nitrogen-containing heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl; (R ａ３ ) ｍ３ Is Ring W ４が Arbitrarily, m3 R ａ３ represents a group substituted with ａ３ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １６ａ -R １５ａ -, where R １５ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １６ａ is halogen, R １７ａ R １８ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R １７ａ and R １８ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; wherein m1, m2, and m3 each independently represent an integer from 0 to 20. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof according to claim 1 or 2.

4. R is NR ７ R ８ where R ７ and R ８ are the same or different and each independently: Hydrogen, C １－６ Alkyl, C ２－６ Alkynyl-C １－６ Alkylene-, C ２－６ Alkenyl-C １－６ alkylene-; or optionally substituted 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, optionally substituted 4- to 15-membered nitrogen-containing bridged heterocyclyl, or optionally substituted 4- to 15-membered nitrogen-containing spiroheterocyclyl, for example: Piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, diazacyclooctyl, azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octani diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl, diazabicyclo[2.2.2]octanyl, 3-azaspiro[5.5]undecan-3-yl, 8-azaspiro[4.5]decan-4-yl, 2-oxa-8-azaspiro[4.5]decan-4-yl, or 3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl, or [C13] [C14] [C15] [C16] [C17] [C18] [C19] R ２ａ -R １ａ -, where R １ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ represents alkenylene, R ２ａ is halogen, amino, hydroxy, carboxy, CHO, C ２－６ Alkynyl, C ２－６ represents an alkenyl or a leaving group, represents Here, the 4- to 15-membered nitrogen-containing monocyclic heterocyclyl, the 4- to 15-membered nitrogen-containing bridged heterocyclyl, and the 4- to 15-membered nitrogen-containing spiroheterocyclyl are each independently selected from the group consisting of deuterium, C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, R ４ａ -R ３ａ -, or any combination thereof, wherein R ３ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ represents alkenylene, R ４ａ is halogen, R ５ａ R ６ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R ５ａ and R ６ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; or R is a structure of the formula: [C24] A group W represented by １ represents Here, ring W ２ is a 4- to 20-membered nitrogen-containing heterocyclyl, for example, Piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, diazacyclooctyl, 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, diazabicyclo[2.2.2]octanyl, 3-azaspiro[5.5]undecanyl, 8-azaspiro[4.5]decanyl, 2-oxa-8-azaspiro[4.5]decanyl, or 3-methyl-2-oxa-8-azaspiro[4.5]decanyl, or [C25] [C26] [C27] [C28] [C29] [C30] [C31] represents; (R ａ１ ) ｍ１ Is Ring W ２ There are m R ａ１ represents that the group is optionally substituted with a group, and each R ａ１ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R ８ａ -R ７ａ -, where R ７ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R ８ａ is halogen, R ９ａ R １０ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R ９ａ and R １０ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; or Base W １ is a structure of the formula: [C33] is expressed as Here, each ring W ３ are the same or different and each independently represent a 4- to 20-membered nitrogen-containing heterocyclylene, for example, Piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene, diazacyclooctylene, azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo 2-azaspiro[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]undecanylene, 8-azaspiro[4.5]decanylene, 2-oxa-8-azaspiro[4.5]decanylene, or 3-methyl-2-oxa-8-azaspiro[4.5]decanylene, or [C34] [C35] [C36] [C37] [C38] [C39] [C40] represents t represents an integer of 1 or 2, (R ａ２ ) ｍ２ is each ring W ３ If m2 R ａ２ represents a group substituted with ａ２ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １２ａ -R １１ａ -, where R １１ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １２ａ is halogen, R １３ａ R １４ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R １３ａ and R １４ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; and Ring W ４ is a 4- to 15-membered nitrogen-containing heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl, for example: Piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, diazacyclooctyl, 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, diazabicyclo[2.2.2]octanyl, 3-azaspiro[5.5]undecanyl, 8-azaspiro[4.5]decanyl, 2-oxa-8-azaspiro[4.5]decanyl, 3-methyl-2-oxa-8-azaspiro[4.5]decanyl, phenyl, naphthyl, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, Thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, 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]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl, or [C41] [C42] [C43] [C44] [C45] [C46] [C31] represents (R ａ３ ) ｍ３ Is Ring W ４ If m3 R ａ３ represents a group substituted with ａ３ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, leaving group, amino, hydroxy, mercapto, cyano, carboxy, CHO, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １６ａ -R １５ａ -, where R １５ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １６ａ is halogen, R １７ａ R １８ａ represents N-, hydroxy, carboxy, CHO, ethynyl, vinyl or a leaving group, where R １７ａ and R １８ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; wherein m1, m2, and m3 each independently represent an integer from 0 to 20. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof according to claim 1 or 2.

5. R is the following group: Chlorine, bromine, iodine, hydroxy, -N ３ , sulfonate groups, such as methanesulfonyloxy (MsO-), trifluoromethanesulfonyloxy (TfO-) or p-toluenesulfonyloxy (TsO-), NH ２ , or [C47] [C48] [C49] [50] [C51] [C52] [C53] [C54] [C55] [C56] [C57] [C58] [C59] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [C70] [C71] [C72] [C73] [C74] [C75] [C76] [C77] 3. A compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, which represents:

6. R ５ and R ６ are each independently, Hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C ２－３０ represents alkyl, wherein the linear or branched chain C ２－３０ The alkyl carbon backbone may contain one or more groups R ｃ and / or one or more groups R ｄ or one or more groups R ｃ and R ｄ and any combination of the groups R ｃ , R ｄ or group R ｃ and R ｄ The combination of R ｃ is O, N (R ｅ ), C(O), C(O)O, S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , OC(O), C(O)N(R ｅ ), N(R ｅ ) C(O), or N(R ｅ )C(O)N(R ｅ ), wherein each R ｅ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ Two or more groups R in the carbon backbone of the alkyl ｃ When inserted, each group R ｃ are not directly connected to each other; ｄ is cycloalkylene (e.g., C ３－２０ cycloalkylene), arylene (e.g., C ３－２０ arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 4- to 20-membered heteroarylene), alkynylene (e.g., C ２－６ alkynylene), alkenylene (e.g., C ２－６alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene are each independently selected from the group consisting of: deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; and The hydrogen of the methyl and the C ２－３０ One or more CH of alkyl ２ The hydrogen of may further be deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ 3. A compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- or any combination thereof.

7. R and R ５10. The compound of formula (I) of claim 1, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein:

8. R ６ is a structure of the formula: -C １－３０ Alkyl; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｃ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｃ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ - (R ｃ -(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｃ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ - (R ｃ -(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ - (R ｃ -(C(R ａ１０ ) (R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｄ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｄ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(R ｄ -(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｄ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(R ｄ -(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(R ｄ -(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｃ -R ｄ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｃ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(R ｄ -(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｄ -R ｃ-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; or -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｄ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ - (R ｃ -(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ represents —H; where each group R ｃ is O, N (R ｅ ), C(O), C(O)O, OC(O), S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , C(O)N(R ｅ ), N(R ｅ ) C(O), or N(R ｅ )C(O)N(R ｅ ) wherein each R ｅ are independently H or C １－６ represents alkyl; each group R ｄ is cycloalkylene (e.g., C ３－２０ cycloalkylene), arylene (e.g., C ５－２０ arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 5- to 20-membered heteroarylene), alkynylene (e.g., C ２－６ alkynylene), alkenylene (e.g., C ２－６ alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene are each independently selected from the group consisting of: deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; Said C １－３０ One or more CH of alkyl ２ The hydrogen of may further be deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; R ａ４ , R ａ５ , R ａ６ , R ａ７ , R ａ８ , R ａ９ , R ａ１０ and R ａ１１ are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)- or optionally deuterated C １－６ represents alkyl-C(O)NH—; and 8. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to any one of claims 1-2 and 6-7, wherein n1, n2, n3, n4, m4, m5, m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

9. R ６ is a structure of the formula: -(C(R ａ４ ) (R ａ５ )) ｎ１ -(O-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(O-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(O-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -(O-(C(R ａ１０ ) (R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(N(R ｅ )-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(N(R ｅ )-(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(C(O)N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１-(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(C(O)N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(C(O)N(R ｅ )-(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(O-(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -N(R ｅ )C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(アリーレン-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(arylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -arylene-(C(R ａ８ ) (R ａ９ )) ｎ３ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heterocyclylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heterocyclylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(heterocyclylene-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heteroarylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heteroarylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(heteroarylene-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(cycloalkylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; or -(C(R ａ４ ) (R ａ５ )) ｎ１ -(cycloalkylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(cycloalkylene-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; represents Here, each R ｅ are independently H or C １－６ represents alkyl; The cycloalkylene, the arylene, the heterocyclylene and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; R ａ４ , R ａ５ , R ａ６ , R ａ７ , R ａ８ , R ａ９ , R ａ１０ and R ａ１１ are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)- or optionally deuterated C １－６ represents alkyl-C(O)NH—; and 9. The compound of formula (I) of claim 8, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein n1, n2, n3, n4, m4, m5, and m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

10. R ６ is the following group: H, fluorine, chlorine, bromine, iodine, -CH ３ , -CH ２ -CH ３ , -(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -CH ３ , -(CH ２ ) ４ -CH ３ , -(CH ２ ) ５ -CH ３ , -(CH ２ ) ６ -CH ３ , -(CH ２ ) ７ -CH ３ , -(CH ２ ) ８ -CH ３ , -(CH ２ ) ９ -CH ３ , -(CH ２ ) １０ -CH ３ , -(CH ２ ) １１ -CH ３ , -(CH ２ ) １２ -CH ３ , -(CH ２ ) １３ -CH ３ 、-(CH ２ ) １４ -CH ３ 、-(CH ２ ) １５ -CH ３ 、-(CH ２ ) １６ -CH ３ 、-(CH ２ ) １７ -CH ３ 、-(CH ２ ) １８ -CH ３ 、-(CH ２ ) １９ -CH ３ 、-(CH ２ ) ２０ -CH ３ 、-(CH ２ ) ２１ -CH ３ 、-(CH ２ ) ２２ -CH ３ 、-(CH ２ ) ２５ -CH ３ 、-(CH ２ ) ２９ -CH ３ ;-CH ２ -O-CH ３ 、-CH ２ -O-CH ２ -CH ３ 、-CH ２ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ６-CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ７ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ８ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ９ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) １０ -CH ３ 、-(CH ２ ) ２ -O-CH ３ 、-(CH ２ ) ２ -O-CH ２ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ７ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ８ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) １０ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) １１ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) １２ -CH ３ 、-(CH ２ ) ３ -O-CH ３ 、-(CH ２ ) ３ -O-CH ２ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ７ -CH ３ 、-(CH ２ ) ４ -O-CH ３、-(CH ２ ) ４ -O-CH ２ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ５ -O-CH ３ 、-(CH ２ ) ５ -O-CH ２ -CH ３ 、-(CH ２ ) ５ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ５ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ５ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ６ -O-CH ３ 、-(CH ２ ) ６ -O-CH ２ -CH ３ 、-(CH ２ ) ６ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ６ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ６ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ７ -O-CH ３ 、-(CH ２ ) ７ -O-CH ２ -CH ３ 、-(CH ２ ) ７ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ７ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ８ -O-CH ３ 、-(CH ２ ) ８ -O-CH ２ -CH ３ 、-(CH ２ ) ８ -O-(CH ２ ) ２ -CH ３ 、-CH(CH ３ )-O-CH ３ 、-CH(CH ３ )-O-CH ２ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ２ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ３ -CH ３ 、-CH(CH ３)-O-(CH ２ ) ４ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ５ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ６ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ７ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ８ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ９ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) １０ -CH ３ 、-CH ２ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) １ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ２ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ３ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ４ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ５ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ６ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ７ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ８ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ９ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) １０ -OCH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ５ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ６ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ７ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ８ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ９ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) １０ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ５ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ６ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ７ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ８ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ５ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ６ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ７ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ８ -OCH ２ CH ２ CH ３ 、-CH ２ -O-(CH) ２ ) ２ -O-(CH) ２ ) ２ -CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ２ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ２ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３) ４ -OCH ２ CH ２ CH ３ 、-CH ２ -O-(CH ２ ) ３ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) １ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ２ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ３ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ４ -O-CH ２ CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) １ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ２ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ４ -O-CH ２ CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) １ -O-CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ２ -O-CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ４ -O-CH ２ CH ３ 、-CH ２ -O-(CH ２ ) ２ -O-CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ２ -O-CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ４ CH ３ 、-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ５ CH ３ 、-(CH ２ ) １ -N(R ｅ )-CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ４ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ５ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ６ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ７ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ８ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-CH ３、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ７ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ８ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) １０ -CH ３ 、-(CH ２ ) ２-N(R ｅ )-(CH ２ ) １１ -CH ３ 、-(CH ２ ) ３ -N(R ｅ )-CH ３ 、-(CH ２ ) ３ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ３ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ４ -N(R ｅ )-CH ３ 、-(CH ２ ) ４ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ４ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ４ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-CH ３ 、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ６ -N(R ｅ )-CH ３ 、-(CH ２ ) ６ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ６ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ７ -N(R ｅ )-CH ３ 、-(CH ２ ) ７ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ７ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ８ -N(R ｅ )-CH ３ 、-(CH ２ ) ８ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ８ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-CH(CH ３ )-N(R ｅ )-CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) １ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ２ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ３ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ４ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ５ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ６ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ７ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ８ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ９ -CH ３ 、-CH ２ C(O)NHCH ３ 、-(CH ２ ) ２ C(O)NHCH ２ CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ４ -CH ３ 、-(CH ２ ) ３ C(O)NH(CH ２ ) ２ -CH ３ 、-(CH ２ ) ３ C(O)NH(CH ２ ) ３ -CH ３ 、-(CH ２ ) ４ C(O)NH(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ C(O)NH(CH ２ ) ４ -CH ３ 、-(CH ２ ) ６ C(O)NH(CH ２ ) ６ -CH ３ 、-(CH ２ ) ６ C(O)NH(CH ２ ) ５ -CH ３ 、-(CH ２ ) ７ C(O)NH(CH ２ ) ６ -CH ３ 、-(CH ２ ) ８ C(O)NH(CH ２ ) ７ -CH ３ 、U-(CH ２ ) ９ C(O)NH(CH ２ ) ８ -CH ３ 、-(CH ２ ) １０ C(O)NH(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -O-CH ２ -CH ３ 、-CH ２ NHC( O)CH ３ 、-(CH ２ ) ２ NHC(O)CH ２ CH ３ 、-(CH ２ ) ２ NHC(O)(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ NHC(O)(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ NHC(O)(CH ２ ) ４ -CH ３ 、-(CH ２ ) ３ NHC(O)(CH ２ ) ２ -CH ３ 、-(CH ２ ) ３ NHC(O)(CH ２ ) ３ -CH ３ 、-(CH ２ ) ４ NHC(O)(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ NHC(O)(CH ２ ) ４ -CH ３ 、-(CH ２ ) ６ NHC(O)(CH ２ ) ６ -CH ３ 、-(CH ２ ) ６ NHC(O)(CH ２ ) ５ -CH ３ 、-(CH ２ ) ７ NHC(O)(CH ２ ) ６-CH ３ , -(CH ２ ) ８ NHC(O)(CH ２ ) ７ -CH ３ , -(CH ２ ) ９ NHC(O)(CH ２ ) ８ -CH ３ , -(CH ２ ) １０ NHC(O)(CH ２ ) ９ -CH ３ , -(CH ２ ) ４ NHC(O)(CH ２ ) ７ -CH ３ , -(CH ２ ) ２ NHC(O)(CH ２ ) ２ -O-CH ２ -CH ３ , -(CH ２ ) ４ NHC(O)CH ３ , -CH ２ -piperidinylene-CH ３ , -CH ２ -piperidinylene-CH ２ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ２ -piperidinylene-CH ３ , -(CH ２ ) ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ３ -piperidinylene-CH ３ , -(CH ２ ) ３ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ４ -piperidinylene-CH ３ , -(CH ２ ) ４ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ５ -piperidinylene-CH ３ , -(CH ２ ) ５ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ６ -piperidinylene-CH ３ , -(CH ２ ) ６ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２) ４ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ７ -piperidinylene-CH ３ , -(CH ２ ) ７ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ７ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ７ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ７ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ８ -piperidinylene-CH ３ , -(CH ２ ) ８ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ７ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-CH ２ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , - ( CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ５ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ５ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ６ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ６ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ７ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ７ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -CH ２ -piperazinylene-CH ３ , -CH ２ -piperazinylene-CH ２ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ２ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ３ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ４ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ５ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ６ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ２ -piperazinylene-CH ３ , -(CH ２ ) ２ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ３ -piperazinylene-CH ３ , -(CH ２ ) ３ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ４ -piperazinylene-CH ３ , -(CH ２ ) ４ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ５ -piperazinylene-CH ３ , -(CH ２ ) ５ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ６ -piperazinylene-CH ３ , -(CH ２ ) ６ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２) ４ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ７ -piperazinylene-CH ３ , -(CH ２ ) ７ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ７ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ７ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ７ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ８ -piperazinylene-CH ３ , -(CH ２ ) ８ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ６ -CH ３ , or -(CH ２ ) ８ -piperazinylene-(CH ２ ) ７ -CH ３ represents; wherein the piperidinylene and the piperazinylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, nitro, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; CH in the above group ３ and one or more CH ２ The hydrogen of may further be deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; Each R ｅ are independently H or C １－６ represents alkyl; and 9. The compound of formula (I) of claim 8, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein n1, n2, n3, n4, m4, m5, and m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

11. The following: 3-(5-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(chloromethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(iodomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(aminomethyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(aminomethyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(aminomethyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl 4-methylbenzenesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl trifluoromethanesulfonate; 3-(5-(bromomethyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(bromomethyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(bromomethyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-bromo-5-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-bromo-5-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-bromo-5-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2,6-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-chloro-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-bromo-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-chloro-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-bromo-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-chloro-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-bromo-1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(chloromethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(iodomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-fluoro-4-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-4-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-4-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(aminomethyl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(aminomethyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(aminomethyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl 4-methylbenzenesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl methanesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl trifluoromethanesulfonate; 3-(4-(bromomethyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(bromomethyl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(bromomethyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-bromo-4-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-bromo-4-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-bromo-4-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2,6-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-chloro-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-bromo-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-fluoro-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-chloro-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-bromo-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-chloro-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-bromo-1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((R)-3-aminopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((S)-3-aminopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-aminopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-(piperidin-4-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(azetidin-3-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((R)-3-aminopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((S)-3-aminopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-aminopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione 3-(1-oxo-4-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(azetidin-3-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-(chloromethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(iodomethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(hydroxymethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-5-(hydroxymethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(hydroxymethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-6-(hydroxymethyl)isoindoline-1,3-dione; 5-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl 4-methylbenzenesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl methanesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl trifluoromethanesulfonate; 6-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-bromo-6-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-bromo-6-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-bromo-5-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)isoindoline-1,3-dione; 5-((2,6-dimethylpiperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,5-dimethylpiperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-6-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 4-chloro-2-(2,6-dioxopiperidin-3-yl)-6-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 4-bromo-2-(2,6-dioxopiperidin-3-yl)-6-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-5-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 4-chloro-2-(2,6-dioxopiperidin-3-yl)-5-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 4-bromo-2-(2,6-dioxopiperidin-3-yl)-5-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 5-chloro-2-(2,6-dioxopiperidin-3-yl)-6-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 5-bromo-2-(2,6-dioxopiperidin-3-yl)-6-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 4-(chloromethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(iodomethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(hydroxymethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-4-(hydroxymethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-6-fluoro-4-(hydroxymethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-7-(hydroxymethyl)isoindoline-1,3-dione; 4-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl 4-methylbenzenesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl methanesulfonate; (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl trifluoromethanesulfonate; 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-bromo-7-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 6-bromo-4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-bromo-4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)isoindoline-1,3-dione; 4-((2,6-dimethylpiperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((3,5-dimethylpiperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-7-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 4-chloro-2-(2,6-dioxopiperidin-3-yl)-7-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 4-bromo-2-(2,6-dioxopiperidin-3-yl)-7-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-4-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 5-chloro-2-(2,6-dioxopiperidin-3-yl)-4-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 5-bromo-2-(2,6-dioxopiperidin-3-yl)-4-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-6-fluoro-4-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 6-chloro-2-(2,6-dioxopiperidin-3-yl)-4-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 6-bromo-2-(2,6-dioxopiperidin-3-yl)-4-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 5-(((R)-3-aminopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-3-aminopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-aminopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(piperazin-1-ylmethyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(piperidin-4-ylmethyl)isoindoline-1,3-dione; 5-(azetidin-3-ylmethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(((R)-3-aminopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(((S)-3-aminopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-aminopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(azetidin-3-ylmethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (E)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)but-2-enoic acid; (E)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)piperazin-1-yl)but-2-enoic acid; (E)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)but-2-enoic acid; (E)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl)piperazin-1-yl)but-2-enoic acid; 3-(5-((4-(3-hydroxypropyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(3-hydroxypropyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-hydroxypropyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(3-hydroxypropyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-((4-(3-bromopropyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(3-bromopropyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(3-bromopropyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(3-bromopropyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-hydroxypiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-hydroxypiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-hydroxypiperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-hydroxypiperidin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-((4-bromopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-bromopiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-bromopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-bromopiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(((2-bromoethyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((2-bromoethyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-(((2-bromoethyl)(methyl)amino)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(((2-bromoethyl)(methyl)amino)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((methyl(piperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((methyl(piperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((methyl(piperidin-4-yl)amino)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((methyl(piperidin-4-yl)amino)methyl)isoindoline-1,3-dione; 3-(1-oxo-5-((4-(piperazin-1-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(piperazin-1-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 3-(1-oxo-5-((4-(piperidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(piperidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(piperidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(piperidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 3-(1-oxo-5-((4-phenylpiperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-phenylpiperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-phenylpiperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-phenylpiperazin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-((4-(4-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(4-bromophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(4-bromophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(1-oxo-5-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-((4-(6-chloropyridazin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(6-chloropyridazin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(6-chloropyridazin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(6-chloropyridazin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3-fluoropiperidin-4-yl methanesulfonate; 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-3-fluoropiperidin-4-yl methanesulfonate; 1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)-3-fluoropiperidin-4-yl methanesulfonate; 1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl)-3-fluoropiperidin-4-yl methanesulfonate; 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl trifluoromethanesulfonate; 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)piperidin-3-yl trifluoromethanesulfonate; 1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-3-yl trifluoromethanesulfonate; 1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl)piperidin-3-yl trifluoromethanesulfonate; 3-(5-((4-(6-aminopyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(6-aminopyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(6-aminopyridin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(6-aminopyridin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(azetidin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(azetidin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(azetidin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(azetidin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(1-oxo-5-((3-(piperazin-1-yl)azetidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-(piperazin-1-yl)azetidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(piperazin-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((3-(piperazin-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-((4-methylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-methylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-methylpiperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-methylpiperazin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-((4-(difluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(difluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(difluoromethyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(difluoromethyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(1-oxo-5-((piperidin-4-ylamino)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((piperidin-4-ylamino)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((piperidin-4-ylamino)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((piperidin-4-ylamino)methyl)isoindoline-1,3-dione; 3-(5-((4-(2-aminoethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-aminoethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(2-aminoethyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(2-aminoethyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(1-oxo-5-((4-propylpiperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-propylpiperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-propylpiperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-propylpiperazin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-(((2-hydroxyethyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((2-hydroxyethyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(((2-hydroxyethyl)amino)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(((2-hydroxyethyl)amino)methyl)isoindoline-1,3-dione; 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxylic acid; 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)piperidine-4-carboxylic acid; 1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidine-4-carboxylic acid; 1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl)piperidine-4-carboxylic acid; 1'-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-[1,4'-bipiperidine]-4-carboxylic acid; 1'-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-[1,4'-bipiperidine]-4-carboxylic acid; 1'-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)-[1,4'-bipiperidine]-4-carboxylic acid; 1'-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl)-[1,4'-bipiperidine]-4-carboxylic acid; 3-(5-((4-ethynylpiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-ethynylpiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-ethynylpiperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-ethynylpiperidin-1-yl)methyl)isoindoline-1,3-dione; 3-(1-oxo-5-((3-(piperazin-1-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-(piperazin-1-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((3-(piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-(((4-methylpiperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-methylpiperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(((4-methylpiperidin-4-yl)amino)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(((4-methylpiperidin-4-yl)amino)methyl)isoindoline-1,3-dione; 3-(5-(((3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(((3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(((3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindoline-5-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindoline-5-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-1-oxoisoindoline-4-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindoline-4-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindoline-4-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindoline-5-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindoline-5-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindoline-5-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-1,3-dioxoisoindoline-4-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindoline-4-carbaldehyde; 2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindoline-4-carbaldehyde; 3-(4-bromo-6-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-bromo-6-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-bromo-6-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(bromomethyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(bromomethyl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(bromomethyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-bromo-7-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-bromo-7-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-bromo-7-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(bromomethyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(bromomethyl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(bromomethyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-bromo-6-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-bromo-6-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-bromo-5-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 6-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-bromo-7-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 6-bromo-4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-bromo-4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; and 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to claim 1, selected from the group consisting of: 4-(bromomethyl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione.

12. 1. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, PBM-R ｆ -LIN-ULM Formula (II) Here, PBM-R ｆ - represents a targeting moiety capable of binding to a protein, ULM represents a ligand moiety capable of binding to an E3 ubiquitin ligase, LIN is a connecting moiety, and PBM-R ｆ - is covalently linked to the ULM by the group LIN; ULM has the structure of the following formula (ULM): [C7] Formula (ULM) where: A is CO, CH ２ or CD ２ represents; R １ , R ２ , R ３ and R ４ are the same or different and each independently represent hydrogen, deuterium, halogen, or optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy or halogenated C １－６ represents alkyl; (R ｂ ) ｎ The benzene ring is optionally connected to n R ｂ and each R ｂ are the same or different and each independently represent deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, optionally substituted C ３－６ Cycloalkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; n represents an integer of 0, 1, 2, or 3; LIN has the structure of the following formula: [C8] represents; Here, R ５ and R ６ are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C ２－３０ alkyl, wherein the straight or branched C ２－３０ The alkyl carbon backbone may contain one or more groups R ｃ and / or one or more groups R ｄ or one or more groups R ｃ and R ｄ and any combination of the groups R ｃ , R ｄ or group R ｃ and R ｄ The combination of R ｃ is O, N (R ｅ ), C(O), C(O)O, S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , OC(O), C(O)N(R ｅ ), N(R ｅ ) C(O), or N(R ｅ)C(O)N(R ｅ ) wherein each R ｅ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ Two or more groups R in the carbon backbone of the alkyl ｃ When inserted, each group R ｃ are not directly connected to each other; ｄ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with substituents selected from the group consisting of alkyl-C(O)NH—, or any combination thereof; R ｆ is a bond, -O-, -N(R ｇ )-,-NHC(O)-R ｈ -W ５ -*, -C(O)NH-R ｈ -W ５ -*, -NHC(O)-W ５ -*, -C(O)NH-W ５ -*, -NHC(O)-*, -C(O)NH-*, -OR ｈ -W ５ -*, -O-W ５ -*, -O-R ｈ -N(R ｉ ) - *, -N (R ｇ )-R ｈ -N(R ｉ) - *, - W ５ -, -W ５ -N(R ｇ ) - *, -N (R ｇ )-W ５ -*, -N(R ｇ )-W ５ -N(R ｉ ) - *, - R ｈ -W ５ -*, -R ｈ -C(O)-W ５ -*, -C(O)-W ５ -*, -R ｈ —C(O)NH—R ｊ -W ５ -*, -R ｈ -NHC(O)-R ｊ -W ５ -*, -R ｈ -C(O)NH-*, -R ｈ -NHC(O)-*, -R ｈ -, -R ｈ -N(R ｉ ) - *, or [C9] represents Here, the group W ５ is a structure of the formula: [C10] represents Here, each ring W ６ are the same or different and each independently represent a nitrogen-containing heterocyclylene; t1 represents an integer of 1 or 2; (R ａ２ ) ｍ２ is each ring W ６ There are m2 R ａ２ represents that the group is optionally substituted with a group, and each R ａ２ are independently deuterium, optionally deuterated C １－６ Alkyl, optionally halogenated C １－６ Alkyl, C １－６ Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １２ａ -R １１ａ-, where R １１ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １２ａ is halogen, R １３ａ R １４ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １３ａ and R １４ａ are the same or different and each independently represent hydrogen or C １－３ alkyl, and m2 represents an integer of 0-20; Each ring W ７ are the same or different and each independently represent a nitrogen-containing heterocyclylene, arylene, or heteroarylene; t2 represents an integer of 0 or 1; (R ａ３ ) ｍ３ is each ring W ７ are independently m3 R ａ３ represents that the group is optionally substituted with a group, and each R ａ３ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １６ａ -R １５ａ -, where R １５ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １６ａ is halogen, R １７ａ R １８ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １７ａ and R １８ａ are the same or different and each independently represent hydrogen or C １－３ alkyl, and m3 represents an integer of 0-20; and R ｇ and R ｉ are each independently hydrogen or C １－６ represents alkyl, and R ｈand R ｊ each independently represents an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ represents alkenylene, and the symbol * represents the point of attachment to LIN; wherein the PBM has the following structural formula: [C11] represents And-R ｆ -LIN- [C12] where the symbol ** represents the connection point with the ULM. ｂ ) ｎ The benzene ring of formula (ULM) is one, two or three R ｂ and each R ｂ are the same or different and each independently represent deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, optionally substituted C ３－６ Cycloalkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; The conditions include the following compounds: 3-(4-((3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)pyrrolidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)piperidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)azetidin-3-yl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; and A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, excluding 2-(2,6-dioxopiperidin-3-yl)-5-((3-(4-(6-(6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione.

13. Said PBM-R ｆ- denotes the following proteins: epidermal growth factor receptor (EGFR), cyclin-dependent protein kinase 4 / 6 (CDK4 / 6), anaplastic lymphoma kinase (ALK), activin receptor-like kinase 2 (ALK2), fibroblast growth factor receptors (FGFRs), and proto-oncogene tyrosine-protein kinase receptor RET (RET). receptor RET), 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), and bromodomain and extra-terminal domain protein (BRODOMAIN). protein (BET), interleukin-1 receptor-associated kinase 4 (IRAK4), cyclin-dependent protein kinase 9 (CDK9), histone-lysine N-methyltransferase EZH2 (EZH2), neurotrophic receptor tyrosine kinase (NTRK), Src homology 2 domain-containing protein tyrosine phosphatase (Src homology 2 domaincontaining 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 (SOS Ras / Rac guanine nucleotide exchange factor 1), and ATP-dependent transcription factor 1 (ATP1A1).

13. The compound of formula (II) of claim 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, which represents a small molecule ligand that binds to the GTPase Kras (SOS1) or GTPase Kras (KRAS).

14. The PBM has a structure selected from the following formulas: [chemical 82] [chemical 83] [chemical 84] [C85] [chemical 86] [chemical 87] [C88] [C89] [C90] [C91] [C92] [C93] [C739] [C740] Including; where: (R １ ) ｐ１ is a group in which the benzene ring in formula (PBM-1) is p1 R １ and each R １ are the same or different and each independently represent halogen, hydroxy, NH ２ , NO ２ , Cyano, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ represents alkoxy; (R ２ ) ｐ２ In formula (PBM-1), the quinazoline ring is R ２ and each R ２ are the same or different and each independently represent a halogen, NO ２ , cyano, halogenated C １－６ Alkyl, C １－１０ Alkyl, deuterated C １－１０ Alkyl, C １－１０ Alkoxy, halogenated C １－１０ alkoxy, —O-optionally substituted heterocyclyl, or —NHC(O)R ３ where R ３ is C １－１０ Alkyl, deuterated C １－１０ Alkyl or C ２－１０ alkenyl, for example, R ２ is methyl, methoxy, [C96] or [C97] For example, [C98] represents; p1 represents an integer of 1, 2, 3, 4, or 5; p2 represents an integer of 1, 2, or 3; (R ４ ) ｐ３ In formula (PBM-2), the benzene ring is p3 R ４and each R ４ are the same or different and each independently represent a halogen, a nitro, a cyano, a halogenated C １－６ Alkyl, C １－１０ Alkyl, deuterated C １－１０ Alkyl, C １－１０ Alkoxy or -NHC(O)R １５ａ where R １５ａ is C １－１０ Alkyl, deuterated C １－１０ Alkyl or C ２－１０ alkenyl, for example, R ４ is a methyl, methoxy, nitro group or [C96] represents; p3 represents an integer of 1, 2, 3, or 4; (R ５ ) ｐ４ In formula (PBM-2), the 1H-indole ring is ５ p4 represents an integer of 0, 1, 2, or 3, and each R ５ are the same or different and each independently represent C １－１０ Alkyl or deuterated C １－１０ represents alkyl; R ６ is hydrogen, C １－１０ Alkyl or deuterated C １－１０ represents alkyl; (R ７ ) ｐ５ In formula (PBM-3), the benzene ring is p5 R ７ and each R ７ are the same or different and each independently represent a halogen, a hydroxyl, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, NO ２ , N.H. ２ or a cyano group; p5 represents an integer of 0, 1, 2, 3, 4, or 5; R ８ is a substituted or unsubstituted C ３－１５cycloalkyl, for example cyclopentyl; (R ９ ) ｐ６ In formula (PBM-4), the benzene ring is p6 R ９ and each R ９ are the same or different and each independently represent a halogen, a hydroxyl, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, NO ２ , N.H. ２ , C １－６ Alkoxy, halogenated C １－６ represents an alkoxy or cyano group; p6 represents 2, 3, 4 or 5; R １０ is C ６－１０ aryl, or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein ６－１０ The aryl and the heteroaryl each optionally have one or more R ｂ１ and each R ｂ１ are the same or different and each independently represent 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 is alkoxy; (R １１ ) ｐ７ In formula (PBM-5), the benzene ring and the pyridine ring each optionally have p7 R １１ each p7 is the same or different and independently represents an integer of 0, 1, 2, or 3; and each R １１ are the same or different and each independently represent a halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; R １２is hydrogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; R in formula (PBM-6) １３ is hydrogen, C １－１０ Alkyl (e.g., [C99] ), deuterated C １－１０ Alkyl or halogenated C １－１０ represents alkyl; R １４ teeth [C100] where (R ｂ２ ) ｐ８ The piperidine ring is optionally selected from p8 R ｂ２ and each R ｂ２ are the same or different and each independently represent deuterium, halogen, hydroxy, 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, NO ２ , N.H. ２ or a cyano group, and p8 represents an integer of 1, 2, 3, 4, or 5; Ring A in formula (PBM-7) is C ６－１０ aryl, or a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring A optionally contains one or more R ｂ３ and each R ｂ３ are the same or different and each independently represent 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, C ２－６ Alkenyl, or C ２－６alkynyl; Ring B in formula (PBM-7) is C ３－１５ cycloalkyl or a 3- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein said ring B optionally has one or more R ｂ４ and each R ｂ４ are the same or different and each independently represent 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 is alkoxy; Ring C in formula (PBM-7) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and said ring C optionally contains one or more R ｂ５ and each R ｂ５ are the same or different and each independently represent deuterium, halogen, hydroxy, 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 is alkoxy; R in formula (PBM-8) １５ represents a 4- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein said heterocyclyl is optionally joined to one or more R ｂ６ and each R ｂ６ are the same or different and each independently represent 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 is alkoxy; (R １６ ) ｐ９ In formula (PBM-8), the benzene ring is p9 R １６and each R １６ are the same or different and each independently represent a halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ alkyl, and p9 represents an integer of 1, 2, 3, or 4; X in formula (PBM-9) １ is N or CR ｂ７ where R ｂ７ is hydrogen or represents amino, X ２ is N or CR １７ where R １７ is hydrogen or represents a bond, and X ３ represents CH or N; R １８ and R １９ each independently represents hydrogen or a bond; (R ２０ ) ｐ１０ In formula (PBM-9), the benzene ring is p10 R ２０ and each R ２０ are the same or different and each independently represent —O-aryl, —O-heteroaryl, —C １－３ alkylene-NHC(O)-heteroaryl, -C １－３ alkylene-C(O)NH-heteroaryl or halogen, wherein the aryl and heteroaryl are each independently optionally selected from one or more R ｂ８ and each R ｂ８ are the same or different and each independently represent deuterium, halogen, hydroxy, 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 is alkoxy; p10 represents an integer of 1, 2, 3, or 4; R ２１ is a bond, deuterium, hydrogen, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６Alkyl, or C １－６ represents alkoxy; R ２２ represents hydrogen, halogen, cyano, or amino; Here, R １７ , R １８ , R １９ and R ２１ is not simultaneously hydrogen, and R １７ , R １８ , R １９ and R ２１ are not simultaneously bonds, and R １７ , R １８ , R １９ and R ２１ where only one represents a bond, R １８ When represents a bond, R １８ The ring carbon atom connecting to R ｆ Directly connected to X ２ represents CH or N, and R １９ is hydrogen, and R ２１ is not a bond; X ２ is CR １７ where R １７ When represents a bond, R １７ The ring carbon atom connected to R ｆ directly connected to R １８ and R １９ are both hydrogen, and R ２１ is not a bond; R １９ When represents a bond, R １９ The nitrogen atom of the ring connected to is R ｆ Directly connected to X ２ represents N or CH, and R １８ is hydrogen, and R ２１ is not a bond; and R ２１ When represents a bond, R ２１ The ring carbon atom connected to R ｆ directly connected to X ２ represents N or CH, and R １８ and R １９ are both hydrogen; (R ２３ ) ｐ１１ In formula (PBM-10), the cyclopentene ring is p11 R ２３ and each R ２３ are the same or different and each independently represent a halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ alkyl, and p11 represents an integer of 1, 2, 3, or 4; (R ２４ ) ｐ１２ In formula (PBM-10), the pyridine is p12 R ２４ and each R ２４ are the same or different and each independently represent a halogen, —C １－３ Alkylene-OH, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ alkyl, and p12 represents an integer of 1, 2, or 3; R ２５ is hydrogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; X in formula (PBM-11) ４ is CR ２６ or fragment [C101] where the symbol # represents X ４ and the adjacent N, and the symbol ## represents the connection point of X ５ represents the connection point with, and R ２６ are 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 ｂ９ R ｂ１０ where R ｂ９ , R ｂ１０ are the same or different and each independently represent hydrogen, C １－６ Alkyl or deuterated C １－６ represents alkyl; X in formula (PBM-11) ５ is N or CR ２７ where R ２７ are hydrogen, deuterium, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; X ６ and X ７ each independently represents CH or N; R ２８ represents a bond or an optionally substituted heteroarylene (e.g., halogen-substituted heteroarylene); R ２９ is hydrogen, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ alkyl, or optionally substituted C ３－７ represents cycloalkyl; R ３０ and R ３１ are the same or different and each independently represent hydrogen, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R in formula (PBM-12) ３２ is hydrogen, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; R ３３ is hydrogen, cyano, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; (R ３４ ) ｐ１３ In formula (PBM-13), the benzene ring is p13 R ３４ and each R ３４are the same or different and each independently represent halogen, hydroxy, amino, cyano, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; p13 represents an integer of 1, 2, 3, 4, or 5; R ３５ is NR ｂ１１ R ｂ１２ where R ｂ１１ , R ｂ１２ are the same or different and each independently represent hydrogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; (R ３６ ) ｐ１４ The benzene ring in formula (PBM-14) is optionally selected from p14 R ３６ p14 represents an integer of 1, 2 or 3; and each R in formula (PBM-14) ３６ are the same or different and each independently represent a halogen, amino, cyano, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; R ３７ is hydrogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; X in formula (PBM-15) ８ , X ９ , X １０ , X １１ and X １２ are the same or different and each independently represent N or CH; R ３８ represents a bond or an optionally substituted methylene (e.g., methylene substituted with a halogen); R ３９ -C(O)NHR ｂ１３ , -NHC(O)-R ｂ１３ , -S(O) ２ NHR ｂ１３ , -N(R ｂ１４ ) S (O) ２ R ｂ１３ , -S(O) ２ R ｂ１３ or -P(O)(R ｂ１３ ) ２ where each R ｂ１３ are the same or different and each independently represent C １－６ Alkyl or deuterated C １－６ represents alkyl, and R ｂ１４ is hydrogen or C １－６ represents alkyl; (R ４０ ) ｐ１５ represents the X in formula (PBM-15). ９ and X １０ A six-membered ring containing p15 R ４０ and each R ４０ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p15 represents an integer of 0, 1, 2, 3, or 4; R ４１ is halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; (R ４２ ) ｐ１６ The benzene ring in formula (PBM-16) is optionally selected from p16 R ４２ and each R in formula (PBM-16) represents a substituent. ４２ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; each p16 is the same or different and independently represents an integer of 0, 1, 2, 3, or 4; (R ４３ ) ｐ１７In formula (PBM-17), the benzene ring is p17 R ４３ p17 represents an integer of 0, 1, 2, 3, or 4; and each R in formula (PBM-17) ４３ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; (R ４４ ) ｐ１８ The benzene ring in formula (PBM-18) is optionally selected from p18 R ４４ and each R ４４ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p18 represents an integer of 0, 1, 2, 3 or 4; (R ４５ ) ｐ１９ In formula (PBM-18), the 4-oxo-3,4-dihydroquinazoline ring is p19 R ４５ and each R ４５ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p19 represents an integer of 1, 2, 3, or 4; (R ４６ ) ｐ２０ In formula (PBM-19), the benzene ring is p20 R ４６ and each R ４６ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p20 represents an integer of 1, 2, 3, 4, or 5; R ４７ is halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; (R ４８ ) ｐ２１ In formula (PBM-20), the quinoline ring is p21 R ４８ and each R ４８ are the same or different and each independently represent a halogen, a cyano, １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p21 represents an integer of 1, 2, 3, or 4; (R ４９ ) ｐ２２ In formula (PBM-20), the benzene ring is p22 R ４９ and each R ４９ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p22 represents an integer of 2, 3 or 4; R in formula (PBM-21) ５０ represents —NHC(O)— or —C(O)NH—; R ５１ represents —NH— or ethynylene; (R ５２ ) ｐ２３ In formula (PBM-21), each benzene ring is arbitrarily selected from p23 R ５２ and each R ５２ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; each p23 is the same or different and independently represents an integer of 0, 1, 2, 3, or 4; Ring D in formula (PBM-21) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and (R ５３ ) ｐ２４ The ring D is optionally selected from p24 R ５３ and each R ５３ are the same or different and each independently represent an optionally substituted 5- to 15-membered heteroaryl, deuterium, halogen, hydroxy, 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 represents alkoxy; p24 represents an integer of 0, 1, 2, or 3; R in formula (PBM-22) ５４ , R ５５ , R ５６ and R ５７ where only one represents a bond, and the remaining three are the same or different and each independently represent hydrogen, halogen, or hydroxy, and ５４ , R ５５ , R ５６ and R ５７ When one of them represents a bond, the benzene ring or methylene in formula (PBM-22) connected by the bond is R ｆ directly connected to; In formula (PBM-22), the symbol " [Case 101A] " may be a bond in any spatial configuration (cis or trans, or E or Z); X in formula (PBM-23) １３ is -O- or -CH ２ represents -; (R ５８ ) ｐ２５ In formula (PBM-23), 1,2,3,4-tetrahydronaphthalene rings are p25 R ５８ and each R ５８ are the same or different and each independently represent hydrogen, hydroxy, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p25 represents an integer of 1, 2, 3, or 4; R ５９ and R ６０ Only one of them represents a bond, and the other is hydrogen, halogen, or C. １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl, where R ５９ and R ６０ When one of them represents a bond, the ring carbon atom in formula (PBM-23) connected by said bond is R ｆ directly connected to; Ring E in formula (PBM-24) represents a 5- to 20-membered monocyclic or bicyclic heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S; R ６２ is an optionally substituted 5- to 15-membered heteroaryl, an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen, hydroxy, 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 represents alkoxy; R ６１ is halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; R in formula (PBM-25) ６３ is an optionally substituted 5- to 15-membered heterocyclyl, deuterium, halogen, hydroxy, 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 represents alkoxy; R ６４ represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the heteroaryl is selected from the group consisting of deuterium, halogen, hydroxy, cyano, amino, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ optionally substituted with a substituent selected from the group consisting of alkoxy, or any combination thereof; (R ６５ ) ｐ２６ In formula (PBM-26), the isoquinoline ring is p26 R ６５ and each R ６５ are the same or different and each independently represent hydrogen, hydroxy, halogen, C １－６ Alkyl, C １－６ Alkoxy, —C(O)NH ２ , deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p26 represents an integer of 1, 2, 3, or 4; R ６６ are the same or different and each independently represent hydrogen, hydroxy, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; X in formula (PBM-27) １４ is N or CR ｂ２３ where R ｂ２３ represents hydrogen or halogen, and X １５ represents N or CH; R ６７ represents a bond, —C(O)NH—, or —NHC(O)—; R ６８ is halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６represents alkyl; R ６９ is hydrogen, C １－６ Alkyl, deuterated C １－６ Alkyl, halogenated C １－６ Alkyl or -C １－３ Alkylene-C ３－６ represents cycloalkyl; R ７０ is hydrogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; or R ６９ and R ７０ together with the corresponding nitrogen and carbon atoms attached thereto form an optionally substituted 5- to 7-membered nitrogen-containing heterocycle; R ７１ represents hydrogen or a bond, R ７２ represents hydrogen or a bond, where R ７１ and R ７２ is not simultaneously hydrogen, and R ７１ and R ７２ where only one represents a bond and the other represents hydrogen, and where R ７１ When represents a bond, R ７１ The ring carbon atom connected to R ｆ is connected directly to R ７２ When represents a bond, R ７２ The ring carbon atom connected to R ｆ directly connected to; R in formula (PBM-28) ７４ is a bond, C １－３ Alkylene or halogenated C １－３ represents alkylene; R ７３ is an optionally substituted C ３－６ Cycloalkyl, halogenated C ３－６ cycloalkyl, or optionally substituted C １－６ represents alkyl; R in formula (PBM-29) ７５ is C １－３ Alkylene or halogenated C １－３ represents alkylene; R ７６ is C １－６ Alkyl, deuterated C １－６ Alkyl, halogenated C １－６ alkyl, or optionally substituted C ３－６ represents cycloalkyl; R in formula (PBM-30) ７７ is C １－３ Alkylene or halogenated C １－３ represents alkylene; R ７８ is hydroxy, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R ７９ and R ８０ are the same or different and each independently represent hydrogen, optionally substituted C １－１０ Alkyl or optionally substituted C ３－６ represents cycloalkyl; R ８１ is hydrogen, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; X in formula (PBM-31) １６ is -S- or fragment [C103] where X １６ represents —S—, X in formula (PBM-31) １６ and heteroaryl containing a nitrogen atom is thiazolyl, and X １６ is a fragment [C103] When X in formula (PBM-31) represents １６ and heteroaryl containing a nitrogen atom is pyridyl; X １７ represents N or CH; R ８２ is hydrogen or optionally substituted C １－１０ represents alkyl; R ８３ is hydrogen, -C １－３ alkylene-represents an optionally substituted 4- to 10-membered heterocyclyl or an optionally substituted 4- to 10-membered heterocyclyl; R ８４ is hydroxy, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R in formula (PBM-32) ８５ and R ８６ are the same or different and each independently represent hydroxy, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R ８７ Ha-S(O) ２ NH ２ or -C(O)NH ２ represents; R in formula (PBM-33) ８８ is hydrogen, hydroxy, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R ８９ is C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; or R ８８ and R ８９ together with the corresponding carbon and nitrogen atoms attached thereto form an optionally substituted 4- to 6-membered heteroaromatic ring or an optionally substituted 4- to 6-membered heterocyclic ring; R ９０ is an optionally substituted C ３－６ Cycloalkyl, C １－６ Alkyl, deuterated C １－６ Alkyl, halogenated C １－６ represents alkyl or an optionally substituted 4- to 10-membered heterocyclyl; (R ９１ ) ｐ２７ In formula (PBM-33), the pyridin-2(1H)-one ring has p27 R ９１ and each R ９１ are the same or different and each independently represent hydroxy, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p27 represents an integer of 1, 2 or 3; Ring F in formula (PBM-33) represents an arylene or a 5- to 20-membered monocyclic or bicyclic heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S; (R ９２ ) ｐ２８ The ring F is optionally selected from p28 R ９２ and each R ９２ are the same or different and each independently represent deuterium, halogen, hydroxy, 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 represents alkoxy; p28 represents an integer of 0, 1, 2, 3 or 4; (R ９３ ) ｐ２９ R in formula (PBM-34) has p29 benzene rings ９３ and each R ９３ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p29 represents an integer of 1, 2, 3, 4, or 5; R ９４ is hydrogen, hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R ９５ is NR ｂ１５ R ｂ１６ where R ｂ１５ , R ｂ１６ 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 ３－６ represents cycloalkyl or an optionally substituted 4- to 8-membered heterocyclyl; X in formula (PBM-35) １８ , X １９ and X ２０ are the same or different and each independently represent CH or N, where X １８ , X １９ and X ２０ is not simultaneously N, and X １８ , X １９ , X ２０ and six-membered rings containing nitrogen atoms may further include halogen, cyano, C １－６ Alkyl, deuterated C １－６ Alkyl, halogenated C １－６ optionally substituted with 1 or 2 substituents selected from the group consisting of alkyl, aryl, arylsulfonyl ... X in formula (PBM-35) ２１ and X ２２ are the same or different and each independently represent C or N, where X ２１ and X ２２ is not simultaneously N; (R ９６ ) ｐ３０ R in formula (PBM-35) has p30 benzene rings ９６ and each R ９６ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p30 represents an integer of 1, 2, 3, 4, or 5; (R ９７ ) ｐ３１ In formula (PBM-35), the tetrahydropyrrole ring is optionally selected from p31 R ９７ and each R ９７ are the same or different and each independently represent hydrogen, hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p31 represents an integer of 0, 1, 2, 3, 4, 5, or 6; R ９８ , R ９９ , R １００ are the same or different and each independently represent hydrogen, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; X in formula (PBM-36) ２３ represents CH or N; R １０１ represents a bond or -S-; R １０２ represents a bond or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclyl; R １０３ is a bond, halogen, amino, C １－６ Alkyl, deuterated C １－６ Alkyl, halogenated C １－６ alkyl, or an optionally substituted 4- to 15-membered nitrogen-containing heterocyclyl; Here, R １０２ and R １０３ is not simultaneously a bond, and R １０２ and R １０３ where only one of R １０２ When represents a bond, R １０２ The ring carbon atom connected to R ｆ is connected directly to R １０３ When represents a bond, R １０３The ring carbon atom connected to R ｆ directly connected to; (R １０４ ) ｐ３２ In formula (PBM-36), the six-membered ring is optionally selected from p32 R １０４ and each R １０４ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p32 represents an integer of 0, 1, 2, 3, or 4; (R １０５ ) ｐ３３ The benzene ring in formula (PBM-37) may be any of p33 R １０５ and each R １０５ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p33 represents an integer of 1, 2, 3, or 4; (R １０６ ) ｐ３４ The phthalazinone ring in formula (PBM-37) may be optionally selected from p34 R １０６ and each R １０６ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p34 represents an integer of 0, 1, 2, 3, or 4; (R １０７ ) ｐ３５ In formula (PBM-38), the 2H-indazole ring is optionally selected from p35 R １０７ and each R １０７are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p35 represents an integer of 0, 1, 2 or 3; (R １０８ ) ｐ３６ The benzene ring in formula (PBM-38) may be any of p36 R １０８ and each R １０８ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p36 represents an integer of 0, 1, 2 or 3; (R １０９ ) ｐ３７ In formula (PBM-39), the 2H-indazole ring is optionally selected from p37 R １０９ and each R １０９ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p37 represents an integer of 0, 1, 2 or 3; (R １１０ ) ｐ３８ The benzene ring in formula (PBM-39) may be any of p38 R １１０ and each R １１０ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p38 represents an integer of 0, 1, 2 or 3; (R １１１ ) ｐ３９ The benzene ring in formula (PBM-40) may be any of p39 R １１１ and each R １１１ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p39 represents an integer of 0, 1, 2, 3 or 4; R １１２ , R １１３ , R １１４ are the same or different and each independently represent hydrogen, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R in formula (PBM-41) １１５ is hydrogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R １１６ , R １１７ , R １１８ are the same or different and each independently represent hydrogen, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; (R １１９ ) ｐ４０ The benzene ring in formula (PBM-41) is optionally p40 R １１９ and each R １１９ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p40 represents an integer of 0, 1, 2, 3, or 4; R in formula (PBM-42) １２０ , R １２１ are the same or different and each independently represent hydrogen, halogen, C １－３ Alkyl or halogenated C １－３ represents alkyl; R １２２ is a bond, hydrogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R １２３ is a structure of the formula: [C104] represents Here, R １２４ represents a bond or hydrogen; (R １２５ ) ｐ４１ The benzene ring is optionally １２５ and each R １２５ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl, and p41 represents an integer of 0, 1, 2, 3, or 4; or R １２３ is a structure of the formula: [C105] represents Here, (R １２６ ) ｐ４２ The benzene ring is optionally p42 R １２６ and each R １２６ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ alkyl, and p42 represents an integer of 0, 1, 2, 3, 4, or 5; Here, R １２２ and R １２４is not simultaneously a bond, and R １２２ and R １２４ where only one represents a bond, and R １２２ When represents a bond, R １２２ The nitrogen atom of the ring connected to is R ｆ is connected directly to R １２４ When represents a bond, R １２４ The ring carbon atom connected to R ｆ directly connected to; (R １２７ ) ｐ４３ The benzene ring in formula (PBM-43) may be any of p43 R １２７ and each R １２７ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p43 represents an integer of 0, 1, 2, 3, or 4; R in formula (PBM-45) １３１ is C １－６ Alkyl, deuterated C １－６ Alkyl, halogenated C １－６ represents alkyl or hydrogen; R １３２ is C １－６ Alkyl, deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally substituted C ３－６ cycloalkyl, optionally substituted 4- to 8-membered nitrogen-containing heterocyclyl or NR ｂ１７ R ｂ１８ where R ｂ１７ , R ｂ１８ are the same or different and each independently represent hydrogen, C １－６ Alkyl, deuterated C １－６ represents alkyl or an optionally substituted 4- to 8-membered heterocyclyl; (R １３３ ) ｐ４６ The benzene ring in formula (PBM-45) is optionally p46 R １３３and each R １３３ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p46 represents an integer of 0, 1, 2, 3, or 4; (R １３４ ) ｐ４７ The benzene ring in formula (PBM-46) is optionally p47 R １３４ and each R １３４ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p47 represents an integer of 0, 1, 2, 3 or 4; (R １３５ ) ｐ４８ The benzene ring in formula (PBM-46) is optionally p48 R １３５ and each R １３５ are the same or different and each independently represent hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p48 represents an integer of 0, 1, 2, 3 or 4; Ring H in formula (PBM-48) is C ６－１０ Arylene or C ５－１０ represents heteroarylene, (R １３７ ) ｐ４９ The ring H is optionally p49 R １３７ and each R １３７ are the same or different and each independently represent deuterium, halogen, hydroxy, cyano, amino, nitro, C １－６ Alkyl, halogenated C １－６Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ is alkoxy; p49 represents an integer of 0, 1, 2, 3 or 4; R １３６ represents an optionally substituted 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, and is selected from the group consisting of hydroxy, amino, cyano, halogen, C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkyl or halogenated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl; X in formula (PBM-49) ２４ , X ２５ , X ２６ each independently represents CH or N; R １３８ -C(O)NHR ｂ１９ , -NHC(O)-R ｂ１９ , -S(O) ２ NHR ｂ１９ , -NHS(O) ２ R ｂ１９ , -S(O) ２ R ｂ１９ or -P(O)(R ｂ１９ ) ２ where each R ｂ１９ are the same or different and each independently represent C １－６ Alkyl or deuterated C １－６ represents alkyl; R １３９ and R １４０ are each 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 represents alkoxy; (R １４１ ) ｐ５０ The benzene ring is optionally divided into p50 R １４１and each R １４１ are each 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 is alkoxy; p50 represents an integer of 0, 1, 2, 3, or 4; and (R １４３ ) ｐ５１ The benzene ring is optionally divided into p51 R １４３ and each R １４３ are each 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 is alkoxy; p51 represents an integer of 0, 1, 2, 3, 4, or 5; R １４２ is H, C １－６ Alkyl or halogenated C １－６ represents alkyl; (R １４４ ) ｐ５２ The quinazoline ring in formula (PBM-50) may be optionally selected from p52 R １４４ and each R １４４ are each 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 p52 represents an integer of 1, 2, or 3; R in formula (PBM-51) ｆ２ represents a bond, or R ｆ２ Ha-NH-R ｆ３ -C(O)-***, where *** is R ｆ１ represents the connection point with, and R ｆ３ is an optionally substituted C ３－８ represents cycloalkyl; (R １４５ ) ｐ５３ In formula (PBM-51), the 1H-pyrrolo[2,3-b]pyridine ring is optionally selected from p53 R １４５ and each R １４５ are each 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 p53 represents an integer of 0, 1, 2, 3, 4, or 5; (R １４６ ) ｐ５４ The pyridine ring in formula (PBM-51) is optionally selected from p54 R １４６ and each R １４６ are each independently cyano, halogen, hydroxy, 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 ｂ２５ R ｂ２６ where R ｂ２５ , R ｂ２６ 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 ３－６ represents cycloalkyl or an optionally substituted 4- to 8-membered heterocyclyl, and p54 represents an integer of 0, 1, 2, or 3; and (R １４７ ) ｐ５５ The benzene ring is optionally divided into p55 R １４７ and each R １４７ are each 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 p55 represents an integer of 0, 1, 2, 3, 4, or 5; R １４８ represents NHC(O) or C(O)NH; (R １４９ ) ｐ５６ In formula (PBM-52), the 1H-pyrazole ring is optionally selected from p56 R １４９ and each R １４９ are each 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 p56 represents an integer of 0, 1 or 2; and X in formula (PBM-53) ２７ represents N or CH; R １５０ represents a bond or an optionally substituted methylene (e.g., methylene substituted with a halogen); Ring I is C ６－１０ (R １５１ ) ｐ５７ wherein the ring I is optionally selected from p57 R １５１ and each R １５１ are the same or different and each independently represent a deuterium atom, a halogen atom, a hydroxyl group, a cyano group, an amino group, a nitro group, an oxo group, 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 p57 represents an integer of 0, 1, 2, 3, or 4; (R １５２ ) ｐ５８ represents the X in formula (PBM-53). ２７ A six-membered ring containing p58 R １５２and each R １５２ are each independently a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ p58 represents an integer of 0, 1 or 2; (R １５３ ) ｐ５９ The benzene ring in formula (PBM-53) may be any of p59 R １５３ and each R １５３ are the same or different and each independently represent a halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ alkyl, and p15 represents an integer of 0, 1, 2, 3, or 4; X in formula (PBM-54) ２８ , X ２９ and X ３０ each independently represents N or CH; (R １５４ ) ｐ６０ In formula (PBM-54), the naphthyl is optionally selected from p60 R １５４ and each R １５４ are each independently a halogen, a hydroxy, an amino, a mercapto, a nitro, a cyano, ２－６ Alkynyl, C ２－６ Alkenyl, C １－６ Alkoxy, C １－６ Alkyl or halogenated C １－６ alkyl, and p60 represents 0, 1, 2, 3, 4, 5, 6, or 7; R １５５ is an optionally substituted C ３－１１ cycloalkyl or optionally substituted 4-15 membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O and S; R １５６ is hydrogen, halogen, hydroxy, cyano, amino, mercapto, nitro, C ２－６ Alkynyl, C ２－６ Alkenyl, C １－６Alkoxy, C １－６ Alkyl or halogenated C １－６ represents alkyl; R in formula (PBM-55) １５７ is C ６－１０ aryl, or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein ６－１０ The aryl and heteroaryl are each selected from halogen, hydroxy, 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 optionally substituted with one or more substituents selected from the group consisting of alkoxy; R １５８ represents a 5- to 15-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein said 5- to 15-membered heteroaryl is selected from halogen, hydroxy, 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 optionally substituted with one or more substituents selected from the group consisting of alkoxy; (R １５９ ) ｐ６１ In formula (PBM-55), the isoindolinone ring is １５９ and each R １５９ are the same or different and each independently represent halogen, hydroxy, 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 represents alkoxy, and p61 represents an integer of 0, 1, 2, or 3; X in formula (PBM-56) ３１represents N or CH; (R １６０ ) ｐ６２ is X in formula (PBM-56) ３１ The aromatic ring containing p62 R １６０ and each R １６０ are the same or different and each independently represent halogen, hydroxy, 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 p62 represents an integer of 0, 1, 2, 3, or 4; and Ring J represents a 5- to 15-membered heteroarylene; (R １６１ ) ｐ６３ The ring J is optionally selected from p63 R １６１ and each R １６１ are the same or different and each independently represent halogen, hydroxy, mercapto, cyano, amino, nitro, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, hydroxy-substituted C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ 13. The compound of formula (III) of claim 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein p63 represents alkoxy and p63 represents an integer of 0, 1, 2 or 3.

15. The PBM has the structure: [C741] [C742] [C743] [C744] [C745] [C746] [C747] [C748] [C749] [C750] [C751] [C752] [C753] [C754] [C755] [C756] [C757] [C758] [C759] [C760] [C761] [C762] [C763] [C764] [C765] [C766] 3. The compound of formula (II) of claim 2, wherein:

16. The R ｆ represents a bond, —O—, —NHC(O)—*, —C(O)NH—*, or —NH—, or R ｆ is a structure of the formula: -N(R ｇ )-,-NHC(O)-C １－６ Alkylene-W ５ -*, -NHC(O)-C ２－６ Alkenylene-W ５ -*, -C(O)NH-C １－６ Alkylene-W ５-*, -C(O)NH-C ２－６ Alkenylene-W ５ -*, -NHC(O)-W ５ -*, -C(O)NH-W ５ -*, -O-C １－６ Alkylene-W ５ -*, -O-C ２－６ Alkenylene-W ５ -*, -O-W ５ -*, -O-C １－６ Alkylene-N(R ｉ ) - *, -O-C ２－６ Alkenylene-N(R ｉ ) - *, -N (R ｇ )-C １－６ Alkylene-N(R ｉ ) - *, -N (R ｇ )-C ２－６ Alkenylene-N(R ｉ ) - *, - W ５ -, -W ５ -N(R ｇ ) - *, -N (R ｇ )-W ５ -*, -N(R ｇ )-W ５ -N(R ｉ ) - *, - C １－６ Alkylene-W ５ -*, -C ２－６ Alkenylene-W ５ -*, -C １－６ Alkylene-C(O)-W ５ -*, -C ２－６ Alkenylene-C(O)-W ５ -*, -C(O)-W ５ -*, -C １－６ Alkylene-C(O)NH-C １－６ Alkylene-W ５ -*, -C １－６ Alkylene-C(O)NH-C ２－６ Alkenylene-W ５ -*, -C ２－６ Alkenylene-C(O)NH-C １－６ Alkylene-W ５ -*, -C ２－６ Alkenylene-C(O)NH-C ２－６ Alkenylene-W ５-*, -C １－６ Alkylene-NHC(O)-C １－６ Alkylene-W ５ -*, -C １－６ Alkylene-NHC(O)-C ２－６ Alkenylene-W ５ -*, -C ２－６ Alkenylene-NHC(O)-C １－６ Alkylene-W ５ -*, -C ２－６ Alkenylene-NHC(O)-C ２－６ Alkenylene-W ５ -*, -C １－６ Alkylene -C(O)NH-*, -C ２－６ Alkenylene -C(O)NH-*, -C １－６ Alkylene -NHC(O)-*, -C ２－６ Alkenylene-NHC(O)-*, -C １－６ Alkylene-, -C ２－６ Alkenylene-, -C １－６ Alkylene-N(R ｉ ) - *, - C ２－６ Alkenylene-N(R ｉ )-*, [C9] represents Here, R ｇ and R ｉ are each independently hydrogen or C １－６ represents alkyl, and １－６ Alkylene and the C ２－６ Alkenylene is a group selected from the group consisting of halogen, hydroxy, mercapto, cyano, amino, nitro, C １－６ Alkyl, halogenated C １－３ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with one or more substituents selected from the group consisting of alkoxy, or any combination thereof; Here, the group W ５ is a structure of the formula: [C272] represents Here, each ring W ６are the same or different and each independently represent a nitrogen-containing heterocyclylene; t1 represents an integer of 1 or 2; (R ａ２ ) ｍ２ is each ring W ６ There are m2 R ａ２ represents that the group is optionally substituted with a group, and each R ａ２ are independently deuterium, optionally deuterated C １－６ Alkyl, optionally halogenated C １－６ Alkyl, C １－６ Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １２ａ -R １１ａ -, where R １１ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １２ａ is halogen, R １３ａ R １４ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １３ａ and R １４ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl, and １－６ Alkylene and the C ２－６ Alkenylene is a group selected from the group consisting of halogen, hydroxy, mercapto, cyano, amino, nitro, C １－６ Alkyl, halogenated C １－３ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with one or more substituents selected from the group consisting of alkoxy or any combination thereof, and m2 represents an integer of 0-20; Each ring W ７ are the same or different and each independently represent a nitrogen-containing heterocyclylene, arylene, or heteroarylene; t2 represents an integer of 0 or 1; (R ａ３ ) ｍ３ is each ring W ７ are independently m3 R ａ３ represents that the group is optionally substituted with a group, and each R ａ３ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １６ａ -R １５ａ -, where R １５ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １６ａ is halogen, R １７ａ R １８ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １７ａ and R １８ａ are the same or different and each independently represent hydrogen or C １－３ alkyl, and m3 represents an integer of 0-20; and 13. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to claim 12, wherein the symbol * represents the point of attachment to LIN.

17. R ｆ Ha-W ７ -R ｈ -W ５ -*, where R ｈ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ represents alkenylene, W ５ and W ７ 16. A compound of formula (II) according to claim 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein:

18. The W ５ is a structure of the formula: [C767] represents Here, each ring W ６ are the same or different and each independently represent a 4- to 20-membered nitrogen-containing heterocyclylene, for example, Piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene, diazacyclooctylene, azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo 2-azaspiro[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]undecanylene, 8-azaspiro[4.5]decanylene, 2-oxa-8-azaspiro[4.5]decanylene, or 3-methyl-2-oxa-8-azaspiro[4.5]decanylene, or [C768] [C769] [C770] [C771] [C772] [C773] [C279] represents; t1 represents an integer of 1 or 2, (R ａ２ ) ｍ２ is each ring W ６ There are m2 R ａ２ represents that the group is optionally substituted with a group, and each R ａ２ are independently deuterium, optionally deuterated C １－６ Alkyl, optionally halogenated C １－６ Alkyl, C １－６ Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １２ａ -R １１ａ -, where R １１ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １２ａ is halogen, R １３ａ R １４ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １３ａ and R １４ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl, and １－６ Alkylene and the C ２－６ Alkenylene is a group selected from the group consisting of halogen, hydroxy, mercapto, cyano, amino, nitro, C １－６ Alkyl, halogenated C １－３ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with one or more substituents selected from the group consisting of alkoxy or any combination thereof, and m2 represents an integer of 0-20; Each ring W ７ are the same or different and each independently represent a 4- to 15-membered nitrogen-containing heterocyclylene, a 6- to 10-membered arylene, or a 5- to 10-membered heteroarylene, for example: Piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene, diazacyclooctylene, 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]undecanylene, 8-azaspiro[4.5]decanylene, 2-oxa-8-azaspiro[4.5]decanylene, 3-methyl-2-oxa-8-azaspiro[4.5]decanylene, phenylene, naphthylene, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene , isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, 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, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene, or imidazo[2,1-b]thiazolylene, or [C774] [C775] [C776] [C777] [C778] [C779] [C40] represents t2 represents an integer of 0 or 1, (R ａ３ ) ｍ３ is each ring W ７ are independently m3 R ａ３ represents that the group is optionally substituted with a group, and each R ａ３ are independently deuterium, optionally deuterated C １－６ Alkyl, C １－６ Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, or R １６ａ -R １５ａ -, where R １５ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １６ａ is halogen, R １７ａ R １８ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １７ａ and R １８ａ are the same or different and each independently represent hydrogen or C １－３ alkyl, and m3 represents an integer of 0-20; and 18. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to any one of claims 12 or 16-17, wherein the symbol * represents the point of attachment to LIN.

19. The W ５ is the following group: [C780] [C781] [C782] [C783] [C784] [C785] [C786] [C787] [C788] [C789] [C790] [C791] [C792] [C793] [C794] [C795] [C796] [C797] [C798] [C799] [800] [chemical 801] [chemical 802] [chemical 803] [chemical 804] [chemical 805] [C313] represents; wherein the group may further comprise deuterium, optionally 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, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ Cycloalkyl, R １２ａ -R １１ａ -, or any combination thereof, wherein R １１ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １２ａ is halogen, R １３ａ R １４ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １３ａ and R １４ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; and 18. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to claim 16 or 17, wherein the symbol * represents the point of attachment to LIN.

20. The R ｆ is the following group: Bond, -O-, -NHC(O)-*, -C(O)NH-*, -NH-, -N(CH ３ ) -, -N(CH ３ )-(CH ２ ) ２ -N(CH ３ ) - *, -N(CH ３ )-(CH ２ ) ３ -N(CH ３ )-*, -NH-(CH ２ ) ２ -N(CH ３ ) - *, -N(CH ３ )-(CH ２ ) ３ -NH-*, -CH ２ -NHC(O)-*, -CH ２ -C(O)NH-*, -CH ２ -NH-*, -O-(CH ２ ) ２ -N(CH ３ )-*, -O-(CH ２ ) ２ -NH-* or -CH ２ -N(CH ３ ) - *, or [chemical 806] [chemical 807] [C316] [chemical 808] [chemical 809] [chemical 810] [chemical 811] [chemical 812] [chemical 813] [chemical 814] [chemical 815] [chemical 816] [chemical 817] [chemical 818] [chemical 819] [chemical 820] [C330] [chemical 821] [chemical 822] [chemical 823] [chemical 824] [chemical 825] [chemical 826] [chemical 827] [chemical 828] [chemical 829] [chemical 830] [chemical 831] [chemical 832] [chemical 833] [chemical 834] [chemical 835] [chemical 836] [chemical 837] [chemical 838] [chemical 839] [chemical 840] [chemical 841] [chemical 842] [chemical 843] [chemical 844] [chemical 845] [chemical 846] [chemical 847] [chemical 848] [C359] represents; wherein the group may further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally halogenated C １－６ Alkyl, C １－６ Alkoxy, halogen, amino, hydroxy, mercapto, cyano, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ Cycloalkyl, R １２ａ -R １１ａ -, or any combination thereof, wherein R １１ａ is an optionally substituted C １－６ Alkylene or optionally substituted C ２－６ alkenylene, and R １２ａ is halogen, R １３ａR １４ａ represents N-, hydroxy, carboxy, ethynyl, or vinyl, where R １３ａ and R １４ａ are the same or different and each independently represent hydrogen or C １－３ represents alkyl; and 18. A compound of formula (III) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to any one of claims 12 or 16-17, wherein the symbol * represents the point of attachment to LIN.

21. The ULM has a structure of the following formula (ULM-1), (ULM-2), (ULM-3), (ULM-4), (ULM-5), (ULM-6), (ULM-7), (ULM-8), (ULM-9), (ULM-10), (ULM-11), or (ULM-12): [chemical 849] [chemical 850] [C362] represents where: A is CO, CH ２ or CD ２ represents; R １ , R ２ , R ３ and R ４ are the same or different and each independently represent hydrogen, deuterium, halogen, or optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy or halogenated C １－６ represents alkyl; (R ｂ ) ｎ The benzene ring is optionally connected to n R ｂ and each R ｂ are the same or different and each independently represent deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, optionally substituted C ３－６ Cycloalkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; and 13. The compound of formula (II) according to claim 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein n represents an integer of 0, 1, 2 or 3.

22. The ULM has a structure of the following formula (ULM-13), (ULM-14), (ULM-15), (ULM-16), (ULM-17), (ULM-18), (ULM-19), (ULM-20), (ULM-21), (ULM-22), (ULM-23), or (ULM-24): [chemical 851] [chemical 852] [C365] represents Here, the A, (R ｂ ) ｎ , R ｂ 21. The compound of formula (II) according to claim 20, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein:

23. The ULM has the structure of the following formula: [C366] [C367] [C368] [C369] [C370] [C371] [C372] [C373] [C374] [C375] 【Chemical 376】 【Chemical 377】 【Chemical 378】 【Chemical 379】 【Chemical 380】 【Chemical 381】 【Chemical 382】 【Chemical 383】 【Chemical 384】 【Chemical 385】 【Chemical 386】 【Chemical 387】 【Chemical 388】 【Chemical 389】 【Chemical 390】 【Chemical 391】 【Chemical 392】 【Chemical 393】 【Chemical 394】 【Chemical 395】 【Chemical 396】 【Chemical 397】 【Chemical 398】 【Chemical 399】 【Chemical 400】 【Chemical 401】 【Chemical 402】 【Chemical 403】 【Chemical 404】 【Chemical 405】 【Chemical 406】 【Chemical 407】 【Chemical 408】 【Chemical 409】 【Chemical 410】 【Chemical 411】 【Chemical 412】 【Chemical 413】 【Chemical 414】 【Chemical 415】 【Chemical 416】 【Chemical 417】 【Chemical 418】 【Chemical 419】 【Chemical 420】 【Chemical 421】 【Chemical 422】 【Chemical 423】 【Chemical 424】 【Chemical 425】 【Chemical 426】 ​​​​​​​​​​​​​​​​​​​​​​​​​​​​ [C437] [C438] [C439] 21. The compound of formula (III) of claim 20, wherein:

24. The LIN has the structure of the following formula: [C8] represents; Here, R ５ and R ６ are the same or different and each independently: Hydrogen, fluorine, chlorine, bromine, iodine, optionally substituted methyl, or optionally substituted straight or branched chain C ２－３０ represents alkyl, wherein the linear or branched chain C ２－３０ The alkyl carbon backbone may contain one or more groups R ｃ and / or one or more groups R ｄ or one or more groups R ｃ and R ｄ and any combination of the groups R ｃ , R ｄ or group R ｃ and R ｄ The combination of R ｃ is O, N (R ｅ ), C(O), C(O)O, S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , OC(O), C(O)N(R ｅ ), N(R ｅ ) C(O), or N(R ｅ )C(O)N(R ｅ ) wherein each R ｅ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ Two or more groups R in the carbon backbone of the alkyl ｃ When inserted, each group R ｃ are not directly connected to each other; ｄ is cycloalkylene (e.g., C ３－２０ cycloalkylene), arylene (e.g., C ３－２０ arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 4- to 20-membered heteroarylene), alkynylene (e.g., C ２－６ alkynylene), alkenylene (e.g., C ２－６ alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene are each independently selected from the group consisting of: deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; and The hydrogen of the methyl and the C ２－３０ One or more CH of alkyl ２ The hydrogen of may further be deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ 23. A compound of formula (II) according to any one of claims 12 to 22, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- or any combination thereof.

25. R ５ and R ６ are the same or different and each independently represent hydrogen, fluorine, chlorine, bromine or iodine, or a structure of the following formula: -C １－３０ Alkyl; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｃ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｃ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ - (R ｃ -(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｃ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ - (R ｃ -(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ - (R ｃ -(C(R ａ１０ ) (R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｄ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｄ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(R ｄ -(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｄ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(R ｄ -(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(R ｄ -(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｃ -R ｄ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -CH ３ ; -(C(R ａ４ )(R ａ５ )) ｎ１ -(R ｃ -(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(R ｄ-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｄ -R ｃ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; or -(C(R ａ４ ) (R ａ５ )) ｎ１ - (R ｄ -(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ - (R ｃ -(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ represents —H; where each group R ｃ is O, N (R ｅ ), C(O), C(O)O, OC(O), S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , C(O)N(R ｅ ), N(R ｅ ) C(O), or N(R ｅ )C(O)N(R ｅ ), wherein each R ｅ are independently H or C １－６ represents alkyl; each group R ｄ is cycloalkylene (e.g., C ３－２０ cycloalkylene), arylene (e.g., C ３－２０ arylene), heterocyclylene (e.g., 4- to 20-membered heterocyclylene), heteroarylene (e.g., 4- to 20-membered heteroarylene), alkynylene (e.g., C ２－６ alkynylene), alkenylene (e.g., C ２－６alkenylene), or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene are each independently selected from the group consisting of: deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; Said C １－３０ One or more CH of alkyl ２ The hydrogen of may further be deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; R ａ４ , R ａ５ , R ａ６ , R ａ７ , R ａ８ , R ａ９ , R ａ１０ and R ａ１１ are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)- or optionally deuterated C １－６ represents alkyl-C(O)NH—; and 23. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to any one of claims 12 to 22, wherein n1, n2, n3, n4, m4, m5, m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

26. R ５ and R ６ are the same or different and each independently represent a structure of the formula: -(C(R ａ４ ) (R ａ５ )) ｎ１ -(O-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(O-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(O-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -(O(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(N(R ｅ )-(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(C(O)N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(C(O)N(R ｅ )-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(C(O)N(R ｅ )-(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -(N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ ) ｍ４ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ５ -(O-(C(R ａ１０ )(R ａ１１ )) ｎ４ ) ｍ６ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -N(R ｅ )C(O)-(C(R ａ６ )(R ａ７ )) ｎ２ -(O-(C(R ａ８ )(R ａ９ )) ｎ３ ) ｍ４ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -N(R ｅ )C(O)N(R ｅ )-(C(R ａ６ )(R ａ７ )) ｎ２ -H; -(C(R ａ４ )(R ａ５ )) ｎ１ -C(O)-(C(R ａ６ ) (R ａ７ )) ｎ２ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(arylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(arylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -arylene-(C(R ａ８ ) (R ａ９ )) ｎ３ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heterocyclylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heterocyclylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(heterocyclylene-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heteroarylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(heteroarylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(heteroarylene-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ -H; -(C(R ａ４ ) (R ａ５ )) ｎ１ -(cycloalkylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -H; or -(C(R ａ４ ) (R ａ５ )) ｎ１ -(cycloalkylene-(C(R ａ６ ) (R ａ７ )) ｎ２ ) ｍ４ -(cycloalkylene-(C(R ａ８ ) (R ａ９ )) ｎ３ ) ｍ５ represents —H; Here, each R ｅ are independently H or C １－６ represents alkyl; The cycloalkylene, the arylene, the heterocyclylene and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; R ａ４ , R ａ５ , R ａ６ , R ａ７ , R ａ８ , R ａ９ , R ａ１０ and R ａ１１ are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)- or optionally deuterated C １－６ represents alkyl-C(O)NH—; and 13. The compound of formula (II) of claim 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein n1, n2, n3, n4, m4, m5, and m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

27. R ５ and R ６ are the same or different and each independently represent one of the following groups: H, fluorine, chlorine, bromine, iodine, -CH ３ , -CH ２ -CH ３ , -(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -CH ３ , -(CH ２ ) ４ -CH ３ , -(CH ２ ) ５ -CH ３ , -(CH ２ ) ６ -CH ３ , -(CH ２ ) ７ -CH ３ , -(CH ２ ) ８-CH ３ 、-(CH ２ ) ９ -CH ３ 、-(CH ２ ) １０ -CH ３ 、-(CH ２ ) １１ -CH ３ 、-(CH ２ ) １２ -CH ３ 、-(CH ２ ) １３ -CH ３ 、-(CH ２ ) １４ -CH ３ 、-(CH ２ ) １５ -CH ３ 、-(CH ２ ) １６ -CH ３ 、-(CH ２ ) １７ -CH ３ 、-(CH ２ ) １８ -CH ３ 、-(CH ２ ) １９ -CH ３ 、-(CH ２ ) ２０ -CH ３ 、-(CH ２ ) ２１ -CH ３ 、-(CH ２ ) ２２ -CH ３ 、-(CH ２ ) ２５ -CH ３ 、-(CH ２ ) ２９ -CH ３ ;-CH ２ -O-CH ３ 、-CH ２ -O-CH ２ -CH ３ 、-CH ２ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ３-CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ６ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ７ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ８ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) ９ -CH ３ 、-(CH ２ ) １ -O-(CH ２ ) １０ -CH ３ 、-(CH ２ ) ２ -O-CH ３ 、-(CH ２ ) ２ -O-CH ２ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ７ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ８ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) １０ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) １１ -CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) １２ -CH ３ 、-(CH ２ ) ３ -O-CH ３ 、-(CH ２ ) ３ -O-CH ２ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ７ -CH ３ 、-(CH ２ ) ４ -O-CH ３ 、-(CH ２ ) ４ -O-CH ２ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ４ -O-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ５ -O-CH ３ 、-(CH ２ ) ５ -O-CH ２ -CH ３ 、-(CH ２ ) ５ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ５ -O-(CH ２ ) ３ -CH ３、-(CH ２ ) ５ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ５ -O-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ６ -O-CH ３ 、-(CH ２ ) ６ -O-CH ２ -CH ３ 、-(CH ２ ) ６ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ６ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ６ -O-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ７ -O-CH ３ 、-(CH ２ ) ７ -O-CH ２ -CH ３ 、-(CH ２ ) ７ -O-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ７ -O-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ８ -O-CH ３ 、-(CH ２ ) ８ -O-CH ２ -CH ３ 、-(CH ２ ) ８ -O-(CH ２ ) ２ -CH ３、-CH(CH ３ )-O-CH ３ 、-CH(CH ３ )-O-CH ２ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ２ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ３ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ４ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ５ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ６ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ７ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ８ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) ９ -CH ３ 、-CH(CH ３ )-O-(CH ２ ) １０ -CH ３ 、-CH ２ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) １ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ２ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ３ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ４ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ５ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ６ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ７ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ８ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) ９ -OCH ３ 、-CH ２ -(O(CH ２ ) ２ ) １０ -OCH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) １ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ２ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ３ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ４ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ５ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ６ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ７ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ８ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) ９ -OCH ２ CH ３ ,-(EH ２ ) ４ -(O(CH ２ ) ２ ) １０ -OCH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ５ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ６ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ７ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ８ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ９ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) １０ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ５ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ６ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ７ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ２ -(O(CH ２ ) ３ ) ８ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３-(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ５ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ６ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ７ -OCH ２ CH ２ CH ３ ,-(EH ２ ) ３ -(O(CH ２ ) ３ ) ８ -OCH ２ CH ２ CH ３ 、-CH ２ -O-(CH) ２ ) ２ -O-(CH ２ ) ２ -CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ２ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ２ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) １ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ２ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３-(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ３ -OCH ２ CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ４ -OCH ２ CH ２ CH ３ 、-CH ２ -O-(CH ２ ) ３ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) １ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ２ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ３ -O-CH ２ CH ３ 、-CH ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ４ -O-CH ２ CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) １ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ２ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ４ -O-CH ２ CH ３ 、-(CH ２ ) ３ -O-(CH ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) １ -O-CH ２ CH ３ 、-(CH ２) ３ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ２ -O-CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ３ -O-CH ２ CH ３ 、-(CH ２ ) ３ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ４ -O-CH ２ CH ３ 、-CH ２ -O-(CH ２ ) ２ -O-CH ３ 、-(CH ２ ) ２ -O-(CH ２ ) ２ -O-CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -O-(CH ２ ) ２ CH ３ 、-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ４ CH ３ 、-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ５ CH ３ 、-(CH ２ ) １ -N(R ｅ )-CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ４ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ５ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ６ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ７ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ８ -CH ３ 、-(CH ２ ) １ -N(R ｅ )-(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ５ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ６ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ７ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ８ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) １０ -CH ３ 、-(CH ２ ) ２ -N(R ｅ )-(CH ２ ) １１ -CH ３ 、-(CH ２ ) ３ -N(R ｅ )-CH ３ 、-(CH ２ ) ３ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ３ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ４ -N(R ｅ )-CH ３ 、-(CH ２ ) ４ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ４ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ４ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-CH ３、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ -N(R ｅ )-(CH ２ ) ４ -CH ３ 、-(CH ２ ) ６ -N(R ｅ )-CH ３ 、-(CH ２ ) ６ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ６ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ７ -N(R ｅ )-CH ３ 、-(CH ２ ) ７ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ７ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-(CH ２ ) ８ -N(R ｅ )-CH ３ 、-(CH ２ ) ８ -N(R ｅ )-(CH ２ ) １ -CH ３ 、-(CH ２ ) ８ -N(R ｅ )-(CH ２ ) ２ -CH ３ 、-CH(CH ３ )-N(R ｅ )-CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) １ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ２ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ３ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ４ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ５ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ６ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ７ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ８ -CH ３ 、-CH(CH ３ )-N(R ｅ )-(CH ２ ) ９ -CH ３、-CH ２ C(O)NHCH ３ 、-(CH ２ ) ２ C(O)NHCH ２ CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ４ -CH ３ 、-(CH ２ ) ３ C(O)NH(CH ２ ) ２ -CH ３ 、-(CH ２ ) ３ C(O)NH(CH ２ ) ３ -CH ３ 、-(CH ２ ) ４ C(O)NH(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ C(O)NH(CH ２ ) ４ -CH ３ 、-(CH ２ ) ６ C(O)NH(CH ２ ) ６ -CH ３ 、-(CH ２ ) ６ C(O)NH(CH ２ ) ５ -CH ３ 、-(CH ２ ) ７ C(O)NH(CH ２ ) ６ -CH ３ 、-(CH ２ ) ８ C(O)NH(CH ２ ) ７ -CH ３ 、U-(CH ２ ) ９ C(O)NH(CH ２ ) ８ -CH ３ 、-(CH ２ ) １０ C(O)NH(CH ２ ) ９ -CH ３ 、-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -O-CH ２ -CH ３ 、-CH ２ NHC( O)CH ３ 、-(CH ２ ) ２ NHC(O)CH ２ CH ３ 、-(CH ２ ) ２ NHC(O)(CH ２ ) ２ -CH ３ 、-(CH ２ ) ２ NHC(O)(CH ２ ) ３ -CH ３ 、-(CH ２ ) ２ NHC(O)(CH ２ ) ４ -CH ３ 、-(CH ２ ) ３ NHC(O)(CH ２ ) ２ -CH ３ 、-(CH ２ ) ３ NHC(O)(CH ２ ) ３ -CH ３ 、-(CH ２ ) ４ NHC(O)(CH ２ ) ３ -CH ３ 、-(CH ２ ) ５ NHC(O)(CH ２ ) ４ -CH ３ 、-(CH ２ ) ６ NHC(O)(CH ２ ) ６ -CH ３ 、-(CH ２ ) ６ NHC(O)(CH ２ ) ５ -CH ３ 、-(CH ２ ) ７ NHC(O)(CH ２ ) ６ -CH ３ 、-(CH ２ ) ８ NHC(O)(CH ２ ) ７ -CH ３ 、-(CH ２ ) ９ NHC(O)(CH ２ ) ８ -CH ３ 、-(CH ２ ) １０ NHC(O)(CH ２ ) ９ -CH ３ 、-(CH ２ ) ４ NHC(O)(CH ２ ) ７ -CH ３ 、-(CH ２ ) ２ NHC(O)(CH ２ ) ２ -O-CH ２ -CH ３ 、-(CH ２ ) ４ NHC(O)CH ３ 、-CH ２ -ピペリジニレン-CH ３ 、-CH ２ -ピペリジニレン-CH ２ -CH ３ 、-CH ２ -ピペリジニレン-(CH ２ ) ２ -CH ３ 、-CH ２ -ピペリジニレン-(CH ２ ) ３ -CH ３ 、-CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ２ -piperidinylene-CH ３ , -(CH ２ ) ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ３ -piperidinylene-CH ３ , -(CH ２ ) ３ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ３ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ４ -piperidinylene-CH ３ , -(CH ２ ) ４ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ４ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ５ -piperidinylene-CH ３ , -(CH ２ ) ５ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ５ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ６ -piperidinylene-CH ３ , -(CH ２ ) ６ -piperidinylene-CH ２-CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ６ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ７ -piperidinylene-CH ３ , -(CH ２ ) ７ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ７ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ７ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ７ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ８ -piperidinylene-CH ３ , -(CH ２) ８ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ８ -piperidinylene-(CH ２ ) ７ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -CH ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-CH ２ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -CH ２ -N(R ｅ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , - ( CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ２ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ４ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ５ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ５ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ６ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ６ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ７ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ７ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-CH ２ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ８ -N(R ｅ )-CH ２ -piperidinylene-(CH ２ ) ７ -CH ３ , -CH ２ -piperazinylene-CH ３ , -CH ２ -piperazinylene-CH ２ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ２ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ３ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ４ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ５ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ６ -CH ３ , -CH ２ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ２ -piperazinylene-CH ３ , -(CH ２ ) ２ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ２ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ３ -piperazinylene-CH ３ , -(CH ２ ) ３ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ３ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ４ -piperazinylene-CH ３ , -(CH ２ ) ４ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ４ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ５ -piperazinylene-CH ３ , -(CH ２ ) ５ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ５ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ６ -piperazinylene-CH ３ , -(CH ２ ) ６ -piperazinylene-CH ２-CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ６ -CH ３ , -(CH ２ ) ６ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ７ -piperazinylene-CH ３ , -(CH ２ ) ７ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ７ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ７ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ７ -piperazinylene-(CH ２ ) ７ -CH ３ , -(CH ２ ) ８ -piperazinylene-CH ３ , -(CH ２) ８ -piperazinylene-CH ２ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ２ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ３ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ４ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ５ -CH ３ , -(CH ２ ) ８ -piperazinylene-(CH ２ ) ６ -CH ３ , or -(CH ２ ) ８ -piperazinylene-(CH ２ ) ７ -CH ３ represents; wherein the piperidinylene and the piperazinylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto, nitro, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; CH in the above group ３and one or more CH ２ The hydrogen of may further be selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; Each R ｅ are independently H or C １－６ represents alkyl; and 13. The compound of formula (II) of claim 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein n1, n2, n3, n4, m4, m5, and m6 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

28. Said -R ｆ -LIN- is the following group: -CH ２ --, --O-CH ２ -**, -NHC(O)-CH ２ -**, -C(O)NH-CH ２ -**, -NH-CH ２ -**, -N(CH ３ )-CH ２ -**, -N(CH ３ )-(CH ２ ) ２ -N(CH ３ )-CH ２ -**, -N(CH ３ )-(CH ２ ) ３ -N(CH ３ )-CH ２ -**, -NH-(CH ２ ) ２ -N(CH ３ )-CH ２ -**, -N(CH ３ )-(CH ２ ) ３ -NH-CH ２ -**, -CH ２ -NHC(O)-CH ２ -**, -CH ２ -C(O)NH-CH ２ -**, -CH ２ -NH-CH ２ -**, -O-(CH ２ ) ２ -N(CH ３ )-CH ２ -**, -O-(CH ２ ) ２ -NH-CH ２ -** or -CH ２ -N(CH ３ ) -CH ２ -**, or [C440] [C441] [C442] [C443] [C444] [C445] [C446] [C447] [C448] [C449] [C450] [C451] [C452] [C453] [C454] [C455] [C456] 【Chemical 457】 【Chemical 458】 【Chemical 459】 【Chemical 460】 【Chemical 461】 【Chemical 462】 【Chemical 463】 【Chemical 464】 【Chemical 465】 【Chemical 466】 【Chemical 467】 【Chemical 468】 【Chemical 469】 【Chemical 470】 [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ [C853A] represents; wherein the group may further comprise deuterium, optionally 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, carboxy, C ２－６ Alkynyl, C ２－６ Alkenyl, optionally deuterated C ３－６ cycloalkyl, cyclohexane ...

28. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to any one of claims 12 to 27, wherein the symbol ** represents the point of attachment to the ULM.

29. The following formulas (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (II-8), (II-9), (II-10), (II-11), (II-12), (II-13), (II-14), (II-15), (II-16), (II-17), (II-18), (II-19), (II-20), (II-21), (II-22), (II-23), (II-24), (II-25), (II-26), (II-27), (II-28), (II-29), (II-30), (II-31), (II-32), (II-33), (II-34), Formula (II-35), Formula (II-36), Formula (II-37), Formula (II-38), Formula (II-39), Formula (II-40), Formula (II-41), Formula (II-42), Formula (II-43), Formula (II-44), Formula (II-45), Formula (II-46), Formula (II-47), Formula (II-48), Formula (II-49), Formula (II-50), Formula (II-51), Formula (II-52), Formula (II-53), Formula (II-55), Formula (II-56), Formula (II-57), Formula (II-58), Formula (II-59), Formula (II-60), Formula (II-61), Formula (II-62), Formula (II-63), Formula (II-64), Formula (II-65), or Formula (II-66): [C488] [C489] [C490] [C491] [C492] [C493] [C494] [C495] [C496] [C497] [C498] [C499] [500] [501] [502] [C503] [504] [C505] [506] [507] [508] [C509] [C510] [C511] [C512] [C513] [514] [C515] [516] [C517] [518] [chemical 854] [chemical 855] Also represented by; Here, A and R １ , R ２ , R ３ , R ４ , (R ｂ ) ｎ , LIN, R ｆ , (R １ ) ｐ１ , (R ２ ) ｐ２ , (R ４ ) ｐ３ , (R ５ ) ｐ４ , (R ７ ) ｐ５ , R ８ , (R ９ ) ｐ６ , R １０ , (R １１ ) ｐ７ , R １２ , R １３ , R １４ , ring A, ring B, ring C, R １５ , (R １６ ) ｐ９ , X １ , X ２ , X ３ , (R ２０ ) ｐ１０ , R ２１ , R ２２ , (R ２３ ) ｐ１１ , (R ２４ )<  ｐ１２ , R ２５ , X ４ >, X ５ , X ６ , X ７ , R ２８ [[ID= 53]], R ２９ , R ３０ , R ３１ , R ３２ , R ３３ , (R ３４ ) ｐ１３ , R ３５ , (R ３６ ) ｐ１４ , R ３７ , X ８ , X ９ , X １０ , X １１ , X １２ , R ３８ [[ID= 87]], R ３９ , (R ４０ ) ｐ１５ , (R ４２ ) ｐ１６ , (R ４３ ) ｐ１７ , (R<  ４４ ) ｐ１８ , (R ４５ ) ｐ１９ , (R ４６ )[[ID= 112]] ｐ２０ , (R ４８ ) ｐ２１ , (R ４９ ) ｐ２２ , R ５０ , R ５１ , (R ５２ ) ｐ２３ , (R ５３ ) ｐ２４ 、R ５４ 、R ５５ 、R ５６ 、R ５７ 、(R ５８ ) ｐ２５ 、X １３ 、R ５９ 、R ６０ 、R ６１ 、R ６２ 、R ６３ 、R ６４ 、(R ６５ ) ｐ２６ 、R ６６ 、R ６７ 、R ６８ 、R ６９ 、R ７０ 、X １４ 、X １５ 、R ７３ 、R ７４ 、R ７５ 、R ７６ 、R ７７ 、R ７８ 、R ７９ 、R ８０ 、R ８１ 、X １６ 、X １７ 、R ８２ 、R ８３ 、R ８４ 、R ８５ 、R ８６ 、R ８７ 、R ８８ 、R ８９ 、R ９０ 、(R ９１ ) ｐ２７ 、(R ９２ ) ｐ２８ 、(R ９３ ) ｐ２９ 、R ９４ 、R ９５ 、(R ９６ ) ｐ３０ 、(R ９７ ) ｐ３１ 、X １８ 、X １９ 、X ２０ 、X ２１ 、X ２２ 、R ９８ 、R ９９ 、R １００ 、R １０１ 、R １０２ 、R １０３ 、X ２３、(R １０４ ) ｐ３２ 、(R １０５ ) ｐ３３ 、(R １０６ ) ｐ３４ 、(R １０７ ) ｐ３５ 、(R １０８ ) ｐ３６ 、(R １０９ ) ｐ３７ 、(R １１０ ) ｐ３８ 、(R １１１ ) ｐ３９ 、R １１２ 、R １１３ 、R １１４ 、R １１５ 、R １１６ 、R １１７ 、R １１８ 、(R １１９ ) ｐ４０ 、R １２０ 、R １２１ 、R １２２ 、R １２３ 、(R １２５ ) ｐ４１ 、(R １２７ ) ｐ４３ 、R １３１ 、R １３２ 、(R １３３ ) ｐ４６ 、(R １３４ ) ｐ４７ 、(R １３５ ) ｐ４８ 、R １３６ 、(R １３７ ) ｐ４９ 、X ２４ 、X ２５ 、X ２６ 、R １３８ 、R １３９ 、R １４０ 、(R １４１ ) ｐ５０ 、R １４２ 、(R １４３ ) ｐ５１ 、(R １４４ ) ｐ５２ 、(R １４５ ) ｐ５３ 、(R １４６ ) ｐ５４ 、R ｆ２ 、(R １４７ ) ｐ５５ 、R １４８ 、(R １４９ ) ｐ５６ , X ２７ , ring I, R １５０ , (R １５１ ) ｐ５７ , (R １５２ ) ｐ５８ , (R １５３ ) ｐ５９ , X ２８ , X ２９ , X ３０ , (R １５４ ) ｐ６０ , R １５５ , R １５６ , R １５７ , R １５８ , (R １５９ ) ｐ６１ , X ３１ , (R １６０ ) ｐ６２ , ring J and (R １６１ ) ｐ６３ 14. A compound of formula (II) according to claim 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein:

30. The following: N-(2-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)ethyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; N-(2-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)ethyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; N-(2-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)ethyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; N-(2-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)ethyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; N-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; N-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; N-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-2-carboxamide; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((2S)-5-amino-1-(2-chloro-3-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-3-methyl-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-3-oxoisoindolin-5-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-3-oxoisoindolin-5-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-3-oxoisoindolin-5-yl)methyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; 6-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 6-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(5-((4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)azetidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)azetidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)azetidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(((1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(((1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(((1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(((1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)(methyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-((2'-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3'-(hydroxymethyl)-1-methyl-6-oxo-1,6-dihydro-[3,4'-bipyridine]-5-yl)amino)pyridin-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (S)-3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (S)-3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (S)-3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (S)-3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3R,4R)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3S,4S)-4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(4-(1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(4-(1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(4-(1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-chloro-1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)phenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(((1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(((1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(((1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(1-(4-((3S,4R)-7-hydroxy-3-phenylchroman-4-yl)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(((1-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(((1-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(((1-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-bis(4-hydroxyphenyl)but-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((2-(4-(4-chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl)(methyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(3-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4-methylpiperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(3-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4-methylpiperidin-4-yl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(3-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4-methylpiperidin-4-yl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(3-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-4-methylpiperidin-4-yl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(6-(4-amino-4-methylpiperidin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-3-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(6-(4-amino-4-methylpiperidin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-3-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(6-(4-amino-4-methylpiperidin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-3-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(6-(4-amino-4-methylpiperidin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-3-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3-((3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)thio)-2-chlorophenyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl)-2-chlorophenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-aminopyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-aminopyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-aminopyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3S,4S)-8-(6-amino-5-((2-aminopyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-yl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)pyridin-2-yl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)pyridin-2-yl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)pyridin-2-yl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)-3-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)-3-chloropyridin-2-yl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)-3-chloropyridin-2-yl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3-amino-5-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yl)thio)-3-chloropyridin-2-yl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(6-amino-5-(2,3-dichlorophenyl)pyrazin-2-yl)-4-methylpiperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(6-amino-5-(2,3-dichlorophenyl)pyrazin-2-yl)-4-methylpiperidin-4-yl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(6-amino-5-(2,3-dichlorophenyl)pyrazin-2-yl)-4-methylpiperidin-4-yl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(6-amino-5-(2,3-dichlorophenyl)pyrazin-2-yl)-4-methylpiperidin-4-yl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2,3-difluoro-6-(2-morpholinothiazol-4-yl)phenoxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2,3-difluoro-6-(2-morpholinothiazol-4-yl)phenoxy)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2,3-difluoro-6-(2-morpholinothiazol-4-yl)phenoxy)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2,3-difluoro-6-(2-morpholinothiazol-4-yl)phenoxy)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)nicotinamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(8-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(8-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(8-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(6-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(6-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(6-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)pyridazine-3-carboxamide; 3-(5-((4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)(methyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(5-((4-(1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((9-cyclopentyl-8-(phenylamino)-9H-purin-2-yl)amino)phenyl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(((5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(((5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(((5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(2-((2-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; 3-(5-((4-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)quinazolin-6-yl)acrylamide; 3-(5-(((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)but-2-enamide; 2-(7-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)amino)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(7-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)amino)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(7-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)amino)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(7-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)amino)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(4-((2-(2,6-dioxopiperidin-3-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-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-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-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-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-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-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-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-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-(6-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(6-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(6-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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; 3-(1-oxo-5-((4-(((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-1-oxo-5-((4-(((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １ H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-5-((4-(((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １ H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-1-oxo-5-((4-(((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １ H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １ H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-1-oxo-5-((4-((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １ H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-1-oxo-5-((4-((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １ H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-5-((4-((R,E)-1 １ , 2 ６ ,7-trimethyl-3-oxo-5 ２ , 5 ３ -dihydro-1 １ H,5 １H-11-oxa-4-aza-5(2,1)-benzo[d]imidazola-2(2,4)-pyridina-1(4,5)-pyrazolacycloundecaphane-5 ６ -yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(4-fluoro-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)piperidine-2,6-dione; 3-(6-fluoro-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)piperidine-2,6-dione; 3-(7-fluoro-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)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(4-fluoro-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)piperidine-2,6-dione; 3-(6-fluoro-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)piperidine-2,6-dione; 3-(7-fluoro-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)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(4-fluoro-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)piperidine-2,6-dione; 3-(6-fluoro-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)piperidine-2,6-dione; 3-(7-fluoro-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)piperidine-2,6-dione; 3-(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)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-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)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-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)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-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)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1'-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-[1,4'-bipiperidine]-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1'-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)-[1,4'-bipiperidine]-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1'-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)-[1,4'-bipiperidine]-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1'-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)-[1,4'-bipiperidine]-4-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazine-1-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-4-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazine-1-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-4-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazine-1-carboxamide; N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-4-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazine-1-carboxamide; 4-(2,6-dichlorobenzamido)-N-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide; 4-(2,6-dichlorobenzamido)-N-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide; 4-(2,6-dichlorobenzamido)-N-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide; 4-(2,6-dichlorobenzamido)-N-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)-1H-pyrazole-3-carboxamide; N-(5-chloro-4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-chloro-4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-chloro-4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-chloro-4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl)-1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidine-4-carboxamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methoxy)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methoxy)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methoxy)phenyl)acetamide; N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methoxy)phenyl)acetamide; 3-(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)piperidine-2,6-dione; 3-(5-((4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-N-(4-(((5-(((S)-1-hydroxybutan-2-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)piperazine-1-carboxamide; 4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)-N-(4-(((5-(((S)-1-hydroxybutan-2-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)piperazine-1-carboxamide; 4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)-N-(4-(((5-(((S)-1-hydroxybutan-2-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)piperazine-1-carboxamide; 4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)-N-(4-(((5-(((S)-1-hydroxybutan-2-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)piperazine-1-carboxamide; 4-(((4-(5-chloro-2-((1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-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-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-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-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-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-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridin]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((5'-chloro-2'-((1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridin]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((5'-chloro-2'-((1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridin]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 4-(((5'-chloro-2'-((1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)amino)-[2,4'-bipyridin]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; 3-((4-(2-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)-4-methylthiazol-5-yl)-5-fluoropyrimidin-2-yl)amino)benzenesulfonamide; 3-((4-(2-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)-4-methylthiazol-5-yl)-5-fluoropyrimidin-2-yl)amino)benzenesulfonamide; 3-((4-(2-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)-4-methylthiazol-5-yl)-5-fluoropyrimidin-2-yl)amino)benzenesulfonamide; 3-((4-(2-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)-4-methylthiazol-5-yl)-5-fluoropyrimidin-2-yl)amino)benzenesulfonamide; N-(2-chloro-6-methylphenyl)-2-((6-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)amino)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)amino)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)amino)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)amino)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; 4-((4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)amino)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)amino)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)amino)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)amino)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)-6-methoxyquinoline-3-carbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)-6-methoxyquinoline-3-carbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)-6-methoxyquinoline-3-carbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)propoxy)-6-methoxyquinoline-3-carbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methoxy)-6-methoxyquinoline-3-carbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methoxy)-6-methoxyquinoline-3-carbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methoxy)-6-methoxyquinoline-3-carbonitrile; 4-((2,4-dichloro-5-methoxyphenyl)amino)-7-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methoxy)-6-methoxyquinoline-3-carbonitrile; N-(4-((4-((2-(2,6-dioxopiperidin-3-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-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-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-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-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-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; N-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)(methyl)amino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide; 2-(4-((3S)-1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-((3S)-1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-((3S)-1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-((3S)-1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-2H-indazole-7-carboxamide; 2-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)phenyl)-2H-indazole-7-carboxamide; 3-(5-((4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(((4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-5-yl)benzyl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)ethynyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-((2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)ethynyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-((2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)ethynyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-((2-fluoro-5-((8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxo-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-8-yl)phenyl)ethynyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 7-cyclopentyl-2-((5-(4-((2-(2,6-dioxopiperidin-3-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-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(((2-(2,6-dioxopiperidin-3-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-(((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-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-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-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-(((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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-(2,6-dioxopiperidin-3-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; 7-cyclopentyl-2-((5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-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; 7-cyclopentyl-2-((5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-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; 7-cyclopentyl-2-((5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-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; 7-cyclopentyl-2-((5-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(1-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 3-(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)piperidine-2,6-dione; 3-(4-fluoro-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)piperidine-2,6-dione; 3-(6-fluoro-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)piperidine-2,6-dione; 3-(7-fluoro-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)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(4-fluoro-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)piperidine-2,6-dione; 3-(6-fluoro-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)piperidine-2,6-dione; 3-(7-fluoro-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)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(4-fluoro-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)piperidine-2,6-dione; 3-(6-fluoro-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)piperidine-2,6-dione; 3-(7-fluoro-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)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(4-fluoro-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)piperidine-2,6-dione; 3-(6-fluoro-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)piperidine-2,6-dione; 3-(7-fluoro-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)piperidine-2,6-dione; 3-(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)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-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)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-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)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-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)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(difluoro(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-((4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide; 3-((4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide; 3-((4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide; 3-((4-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl)piperazin-1-yl)piperidin-1-yl)-3-methoxyphenyl)amino)-6-ethyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazine-2-carboxamide; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)(methyl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)amino)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)amino)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)amino)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(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)piperidine-2,6-dione; 3-(5-((4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(...

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