Compounds with two azaheterocycles substituted isoindolinone skeleton and uses thereof

Abstract

The present disclosure relates to a compound represented by formula (I) or a salt, enantiomer, stereoisomer, solvate, polymorph thereof and a use thereof. The present disclosure also relates to pharmaceutical compositions comprising, as an active ingredient, the compound represented by formula (I) or the salt, enantiomer, stereoisomer, solvate, polymorph thereof, and a use thereof. In the present disclosure, the compounds designed and synthesized can effectively prevent or treat diseases or conditions related to celeblon protein, including tumors or cancers.

Description

Compounds having a dinitrogen heterocycle-substituted isoindolinone skeleton and their applications Technical Field

[0001] The present disclosure relates to compounds of formula (I) or salts, enantiomers, stereoisomers, solvates or polymorphs thereof and uses thereof, in particular their use for preventing or treating diseases or conditions including tumors or cancers. Background Art

[0002] Phthalimide immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, are highly effective in treating multiple myeloma and autoimmune diseases. However, it wasn't until 2010 that their direct binding protein, the E3 ubiquitin ligase cereblon (CRBN), was identified. Subsequently, it was demonstrated that upon binding to CRBN, these drugs act as molecular glues to recruit substrate proteins (such as the transcription factors IKZF1 / 3), enabling protein-protein interactions between CRBN and substrate proteins and subsequently ubiquitination of these substrate proteins. Polyubiquitinated substrate proteins are then recognized and degraded by the proteasome, resulting in pharmacological effects including anti-tumor and immunomodulatory effects. Molecular glue protein degraders directly target and degrade target proteins, offering potential advantages such as targeting undruggable targets. Furthermore, molecular glue degraders typically have a small molecular weight and good drugability, making their development highly valued. Based on the CRBN E3 ubiquitin ligase and molecular glue degradation mechanism, a series of compounds have been developed, including the marketed pomalidomide, as well as Bristol-Myers Squibb (BMS)'s CC-122, CC-220, CC-90009, CC-99282, and CC-92480, BMS-986470, which are currently undergoing clinical trials, Novartis's DKY709, C4 Therapeutics' CFT7455, and Monte Rosa's MRT-6160. The degradation substrates of these molecular glues have also expanded from the initially discovered transcription factors IKZF1 / 3 to casein kinase 1α (CK1α), zinc finger protein 91 (ZFP91), WIZ, transcription factor IKZF2, translation factor GSPT1, and the immune disease target Vav1. The degradation of these protein substrates enables the molecular glue to exert its pharmacological activities, including immunomodulatory, anti-inflammatory, and anti-tumor effects. The structural novelty of the molecular glue candidate compounds discovered so far is very limited, and diversified skeleton design and development of more molecular glues have become research hotspots in this field.

[0003] Therefore, this patent application designs and develops a series of novel molecular glue degraders based on CRBN E3 ubiquitin ligase, which can be used to treat and / or prevent diseases or conditions mediated by or related to degraded proteins. Summary of the Invention

[0004] In view of the above, the object of the present disclosure is to provide novel protein degradation compounds having a dinitrogen heterocycle-substituted isoindolinone skeleton, their preparation methods, uses, and methods of using them.

[0005] To achieve the above-mentioned and other related purposes, in one aspect, the present disclosure provides a compound of formula (I) or its salt, stereoisomer (including enantiomer, diastereomer), solvate or polymorph: wherein Z1 represents C(O), C(S), CH2 or CD2, Z2, Z3 and Z4 each independently represent C(O) or C(S); Z5 represents CH or N; R a1 、R a2 、R a3 and R a4 Each independently represents hydrogen, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy or halogenated C 1-6 Alkoxy; (R a5 ) m represents that the isoindoline ring connected thereto is optionally replaced by m R a5 Replace, each R a5 The same or different and each independently represents deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl or C 2-6 Alkynyl; m represents an integer of 0, 1, 2 or 3; R represents C(O) or an optionally substituted linear or branched C 1-5 Alkylene; X represents: wherein ring A represents a nitrogen-containing heterocyclic group, (R d1 ) n1 Indicates that ring A is optionally replaced by n1 R d1 Group substitution, each R d1 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C2-6 alkenyl, and n1 represents an integer of 0-20; Ring B represents a nitrogen-containing heterocyclic group, (R d2 ) n2 Indicates that ring B is optionally replaced by n2 R d2 Group substitution, each R d2 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n2 represents an integer of 0-20; R c Indicates C(O), CR c1 R c2 or key, where R c1 and R c2 Each independently represents H, deuterium, halogen, an optionally substituted linear or branched alkyl group, an optionally substituted cycloalkyl group, an optionally substituted heterocyclyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group; Ring C represents a cycloalkylene group, a heterocyclylene group, an arylene group, or a heteroarylene group; m1 represents an integer of 0 or 1; (R d3 ) n3 represents ring C optionally replaced by n3 R d3 Group substitution, each R d3 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n3 represents an integer of 0-20; and ring D represents a heterocyclic group, a cycloalkyl group, an aryl group or a heteroaryl group, (R d4 ) n4 represents a ring D optionally replaced by n4 R d4 Group substitution, each R d4 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n4 represents an integer of 0-20.

[0006] In another aspect, the present disclosure provides a pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph thereof, and at least one pharmaceutically acceptable carrier.

[0007] In another aspect, the present disclosure further provides a drug box or a test kit comprising: a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same.

[0008] In another aspect, the present disclosure provides a compound of formula (I), or a pharmaceutically acceptable salt, enantiomer, diastereomer, solvate, prodrug or polymorph thereof, for use as a medicament.

[0009] In another aspect, the present disclosure provides the compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph thereof, or a pharmaceutical composition of the present disclosure, for use in treating or preventing a disease or condition associated with cereblon protein.

[0010] In another aspect, the present disclosure provides the compound of formula (I), or its pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph, or the pharmaceutical composition of the present disclosure, for use in treating or preventing a disease or condition selected from the following: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure and diabetes.

[0011] In another aspect, the present disclosure further provides the use of the compound of formula (I) or its pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph, or the pharmaceutical composition of the present disclosure, for preparing a medicament for treating or preventing a disease or condition associated with the cereblon protein.

[0012] On the other hand, the present disclosure also provides the use of the compound of formula (I) or its pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph, or the pharmaceutical composition of the present disclosure, which is used to prepare a medicament for preventing or treating a disease or condition selected from the following: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure and diabetes.

[0013] In another aspect, the present disclosure also provides a method for treating or preventing a disease or condition associated with cereblon protein, comprising administering to a subject a therapeutically effective amount of the compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer (including enantiomers, diastereomers), solvate, isotopically enriched analog, prodrug or polymorph thereof, or the pharmaceutical composition described herein.

[0014] On the other hand, the present disclosure also provides a method for treating or preventing a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition, wherein the disease or condition is selected from: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure and diabetes.

[0015] In another aspect, the present disclosure also provides a method for preparing a compound of formula (I), comprising reacting a compound of formula (M1) with a compound of formula (M2) to obtain a compound of formula (I): The group R a1 、R a2 、R a3 、R a4 、(R a5 ) m 、Z1、Z2、Z3、Z4、Z5、Nitrogen-containing heterocyclic ring A、(R d1 ) n1 , Ring B, (R d2 ) n2 、R c 、ring C、m1、(R d3 ) n3 , Ring D, and (R d4 ) n4As defined in the compounds of formula (I) and its various sub-embodiments disclosed herein; and R represents an optionally substituted linear or branched C 1-5 Alkylene; LE represents Cl, Br, I, methanesulfonyloxy, p-toluenesulfonyloxy, o-nitrobenzenesulfonyl, C(O)Cl or COOH; and X of the compound of formula (I) a The structure represented by the following general formula is represented accordingly: wherein the nitrogen-containing heterocyclic group A is a divalent group obtained by removing a hydrogen atom from nitrogen-containing heterocyclic ring A, the nitrogen-containing heterocyclic group A represents a 4- to 30-membered nitrogen-containing heterocyclic group (preferably, a 4- to 20-membered nitrogen-containing heterocyclic group; more preferably, a 4- to 15-membered nitrogen-containing heterocyclic group), the nitrogen-containing heterocyclic ring A represents a 4- to 30-membered nitrogen-containing heterocycle (preferably, a 4- to 20-membered nitrogen-containing heterocycle; more preferably, a 4- to 15-membered nitrogen-containing heterocycle), and (R d1 ) n1 , Ring B, (R d2 ) n2 、R c , Ring C, m1, (R d3 ) n3 , Ring D, and (R d4 ) n4 As defined in the compounds of formula (I) and its various sub-embodiments disclosed herein.

[0016] The following detailed description is provided as an exemplary embodiment to help those skilled in the art understand and implement the present disclosure. However, it should be understood that such description is not intended to limit the scope of the present disclosure. Without departing from the spirit and scope of the present disclosure, the specific embodiments described in the present disclosure may be subjected to various modifications and changes, and these changes and improvements fall within the scope of the present disclosure. I. Compounds Formula (I) Compound

[0017] The present disclosure provides a compound of formula (I) or its salt (including pharmaceutically acceptable salt), stereoisomer (including enantiomer, diastereomer), solvate, isotopically enriched analog, prodrug or polymorph: Among them, Z1, Z2, Z3, Z4, Z5, R a1 、R a2 、R a3 、R a4 、(R a5 ) m , R and X are as defined above for the compounds of formula (I) and its embodiments.

[0018] The compounds of formula (I) or their salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, prodrugs, or polymorphs provided herein have binding affinity for CRBN, help recruit substrate proteins, and can act as molecular glues to bind to CRBN E3 ubiquitin ligases. The compounds of formula (I) or their salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, prodrugs, or polymorphs disclosed herein can also degrade substrate proteins (e.g., IKZF1 / 2 / 3 / 4 proteins, WEE1 proteins, CK1α proteins, GSPT1 proteins, ZFP91 proteins, etc.). The compounds of formula (I) or their salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, prodrugs, or polymorphs disclosed herein have anti-tumor activity or excellent pharmacokinetic properties and can be used as therapeutic drugs for cancer patients.

[0019] In some embodiments of the present disclosure, R a1 、R a2 、R a3 and R a4 The same or different and each independently represents H, deuterium (ie, D), C 1-6 Alkyl (e.g. C 1-3 Alkyl, such as methyl, ethyl, or propyl), halo C 1-6 Alkyl (e.g. halo-C 1-4 alkyl, such as trifluoromethyl), deuterated C 1-6 Alkyl, C 1-6 Alkoxy (e.g. C 1-4 Alkoxy, such as methoxy), deuterated C 1-6 Alkoxy or halogenated C 1-6 Alkoxy (e.g., halo-C 1-4 In some sub-embodiments of the present disclosure, R a1 、R a2 、R a3 and R a4 Each independently represents H.

[0020] In some embodiments of the present disclosure, Z1 represents C(O), C(S), CH2 or CD2.

[0021] In some embodiments of the present disclosure, Z2, Z3 and Z4 represent C(O) or C(S).

[0022] In some embodiments of the present disclosure, Z1, Z2, Z3 and Z4 represent C(O).

[0023] In some embodiments of the present disclosure, Z1 represents CH2, and Z2, Z3, and Z4 represent C(O).

[0024] In some embodiments of the present disclosure, Z1 represents CH2, Z2 represents C(S), and Z3 and Z4 represent C(O).

[0025] In some embodiments of the present disclosure, Z1 represents CH2, Z3 represents C(S), and Z2 and Z4 represent C(O).

[0026] In some embodiments of the present disclosure, Z1 represents CH2, Z4 represents C(S), and Z2 and Z3 represent C(O).

[0027] In some embodiments of the present disclosure, Z1 represents CH2, Z2 and Z4 represent C(S), and Z3 represents C(O).

[0028] In some embodiments of the present disclosure, Z1 represents CH2, Z2 and Z3 represent C(S), and Z4 represents C(O).

[0029] In some embodiments of the present disclosure, Z1 represents CH2, and Z2, Z3, and Z4 represent C(S).

[0030] In some embodiments of the present disclosure, Z1 represents C(S), and Z2, Z3, and Z4 represent C(O).

[0031] In some embodiments of the present disclosure, Z2 represents C(S), and Z1, Z3, and Z4 represent C(O).

[0032] In some embodiments of the present disclosure, Z3 represents C(S), and Z1, Z2, and Z4 represent C(O).

[0033] In some embodiments of the present disclosure, Z4 represents C(S), and Z1, Z2, and Z3 represent C(O).

[0034] In some embodiments of the present disclosure, Z1 and Z2 represent C(S), and Z3 and Z4 represent C(O).

[0035] In some embodiments of the present disclosure, Z1 and Z3 represent C(S), and Z2 and Z4 represent C(O).

[0036] In some embodiments of the present disclosure, Z1 and Z4 represent C(S), and Z2 and Z3 represent C(O).

[0037] In some embodiments of the present disclosure, Z1, Z2, and Z3 represent C(S), and Z4 represents C(O).

[0038] In some embodiments of the present disclosure, Z1, Z2, and Z4 represent C(S), and Z3 represents C(O).

[0039] In some embodiments of the present disclosure, Z1, Z3, and Z4 represent C(S), and Z2 represents C(O).

[0040] In some embodiments of the present disclosure, Z1, Z2, Z3, and Z4 represent C(S).

[0041] In some embodiments of the present disclosure, Z5 represents CH or N.

[0042] In some embodiments of the present disclosure, (R a5 ) m represents that the isoindoline ring of formula (I) attached thereto is optionally substituted by m R a5 Replace, each R a5 The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halo-C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1- 4 alkyl groups, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g. C 1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy (e.g., halo-C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 2-6 Alkenyl (e.g. vinyl) or C 2-6Alkynyl (e.g., ethynyl), and m represents an integer of 0, 1, 2, or 3. In some sub-embodiments of the present disclosure, m represents an integer of 0, 1, or 2. In some sub-embodiments of the present disclosure, each R a5 The same or different and each independently represents deuterium, halogen (such as fluorine, chlorine, bromine or iodine), hydroxyl, mercapto, nitro, amino, cyano, C 1-4 Alkyl (e.g. C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-4 Alkyl (e.g. halo-C 1-3 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-4 Alkoxy (e.g. C 1-3 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy) or halogenated C 1-4 Alkoxy (e.g., halo-C 1-3 Alkoxy groups, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0043] In the embodiments of the present disclosure, the number of substituents is in principle not subject to any restrictions or automatically limited by the size of the building block.

[0044] In some embodiments of the present disclosure, R represents C(O) or an optionally substituted linear or branched C 1-5 Alkylene (e.g. C 1-4 Alkylene, C 1-3 Alkylene, C 1-2 alkylene or methylene). The C 1-5 The alkylene group is optionally selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0045] In some embodiments of the present disclosure, R represents C(O).

[0046] In some embodiments of the present disclosure, R represents -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4-, or -(CH2)5-; wherein the above groups are optionally selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0047] In some embodiments of the present disclosure, X represents: wherein ring A represents a nitrogen-containing heterocyclic group, (R d1 ) n1 Indicates that ring A is optionally replaced by n1 R d1 Group substitution, each R d1 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n1 represents an integer of 0-20; Ring B represents a nitrogen-containing heterocyclic group, (R d2 ) n2 Indicates that ring B is optionally replaced by n2 R d2 Group substitution, each R d2 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n2 represents an integer of 0-20; R c Indicates C(O), CR c1 R c2 or key, where R c1 and R c2 Each independently represents H, deuterium, halogen, an optionally substituted linear or branched alkyl group, an optionally substituted cycloalkyl group, an optionally substituted heterocyclyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group; Ring C represents a cycloalkylene group, a heterocyclylene group, an arylene group, or a heteroarylene group; m1 represents an integer of 0 or 1; (R d3 )n3 represents ring C optionally replaced by n3 R d3 Group substitution, each R d3 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n3 represents an integer of 0-20; and ring D represents a heterocyclic group, a cycloalkyl group, an aryl group or a heteroaryl group, (R d4 ) n4 represents a ring D optionally replaced by n4 R d4 Group substitution, each R d4 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n4 represents an integer of 0-20.

[0048] In some embodiments of the present disclosure, ring A represents a 4- to 30-membered nitrogen-containing heterocyclylene group (including a 4- to 25-membered nitrogen-containing heterocyclylene group, a 4- to 20-membered nitrogen-containing heterocyclylene group, a 4- to 15-membered nitrogen-containing heterocyclylene group, and a 5- to 20-membered nitrogen-containing heterocyclylene group). Ring A is optionally substituted by n1 R d1 Group substitution, each R d1 Deuterium, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6Alkoxy (e.g. C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), halogen (such as fluorine, chlorine, bromine or iodine), amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl (e.g., ethynyl) or C 2-6 an alkenyl group (e.g., a vinyl group), and n1 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0049] In some embodiments of the present disclosure, ring A represents an azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, azepanylidene, diazacycloheptylidene, azaoctylene, diazaoctylene, azabicyclo[3.1.1]heptanylidene, azabicyclo[2.2.1]heptanylidene, azabicyclo[3.2.1]octanylidene, azabicyclo[2.2.2]octanylidene, diazabicyclo[3.1.1]heptanylidene, diazabicyclo[2.2.1]heptanylidene, diazabicyclo[3.2.1 ... bicyclo[2.2.2]octanylidene, quinuclidinyl, 2,6-diazaspiro[3.3]heptanylidene, 2,7-diazaspiro[3.5]nonanylidene, 2,8-diazaspiro[4.5]decanylidene, 3,9-diazaspiro[5.5]undecanylidene, 3-azaspiro[5.5]undecanylidene, 7-azaspiro[3.5]nonanylidene, 8-azaspiro[4.5]decanylidene or octahydropyrrolo[3,4-c]pyrroleylidene, which may be optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-5, 1-4 or 1-3) selected from deuterium, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl (e.g. halo-C 1-4Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6 Alkoxy (e.g. C 1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), halogen (such as fluorine, chlorine, bromine or iodine), amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl (e.g. ethynyl) and C 2-6 The substituents of the alkenyl group (eg, vinyl group) are substituted.

[0050] In some embodiments of the present disclosure, ring B represents a 4- to 30-membered nitrogen-containing heterocyclylene group (including a 4- to 25-membered nitrogen-containing heterocyclylene group, a 4- to 20-membered nitrogen-containing heterocyclylene group, a 4- to 15-membered nitrogen-containing heterocyclylene group, and a 5- to 20-membered nitrogen-containing heterocyclylene group). Ring B is optionally substituted by n2 R d2 Group substitution, each R d2 Deuterium, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., perdeuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or perdeuterated C 1-4 Alkyl, such as CD3, CD3CD2-, CD3CD2CD2-, etc.), halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6 Alkoxy (e.g. C 1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo-C 1-6 Alkoxy (e.g., halo-C 1-4alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), halogen (such as fluorine, chlorine, bromine or iodine), amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl (e.g., ethynyl) or C 2-6 an alkenyl group (e.g., a vinyl group), and n2 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0051] In some embodiments of the present disclosure, ring B represents an azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, azepanylidene, diazacycloheptylidene, azaoctylene, diazaoctylene, azabicyclo[3.1.1]heptanylidene, azabicyclo[2.2.1]heptanylidene, azabicyclo[3.2.1]octanylidene, azabicyclo[2.2.2]octanylidene, diazabicyclo[3.1.1]heptanylidene, diazabicyclo[2.2.1]heptanylidene, diazabicyclo[3.2.1 ... bicyclo[2.2.2]octanylidene, quinuclidinyl, 2,6-diazaspiro[3.3]heptanylidene, 2,7-diazaspiro[3.5]nonanylidene, 2,8-diazaspiro[4.5]decanylidene, 3,9-diazaspiro[5.5]undecanylidene, 3-azaspiro[5.5]undecanylidene, 7-azaspiro[3.5]nonanylidene, 8-azaspiro[4.5]decanylidene or octahydropyrrolo[3,4-c]pyrroleylidene, which may be optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-5, 1-4 or 1-3) selected from deuterium, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6 Alkoxy (e.g. C 1-4alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), halogen (such as fluorine, chlorine, bromine or iodine), amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl (e.g. ethynyl) and C 2-6 The substituents of the alkenyl group (eg, vinyl group) are substituted.

[0052] In some embodiments of the present disclosure, R c Represents C(O).

[0053] In some embodiments of the present disclosure, R c Indicates a bond. When R c When a bond is represented, ring B is directly connected to ring C.

[0054] In some embodiments of the present disclosure, R c Indicates CR c1 R c2 , where R c1 and R c2 Each independently represents H, deuterium, halogen, an optionally substituted linear or branched C 1-10 Alkyl (e.g., optionally substituted linear or branched C 1-6 Alkyl or optionally substituted linear or branched C 1-3 alkyl), optionally substituted C 3-30 Cycloalkyl (eg, optionally substituted C 3-20 Cycloalkyl, or optionally substituted C 3-15 cycloalkyl), optionally substituted C 5-30 Aryl (eg, optionally substituted C 5-20 Aryl, or optionally substituted C 5-15 aryl), an optionally substituted 4- to 30-membered heterocyclyl (e.g., an optionally substituted 4- to 20-membered heterocyclyl, or an optionally substituted 4- to 15-membered heterocyclyl), or an optionally substituted 5- to 30-membered heteroaryl (e.g., an optionally substituted 5- to 20-membered heteroaryl, or an optionally substituted 5- to 15-membered heteroaryl). In some embodiments, the straight chain or branched C 1-10 Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, and octyl. In some embodiments, the linear or branched C1-10 The alkyl group may be optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups selected from deuterium, halogen, amino, hydroxyl, thiol, cyano, nitro, oxo, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1- 6 alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkynyl and C 2-6 In some embodiments, C 3-30 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C5-C 20 Spirocyclyl, for example, spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or a bridged cycloalkyl group (e.g., C6-C 20 bridged ring group, such as adamantyl, noradamantyl, bornyl, norbornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptanyl, or bicyclo[2.2.1]heptenyl). In some embodiments, C 3-30 The cycloalkyl group may be optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups selected from deuterium, halogen, hydroxy, thiol, nitro, amino, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl and C 2-6In some embodiments, examples of 4 to 30 membered heterocyclic groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxane, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazacycloheptane, 4,5-diazacycloheptane, 1,3-diazacycloheptane), diazacycloheptane, bridged heterocyclic groups (e.g., 6 to 20 membered bridged heterocyclic groups, such as 6-azabicyclo[3.1.1]heptane, 2,5-diazabicyclo[3.1.1]heptane, ]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2.2.2]octanyl and quinuclidine), and azaspirocyclyl (e.g., a 5- to 20-membered azaspirocyclyl, such as 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecyl, 3-azaspiro[5.5]undecyl and 7-azaspiro[3.5]nonanyl), or octahydropyrrolo[3,4-c]pyrrolyl. In some embodiments, the 4- to 30-membered heterocyclyl is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) selected from deuterium, halogen, hydroxyl, thiol, amino, cyano, oxo, C 1-6 Alkyl, halogenated C 1- 6-alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl and C 2-6 In some embodiments, C 5-30 Examples of aryl groups include, but are not limited to, phenyl or naphthyl. 5-30 The aryl group may be optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups selected from deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, 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 and C2-6 In some embodiments, examples of 5- to 30-membered heteroaryl groups include, but are not limited to, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl , benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydroquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4- Tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazole pyrimidinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,1-b]thiazolyl, 1H-imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl. In some embodiments, the 5- to 30-membered heteroaryl group is optionally replaced by one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) selected from deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl and C 2-6 The substituents of the alkynyl group are substituted.

[0055] In some embodiments of the present disclosure, m1 represents an integer of 1, ring C represents a 4- to 30-membered heterocyclylene group (e.g., a 4- to 20-membered heterocyclylene group, or a 4- to 15-membered heterocyclylene group), C 3-30 Cycloalkylene (e.g. C 3-20 Cycloalkylene, or C 3-15 Cycloalkylene), C 5-30 Arylene (e.g. C 5-20 Arylene, or C 5-15 arylene) or 5 to 30 membered heteroarylene (e.g. 5 to 20 membered heteroarylene, or 5 to 15 membered heteroarylene). Ring C is optionally substituted by n3 R d3 Group substitution, each R d3 Each independently represents deuterium, C 1-6 Alkyl (e.g. C 1-5 Alkyl, C 1-4 Alkyl or C 1-3 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl (e.g. halo-C 1-4 Alkyl groups, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6 Alkoxy (e.g. C 1-4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), halo-C 1-6 Alkoxy (e.g., halo-C 1-4 alkoxy, such as F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), halogen (such as fluorine, chlorine, bromine or iodine), amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl (e.g., ethynyl) or C 2-6 alkenyl (e.g., vinyl), n3 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0056] In some embodiments, ring C represents a 4- to 30-membered heterocyclylene, examples of which include, but are not limited to, 4- to 20-membered, 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, and 5- to 9-membered heterocyclylene, such as azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, furanyl, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azocanylidene, dioxanylene, azepanylene, azocanylidene, diazepanylene, diazepanylene (e.g., 1,4-diazepanylene, 4,5-diazepanylene, 1,3-diazepanylene), diazepanylene , a 6- to 20-membered bridging heterocyclic group, such as a 6-azabicyclo[3.1.1]heptanylene, a 2,5-diazabicyclo[2.2.1]heptanylene, a 3,6-diazabicyclo[3.1.1]heptanylene, a 3-azabicyclo[3.2.1]octanylene, a 3,8-diazabicyclo[3.2.1]octanylene, a 3,8-diazabicyclo[3.2.1]octanylene, a 2,5-diazabicyclo[2.2.2] The heterocyclyl group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6 or 1) groups selected from deuterium, hydroxyl, amino, sulfhydryl, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1- 6 alkyl, hydroxy substituted C 1-6 Alkyl, amino substituted C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl and C 2-6 The substituents of the alkynyl group are substituted.

[0057] In some embodiments, ring C represents sub-C 3-30 Cycloalkyl, examples of which include but are not limited to C 3-20 Cycloalkylene, C3- 15 Cycloalkylene and C 3-11 Cycloalkylene, for example, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, spirocyclylene (for example, C5-C 20 Spirocycloalkylene and C 5-15 spirocyclylene, such as spiro[3.3]heptanylene, spiro[2.5]octanylene, spiro[3.5]nonanylene, spiro[4.4]nonanylene, spiro[4.5]decanylene, spiro[5.5]undecanylene), p-menthanylene, m-menthanylene, or bridged cycloalkylene (e.g., C6-C 20 The cycloalkylene group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6 or 1) groups selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, hydroxy substituted C 1-6 Alkyl, amino substituted C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl and C 2-6 The substituents of the alkynyl group are substituted.

[0058] In some embodiments, Ring C represents C 5-30 Arylene, examples of which include but are not limited to C 5-20 Arylene, C 6-20 Arylene, C 5-15 Arylene and C 6-15 Arylene, such as phenylene or naphthylene. Arylene is optionally substituted by one or more (e.g., 1-6, 1-4, 1-3, 2-6 or 1) groups selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, hydroxy substituted C 1-6 Alkyl, amino substituted C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogenated C1-6 Alkoxy, C 2-6 Alkenyl and C 2-6 The substituents of the alkynyl group are substituted.

[0059] In some embodiments, ring C represents a 5- to 30-membered heteroarylene group, examples of which are not limited to 5- to 20-membered heteroarylene groups, 5- to 15-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, and 5- to 6-membered heteroarylene groups, such as furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, triazinylene, indolylene, isoindolylene, indolinylene, Benzofurylene, benzodihydropyranylene, isobenzofurylene, benzothiophenylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolylene, benzo[b][1,4]oxazinylene, 3,4-dihydro-2H-benzo[b][1,4]oxazinylene, quinolinylene, isoquinolinylene , 1,2,3,4-tetrahydroquinolinylidene, naphthyridinylidene, cinnolinylidene, quinazolinylidene, quinoxalinylidene, 1,2,3,4-tetrahydroquinoxalinylidene, phthalazinylidene, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinylidene, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinylidene, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinylidene, thieno[2,3-d]pyrimidinylidene, thieno[3,2-d]pyrimidinylidene, isoxazolo[4,5-c]pyridinylidene, isoxazolo[4,5-c] pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyrimidinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyrimidinyl, 1H-pyrrolo[3,2-b]pyrimidinyl, 1H-pyrrolo[2,3-b]pyrimidinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl. The heteroarylene group is optionally substituted by one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) groups selected from deuterium, halogen, hydroxyl, thiol, nitro, amino, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C1-6 Alkyl, hydroxy substituted C 1-6 Alkyl, amino substituted C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl and C 2-6 The substituents of the alkynyl group are substituted.

[0060] In some embodiments of the present disclosure, when m1 represents 0, ie, ring C is absent, R c Connect directly to ring D.

[0061] In some embodiments of the present disclosure, ring D represents C 3-30 Cycloalkyl (e.g. C 3-20 Cycloalkyl, or C 3-15 cycloalkyl), 4 to 30-membered heterocyclyl (e.g., 4 to 20-membered heterocyclyl, or 4 to 15-membered heterocyclyl), C 5-30 Aryl (e.g. C 5-20 Aryl, or C 5-15 aryl) or 5 to 30 membered heteroaryl (e.g. 5 to 20 membered heteroaryl, or 5 to 15 membered heteroaryl). Ring D is optionally substituted by n4 R d4 Group substitution, each R d4 Deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2- 6 alkenyl, and n4 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0062] In some embodiments, Ring D represents C 3-30 Cycloalkyl, examples of which include but are not limited to C 3-20 Cycloalkyl, C 3-15 Cycloalkyl and C 3-11 Cycloalkyl, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (for example C5-C 20Spirocyclyl, for example, spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or a bridged cycloalkyl group (e.g., C6-C 20 The cycloalkyl group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6 or 1) radicals selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0063] In some embodiments, ring D represents a 4- to 30-membered heterocyclic group, examples of which include, but are not limited to, 4- to 20-membered, 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, and 5- to 9-membered heterocyclic groups, such as azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, pyranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxanyl, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazepanyl, 4,5-diazepanyl, 1,3-diazepanyl), diazepanyl, heterocyclooctanyl, bridged heterocyclic groups (e.g., 6- to 20-membered bridged heterocyclic groups, such as 6-azabicyclo[3.1.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 3,6-diazabicyclo[3.1.1]heptyl, 3-azabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2. The heterocyclic group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6 or 1) radicals selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0064] In some embodiments, Ring D represents C 5-30 Aryl, examples of which include but are not limited to C 5-20 Aryl, C 6-20 Aryl, C 5-15 Aryl and C 6-15Aryl, such as phenyl or naphthyl, which may be optionally substituted with one or more (e.g. 1-7, 1-6, 1-4, 1-3, 2-6 or 1) selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0065] In some embodiments, ring D represents a 5- to 30-membered heteroaryl, examples of which are not limited to 5- to 20-membered heteroaryl, 5- to 15-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, and 5- to 6-membered heteroaryl, such as furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolinyl, indolinyl, benzofuranyl, benzophenone ... dihydropyranyl, isobenzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolyl, isoquinolyl, 1,2,3,4- tetrahydroquinolinyl, naphthridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridinyl, isoxazolo[4,5-c]pyrimid ... oxazolo[4,5-d]pyrimidinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl. The heteroaryl group is optionally substituted with one or more (e.g., 1-20, 1-15, 1-10, 1-6, 1-4, 1-3, 2-6, or 1) selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0066] In some embodiments of the present disclosure, X represents: wherein Ring A represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group, and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d1 ) n1 Indicates that ring A is optionally replaced by n1 R d1 Group substitution, each R d1 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n1 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; Ring B represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d2 ) n2 Indicates that ring B is optionally replaced by n2 R d2 Group substitution, each R d2 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n2 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; R c Indicates C(O), CR c1 R c2 or key, where R c1 and R c2 Each independently represents H, deuterium, halogen, an optionally substituted linear or branched alkyl group (e.g., an optionally substituted linear or branched C 1-10 Alkyl, optionally substituted linear or branched C 1-6 Alkyl or optionally substituted linear or branched C 1-3 alkyl), optionally substituted cycloalkyl (e.g., optionally substituted C 3-30 Cycloalkyl, optionally substituted C 3-20Cycloalkyl or optionally substituted C 3-15 cycloalkyl), optionally substituted heterocyclyl (e.g., optionally substituted 4- to 30-membered heterocyclyl, optionally substituted 4- to 20-membered heterocyclyl, or optionally substituted 4- to 15-membered heterocyclyl), optionally substituted aryl (e.g., optionally substituted C 5- 30 Aryl, optionally substituted C 5-20 Aryl or optionally substituted C 5-15 aryl) or an optionally substituted heteroaryl (eg, an optionally substituted 5- to 30-membered heteroaryl, an optionally substituted 5- to 20-membered heteroaryl, or an optionally substituted 5- to 15-membered heteroaryl); Ring C represents a cycloalkylene group (eg, C 3-30 Cycloalkylene, C 3-20 Cycloalkylene or C 3-15 cycloalkylene), heterocyclylene (e.g., 4- to 30-membered heterocyclylene, 4- to 20-membered heterocyclylene, or 4- to 15-membered heterocyclylene), arylene (e.g., C 5-30 Arylene, C 5-20 Arylene or C 5-15 arylene) or heteroarylene (e.g., 5- to 30-membered heteroarylene, 5- to 20-membered heteroarylene, or 5- to 15-membered heteroarylene), m1 represents an integer of 0 or 1, (R d3 ) n3 represents ring C optionally replaced by n3 R d3 Group substitution, each R d3 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n3 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; and ring D represents a heterocyclic group (e.g., a 4- to 30-membered heterocyclic group, a 4- to 20-membered heterocyclic group or a 4- to 15-membered heterocyclic group), a cycloalkyl group (e.g., C 3-30 Cycloalkyl, C 3-20 Cycloalkyl or C 3-15 Cycloalkyl), aryl (e.g. C 5-30 Aryl, C 5-20 Aryl or C 5-15 aryl) or heteroaryl (e.g., 5- to 30-membered heteroaryl, 5- to 20-membered heteroaryl, or 5- to 15-membered heteroaryl), (R d4 ) n4 represents a ring D optionally replaced by n4 R d4Group substitution, each R d4 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n4 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0067] In some embodiments of the present disclosure, X represents: wherein Ring A represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group, and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d1 ) n1 Indicates that ring A is optionally replaced by n1 R d1 Group substitution, each R d1 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n1 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; Ring B represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d2 ) n2 Indicates that ring B is optionally replaced by n2 R d2 Group substitution, each R d2 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6alkenyl, and n2 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; R c1 and R c2 Each independently represents H, deuterium, halogen, an optionally substituted linear or branched alkyl group (e.g., an optionally substituted linear or branched C 1-10 Alkyl, optionally substituted linear or branched C 1-6 Alkyl or optionally substituted linear or branched C 1-3 alkyl), optionally substituted cycloalkyl (e.g., optionally substituted C 3-30 Cycloalkyl, optionally substituted C 3-20 Cycloalkyl or optionally substituted C 3-15 cycloalkyl), optionally substituted heterocyclyl (e.g., optionally substituted 4- to 30-membered heterocyclyl, optionally substituted 4- to 20-membered heterocyclyl, or optionally substituted 4- to 15-membered heterocyclyl), optionally substituted aryl (e.g., optionally substituted C 5-30 Aryl, optionally substituted C 5-20 Aryl or optionally substituted C 5-15 aryl) or an optionally substituted heteroaryl (eg, an optionally substituted 5- to 30-membered heteroaryl, an optionally substituted 5- to 20-membered heteroaryl, or an optionally substituted 5- to 15-membered heteroaryl); Ring C represents a cycloalkylene group (eg, C 3-30 Cycloalkylene, C 3-20 Cycloalkylene or C 3-15 cycloalkylene), heterocyclylene (e.g., 4- to 30-membered heterocyclylene, 4- to 20-membered heterocyclylene, or 4- to 15-membered heterocyclylene), arylene (e.g., C 5-30 Arylene, C 5-20 Arylene or C 5-15 arylene) or heteroarylene (e.g., 5- to 30-membered heteroarylene, 5- to 20-membered heteroarylene, or 5- to 15-membered heteroarylene), m1 represents an integer of 0 or 1, (R d3 ) n3 represents ring C optionally replaced by n3 R d3 Group substitution, each R d3 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6alkenyl, and n3 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; and ring D represents a heterocyclic group (e.g., a 4- to 30-membered heterocyclic group, a 4- to 20-membered heterocyclic group or a 4- to 15-membered heterocyclic group), a cycloalkyl group (e.g., C 3-30 Cycloalkyl, C 3-20 Cycloalkyl or C 3-15 Cycloalkyl), aryl (e.g. C 5-30 Aryl, C 5-20 Aryl or C 5-15 aryl) or heteroaryl (e.g., 5- to 30-membered heteroaryl, 5- to 20-membered heteroaryl, or 5- to 15-membered heteroaryl), (R d4 ) n4 represents a ring D optionally replaced by n4 R d4 Group substitution, each R d4 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n4 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0068] In some embodiments of the present disclosure, X represents: wherein Ring A represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group, and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d1 ) n1 Indicates that ring A is optionally replaced by n1 R d1 Group substitution, each R d1 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6alkenyl, and n1 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; Ring B represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d2 ) n2 Indicates that ring B is optionally replaced by n2 R d2 Group substitution, each R d2 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n2 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; R c1 represents H, deuterium, halogen or an optionally substituted straight-chain or branched alkyl group (e.g. an optionally substituted straight-chain or branched C 1- 10 Alkyl, optionally substituted linear or branched C 1-6 Alkyl or optionally substituted linear or branched C 1-3 alkyl); R c2 represents H, deuterium, halogen, an optionally substituted straight-chain or branched alkyl group (e.g. an optionally substituted straight-chain or branched C 1- 10 Alkyl, optionally substituted linear or branched C 1-6 Alkyl or optionally substituted linear or branched C 1-3 alkyl), optionally substituted cycloalkyl (e.g., optionally substituted C 3-30 Cycloalkyl, optionally substituted C 3-20 Cycloalkyl or optionally substituted C 3-15 cycloalkyl), optionally substituted heterocyclyl (e.g., optionally substituted 4- to 30-membered heterocyclyl, optionally substituted 4- to 20-membered heterocyclyl, or optionally substituted 4- to 15-membered heterocyclyl), optionally substituted aryl (e.g., optionally substituted C 5-30 Aryl, optionally substituted C 5-20 Aryl or optionally substituted C 5- 15aryl) or an optionally substituted heteroaryl (e.g., an optionally substituted 5- to 30-membered heteroaryl, an optionally substituted 5- to 20-membered heteroaryl, or an optionally substituted 5- to 15-membered heteroaryl); and ring D represents a heterocyclyl (e.g., a 4- to 30-membered heterocyclyl, a 4- to 20-membered heterocyclyl, or a 4- to 15-membered heterocyclyl), a cycloalkyl (e.g., C 3-30 Cycloalkyl, C 3-20 Cycloalkyl or C 3-15 Cycloalkyl), aryl (e.g. C 5-30 Aryl, C 5-20 Aryl or C 5-15 aryl) or heteroaryl (e.g., 5- to 30-membered heteroaryl, 5- to 20-membered heteroaryl, or 5- to 15-membered heteroaryl), (R d4 ) n4 represents a ring D optionally replaced by n4 R d4 Group substitution, each R d4 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n4 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0069] In some embodiments of the present disclosure, X represents: wherein Ring A represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group, and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d1 ) n1 Indicates that ring A is optionally replaced by n1 R d1 Group substitution, each R d1 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6alkenyl, and n1 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; Ring B represents a nitrogen-containing heterocyclic group (including a 4- to 30-membered nitrogen-containing heterocyclic group, a 4- to 25-membered nitrogen-containing heterocyclic group, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group and a 5- to 20-membered nitrogen-containing heterocyclic group), (R d2 ) n2 Indicates that ring B is optionally replaced by n2 R d2 Group substitution, each R d2 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n2 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; Ring C represents a cycloalkylene group (e.g., C 3-30 Cycloalkylene, C 3-20 Cycloalkylene or C 3-15 cycloalkylene), heterocyclylene (e.g., 4- to 30-membered heterocyclylene, 4- to 20-membered heterocyclylene, or 4- to 15-membered heterocyclylene), arylene (e.g., C 5-30 Arylene, C 5-20 Arylene or C 5-15 arylene) or heteroarylene (e.g., 5- to 30-membered heteroarylene, 5- to 20-membered heteroarylene, or 5- to 15-membered heteroarylene), m1 represents an integer of 0 or 1, (R d3 ) n3 represents ring C optionally replaced by n3 R d3 Group substitution, each R d3 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n3 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; and ring D represents a heterocyclic group (e.g., a 4- to 30-membered heterocyclic group, a 4- to 20-membered heterocyclic group or a 4- to 15-membered heterocyclic group), a cycloalkyl group (e.g., C 3-30Cycloalkyl, C 3-20 Cycloalkyl or C 3-15 Cycloalkyl), aryl (e.g. C 5-30 Aryl, C 5-20 Aryl or C 5-15 aryl) or heteroaryl (e.g., 5- to 30-membered heteroaryl, 5- to 20-membered heteroaryl, or 5- to 15-membered heteroaryl), (R d4 ) n4 represents a ring D optionally replaced by n4 R d4 Group substitution, each R d4 Each independently represents deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl or C 2-6 alkenyl, and n4 represents an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0070] In some embodiments of the present disclosure, examples of X include, but are not limited to:

[0071] In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (I-1), a compound of formula (I-2), a compound of formula (I-3), or a compound of formula (I-4): The group R a1 、R a2 、R a3 、R a4 , Z1, Z2, Z3, Z4, Z5, (R a5 ) m , R and X are as defined above for the compound of formula (I) and its embodiments.

[0072] In some embodiments of the present disclosure, the compound of formula (I) is also a compound of formula (I-5): Among them, Z1, Z2, Z3, Z4, Z5, (R a5 ) m , R and X are as defined above for the compound of formula (I) and its embodiments.

[0073] In some embodiments of the present disclosure, the compound of formula (I-5) is also a compound of formula (I-5-1): Among them, Z1, (R a5 ) m, R and X are as defined above for the compound of formula (I) and its embodiments.

[0074] In some embodiments of the present disclosure, the compound of formula (I-5) is also a compound of formula (I-5-1A): Among them (R a5 ) m , R and X are as defined above for the compound of formula (I) and its embodiments.

[0075] In some embodiments of the present disclosure, the compound of formula (I-5) is also a compound of formula (I-5-1B): Among them (R a5 ) m , R, L and X are as defined above for the compound of formula (I) and its embodiments.

[0076] In some embodiments of the present disclosure, the compound of formula (I-5) is also a compound of formula (I-5-2): Among them, Z1, (R a5 ) m , R, L and X are as defined above for the compound of formula (I) and its embodiments.

[0077] In some embodiments of the present disclosure, the compound of formula (I-5) is also a compound of formula (I-5-2A): Among them (R a5 ) m , R, L and X are as defined above for the compound of formula (I) and its embodiments.

[0078] In some embodiments of the present disclosure, the compound of formula (I-5) is also a compound of formula (I-5-2B): Among them (R a5 ) m , R, L and X are as defined above for the compound of formula (I) and its embodiments.

[0079] In some embodiments of the present disclosure, the compound of formula (I-5) is also a compound of formula (I-5-3): Among them, Z1, (R a5 ) m , R and X are as defined above for the compound of formula (I) and its embodiments.

[0080] Particularly preferred are the compounds of Table 1 of the present invention and their salts (especially pharmaceutically acceptable salts, such as their hydrochlorides), enantiomers, diastereomers, solvates or polymorphs: Table 1 Compounds of the present invention II. Other Forms of the Compound (including Salts, Enantiomers, Stereoisomers, Solvates, Isotopically Enriched Analogs, Prodrugs, or Polymorphs of the Compound)

[0081] The compounds of the present disclosure have the structure of any one of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (I-5-1), Formula (I-5-1A), Formula (I-5-1B), Formula (I-5-2), Formula (I-5-2A), Formula (I-5-2B), or Formula (I-5-3). Unless otherwise indicated, when referring to the compounds of the present disclosure, it refers to compounds including any one of Formula (I), Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (I-5-1), Formula (I-5-1A), Formula (I-5-1B), Formula (I-5-2), Formula (I-5-2A), Formula (I-5-2B), or Formula (I-5-3), as well as specific compounds falling within the scope of these general formulas.

[0082] It will be appreciated that the compounds of the present disclosure (including compounds of Formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (I-5-1), (I-5-1A), (I-5-1B), (I-5-2), (I-5-2A), (I-5-2B), or (I-5-3)) may have stereo configurations and, therefore, may exist as more than one stereoisomer. The present disclosure also relates to optically enriched compounds having stereo configurations, such as about greater than 90% ee, such as about 95% ee or 97% ee, or greater than 99% ee, and mixtures thereof, including racemic mixtures. As used herein, "optically enriched" means that the mixture of enantiomers is composed of a significantly greater proportion of one enantiomer and can be described by enantiomeric excess (ee%). Purification of isomers and separation of isomeric mixtures can be achieved by standard techniques known in the art (e.g., column chromatography, preparative TLC, preparative HPLC, asymmetric synthesis (e.g., by using chiral intermediates) and / or chiral resolution, etc.).

[0083] In some embodiments, polymorphic forms of the compounds of the present disclosure or salts of the compounds of the present disclosure are also provided. The salts of the compounds of the present disclosure may be pharmaceutically acceptable salts, including but not limited to hydrohalides (including hydrochlorides, hydrobromides), sulfates, citrates, maleates, benzenesulfonates, glycolates, α-D-glucoheptonates, D-gluconates, L-lactates, L-malates, malonates, mandelates, phosphates, propionates, succinates, tartrates, p-toluenesulfonates, valerates, palmitates, sebacates, stearates, laurates, acetates, adipates, carbonates, p-chlorobenzenesulfonates, edisylate, fumarates. The compounds of the present invention can be present in pharmaceutically acceptable solvents such as water, ethanol, etc. in the form of non-solvates or solvates. In some embodiments, the compounds of the present invention can be prepared into prodrugs or prodrugs. Prodrugs can be converted into parent drugs in the body and play a role. In some embodiments, isotope-labeled compounds of the present invention are also provided, and examples of isotopes include deuterium (D or 2 H). III. Pharmaceutical Compositions / Formulations

[0084] In some embodiments, the present disclosure provides a pharmaceutical composition comprising as an active ingredient a compound of the present disclosure or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, polymorph, prodrug, stereoisomer (including enantiomer), or mixture of stereoisomers thereof, and at least one pharmaceutically acceptable carrier.

[0085] In some embodiments, pharmaceutically acceptable carriers include, but are not limited to, fillers, stabilizers, dispersants, suspending agents, diluents, excipients, thickeners, colorants, solvents, or encapsulating materials. A carrier must be "acceptable" if it is compatible with the other ingredients of the formulation (including the compounds useful in the present disclosure) and is not harmful to the patient. Some examples of materials that are pharmaceutically acceptable carriers include: sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols, such as propylene glycol; polyols, such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffers, such as magnesium hydroxide and aluminum hydroxide; phosphate buffered saline surfactants; polyoxyethylene, polyvinyl pyrrolidone, polyacrylamide, poloxamer; and other nontoxic compatible substances used in pharmaceutical formulations.

[0086] The pharmaceutical composition of the present disclosure further includes at least one second therapeutic agent, such as an anticancer agent. The second therapeutic agent can be combined with the compound of formula (I) described herein to treat the disease or condition described herein. The second therapeutic agent includes, but is not limited to, a chemotherapeutic agent, an immunotherapeutic agent, a gene therapy agent, and the like.

[0087] The pharmaceutical composition of the present disclosure comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient can be prepared into a suitable dosage form according to a suitable administration route (including but not limited to nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration, peritoneal administration, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration and intravenous administration), such as spray preparations, patches, tablets (such as conventional tablets, dispersible tablets, orally disintegrating tablets), capsules (such as soft capsules, hard capsules, enteric-coated capsules), dragees, lozenges, powders, granules, powder injections, suppositories, or liquid preparations (such as suspensions (such as aqueous or oily suspensions), solutions, emulsions or syrups), or conventional injection forms such as injectable solutions (such as sterile injection solutions prepared according to methods known in the art using water, Ringer's solution or isotonic sodium chloride solution as a carrier or solvent) or lyophilized compositions. Those skilled in the art can also prepare the compound of formula (I) into conventional, dispersible, chewable, orally rapidly disintegrating or rapidly dissolving preparations, or sustained-release capsules or controlled-release capsules as needed.

[0088] As the active ingredient, the compound of formula (I) as described in the present disclosure is contained in a pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver to the subject a therapeutically effective amount for the indication to be treated without causing serious toxic effects in the treated subject. The dosage of the active compound for all diseases or conditions mentioned herein is, for example, from about 5 ng / kg subject weight / day to 500 mg / kg subject weight / day, from about 10 ng / kg subject weight / day to 300 mg / kg subject weight / day, for example, from 0.1 to 100 mg / kg subject weight / day, or from 0.5 to about 25 mg / kg subject weight / day.

[0089] The compounds of formula (I) or pharmaceutically acceptable salts thereof described herein can be conveniently administered in any suitable dosage form, including but not limited to dosage forms containing less than 1 mg, 1 mg to 3000 mg, 5 mg to 1000 mg, such as 5 to 500 mg, 25 to 250 mg of active ingredient per unit dosage form. IV. Kits / Packaging

[0090] The compound of formula (I) described in the present disclosure, or its pharmaceutically acceptable salt, solvate, isotopically enriched analog, polymorph, prodrug, stereoisomer (including enantiomer), or mixture of stereoisomers, is used as a medicament. The medicament of the present disclosure or the pharmaceutical composition of the present disclosure may be present in a medicine box / packaged product. The medicine box / packaged product may include packaging or container. The packaging or container includes, but is not limited to, ampoules, blister packs, pharmaceutical plastic bottles, vials, pharmaceutical glass bottles, containers, syringes, laminated flexible packaging, co-extruded film infusion containers, test tubes and dispensing devices, etc. The medicine box / packaged product may include product instructions. V. Methods of treatment and use

[0091] The compounds of formula (I) described herein, or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polymorphs, prodrugs, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, can also be used as pharmaceutical agents. In particular, the compounds of formula (I) described herein, or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polymorphs, prodrugs, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, can be used to prepare medicaments for preventing and / or treating diseases or conditions. The diseases or conditions include medicaments for diseases or conditions associated with cereblon proteins.

[0092] In some embodiments, the disease or condition comprises: tumor, infectious disease, inflammatory disease, autoimmune disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure and diabetes.

[0093] In some embodiments, the disease or condition includes, but is not limited to, myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; neutropenia; leukemia, including acute myeloid leukemia, chronic myeloid leukemia (CML), chronic myeloid leukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, anemia associated with leukemia, acute B lymphocytic leukemia, T Lymphocytic leukemia, acute T-lymphocytic leukemia, lymphoma cell leukemia, monocytic leukemia, myelomonocytic leukemia; lymphoma, including diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, immunoblastic T-cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin's lymphoma, relapsed diffuse large B-cell lymphoma, relapsed mediastinal (thymic) large B-cell lymphoma, Primary mediastinal (thymic) large B-cell lymphoma, relapsed transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin's lymphoma; Burkitt's lymphoma; thyroid cancer; melanoma; lung cancer, including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; glioma; glioblastoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and breast Patients with pancreatic cancer, central nervous system cancer, neuroblastoma, glioma, peripheral neuroepithelial tumor, extramedullary plasmacytoma, plasmacytoma, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, colorectal adenocarcinoma, esophageal squamous cell carcinoma, liver cancer, renal cell carcinoma, bladder cancer, endometrial cancer, uterine cancer, head and neck cancer, brain cancer, oral cancer, sarcomas, including rhabdomyosarcoma, various adipose tumors, Ewing sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma, urothelial carcinoma, basal cell carcinoma, oral squamous cell carcinoma, bile duct cancer, bone cancer, cervical cancer, skin cancer, Richter syndrome (RS), and sepsis syndrome.Autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjögren's syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type 1 diabetes, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, AIDS, COVID-19 novel coronavirus infection, Gram-negative bacterial infection, Gram-positive bacterial infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular disease (such as coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure caused by cachexia and septic shock; and acute liver failure.

[0094] The present disclosure provides a method for preventing and / or treating a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I) as described herein or a pharmaceutically acceptable salt thereof as an active ingredient. In some embodiments, the disease or condition includes a disease or condition associated with cereblon protein. The disease or condition is as defined herein.

[0095] In the method for preventing and / or treating a disease or condition associated with cereblon protein in a subject, a therapeutically effective amount of a compound of formula (I) according to the present disclosure, or a pharmaceutical composition comprising a compound of formula (I) as an active ingredient according to the present disclosure, is administered to the subject by at least one administration route selected from nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration, peritoneal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural space administration, intrathecal administration, and intravenous administration.

[0096] The term "treatment" or "treating" refers to administering to a subject a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient, to slow (mitigate) the development of an undesirable disease or condition (e.g., a tumor). Beneficial or desired clinical outcomes of the present disclosure include, but are not limited to, alleviating symptoms, reducing the severity of the disease, stabilizing the state of the disease, delaying or slowing the progression of the disease, improving or alleviating the condition, and alleviating the disease.

[0097] A "therapeutically effective amount" of a compound of the present disclosure depends on a variety of factors, including the activity of the particular compound used, the metabolic stability and duration of action of the compound, the age, sex, and weight of the patient, the patient's overall medical condition, the route and timing of administration, the rate of excretion, concomitant medications, and the progression of the disease or condition being treated in the patient. One skilled in the art will be able to determine an appropriate dosage based on these and other factors.

[0098] It should be understood that the choice of using one or more active compounds and / or compositions and their dosages depends on the individual's basic conditions (generally, the individual's conditions should be optimized). Administration and dosing regimens should be within the capabilities of those skilled in the art, and appropriate dosages depend on many factors including the knowledge and ability level of the ordinary skilled physician, veterinarian, or researcher (see, for example, Li Jun, ed., "Clinical Pharmacology," 4th edition, People's Medical Publishing House (2008)).

[0099] The patient or subject for treatment is an animal, such as a mammal, including but not limited to primates (such as humans), cattle, sheep, goats, horses, dogs, cats, rabbits, guinea pigs, rats, mice, etc. VI. Preparation Method

[0100] The compound of formula (I) disclosed herein can be prepared by reacting a compound of formula (M1) with a compound of formula (M2): The group R a1 、R a2 、R a3 、R a4 、(R a5 ) m , Z1, Z2, Z3, Z4, Z5, (R d1 ) n1 , Ring B, (R d2 ) n2 、R c 、 Ring C、m1、(R d3 ) n3 , Ring D, and (R d4 ) n4As defined in the compounds of formula (I) and its various sub-embodiments disclosed herein; Nitrogen-containing heterocycle A represents a 4- to 30-membered nitrogen-containing heterocycle (preferably, a 4- to 20-membered nitrogen-containing heterocycle; more preferably, a 4- to 15-membered nitrogen-containing heterocycle); R represents an optionally substituted linear or branched C 1-5 Alkylene; LE represents Cl, Br, I, methanesulfonyloxy, p-toluenesulfonyloxy, o-nitrobenzenesulfonyl, C(O)Cl or COOH; and X of the compound of formula (I) a The structure represented by the following general formula is represented accordingly: wherein the nitrogen-containing heterocyclic group A represents a 4- to 30-membered nitrogen-containing heterocyclic group (preferably, a 4- to 20-membered nitrogen-containing heterocyclic group; more preferably, a 4- to 15-membered nitrogen-containing heterocyclic group), (R d1 ) n1 , Ring B, (R d2 ) n2 、R c 、ring C、m1、(R d3 ) n3 , Ring D, and (R d4 ) n4 As defined in the compounds of formula (I) and its various subembodiments disclosed herein.

[0101] In some embodiments of the method of preparing the compound of formula (I) disclosed herein, R represents -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4- or -(CH2)5-; wherein the above groups are optionally selected from deuterium, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0102] In some embodiments of the method for preparing the compound of formula (I) disclosed herein, the nitrogen-containing heterocycle A, after reacting to remove the hydrogen atom on the N, obtains a nitrogen-containing heterocyclic group A. In some embodiments, the nitrogen-containing heterocycle A represents a 4- to 30-membered nitrogen-containing heterocycle (preferably, a 4- to 20-membered nitrogen-containing heterocycle; more preferably, a 4- to 15-membered nitrogen-containing heterocycle). The nitrogen-containing heterocyclic group A represents a 4- to 30-membered nitrogen-containing heterocyclic group (preferably, a 4- to 20-membered nitrogen-containing heterocyclic group; more preferably, a 4- to 15-membered nitrogen-containing heterocyclic group).

[0103] In some embodiments of the method for preparing a compound of formula (I) disclosed herein, when LE represents Cl, Br, I, methanesulfonyloxy, p-toluenesulfonyloxy, or o-nitrobenzenesulfonyl, the compound of formula (M1) undergoes an amine alkylation reaction with the compound of formula (M2). In some embodiments, the amine alkylation reaction can be carried out, for example, in the presence of an organic base and sodium iodide at room temperature to 80°C (e.g., 40°C to 60°C, 40°C to 50°C, or 50°C to 60°C). Examples of organic bases include, but are not limited to, DIEA or triethylamine. In some embodiments, the molar ratio of the compound of formula (M1) to the compound of formula (M2) can be, for example, 1:1.0-2, 1:1.1-2, 1:1.1-1.5, 1:1.1-1.2, or 1:1.2-1.3, etc.

[0104] In some embodiments of the method for preparing a compound of formula (I) disclosed herein, when LE represents COOH, an amide condensation reaction occurs between the compound of formula (M1) and the compound of formula (M2). In some embodiments, the amide condensation reaction can be carried out, for example, in the presence of an organic base and HATU at room temperature. Examples of organic bases include, but are not limited to, DIEA or triethylamine. In some embodiments, the molar ratio of the compound of formula (M1) to the compound of formula (M2) can be, for example, 1:1.0-2, 1:1.1-2, 1:1.1-1.5, 1:1.1-1.2, or 1:1.2-1.3, etc.

[0105] In some embodiments of the method of preparing the compound of formula (I) disclosed herein, when the group LE represents a methanesulfonyloxy group, the compound of formula (M1) is prepared by reacting the compound of formula (M3) with methanesulfonic anhydride or methanesulfonyl chloride: The group R a1 、R a2 、R a3 、R a4 、(R a5 ) m , Z1, Z2, Z3, Z4, Z5 and R are as defined in the compounds of formula (I) and its various sub-embodiments disclosed herein. In some embodiments, R may represent CH2.

[0106] In some embodiments of the method for preparing the compound of formula (I) disclosed herein, when the group LE represents Cl, Br or I, the compound of formula (M1) can be prepared by a halogenation reaction of a compound of formula (M3) with a hydrohalic acid: The group R a1 、R a2 、R a3 、R a4 、(R a5 ) m, Z1, Z2, Z3, Z4, Z5 and R are as defined in the compounds of formula (I) and its various sub-embodiments disclosed herein. In some embodiments, R may represent CH2.

[0107] In some embodiments of the method for preparing the compound of formula (I) disclosed herein, the compound of formula (M3) (wherein R represents CH2) can be prepared by coupling a compound of formula (M4) with (tributyltin)methanol in the presence of a palladium catalyst: The group R a1 、R a2 、R a3 、R a4 、(R a5 ) m , Z1, Z2, Z3, Z4 and Z5 are as defined in the compounds of formula (I) and various sub-embodiments thereof disclosed herein.

[0108] In some embodiments, the coupling reaction can be carried out, for example, in the presence of tetrakis(triphenylphosphine)palladium and 1,4-dioxane (or DMF) at 40°C to 120°C.

[0109] In some embodiments, when Z5 in the compound of formula (M4) represents N, and Z1 represents C(O), CH2 or CD2, and Z2, Z3 and Z4 each independently represent C(O), the compound of formula (M4) is prepared by subjecting the compound of formula (M5) to an amine transesterification reaction with the compound of formula (M6): The group R a1 、R a2 、R a3 、R a4 and (R a5 ) m As defined in the compounds of formula (I) and various subembodiments thereof of the present disclosure.

[0110] In some embodiments, the amine transesterification reaction can be carried out in the presence of CH3ONa and methanol at room temperature. Alternatively, the amine transesterification reaction can be carried out in the presence of CH3OLi or Cs2CO3 and methanol at 40°C to 90°C, or in the presence of DBU and THF at 40°C to 90°C.

[0111] In some embodiments, when Z1 in the compound of formula (M4) represents C(O), C(S), CH2 or CD2, Z2, Z3 and Z4 each independently represent C(O) or C(S), and at least one of Z1, Z2, Z3 and Z4 represents C(S), the compound of formula (M4) is prepared by thionating the compound of formula (M7) with a thionating agent: wherein Z6 of the compound of formula (M7) represents C(O), CH2 or CD2; and the group R a1 、R a2 、R a3 、R a4 and (R a5 ) m As defined in the compounds of formula (I) and its various sub-embodiments of the present disclosure. When Z6 of the compound of the starting material formula (M7) represents CH2 or CD2, the corresponding Z1 in the thiocarbonyl compound of the product formula (M4) represents CH2 or CD2. When Z6 of the compound of the starting material formula (M7) represents C(O), the corresponding Z1 in the thiocarbonyl compound of the product formula (M4) represents C(O) or C(S).

[0112] In some embodiments, examples of sulfurizing agents include, but are not limited to, carbon disulfide, hexamethyldisilathioane, sulfur, thiourea, hydrogen sulfide, phosphorus pentasulfide, Lawesson's Reagent (CAS No.: 19172-47-5), Belleau's Reagent (CAS No.: 88816-02-8), and Davy's Reagent (CAS No.: 82737-61-9), etc.

[0113] In some embodiments, the compound of formula (M7) is reacted with a sulfiding reagent (eg, Lawesson's reagent) in a solvent (eg, 1,4-dioxane) at 40° C. to 150° C. to prepare a thiocarbonyl compound of formula (M4).

[0114] In some embodiments, at least one of Z1, Z2, Z3, and Z4 of the thiocarbonyl compound of formula (M4) represents C(S). In some embodiments, at least two of Z1, Z2, Z3, and Z4 of the thiocarbonyl compound of formula (M4) represent C(S). In some embodiments, at least three of Z1, Z2, Z3, and Z4 represent C(S). In some embodiments, Z1, Z2, Z3, and Z4 all represent C(S). VII. Definitions

[0115] Unless otherwise specified, the following words, phrases and symbols used in this specification generally have the meanings described below.

[0116] In general, the nomenclature used herein (including IUPAC nomenclature) and the laboratory procedures described below (including for cell culture, organic chemistry, analytical chemistry and pharmacology, etc.) are those well known and commonly used in the art. Unless otherwise defined, all scientific and technical terms used herein in conjunction with the present disclosure described herein have the same meaning as commonly understood by those skilled in the art. In addition, in the claims and / or the specification, when the term "one" or "an" is used in conjunction with the term "comprising" or a noun, its meaning may be "one", but is also consistent with the meaning of "one or more", "at least one" and "one or more than one". Similarly, the term "another" or "other" can mean at least a second or more.

[0117] It should be understood that whenever various aspects are described herein using the terms "including" or "comprising," other similar aspects described by "consisting of" and / or "consisting essentially of" are also provided.

[0118] The term "about," used alone or in combination, is used herein to mean approximately, roughly, roughly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values ​​recited. Generally, the term "about" can modify a numerical value above and below the recited value by a variation, for example, 10%, 5%, 2%, or 1%, above or below the recited value.

[0119] In this document, the term " ... represents a bond" used alone or in combination means that it is a bond linker (ie, it does not exist). For example, the term "R c "Represents a key" means R c is a bond linker. In other words, when R c When it is a bond, the ring B group of the structure of formula (I) is directly connected to the ring C in the structure of formula (I).

[0120] As used herein, the term "optionally substituted" used alone or in combination means that the indicated group may be unsubstituted or substituted with one or more substituents as defined herein. The terms "optionally substituted with" and "unsubstituted or substituted" are used interchangeably herein. The term "substituted" generally means that one or more hydrogen atoms in the structure being referred to are replaced with the same or different specific substituents. The number of substituents is not subject to any limitation in principle, or is automatically limited by the size of the building block (i.e., the total number of hydrogen atoms of the building block that can be replaced), or as explicitly defined herein.

[0121] In this document, a bond broken by a wavy line shows the point of attachment of the depicted group to the rest of the molecule. For example, the monovalent group X shown below The ring A representing the group X is connected to the group R of the structure of formula (I).

[0122] As used herein, the term "substituted by one or more substituents selected from...", used alone or in combination, may mean that some or all of the hydrogen atoms of the group mentioned are replaced by substituents, and the number of substituents includes, but is not limited to, 1-40, such as 1-30, such as 1-25, 1-20, 1-15, 1-10, 1-5, 1-4, 1-3, 1-2 or 1. This number is not subject to any limitation in principle and is not automatically limited by the size of the building block. For example, when the group mentioned is a methyl group, the number of substituents may be 1-3.

[0123] As used herein, the term "deuterated," alone or in combination, means that one or more hydrogens of the referenced group are replaced by a deuterium atom.

[0124]

[0046] As used herein, the term "oxo" or "oxo," alone or in combination, refers to =0.

[0125] As used herein, the term "carbonyl," alone or in combination, refers to C(O) or C(=O).

[0126]

[0046] As used herein, the term "thiocarbonyl" or "thiocarbonyl," used alone or in combination, refers to C(S) or C(=S).

[0127] As used herein, the term "halogen atom" or "halogen" alone or in combination refers to fluorine, chlorine, bromine or iodine.

[0128] As used herein, the term "alkyl" used alone or in combination refers to a straight chain or branched chain alkyl group. x -C y Alkyl" or "C x-y "alkyl" (x and y are each an integer) refers to a straight or branched chain alkyl group containing x to y carbon atoms. The term "C1-C 10 "Alkyl" refers to a straight or branched chain alkyl group containing 1 to 10 carbon atoms. The term "C1-C 10 Examples of "alkyl" include C 1-9 Alkyl, C 1-8 Alkyl, C 2-8 Alkyl, C 1-7 Alkyl, C 1-6 Alkyl, C 1-5 Alkyl, C 1-4 Representative examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl. The term "C1-C3 alkyl" in this disclosure refers to a group consisting of a C1-C2 alkyl group and a C1-C2 alkyl group. 1-3"Alkyl" or "C1-C3 alkyl" refers to an alkyl group containing 1 to 3 carbon atoms, representative examples of which include methyl, ethyl, n-propyl and isopropyl. In the present disclosure, the "alkyl" is optionally substituted, and the substituents are optionally one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) selected from, for example, halogen, hydroxyl, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl (e.g. trifluoromethyl), C 3-6 Substituents of the cycloalkyl group and the 4- to 7-membered heterocyclic group.

[0129] As used herein, the term "haloalkyl" alone or in combination refers to a linear or branched alkyl group substituted with one or more halogens, wherein one or more hydrogen atoms in the alkyl group are replaced with halogen atoms. x -C y Alkyl" or "halogenated C x-y "alkyl" (x and y are each an integer) refers to a straight or branched chain alkyl group containing x to y carbon atoms substituted by one or more halogens. The term "halogenated C 1-10 "Alkyl" refers to a straight or branched chain alkyl group containing 1 to 10 carbon atoms substituted by one or more halogens. 1-10 Examples of alkyl groups include halo-C 1-9 Alkyl groups, such as halogenated C 1-8 Alkyl, halogenated C 2-8 Alkyl, halogenated C 1-7 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-5 Alkyl, or halogenated C 1-4 Representative examples include halogenated methyl, halogenated ethyl, halogenated n-propyl, halogenated isopropyl, halogenated n-butyl, halogenated isobutyl, halogenated sec-butyl, halogenated tert-butyl, halogenated pentyl, halogenated isopentyl, halogenated neopentyl, halogenated tert-pentyl, halogenated hexyl, halogenated heptyl, halogenated octyl, halogenated nonyl and halogenated decyl. The term "halogenated C 1-3 "Alkyl" or "halogenated C1-C3 alkyl" refers to an alkyl group containing 1 to 3 carbon atoms substituted by one or more halogens, representative examples of which include halomethyl (e.g., trifluoromethyl), haloethyl, halo-n-propyl, and halo-isopropyl.

[0130] As used herein, the term "deuterated alkyl" alone or in combination refers to a straight or branched chain alkyl group substituted with one or more deuterium atoms, wherein one or more hydrogen atoms in the alkyl group are replaced with deuterium atoms. x -C y Alkyl" or "deuterated C x-y"alkyl" (x and y are each an integer) refers to a straight or branched chain alkyl group containing x to y carbon atoms substituted by one or more deuterium atoms. The term "deuterated C 1-10 "Alkyl" refers to a straight or branched chain alkyl group containing 1 to 10 carbon atoms substituted by one or more deuterium atoms. 1-10 Examples of alkyl groups include deuterated C 1-9 Alkyl groups, such as deuterated C 1-8 Alkyl, deuterated C 2-8 Alkyl, deuterated C 1-7 Alkyl, deuterated C 1-6 Alkyl, deuterated C 1-5 Alkyl, or deuterated C 1-4 Representative examples include perdeuterated methyl (CD3), perdeuterated ethyl (CD3CD2), perdeuterated n-propyl, perdeuterated isopropyl, perdeuterated n-butyl, perdeuterated isobutyl, perdeuterated sec-butyl, perdeuterated tert-butyl, perdeuterated pentyl, perdeuterated isopentyl, perdeuterated neopentyl, perdeuterated tert-pentyl, and perdeuterated hexyl. The term "deuterated C 1-3 "Alkyl" or "deuterated C1-C3 alkyl" refers to an alkyl group containing 1 to 3 carbon atoms substituted by one or more deuterium atoms, representative examples of which include perdeuterated methyl (CD3-) and perdeuterated ethyl (CD3CD2).

[0131] As used herein, the term "alkylene" (which is used interchangeably with "alkylene chain"), used alone or in combination, refers to a straight or branched divalent saturated hydrocarbon group consisting of carbon and hydrogen, which is a divalent radical form of a straight or branched alkyl group. x -C y "Alkylene" or "C x-y "alkylene" (x and y are each an integer) refers to a straight or branched chain alkylene containing x to y carbon atoms. The term "C1-C5 alkylene" as used herein, alone or in combination, refers to a straight or branched chain alkylene containing 1 to 5 carbon atoms, examples of which include, but are not limited to, C1-C4 alkylene, C1-C3 alkylene, and C1-C2 alkylene. Representative examples include, but are not limited to, methylene (i.e., -CH2-), ethylene (e.g., -CH2CH2-), propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, pentylene, isopentylene, neopentylene, and tert-pentylene. In the present disclosure, the "alkylene" is optionally substituted, and the substituents are optionally one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) selected from, for example, deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Substituents of an alkenyl group.

[0132] As used herein, the term "alkoxy" used alone or in combination refers to a straight or branched chain alkoxy group having the formula alkyl-O-. Optionally, the alkyl portion of the alkoxy group may contain 1-10 (e.g., 1-6, 1-4, or 1-3) carbon atoms. Representative examples of "alkoxy" include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentoxy, 2-pentoxy, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, 3-hexoxy, 3-methylpentoxy, and the like. The term "C1-C6 alkoxy" or "C 1-6 "Alkoxy" refers to a straight or branched chain alkoxy group containing 1 to 6 carbon atoms. 1- Representative examples of 6-alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, butoxy, pentyloxy, and hexyloxy.

[0133] As used herein, the term "haloalkoxy" alone or in combination refers to an alkoxy group substituted with one or more halogens. Optionally, the alkyl portion of the alkoxy group may contain 1-10 (e.g., 1-6, 1-4, or 1-3) carbon atoms. Examples of "haloalkoxy" include halogenated C 1-6 Alkoxy and halogenated C 1-4 Representative examples include, but are not limited to, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-.

[0134] In the present invention, the term "heteroaryl", used alone or in combination, refers to a 5- to 30-membered (alternatively 5- to 20-membered, 5- to 15-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 6- to 15-membered, 6- to 9-membered or 6- to 20-membered) monocyclic or bicyclic or polycyclic hydrocarbon group containing at least one aromatic ring having 1 or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen and sulfur. Bicyclic or polycyclic heteroaryl groups include bicyclic, tricyclic, tetracyclic or polycyclic heteroaryl groups, one of which is an aromatic ring having one or more (e.g., 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from O, S, and N, and the other rings of which may be saturated, partially unsaturated, or aromatic and may be carbocyclic or contain one or more (e.g., 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from O, S, and N. Examples of monocyclic heteroaryl groups include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, tetrazolyl, and triazinyl. Examples of bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindolyl, isoindolinyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, oxazolopyridinyl, furopyridinyl, pteridinyl, purinyl, pyridopyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrrolo[2,1-b]thiazolyl, imidazo[2,1-b]thiazolyl, chromanyl and 6,7-dihydrothieno[3,2-d]pyrimidinyl. Examples of tricyclic or polycyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, xanthenyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl. The heteroaryl groups may be unsubstituted or substituted. Substituted heteroaryl refers to heteroaryl groups substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with substituents, wherein the substituents are optionally selected from, for example, deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0135] In the present invention, the term "heteroarylene" used alone or in combination refers to a divalent group of a 5- to 30-membered (alternatively 5- to 20-membered, 5- to 15-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 6- to 15-membered, 6- to 9-membered or 6- to 20-membered) monocyclic or bicyclic or polycyclic hydrocarbon containing at least one aromatic ring having 1 or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen and sulfur. Bicyclic or polycyclic heteroarylene groups include bicyclic, tricyclic, tetracyclic or polycyclic heteroarylene groups, one of which is an aromatic ring having one or more (e.g., 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from O, S, and N, and the other rings may be saturated, partially unsaturated, or aromatic and may be carbocyclic or contain one or more (e.g., 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from O, S, and N. Examples of monocyclic heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, tetrazolylene, and triazinylene. Examples of bicyclic heteroarylene groups include, but are not limited to, indolylene, isoindolylene, isoindolinylene, benzofuranylene, isobenzofuranylene, benzothiophenylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoline oxalinyl, phthalazinyl, oxazolopyridylene, furopyridylene, pteridylene, purinylene, pyridopyridylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]pyridinylene, 1H-pyrrolo[2,3-b]pyridinylene, pyrrolo[2,1-b]thiazolylene, imidazo[2,1-b]thiazolylene, chromanylene and 6,7-dihydrothieno[3,2-d]pyrimidinylene. Examples of tricyclic or polycyclic heteroarylene groups include, but are not limited to, acridinylene, benzindolylene, carbazolylene, dibenzofuranylene, xanthenylene, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinylene, and 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinylene. The heteroarylene groups may be unsubstituted or substituted.Substituted heteroarylene refers to a heteroarylene group substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with substituents, wherein the substituents are optionally selected from, for example, deuterium, hydroxy, amino, thiol, 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, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0136] As used herein, the term "aryl" used alone or in combination refers to a monovalent aromatic hydrocarbon group comprising 5 to 30 (e.g., 5-20, 5-15, 5-12, 5-10, 5-9, 5-8, 5-7, 5-6, 6-15, 6-9, or 6-20) carbon atoms and optionally comprising one or more fused rings, such as phenyl or naphthyl or fluorenyl. In the present disclosure, the "aryl" is an optionally substituted aryl. A substituted aryl refers to an aryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) by a substituent, e.g., an aryl monosubstituted, disubstituted, trisubstituted, or polysubstituted aryl, wherein the substituent is optionally selected from, for example, deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0137] In the present disclosure, the term "arylene", used alone or in combination, refers to a divalent aromatic hydrocarbon group containing 5 to 30 (e.g., 5-20, 5-15, 5-12, 5-10, 5-9, 5-8, 5-7, 5-6, 6-15, 6-9, or 6-20) carbon atoms and optionally containing one or more fused rings, such as phenylene (e.g., ) or naphthylene or fluorenylene. In the present disclosure, the "arylene" is an optionally substituted arylene. Substituted arylene refers to an arylene substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) by a substituent, for example, an arylene is monosubstituted, disubstituted, trisubstituted, or polysubstituted by a substituent, wherein the substituent is optionally selected from, for example, deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0138] As used herein, the term "cycloalkyl" alone or in combination refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) monocyclic, bicyclic, tricyclic, or polycyclic hydrocarbon radical containing, but not limited to, 3 to 30 carbon atoms (i.e., C 3-30 Cycloalkyl), 3 to 25 carbon atoms (i.e., C 3-25 Cycloalkyl), 3 to 20 carbon atoms (i.e., C 3-20 Cycloalkyl), 3 to 15 carbon atoms (i.e., C 3-15 Cycloalkyl), 3 to 12 carbon atoms (i.e., C 3-12 Cycloalkyl), 3 to 11 carbon atoms (i.e., C 3-11 Cycloalkyl), 3 to 10 carbon atoms (i.e., C 3-10 Cycloalkyl), 3 to 8 carbon atoms (i.e., C 3-8 Cycloalkyl), 3 to 7 carbon atoms (i.e., C 3-7 Cycloalkyl), 3 to 6 carbon atoms (i.e., C 3-6 Cycloalkyl), 4 to 20 carbon atoms (i.e., C 4-20 Cycloalkyl), 4 to 15 carbon atoms (i.e., C 4-15 Cycloalkyl), 4 to 12 carbon atoms (i.e., C 4-12 cycloalkyl), and 4 to 10 carbon atoms (i.e., C 4-10 The term "cycloalkyl" includes monocyclic, bicyclic, tricyclic and polycyclic cycloalkyl groups having 3 to 30 carbon atoms. Examples of the term "cycloalkyl" include, but are not limited to, monocyclic cycloalkyl groups, bridged cycloalkyl groups (e.g., C 5-30 Bridged cycloalkyl, C 5-20Bridged cycloalkyl, C 5-15 Bridged cycloalkyl and C 7-15 Bridged cycloalkyl), fused cycloalkyl (e.g. C 5-30 Condensed cycloalkyl, C 5-20 Condensed cycloalkyl, C 5-15 Condensed cycloalkyl, C 6-30 Condensed cycloalkyl, C 6-20 Condensed cycloalkyl, C 6-15 Condensed cycloalkyl, C 7-30 Condensed cycloalkyl, C 7-20 Condensed cycloalkyl, C 7-15 Fused cycloalkyl and C 8-15 fused cycloalkyl) and spirocycloalkyl (e.g. C 5-30 Spiroalkyl, C 5-20 Spiroalkyl, C 5-15 Spiroalkyl, C 6-30 Spiroalkyl, C 6-20 Spiroalkyl, C 6-15 Spiroalkyl, C 7-30 Spiroalkyl, C 7-20 Spiroalkyl, C 7-15 Spiroalkyl and C 8-15 Representative examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Examples of fused cycloalkyl groups, spirocycloalkyl groups, and bridged cycloalkyl groups include, but are not limited to, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, C 5-20 Spiroalkyl, C 5-15 Spirocycloalkyl, adamantyl, noradamantyl, bornyl and norbornyl (IUPAC system named bicyclo [2.2.1] heptyl). Herein, the "cycloalkyl" is optionally monosubstituted or polysubstituted, for example but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl. The substituents of the substituted "cycloalkyl" are optionally one or more (for example 1-5, 1-4, 1-3, 1-2, or 1) selected from, for example, deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C2-6 The term "C 3-6 Examples of "cycloalkyl" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, and cyclohexyl.

[0139] In this document, the term “C x-y Spirocycloalkyl" (x and y are each an integer) refers to a spirocycloalkyl group containing x to y carbon atoms. The term "C 5-30 The term "spirocycloalkyl" refers to a spirocycloalkyl group containing 5 to 30 (for example, but not limited to, 5-20, 5-15, 7-20, 7-15, 5-11, 5-10, and 7-9) carbon atoms. 5-30 Spirocyclyl" includes "C 5-20 Spirocyclyl", "C 5-15 Spirocyclyl", "C 7-15 Spirocycloalkyl" and "C 7-20 Spirocycloalkyl”, representative examples of which include, but are not limited to, spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl and spiro[5.5]undecyl. The “C 5-30 The spirocycloalkyl group is optionally further selected from, for example, deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 The alkenyl group is substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) of the substituents of the alkenyl group.

[0140] In this document, the term “C x-y "C-bridged cycloalkyl" (x and y are each an integer) refers to a bridged cycloalkyl group containing x to y carbon atoms. The term "C-bridged cycloalkyl" used alone or in combination in the present invention refers to a bridged cycloalkyl group containing x to y carbon atoms. 5-30 The term "bridged cycloalkyl" refers to a bridged cycloalkyl group containing 5 to 30 (for example, but not limited to, 5-20, 6-20, 7-20, 5-15, 7-15, 5-11, 5-10, and 7-9) carbon atoms. 5-30 "Bridged cycloalkyl" includes "C5-C20 Bridged ring group", "C6-C 20 Bridged ring group", "C7-C 20 Bridged ring group", "C 5-15 Bridged cycloalkyl" and "C7-C 15 "bridged ring group", representative examples of which include but are not limited to adamantyl, noradamantyl, bornyl, norbornyl (systematically named bicyclo[2.2.1]heptyl), 2-oxobicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl and cubanyl. The "C 5-30 The bridged cycloalkyl group is optionally substituted with 1 to 10 (e.g., 1-6, 1-5, 1-4, or 1-3) substituents selected from the group consisting of deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0141] In the present invention, the term "cycloalkylene" used alone or in combination refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not completely conjugated) monocyclic, bicyclic, tricyclic, or polycyclic hydrocarbon divalent group, which contains, but is not limited to, 3 to 30 carbon atoms (i.e., C 3-30 Cycloalkyl), 3 to 25 carbon atoms (i.e., C 3-25 Cycloalkyl), 3 to 20 carbon atoms (i.e., C 3-20 Cycloalkylene), 3 to 15 carbon atoms (i.e., C 3-15 Cycloalkylene), 3 to 12 carbon atoms (i.e., C 3-12 Cycloalkylene), 3 to 11 carbon atoms (i.e., C 3-11 Cycloalkylene), 3 to 10 carbon atoms (i.e., C 3-10 Cycloalkylene), 3 to 8 carbon atoms (i.e., C 3-8 Cycloalkylene), 3 to 7 carbon atoms (i.e., C 3-7 Cycloalkylene), 3 to 6 carbon atoms (i.e., C 3-6 Cycloalkylene), 4 to 20 carbon atoms (i.e., C 4-20 Cycloalkylene), 4 to 15 carbon atoms (i.e., C4-15 Cycloalkylene), 4 to 12 carbon atoms (i.e., C 4-12 cycloalkylene), and 4 to 10 carbon atoms (i.e., C 4-10 The term "cycloalkylene" includes monocyclic, bicyclic, tricyclic and polycyclic hydrocarbon divalent groups having 3 to 30 carbon atoms. Examples of the term "cycloalkylene" include, but are not limited to, monocyclic cycloalkylene, bridged cycloalkylene (e.g., C 5-30 Cycloalkylene bridged, C 5-20 Cycloalkylene bridged, C 5-15 Bridged cycloalkyl and C 7-15 bridged cycloalkylene), fused cycloalkylene (e.g. C 5-30 Fused cycloalkylene, C 5- 20 Fused cycloalkylene, C 5-15 Fused cycloalkylene, C 6-30 Fused cycloalkylene, C 6-20 Fused cycloalkylene, C 6-15 Fused cycloalkylene, C 7-30 Fused cycloalkylene, C 7-20 Fused cycloalkylene, C 7-15 Fused cycloalkylene and C 8-15 fused cycloalkylene) and spirocycloalkylene (e.g. C 5- 30 Spirocycloalkylene, C 5-20 Spirocycloalkylene, C 5-15 Spirocycloalkylene, C 6-30 Spirocycloalkylene, C 6-20 Spirocycloalkylene, C 6-15 Spirocycloalkylene, C 7-30 Spirocycloalkylene, C 7-20 Spirocycloalkylene, C 7-15 Spirocycloalkylene and C 8-15 Representative examples of monocyclic cycloalkylene groups include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, and cyclooctylene. Examples of fused cycloalkylene groups, spirocycloalkylene groups, and bridged cycloalkylene groups include, but are not limited to, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C 5- 20 Spirocyclylene (e.g. C 5-15spirocyclylene), adamantylene, noradamantylene and norbornylene (IUPAC system named bicyclo[2.2.1]heptanylene). In the present disclosure, the "cycloalkylene" is optionally monosubstituted or polysubstituted, for example but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl. The substituents of the substituted "cycloalkylene" are optionally one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Substituents of an alkenyl group.

[0142] In this document, the term “C x-y Spirocycloalkylene" or "C x-y Spirocyclylene" (x and y are each an integer) refers to a spirocycloalkylene group containing x to y carbon atoms. The term "C 5-30 Spirocycloalkylene refers to a spirocycloalkylene group containing 5 to 30 (e.g., 5-20, 5-15, 7-20, 7-15, 5-11, 5-10, 7-9) carbon atoms. The term "C 5-30 Spirocycloalkylene" includes "C 5-20 Spirocycloalkylene", "C 5-15 Spirocycloalkylene", "C 7-15 Spirocycloalkylene" and "C 7-20 Spirocycloalkylene”, representative examples of which include but are not limited to spiro[3.3]heptanediyl, spiro[2.5]octandiyl, spiro[3.5]nonanediyl, spiro[4.4]nonanediyl, spiro[4.5]decanediyl and spiro[5.5]undecanediyl. The “C 5-30 The spirocycloalkylene group is optionally further substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) groups selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0143] In this document, the term “C x-y "C-bridged cycloalkyl" or "C x-y "C-bridged cycloalkyl" (x and y are each an integer) refers to a bridged cycloalkyl group containing x to y carbon atoms. The term "C-bridged cycloalkyl" used alone or in combination in the present invention refers to a bridged cycloalkyl group containing x to y carbon atoms. 5-30 "Cycloalkylene" refers to a cycloalkylene group containing from 5 to 30 (for example, but not limited to, 5-20, 6-20, 7-20, 5-15, 7-15, 5-11, 5-10, and 7-9) carbon atoms. The term "C 5-30 "Cycloalkylene bridged" includes "C 5-20 Sub-bridged cycloalkyl", "C 6-20 Sub-bridged cycloalkyl", "C 7-20 Sub-bridged cycloalkyl", "C 5-15 "Cycloalkylene" and "C 7-15 "C-bridged cycloalkylene", representative examples of which include, but are not limited to, adamantylene, noradamantylene, bornylene, bicyclo[2.2.1]heptanylene, 2-oxobicyclo[2.2.1]heptanylene, bicyclo[2.2.1]heptenylene and cubanylene. The "C-bridged cycloalkylene" is a cycloalkylene radical having a cycloalkylene radical, ... 5-30 The "bridged cycloalkylene" may be further substituted with one or more (e.g., 1-10, 1-6, 1-5, 1-4, or 1-3) selected from deuterium, hydroxyl, amino, thiol, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 The substituents of the alkenyl group are substituted.

[0144] As used herein, the term "heterocyclyl" or "heterocycloalkyl," alone or in combination, refers to a 4- to 30-membered (alternatively 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 4- to 14-membered, 4- to 13-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, 4- to 5-membered, 5- to 9-membered, 5- to 30-membered, 5- to 20-membered, or 5- to 15-membered) monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) cyclic hydrocarbon group containing one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the term “heterocyclyl” include, but are not limited to, monocyclic heterocyclyl (e.g., 4- to 30-membered monocyclic heterocyclyl and 4- to 20-membered monocyclic heterocyclyl), bridged heterocyclyl (e.g., 5- to 30-membered bridged heterocyclyl, 5- to 20-membered bridged heterocyclyl, 7- to 20-membered bridged heterocyclyl and 7- to 15-membered bridged heterocyclyl), fused heterocyclyl (e.g., 5- to 30-membered fused heterocyclyl and 5- to 20-membered fused heterocyclyl) and spiro heterocyclyl (e.g., 5- to 30-membered spiro heterocyclyl and 5- to 20-membered spiro heterocyclyl). Representative examples of monocyclic heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazepan-1-yl), and diazacyclooctanyl. Examples of bridged heterocyclic groups, fused heterocyclic groups, and spiro heterocyclic groups include, but are not limited to, 6-azabicyclo[3.1.1]heptan-3-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl, octahydro-1H-indolyl, and azaspirocyclic groups (e.g., a 5- to 20-membered azaspirocyclic group, such as 3-azaspiro[5.5]undec-3-yl). The heterocyclyl group may be unsubstituted or substituted as defined herein (e.g., mono-, di-, tri-, or polysubstituted), wherein the substituents are optionally selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0145] As used herein, the term "nitrogen-containing heterocyclyl" or "nitrogen-containing heterocycloalkyl", alone or in combination, refers to a 4- to 30-membered (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 4- to 14-membered, 4- to 13-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, 4- to 5-membered, 5- to 9-membered, 5- to 30-membered, 5- to 20-membered, or 5- to 15-membered) monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) cyclic hydrocarbon group containing one nitrogen atom and optionally containing one or more (e.g., containing 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the term “nitrogen-containing heterocyclic group” include, but are not limited to, nitrogen-containing monocyclic heterocyclic groups (e.g., 4- to 30-membered nitrogen-containing monocyclic heterocyclic groups and 4- to 20-membered nitrogen-containing monocyclic heterocyclic groups), nitrogen-containing bridged heterocyclic groups (e.g., 5- to 30-membered nitrogen-containing bridged heterocyclic groups, 5- to 20-membered nitrogen-containing bridged heterocyclic groups, 5- to 15-membered nitrogen-containing bridged heterocyclic groups, 7- to 20-membered nitrogen-containing bridged heterocyclic groups, or 7- to 15-membered nitrogen-containing bridged heterocyclic groups), nitrogen-containing fused heterocyclic groups (e.g., 5- to 30-membered nitrogen-containing fused heterocyclic groups and 5- to 20-membered nitrogen-containing fused heterocyclic groups), and nitrogen-containing spiro heterocyclic groups (e.g., 5- to 30-membered nitrogen-containing spiro heterocyclic groups and 5- to 20-membered nitrogen-containing spiro heterocyclic groups). Representative examples of nitrogen-containing monocyclic heterocyclic groups include, but are not limited to, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazepan-1-yl), and diazacyclooctanyl. Examples of nitrogen-containing bridged heterocyclic groups, nitrogen-containing fused heterocyclic groups, and nitrogen-containing spiro heterocyclic groups include, but are not limited to, 6-azabicyclo[3.1.1]heptan-3-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl, octahydro-1H-indolyl, and azaspirocyclic groups (e.g., a 5- to 20-membered azaspirocyclic group, such as 3-azaspiro[5.5]undec-3-yl). The nitrogen-containing heterocyclic group may be unsubstituted or substituted as defined (e.g., mono-, di-, tri-, or polysubstituted), wherein the substituents are optionally selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0146] As used herein, the term "heterocyclylene" or "heterocycloalkylene," alone or in combination, refers to a 4- to 30-membered (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 4- to 14-membered, 4- to 13-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, 4- to 5-membered, 5- to 9-membered, 5- to 30-membered, 5- to 20-membered, or 5- to 15-membered) monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) divalent cyclic hydrocarbon radical containing one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the term “heterocyclylene” include, but are not limited to, monocyclic heterocyclylene (e.g., 4- to 30-membered monocyclic heterocyclylene, and 4- to 20-membered monocyclic heterocyclylene), bridged heterocyclylene (e.g., 5- to 30-membered bridged heterocyclylene, 5- to 20-membered bridged heterocyclylene, 7- to 20-membered bridged heterocyclylene, or 7- to 15-membered bridged heterocyclylene), fused heterocyclylene (e.g., 5- to 30-membered fused heterocyclylene, and 5- to 20-membered fused heterocyclylene), and spiro heterocyclylene (e.g., 5- to 30-membered spiro heterocyclylene, and 5- to 20-membered spiro heterocyclylene). Representative examples of monocyclic heterocyclylene groups include, but are not limited to, azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azoctanylene, dioxanylene, diazepanylene (e.g., 1,4-diazepanylene, 4,5-diazepanylene, 1,3-diazepanylene), and diazaoctanylene. Examples of bridged heterocyclylenes, fused heterocyclylenes, and spiro heterocyclylenes include, but are not limited to, 6-azabicyclo[3.1.1]heptanylidene, 2,5-diazabicyclo[2.2.1]heptanylidene, 3,6-diazabicyclo[3.1.1]heptanylidene, 3-azabicyclo[3.2.1]octanylidene, 3,8-diazabicyclo[3.2.1]octanylidene, 3,8-diazabicyclo[3.2.1]octanylidene, 2,5-diazabicyclo[2.2.2]octanylidene, octahydro-1H-indolylidene, and azaspiroylidene (e.g., a 5- to 20-membered azaspiroylidene, such as 3-azaspiro[5.5]undecanylidene). The heterocyclylene group may be unsubstituted or substituted as defined above (e.g., mono-, di-, tri-, or polysubstituted), wherein the substituents are optionally selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1- 6 Alkoxy, halogenated C 1-6Alkoxy, 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0147] As used herein, the term “nitrogen-containing heterocyclylene” or “nitrogen-containing heterocycloalkylene”, alone or in combination, refers to a 4- to 30-membered (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 4- to 14-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, 4- to 5-membered, 5- to 9-membered, 5- to 30-membered, 5- to 20-membered, or 5- to 15-membered) monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) divalent cyclic hydrocarbon group containing one nitrogen atom and optionally containing one or more (e.g., containing 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from sulfur, oxygen, and nitrogen. Examples of the term “nitrogen-containing heterocyclylene” include, but are not limited to, nitrogen-containing monocyclic heterocyclylene (e.g., a 4- to 30-membered nitrogen-containing monocyclic heterocyclylene, and a 4- to 20-membered nitrogen-containing monocyclic heterocyclylene), nitrogen-containing bridged heterocyclyl (e.g., a 5- to 30-membered nitrogen-containing bridged heterocyclyl, a 5- to 20-membered nitrogen-containing bridged heterocyclyl, a 7- to 20-membered nitrogen-containing bridged heterocyclyl, or a 7- to 15-membered nitrogen-containing bridged heterocyclyl), nitrogen-containing fused heterocyclyl (e.g., a 5- to 30-membered nitrogen-containing fused heterocyclyl and a 5- to 20-membered nitrogen-containing fused heterocyclyl), and nitrogen-containing spiro heterocyclyl (e.g., a 5- to 30-membered nitrogen-containing spiro heterocyclyl and a 5- to 20-membered nitrogen-containing spiro heterocyclyl). Representative examples of nitrogen-containing monocyclic heterocyclylene groups include, but are not limited to, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azepanylene, diazepanylene (e.g., 1,4-diazepanylene, 4,5-diazepanylene, 1,3-diazepanylene), and diazepanylene. Examples of nitrogen-containing bridged heterocyclyl groups, nitrogen-containing fused heterocyclyl groups, and nitrogen-containing spiro heterocyclyl groups include, but are not limited to, 6-azabicyclo[3.1.1]heptanylidene, 2,5-diazabicyclo[2.2.1]heptanylidene, 3,6-diazabicyclo[3.1.1]heptanylidene, 3-azabicyclo[3.2.1]octanylidene, 3,8-diazabicyclo[3.2.1]octanylidene, 3,8-diazabicyclo[3.2.1]octanylidene, 2,5-diazabicyclo[2.2.2]octanylidene, octahydro-1H-indolylidene, and azaspirocyclyl groups (e.g., a 5- to 20-membered azaspirocyclyl group, such as 3-azaspiro[5.5]undecylidene). The nitrogen-containing heterocyclylene group may be unsubstituted or substituted as defined above (e.g., mono-, di-, tri-, or polysubstituted), wherein the substituents are optionally selected from deuterium, hydroxyl, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C1-6 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 Alkyl-C(O)NH-, C 2-6 Alkynyl and C 2-6 Alkenyl.

[0148] As used herein, the term "alkynyl" alone or in combination refers to a straight or branched monovalent hydrocarbon group containing 2 to 8 (e.g., 2 to 6, 2 to 5, 2 to 4, more preferably 2) carbon atoms and having one or more (e.g., 1 to 3, 1 to 2, or 1) carbon-carbon triple bonds. Examples of "alkynyl" include C 2-8 Alkynyl, C 2-6 Alkynyl or C 2-4 Alkynyl, representative examples of which include, but are not limited to, ethynyl, 1-propynyl, 1-butynyl, and 1,3-diynyl.

[0149] As used herein, the term "alkenyl" alone or in combination refers to a straight or branched monovalent hydrocarbon group containing 2 to 8 carbon atoms (e.g., 2 to 6, 2 to 5 carbon atoms, or 2 to 4, 2 to 3 or 2 carbon atoms) having one or more (e.g., 1 to 3, 1 to 2 or 1) carbon-carbon double bonds. Examples of "alkenyl" include C 2-8 Alkenyl, C 2-6 Alkenyl or C 2- Representative examples of the group include, but are not limited to, vinyl (e.g., CH2=CH-), 1-propenyl, allyl, 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl, pentenyl, n-penta-2,4-dienyl, 1-methyl-but-1-enyl, 2-methyl-but-1-enyl, 3-methyl-but-1-enyl, 1-methyl-but-2-ylidene, 2-methyl-but-2-ylidene, 3-methyl-but-2-ylidene, 1-methyl-but-3-enyl, 2-methyl-but-3-enyl, 3-methyl-but-3-enyl, and hexenyl.

[0150] As used herein, the term "bornyl" or "bornane" (also known as 1,7,7-trimethylbicyclo[2.2.1]heptane; camphane; bornylane) has the definition known to those skilled in the art. As used herein, the term "bornyl" or "bornyl" refers to a monovalent radical of bornane, i.e., the radical remaining after any one of the hydrogen atoms in bornane is removed. Representative examples of "bornyl" include, but are not limited to, 1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl, 1,7,7-trimethylbicyclo[2.2.1]heptane-3-yl, 1,7,7-trimethylbicyclo[2.2.1]heptane-4-yl, 1,7,7-trimethylbicyclo[2.2.1]heptane-5-yl, or 1,7,7-trimethylbicyclo[2.2.1]heptane-6-yl,

[0151] As used herein, the term "bicyclo[2.2.1]heptane" (also known as bicyclo[2.2.1]heptane) or "norbornane" has the meaning known to those skilled in the art. As used herein, "bicyclo[2.2.1]heptane" or "norbornane" refers to a monovalent radical of bicyclo[2.2.1]heptane, i.e., the radical remaining after any one of the hydrogen atoms in bicyclo[2.2.1]heptane is removed. Representative examples of "bicyclo[2.2.1]heptane" include, but are not limited to, bicyclo[2.2.1]heptane-2-yl, bicyclo[2.2.1]heptane-3-yl, bicyclo[2.2.1]heptane-4-yl, bicyclo[2.2.1]heptane-5-yl, and bicyclo[2.2.1]heptane-6-yl.

[0152] As used herein, the term "bicyclo[2.2.1]heptene" (also known as bicyclo[2.2.1]heptene) has the same definition as known to those skilled in the art. As used herein, "bicyclo[2.2.1]heptenyl" refers to a monovalent radical of bicyclo[2.2.1]heptene, i.e., the radical remaining after any one of the hydrogen atoms in bicyclo[2.2.1]heptene is removed. Representative examples of "bicyclo[2.2.1]heptenyl" include, but are not limited to, bicyclo[2.2.1]hept-5-en-2-yl, bicyclo[2.2.1]hept-5-en-3-yl, and bicyclo[2.2.1]hept-5-en-7-yl.

[0153] In this article, the term "adamantane" (also known as Tricyclo[3.3.1.1 3，7 ]decane) has a definition known to those skilled in the art, and its structural formula is shown below, for example: As used herein, "adamantyl" refers to a monovalent radical of adamantane, i.e., the radical remaining after any hydrogen atom in adamantane is removed. Representative examples of "adamantyl" include, but are not limited to, 1-adamantyl, 2-adamantyl, 3-adamantyl, 4-adamantyl, 5-adamantyl, 6-adamantyl, 7-adamantyl, 8-adamantyl, 9-adamantyl, and 10-adamantyl.

[0154] As used herein, the term "noradamantane" (also known as noradamantane or octahydro-2,5-methanopentalene) has the definition known to those skilled in the art, and its structural formula is shown below, for example: As used herein, "noradamantyl" refers to a monovalent radical of noradamantane, i.e., the radical remaining after any hydrogen atom in noradamantane is removed. Representative examples of "noradamantyl" include, but are not limited to, 1-noradamantyl, 2-noradamantyl, 3-noradamantyl, 4-noradamantyl, 5-noradamantyl, 6-noradamantyl, 7-noradamantyl, 8-noradamantyl, and 9-noradamantyl.

[0155] As used herein, the term "adamantanamine" has the meaning known to those skilled in the art, i.e., refers to an adamantane having an amino substituent, wherein the amino group can replace a hydrogen on any carbon position of the adamantane. An example of an "adamantanamine" can be adamantane-1-amine (also known as adamantane-1-amine or Tricyclo[3.3.1.1 3，7 ]decan-1-amine; CAS: 768-94-5), having the following structural formula

[0156] The salts or pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates, and polymorphs of the compounds of formula (I) described in the present disclosure are also encompassed within the scope of the present disclosure.

[0157] In all embodiments of the present disclosure, the salt or pharmaceutically acceptable salt of the compound of formula (I) refers to a non-toxic inorganic or organic acid and / or base addition salt. Examples include: sulfate, hydrohalide (including hydrochloride, hydrobromide), maleate, sulfonate, citrate / citrate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, α-ketoglutarate, hippurate, D-glucuronate, D-gluconate, α-D-glucoheptonate, glycolate, mucate, L-ascorbate, orotate, picrate, glycinate, alanine, arginine, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, methanesulfonate, ethanesulfonate, edisylate, formate, acetate, 2,2-dichloroacetate, pivalate, propionate, valerate, palmitate, triphenylacetate , 2-ethyl-succinate, iodate, nicotinate, L-pyroglutamate, L-proline salt, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecylenate, camphorate, camphorsulfonate, dodecylsulfonate, phosphate, thiocyanate, dihydrogenphosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalenesulfonate, glycolate, trifluoroacetate, terephthalate and p-toluenesulfonate, etc.

[0158] "Pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, such as a filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickener, solvent, or encapsulating material, that carries or transports a compound useful in the present disclosure into or to a patient so that it can perform its intended function. Typically, such a construct carries or transports a compound from one organ or part of the body to another. A carrier must be "acceptable" if it is compatible with the other ingredients of the formulation (including the compound useful in the present disclosure) and is not harmful to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols, such as propylene glycol; polyols, such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffers, such as magnesium hydroxide and aluminum hydroxide; phosphate buffered saline as a surfactant; and other nontoxic, compatible substances used in pharmaceutical formulations.

[0159] The term "room temperature" of the present disclosure refers to ambient temperature, for example, a temperature of 20-30°C.

[0160] As used herein, "stereoisomers" refer to compounds that have identical chemical constitution but differ in the way the atoms or groups are arranged in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis / trans) isomers, atropisomers, and the like.

[0161] As used herein, the term "solvate" refers to an association or complex of one or more solvent molecules and a compound of the present invention. Examples of solvents include water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, and ethanolamine. The term "hydrate" refers to a complex in which the solvent molecule is water.

[0162] As used herein, the term "chiral" refers to a molecule that is non-superimposable on its mirror image, while "achiral" refers to a molecule that is superimposable on its mirror image.

[0163] As used herein, the term "enantiomers" refers to two non-superimposable isomers of a compound that are mirror images of each other.

[0164] As used herein, the term "diastereoisomer" refers to stereoisomers that have two or more chiral centers and whose molecules are not mirror images of each other. Diastereoisomers have different physical properties, such as melting points, boiling points, spectral properties, and reactivity. Diastereomeric mixtures can be separated by high-resolution analytical procedures such as electrophoresis and chromatography, for example, HPLC.

[0165] In this document, "p-menthane" (also known as p-methane) has a definition known to those skilled in the art, and its structural formula is shown below: In this article, "p-menthanyl" refers to a monovalent group of p-menthane, that is, the group remaining after any hydrogen on any carbon position of p-menthane is removed. Representative examples include but are not limited to

[0166] In this document, "m-menthane" (also known as m-methane) has a definition known to those skilled in the art, and its structural formula is shown below: In this article, "m-menthanyl" refers to a monovalent group of m-menthane, that is, the group remaining after any hydrogen on any carbon position of m-menthane is removed. Representative examples include but are not limited to

[0167] As used herein, "quinuclidine" (also known as Quihuclidine), whose chemical name is 1-azabicyclo[2.2.2]octane, has a definition known to those skilled in the art, and its structural formula is shown below: In this article, "quinuclidine" refers to a monovalent group of quinuclidine, that is, the group remaining after any hydrogen on any carbon position of quinuclidine is removed. Representative examples include but are not limited to BRIEF DESCRIPTION OF THE DRAWINGS

[0168] FIG1 shows the results of a Western Blot experiment showing that the compounds of the present invention degrade target substrate proteins in hPBMC cells. Example

[0169] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. The present invention may be practiced without some or all of these specific details. In other cases, well-known process operations are not described in detail in order to avoid unnecessary obfuscation of the present invention. Although the present invention will be described in conjunction with specific embodiments, it should be understood that this is not intended to limit the invention to these embodiments.

[0170] The following abbreviations are used throughout the specification and examples: AcOH acetic acid Boc tert-butoxycarbonyl DCM dichloromethane DIEA or DIPEA N,N-diisopropylethylamine DMF N,N-dimethylformamide DMSO dimethyl sulfoxide EA ethyl acetate ESI electrospray ionization equiv. EtOH ethanol EtOAc ethyl acetate HPLC high performance liquid chromatography HRMS high resolution mass spectrometry LC-MS liquid chromatography-mass spectrometry LRMS low resolution mass spectrometry LC liquid chromatography Me methyl MeCN acetonitrile MeOH methanol MS mass spectrometry MsCl methanesulfonyl chloride MsO- methanesulfonyloxy Ms2O methanesulfonic anhydride 1H NMR nuclear magnetic resonance hydrogen spectrum MeO- methoxy ONs o-nitrobenzenesulfonyl rt room temperature tBu tert-butyl TEA triethylamine TFA trifluoroacetic acid T f O-Trifluoromethanesulfonyloxy TLC Thin Layer Chromatography TMS Trimethylsilyl TsO- p-Toluenesulfonyloxy Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene X-Phos 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl

[0171] In the present invention, 1 H NMR spectra were measured using a Bruker-500 MHz nuclear magnetic resonance instrument, using CD3OD (δ = 3.31 ppm) containing 0.1% TMS (as an internal standard) as the solvent; CDCl3 (δ = 7.26 ppm) containing 0.1% TMS (as an internal standard) as the solvent; or DMSO-d6 (δ = 2.50 ppm) containing 0.03% TMS (as an internal standard) as the solvent. LC-MS spectra were measured on a Sciex API 2000 mass spectrometer equipped with an Agilent 1100 binary pump, DAD, and ELSD, or on an Agilent 1260-6125B single quadrupole liquid chromatography-mass spectrometer equipped with an Agilent 1260 quaternary pump, DAD, and ELSD. HPLC preparations were measured on a SHIMADZU LC-20AP instrument, and HPLC purity was measured on a SHIMADZU LC-30AP or Waters 1525 instrument. All reactions were carried out under air atmosphere unless otherwise specified; the reactions were monitored by TLC or LC-MS.

[0172] Solvent and reagent treatment was as follows: the reaction solvents DCM, DMF, anhydrous EtOH, and anhydrous MeOH were purchased from Sinopharm Group; preparative-grade CH3CN and deionized water were used for HPLC preparation; other reaction substrates, reagents, and drugs, unless otherwise specified, were directly purchased from commercial channels or synthesized using or according to methods known in the art.

[0173] Unless otherwise specified, the materials and reagents used in the following examples can be purchased from commercial sources and used directly, or can be synthesized using or according to methods known in the art.

[0174] General synthetic method

[0175] The compounds and / or pharmaceutically acceptable salts thereof disclosed herein can be synthesized using commercially available raw materials by synthetic techniques known in the art. The synthetic schemes described below illustrate the preparation methods of most compounds. The starting materials or reagents used in each scheme can be purchased from commercial sources or prepared by methods known to those skilled in the art. Salts, racemates, enantiomers, phosphates, sulfates, hydrochlorides and prodrug forms of the compounds of formula (I) disclosed herein can be prepared by those skilled in the art according to conventional techniques in the art.

[0176] Synthesis Scheme 1: Solution 1

[0177] In Scheme 1, the group R a1 、R a2 、R a3 、R a4 、(R a5 ) m 、Z1、Z2、Z3、Z4、Z5、Nitrogen-containing heterocyclic ring A、(R d1 ) n1 , Ring B, (R d2 ) n2 、R c 、ring C、m1、(R d3 ) n3 , Ring D and (R d4 ) n4 As defined in the compounds of formula (I) and its various subembodiments disclosed herein. The group LE of substrate 1 represents Cl, Br, I, OMs, OTs, or ONs. Substrate 2 is a compound corresponding to the X moiety containing a nitrogen-containing heterocycle in the compound of formula (I).

[0178] The amine alkylation reaction in Scheme 1 can be carried out, for example, in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at room temperature to 80°C (e.g., 40°C to 60°C, 40°C to 50°C, or 50°C to 60°C). The molar ratio of substrate 1 to substrate 2 can be, for example, 1:1.1-2, 1:1.1-1.5, 1:1.1-1.2, or 1:1.2-1.3.

[0179] For example, the specific operations of solution 1 can be as follows:

[0180] Bromosubstrate 1 (1.3 eq.) and substrate 2 (1.0 eq.) were dissolved in anhydrous DMF (2 mL). Triethylamine (3.0 eq.) and sodium iodide (1.0 eq.) were then added to the solution. The reaction mixture was stirred at 50°C for 2 hours. LCMS confirmed the reaction was complete. The reaction mixture was filtered, and the filtrate was purified by HPLC to yield the title compound.

[0181] Synthesis Scheme 2: (Sulfonate ester formation) Option 2

[0182] In Scheme 2, group R a1 、R a2 、R a3 、R a4 、(R a5 ) m , Z1, Z2, Z3, Z4 and Z5 are as defined in the compounds of formula (I) and various sub-embodiments thereof disclosed herein.

[0183] In Scheme 2, the substituent -CH2-OH of the reaction substrate can be located at the 4-, 5-, 6-, or 7-position on the phenyl ring of the isoindoline group, and the substituent -CH2-OMs of the obtained products 2-2 and 2-3 are also located at the 4-, 5-, 6-, or 7-position on the phenyl ring of the isoindoline group, respectively.

[0184] Synthesis Scheme 3: Option 3

[0185] In Scheme 3, the group R a1 、R a2 、R a3 、R a4 、(R a5 ) m 、Z1、Z2、Z3、Z4、Z5、Nitrogen-containing heterocyclic ring A、(R d1 ) n1 , Ring B, (R d2 ) n2 、R c 、ring C、m1、(R d3 ) n3 , Ring D and (R d4 ) n4 As defined in the compounds of formula (I) and its various subembodiments of the present disclosure. Step (2) Substrate 2 is the same compound as Substrate 2 in Synthesis Scheme 1.

[0186] For example, the specific operations of solution 3 can be as follows:

[0187] The hydroxyl substrate (1.0 eq.) was dissolved in anhydrous DMF (0.5 mL) and DCM (5 mL), and then diisopropylethylamine (3.0 eq.) and methanesulfonic anhydride (0.9 eq.) were added to the solution. The reaction solution was stirred at room temperature for 5 minutes. After TLC detection of the reaction completion, a solution of the corresponding substrate amine (1.0 eq.) in DMF (0.5 mL) was added to the solution, and the reaction was continued to stir at room temperature for 3 hours. LCMS detection of the reaction completion was performed. The reaction solution was filtered and concentrated, and the residue was purified by high-performance liquid chromatography to obtain the target compound.

[0188] Synthesis Scheme 4: Option 4

[0189] In Scheme 4, the group R a1 、R a2 、R a3 、R a4 、(R a5 ) m 、Z1、Z2、Z3、Z4、Z5、Nitrogen-containing heterocyclic ring A、(R d1 ) n1 , Ring B, (R d2 ) n2 、R c , Ring C, m1, (R d3 ) n3 , Ring D and (R d4 ) n4 As defined in the compounds of formula (I) and various subembodiments thereof of the present disclosure.

[0190] The specific operations of Solution 4 can be as follows:

[0191] Carboxylic acid substrate 1 (1.1 eq.) and substrate 2 (1.0 eq.) were dissolved in anhydrous DMF (2 mL). Triethylamine (3.0 eq.) and HATU (1.3 eq.) were then added to the solution. The reaction mixture was stirred at room temperature for 2 hours. LCMS confirmed the reaction was complete. The reaction mixture was filtered, and the filtrate was purified by HPLC to yield the title compound.

[0192] Synthesis Scheme 5: Option 5

[0193] In Scheme 5, Z6 represents C(O), CH2, or CD2. Z1 represents C(O), C(S), CH2, or CD2, and Z2, Z3, and Z4 each independently represent C(O) or C(S), wherein at least one of Z1, Z2, Z3, and Z4 represents C(S). When Z6 represents C(O), Z1 represents C(O) or C(S). When Z6 represents CH2 or CD2, Z1 represents CH2 or CD2 accordingly.

[0194] The sulfurizing agent Lawesson's reagent in Scheme 5 can also be replaced by other suitable sulfurizing agents, such as but not limited to carbon disulfide, hexamethyldisilathioethane, sulfur, thiourea, hydrogen sulfide, phosphorus pentasulfide, Belleau's reagent, and Davy's reagent.

[0195] In Scheme 5, the Br substituent of the reaction substrate 5-1 in step 1 can be located at the 4-, 5-, 6-, or 7-position on the phenyl ring of the isoindolinyl group, and the Br substituent of the intermediate product and the substituent -CH2-OH of the product in step 2 are also located at the 4-, 5-, 6-, or 7-position on the phenyl ring of the isoindolinyl group. a1 、R a2 、R a3 、R a4 and (R a5 ) m As defined in the compounds of formula (I) and various subembodiments thereof of the present disclosure.

[0196] In some embodiments of Scheme 5, at least one of Z1, Z2, Z3, and Z4 of the compound of Formula (I) represents C(S). In some embodiments, at least two of Z1, Z2, Z3, and Z4 of the compound of Formula (I) represent C(S). In some embodiments, at least three of Z1, Z2, Z3, and Z4 represent C(S). In some embodiments, Z1, Z2, Z3, and Z4 all represent C(S).

[0197] Depending on the target compound, the above schemes and their reaction substrates, reaction conditions (including reaction amount, temperature, time, etc.), post-treatment, etc. can be appropriately modified and adjusted by techniques and methods well known to those skilled in the art to obtain the desired target compound, and the obtained target compound can be further modified by substituents, etc. according to methods well known to those skilled in the art to obtain other target compounds.

[0198] Intermediate Example 1: Preparation of 3-(5-(hydroxymethyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GTC00170)

[0199] The target compound (GTC00170) was prepared according to the method of Synthesis Scheme 5.

[0200] Step 1: To a solution of 3-(5-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione (20 g, 61.891 mmol) in 1,4-dioxane (200 mL) was added Lawesson's reagent (11.26 g, 27.851 mmol). The reaction mixture was stirred at 110°C for 12 hours. The reaction was complete as determined by TLC. The reaction mixture was concentrated and the residue was purified by column chromatography to afford 3-(5-bromo-1-thioisoindolin-2-yl)piperidine-2,6-dione (10 g, 29.480 mmol, 47.64% yield) as an off-white solid.

[0201] Step 2: To a solution of 3-(5-bromo-1-thioisoindolin-2-yl)piperidine-2,6-dione (6 g, 17.688 mmol) and (tributyl-λ4-stannyl)methanol (8.52 g, 26.532 mmol) in 1,4-dioxane (60 mL) was added XPhos Pd G3 (0.1 g, 0.147 mmol). The reaction mixture was stirred at 100°C under argon for 3 hours. The reaction mixture was concentrated and the residue was purified by column chromatography to afford 3-(5-(hydroxymethyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (1 g, 19.46% yield) as a gray solid. 1 H NMR (400MHz, DMSO) δ11.17 (s, 1H), 7.91 (d, J=7.9Hz, 1H), 7.66 (s, 1H), 7.55 (d, J=8.0Hz, 1H), 6.09-5.91 (m, 1H), 5.4 9 (t, J=5.7Hz, 1H), 4.91-4.67 (m, 4H), 3.13-2.93 (m, 1H), 2.79-2.58 (m, 2H), 2.16 (dd, J=8.9, 3.6Hz, 1H). LCMS (ESI) C 14 H 15 N2O3S + [M+H]+: Calculated, 291.08 Found, 291.0.

[0202] Intermediate Example 2: Preparation of 3-(4-(hydroxymethyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GTC00504)

[0203] The target compound (GTC00504) (gray solid, 0.8 g, yield 33.32%) was prepared by referring to the method of Synthesis Scheme 5 or the method of Intermediate Example 1. 1HNMR (400MHz, DMSO) δ11.12 (s, 1H), 7.80 (d, J=7.4Hz, 1H), 7.61 (d, J=7.4Hz, 1H), 7.53 (t, J=7.6Hz, 1H), 5.98 (d, J=8.3Hz, 1H), 5.37 (d, J=5. 4Hz, 1H), 4.79 (dd, J=49.7, 20.2Hz, 2H), 4.65 (d, J=4.1Hz, 2H), 2.96 (s, 1H), 2.64 (d, J=18.4Hz, 2H), 2.09 (dd, J=8.9, 3.5Hz, 1H). LCMS (ESI) C 14 H 15 N2O3S + [M+H]+: Calculated, 291.08 Found, 291.0.

[0204] Intermediate Example 3: Preparation of 3-(6-(hydroxymethyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GTC00505)

[0205] The target compound (GTC00505) (grey solid, 1 g, yield 38.91%) was prepared by referring to the method of Synthesis Scheme 5 or the method of Intermediate Example 1. 1 HNMR (400MHz, DMSO) δ11.06 (d, J=31.4Hz, 1H), 7.86 (d, J=19.3Hz, 1H), 7.60 (d, J=7.8Hz, 2H), 5.95 (d, J=8.9Hz, 1H), 5.41 ( t, J=5.7Hz, 1H), 4.82-4.60 (m, 4H), 3.00-2.90 (m, 1H), 2.64 (d, J=17.9Hz, 1H), 2.54 (s, 1H), 2.16-2.05 (m, 1H). LCMS (ESI) C 14 H 15 N2O3S + [M+H]+: Calculated, 291.08 Found, 291.0.

[0206] Intermediate Example 4: Preparation of (2-(2,6-dioxopiperidin-3-yl)-1-thioisoindolin-5-yl)methyl methanesulfonate (GTC00505)

[0207] The target compound (GTC00505) (grey solid, 1 g, yield 38.91%) was prepared by referring to the method of Synthesis Scheme 5 or the method of Intermediate Example 1. 1HNMR (400MHz, DMSO) δ11.06 (d, J=31.4Hz, 1H), 7.86 (d, J=19.3Hz, 1H), 7.60 (d, J=7.8Hz, 2H), 5.95 (d, J=8.9Hz, 1H), 5.41 ( t, J=5.7Hz, 1H), 4.82-4.60 (m, 4H), 3.00-2.90 (m, 1H), 2.64 (d, J=17.9Hz, 1H), 2.54 (s, 1H), 2.16-2.05 (m, 1H). LCMS (ESI) C 14 H 15 N2O3S + [M+H]+: Calculated, 291.08 Found, 291.0.

[0208] Example 1: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04329)

[0209] The target compound (GT-04329) (white solid, 28 mg, yield 37%) was prepared by referring to the method of synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.82 (d, J=7.8Hz, 1H), 7.74 (s, 1H), 7.62 (d, J=7.7Hz, 1H), 7.6 1-7.50 (m, 4H), 7.32-7.29 (m, 4H), 7.25-7.22 (m, 2H), 5.08 (dd, J=13.3, 5.2Hz, 1H) ,5.04-4.88(m,1H),4.48-4.40(m,4H),3.60-3.56(m,2H),3.51-3.42(m,5H),3.18 -3.01(m,5H),2.88-2.67(m,2H),2.48-2.23(m,4H),2.17-1.97(m,3H).LCMS(ESI)C 36 H 42 N5O3 + [M+H] + : Calculated value 592.23, measured value 592.3.

[0210] Example 2: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04330)

[0211] The target compound (GT-04330) (white solid, 34 mg, yield 43%) was prepared by referring to the method of synthesis scheme 1.1 H NMR (400MHz, MeOD) δ7.76-7.70 (m, 1H), 7.66 (d, J=7.8Hz, 1H), 7.58-7.55 (m, 4H), 7.33- 7.29 (m, 4H), 7.25-7.22 (m, 2H), 5.08 (dd, J=13.3, 5.2Hz, 1H), 5.04-4.89 (m, 1H), 4.60-4 .48(m, 4H), 3.70-3.61(m, 2H), 3.59-3.40(m, 5H), 3.20-2.98(m, 6H), 2.91-2.75(m, 1H), 2.73-2.66(m, 1H), 2.51-2.39(m, 1H), 2.38-2.31(m, 2H), 2.17-1.95(m, 3H).LCMS(ESI)C 36 H 41 FN5O3 + [M+H] + : Calculated value 610.32, measured value 610.3.

[0212] Example 3: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04331)

[0213] The target compound (GT-04331) (white solid, 34 mg, yield 43%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.82 (d, J=6.0Hz, 1H), 7.65-7.50 (m, 5H), 7.35-7.29 (m, 4 H), 7.25-7.22 (m, 2H), 5.08 (dd, J=13.3, 5.2Hz, 1H), 5.04-4.89 (m, 1H), 4.55-4 .36(m, 4H), 3.68-3.62(m, 2H), 3.57-3.38(m, 5H), 3.20-2.94(m, 6H), 2.88-2.7 5(m,1H),2.72-2.66(m,1H),2.49-2.26(m,3H),2.12-2.03(m,3H).LCMS(ESI)C 36 H 41 FN5O3 + [M+H] + : Calculated value 610.32, measured value 610.3.

[0214] Example 4: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04597)

[0215] The target compound (GT-04597) (white solid, 39 mg, yield 45%) was prepared by referring to the method of synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.54 (s, 1H), 7.52-7.40 (m, 4H), 7.37 (d, J=9.6Hz, 1H), 7.27 (t, J=6.9Hz, 4H ), 7.23-7.16 (m, 2H), 5.05 (dd, J=13.3, 5.1Hz, 1H), 4.71 (s, 2H), 4.48 (q, J=17.9Hz, 2H), 4.39 (s, 2H), 3.60-3.54(m, 2H), 3.41-3.23(m, 5H), 3.14-3.06(m, 3H), 3.01-2.92(m, 1H), 2.89-2.76(m, 2 H), 2.69 (d, J=15.5Hz, 1H), 2.48-2.36 (m, 1H), 2.36-2.22 (m, 2H), 2.16-1.88 (m, 3H).LCMS (ESI) C 36 H 41 FN5O3 + [M+H] + : Calculated value 610.32, measured value 610.3.

[0216] Example 5: Preparation of 3-(4-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04598)

[0217] The target compound (GT-04598) (white solid, 46 mg, yield 54%) was prepared by referring to the method of synthesis scheme 1. 1H NMR (400MHz, MeOD) δ7.97 (d, J=7.6Hz, 1H), 7.90 (d, J=7.6Hz, 1H), 7.72 (t, J=7.6Hz, 1H), 7.63-7.52 (m, 4H), 7.41-7.3 7 (m, 4H), 7.34-7.21 (m, 2H), 5.24 (dd, J=13.4, 5.1Hz, 1H), 4.80 (d, J=17.4Hz, 1H), 4.67 (d, J=17.4Hz, 1H), 4.58-4.42 (m, 2H), 3.82-3.65 (m, 2H), 3.56-3.49 (m, 1H), 3.46-3.37 (m, 4H), 3.32-3.27 (m, 5H), 3.26-3.20 (m, 1H), 3.03-2.90 (m , 2H), 2.83 (d, J=15.8Hz, 1H), 2.61-2.53 (m, 1H), 2.46-2.38 (m, 2H), 2.31-2.20 (m, 1H), 2.18-2.09 (m, 2H).LCMS (ESI) C 36 H 42 N5O3 + [M+H] + : Calculated value 592.33, measured value 592.3.

[0218] Example 6: Preparation of 3-(6-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04599)

[0219] The target compound (GT-04599) (white solid, 8 mg, yield 9%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.98 (s, 1H), 7.87 (d, J=7.9Hz, 1H), 7.77 (d, J=7.9Hz, 1H), 7.63 (d, J=6.3 Hz, 4H), 7.40 (t, J=7.2Hz, 4H), 7.34-7.32 (m, 2H), 5.19 (dd, J=13.3, 5.1Hz, 1H), 4.64-4.52 (m, 4H), 3.70-3.67(m, 2H), 3.61-3.40(m, 6H), 3.24-3.05(m, 5H), 3.03-2.86(m, 2H), 2.87-2.75(m , 1H), 2.59-2.51(m, 1H), 2.48-2.41(m, 2H), 2.28-2.16(m, 1H), 2.14-2.03(m, 2H).LCMS(ESI)C 36 H42 N5O3 + [M+H] + : Calculated value 592.33, measured value 592.3.

[0220] Example 7: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04376)

[0221] The target compound (GT-04376) (white solid, 31 mg, yield 45%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.82 (d, J=7.8Hz, 1H), 7.69 (s, 1H), 7.60-7.58 (m, 5H), 7.40-7.3 7(m, 4H), 7.34-7.30(m, 2H), 5.36(s, 1H), 5.08(dd, J=13.3, 5.2Hz, 1H), 4.56-4.36(m , 4H), 3.68-3.61(m, 1H), 3.53-3.50(m, 1H), 3.43-3.31(m, 2H), 3.14-3.09(m, 9H), 2. 88-2.78(m, 1H), 2.73-2.65(m, 1H), 2.44-2.31(m, 1H), 2.17-2.01(m, 3H).LCMS(ESI)C 36 H 40 F2N5O3 + [M+H] + : Calculated value 628.31, measured value 628.3.

[0222] Example 8: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04377)

[0223] The target compound (GT-04377) (white solid, 41 mg, yield 58%) was prepared by referring to the synthesis scheme 1. 1H NMR (400MHz, MeOD) δ7.68-7.62(m, 2H), 7.59-7.55(m, 4H), 7.40-7.36(m, 4H), 7.34-7 .30 (m, 2H), 5.35 (s, 1H), 5.08 (dd, J=13.4, 5.1Hz, 1H), 4.62-4.44 (m, 3H), 4.36 (brs, 2H), 3.70-3.62(m, 1H), 3.53-3.40(m, 1H), 3.35-3.28(m, 1H), 3.16-3.01(m, 9H), 2.8 7-2.78(m, 1H), 2.74-2.64(m, 1H), 2.48-2.38(m, 1H), 2.16-1.99(m, 3H).LCMS(ESI)C 36 H 39 F3N5O3 + [M+H] + : Calculated value 646.30, measured value 646.3.

[0224] Example 9: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04378)

[0225] The target compound (GT-04378) (white solid, 40 mg, yield 57%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.74 (d, J=5.9Hz, 1H), 7.60-7.58 (m, 4H), 7.54 (d, J=8.6Hz, 1H), 7.4 0-7.36(m, 4H), 7.35-7.29(m, 2H), 5.35(s, 1H), 5.12-5.03(m, 1H), 4.53-4.39(m, 2H), 4. 36(brs, 2H), 3.68-3.59(m, 1H), 3.53-3.39(m, 1H), 3.36-3.23(m, 2H), 3.20-2.93(m, 9H) , 2.88-2.76(m, 1H), 2.74-2.64(m, 1H), 2.43-2.36(m, 1H), 2.15-1.97(m, 3H).LCMS(ESI)C 36 H 39 F3N5O3 + [M+H] + : Calculated value 646.30, measured value 646.3.

[0226] Example 10: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04379)

[0227] The target compound (GT-04379) (white solid, 35 mg, yield 50%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.57 (d, J=7.4Hz, 4H), 7.42-7.36 (m, 5H), 7.34-7.32 (m, 2H) , 7.29-7.23 (m, 1H), 5.35 (s, 1H), 5.03 (dd, J=13.2, 6.6Hz, 1H), 4.53-4.34 (m, 2H) , 4.16(brs, 2H), 3.48-3.39(m, 1H), 3.33-3.22(m, 2H), 3.20-2.95(m, 9H), 2.82-2 .77(m, 2H), 2.74-2.63(m, 1H), 2.44-2.33(m, 1H), 2.10-1.94(m, 3H).LCMS(ESI)C 36 H 39 F3N5O3 + [M+H] + : Calculated value 646.30, measured value 646.3.

[0228] Example 11: Preparation of 3-(4-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04380)

[0229] The target compound (GT-04380) (white solid, 19 mg, yield 28%) was prepared by referring to the synthesis scheme 1. 1H NMR (400MHz, MeOD) δ7.79-7.77(m, 1H), 7.65(t, J=7.0Hz, 1H), 7.60-7.55(m, 4H), 7.54-7.50( m, 1H), 7.40-7.36 (m, 4H), 7.35-7.28 (m, 2H), 5.35 (brs, 1H), 5.18-5.04 (m, 1H), 4.68-4.47 (m, 2H), 4.31-4.03(m, 2H), 3.52-3.43(m, 1H), 3.41-3.25(m, 2H), 3.20-2.94(m, 9H), 2.94-2.75(m , 2H), 2.72-2.68(m, 1H), 2.51-2.29(m, 1H), 2.19-2.06(m, 1H), 2.06-1.90(m, 2H).LCMS(ESI)C 36 H 40 F2N5O3 + [M+H] + : Calculated value 628.31, measured value 628.3.

[0230] Example 12: Preparation of 3-(5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-5037)

[0231] The target compound (GT-5037) (white solid, 49 mg, yield 52%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, DMSO-d6) δ11.00 (s, 1H), 8.73 (d, J=4.8Hz, 1H), 7.93-7.89 (m, 1H), 7.87-7.78 (m, 2 H), 7.74-7.70 (m, 4H), 7.50-7.36 (m, 4H), 5.89 (s, 1H), 5.14 (dd, J=13.2, 5.1Hz, 1H), 4.52-4.36 (m, 4H), 3.63-3.52 (m, 4H), 3.47-3.23 (m, 4H), 3.21-3.12 (m, 4H), 2.98-2.82 (m, 2H), 2.61 (d, J= 16.8Hz, 1H), 2.43 (dd, J=13.2, 4.5Hz, 1H), 2.26-2.09 (m, 1H), 2.03-1.99 (m, 2H).LCMS (ESI) C35H 39 F2N6O3 + [M+H] + : Calculated value 629.30, measured value 629.3.

[0232] Example 13: Preparation of 3-(5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04595)

[0233] The target compound (GT-04595) (white solid, 16 mg, yield 35%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.91 (d, J=8.0Hz, 1H), 7.71 (s, 1H), 7.64 (d, J=7.8Hz, 1H), 7.36 (d, J=8.2Hz, 2H) , 7.28 (d, J=8.2Hz, 2H), 5.20 (dd, J=13.4, 5.0Hz, 1H), 4.64-4.50 (m, 2H), 4.43-4.25 (m, 2H), 3.65-3. 56(m, 2H), 3.31-3.09(m, 6H), 3.01-2.86(m, 3H), 2.84-2.78(m, 2H), 2.72-2.66(m, 1H), 2.59-2.44(m , 4H), 2.28-2.11(m, 2H), 2.09-1.93(m, 3H), 1.62-1.48(m, 2H), 1.08(s, 3H), 1.05(s, 3H).LCMS(ESI)C 38 H 45 ClF2N5O4 + [M+H] + : Calculated value 708.31, measured value 708.3.

[0234] Example 14: Preparation of 3-(5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04596)

[0235] The target compound (GT-04596) (white solid, 17 mg, yield 37%) was prepared by referring to the synthesis scheme 1. 1H NMR (400MHz, MeOD) δ7.77-7.68 (m, 2H), 7.37 (d, J=8.4Hz, 2H), 7.29 (d, J=8.5Hz, 2H), 5.20 ( dd, J=13.3, 5.0Hz, 1H), 4.63 (qJ=17.3Hz, 2H), 4.33-4.21 (m, 2H), 3.66-3.56 (m, 2H), 3.47-3 .39(m,3H),3.29-3.18(m,2H),3.07-2.88(m,3H),2.85-2.78(m,3H),2.70-2.42(m,4H),2.2 9-2.14(m, 2H), 2.04-1.95(m, 4H), 1.57-1.52(m, 2H), 1.08(s, 3H), 1.05(s, 3H).LCMS(ESI)C 38 H 44 ClF3N5O4 + [M+H] + : Calculated value 726.30, measured value 726.3.

[0236] Example 15: Preparation of 3-(5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05160)

[0237] The target compound (GT-05160) (white solid, 50 mg, yield 48%) was prepared by referring to the synthesis scheme 1. 1H NMR (400MHz, DMSO-d6) δ11.01 (s, 1H), 7.77 (d, J = 7.8Hz, 1H), 7.69-7.64 (m, 1H), 7.60-7.54 (m, 1H), 7.44 (d, J = 8.3Hz , 2H), 7.14 (d, J=8.3Hz, 2H), 5.13 (dd, J=13.2, 5.1Hz, 1H), 4.48 (d, J=16.8Hz, 1H), 4.35 (d, J=16.8Hz, 1H), 4.15-3.8 7(m, 1H), 3.55(brs, 3H), 3.28-3.20(m, 3H), 3.05-2.97(m, 4H), 2.91-2.82(m, 4H), 2.66-2.59(m, 4H), 2.47-2.36(m, 1H), 2.34-2.21(m, 3H), 2.02(brs, 3H), 1.96-1.84(m, 1H), 1.83-1.73(m, 1H), 1.44(m, 2H), 0.96(s, 6H).LCMS(ESI)C 38 H 47 ClF2N5O3 + [M+H] + : Calculated value 694.33, measured value 694.4.

[0238] Example 16: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04604)

[0239] The target compound (GT-04604) (white solid, 29 mg, yield 33%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.94 (d, J=7.8Hz, 1H), 7.84 (s, 1H), 7.73 (d, J=7.6Hz, 1H) , 7.34-7.30 (m, 2H), 7.17-7.15 (m, 1H), 5.19 (dd, J=13.7, 4.9Hz, 1H), 4.64-4. 46(m, 4H), 3.79-3.58(m, 7H), 3.50-3.43(m, 2H), 3.20-3.13(m, 4H), 3.01-2.8 6(m, 1H), 2.84-2.78(m, 1H), 2.60-2.45(m, 3H), 2.25-2.12(m, 3H).LCMS(ESI)C 29 H 34 Cl2N5O3 + [M+H] +: Calculated value 570.20, measured value 570.2.

[0240] Example 17: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04605)

[0241] The target compound (GT-04605) (white solid, 30 mg, yield 34%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.82-7.77(m, 2H), 7.35-7.27(m, 2H), 7.18-7.16(m, 1H), 5.19(dd, J=13.4, 5.2Hz, 1H), 4.72-4.50(m, 4H), 3.78-3.73(m, 3H), 3.68-3.54(m, 4H), 3.49-3.47(m, 2H), 3.28-3.11(m, 4H), 3.02-2.85(m, 2 H), 2.84-2.74(m, 1H), 2.59-2.44(m, 3H), 2.22-2.13(m, 3H).LCMS(ESI)C 29 H 33 Cl2FN5O3 + [M+H] + : Calculated value 588.19, measured value 588.2.

[0242] Example 18: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04606)

[0243] The target compound (GT-04606) (white solid, 23 mg, yield 26%) was prepared by referring to the synthesis scheme 1. 1H NMR (400MHz, MeOD) δ7.93 (d, J=6.1Hz, 1H), 7.71 (d, J=8.6Hz, 1H), 7.39-7.28 (m, 2 H), 7.19 (dd, J=7.1, 2.5Hz, 1H), 5.20 (dd, J=13.3, 5.1Hz, 1H), 4.65-4.46 (m, 4H), 3 .83-3.72(m, 3H), 3.68-3.59(m, 4H), 3.52-3.41(m, 2H), 3.30-3.12(m, 4H), 2.97- 2.88(m, 1H), 2.85-2.78(m, 1H), 2.57-2.50(m, 3H), 2.30-2.13(m, 3H).LCMS(ESI)C 29 H 33 Cl2FN5O3 + [M+H] + : Calculated value 588.19, measured value 588.2.

[0244] Example 19: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04607)

[0245] The target compound (GT-04607) (white solid, 25 mg, yield 28%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.64 (s, 1H), 7.46 (d, J = 9.6Hz, 1H), 7.33-7.32 (m, 2H), 7.20-7.16 (m, 2H), 5.21-5.14 (m, 1H), 4.58 (d, J = 8.2Hz, 2H), 4.50-4.48(m, 3H), 3.74-3.62(m, 6H), 3.22-3.18(m, 4H), 3.04-2.71(m, 4H), 2.52-2.49(m, 4H), 2.23-2.16(m, 4H).LCMS(ESI)C 29 H 33 Cl2FN5O3 + [M+H] + : Calculated value 588.19, measured value 588.2.

[0246] Example 20: Preparation of 3-(4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04609)

[0247] The target compound (GT-04609) (white solid, 8 mg, yield 10%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.96 (d, J=7.7Hz, 1H), 7.92 (d, J=7.7Hz, 1H), 7.71 (t, J=7.7Hz, 1H), 7. 35-7.26 (m, 2H), 7.18-7.16 (m, 1H), 5.23 (dd, J=13.2, 5.2Hz, 1H), 4.68 (d, J=17.4Hz, 1H), 4 .52-4.49(m, 2H), 3.84-3.66(m, 5H), 3.59-3.57(m, 2H), 3.46-3.32(m, 5H), 3.24-3.18(m, 2 H), 3.03-2.89(m, 1H), 2.84-2.81(m, 1H), 2.60-2.47(m, 3H), 2.38-2.16(m, 3H).LCMS(ESI)C 29 H 34 Cl2N5O3 + [M+H] + : Calculated value 570.20, measured value 570.2.

[0248] Example 21: Preparation of 3-(6-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04608)

[0249] The target compound (GT-04608) (white solid, 5 mg, yield 6%) was prepared by referring to the synthesis scheme 1. 1 H NMR (400MHz, MeOD) δ7.89 (s, 1H), 7.73 (d, J=7.3Hz, 1H), 7.66 (d, J=8.1Hz, 1H), 7.24-7.20 (m, 2H) , 7.08 (dd, J=6.4, 2.9Hz, 1H), 5.08 (dd, J=13.3, 5.2Hz, 1H), 4.47 (dd, J=31.5, 17.7Hz, 2H), 4.38-4 .32(m, 2H), 3.61-3.50(m, 2H), 3.48-3.25(m, 8H), 3.06-2.91(m, 3H), 2.83-2.78(m, 1H), 2.74-2.6 5(m, 1H), 2.46-2.39(m, 1H), 2.38-2.33(m, 2H), 2.11-2.07(m, 1H), 2.04-1.90(m, 2H).LCMS(ESI)C 29 H 34 Cl2N5O3+ [M+H] + : Calculated value 570.20, measured value 570.2.

[0250] Example 22: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05212)

[0251] The target compound (GT-05212) (white solid, 23 mg, 25%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ11.02 (s, 1H), 7.79 (d, J=7.7Hz, 1H), 7.75-7.69 (m, 2H), 7.66-7.58 (m, 1H), 7.39 -7.33 (m, 2H), 7.18-7.16 (m, 1H), 5.14 (dd, J=13.1, 5.2Hz, 1H), 4.90 (s, 1H), 4.51 (d, J=17.2Hz, 1H), 4.38 (d, J=17.2Hz, 1H), 4.27-4.06 (m, 2H), 3.35-3.08 (m, 10H), 3.00-2.84 (m, 2H), 2.82-2.65 (m, 1H), 2.61 (d , J=16.9Hz, 1H), 2.47-2.38(m, 1H), 2.33-2.30(m, 1H), 2.25-2.09(m, 1H), 2.08-1.95(m, 1H).LCMS(ESI)C 29 H 32 Cl2F2N5O3 + [M+H] + : Calculated value 606.18, measured value 606.2.

[0252] Example 23: Preparation of 3-(5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04989)

[0253] The target compound (GT-04989) (white solid, 14 mg, 17%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO-d6) δ11.52 (s, 1H), 11.02 (s, 1H), 8.10 (dd, J=8.9, 5.2Hz, 1H), 7.87-7.81 (m, 2H), 7.74-7.71 (m, 1H), 7.61 (dd, J=9.1, 2.1Hz, 1H), 7.28-7.23 (m, 1H), 5.15 (dd, J=13.4, 5.1Hz, 1H), 4.63 -4.33 (m, 5H), 4.24-4.01 (m, 2H), 3.69-3.39 (m, 8H), 3.08-3.04 (m, 1H), 3.04-2.85 (m, 3H), 2.61 (d, J= 15.4Hz, 1H), 2.47-2.41(m, 1H), 2.39-2.32(m, 2H), 2.28-2.09(m, 2H), 2.03-1.98(m, 1H).LCMS(ESI)C 30 H 34 FN6O4 + [M+H] + : Calculated value 561.26, measured value 561.3.

[0254] Example 24: Preparation of 3-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04931)

[0255] The target compound (GT-04931) (white solid, 23 mg, 26%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.01 (s, 1H), 8.05 (dd, J=8.9, 5.2Hz, 1H), 7.79 (d, J=7.5Hz, 1H), 7.70 (dd, J=16.6 , 7.1Hz, 1H), 7.62-7.56 (m, 2H), 7.21 (td, J=9.1, 2.1Hz, 1H), 5.14 (dd, J=13.2, 5.1Hz, 1H), 4.50 (d, J=17 .0Hz, 1H), 4.37 (d, J=17.2Hz, 1H), 4.14 (dd, J=48.4, 14.3Hz, 1H), 3.83-3.57 (m, 6H), 3.36-2.99 (m, 6H), 2.99-2.84(m, 2H), 2.61(d, J=16.6Hz, 1H), 2.42(dd, J=13.3, 4.5Hz, 2H), 2.25-1.93(m, 3H).LCMS(ESI)C 30 H 32F3N6O4 + [M+H] + : Calculated value 597.24, measured value 597.3.

[0256] Example 25: Preparation of 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04932)

[0257] The target compound (GT-04932) (white solid, 32 mg, 36%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO) δ11.00 (s, 1H), 8.25 (s, 1H), 7.80-7.69 (m, 2H), 7.63 (s, 1H), 7.54 (d, J=7.6Hz, 1H), 7.34 ( td, J=9.1, 2.1Hz, 1H), 5.13 (dd, J=13.2, 5.0Hz, 1H), 4.49 (d, J=17.4Hz, 1H), 4.36 (d, J=17.5Hz, 1H), 4.21-4. 04(m, 1H), 3.99-3.90(m, 4H), 3.64-3.50(m, 3H), 3.48-3.35(m, 3H), 3.22-3.10(m, 1H), 3.00-2.85(m, 1H), 2. 85-2.67(m, 1H), 2.61(d, J=16.8Hz, 2H), 2.47-2.31(m, 3H), 2.26-2.14(m, 3H), 2.07-1.92(m, 1H).LCMS(ESI)C 31 H 33 F3N5O4 + [M+H] + : Calculated value 596.25, measured value 596.3.

[0258] Example 26: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-05105)

[0259] The target compound (GT-05105) (white solid, 12 mg, 10%) was prepared by referring to the method of synthetic scheme 1. 1H NMR (400MHz, DMSO-d6) δ11.14 (s, 1H), 7.91 (d, J=7.7Hz, 1H), 7.88-7.79 (m, 4H), 7.60 (s , 1H), 7.49 (d, J=8.3Hz, 1H), 7.47-7.43 (m, 4H), 7.41-7.34 (m, 2H), 6.05-5.86 (m, 2H), 5. 62-5.59 (m, 1H), 4.80 (d, J=9.3Hz, 1H), 4.70 (t, J=10.3Hz, 1H), 3.21-3.08 (m, 6H), 3.08 -2.89(m, 8H), 2.65(d, J=17.9Hz, 2H), 2.12-2.06(m, 2H), 1.97-1.74(m, 2H).LCMS(ESI)C 36 H 40 F2N5O2S + [M+H] + : Calculated value 644.29, measured value 644.3.

[0260] Example 27: Preparation of 3-(5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-05208)

[0261] The target compound (GT-05208) (white solid, 20 mg, 17%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ11.15 (s, 1H), 8.74 (d, J=4.7Hz, 1H), 7.95-7.91 (m, 2H), 7.84-7.81 (m, 1H), 7.72-7.67 (m, 3H), 7.63 (d, J=7.9Hz, 1H), 7.53-7.36 (m, 4H), 6.04-5.85 (m, 1H), 4.9 4-4.81(m, 1H), 4.75-4.70(m, 1H), 4.48-4.15(m, 2H), 3.36-3.19(m, 5H), 3.11-3.03(m, 8H), 2.98-2.80(m, 2H), 2.68-2.63(m, 1H), 2.18-1.88(m, 3H), 1.32(t, J=6.5Hz, 1H).LCMS(ESI)C 35 H 39 F2N6O2S + [M+H] + : Calculated value 645.28, measured value 645.3.

[0262] Example 28: Preparation of 3-(6-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-05042)

[0263] The target compound (GT-05042) (white solid, 11 mg, 9%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ11.15 (s, 1H), 8.74 (d, J=4.6Hz, 1H), 7.87-7.82 (m, 2H), 7 .71-7.67(m, 4H), 7.67-7.62(m, 1H), 7.49-7.43(m, 4H), 5.95-5.86(m, 1H), 4.90- 4.85(m, 1H), 4.73-4.62(m, 1H), 4.48-4.34(m, 2H), 3.16-3.05(m, 6H), 2.98-2.82 (m, 4H), 2.66 (d, J=16.7Hz, 2H), 2.15-1.96 (m, 5H), 1.34-1.31 (m, 4H). LCMS (ESI) C 35 H 39 F2N6O2S + [M+H] + : Calculated value 645.28, measured value 645.3.

[0264] Example 29: Preparation of 1-(5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-04941)

[0265] The target compound (GT-04941) (white solid, 15 mg, 18%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.69 (s, 1H), 7.91-7.82 (m, 2H), 7.75 (d, J=7.4Hz, 1H), 7.53 -7.43(m, 4H), 7.38-7.31(m, 4H), 7.27-7.21(m, 2H), 4.80(d, J=17.0Hz, 1H), 4.57( d, J=15.6Hz, 1H), 4.42 (brs, 2H), 3.79 (t, J=7.0Hz, 2H), 3.67-3.47 (m, 7H), 3.14- 3.06(m, 2H), 3.03-2.73(m, 7H), 2.33-2.22(m, 2H), 2.17-2.06(m, 2H).LCMS(ESI)C 35 H 41 N6O3 + [M+H] + : Calculated value 593.32, measured value 593.3.

[0266] Example 30: Preparation of 5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-05255)

[0267] The target compound (GT-05255) (white solid, 34 mg, 37%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ10.93 (s, 1H), 8.15-8.10 (m, 1H), 7.65-7.44 (m, 4H) ,7.40-7.31(m,5H),7.31-7.14(m,3H),4.52-4.41(m,2H),3.82(t,J=6.7Hz , 1H), 3.63-3.48(m, 4H), 3.27-3.13(m, 4H), 3.06-2.94(m, 3H), 2.90-2.83( m, 4H), 2.35-2.22 (m, 3H), 2.14-2.04 (m, 2H), 1.96-1.85 (m, 1H). LCMS (ESI) C 35 H 39 N6O4 + [M+H] + : Calculated value 607.30, measured value 607.3.

[0268] Example 31: Preparation of 1-(5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-04942)

[0269] The target compound (GT-04942) (white solid, 22 mg, 24%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO) δ10.67 (s, 1H), 7.92-7.76 (m, 5H), 7.74-7.63 (m, 1H), 7.63-7.52 (m , 1H), 7.45-7.42 (m, 4H), 7.40-7.31 (m, 2H), 5.59 (d, J = 9.0Hz, 1H), 4.77 (d, J = 16.4Hz, 1 H), 4.55 (d, J=16.1Hz, 1H), 3.80-3.76 (m, 3H), 3.28-3.19 (m, 4H), 3.14-3.10 (m, 3H), 3 .05-2.96(m, 5H), 2.93-2.81(m, 2H), 2.78-2.72(m, 2H), 1.99-1.81(m, 2H).LCMS(ESI)C 35 H 39 F2N6O3 + [M+H] + : Calculated value 629.30, measured value 629.3.

[0270] Example 32: Preparation of 5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-05256)

[0271] The target compound (GT-05256) (white solid, 22 mg, 23%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ10.91 (s, 1H), 8.08-8.00 (m, 2H), 7.98-7.95 (m, 1H), 7.90-7.79 (m, 4H), 7.44 (t, J=7.4Hz, 4H), 7.38-7.35 (m, 2H), 5. 59(brs, 1H), 4.20-4.04(m, 2H), 3.65-3.61(m, 4H), 3.27-3.17(m, 4H), 3.18-3.08(m, 4H), 3.06-2.98(m, 5H), 2.02-1.78(m, 2H).LCMS(ESI)C 35 H37 F2N6O4 + [M+H] + : Calculated value 643.28, measured value 643.3.

[0272] Example 33: Preparation of 1-(5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-05082)

[0273] The target compound (GT-05082) (white solid, 80 mg, 71%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ10.69 (s, 1H), 8.74 (d, J=4.8Hz, 1H), 7.94-7.89 (m, 1H), 7.85 -7.80 (m, 2H), 7.76-7.61 (m, 4H), 7.44-7.40 (m, 4H), 5.87 (s, 1H), 4.80 (d, J=16.7Hz, 1H), 4.57 (d, J=16.5Hz, 1H), 4.31 (brs, 2H), 3.80-3.77 (m, 4H), 3.23-3.10 (m, 4H), 3. 10-2.97(m, 6H), 2.88-2.81(m, 2H), 2.79-2.73(m, 1H), 2.19-1.90(m, 2H).LCMS(ESI)C 34 H 38 F2N7O3 + [M+H] + : Calculated value 630.30, measured value 630.3.

[0274] Example 34: Preparation of 5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-05257)

[0275] The target compound (GT-05257) (white solid, 13 mg, 13%) was prepared by referring to the method of synthetic scheme 1. 1H NMR (400MHz, DMSO-d6) δ10.92 (s, 1H), 8.74 (d, J=4.7Hz, 1H), 8.06 (s, 1H), 7.92 (t, J=7.5Hz, 1H), 7.76-7.61 (m, 4H), 7.49-7.40(m, 5H), 5.86(s, 1H), 4.30(s, 2H), 3.80-3.75(m, 4H), 3.19-3.00(m, 13H), 2.09-1.93(m, 2H).LCMS(ESI)C 34 H 36 F2N7O4 + [M+H] + : Calculated value 644.28, measured value 644.3.

[0276] Example 35: Preparation of 1-(5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-05335)

[0277] The target compound (GT-05335) (white solid, 25 mg, 23%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ10.68 (s, 1H), 7.82 (d, J = 7.7Hz, 1H), 7.69 (s, 1H), 7.60 (s, 1H), 7.38 (d, J = 8.5Hz, 2H ), 7.25 (d, J=8.4Hz, 2H), 4.78 (d, J=17.1Hz, 1H), 4.56 (d, J=16.9Hz, 1H), 4.36-3.92 (m, 2H), 3.78 (t, J=6.1Hz , 3H), 3.25-3.17(m, 7H), 3.07-2.95(m, 2H), 2.94-2.82(m, 2H), 2.79-2.73(m, 2H), 2.44-2.33(m, 3H), 2.18- 2.00(m,1H),1.96-1.89(m,2H),1.83-1.72(m,2H),1.50-1.34(m,2H),1.00(s,3H),0.97(s,3H).LCMS(ESI)C 37 H 44 F2N6O4 + [M+H] + : Calculated value 709.31, measured value 709.3.

[0278] Example 36: Preparation of 5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-05271)

[0279] The target compound (GT-05271) (white solid, 20 mg, 19%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ10.92 (s, 1H), 8.08-8.01 (m, 2H), 7.93-7.90 (m, 1H), 7.39 (d , J=8.4Hz, 2H), 7.25 (d, J=8.4Hz, 2H), 4.12-3.96 (m, 3H), 3.33-3.13 (m, 9H), 3.12-2. 96 (m, 4H), 2.69-2.57 (m, 2H), 2.42-2.37 (m, 3H), 2.19-2.04 (m, 1H), 1.90 (d, J=16.6 Hz, 1H), 1.82-1.70 (m, 3H), 1.50-1.35 (m, 2H), 1.00 (s, 3H), 0.97 (s, 3H). LCMS (ESI) C 37 H 42 ClF2N6O5 + [M+H] + : Calculated value 723.29, measured value 723.3.

[0280] Example 37: Preparation of 5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-05270)

[0281] The target compound (GT-05270) (white solid, 26 mg, 25%) was prepared by referring to the method of synthetic scheme 1. 1H NMR (400MHz, DMSO-d6) δ10.92 (s, 1H), 8.04-8.00 (m, 2H), 7.98-7.90 (m, 1H), 7. 45 (d, J=8.4Hz, 2H), 7.14 (d, J=8.4Hz, 2H), 4.99 (s, 1H), 3.82 (t, J=6.7Hz, 4H), 3.27-3.19(m, 6H), 3.12-2.96(m, 6H), 2.86(t, J=6.7Hz, 4H), 2.70-2.57(m, 3H) , 2.29(brs, 2H), 2.04(brs, 2H), 1.47(t, J=6.8Hz, 2H), 0.96(s, 6H).LCMS(ESI)C 37 H 44 ClF2N6O4 + [M+H] + : Calculated value 709.31, measured value 709.3.

[0282] Example 38: Preparation of 5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-05258)

[0283] The target compound (GT-05258) (white solid, 16 mg, 17%) was prepared by referring to the method of synthetic scheme 1. 1 H NMR (400MHz, DMSO-d6) δ10.92(s, 1H), 8.02(s, 2H), 7.94-7.92(m, 1H), 7.36-7.32(m, 2H), 7.20-7.17(m, 1H), 4.99( s, 1H), 4.11-3.91 (m, 2H), 3.36-3.17 (m, 13H), 3.13-3.01 (m, 3H), 2.28-2.18 (m, 1H), 2.09-1.89 (m, 1H). LCMS (ESI) C 28 H 29 Cl2F2N6O4 + [M+H] + : Calculated value 621.16, measured value 621.2.

[0284] Example 39: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05333)

[0285] The target compound GT-05333 (26 mg, white solid, yield 24%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.01 (s, 1H), 7.77 (dd, J=7.9, 1.7Hz, 1H), 7.68 (d, J=8.9Hz, 1H), 7.63-7.58 ( m, 2H), 7.38 (t, J=7.9Hz, 1H), 7.26 (dd, J=7.6, 1.3Hz, 1H), 5.75 (s, 1H), 5.13 (dd, J=13.3, 5.1Hz, 2 H), 4.49 (d, J=17.9Hz, 2H), 4.37 (d, J=17.9Hz, 2H), 4.10-3.82 (m, 5H), 3.43-3.39 (m, 4H), 3.23-3. 14(m,1H),2.96-2.89(m,2H),2.67-2.63(m,2H),2.47-2.39(m,2H),2.07-1.98(m,2H).LCMS(ESI)C 30 H 31 Cl2F2N4O3 + [M+H] + : Calculated value 603.17, measured value 603.2.

[0286] Example 40: Preparation of 3-(5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09941)

[0287] The target compound GT-09941 (7 mg, white solid, yield 11%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.14 (s, 1H), 7.96 (d, J=7.9Hz, 1H), 7.89 (s, 1H), 7.85 (d, J=8.0Hz, 1H), 7.75 (d, J=8.2Hz, 1H), 7.60 (s, 1H), 7.49 (d, J=8.1Hz, 2H), 7.40-7.30 (m, 4H), 7.24 (brs, 2H), 5.95 (d, J=8.9Hz, 1H), 4.87 (d, J=20.5Hz, 1H), 4.77 (d, J=20.4Hz, 1H), 4.63 (s, 1H), 4.43 (s, 2H), 3.59-3.48 (m, 4H), 3.32 -3.18(m, 4H), 3.05-2.83(m, 6H), 2.67-2.63(m, 2H), 2.31-2.21(m, 2H), 2.17-2.06(m, 3H).LCMS(ESI)C 36 H 42 N5O2S + [M+H] + : Calculated value 608.31, measured value 608.3.

[0288] Example 41: Preparation of 3-(4-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09938)

[0289] The target compound GT-09938 (8 mg, white solid, yield 12%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.20 (s, 1H), 7.99 (d, J = 7.6Hz, 1H), 7.94 (d, J = 7.4Hz, 1H), 7.67 (t, J = 7.8Hz, 1H), 7.56-7.43(m, 4H), 7.38-7.32(m, 4H), 7.26-7.22(m, 2H), 6.07-5.94(m, 1H), 5.24(d, J=20.0H z, 1H), 4.88 (d, J=20.6Hz, 1H), 4.53-4.33 (m, 3H), 3.65-3.55 (m, 2H), 3.14-3.05 (m, 4H), 2.98-2.8 2(m, 4H), 2.74-2.66(m, 2H), 2.46-2.38(m, 2H), 2.32-2.22(m, 3H), 2.20-2.06(m, 4H).LCMS(ESI)C 36 H 42 N5O2S + [M+H]+ : Calculated value 608.31, measured value 608.3.

[0290] Example 42: Preparation of 3-(6-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09862)

[0291] The target compound GT-09862 (8 mg, white solid, yield 12%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 8.10 (s, 1H), 7.87 (d, J = 7.3Hz, 1H), 7.77 (d, J = 8.1Hz, 1H), 7.51- 7.44(m, 4H), 7.37-7.31(m, 4H), 7.25-7.21(m, 2H), 6.01-5.86(m, 1H), 4.88(d, J=20.7Hz, 1H), 4.74 (d, J=20.2Hz, 1H), 4.46 (brs, 3H), 3.56-3.51 (m, 2H), 3.13-3.04 (m, 2H), 3.03-2.92 (m, 4H), 2.89-2 .80(m,2H),2.67-2.62(m,2H),2.45-2.42(m,3H),2.34-2.26(m,2H),2.14-1.98(m,4H).LCMS(ESI)C 36 H 42 N5O2S + [M+H] + : Calculated value 608.31, measured value 608.3.

[0292] Example 43: Preparation of 3-(4-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09617)

[0293] The target compound GT-09617 (12 mg, white solid, yield 16%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.12 (s, 1H), 7.91-7.77 (m, 5H), 7.67-7.52 (m, 2H), 7.48-7.43 (m, 4 H), 7.37-7.35 (m, 2H), 5.97 (d, J = 10.5Hz, 1H), 5.60 (d, J = 7.3Hz, 1H), 4.86 (d, J = 19.2Hz, 1 H), 4.74 (d, J=18.1Hz, 1H), 3.89-3.67 (m, 1H), 3.26-3.09 (m, 6H), 3.08-2.94 (m, 7H), 2.6 5(d, J=16.8Hz, 2H), 2.47-2.39(m, 2H), 2.15-2.03(m, 1H), 1.82-1.73(m, 2H).LCMS(ESI)C 36 H 40 F2N5O2S + [M+H] + : Calculated value 644.29, measured value 644.3.

[0294] Example 44: Preparation of 3-(6-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09691)

[0295] The target compound GT-09691 (14 mg, white solid, yield 20%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.06 (s, 1H), 7.95-7.84 (m, 1H), 7.81-7.66 (m, 4H), 7.61 (s, 2H), 7. 44-7.33(m, 4H), 7.34-7.23(m, 2H), 5.93-5.82(m, 1H), 5.57-5.47(m, 1H), 4.77(d, J=20.2 Hz, 1H), 4.63 (d, J=19.9Hz, 1H), 4.01-3.68 (m, 2H), 3.65-3.38 (m, 6H), 3.13-3.02 (m, 5H) , 3.07-2.92(m, 5H), 2.61-2.55(m, 2H), 2.08-1.96(m, 1H), 1.89-1.70(m, 1H).LCMS(ESI)C 36 H 40 F2N5O2S + [M+H] + : Calculated value 644.29, measured value 644.3.

[0296] Example 45: Preparation of 3-(4-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09618)

[0297] The target compound GT-09618 (15 mg, white solid, yield 20%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.15 (s, 1H), 8.74 (d, J=4.8Hz, 1H), 7.93-7.90 (m, 2H), 7.68 (d, J=7.0H z, 3H), 7.61 (dd, J=13.9, 7.5Hz, 2H), 7.51-7.37 (m, 4H), 5.98 (d, J=8.0Hz, 1H), 5.84 (s, 1H), 5 .01 (dd, J=33.7, 18.0Hz, 1H), 4.80 (d, J=20.1Hz, 1H), 4.29-3.92 (m, 2H), 3.27-2.90 (m, 13H), 2.66(d, J=14.1Hz, 2H), 2.47-2.38(m, 1H), 2.17-2.05(m, 1H), 2.06-1.82(m, 2H).LCMS(ESI)C 35 H 39 F2N6O2S + [M+H] + : Calculated value 645.28, measured value 645.3.

[0298] Example 46: Preparation of 3-(5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09679)

[0299] The target compound GT-09679 (11 mg, white solid, yield 14%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.13 (s, 1H), 7.91 (d, J=7.5Hz, 1H), 7.70-7.65 (m, 1H), 7.63-7.50 (m, 1H), 7.3 7 (d, J=8.4Hz, 2H), 7.24 (d, J=8.5Hz, 2H), 6.03-5.90 (m, 1H), 4.84 (d, J=19.7Hz, 1H), 4.70 (d, J=20.2 Hz, 1H), 3.17-3.08 (m, 4H), 3.02-2.93 (m, 4H), 2.71-2.61 (m, 2H), 2.42-2.33 (m, 6H), 2.15-2.00 (m, 4H), 1.96-1.85(m, 2H), 1.74-1.59(m, 2H), 1.51-1.37(m, 3H), 0.99(s, 3H), 0.96(s, 3H).LCMS(ESI)C 38 H 45 ClF2N5O3S + [M+H] + : Calculated value 724.29, measured value 724.3.

[0300] Example 47: Preparation of 3-(4-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09619)

[0301] The target compound GT-09619 (19 mg, white solid, yield 23%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.15 (d, J=4.5Hz, 1H), 7.87 (d, J=7.5Hz, 1H), 7.67-7.50 (m, 2H), 7.37 (d, J=8.4Hz , 2H), 7.24 (d, J=8.5Hz, 2H), 6.07-5.91 (m, 1H), 4.86 (d, J=18.8Hz, 1H), 4.75 (d, J=21.0Hz, 1H), 3.91-3 .74(m, 1H), 3.27-3.19(m, 7H), 3.05-2.86(m, 4H), 2.72-2.62(m, 2H), 2.44-2.29(m, 4H), 2.19-2.00(m, 3H), 1.90 (d, J=17.2Hz, 1H), 1.80-1.57 (m, 2H), 1.52-1.36 (m, 2H), 0.98 (d, J=13.3Hz, 6H). LCMS (ESI) C38 H 45 ClF2N5O3S + [M+H] + : Calculated value 724.29, measured value 724.3.

[0302] Example 48: Preparation of 3-(6-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09692)

[0303] The target compound GT-09692 (10 mg, white solid, yield 13%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.13 (s, 1H), 7.90-7.85 (m, 1H), 7.72-7.69 (m, 2H), 7.37 (d, J=8.3Hz, 2H), 7.2 4 (d, J=8.5Hz, 2H), 5.98-5.92 (m, 1H), 4.84 (d, J=20.9Hz, 1H), 4.70 (d, J=20.1Hz, 1H), 3.31-3.17 (m , 6H), 3.15-3.02(m, 3H), 3.03-2.90(m, 3H), 2.68-2.62(m, 2H), 2.43-2.33(m, 4H), 2.14-2.04(m, 3H ), 1.90 (d, J = 15.5Hz, 1H), 1.79-1.60 (m, 3H), 1.47-1.38 (m, 2H), 0.98 (d, J = 12.9Hz, 6H). LCMS (ESI) C 38 H 45 ClF2N5O4 + [M+H] + : Calculated value 708.31, measured value 708.3.

[0304] Example 49: Preparation of 3-(5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09680)

[0305] The target compound GT-09680 (21 mg, white solid, yield 27%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.13 (s, 1H), 7.90 (d, J = 8.0Hz, 1H), 7.65-7.51 (m, 2H), 7.44 (d, J = 8.4Hz, 2H), 7.13 (d, J=8.4Hz, 2H), 6.01-5.90 (m, 1H), 4.83 (d, J=18.0Hz, 1H), 4.70 (d, J=20.4Hz, 1H), 3 .57-3.53(m, 2H), 3.24-3.19(m, 4H), 3.03-2.96(m, 3H), 2.89-2.81(m, 4H), 2.65-2.58(m, 4H), 2.30-2.24(m, 4H), 2.03(s, 4H), 1.80-1.67(m, 2H), 1.47-1.45(m, 2H), 0.96(s, 6H).LCMS(ESI)C 38 H 47 ClF2N5O2S + [M+H] + : Calculated value 710.31, measured value 710.3.

[0306] Example 50: Preparation of 3-(4-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09576)

[0307] The target compound GT-09576 (23 mg, white solid, yield 28%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.15 (s, 1H), 7.86 (d, J=6.5Hz, 1H), 7.84-7.77 (m, 1H), 7.60-7.55 (m, 1H), 7.44 (d, J=8.3Hz , 2H), 7.14 (d, J=8.3Hz, 2H), 5.97 (s, 1H), 4.90 (d, J=20.5Hz, 1H), 4.78 (d, J=20.1Hz, 1H), 3.94-3.64 (m, 2H), 3.5 5(brs, 2H), 3.39-3.31(m, 4H), 3.25-3.18(m, 3H), 3.07-2.97(m, 4H), 2.94-2.79(m, 3H), 2.67-2.60(m, 3H), 2.33 -2.25(m, 3H), 2.17-2.07(m, 1H), 2.04(s, 2H), 1.85-1.72(m, 2H), 1.46(t, J=6.1Hz, 2H), 0.96(s, 6H).LCMS(ESI)C 38 H 47 ClF2N5O2S + [M+H] + : Calculated value 710.31, measured value 710.3.

[0308] Example 51: Preparation of 3-(6-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09863)

[0309] The target compound GT-09863 (16 mg, white solid, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.13 (s, 1H), 7.99-7.92 (m, 1H), 7.75-7.62 (m, 2H), 7.44 (d, J=8.3Hz, 2 H), 7.13 (d, J = 8.3Hz, 2H), 5.98-5.94 (m, 1H), 4.84 (d, J = 20.2Hz, 1H), 4.69 (d, J = 19.6Hz, 1H), 3.54(s, 2H), 3.25-3.17(m, 4H), 3.07-2.96(m, 4H), 2.93-2.75(m, 4H), 2.71-2.53(m, 6H), 2. 33-2.25(m, 3H), 2.15-2.07(m, 1H), 2.03(s, 3H), 1.92-1.63(m, 2H), 0.96(s, 6H).LCMS(ESI)C 38 H 47 ClF2N5O2S + [M+H] + : Calculated value 710.31, measured value 710.3.

[0310] Example 52: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09934)

[0311] The target compound GT-09934 (8 mg, white solid, yield 12%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.15 (s, 1H), 8.03-7.94 (m, 1H), 7.85 (d, J=8.0Hz, 1H), 7.81-7.69 (m, 1H) ), 7.42-7.34 (m, 2H), 7.20 (dd, J=7.0, 2.3Hz, 1H), 6.04-5.88 (m, 1H), 4.86 (d, J=20.5Hz, 1H), 4 .76(d, J=20.2Hz, 1H), 4.52-4.40(m, 1H), 3.68-3.61(m, 2H), 3.29-3.23(m, 4H), 3.21-3.13(m , 4H), 3.05-2.90(m, 4H), 2.67-2.61(m, 2H), 2.41-2.36(m, 2H), 2.18-2.03(m, 4H).LCMS(ESI)C 29 H 34 Cl2N5O2S + [M+H] + : Calculated value 586.18, measured value 586.3.

[0312] Example 53: Preparation of 3-(4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09939)

[0313] The target compound GT-09939 (14 mg, white solid, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.21 (s, 1H), 8.07-7.87 (m, 2H), 7.78-7.62 (m, 1H), 7.40-7.30 ( m, 2H), 7.25-7.14 (m, 1H), 6.02-5.98 (m, 1H), 5.24 (d, J=18.2Hz, 1H), 4.89 (d, J=18.3H z, 1H), 4.53-4.30 (m, 2H), 3.70-3.55 (m, 4H), 3.17-3.07 (m, 4H), 2.97-2.82 (m, 2H), 2. 74-2.66(m, 2H), 2.44-2.39(m, 2H), 2.30-2.18(m, 3H), 2.18-2.04(m, 4H).LCMS(ESI)C 29 H 34 Cl2N5O2S + [M+H] + : Calculated value 586.18, measured value 586.3.

[0314] Example 54: Preparation of 3-(6-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09935)

[0315] The target compound GT-09935 (8 mg, white solid, yield 12%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.14 (s, 1H), 8.14-8.10 (m, 1H), 7.93-7.86 (m, 1H), 7.82-7.74 (m , 1H), 7.42-7.35 (m, 2H), 7.22-7.18 (m, 1H), 5.96 (d, J=10.3Hz, 2H), 4.89 (d, J=20.8Hz, 1H), 4.75 (d, J=20.4Hz, 2H), 4.55-4.42 (m, 2H), 3.65-3.54 (m, 4H), 3.24-3.16 (m, 6H), 3 .03-2.92(m, 4H), 2.67-2.63(m, 2H), 2.44-2.33(m, 2H), 2.18-2.04(m, 3H).LCMS(ESI)C 29 H 34 Cl2N5O2S + [M+H] + : Calculated value 586.18, measured value 586.3.

[0316] Example 55: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09687)

[0317] The target compound GT-09687 (13 mg, white solid, yield 19%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.07 (s, 1H), 7.86 (d, J = 8.0Hz, 1H), 7.63 (s, 1H), 7.53 (d, J = 7.6Hz, 1H) , 7.29-7.24 (m, 2H), 7.14-7.05 (m, 1H), 5.89 (d, J = 11.3Hz, 1H), 4.79 (d, J = 20.5Hz, 1H), 4.65 (d, J=20.6Hz, 1H), 4.10-3.83(m, 2H), 3.17-2.98(m, 10H), 2.95-2.84(m, 2H), 2.63-2.55(m, 2H), 2.50-2.45(m, 2H), 2.17-2.08(m, 1H), 2.06-2.01(m, 1H), 1.99-1.87(m, 1H).LCMS(ESI)C 29 H 32 Cl2F2N5O2S + [M+H] + : Calculated value 622.16, measured value 622.2.

[0318] Example 56: Preparation of 3-(4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09575)

[0319] The target compound GT-09575 (31 mg, white solid, yield 43%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.15 (s, 1H), 7.87 (d, J=7.7Hz, 1H), 7.70-7.61 (m, 1H), 7.58 (d , J=7.4Hz, 1H), 7.34(d, J=5.3Hz, 2H), 7.21-7.15(m, 1H), 6.01-5.95(m, 1H), 4.89(d , J=19.8Hz, 1H), 4.77 (d, J=20.9Hz, 1H), 3.97-3.72 (m, 2H), 3.24-3.14 (m, 9H), 3.06 -2.86(m, 4H), 2.70-2.64(m, 2H), 2.18-2.07(m, 2H), 2.03-1.84(m, 2H).LCMS(ESI)C 29 H 32 Cl2F2N5O2S + [M+H] + : Calculated value 622.16, measured value 622.2.

[0320] Example 57: Preparation of 3-(6-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09693)

[0321] The target compound GT-09693 (11 mg, white solid, yield 16%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.13 (s, 1H), 8.06-7.95 (m, 1H), 7.78-7.68 (m, 2H), 7.33 (d, J=4.7Hz, 2H), 7.16 (t, J=4.8Hz, 1H), 6.01-5.90 (m, 1H), 4.86 (d, J=20.7Hz, 1H), 4.72 (d, J=20.1Hz, 1H), 4.30-3.84 (m, 2H), 3.18-3.05 (m, 11H), 2.70-2.62 (m, 2H), 2.22-1.93 (m, 6H). LCMS (ESI) C 29 H 32 Cl2F2N5O2S+ [M+H] + : Calculated value 622.16, measured value 622.2.

[0322] Example 58: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09688)

[0323] The target compound GT-09688 (12 mg, white solid, yield 17%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 7.92 (d, J=7.8Hz, 1H), 7.66 (s, 1H), 7.63-7.54 (m, 2H), 7.38 (t, J=7.7Hz, 1H), 7.26 (d, J=6.2Hz, 1H), 6.02-5.88 (m, 1H), 5.75 (s, 1H), 4.85 (d, J=20 .1Hz, 1H), 4.71 (d, J=19.7Hz, 1H), 3.98-3.84 (m, 2H), 3.31-3.21 (m, 6H), 3.17-3.06 (m, 3H) ), 3.01-2.92(m, 2H), 2.70-2.61(m, 4H), 2.14-2.06(m, 1H), 2.04-1.94(m, 1H).LCMS(ESI)C 30 H 31 Cl2F2N4O2S + [M+H] + : Calculated value 619.15, measured value 619.2.

[0324] Example 59: Preparation of 3-(4-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09614)

[0325] The target compound GT-09614 (10 mg, white solid, yield 14%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.14 (s, 1H), 7.87 (d, J=7.4Hz, 1H), 7.68-7.54 (m, 3H), 7.39 (t, J=7.9Hz, 1H), 7.26 (dd, J=7.6, 1.2Hz, 1H), 6.00 (d, J=11.0Hz, 1H), 5.77 (s, 1H), 4.89 (d, J=18.7Hz, 1H), 4.76 (d, J=20.2Hz, 1H), 3.97-3.74 (m, 4H), 3.37-3.19 (m, 9H), 3.0 8-2.92(m, 2H), 2.71-2.65(m, 2H), 2.17-2.09(m, 1H), 2.02-1.93(m, 1H).LCMS(ESI)C 30 H 31 Cl2F2N4O2S + [M+H] + : Calculated value 619.15, measured value 619.2.

[0326] Example 60: Preparation of 3-(6-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09694)

[0327] The target compound GT-09694 (10 mg, white solid, yield 15%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.13 (s, 1H), 8.00-7.88 (m, 1H), 7.73-7.64 (m, 2H), 7.60 (d, J=8.0Hz, 1H), 7.38 (t, J=7.8Hz, 1H), 7.25 (d, J=7.7Hz, 1H), 6.03-5.89 (m, 1H), 5.74 (s, 1H), 4.85 (d, J =20.6Hz, 1H), 4.71 (d, J = 20.2Hz, 1H), 4.07-3.84 (m, 2H), 3.65-3.52 (m, 2H), 3.37-3.31 (m, 6 H), 3.32-3.05(m, 4H), 2.99-2.92(m, 1H), 2.69-2.63(m, 2H), 2.14-1.99(m, 3H).LCMS(ESI)C 30 H 31 Cl2F2N4O2S + [M+H] + : Calculated value 619.15, measured value 619.2.

[0328] Example 61: Preparation of 3-(5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09861)

[0329] The target compound GT-09861 (13 mg, white solid, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.15 (s, 1H), 8.09 (dd, J=8.8, 5.2Hz, 1H), 7.97 (d, J=8.0Hz, 1H), 7.89 (s, 1H), 7. 77 (t, J=6.8Hz, 1H), 7.61 (dd, J=8.9, 1.7Hz, 1H), 7.26 (t, J=8.5Hz, 1H), 5.97 (d, J=14.1Hz, 1H), 4.88 ( d, J=20.4Hz, 1H), 4.74 (d, J=20.3Hz, 1H), 4.45 (brs, 2H), 4.25-4.01 (m, 2H), 3.61-3.50 (m, 6H), 3.02- 2.95(m, 4H), 2.67-2.63(m, 2H), 2.37-2.31(m, 2H), 2.26-2.15(m, 2H), 2.15-1.96(m, 3H).LCMS(ESI)C 30 H 34 FN6O3S + [M+H] + : Calculated value 577.24, measured value 577.3.

[0330] Example 62: Preparation of 3-(4-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09940)

[0331] The target compound GT-09940 (10 mg, white solid, yield 15%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.21 (s, 1H), 8.12-8.08 (m, 1H), 8.04-7.90 (m, 2H), 7.68 (t, J=7.7Hz, 1H), 7.61 (dd, J=9.1, 2.0Hz, 1H), 7.26 (td, J=9.0, 2.1Hz, 1H), 6.05-6.00 (m, 1H), 5.25 (d, J=21.4Hz, 1H), 4.88 ( d, J=20.4Hz, 1H), 4.49-4.36 (m, 1H), 4.22-4.00 (m, 2H), 3.64-3.50 (m, 6H), 3.21-3.07 (m, 4H), 3.02- 2.89(m, 2H), 2.74-2.66(m, 2H), 2.40-2.33(m, 2H), 2.29-2.19(m, 2H), 2.18-2.06(m, 2H).LCMS(ESI)C 30 H 34 FN6O3S + [M+H] + : Calculated value 577.24, measured value 577.3.

[0332] Example 63: Preparation of 3-(6-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09864)

[0333] The target compound GT-09864 (11 mg, white solid, yield 16%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 8.14-8.05 (m, 2H), 7.90 (d, J=8.1Hz, 1H), 7.78 (d, J=7. 9Hz, 1H), 7.61 (dd, J=9.0, 2.0Hz, 1H), 7.26 (t, J=9.0Hz, 1H), 5.96 (d, J=9.3Hz, 1H), 4.89 (d , J=20.5Hz, 1H), 4.75 (d, J=20.5Hz, 1H), 4.49 (s, 2H), 4.22-4.03 (m, 2H), 3.61-3.49 (m, 6H ), 3.04-2.89(m, 4H), 2.72-2.67(m, 2H), 2.41-2.32(m, 3H), 2.22-2.04(m, 4H).LCMS(ESI)C 30 H 34 FN6O3S + [M+H] +: Calculated value 577.24, measured value 577.3.

[0334] Example 64: Preparation of 3-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09689)

[0335] The target compound GT-09689 (13 mg, white solid, yield 19%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.13 (s, 1H), 8.05 (dd, J=8.9, 5.3Hz, 1H), 7.93 (d, J=7.6Hz, 1H), 7.71 (br s, 1H), 7.62 (brs, 1H), 7.56 (dd, J=9.1, 2.1Hz, 1H), 7.21 (t, J=9.0Hz, 1H), 6.04-5.87 (m, 1H), 4. 85 (d, J=20.3Hz, 1H), 4.72 (d, J=19.7Hz, 1H), 4.19-3.89 (m, 2H), 3.70-3.56 (m, 3H), 3.58-3.48 ( m, 6H), 3.20-3.03 (m, 3H), 3.01-2.93 (m, 2H), 2.71-2.61 (m, 2H), 2.19-1.92 (m, 3H). LCMS (ESI) C 30 H 32 F3N6O3S + [M+H] + : Calculated value 613.22, measured value 613.3.

[0336] Example 65: Preparation of 3-(4-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09615)

[0337] The target compound GT-09615 (15 mg, white solid, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.16 (s, 1H), 8.06 (dd, J=8.9, 5.3Hz, 1H), 7.88 (d, J=7.3Hz, 1H), 7.6 5 (s, 1H), 7.57 (dd, J=9.1, 2.1Hz, 2H), 7.22 (t, J=8.0Hz, 1H), 6.08-5.91 (m, 1H), 4.91 (d, J =23.1Hz, 1H), 4.83-4.69(m, 1H), 3.92-3.85(m, 2H), 3.65-3.54(m, 4H), 3.31-3.24(m, 9H) , 3.11-2.94(m, 2H), 2.70-2.67(m, 2H), 2.21-2.04(m, 2H), 2.01-1.85(m, 1H).LCMS(ESI)C 30 H 32 F3N6O3S + [M+H] + : Calculated value 613.22, measured value 613.3.

[0338] Example 66: Preparation of 3-(6-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09695)

[0339] The target compound GT-09695 (9 mg, white solid, yield 13%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 8.04 (dd, J=8.9, 5.3Hz, 1H), 8.00-7.98 (m, 1H) , 7.71 (brs, 2H), 7.56 (dd, J=9.1, 2.2Hz, 1H), 7.20 (t, J=7.9Hz, 1H), 5.99-5.94 (m , 1H), 4.86 (d, J=20.4Hz, 1H), 4.72 (d, J=20.2Hz, 1H), 4.27-4.21 (m, 2H), 3.74-3. 66(m, 2H), 3.11-2.93(m, 12H), 2.69-2.65(m, 2H), 2.12-2.03(m, 3H).LCMS(ESI)C 30 H 32 F3N6O3S + [M+H] + : Calculated value 613.22, measured value 613.3.

[0340] Example 67: Preparation of 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09690)

[0341] The target compound GT-09690 (14 mg, white solid, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.13 (s, 1H), 8.18 (s, 1H), 7.90 (d, J=7.9Hz, 1H), 7.73 (dd, J=9.1, 2.1Hz, 1H), 7.63 (s, 1H), 7.54 (d, J = 7.5Hz, 1H), 7.35 (dd, J = 10.0, 8.1Hz, 1H), 5.98-5.92 (m, 1H), 4.84 (d, J = 19.6Hz, 1H), 4.70 (d, J=20.1Hz, 1H), 3.94-3.78 (m, 2H), 3.76-3.65 (m, 2H), 3.60-3.43 (m, 6H), 3.08-3.03 (m, 1H), 2.9 8-2.92(m, 1H), 2.69-2.63(m, 2H), 2.45-2.29(m, 4H), 2.28-2.16(m, 2H), 2.15-2.03(m, 2H).LCMS(ESI)C 31 H 33 F3N5O3S + [M+H] + : Calculated value 612.23, measured value 612.2.

[0342] Example 68: Preparation of 3-(4-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09616)

[0343] The target compound GT-09616 (13 mg, white solid, yield 18%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.13 (s, 1H), 8.26-8.14 (m, 1H), 7.86 (d, J=7.4Hz, 1H), 7.73 (dd, J=9.0, 1.9 Hz, 1H), 7.66-7.53 (m, 2H), 7.39-7.30 (m, 1H), 6.06-5.89 (m, 1H), 4.95-4.83 (m, 1H), 4.75 (d, J=19 .9Hz, 1H), 4.16-3.94(m, 1H), 3.89-3.61(m, 4H), 3.60-3.44(m, 4H), 3.26-3.12(m, 2H), 3.01-2.9 5(m, 2H), 2.75-2.62(m, 2H), 2.46-2.33(m, 3H), 2.27-2.19(m, 2H), 2.17-1.95(m, 2H).LCMS(ESI)C 31 H 33 F3N5O3S + [M+H] + : Calculated value 612.23, measured value 612.2.

[0344] Example 69: Preparation of 3-(6-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione (GT-09936)

[0345] The target compound GT-09936 (12 mg, white solid, yield 17%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.13 (s, 1H), 8.15-8.06 (m, 1H), 7.94-7.86 (m, 1H), 7.72 (d, J=8. 9Hz, 1H), 7.69-7.62 (m, 2H), 7.38-7.30 (m, 1H), 5.99-5.91 (m, 1H), 4.83 (d, J=20.6Hz, 1 H), 4.69 (d, J=20.3Hz, 1H), 3.87-3.82 (m, 2H), 3.28-3.14 (m, 6H), 3.08-2.90 (m, 4H), 2 .71-2.64(m, 2H), 2.30-2.22(m, 4H), 2.14-2.06(m, 2H), 2.02-1.98(m, 2H).LCMS(ESI)C 31 H 33 F3N5O3S + [M+H] + : Calculated value 612.23, measured value 612.2.

[0346] Example 70: Preparation of 1-(5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-05334)

[0347] The target compound GT-05334 (32 mg, white solid, yield 30%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO-d6) δ10.61 (s, 1H), 9.41 (s, 1H), 7.72 (d, J=7.7Hz, 1H), 7.62-7.54 (m, 1H), 7.54-7.44 (m, 1H), 7.37 (d, J=8.3Hz, 2H), 7.07 (d, J=8.3Hz, 2H), 4.70 (d, J=16.2Hz, 1H), 4.48 (d, J=16.3Hz, 1H), 4.01-3.80 (m, 1H), 3.73-3.68 (m, 3H), 3.48 (s, 2H), 3.15 (d, J=10.1Hz, 4H), 3.01-2.87 (m, 4H), 2.84-2.76 (m, 4H), 2.73-2.63 (m, 1H), 2.59-2.49 (m, 2 H), 2.20 (brs, 2H), 1.97 (s, 2H), 1.86-1.74 (m, 1H), 1.72-1.65 (m, 1H), 1.39 (t, J=6.1Hz, 2H), 0.89 (s, 6H).LCMS (ESI) C 37 H 46 ClF2N6O3 + [M+H] + : Calculated value 695.33, measured value 695.3.

[0348] Example 71: Preparation of 1-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-09355)

[0349] The target compound GT-09355 (11 mg, white solid, yield 20%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.70 (s, 1H), 7.94-7.82 (m, 2H), 7.83-7.73 (m, 1H), 7.43-7.31 (m, 2H), 7. 22-7.19 (m, 1H), 4.82 (d, J = 16.1Hz, 1H), 4.59 (d, J = 16.6Hz, 1H), 4.45 (brs, 1H), 3.79 (t, J = 6.8H z, 2H), 3.67-3.58 (m, 2H), 3.51-3.43 (m, 4H), 3.25-3.17 (m, 4H), 3.04-2.95 (m, 2H), 2.94-2.82 ( m, 2H), 2.81-2.76 (m, 1H), 2.40-2.30 (m, 2H), 2.29-2.12 (m, 2H), 2.06-1.92 (m, 1H). LCMS (ESI) C 28 H 33 Cl2N6O3 + [M+H] + : Calculated value 571.20, measured value 571.2.

[0350] Example 72: Preparation of 5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-09357)

[0351] The target compound GT-09357 (17 mg, white solid, yield 32%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.93 (s, 1H), 8.28 (s, 1H), 8.20-8.04 (m, 2H), 7.39-7.34 ( m, 2H), 7.26-7.15 (m, 1H), 4.65-4.34 (m, 2H), 3.83 (t, J=6.8Hz, 2H), 3.69-3.65 ( m, 2H), 3.24-3.13 (m, 6H), 3.09-2.96 (m, 2H), 2.86 (t, J=6.8Hz, 2H), 2.76 (t, J=6 .8Hz, 1H), 2.46-2.29(m, 3H), 2.26-2.10(m, 2H), 2.10-1.92(m, 1H).LCMS(ESI)C 28 H 31 Cl2N6O4 + [M+H] + : Calculated value 585.18, measured value 585.2.

[0352] Example 73: Preparation of 1-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-09205)

[0353] The target compound GT-09205 (43 mg, white solid, yield 57%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.68 (s, 1H), 7.82 (d, J=7.8Hz, 1H), 7.71 (s, 1H), 7.62 (d, J=7 .7Hz, 1H), 7.40-7.32 (m, 2H), 7.17 (dd, J=5.7, 3.8Hz, 1H), 4.80 (d, J=16.6Hz, 1H), 4 .57(d, J=16.5Hz, 1H), 4.10(s, 2H), 3.81-3.77(m, 4H), 3.33-3.14(m, 10H), 2.90-2. 84(m, 2H), 2.78(t, J=5.3Hz, 1H), 2.40-2.25(m, 1H), 2.20-2.04(m, 1H).LCMS(ESI)C 28 H 31 Cl2F2N6O3 + [M+H] + : Calculated value 607.18, measured value 607.2.

[0354] Example 74: Preparation of 1-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-09206)

[0355] The target compound GT-09206 (31 mg, white solid, yield 41%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.68 (s, 1H), 7.81 (d, J=7.8Hz, 1H), 7.70-7.53 (m, 3H), 7.39 (t, J=7 .9Hz, 1H), 7.26 (dd, J=7.6, 1.5Hz, 1H), 5.75 (s, 1H), 4.79 (d, J=16.7Hz, 1H), 4.56 (d, J=1 6.7Hz, 1H), 4.12-3.88(m, 4H), 3.88-3.77(m, 5H), 3.56-3.33(m, 3H), 3.26-3.11(m, 1H), 2.95-2.82(m, 2H), 2.81-2.70(m, 2H), 2.40-2.33(m, 1H), 2.21-2.05(m, 1H).LCMS(ESI)C 29 H 30 Cl2F2N5O3 + [M+H] + : Calculated value 604.17, measured value 604.2.

[0356] Example 75: Preparation of 5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-09358)

[0357] The target compound GT-09358 (17 mg, white solid, yield 31%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.92 (s, 1H), 8.03-7.99 (m, 2H), 7.95-7.91 (m, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.39 (t, J=7.9Hz, 1H), 7.27 (d, J=6.6Hz, 1H), 5.76 (s, 1H), 4.09-3.87 (m, 4H), 3. 82 (t, J=6.7Hz, 2H), 3.29-3.20 (m, 2H), 3.11-3.04 (m, 3H), 2.89 (s, 1H), 2.85 (t, J=6.8Hz , 2H), 2.74(s, 1H), 2.72-2.59(m, 2H), 2.44-2.26(m, 2H), 2.15-1.96(m, 1H).LCMS(ESI)C 29 H 28 Cl2F2N5O4 + [M+H] + : Calculated value 618.15, measured value 618.2.

[0358] Example 76: Preparation of 1-(5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-09356)

[0359] The target compound GT-09356 (19 mg, white solid, yield 36%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.70 (s, 1H), 8.10 (dd, J=8.9, 5.2Hz, 1H), 7.88 (d, J=7.8Hz, 2H), 7.77 (d, J=7.3Hz , 1H), 7.61 (dd, J=9.0, 2.0Hz, 1H), 7.26 (dd, J=10.0, 8.1Hz, 1H), 4.82 (d, J=16.5Hz, 1H), 4.58 (d, J=16.6 Hz, 1H), 4.44 (s, 1H), 4.11 (brs, 2H), 3.79 (t, J=6.9Hz, 2H), 3.66-3.47 (m, 6H), 3.230-3.22 (m, 4H), 3.0 9-2.93(m, 2H), 2.90-2.83(m, 1H), 2.80-2.75(m, 1H), 2.41-2.28(m, 2H), 2.27-2.09(m, 2H).LCMS(ESI)C 29 H 33 FN7O4 + [M+H] + : Calculated value 562.26, measured value 562.3.

[0360] Example 77: Preparation of 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-09359)

[0361] The target compound GT-09359 (17 mg, white solid, yield 33%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.93 (s, 1H), 8.34-8.20 (m, 1H), 8.11-8.08 (m, 2H), 7.86- 7.80 (m, 1H), 7.64-7.58 (m, 1H), 7.26 (t, J=8.9Hz, 1H), 4.61-4.52 (m, 1H), 4.47- 4.32(m, 1H), 4.22-3.98(m, 2H), 3.72-3.64(m, 2H), 3.62-3.47(m, 8H), 3.25-3. 18(m, 4H), 3.07-2.91(m, 2H), 2.41-2.32(m, 1H), 2.21-1.98(m, 2H).LCMS(ESI)C 29 H 31 FN7O5 + [M+H] + : Calculated value 576.24, measured value 576.3.

[0362] Example 78: Preparation of 1-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-09207)

[0363] The target compound GT-09207 (49 mg, white solid, yield 65%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.68 (s, 1H), 8.06 (dd, J=8.9, 5.3Hz, 1H), 7.83 (d, J=7.7Hz, 1H), 7.71 ( brs, 1H), 7.63 (brs, 1H), 7.57 (dd, J=9.1, 2.1Hz, 1H), 7.21 (td, J=9.1, 2.1Hz, 1H), 4.79 (d, J =16.2Hz, 1H), 4.57 (d, J = 16.4Hz, 1H), 4.32-3.97 (m, 2H), 3.81-3.77 (m, 4H), 3.57-3.44 (m, 4 H), 3.40-2.98(m, 6H), 2.90-2.84(m, 2H), 2.81-2.73(m, 1H), 2.26-1.92(m, 2H).LCMS(ESI)C 29 H 31 F3N7O4 + [M+H] + : Calculated value 598.24, measured value 598.3.

[0364] Example 79: Preparation of 5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-09360)

[0365] The target compound GT-09360 (38 mg, white solid, yield 69%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.92 (s, 1H), 8.16-7.99 (m, 3H), 7.95 (s, 1H), 7.58 (dd, J=9.1, 2.2Hz, 1H), 7.22 (td, J=9.1, 2.1Hz, 1H), 4.04 (brs, 2H), 3.82 ( t, J=6.8Hz, 2H), 3.74-3.56(m, 6H), 3.27-3.17(m, 4H), 3.17-2.99(m, 3H) , 2.86 (t, J=6.8Hz, 2H), 2.22-2.10 (m, 1H), 2.08-1.93 (m, 1H).LCMS (ESI) C 29 H 29 F3N7O5 + [M+H] + : Calculated value 612.22, measured value 612.2.

[0366] Example 80: Preparation of 1-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione (GT-09208)

[0367] The target compound GT-09208 (34 mg, white solid, yield 46%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.68 (s, 1H), 8.23 ​​(s, 1H), 7.79 (d, J = 7.8Hz, 1H), 7.73 (d, J = 9.0Hz, 1H), 7.6 3 (s, 1H), 7.54 (s, 1H), 7.34 (t, J=9.0Hz, 1H), 4.78 (d, J=16.7Hz, 1H), 4.55 (d, J=16.7Hz, 1H), 4.20 -3.98 (m, 1H), 3.89 (s, 2H), 3.79 (t, J=7.4Hz, 3H), 3.75-3.65 (m, 2H), 3.35-3.21 (m, 3H), 3.19-3.0 0(m, 2H), 2.97-2.82(m, 2H), 2.82-2.70(m, 2H), 2.47-2.37(m, 3H), 2.27-2.18(m, 2H).LCMS(ESI)C 30 H 32 F3N6O4 + [M+H] + : Calculated value 597.24, measured value 597.3.

[0368] Example 81: Preparation of 5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione (GT-09361)

[0369] The target compound GT-09361 (22 mg, white solid, yield 40%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.91 (s, 1H), 8.24 (s, 1H), 8.01 (d, J = 7.7Hz, 1H), 7.97 (s, 1H), 7.91 (d, J = 7.7Hz, 1H), 7.73 (dd, J=9.1, 2.1Hz, 1H), 7.34 (td, J=9.1, 2.1Hz, 1H), 4.18-3.99 (m, 1H), 3.92 (s, 2H), 3.83 (t , J=6.7Hz, 2H), 3.78-3.65(m, 2H), 3.61-3.54(m, 4H), 3.33-3.20(m, 2H), 3.10-3.02(m, 1H), 2.85(t, J =6.8Hz, 2H), 2.48-2.42(m, 2H), 2.39-2.33(m, 1H), 2.23-2.19(m, 2H), 2.12-2.05(m, 1H).LCMS(ESI)C 30 H 30F3N6O5 + [M+H] + : Calculated value 611.22, measured value 611.2.

[0370] Example 82: Preparation of 3-(6-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09188)

[0371] The target compound (GT-09188) (white solid, 27 mg, yield 46%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.95 (s, 1H), 11.01 (s, 1H), 7.96-7.83 (m, 5H), 7.79 (d, J=7.8Hz, 1H), 7.70 ( d, J=7.8Hz, 1H), 7.43 (t, J=7.5Hz, 4H), 7.35 (t, J=7.3Hz, 2H), 5.60 (s, 1H), 5.13 (dd, J=13.2, 5.0 Hz, 1H), 4.51 (d, J=17.7Hz, 1H), 4.38 (d, J=17.4Hz, 2H), 3.59 (s, 2H), 3.32-3.24 (m, 5H), 3.11 (s, 2H), 3.05-2.86(m, 6H), 2.61(d, J=17.4Hz, 1H), 2.46-2.37(m, 1H), 2.08-1.89(m, 3H).LCMS(ESI)C 36 H 40 F2N5O3 + [M+H] + : Calculated value 628.31, measured value 628.3.

[0372] Example 83: Preparation of 3-(7-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09189)

[0373] The target compound (GT-09189) (white solid, 20 mg, yield 34%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ12.01 (s, 1H), 11.04 (s, 1H), 7.91 (d, J=7.3Hz, 4H), 7.72 (s, 3H), 7.43 (t, J=7.6Hz , 4H), 7.35 (t, J=7.3Hz, 2H), 5.60 (s, 1H), 5.18-5.07 (m, 1H), 4.88 (d, J=37.2Hz, 1H), 4.78-4.61 (m, 1H) , 4.53 (d, J=18.0Hz, 1H), 4.48-4.36 (m, 1H), 3.72 (d, J=30.8Hz, 2H), 3.35-3.25 (m, 4H), 3.09 (d, J=17. 8Hz, 3H), 3.07-2.91 (m, 5H), 2.62 (d, J=16.9Hz, 1H), 2.46-2.36 (m, 1H), 2.09-1.90 (m, 3H). LCMS (ESI) C 36 H 40 F2N5O3 + [M+H] + : Calculated value 628.31, measured value 628.3.

[0374] Example 84: Preparation of 3-(5-(2-(4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09190)

[0375] The target compound (GT-09190) (white solid, 10 mg, yield 17%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.91 (s, 1H), 10.99 (s, 1H), 7.90 (d, J = 6.9Hz, 4H), 7.71 (d, J = 7.8Hz, 1H), 7.52 (s, 1H), 7.44 (t, J = 7.6Hz, 5H), 7.36 (t, 2H), 5.61 (s, 1H), 5.14-5.04 (m, 1H), 4.45 (d, J = 17.6Hz, 1H), 4.32 (d, J=17.5Hz, 1H), 3.96 (s, 1H), 3.58 (s, 2H), 3.34-3.32 (m, 2H), 3.23-3.12 (m, 5H), 3.02 (d, J=1 0.8Hz, 4H), 2.96-2.80(m, 2H), 2.70-2.54(m, 2H), 2.46-2.32(m, 2H), 2.11-1.98(m, 3H).LCMS(ESI)C 37 H 42 F2N5O3+ [M+H] + : Calculated value 642.33, measured value 642.4.

[0376] Example 85: Preparation of 3-(5-(3-(4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09191)

[0377] The target compound (GT-09191) (white solid, 12 mg, yield 15%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.90 (s, 1H), 10.99 (s, 1H), 10.75 (s, 1H), 7.90 (d, J=7.2Hz, 4H), 7 .68 (d, J=7.8Hz, 1H), 7.51-7.34 (m, 8H), 5.60 (s, 1H), 5.16-4.99 (m, 1H), 4.43 (d, J=17.3 Hz, 1H), 4.30 (d, J=17.3Hz, 1H), 3.91 (s, 1H), 3.30 (s, 4H), 3.16-2.89 (m, 11H), 2.75 (t, J=7.4Hz, 2H), 2.60(d, J=17.6Hz, 1H), 2.47-2.31(m, 2H), 2.15-1.94(m, 5H).LCMS(ESI)C 38 H 44 F2N5O3 + [M+H] + : Calculated value 656.34, measured value 656.4.

[0378] Example 86: Preparation of 5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09192)

[0379] The target compound (GT-09192) (white solid, 21 mg, yield 35%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.47 (s, 1H), 11.07 (s, 1H), 7.89 (d, J=7.8Hz, 2H), 7.86- 7.66 (m, 5H), 7.37 (t, J=7.4Hz, 4H), 7.29 (t, J=7.3Hz, 2H), 5.51 (s, 1H), 5.09 ( dd, J=12.8, 5.5Hz, 1H), 4.01 (s, 2H), 3.16 (s, 3H), 2.99 (d, J=31.9Hz, 8H), 2.8 8-2.76(m, 2H), 2.61-2.47(m, 3H), 2.04-1.95(m, 1H), 1.81(s, 2H).LCMS(ESI)C 36 H 38 F2N5O4 + [M+H] + : Calculated value 642.29, measured value 642.3.

[0380] Example 87: Preparation of 4-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09193)

[0381] The target compound (GT-09193) (white solid, 26 mg, yield 43%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.58 (s, 1H), 11.07 (s, 1H), 7.91 (s, 1H), 7.86-7.82 (m, 2H), 7.78 (d, J=5.9Hz, 4H), 7.37 (t, J=7.5Hz, 4H), 7.29 (t, J=7.3Hz, 2H), 5.51 (s, 1H), 5.08(dd, J=12.8, 5.4Hz, 1H), 4.25(s, 2H), 3.18(s, 4H), 3.09-2.89(m, 8H), 2.88- 2.78(m, 2H), 2.62-2.51(m, 2H), 2.02-1.92(m, 1H), 1.90-1.73(m, 2H).LCMS(ESI)C 36 H 38 F2N5O4 + [M+H] + : Calculated value 642.29, measured value 642.3.

[0382] Example 88: Preparation of 3-(7-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09194)

[0383] The target compound (GT-09194) (white solid, 21 mg, yield 34%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.03 (s, 1H), 10.55 (s, 1H), 7.91-7.61 (m, 7H), 7.39 (t, J=7.4Hz, 4H), 7.2 9 (t, J=12.7Hz, 2H), 5.12 (dd, J=13.2, 5.1Hz, 1H), 4.85 (d, J=11.6Hz, 1H), 4.71 (d, J=12.6Hz, 1H ), 4.51 (d, J=17.8Hz, 1H), 4.39 (d, 1H), 3.60-3.55 (m, 6H), 3.21-2.98 (m, 6H), 2.95-2.87 (m, 1H ), 2.70-2.56(m, 2H), 2.49-2.36(m, 2H), 2.29(d, J=11.1Hz, 2H), 2.18-1.97(m, 3H).LCMS(ESI)C 36 H 42 N5O3 + [M+H] + : Calculated value 592.33, measured value 592.4.

[0384] Example 89: Preparation of 3-(5-(2-(4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09195)

[0385] The target compound (GT-09195) (white solid, 20 mg, yield 32%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.92 (s, 1H), 10.75 (s, 1H), 7.65 (d, J = 7.8Hz, 1H), 7.50 (d, J = 22.2Hz, 4H), 7.46 (s, 1H ), 7.37 (d, J=8.1Hz, 1H), 7.29 (t, J=7.4Hz, 5H), 7.20 (t, J=6.9Hz, 2H), 5.07-4.98 (m, 1H), 4.38 (d, J=17.5H z, 1H), 4.25 (d, J = 17.5Hz, 1H), 3.65 (d, J = 11.0Hz, 2H), 3.26-3.18 (m, 6H), 3.16-3.11 (m, 3H), 3.00-2.88 (m , 4H), 2.86-2.78(m, 2H), 2.52(d, 2H), 2.39-2.23(m, 4H), 2.12-2.00(m, 2H), 1.96-1.90(m, 1H).LCMS(ESI)C 37 H 44 N5O3 + [M+H] + : Calculated value 606.34, measured value 606.4.

[0386] Example 90: Preparation of 3-(5-(3-(4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09196)

[0387] The target compound (GT-09196) (yellow solid, 16 mg, yield 19%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.99 (s, 1H), 10.56 (s, 1H), 7.68 (d, J=7.7Hz, 5H), 7.49 (s, 1H), 7.44-7.33 (m, 6H ), 7.30 (t, J = 7.2Hz, 2H), 5.11 (dd, J = 13.2, 5.0Hz, 1H), 4.44 (d, J = 17.3Hz, 1H), 4.31 (d, J = 17.4Hz, 1H), 3.63 (d, J=11.8Hz, 2H), 3.28-3.20 (m, 3H), 3.09-2.99 (m, 4H), 2.97-2.87 (m, 4H), 2.77 (t, J=7.2Hz, 2H ), 2.61 (dd, J=34.8, 17.6Hz, 2H), 2.46-2.36 (m, 2H), 2.35-2.21 (m, 3H), 2.19-1.94 (m, 6H).LCMS (ESI) C 38 H 46N5O3 + [M+H] + : Calculated value 620.36, measured value 620.4.

[0388] Example 91: Preparation of 5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09334)

[0389] The target compound (GT-09334) (white solid, 19 mg, yield 31%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.08 (s, 2H), 8.14 (s, 1H), 8.02 (d, J=7.6Hz, 1H), 7.96 (d, J=7.6Hz , 1H), 7.56 (s, 4H), 7.30 (t, J=7.3Hz, 4H), 7.23-7.17 (m, 2H), 5.12 (dd, J=12.7, 5.4Hz, 1 H), 4.44(s, 2H), 3.44(d, 4H), 3.43-3.41(m, 3H), 3.30-3.29(m, 2H), 3.00-2.88(m, 4H), 2.86-2.77(m, 2H), 2.58-2.47(m, 2H), 2.26-2.18(m, 2H), 2.09-1.96(m, 3H).LCMS(ESI)C 36 H 40 N5O4 + [M+H] + : Calculated value 606.31, measured value 606.3.

[0390] Example 92: Preparation of 4-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09335)

[0391] The target compound (GT-09335) (white solid, 23 mg, yield 37%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.09 (s, 1H), 10.83 (s, 1H), 8.10 (d, J = 7.6Hz, 1H), 7.96 (d, J = 6.8Hz, 1H), 7.89 (t, J=7.6Hz, 1H), 7.51 (s, 4H), 7.29 (t, J=7.3Hz, 4H), 7.20 (t, J=7.0Hz, 2H), 5.1 1(dd, J=12.7, 5.4Hz, 1H), 4.63(s, 2H), 3.54(s, 3H), 3.28-3.22(m, 5H), 3.09-2.99(m, 3H) , 2.97-2.76(m, 4H), 2.61-2.49(m, 2H), 2.24-2.16(m, 2H), 2.10-1.96(m, 3H).LCMS(ESI)C 36 H 40 N5O4 + [M+H] + : Calculated value 606.31, measured value 606.3.

[0392] Example 93: Preparation of 3-(5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09336)

[0393] The target compound (GT-09336) (white solid, 27 mg, yield 45%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.03 (s, 1H), 8.74 (d, J=4.7Hz, 1H), 7.92 (t, 1H), 7.80 (s, 1H), 7.70 -7.61 (m, 4H), 7.49-7.38 (m, 4H), 5.85 (s, 1H), 5.14 (dd, J=13.3, 5.1Hz, 1H), 4.59 (d, J=15 .7Hz, 1H), 4.43 (d, J=17.6Hz, 1H), 4.27 (s, 2H), 3.36-3.28 (m, 3H), 3.16-3.00 (m, 9H), 2.9 4-2.82(m, 2H), 2.61(d, J=16.5Hz, 1H), 2.46-2.40(m, 1H), 2.06-1.91(m, 3H).LCMS(ESI)C 35 H 38 F3N6O3 + [M+H] + : Calculated value 647.30, measured value 647.3.

[0394] Example 94: Preparation of 3-(5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09337)

[0395] The target compound (GT-09337) (white solid, 16 mg, yield 27%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 8.74 (d, J=4.8Hz, 1H), 7.99-7.83 (m, 2H), 7.72-7.60 (m , 4H), 7.50-7.36 (m, 4H), 5.86 (s, 1H), 5.13 (dd, J=13.3, 5.1Hz, 1H), 4.49 (d, J=17.4, 3.8H z, 1H), 4.36 (d, J=17.5, 4.7Hz, 1H), 4.28 (s, 2H), 3.33-3.23 (m, 4H), 3.13-3.03 (m, 7H), 2. 98-2.81(m, 3H), 2.61(d, J=17.4Hz, 1H), 2.45-2.39(m, 1H), 2.07-1.92(m, 3H).LCMS(ESI)C 35 H 38 F3N6O3 + [M+H] + : Calculated value 647.30, measured value 647.3.

[0396] Example 95: Preparation of 3-(5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09338)

[0397] The target compound (GT-09338) (white solid, 20 mg, yield 33%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ 11.02 (s, 1H), 8.74 (d, J = 4.7Hz, 1H), 7.91 (t, J = 7.7, 3.9Hz, 1H), 7.68 (d, J = 7.0Hz, 2H), 7.64 (d , J=7.8Hz, 1H), 7.59 (s, 1H), 7.54 (d, J=9.5Hz, 1H), 7.50-7.39 (m, 4H), 5.86 (s, 1H), 5.10 (dd, J=13.2, 5.0Hz, 1H), 4 .52 (d, J=17.5Hz, 1H), 4.39 (d, J=18.1Hz, 1H), 4.29 (s, 2H), 3.39-3.34 (m, 3H), 3.15-3.10 (m, 2H), 3.10-2.98 (m, 6H ), 2.97-2.87(m, 2H), 2.61(d, J=17.3Hz, 1H), 2.47-2.30(m, 2H), 2.14-2.04(m, 1H), 2.03-1.94(m, 2H).LCMS(ESI)C 35 H 38 F3N6O3 + [M+H] + : Calculated value 647.30, measured value 647.3.

[0398] Example 96: Preparation of 3-(4-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09339)

[0399] The target compound (GT-09339) (yellow solid, 19 mg, yield 32%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.03 (s, 1H), 8.75 (d, J=4.4Hz, 1H), 7.91 (t, J=7.7, 1.6Hz, 1H), 7.76 ( d, J=7.2Hz, 2H), 7.66 (d, J=6.8Hz, 2H), 7.59 (d, J=7.9Hz, 2H), 7.49-7.37 (m, 5H), 5.82 (s, 1 H), 5.20-5.13(m, 1H), 4.63-4.57(m, 1H), 4.40(d, 1H), 4.08(s, 2H), 3.14-3.01(m, 10H), 2. 96-2.88(m, 2H), 2.65-2.60(m, 1H), 2.41-2.28(m, 2H), 1.98(d, J=35.9Hz, 4H).LCMS(ESI)C 35 H39 F2N6O3 + [M+H] + : Calculated value 629.30, measured value 629.3.

[0400] Example 97: Preparation of 3-(6-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09340)

[0401] The target compound (GT-09340) (white solid, 12 mg, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.01 (s, 1H), 8.74 (d, J = 4.5Hz, 1H), 7.96 (s, 1H), 7.91 (t, J = 7.6Hz, 1H), 7.83 (d, J =6.9Hz, 1H), 7.78-7.65 (m, 4H), 7.63 (d, J = 7.9Hz, 1H), 7.53-7.36 (m, 5H), 5.86 (s, 1H), 5.13 (dd, J = 13.2 , 5.0Hz, 1H), 4.51 (d, J=17.7Hz, 1H), 4.41 (s, 1H), 4.36 (d, 1H), 3.34-3.30 (m, 2H), 3.14 (s, 3H), 3.06-3. 00(m, 6H), 2.96-2.86(m, 2H), 2.61(d, J=17.0Hz, 2H), 2.45-2.32(m, 2H), 2.08-1.95(m, 3H).LCMS(ESI)C 35 H 39 F2N6O3 + [M+H] + : Calculated value 629.30, measured value 629.4.

[0402] Example 98: Preparation of 3-(7-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09341)

[0403] The target compound (GT-09341) (yellow solid, 13 mg, yield 22%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.04 (s, 1H), 8.74 (d, J=4.9Hz, 1H), 7.91 (t, J=7.7, 1.5Hz, 1H), 7.74 (s, 3H), 7. 69 (d, J=7.2Hz, 2H), 7.64 (d, J=7.8Hz, 1H), 7.49-7.39 (m, 4H), 5.87 (s, 1H), 5.16-5.09 (m, 1H), 4.98- 4.81 (m, 1H), 4.77-4.64 (m, 1H), 4.53 (d, J=17.8Hz, 1H), 3.75 (s, 2H), 3.42-3.40 (m, 2H), 3.19-2.98 ( m, 10H), 2.89 (t, J=11.7Hz, 1H), 2.62 (d, J=17.2Hz, 1H), 2.45-2.39 (m, 1H), 2.03 (s, 3H).LCMS (ESI) C 35 H 39 F2N6O3 + [M+H] + : Calculated value 629.30, measured value 629.3.

[0404] Example 99: Preparation of 3-(5-(2-(3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09342)

[0405] The target compound (GT-09342) (yellow solid, 18 mg, yield 23%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.99 (s, 1H), 8.75 (d, J=4.6Hz, 1H), 7.92 (t, J=7.8Hz, 1H), 7.75-7.64 (m, 4H), 7.53 (s, 1H), 7.50-7.36 (m, 5H), 5.88 (s, 1H), 5.10 (dd, J=13.3, 5.0Hz, 1H), 4.45 (d, J=17.5Hz, 1H), 4.32 (d, J=17.5Hz, 1H), 4.00 (s, 2H), 3.43-3.35 (m, 4H), 3.27-3.15 (m, 5H), 3.10-3.04 (m, 4H), 2.95 -2.88(m, 1H), 2.60(d, J=16.4Hz, 2H), 2.39(dd, J=17.5, 8.8Hz, 2H), 2.17-1.97(m, 3H).LCMS(ESI)C 36 H 41 F2N6O3+ [M+H] + : Calculated value 643.32, measured value 643.3.

[0406] Example 100: Preparation of 3-(5-(3-(3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09343)

[0407] The target compound (GT-09343) (yellow solid, 18 mg, yield 23%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 10.99 (s, 1H), 8.74 (d, J=4.7Hz, 1H), 7.91 (t, J=7.6Hz, 1H), 7.7 5-7.61 (m, 4H), 7.52-7.35 (m, 6H), 5.88 (s, 1H), 5.11 (dd, J=13.3, 5.0Hz, 1H), 4.43 (d, J=17.2Hz, 1 H), 4.30 (d, J=17.4Hz, 1H), 3.91 (s, 1H), 3.37-3.26 (m, 4H), 3.15-3.00 (m, 10H), 2.96-2.87 (m, 1H) , 2.75 (t, J=7.2Hz, 2H), 2.60 (d, J=16.6Hz, 1H), 2.44-2.38 (m, 1H), 2.16-1.94 (m, 5H). LCMS (ES1) C 37 H 43 F2N6O3 + [M+H] + : Calculated value 657.34, measured value 657.4.

[0408] Example 101: Preparation of 5-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09344)

[0409] The target compound (GT-09344) (white solid, 14 mg, yield 24%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.14 (s, 1H), 8.74 (d, J = 4.1Hz, 1H), 8.11 (s, 1H), 8.05-7.97 (m, 2H), 7.95-7.88 (m, 1H), 7.72-7.62 (m, 3H), 7.50-7.36 (m, 4H), 5.86 (s, 1H), 5. 18(dd, J=12.7, 5.4Hz, 1H), 4.32(s, 2H), 3.34-3.25(m, 2H), 3.22-3.00(m, 10H), 2 .95-2.82(m, 2H), 2.65-2.53(m, 2H), 2.15-2.01(m, 2H), 1.98(s, 1H).LCMS(ESI)C 35 H 37 F2N6O4 + [M+H] + : Calculated value 643.28, measured value 643.3.

[0410] Example 102: Preparation of 4-((3,3-difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09345)

[0411] The target compound (GT-09345) (white solid, 23 mg, yield 38%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 8.74 (d, J=4.7Hz, 1H), 8.05 (s, 1H), 7.9 8-7.86(m, 3H), 7.73-7.57(m, 3H), 7.50-7.33(m, 4H), 5.84(s, 1H), 5.16(dd , J=12.7, 5.4Hz, 1H), 4.42 (s, 2H), 3.24 (s, 2H), 3.20-2.98 (m, 10H), 2.97-2 .82(m,2H),2.69-2.55(m,2H),2.09-1.96(m,2H),1.94(s,1H).LCMS(ESI)C 35 H 37 F2N6O4 + [M+H] + : Calculated value 643.28, measured value 643.3.

[0412] Example 103: Preparation of 3-(5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09346)

[0413] The target compound (GT-09346) (white solid, 26 mg, yield 50%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.73 (s, 1H), 7.58 (d, J = 8.6Hz, 1H), 7.38 (d, J = 8.5Hz, 2H), 7.2 4 (d, J=8.5Hz, 2H), 5.13 (dd, J=13.3, 5.0Hz, 1H), 4.45 (s, 1H), 4.35 (d, J=17.4Hz, 1H), 3.99 (s, 2H) , 3.27-3.22(m, 2H), 3.14-3.02(m, 3H), 2.95-2.89(m, 1H), 2.61(d, J=16.6Hz, 2H), 2.44-2.32(m, 4H), 2.12-1.97(m, 2H), 1.96-1.65(m, 4H), 1.48-1.37(m, 2H), 0.98(d, J=14.0Hz, 6H).LCMS(ESI)C 38 H 44 ClF3N5O4 + [M+H] + : Calculated value 726.30, measured value 726.3.

[0414] Example 104: Preparation of 3-(5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09347)

[0415] The target compound (GT-09347) (white solid, 22 mg, yield 42%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.01 (s, 1H), 7.47 (s, 1H), 7.38 (d, J = 8.5Hz, 3H), 7.25 (d, J = 8.5Hz, 2 H), 5.09 (dd, J=13.2, 5.1Hz, 1H), 4.50 (d, J=17.6Hz, 1H), 4.37 (d, J=17.9Hz, 1H), 4.03 (s, 2H), 3.26-2.99(m, 7H), 2.97-2.86(m, 2H), 2.84-2.67(m, 2H), 2.61(d, J=17.0Hz, 2H), 2.4 6-2.35(m, 4H), 2.14-1.77(m, 6H), 1.47-1.37(m, 2H), 0.98(d, J=13.9Hz, 6H).LCMS(ESI)C 38 H 44 ClF3N5O4 + [M+H] + : Calculated value 726.30, measured value 726.3.

[0416] Example 105: Preparation of 3-(4-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09348)

[0417] The target compound (GT-09348) (white solid, 14 mg, yield 28%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.03 (s, 1H), 7.77-7.69 (m, 1H), 7.64 (s, 1H), 7.55 (t, J=7.2Hz, 1H), 7.37 (d, J=8.4Hz, 2H) , 7.24 (d, J=8.5Hz, 2H), 5.15 (dd, J=13.2, 5.1Hz, 1H), 4.54 (d, J=16.9Hz, 1H), 4.39 (d, J=17.3Hz, 1H), 3.87 (s, 2 H), 3.30-3.12(m, 5H), 3.05(s, 2H), 2.99-2.88(m, 2H), 2.68(s, 2H), 2.64(d, J=17.3Hz, 2H), 2.44-2.32(m, 4H), 2.13-2.01 (m, 2H), 1.90 (d, J=17.0Hz, 1H), 1.80 (s, 2H), 1.48-1.37 (m, 2H), 0.98 (d, J=13.9Hz, 6H). LCMS (ESI) C38 H 45 ClF2N5O4 + [M+H] + : Calculated value 708.31, measured value 708.3.

[0418] Example 106: Preparation of 3-(6-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09349)

[0419] The target compound (GT-09349) (white solid, 24 mg, yield 47%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.01 (s, 1H), 7.89 (s, 1H), 7.73 (s, 1H), 7.68 (d, J = 7.7Hz, 1H), 7.37 (d, J = 8.5Hz, 2H), 7.24 (d, J=8.5Hz, 2H), 5.13 (dd, J=13.3, 5.1Hz, 1H), 4.50 (d, J=17.6Hz, 1H), 4.37 (d, J=17.6Hz, 1H), 4.27 ( s, 2H), 3.25-3.08 (m, 6H), 3.01 (s, 2H), 2.96-2.87 (m, 2H), 2.61 (d, J=16.8Hz, 2H), 2.45-2.34 (m, 4H), 2.31 -2.22(m, 1H), 2.13-1.96(m, 3H), 1.95-1.80(m, 3H), 1.46-1.36(m, 2H), 0.98(d, J=13.1Hz, 6H).LCMS(ESI)C 38 H 45 ClF2N5O4 + [M+H] + : Calculated value 708.31, measured value 708.3.

[0420] Example 107: Preparation of 3-(7-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09350)

[0421] The target compound (GT-09350) (white solid, 22 mg, yield 43%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.04 (s, 1H), 7.70 (s, 3H), 7.37 (d, J = 8.5Hz, 2H), 7.24 (d, J = 8.3Hz, 2H), 5.21-5.04 (m, 1H), 4.77 (s, 1H), 4.55 (s, 1H), 4.52 (d, J=17.9Hz, 1H), 4.45-4.36 (m, 1H), 3.37 -3.27(m, 3H), 3.18(s, 3H), 3.07-2.86(m, 4H), 2.62(d, J=17.4Hz, 3H), 2.45-2.32(m, 4H), 2.1 9-1.99 (m, 3H), 1.90 (d, J = 17.3Hz, 3H), 1.49-1.36 (m, 2H), 0.98 (d, J = 13.5Hz, 6H). LCMS (ESI) C 38 H 45 ClF2N5O4 + [M+H] + : Calculated value 708.31, measured value 708.3.

[0422] Example 108: Preparation of 3-(5-(2-(4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09351)

[0423] The target compound (GT-09351) (white solid, 23 mg, yield 33%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.99 (s, 1H), 7.71 (d, J=7.8Hz, 1H), 7.51 (s, 1H), 7.42 (d, J=7.9Hz, 1H), 7.38 (d, J=8 .5Hz, 2H), 7.26 (d, J=8.5Hz, 2H), 5.11 (dd, J=13.3, 5.0Hz, 1H), 4.45 (d, J=17.4Hz, 1H), 4.32 (d, J=17.5Hz , 1H), 3.90 (s, 1H), 3.33-3.27 (m, 3H), 3.25-3.06 (m, 8H), 3.04-2.88 (m, 3H), 2.61 (d, J=16.2Hz, 2H), 2.45 -2.36 (m, 4H), 2.26 (s, 1H), 2.13-1.83 (m, 6H), 1.44 (d, J = 7.8Hz, 2H), 0.99 (d, J = 13.3Hz, 6H). LCMS (ESI) C 39 H47 ClF2N5O4 + [M+H] + : Calculated value 722.33, measured value 722.4.

[0424] Example 109: Preparation of 3-(5-(3-(4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09378)

[0425] The target compound (GT-09378) (white solid, 14 mg, yield 20%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.99 (s, 1H), 10.65 (s, 1H), 7.71-7.64 (m, 1H), 7.48 (s, 1H), 7.42-7.33 (m, 3H), 7.25 (d, J=8.5Hz, 2H), 5.11 (dd, J=13.3, 5.0Hz, 1H), 4.43 (d, J=17.3Hz, 1H), 4.30 (d, J=17.3Hz, 1H), 3.83 (s, 1H ), 3.32-3.23(m, 2H), 3.18-2.82(m, 9H), 2.74(t, J=7.3Hz, 2H), 2.60(d, J=17.5Hz, 2H), 2.46-2.29(m, 5H), 2.21(s, 1H), 2.14-1.97(m, 4H), 1.93-1.72(m, 3H), 1.50-1.35(m, 2H), 0.98(d, J=12.4Hz, 6H).LCMS(ESI)C 40 H 49 ClF2N5O4 + [M+H] + : Calculated value 736.34, measured value 736.3.

[0426] Example 110: Preparation of 5-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09352)

[0427] The target compound (GT-09352) (white solid, 23 mg, yield 44%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.14 (s, 1H), 7.94 (t, J=11.4Hz, 2H), 7.90 (s, 1H), 7.38 (d, J=8.5H z, 2H), 7.25 (d, J=8.5Hz, 2H), 5.17 (dd, J=12.7, 5.3Hz, 1H), 4.06 (s, 2H), 3.26-2.96 (m, 7H), 2.95-2.83(m, 2H), 2.83-2.67(m, 2H), 2.67-2.57(m, 3H), 2.43-2.33(m, 3H), 2.11- 2.00(m, 2H), 1.97-1.58(m, 4H), 1.52-1.39(m, 2H), 0.98(d, J=13.6Hz, 6H).LCMS(ESI)C 38 H 43 ClF2N5O5 + [M+H] + : Calculated value 722.29, measured value 722.3.

[0428] Example 111: Preparation of 4-((4-(4-(4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09353)

[0429] The target compound (GT-09353) (white solid, 16 mg, yield 31%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.13 (s, 1H), 7.97-7.91 (m, 1H), 7.88 (d, J=4.9Hz, 2H), 7.38 (d, J=8.5Hz, 2H ), 7.25 (d, J=8.5Hz, 2H), 5.15 (dd, J=12.8, 5.4Hz, 1H), 4.21 (s, 2H), 3.33-3.11 (m, 7H), 3.06 (s, 2H ), 2.96-2.84(m, 2H), 2.82-2.65(m, 2H), 2.61(d, J=19.2Hz, 2H), 2.44-2.35(m, 3H), 2.12-2.01(m , 2H), 1.90 (d, J=16.2Hz, 1H), 1.77 (s, 2H), 1.50-1.40 (m, 2H), 0.98 (d, J=14.2Hz, 6H). LCMS (ESI) C 38 H 43 ClF2N5O5 + [M+H]+ : Calculated value 722.29, measured value 722.3.

[0430] Example 112: Preparation of 3-(5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09379)

[0431] The target compound (GT-09379) (white solid, 18 mg, yield 33%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 10.05 (s, 1H), 7.71 (s, 1H), 7.63 (d, 1H), 7.44 (d, J=8.4Hz, 2H), 7.14 (d, J=8. 4Hz, 2H), 5.13 (dd, J=13.2, 5.0Hz, 1H), 4.58 (d, J=17.8Hz, 1H), 4.42 (d, J=17.4Hz, 1H), 4.10 (s, 2H), 3.58-3.52 ( m, 5H), 3.21 (d, J = 10.5Hz, 2H), 3.11-3.01 (m, 3H), 2.97-2.77 (m, 4H), 2.61 (d, J = 13.8Hz, 3H), 2.47-2.42 (m, 1H), 2.32(s, 2H), 2.06-1.95(m, 3H), 1.93-1.83(m, 1H), 1.80(s, 1H), 1.45(t, J=6.1Hz, 2H), 0.95(s, 6H).LCMS(ESI)C 38 H 46 ClF3N5O3 + [M+H] + : Calculated value 712.32, measured value 712.4.

[0432] Example 113: Preparation of 3-(5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09380)

[0433] The target compound (GT-09380) (white solid, 17 mg, yield 31%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.01 (s, 1H), 9.92 (s, 1H), 7.73 (s, 1H), 7.57 (d, J = 8.6Hz, 1H), 7.44 (d, J = 8.4Hz, 2H), 7.14 (d, J=8.4Hz, 2H), 5.13 (dd, J=13.2, 4.9Hz, 1H), 4.47 (d, J=16.7Hz, 1H), 4.34 (d, J=17.4Hz, 1H), 3.96 ( s, 2H), 3.53 (s, 3H), 3.21 (d, J=11.1Hz, 2H), 3.09-2.99 (m, 3H), 2.98-2.76 (m, 4H), 2.66-2.54 (m, 4H), 2.47 -2.37(m, 2H), 2.30(s, 2H), 2.02(s, 3H), 1.90-1.65(m, 2H), 1.46(t, J=6.1Hz, 2H), 0.95(s, 6H).LCMS(ESI)C 38 H 46 ClF3N5O3 + [M+H] + : Calculated value 712.32, measured value 712.3.

[0434] Example 114: Preparation of 3-(5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09381)

[0435] The target compound (GT-09381) (white solid, 16 mg, yield 29%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.01 (s, 1H), 9.98 (s, 1H), 7.55-7.46 (m, 1H), 7.44 (d, J=8.4Hz, 3H), 7.14 (d, J=8.4Hz, 2 H), 5.09 (dd, J=13.3, 5.1Hz, 1H), 4.50 (d, J=17.8Hz, 1H), 4.37 (d, J=17.9Hz, 1H), 4.05 (s, 2H), 3.52 (d, J=10. 4Hz, 4H), 3.22 (d, J=10.9Hz, 3H), 3.07 (d, J=10.5Hz, 3H), 2.92-2.77 (m, 3H), 2.60 (d, J=13.8Hz, 3H), 2.47-2. 35(m, 2H), 2.31(s, 2H), 2.05-1.97(m, 3H), 1.97-1.68(m, 2H), 1.46(t, J=6.1Hz, 2H), 0.96(s, 6H).LCMS(ESI)C 38 H 46 ClF3N5O3 + [M+H] + : Calculated value 712.32, measured value 712.3.

[0436] Example 115: Preparation of 3-(4-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09382)

[0437] The target compound (GT-09382) (white solid, 20 mg, yield 37%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.02 (s, 1H), 9.93 (s, 1H), 7.87-7.59 (m, 2H), 7.57-7.48 (m, 1H), 7.44 (d, J=8.4Hz, 2H), 7.14 (d, J=8.4Hz, 2H), 5.15 (dd, J=13.2, 5.0Hz, 1H), 4.65-4.51 (m, 1H), 4.40 (d, J=17.5Hz, 1H), 3.8 3 (s, 1H), 3.52 (s, 3H), 3.22 (d, J = 10.8Hz, 2H), 3.01 (d, J = 23.7Hz, 4H), 2.97-2.78 (m, 4H), 2.68-2.54 (m, 4H), 2.44-2.25(m, 4H), 2.03(s, 3H), 1.91-1.62(m, 2H), 1.46(t, J=6.1Hz, 2H), 0.96(s, 6H).LCMS(ESI)C 38 H 47 ClF2N5O3 + [M+H] + : Calculated value 694.33, measured value 694.4.

[0438] Example 116: Preparation of 3-(6-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09383)

[0439] The target compound (GT-09383) (white solid, 24 mg, yield 45%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.01 (s, 1H), 10.14 (s, 1H), 7.90 (s, 1H), 7.82-7.72 (m, 1H), 7.71-7.63 (m, 1H), 7.44 (d, J =8.3Hz, 2H), 7.14 (d, J = 8.3Hz, 2H), 5.13 (dd, J = 13.2, 4.8Hz, 1H), 4.50 (d, J = 17.6Hz, 1H), 4.37 (d, 1H), 4.32-4. 18 (m, 1H), 3.53 (s, 3H), 3.21 (d, J = 11.0Hz, 3H), 3.08 (d, J = 10.0Hz, 3H), 2.97-2.76 (m, 4H), 2.68-2.53 (m, 4H), 2 .48-2.37(m, 2H), 2.32(s, 2H), 2.11-1.95(m, 4H), 1.87(s, 1H), 1.45(t, J=6.1Hz, 2H), 0.95(s, 6H).LCMS(ESI)C 38 H 47 ClF2N5O3 + [M+H] + : Calculated value 694.33, measured value 694.4.

[0440] Example 117: Preparation of 3-(7-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09384)

[0441] The target compound (GT-09384) (white solid, 23 mg, yield 43%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.04 (s, 1H), 10.19 (s, 1H), 7.71 (s, 3H), 7.44 (d, J=8.4Hz, 2H), 7.14 (d, J= 8.3Hz, 2H), 5.16-5.06 (m, 1H), 5.01-4.56 (m, 2H), 4.51 (d, J=18.0Hz, 1H), 4.45-4.35 (m, 1H), 3. 53 (s, 3H), 3.22 (d, J = 10.4Hz, 3H), 3.09 (s, 2H), 2.93-2.76 (m, 3H), 2.68-2.57 (m, 3H), 2.48-2.3 6(m, 2H), 2.33(s, 2H), 2.03(s, 4H), 1.89(s, 1H), 1.45(t, J=6.1Hz, 2H), 0.95(s, 6H).LCMS(ESI)C 38 H 47 ClF2N5O3 + [M+H] + : Calculated value 694.33, measured value 694.4.

[0442] Example 118: Preparation of 3-(5-(2-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09385)

[0443] The target compound (GT-09385) (yellow solid, 22 mg, yield 31%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.99 (s, 1H), 10.12 (s, 1H), 7.71 (d, J=7.8Hz, 1H), 7.51 (s, 1H), 7.44 (t, J=8.5Hz, 3H), 7.15 (d, J=8.4Hz, 2H), 5.11 (dd, J=13.2, 5.1Hz, 1H), 4.45 (d, J=17.5Hz, 1H), 4.32 (d, J=17.4Hz, 1H) , 3.92 (s, 1H), 3.55 (s, 4H), 3.24 (d, J = 11.2Hz, 6H), 3.15-3.06 (m, 3H), 2.94-2.83 (m, 3H), 2.68-2.57 (m, 4H), 2.43-2.38(m, 1H), 2.34(s, 2H), 2.08-1.93(m, 5H), 1.46(t, J=6.1Hz, 2H), 0.96(s, 6H).LCMS(ESI)C39 H 49 ClF2N5O3 + [M+H] + : Calculated value 708.35, measured value 708.4.

[0444] Example 119: Preparation of 3-(5-(3-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09386)

[0445] The target compound (GT-09386) (yellow solid, 24 mg, yield 32%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.21 (s, 1H), 10.99 (s, 1H), 10.41 (s, 1H), 7.73-7.63 (m, 1H), 7.52-7.42 (m, 3H), 7.39 (d, J=7.9 Hz, 1H), 7.15 (d, J=8.4Hz, 2H), 5.11 (dd, J=13.3, 5.1Hz, 1H), 4.43 (d, J=17.4Hz, 1H), 4.31 (d, 1H), 3.90 (s, 1H), 3.46 -3.27(m, 4H), 3.22(d, J=11.0Hz, 3H), 3.17-3.02(m, 5H), 2.97-2.79(m, 3H), 2.78-2.73(m, 2H), 2.65-2.55(m, 3H), 2 .47-2.39 (m, 1H), 2.36 (s, 2H), 2.16-2.01 (m, 5H), 2.01-1.88 (m, 2H), 1.45 (t, J=6.1Hz, 2H), 0.96 (s, 6H).LCMS (ESI) C 40 H 51 ClF2N5O3 + [M+H] + : Calculated value 722.36, measured value 722.4.

[0446] Example 120: Preparation of 5-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09387)

[0447] The target compound (GT-09387) (white solid, 15 mg, yield 28%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 9.96 (s, 1H), 8.04-7.87 (m, 3H), 7.44 (d, J=8.3Hz, 2H), 7.14 (d, J=8.3Hz, 2H), 5.17 (dd, J=12.8, 5.4Hz, 1H), 4.08 (s, 2H), 3.54 (s, 3H), 3.21 (d, J=1 0.6Hz, 3H), 3.06 (d, J=10.4Hz, 4H), 2.92-2.81 (m, 3H), 2.68-2.54 (m, 5H), 2.31 (s, 2H), 2. 10-1.99(m, 3H), 1.89(s, 1H), 1.78(s, 1H), 1.46(t, J=6.1Hz, 2H), 0.96(s, 6H).LCMS(ESI)C 38 H 45 ClF2N5O4 + [M+H] + : Calculated value 708.31, measured value 708.3.

[0448] Example 121: Preparation of 4-((4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09388)

[0449] The target compound (GT-09388) (white solid, 12 mg, yield 22%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 9.98 (s, 1H), 7.98 (s, 1H), 7.93-7.85 (m, 2H), 7.44 (d, J=8 .3Hz, 2H), 7.14 (d, J=8.3Hz, 2H), 5.15 (dd, J=12.8, 5.4Hz, 1H), 4.27 (s, 2H), 3.54 (s, 3H), 3. 22(d, J=10.6Hz, 3H), 3.08(s, 4H), 2.91-2.81(m, 3H), 2.68-2.53(m, 5H), 2.31(s, 2H), 2.08- 1.99(m, 3H), 1.95-1.81(m, 1H), 1.76(s, 1H), 1.46(t, J=6.1Hz, 2H), 0.96(s, 6H).LCMS(ESI)C38 H 45 ClF2N5O4 + [M+H] + : Calculated value 708.31, measured value 708.3.

[0450] Example 122: Preparation of 3-(7-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09389)

[0451] The target compound (GT-09389) (white solid, 23 mg, yield 38%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.67 (s, 1H), 11.02 (s, 1H), 10.64 (s, 1H), 7.90-7.67 (m, 3H), 7.41-7.35 (m, 2H) , 7.23-7.14 (m, 1H), 5.13 (dd, J=13.1, 5.0Hz, 1H), 4.86 (d, J=11.5Hz, 1H), 4.73 (d, J=12.6Hz, 1H), 4.5 2(d, J=17.9Hz, 1H), 4.39(d, 1H), 3.63-3.54(m, 4H), 3.49-3.45(m, 2H), 3.29-3.25(m, 2H), 3.19-3.05 (m, 4H), 3.00-2.84 (m, 2H), 2.64 (d, J=16.5Hz, 1H), 2.46-2.35 (m, 3H), 2.22-1.99 (m, 3H). LCMS (ESI) C 29 H 34 Cl2N5O3 + [M+H] + : Calculated value 570.20, measured value 570.3.

[0452] Example 123: Preparation of 3-(5-(2-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09390)

[0453] The target compound (GT-09390) (white solid, 9 mg, yield 11%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.45 (s, 1H), 10.99 (s, 1H), 10.78 (s, 1H), 7.73 (d, J=7.7Hz, 1H), 7.54 (s, 1 H), 7.46-7.36 (m, 2H), 7.21 (d, J=4.4Hz, 1H), 5.17-5.03 (m, 1H), 4.46 (d, J=17.4Hz, 1H), 4.33 (d, J=17.6Hz, 1H), 3.78-3.72 (m, 1H), 3.61 (s, 2H), 3.54-3.44 (m, 3H), 3.30-3.08 (m, 8H), 3.05-2.83 (m, 3H), 2.70-2.57 (m, 2H), 2.46-2.34 (m, 3H), 2.33-2.10 (m, 2H), 2.04-1.94 (m, 1H). LCMS (ESI) C 30 H 36 Cl2N5O3 + [M+H] + : Calculated value 584.22, measured value 584.3.

[0454] Example 124: Preparation of 3-(5-(3-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09391)

[0455] The target compound (GT-09391) (white solid, 31 mg, yield 37%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.57 (s, 1H), 10.99 (s, 1H), 10.73 (s, 1H), 7.69 (d, J=7.8Hz, 1H), 7.50 (s, 1H), 7.4 4-7.36 (m, 3H), 7.23-7.17 (m, 1H), 5.11 (dd, J=13.3, 5.1Hz, 1H), 4.43 (d, J=17.2, 8.4Hz, 1H), 4.31 (d, 1 H), 3.69-3.57(m, 4H), 3.47-3.40(m, 4H), 3.28-3.19(m, 3H), 3.05(s, 2H), 2.99-2.86(m, 3H), 2.81-2.7 1(m, 2H), 2.61(d, J=18.2Hz, 2H), 2.44-2.32(m, 3H), 2.24-2.18(m, 1H), 2.12-1.97(m, 3H).LCMS(ESI)C 31 H 38 Cl2N5O3 +[M+H] + : Calculated value 598.23, measured value 598.3.

[0456] Example 125: Preparation of 5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09392)

[0457] The target compound (GT-09392) (white solid, 15 mg, yield 25%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.51 (s, 1H), 11.26 (s, 1H), 11.16 (s, 1H), 8.23 ​​(s, 1H), 8.11 (d, J=7.0Hz, 1H), 8.04 (d, J=7.6Hz, 1H), 7.43-7.27 (m, 2H), 7.24-7.10 (m, 1H), 5.19 (dd, J=12.8, 5.4Hz, 1H), 4.52(s, 2H), 3.62-3.50(m, 4H), 3.44(s, 2H), 3.30-3.11(m, 5H), 3.11-2.94(m, 2H), 2.94-2.86( m, 1H), 2.65-2.53 (m, 2H), 2.42-2.31 (m, 2H), 2.30-2.13 (m, 2H), 2.12-2.03 (m, 1H). LCMS (ESI) C 29 H 32 Cl2N5O4 + [M+H] + : Calculated value 584.18, measured value 584.2.

[0458] Example 126: Preparation of 4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09393)

[0459] The target compound (GT-09393) (yellow solid, 20 mg, yield 33%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.47 (s, 1H), 11.17 (s, 1H), 10.97 (s, 1H), 8.15 (d, J=8.5Hz, 1H), 8.03 (d, J= 7.3Hz, 1H), 8.01-7.95 (m, 1H), 7.48-7.32 (m, 2H), 7.26-7.14 (m, 1H), 5.19 (dd, J=12.8, 5.4Hz, 1H ), 4.71 (s, 2H), 3.68-3.55 (m, 4H), 3.47-3.43 (m, 2H), 3.27-3.08 (m, 6H), 2.94-2.85 (m, 2H), 2.73 (s, 1H), 2.69-2.55 (m, 2H), 2.42-2.33 (m, 2H), 2.23-2.14 (m, 1H), 2.12-2.03 (m, 1H).LCMS (ESI) C 29 H 32 Cl2N5O4 + [M+H] + : Calculated value 584.18, measured value 584.2.

[0460] Example 127: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09417)

[0461] The target compound (GT-09417) (white solid, 35 mg, yield 59%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.03 (s, 1H), 7.72-7.62 (m, 2H), 7.38-7.31 (m, 2H), 7.21-7.13 (m, 1H ), 5.14 (dd, J=13.2, 5.0Hz, 1H), 4.59 (d, J=17.5Hz, 1H), 4.43 (d, J=17.4Hz, 1H), 4.00 (s, 2 H), 3.83-3.71(m, 3H), 3.32-3.21(m, 6H), 3.15(s, 2H), 2.95-2.89(m, 1H), 2.83-2.71(m, 1 H), 2.61 (d, J=17.3Hz, 2H), 2.47-2.41 (m, 1H), 2.33 (s, 1H), 2.12-2.00 (m, 2H).LCMS (ESI) C 29 H 31 Cl2F3N5O3 + [M+H] +: Calculated value 624.18, measured value 624.2.

[0462] Example 128: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09418)

[0463] The target compound (GT-09418) (white solid, 31 mg, yield 52%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.74 (d, J = 5.5Hz, 1H), 7.58 (d, J = 8.6Hz, 1H), 7.41-7.28 (m , 2H), 7.23-7.11 (m, 1H), 5.13 (dd, J=13.3, 5.1Hz, 1H), 4.49 (d, J=17.4Hz, 1H), 4.36 (d, J=17.4 Hz, 1H), 3.96 (s, 2H), 3.82-3.61 (m, 3H), 3.31-3.20 (m, 6H), 3.12 (s, 2H), 2.97-2.89 (m, 1H), 2 .68(s, 1H), 2.66-2.59(m, 1H), 2.49-2.39(m, 2H), 2.29(s, 1H), 2.11-1.98(m, 2H).LCMS(ES1)C 29 H 31 Cl2F3N5O3 + [M+H] + : Calculated value 624.18, measured value 624.2.

[0464] Example 129: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09419)

[0465] The target compound (GT-09419) (white solid, 24 mg, yield 40%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.48 (s, 1H), 7.42-7.30 (m, 3H), 7.22-7.14 (m, 1H), 5. 09 (dd, J=13.3, 5.1Hz, 1H), 4.51 (d, J=17.9Hz, 1H), 4.38 (d, J=17.9Hz, 1H), 4.00 (s, 2H), 3.65(s, 3H), 3.34-3.16(m, 9H), 2.95-2.88(m, 1H), 2.85-2.71(m, 1H), 2.63-2.57(m, 1H) , 2.45-2.35(m, 1H), 2.35-2.25(m, 1H), 2.15-2.06(m, 1H), 2.06-1.95(m, 1H).LCMS(ESI)C 29 H 31 Cl2F3N5O3 + [M+H] + : Calculated value 624.18, measured value 624.2.

[0466] Example 130: Preparation of 3-(4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09420)

[0467] The target compound (GT-09420) (white solid, 31 mg, yield 54%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.03 (s, 1H), 7.72 (d, J=7.4Hz, 1H), 7.66 (s, 1H), 7.55 (t, J=7.4Hz, 1H), 7 .39-7.31 (m, 2H), 7.21-7.14 (m, 1H), 5.16 (dd, J=13.1, 5.0Hz, 1H), 4.63-4.51 (m, 1H), 4.41 (d, J =17.6Hz, 1H), 3.89 (s, 3H), 3.67-3.58 (m, 3H), 3.42-3.37 (m, 2H), 3.36-3.20 (m, 6H), 3.09 (s, 1H ), 2.98-2.89(m, 1H), 2.63(d, J=16.9Hz, 1H), 2.43-2.24(m, 2H), 2.15-1.99(m, 2H).LCMS(ES1)C 29 H 32 Cl2F2N5O3 + [M+H] + : Calculated value 606.18, measured value 606.2.

[0468] Example 131: Preparation of 3-(6-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09421)

[0469] The target compound (GT-09421) (white solid, 39 mg, yield 67%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.90 (s, 1H), 7.78 (d, J = 6.9Hz, 1H), 7.69 (d, J = 7.8Hz, 1H), 7.33 (d, J =6.8Hz, 2H), 7.16 (t, 1H), 5.14 (dd, J = 13.2, 5.0Hz, 1H), 4.51 (d, J = 17.6Hz, 1H), 4.38 (d, J = 17.6Hz, 1H), 4.26(s, 2H), 3.80-3.73(m, 2H), 3.35(s, 2H), 3.27-3.10(m, 8H), 2.96-2.88(m, 1H), 2.81(s, 1H), 2.62(d , J=17.1Hz, 1H), 2.45-2.36 (m, 1H), 2.32 (d, J=10.2Hz, 1H), 2.20 (s, 1H), 2.06-1.95 (m, 1H).LCMS (ESI) C 29 H 32 Cl2F2N5O3 + [M+H] + : Calculated value 606.18, measured value 606.2.

[0470] Example 132: Preparation of 3-(7-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09422)

[0471] The target compound (GT-09422) (white solid, 27 mg, yield 47%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.03 (s, 1H), 7.77-7.62 (m, 3H), 7.40-7.25 (m, 2H), 7.20 -7.09(m, 1H), 5.17-5.08(m, 1H), 4.85-4.38(m, 4H), 3.71-3.66(m, 2H), 3.41-3 .37(m, 2H), 3.18(s, 8H), 2.98-2.86(m, 2H), 2.62(d, J=17.6Hz, 1H), 2.47-2.3 7(m, 1H), 2.35-2.26(m, 1H), 2.23-2.11(m, 1H), 2.08-1.99(m, 1H).LCMS(ESI)C 29 H 32 Cl2F2N5O3 + [M+H] + : Calculated value 606.18, measured value 606.2.

[0472] Example 133: Preparation of 3-(5-(2-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09430)

[0473] The target compound (GT-09430) (white solid, 23 mg, yield 39%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.00 (s, 1H), 7.72 (d, J = 7.8Hz, 1H), 7.53 (s, 1H), 7.44 (d, J = 7.8Hz, 1H) , 7.39-7.31 (m, 2H), 7.22-7.12 (m, 1H), 5.12 (dd, J=13.2, 5.1Hz, 1H), 4.46 (d, J=17.5Hz, 1H) , 4.33 (d, J=17.5Hz, 1H), 4.03 (s, 1H), 3.66 (s, 3H), 3.39-3.32 (m, 3H), 3.23-3.09 (m, 10H), 2 .97-2.89(m, 1H), 2.61(d, J=16.9Hz, 1H), 2.44-2.20(m, 3H), 2.06-1.97(m, 1H).LCMS(ESI)C 30 H 34 Cl2F2N5O3 + [M+H] + : Calculated value 620.20, measured value 620.3.

[0474] Example 134: Preparation of 3-(5-(3-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09431)

[0475] The target compound (GT-09431) (white solid, 18 mg, yield 31%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.99 (s, 1H), 7.68 (d, J = 7.8Hz, 1H), 7.50 (s, 1H), 7.41 (d, J = 8.0Hz, 1H), 7.35 -7.30 (m, 2H), 7.19-7.13 (m, 1H), 5.14-5.05 (m, 1H), 4.44 (d, J = 17.4Hz, 1H), 4.31 (d, J = 17.4Hz, 1H) , 3.96 (s, 1H), 3.65-3.64 (m, 1H), 3.08 (s, 10H), 2.98-2.84 (m, 2H), 2.77 (t, J=7.4Hz, 2H), 2.67-2. 53(m, 2H), 2.49-2.30(m, 2H), 2.29-2.16(m, 2H), 2.15-2.05(m, 2H), 2.04-1.97(m, 1H).LCMS(ESI)C 31 H 36 Cl2F2N5O3 + [M+H] + : Calculated value 634.22, measured value 634.3.

[0476] Example 135: Preparation of 5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09432)

[0477] The target compound (GT-09432) (white solid, 27 mg, yield 46%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.15 (s, 1H), 7.96 (d, J = 7.4Hz, 2H), 7.90 (d, J = 7.6Hz, 1H ), 7.37-7.32(m, 2H), 7.20-7.15(m, 1H), 5.17(dd, J=12.8, 5.3Hz, 1H), 4.03(s, 2H), 3.82-3.60(m, 3H), 3.29-3.20(m, 6H), 3.17-3.08(m, 2H), 2.94-2.86(m, 1H ), 2.77(s, 1H), 2.67-2.53(m, 3H), 2.27(s, 1H), 2.13-2.01(m, 2H).LCMS(ESI)C 29 H 30 Cl2F2N5O4 + [M+H] + : Calculated value 620.16, measured value 620.2.

[0478] Example 136: Preparation of 4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09433)

[0479] The target compound (GT-09433) (white solid, 30 mg, yield 51%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 7.99-7.92 (m, 1H), 7.92-7.85 (m, 2H), 7.38 -7.33(m, 2H), 7.20-7.14(m, 1H), 5.16(dd, J=12.7, 5.4Hz, 1H), 4.23(s, 2H), 3. 97-3.61(m, 3H), 3.28(s, 6H), 3.12(s, 2H), 2.95-2.86(m, 1H), 2.67(s, 1H), 2.6 5-2.54(m, 2H), 2.49-2.37(m, 1H), 2.33(s, 1H), 2.11-2.01(m, 2H).LCMS(ESI)C 29 H 30 Cl2F2N5O4 + [M+H] + : Calculated value 620.16, measured value 620.2.

[0480] Example 137: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09599)

[0481] The target compound (GT-09599) (white solid, 20 mg, yield 34%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.68-7.58 (m, 3H), 7.39 (t, J=7.9Hz, 1H), 7.26 (dd, J= 7.7, 1.5Hz, 1H), 5.76 (s, 1H), 5.14 (dd, J=13.3, 5.1Hz, 1H), 4.59 (d, J=17.5Hz, 1H), 4.42 (d, J=17.4Hz, 1H), 3.96 (s, 5H), 3.45-3.35 (m, 3H), 3.11 (s, 1H), 2.97-2.88 (m, 1H), 2.77 -2.69(m, 1H), 2.61(d, J=16.6Hz, 2H), 2.48-2.32(m, 3H), 2.12-1.97(m, 2H).LCMS(ESI)C 30 H 30 Cl2F3N4O3 + [M+H] + : Calculated value 621.16, measured value 621.2.

[0482] Example 138: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09600)

[0483] The target compound (GT-09600) (white solid, 20 mg, yield 34%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.72 (d, J=5.6Hz, 1H), 7.65-7.54 (m, 2H), 7.39 (t, J= 7.9Hz, 1H), 7.30-7.21 (m, 1H), 5.76 (s, 1H), 5.19-5.06 (m, 1H), 4.49 (d, J=17.4Hz, 1H), 4 .36(d, J=17.2Hz, 1H), 3.93(s, 5H), 3.36-3.25(m, 2H), 3.10(s, 1H), 2.96-2.87(m, 1H), 2.83-2.66(m, 2H), 2.65-2.55(m, 2H), 2.47-2.31(m, 3H), 2.14-1.98(m, 2H).LCMS(ESI)C 30 H 30 Cl2F3N4O3 + [M+H] + : Calculated value 621.16, measured value 621.2.

[0484] Example 139: Preparation of 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09601)

[0485] The target compound (GT-09601) (white solid, 16 mg, yield 28%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.64-7.59 (m, 1H), 7.45 (s, 1H), 7.39 (t, J=7.9Hz, 1 H), 7.32 (d, J=10.0Hz, 1H), 7.29-7.24 (m, 1H), 5.76 (s, 1H), 5.09 (dd, J=13.3, 5.1Hz, 1 H), 4.51 (d, J=17.6Hz, 1H), 4.37 (d, J=17.9Hz, 1H), 3.91 (s, 5H), 3.19-3.00 (m, 2H), 2. 98-2.83(m, 2H), 2.82-2.56(m, 4H), 2.44-2.23(m, 3H), 2.15-1.96(m, 2H).LCMS(ESI)C 30 H 30 Cl2F3N4O3 + [M+H] + : Calculated value 621.16, measured value 621.2.

[0486] Example 140: Preparation of 3-(4-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09602)

[0487] The target compound (GT-09602) (white solid, 6 mg, yield 11%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 7.70 (d, J=7.5Hz, 1H), 7.66-7.58 (m, 2H), 7.54 (t, J=7.5 Hz, 1H), 7.40 (t, J=10.2, 5.4Hz, 1H), 7.32-7.19 (m, 1H), 5.76 (s, 1H), 5.16 (dd, J=13.2, 5.1 Hz, 1H), 4.63-4.48 (m, 1H), 4.40 (d, J=17.7Hz, 1H), 4.17-3.58 (m, 6H), 3.30-3.15 (m, 2H), 3 .14-2.87(m, 3H), 2.63(d, J=17.5Hz, 2H), 2.44-2.27(m, 3H), 2.09-1.95(m, 2H).LCMS(ESI)C 30 H 31 Cl2F2N4O3 + [M+H] + : Calculated value 603.17, measured value 603.2.

[0488] Example 141: Preparation of 3-(6-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09635)

[0489] The target compound (GT-09635) (white solid, 18 mg, yield 31%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.01 (s, 1H), 7.90-7.78 (m, 1H), 7.76-7.65 (m, 2H), 7.60 (d, J=8.1Hz, 1H) , 7.38 (t, J=7.8Hz, 1H), 7.30-7.19 (m, 1H), 5.74 (s, 1H), 5.14 (dd, J=13.2, 5.0Hz, 1H), 4.50 (d, J =17.6Hz, 1H), 4.37 (d, J = 17.5Hz, 1H), 4.14 (s, 2H), 3.91-3.79 (m, 3H), 3.42-3.18 (m, 4H), 2.98- 2.82(m, 2H), 2.67-2.57(m, 3H), 2.45-2.34(m, 2H), 2.19(s, 1H), 2.05-1.93(m, 1H).LCMS(ESI)C 30 H 31 Cl2F2N4O3 + [M+H] + : Calculated value 603.17, measured value 603.3.

[0490] Example 142: Preparation of 3-(7-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09636)

[0491] The target compound (GT-09636) (white solid, 23 mg, yield 41%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (d, J=5.3Hz, 1H), 9.31 (d, J=6.6Hz, 1H), 8.45 (d, J=6 .9Hz, 1H), 7.68-7.64(m, 2H), 7.61-7.57(m, 2H), 5.74(s, 1H), 5.14-5.10(m, 1H) , 4.51-4.33(m, 4H), 3.81(s, 3H), 3.40-3.14(m, 4H), 2.95-2.85(m, 2H), 2.81-2. 73(m, 1H), 2.69-2.56(m, 3H), 2.46-2.38(m, 2H), 2.05-2.00(m, 1H).LCMS(ES1)C 30 H 31 Cl2F2N4O3 + [M+H] + : Calculated value 603.17, measured value 603.3.

[0492] Example 143: Preparation of 3-(5-(2-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09637)

[0493] The target compound (GT-09637) (white solid, 14 mg, yield 25%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.00 (s, 1H), 9.33 (d, J = 6.6Hz, 1H), 8.48 (d, J = 9.5Hz, 1H), 7.7 4-7.58(m, 3H), 7.53(s, 1H), 7.47-7.43(m, 1H), 5.74(s, 1H), 5.12(dd, J=13.2, 5.1Hz , 1H), 4.45 (d, J=17.2Hz, 1H), 4.33 (d, 1H), 3.94-3.60 (m, 5H), 3.35-3.14 (m, 5H), 3.0 8-2.86(m, 5H), 2.64-2.55(m, 2H), 2.46-2.35(m, 2H), 2.03-1.96(m, 1H).LCMS(ESI)C 31 H 33 Cl2F2N4O3 + [M+H] + : Calculated value 617.19, measured value 617.3.

[0494] Example 144: Preparation of 3-(5-(3-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09638)

[0495] The target compound (GT-09638) (white solid, 17 mg, yield 29%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.99 (s, 1H), 9.31 (d, J=6.4Hz, 1H), 8.47 (d, J=6.8Hz, 1H), 7.73-7.63 (m, 2H), 7.64 -7.57 (m, 1H), 7.50 (s, 1H), 7.44-7.40 (m, 1H), 5.72 (s, 1H), 5.11 (dd, J=13.2, 5.0Hz, 1H), 4.44 (d, J=17.1 Hz, 1H), 4.31 (d, J=17.3Hz, 1H), 3.93 (s, 1H), 3.72-3.55 (m, 6H), 3.09 (s, 3H), 2.96-2.87 (m, 2H), 2.82-2 .73(m, 3H), 2.61(d, J=17.7Hz, 2H), 2.46-2.34(m, 2H), 2.12-2.05(m, 1H), 2.04-1.96(m, 2H).LCMS(ESI)C 32 H 35 Cl2F2N4O3 + [M+H] + : Calculated value 631.20, measured value 631.3.

[0496] Example 145: Preparation of 5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09639)

[0497] The target compound (GT-09639) (white solid, 10 mg, yield 18%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 7.97-7.91 (m, 2H), 7.88 (s, 1H), 7.61 (d, J=7.7Hz , 1H), 7.39 (t, J=7.9Hz, 1H), 7.26 (dd, J=7.7, 1.5Hz, 1H), 5.75 (s, 1H), 5.17 (dd, J=12 .9, 5.3Hz, 1H), 3.97 (d, J=7.7Hz, 5H), 3.10 (d, J=27.5Hz, 2H), 2.90 (ddd, J=30.4, 16 .3, 9.4Hz, 2H), 2.68-2.53(m, 4H), 2.49-2.27(m, 3H), 2.10-2.00(m, 2H).LCMS(ESI)C 30 H 29 Cl2F2N4O4 + [M+H] +: Calculated value 617.15, measured value 617.2.

[0498] Example 146: Preparation of 4-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09640)

[0499] The target compound (GT-09640) (white solid, 12 mg, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 1H), 7.94-7.85 (m, 3H), 7.64-7.55 (m, 1H), 7.39 ( t, J=7.8Hz, 1H), 7.26 (d, J=7.5Hz, 1H), 5.76 (s, 1H), 5.15 (dd, J=12.7, 5.4Hz, 1H ), 4.20 (d, J=23.9Hz, 2H), 3.93 (s, 2H), 3.36-3.20 (m, 4H), 3.06 (s, 1H), 2.93-2. 86(m,1H),2.71-2.53(m,4H),2.46-2.24(m,2H),2.12-1.98(m,2H).LCMS(ESI)C 30 H 29 Cl2F2N4O4 + [M+H] + : Calculated value 617.15, measured value 617.2.

[0500] Example 147: Preparation of 3-(4-fluoro-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09641)

[0501] The target compound (GT-09641) (white solid, 16 mg, yield 26%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.59 (s, 1H), 11.02 (d, J=13.9Hz, 2H), 8.14-8.06 (m, 1H), 7.88 (s, 1H), 7.7 1(d, J=7.6Hz, 1H), 7.63-7.59(m, 1H), 7.31-7.21(m, 1H), 5.18-5.11(m, 1H), 4.66-4.56(m, 2H), 4.55-4.40(m, 3H), 4.11(s, 2H), 3.67-3.53(m, 6H), 3.15-3.00(m, 3H), 2.96-2.90(m, 1H), 2.65- 2.56(m, 2H), 2.47-2.39(m, 2H), 2.38-2.31(m, 2H), 2.18(s, 1H), 2.03-1.99(m, 1H).LCMS(ESI)C 30 H 33 F2N6O4 + [M+H] + : Calculated value 579.25, measured value 579.3.

[0502] Example 148: Preparation of 3-(6-fluoro-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09642)

[0503] The target compound (GT-09642) (white solid, 27 mg, yield 43%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.82 (s, 1H), 11.26 (s, 1H), 11.02 (d, J=13.2Hz, 1H), 8.10 (dd, J=8.8, 5.1Hz, 1H ), 7.98 (dd, J=17.1, 5.3Hz, 1H), 7.68 (d, J=8.5Hz, 1H), 7.61 (d, J=9.0Hz, 1H), 7.26 (t, J=9.1Hz, 1H), 5 .18-5.11(m, 1H), 4.88(s, 1H), 4.52-4.33(m, 4H), 4.11(s, 2H), 3.64-3.47(m, 6H), 3.14-3.01(m, 3H), 2.96-2.89(m, 1H), 2.69-2.55(m, 2H), 2.47-2.34(m, 3H), 2.20(s, 2H), 2.04-1.98(m, 1H).LCMS(ESI)C 30 H 33 F2N6O4 + [M+H]+ : Calculated value 579.25, measured value 579.3.

[0504] Example 149: Preparation of 3-(7-fluoro-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09643)

[0505] The target compound (GT-09643) (white solid, 11 mg, yield 18%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.56 (s, 1H), 11.26 (s, 1H), 11.02 (s, 1H), 8.10 (dd, J=8.8, 5.2Hz , 1H), 7.72-7.55 (m, 3H), 7.26 (t, J=8.9Hz, 1H), 5.11 (dd, J=13.2, 5.1Hz, 1H), 4.60-4.3 8(m, 4H), 4.12(s, 2H), 3.62-3.48(m, 6H), 3.32-3.28(m, 2H), 3.07-2.87(m, 3H), 2.70- 2.55(m, 2H), 2.45-2.31(m, 3H), 2.24(d, J=18.5Hz, 2H), 2.05-1.97(m, 1H).LCMS(ESI)C 30 H 33 F2N6O4 + [M+H] + : Calculated value 579.25, measured value 579.3.

[0506] Example 150: Preparation of 3-(4-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09644)

[0507] The target compound (GT-09644) (white solid, 14 mg, yield 23%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.07 (s, 1H), 10.99 (s, 1H), 8.10 (dd, J=8.9, 5.2Hz, 1H), 7.94 (s, 1H), 7.84 (d, J =7.2Hz, 1H), 7.68-7.56(m, 3H), 7.31-7.22(m, 1H), 5.25-5.16(m, 1H), 4.79(d, J=17.6Hz, 1H), 4.62( s, 1H), 4.55-4.42 (m, 2H), 4.36 (d, J=17.3Hz, 2H), 4.12 (s, 2H), 3.62-3.55 (m, 4H), 3.11 (s, 2H), 3.01 -2.86(m, 2H), 2.65(d, J=17.0Hz, 2H), 2.39-2.29(m, 3H), 2.23(s, 2H), 2.12-1.94(m, 2H).LCMS(ESI)C 30 H 34 FN6O4 + [M+H] + : Calculated value 561.26, measured value 561.3.

[0508] Example 151: Preparation of 3-(6-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09645)

[0509] The target compound (GT-09645) (white solid, 12 mg, yield 20%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.47 (s, 1H), 11.02 (s, 1H), 10.83 (s, 1H), 8.09 (dd, J=9.0, 5.3Hz, 1H), 8.03-7.96 (m, 1H), 7.85 (d, J = 7.6Hz, 1H), 7.73 (d, J = 7.7Hz, 1H), 7.62 (d, J = 9.1Hz, 1H), 7.26 (t, J = 8.3Hz, 1H), 5.13 (dd, J=13.3, 5.1Hz, 1H), 4.54-4.37 (m, 4H), 4.11 (s, 1H), 3.53 (d, J=22.9Hz, 6H), 3.28-3.13 (m, 3H), 3. 01-2.87(m, 4H), 2.62(d, J=16.2Hz, 2H), 2.40-2.31(m, 2H), 2.16(s, 2H), 2.05-1.99(m, 1H).LCMS(ESI)C 30 H 34 FN6O4+ [M+H] + : Calculated value 561.26, measured value 561.3.

[0510] Example 152: Preparation of 3-(7-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09646)

[0511] The target compound (GT-09646) (white solid, 14 mg, yield 23%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.78 (s, 1H), 11.03 (s, 1H), 10.65 (s, 1H), 8.10 (dd, J=8.9, 5.2Hz, 1H), 7.81-7.70 (m, 3H), 7.62 (dd, J=9.1, 2.2Hz, 1H), 7.29-7.23 (m, 1H), 5.17-5.08 (m, 1H), 4.86 (d, J=12.1Hz, 1H), 4.73 (d, J=12.8Hz, 1 H), 4.47 (dd, J=42.8, 17.9Hz, 2H), 4.11 (d, J=12.9Hz, 1H), 3.65-3.53 (m, 6H), 3.34-3.23 (m, 4H), 3.14-3.04 (m, 2H), 2.92-2.85(m, 1H), 2.63(d, J=17.6Hz, 1H), 2.45-2.31(m, 3H), 2.17(s, 2H), 2.07-1.98(m, 1H).LCMS(ES1)C 30 H 34 FN6O4 + [M+H] + : Calculated value 561.26, measured value 561.3.

[0512] Example 153: Preparation of 3-(5-(2-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09647)

[0513] The target compound (GT-09647) (white solid, 15 mg, yield 24%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.68 (s, 1H), 11.00 (s, 1H), 10.92 (s, 1H), 8.11 (dd, J=8.8, 5.2Hz, 1H), 7.72 (d, J=7.8Hz, 1H), 7.64- 7.59 (m, 1H), 7.54 (s, 1H), 7.45 (d, J=7.7Hz, 1H), 7.31-7.22 (m, 1H), 5.12 (dd, J=13.2, 5.1Hz, 1H), 4.46 (d, J=17.4Hz, 1H), 4.33 (d, J=17.4Hz, 1H), 4.13 (s, 1H), 3.75 (d, J=11.7Hz, 2H), 3.70-3.48 (m, 5H), 3.36 (s, 5H), 3.25-3.20 (m, 2H), 3.10-2.9 6 (m, 2H), 2.94-2.85 (m, 1H), 2.61 (d, J=16.6Hz, 1H), 2.47-2.34 (m, 3H), 2.28-2.09 (m, 2H), 2.05-1.94 (m, 1H). LCMS (ESI) C 31 H 36 FN6O4 + [M+H] + : Calculated value 575.28, measured value 575.3.

[0514] Example 154: Preparation of 3-(5-(3-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09648)

[0515] The target compound (GT-09648) (white solid, 18 mg, yield 15%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.62 (s, 1H), 10.99 (s, 1H), 10.67 (s, 1H), 8.10 (dd, J=8.9, 5.2Hz, 1H), 7.69 (d, J=7.8Hz, 1H), 7.65-7.58 (m, 1H), 7.50 (s, 1H), 7.41 (d, J = 7.8Hz, 1H), 7.30-7.22 (m, 1H), 5.11 (dd, J = 13.2, 5.0Hz, 1H), 4.44 (d, J = 17.4Hz, 1H), 4.31 (d, J =17.3Hz, 1H), 4.16-4.09(m, 1H), 3.70-3.52(m, 6H), 3.41(s, 2H), 3.30-3.24(m, 2H), 3.05(s, 2H), 2.99-2.86(m, 3H), 2.78(t, J=7.4Hz, 2H), 2.61(d, J=17.2Hz, 1H), 2.45-2.31(m, 3H), 2.29-2.14(m, 2H), 2.13-2.05(m, 2H), 2.04-1.96(m, 1H).LCMS(ESI)C 32 H 38 FN6O4 + [M+H] + : Calculated value 589.29, measured value 589.3.

[0516] Example 155: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-09649)

[0517] The target compound (GT-09649) (white solid, 10 mg, yield 16%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.61 (s, 1H), 11.26 (s, 1H), 11.16 (s, 1H), 8.22 (s, 1H), 8.13-7.99 (m , 3H), 7.62 (d, J=9.1Hz, 1H), 7.26 (t, J=9.0Hz, 1H), 5.19 (dd, J=12.8, 5.3Hz, 1H), 4.52 (s, 1 H), 4.11(s, 1H), 3.78-3.46(m, 8H), 3.30-3.23(m, 2H), 3.17-3.08(m, 1H), 3.07-2.84(m, 3 H), 2.59 (d, J=23.0, 11.0Hz, 4H), 2.33 (s, 2H), 2.19 (s, 2H), 2.12-2.05 (m, 1H).LCMS (ESI) C 30 H 32 FN6O5 + [M+H] + : Calculated value 575.24, measured value 575.3.

[0518] Example 156: Preparation of 2-(2,6-dioxopiperidin-3-yl)-4-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-09650)

[0519] The target compound (GT-09650) (yellow solid, 10 mg, yield 16%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.67 (s, 1H), 11.16 (s, 1H), 11.08 (s, 1H), 8.22-8.15 (m, 1H), 8.10 (dd, J=8.8, 5.3H z, 1H), 8.03 (d, J=7.1Hz, 1H), 7.97 (t, J=7.5Hz, 1H), 7.62 (dd, J=9.1, 2.1Hz, 1H), 7.30-7.22 (m, 1H), 5.19 (dd, J=12.7, 5.3Hz, 1H), 4.71 (s, 2H), 4.10 (s, 2H), 3.58 (s, 6H), 3.31-3.20 (m, 3H), 3.18-3.03 (m, 2H), 2. 94-2.85(m, 1H), 2.66-2.56(m, 2H), 2.40-2.30(m, 2H), 2.30-2.11(m, 2H), 2.12-2.02(m, 1H).LCMS(ESI)C 30 H 32 FN6O5 + [M+H]+ : Calculated value 575.24, measured value 575.3.

[0520] Example 157: Preparation of 3-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09655)

[0521] The target compound (GT-09655) (white solid, 35 mg, yield 59%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.03 (s, 1H), 8.07 (dd, J=8.9, 5.2Hz, 1H), 7.78-7.68 (m, 1H), 7.65 (d, J=7.7Hz, 1H), 7.58 (dd, J=9.1, 2.2Hz, 1H), 7.27-7.17 (m, 1H), 5.14 (dd, J=13.3, 5.1Hz, 1H), 4.60 (d, J=17.5Hz, 1H), 4.43 (d, J=17 .5Hz, 1H), 4.09(s, 2H), 3.67-3.62(m, 4H), 3.54-3.46(m, 3H), 3.32(s, 4H), 3.22(s, 1H), 3.00-2.82(m, 2H), 2. 61(d, J=17.2Hz, 1H), 2.48-2.39(m, 1H), 2.34-2.23(m, 1H), 2.16-2.06(m, 1H), 2.05-1.97(m, 1H).LCMS(ESI)C 30 H 31 F4N6O4 + [M+H] + : Calculated value 615.23, measured value 615.3.

[0522] Example 158: Preparation of 3-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09656)

[0523] The target compound (GT-09656) (white solid, 26 mg, yield 44%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.02 (s, 1H), 8.07 (dd, J=8.9, 5.2Hz, 1H), 7.77 (d, J=4.9Hz, 1H), 7.64-7 .52 (m, 2H), 7.23 (t, J=9.1, 2.2Hz, 1H), 5.14 (dd, J=13.3, 5.1Hz, 1H), 4.49 (d, J=17.3Hz, 1H), 4 .36(d, J=17.5Hz, 1H), 4.03(s, 2H), 3.69(s, 6H), 3.33-3.23(m, 4H), 3.18(s, 1H), 3.00-2.83(m , 2H), 2.68-2.54(m, 2H), 2.45-2.36(m, 1H), 2.30-2.17(m, 1H), 2.10-1.98(m, 2H).LCMS(ESI)C 30 H 31 F4N6O4 + [M+H] + : Calculated value 615.23, measured value 615.3.

[0524] Example 159: Preparation of 3-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09657)

[0525] The target compound (GT-09657) (white solid, 28 mg, yield 47%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 8.07 (dd, J=8.9, 5.3Hz, 1H), 7.58 (dd, J=9.1, 2.1Hz, 1H), 7.52 (s, 1 H), 7.43 (d, J=9.4Hz, 1H), 7.23 (t, J=9.0, 2.1Hz, 1H), 5.10 (dd, J=13.3, 5.1Hz, 1H), 4.52 (d, J=17.9Hz, 1H), 4.39 (d, J=18.0Hz, 1H), 4.11 (s, 2H), 3.66 (d, J=13.0Hz, 8H), 3.27 (s, 5H), 2.96-2.87 (m, 1H), 2.6 1(d, J=17.2Hz, 1H), 2.44-2.34(m, 1H), 2.27(s, 1H), 2.18-2.07(m, 1H), 2.05-1.97(m, 1H).LCMS(ES1)C 30 H 31 F4N6O4 +[M+H] + : Calculated value 615.23, measured value 615.3.

[0526] Example 160: Preparation of 3-(4-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09658)

[0527] The target compound (GT-09658) (white solid, 36 mg, yield 62%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.04 (s, 1H), 8.07 (dd, J=8.9, 5.2Hz, 1H), 7.83-7.65 (m, 2H), 7.62-7. 52 (m, 2H), 7.23 (t, J=9.0, 2.0Hz, 1H), 5.16 (dd, J=13.2, 5.1Hz, 1H), 4.68-4.54 (m, 1H), 4.43 (d, J=17.5Hz, 1H), 3.95 (s, 2H), 3.77-3.66 (m, 6H), 3.34 (s, 6H), 3.14 (s, 1H), 2.98-2.90 (m, 1H), 2.64(d, J=17.2Hz, 1H), 2.43-2.34(m, 1H), 2.27(s, 1H), 2.14-1.98(m, 2H).LCMS(ESI)C 30 H 32 F3N6O4 + [M+H] + : Calculated value 597.24, measured value 597.3.

[0528] Example 161: Preparation of 3-(6-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09659)

[0529] The target compound (GT-09659) (white solid, 28 mg, yield 499%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.02 (s, 1H), 8.06 (dd, J=8.9, 5.3Hz, 1H), 7.95 (s, 1H), 7.82 (d, J=7.6Hz, 1H), 7 .71 (d, J=7.8Hz, 1H), 7.57 (dd, J=9.1, 2.2Hz, 1H), 7.21 (t, J=9.1, 2.2Hz, 1H), 5.15 (dd, J=13.3, 5.1H z, 1H), 4.50 (d, J=14.8Hz, 1H), 4.43-4.28 (m, 3H), 3.63 (s, 8H), 3.42 (s, 1H), 3.18 (s, 4H), 2.96-2.88 (m, 1H), 2.62 (d, J=16.7Hz, 1H), 2.48-2.36 (m, 1H), 2.35-2.15 (m, 2H), 2.05-1.98 (m, 1H). LCMS (ESI) C 30 H 32 F3N6O4 + [M+H] + : Calculated value 597.24, measured value 597.3.

[0530] Example 162: Preparation of 3-(7-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09660)

[0531] The target compound (GT-09660) (white solid, 24 mg, yield 42%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.04 (s, 1H), 8.06 (dd, J=8.9, 5.3Hz, 1H), 7.72 (s, 3H), 7.57 (dd, J=9.1, 2.2H z, 1H), 7.21 (t, J=9.1, 2.2Hz, 1H), 5.19-5.10 (m, 1H), 4.82 (d, J=37.2Hz, 1H), 4.71-4.58 (m, 1H), 4. 52(d, J=17.9Hz, 1H), 4.47-4.38(m, 1H), 3.65-3.55(m, 6H), 3.45(s, 2H), 3.15(s, 4H), 3.03-2.84(m , 2H), 2.63 (d, J=17.0Hz, 1H), 2.47-2.37 (m, 1H), 2.30-2.10 (m, 2H), 2.09-2.00 (m, 1H).LCMS (ESI) C 30 H 32 F3N6O4+ [M+H] + : Calculated value 597.24, measured value 597.3.

[0532] Example 163: Preparation of 3-(5-(2-(3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09661)

[0533] The target compound (GT-09661) (white solid, 24 mg, yield 41%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.00 (s, 1H), 8.06 (dd, J=8.9, 5.3Hz, 1H), 7.72 (d, J=7.8Hz, 1H), 7.61-7.50 (m, 2 H), 7.44 (d, J=7.8Hz, 1H), 7.21 (t, J=9.1, 2.2Hz, 1H), 5.12 (dd, J=13.3, 5.1Hz, 1H), 4.46 (d, J=17.5Hz , 1H), 4.33 (d, J=17.4Hz, 1H), 4.02 (s, 1H), 3.66 (s, 3H), 3.36 (s, 3H), 3.29-3.12 (m, 4H), 3.07 (s, 4H), 2.96-2.88(m, 1H), 2.69-2.53(m, 2H), 2.49-2.30(m, 2H), 2.23(s, 2H), 2.05-1.96(m, 1H).LCMS(ESI)C 31 H 34 F3N6O4 + [M+H] + : Calculated value 611.26, measured value 611.3.

[0534] Example 164: Preparation of 3-(5-(3-(3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09662)

[0535] The target compound (GT-09662) (white solid, 47 mg, yield 39%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.99 (s, 1H), 8.05 (dd, J=8.8, 5.3Hz, 1H), 7.69 (d, J=7.8Hz, 1H), 7.57 (dd, J=9.1, 2.1Hz, 1H) , 7.50 (s, 1H), 7.41 (d, J = 7.8Hz, 1H), 7.21 (t, J = 9.0, 2.1Hz, 1H), 5.11 (dd, J = 13.3, 5.1Hz, 1H), 4.44 (d, J = 17.3Hz, 1 H), 4.31 (d, J=17.3Hz, 1H), 3.97 (s, 1H), 3.69 (s, 3H), 3.55 (s, 6H), 3.16-3.00 (m, 6H), 2.95-2.87 (m, 1H), 2.77 (t, J =7.2Hz, 2H), 2.66-2.56(m, 1H), 2.44-2.34(m, 1H), 2.21(s, 1H), 2.17-2.05(m, 2H), 2.04-1.95(m, 1H).LCMS(ESI)C 32 H 36 F3N6O4 + [M+H] + : Calculated value 625.27, measured value 625.3.

[0536] Example 165: Preparation of 5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09663)

[0537] The target compound (GT-09663) (white solid, 32 mg, yield 54%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.15 (s, 1H), 8.07 (dd, J=8.9, 5.3Hz, 1H), 8.04-7.89 (m, 3H), 7.58 (dd, J=9.1, 2.1Hz, 1H), 7.22 (t, J=9.1, 2.1Hz, 1H), 5.18 ( dd, J=12.8, 5.3Hz, 1H), 4.13(s, 2H), 3.66(s, 6H), 3.27(s, 5H), 2.98-2.8 2(m, 2H), 2.69-2.54(m, 3H), 2.23(s, 1H), 2.14-2.02(m, 2H).LCMS(ESI)C 30 H 30 F3N6O5 + [M+H] +: Calculated value 611.22, measured value 611.3.

[0538] Example 166: Preparation of 4-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09664)

[0539] The target compound (GT-09664) (white solid, 34 mg, yield 57%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.15 (s, 1H), 8.08 (dd, J=8.9, 5.2Hz, 1H), 8.02-7.95 (m, 1H) , 7.92 (d, J=6.2Hz, 2H), 7.59 (dd, J=9.1, 2.1Hz, 1H), 7.23 (t, J=9.1, 2.0Hz, 1H), 5. 19-5.14(m, 1H), 4.29(s, 2H), 3.84-3.71(m, 6H), 3.37(s, 6H), 3.16(s, 1H), 2.93- 2.87(m, 1H), 2.66-2.56(m, 2H), 2.34-2.24(m, 1H), 2.15-2.03(m, 2H).LCMS(ESI)C 30 H 30 F3N6O5 + [M+H] + : Calculated value 611.22, measured value 611.3.

[0540] Example 167: Preparation of 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09665)

[0541] The target compound (GT-09665) (white solid, 20 mg, yield 34%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.64 (s, 1H), 11.03 (s, 1H), 8.28 (s, 1H), 7.73 (dd, J=9.0, 2.0Hz, 1H), 7.68-7. 62 (m, 2H), 7.34 (t, J=9.1, 2.1Hz, 1H), 5.14 (dd, J=13.2, 5.0Hz, 1H), 4.59 (d, J=17.5Hz, 1H), 4.42 (d , J=17.5Hz, 1H), 4.09 (s, 1H), 3.93 (s, 2H), 3.73 (s, 2H), 3.51-3.32 (m, 4H), 3.11 (d, J=9.7Hz, 1H), 2 .97-2.87(m, 1H), 2.79-2.56(m, 4H), 2.48-2.36(m, 3H), 2.19(s, 3H), 2.04-1.96(m, 1H).LCMS(ESI)C 31 H 32 F4N5O4 + [M+H] + : Calculated value 614.24, measured value 614.3.

[0542] Example 168: Preparation of 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09666)

[0543] The target compound (GT-09666) (white solid, 20 mg, yield 34%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.50 (s, 1H), 11.02 (s, 1H), 8.27 (s, 1H), 7.76-7.66 (m, 2H), 7.57 (d, J=8.7H z, 1H), 7.34 (t, J=9.1, 2.1Hz, 1H), 5.13 (dd, J=13.2, 5.0Hz, 1H), 4.49 (d, J=17.2Hz, 1H), 4.35 (d, J=17.4Hz, 1H), 4.06 (s, 1H), 3.89 (s, 2H), 3.79-3.70 (m, 2H), 3.55-3.30 (m, 6H), 3.08 (s, 1H), 2.9 6-2.85(m, 1H), 2.75-2.56(m, 3H), 2.43-2.34(m, 2H), 2.20(s, 2H), 2.14-1.98(m, 2H).LCMS(ESI)C 31 H 32 F4N5O4+ [M+H] + : Calculated value 614.24, measured value 614.3.

[0544] Example 169: Preparation of 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09667)

[0545] The target compound (GT-09667) (white solid, 16 mg, yield 28%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.56 (s, 1H), 11.02 (s, 1H), 8.28 (s, 1H), 7.73 (dd, J=9.1, 2.0Hz, 1H), 7.4 6 (s, 1H), 7.38-7.26 (m, 2H), 5.09 (dd, J=13.3, 5.1Hz, 1H), 4.51 (d, J=17.9Hz, 1H), 4.37 (d, J=17 .9Hz, 1H), 4.07(s, 1H), 3.90(s, 3H), 3.75(s, 2H), 3.53-3.33(m, 5H), 3.11(s, 1H), 2.98-2.86( m, 1H), 2.75-2.57 (m, 3H), 2.44-2.32 (m, 2H), 2.28-2.12 (m, 3H), 2.05-1.96 (m, 1H). LCMS (ESI) C 31 H 32 F4N5O4 + [M+H] + : Calculated value 614.24, measured value 614.3.

[0546] Example 170: Preparation of 3-(4-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09668)

[0547] The target compound (GT-09668) (white solid, 23 mg, yield 40%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.58 (s, 1H), 11.02 (s, 1H), 8.28 (s, 1H), 7.77-7.67 (m, 2H), 7.62 (d, J=7.2Hz, 1H), 7. 54 (t, J=7.5Hz, 1H), 7.34 (t, J=9.0, 1.9Hz, 1H), 5.15 (dd, J=13.2, 5.1Hz, 1H), 4.63-4.50 (m, 1H), 4.40 (d, J =17.5Hz, 1H), 4.13(s, 1H), 3.85-3.69(m, 5H), 3.48-3.42(m, 2H), 3.26(s, 1H), 3.04(s, 1H), 3.00-2.89(m, 1H), 2.81-2.70(m, 1H), 2.69-2.56(m, 3H), 2.48-2.32(m, 3H), 2.21(s, 2H), 2.14-1.97(m, 2H).LCMS(ESI)C 31 H 33 F3N5O4 + [M+H] + : Calculated value 596.25, measured value 596.3.

[0548] Example 171: Preparation of 3-(6-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09669)

[0549] The target compound (GT-09669) (white solid, 19 mg, yield 34%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.01 (s, 1H), 8.24 (s, 1H), 7.82 (s, 1H), 7.76-7.63 (m, 3H), 7.38-7.29 (m, 1H), 5.14 (dd, J=13.3, 5.1Hz, 1H), 4.49 (d, J=17.5Hz, 1H), 4.36 (d, J=17.5Hz, 1H), 4.06 (s, 3H), 3.73-3.63 (m, 5H), 3.25 (s, 2H), 2.99-2.84 (m, 2H), 2 .68-2.53(m, 4H), 2.48-2.38(m, 2H), 2.22(s, 3H), 2.06-1.98(m, 1H).LCMS(ESI)C 31 H 33 F3N5O4 + [M+H] +: Calculated value 596.25, measured value 596.3.

[0550] Example 172: Preparation of 3-(7-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09670)

[0551] The target compound (GT-09670) (white solid, 26 mg, yield 45%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.45 (s, 1H), 11.02 (s, 1H), 8.24 (s, 1H), 7.72 (dd, J=9.1, 2.0Hz, 1H ), 7.70-7.64 (m, 1H), 7.64-7.54 (m, 2H), 7.34 (t, J=9.2, 2.1Hz, 1H), 5.11 (d, J=10.9Hz, 1H ), 4.56-4.27(m, 4H), 4.12(s, 1H), 3.75-3.58(m, 5H), 3.36-3.07(m, 4H), 2.98-2.77(m, 2H ), 2.62(d, J=17.3Hz, 2H), 2.45-2.32(m, 2H), 2.20(s, 3H), 2.08-1.97(m, 1H).LCMS(ESI)C 31 H 33 F3N5O4 + [M+H] + : Calculated value 596.25, measured value 596.3.

[0552] Example 173: Preparation of 3-(5-(2-(3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09671)

[0553] The target compound (GT-09671) (white solid, 12 mg, yield 21%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ10.99 (s, 1H), 8.20 (s, 1H), 7.78-7.64 (m, 2H), 7.52 (s, 1H), 7.43 (d, J=8.0Hz, 1H), 7.34 (t, J=9.1, 2.1Hz, 1H), 5.17-5.06 (m, 1H), 4.45 (d, J=17.4Hz, 1H), 4.3 2(d, J=17.3Hz, 1H), 3.70-3.54(m, 5H), 3.36-3.19(m, 6H), 3.10(s, 3H), 2.95-2.88(m, 1H ), 2.61(d, J=17.0Hz, 2H), 2.48-2.31(m, 3H), 2.22(s, 3H), 2.07-1.97(m, 1H).LCMS(ESI)C 32 H 35 F3N5O4 + [M+H] + : Calculated value 610.26, measured value 610.3.

[0554] Example 174: Preparation of 3-(5-(3-(3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-09672)

[0555] The target compound (GT-09672) (white solid, 35 mg, yield 29%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ10.99 (s, 1H), 8.14 (s, 1H), 7.76-7.62 (m, 2H), 7.50 (s, 1H), 7.41 (d, J=7.9H z, 1H), 7.33 (t, J=9.1, 1.9Hz, 1H), 5.11 (dd, J=13.2, 5.1Hz, 1H), 4.44 (d, J=17.3Hz, 1H), 4.31 (d , J=17.3Hz, 1H), 4.00 (s, 2H), 3.71-3.54 (m, 6H), 3.03 (s, 3H), 2.98-2.83 (m, 2H), 2.77 (t, J=7.4 Hz, 2H), 2.61 (d, J=17.6Hz, 2H), 2.48-2.28 (m, 4H), 2.21 (s, 2H), 2.12-1.95 (m, 3H).LCMS (ESI) C 33 H 37 F3N5O4 + [M+H] + : Calculated value 624.28, measured value 624.3.

[0556] Example 175: Preparation of 5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09673)

[0557] The target compound (GT-09673) (white solid, 13 mg, yield 22%) was prepared by referring to the method of Synthesis Scheme 1. 1 H NMR (400MHz, DMSO) δ11.14 (s, 2H), 8.23 ​​(s, 1H), 7.99-7.88 (m, 2H), 7.84 (d, J=7.6Hz, 1H), 7. 73 (dd, J=9.1, 2.0Hz, 1H), 7.34 (t, J=9.1, 2.1Hz, 1H), 5.17 (dd, J=12.9, 5.4Hz, 1H), 4.07 (s, 1H), 3.89(s, 2H), 3.72(s, 2H), 3.63-3.47(m, 3H), 3.32-3.20(m, 2H), 3.03(s, 1H), 2.94-2.8 5(m,1H),2.66-2.54(m,3H),2.48-2.33(m,3H),2.22(s,2H),2.13-2.01(m,2H).LCMS(ESI)C 31 H 31 F3N5O5 + [M+H] + : Calculated value 610.23, measured value 610.3.

[0558] Example 176: Preparation of 4-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidinyl]-1′-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-09674)

[0559] The target compound (GT-09674) (white solid, 11 mg, yield 19%) was prepared by referring to the method of Synthesis Scheme 1. 1H NMR (400MHz, DMSO) δ11.14 (s, 2H), 8.23 ​​(s, 1H), 7.92-7.83 (m, 3H), 7.73 (dd, J=9.1, 2.0Hz, 1H), 7.34 (t, J=9.1, 2.1Hz, 1H), 5.15 (dd, J=12.7, 5.4Hz, 1...

Claims

1. A compound of formula (I) or a salt, enantiomer, stereoisomer, isotopically enriched analogue, solvate or polymorph thereof, wherein Z1 represents C(O), C(S), CH2 or CD2, and Z2, Z3 and Z4 each independently represent C(O) or C(S); Z5 represents CH or N; R a1 , R a2 , R a3 and R a4 Each independently represents hydrogen, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy or halogenated C 1-6 Alkoxy; (R a5 ) m represents that the isoindoline ring connected thereto is optionally substituted with m R a5 groups, each R a5 being the same or different and each independently representing deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 alkyl, halo C 1-6 alkyl, deutero C 1-6 alkyl, C 1-6 alkoxy, deutero C 1-6 alkoxy, halo C 1-6 alkoxy, C 2-6 alkenyl or C 2-6 alkynyl; m represents an integer 0, 1, 2 or 3; R represents C(O) or an optionally substituted straight-chain or branched C 1-5 alkylene; X represents: wherein ring A represents a nitrogen-containing heterocyclic group, (R d1 ) n1 indicates that ring A is optionally substituted by n1 R d1 groups, each R d1 independently represents deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, deuterium, halogen, amino, hydroxy, mercapto, nitro, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n1 represents an integer from 0 to 20; Ring B represents a nitrogen-containing heterocyclic group, (R d2 ) n2 represents that Ring B is optionally substituted by n2 R d2 groups, each R d2 independently represents deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n2 represents an integer from 0 to 20; R c represents C(O), CR c1 R c2 or a bond, where R c1 and R c2 each independently represents H, deuterium, a halogen, an optionally substituted straight or branched alkyl, an optionally substituted cycloalkyl, an optionally substituted heterocyclic group, an optionally substituted aryl or an optionally substituted heteroaryl; Ring C represents a cycloalkylidene, heterocycloalkylidene, arylidene or heteroarylidene group, m1 represents an integer of 0 or 1, (R d3 ) n3 indicates that ring C is optionally substituted with n3 R d3 groups, each R d3 independently represents deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n3 represents an integer from 0 to 20; and Ring D represents a heterocyclic group, cycloalkyl group, aryl group or heteroaryl group, (R d4 ) n4 indicates that ring D is optionally substituted with n4 R d4 groups, and each R d4 independently represents deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n4 represents an integer from 0 to 20.

2. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof according to claim 1, wherein (i)R a1 , R a2 , R a3 and R a4 Each independently represents H; and / or (ii) R represents C(O) or an optionally substituted straight-chain or branched C 1-3 alkylene; and / or (iii) X represents: wherein ring A represents a 4- to 30-membered nitrogen-containing heterocyclic group (including a 4- to 20-membered nitrogen-containing heterocyclic group and a 4- to 15-membered nitrogen-containing heterocyclic group), (R d1 ) n1 represents that ring A is optionally substituted by n1 R d1 groups, each R d1 is independently deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n1 represents an integer from 0 to 20; Ring B represents a nitrogen-containing heterocyclic group having 4 to 30 ring atoms, (R d2 ) n2 represents that ring B is optionally substituted with n2 R d2 groups, each R d2 independently being deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n2 represents an integer from 0 to 20; R c represents C(O), CR c1 R c2 or a bond, wherein R c1 and R c2 each independently represents H, deuterium, a halogen, an optionally substituted straight-chain or branched C 1-10 alkyl, an optionally substituted C 3-30 cycloalkyl, an optionally substituted C 5-30 aryl, an optionally substituted 4- to 30-membered heterocyclic group or an optionally substituted 5- to 30-membered heteroaryl; Ring C represents a 4- to 30-membered heteroalicyclic group, C 3-30 subcycloalkyl group, C 5-30 arylene group or 5- to 30-membered heteroarylene group, m1 represents the integer 0 or 1, (R d3 ) n3 indicates that ring C is optionally substituted by n3 R d3 groups, each R d3 is independently deuterium, C 1-6 alkyl group, deuterated C 1-6 alkyl group, halogenated C 1-6 alkyl group, C 1-6 alkoxy group, halogenated C 1-6 alkoxy group, halogen, amino group, hydroxyl group, mercapto group, cyano group, oxo group, C 2-6 alkynyl group or C 2-6 alkenyl group, and n3 represents an integer from 0 to 20; and / or Ring D represents C 3-30 cycloalkyl, 4- to 30-membered heterocyclic group, C 5-30 aryl or 5- to 30-membered heteroaryl, (R d4 ) n4 indicating that Ring D is optionally substituted by n4 R d4 groups, each R d4 independently being deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n4 represents an integer from 0 to 20.

3. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof according to claim 1 or 2, wherein (i) The cyclic A represents a 4- to 20-membered nitrogen-containing heterocyclic group (including a 4- to 15-membered nitrogen-containing heterocyclic group), (R d1 ) n1 indicates that the cyclic A is optionally substituted with n1 R d1 groups, each R d1 is independently deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1- 6-alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n1 represents an integer from 0 to 20; and / or (ii) The ring B represents a nitrogen-containing heterocyclic group having 4 to 20 members (including a nitrogen-containing heterocyclic group having 4 to 15 members), (R d2 ) n2 indicates that the ring B is optionally substituted by n2 R d2 groups, and each R d2 is independently deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1- 6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n2 represents an integer from 0 to 20; and / or (iii) said R c1 and R c2 each independently represents H, deuterium, a halogen, an optionally substituted straight-chain or branched C 1-6 alkyl, an optionally substituted C 3-20 cycloalkyl (including an optionally substituted C 3-15 cycloalkyl), an optionally substituted C 5-20 aryl (including an optionally substituted C 5-15 aryl), an optionally substituted 4- to 20-membered heterocyclic group (including an optionally substituted 4- to 15-membered heterocyclic group) or an optionally substituted 5- to 20-membered heteroaryl (including an optionally substituted 5- to 15-membered heteroaryl); and / or (iv) The cyclic group C represents a 4- to 20-membered heteroalicyclic group (including a 4- to 15-membered heteroalicyclic group), a C 3-20 subcycloalkyl group (including a C 3-15 subcycloalkyl group), a C 5-20 subaryl group (including a C 5-15 subaryl group) or a 5- to 20-membered heteroaryl group (including a 5- to 15-membered heteroaryl group), m1 represents the integer 0 or 1, (R d3 ) n3 indicates that the cyclic group C is optionally substituted with n3 R d3 groups, each R d3 is independently deuterium, a C 1-6 alkyl group, a deuterated C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a halogenated C 1-6 alkoxy group, a halogen, an amino group, a hydroxyl group, a mercapto group, a cyano group, an oxo group, a C 2-6 alkynyl group or a C 2-6 alkenyl group, and n3 represents an integer from 0 to 20; and / or (v) Ring D represents C 3-20 Cycloalkyl (including C 3-15 Cycloalkyl), 4- to 20-membered heterocyclic group (including 4- to 15-membered heterocyclic group), C 5-20 Aryl (including C 5-15 Aryl) or 5- to 20-membered heteroaryl (including 5- to 15-membered heteroaryl), (R d4 ) n4 Indicates that ring D is optionally substituted by n4 R d4 groups, each R d4 is independently deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1- 6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl or C 2-6 alkenyl, and n4 represents an integer from 0 to 20.

4. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof according to any one of claims 1 - 3, wherein (i) R represents C(O) or optionally substituted methylene; and / or (ii) Each of said ring A and ring B independently represents azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, azepanyl, diazepanyl, azocanyl, diazocanyl, 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, quinuclidinyl, 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl, 7-azaspiro[3.5]nonanyl, 8-azaspiro[4.5]decanyl or octahydropyrrolo[3,4-c]pyrrolyl, which is optionally substituted by one or more (e.g., 1-10) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl and C 2-6 alkenyl; and / or (iii) R c1 and R c2 each independently represents: H, deuterium, a halogen or an optionally substituted straight-chain or branched C 1-10 alkyl group; or Cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydrobicyclopentadienyl, octahydro-1H-indenyl, spiroalkyl (e.g., C5-C 20 spiro group, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C 20 bridged cyclo group, such as adamantyl, noradamantyl, borneol group, norborneol group, bicyclo[2.2.1]heptyl, 2-oxobicyclo 2.2.1]heptyl or bicyclo[2.2.1]heptenyl), optionally substituted with one or more (e.g., 1-10) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl and C 2-6 alkenyl; or Azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxanyl, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazepanyl, 4,5-diazepanyl, 1,3-diazepanyl), diazocanyl, bridged heterocyclic group (e.g., 6- to 20-membered bridged heterocyclic group, e.g., 6-azabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2.2.2]octanyl and quinuclidinyl), and azaspiro group (e.g., 5- to 20-membered azaspiro group, e.g., 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl and 7-azaspiro[3.5]nonanyl), or octahydropyrrolo[3,4-c]pyrrolyl, which is optionally substituted by one or more (e.g., 1 - 10) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl and C 2-6 alkenyl; or A phenyl or naphthyl group, which is optionally substituted by one or more (e.g., 1-7) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C 2-6 alkynyl, and C 2-6 alkenyl; or furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, 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, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[f]thieno[2,3-d]pyrimidinyl, which is optionally substituted by one or more (e.g., 1 - 10) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C 2-6 alkynyl and C 2-6 alkenyl; and / or (iv) the ring C represents: Cyclopropylidene, cyclobutylidene, cyclopentylidene, cyclopentenylidene, cyclohexylidene, cyclohexenylidene, cycloheptylidene, cyclooctylidene, decahydronaphthalenylidene, octahydrodicyclopentadienylidene, octahydro-1H-indenylidene, spirocycloalkylidene (e.g., C5-C 20 spirocycloalkylidene, e.g., spiro[3.3]heptylidene, spiro[2.5]octylidene, spiro[3.5]nonylidene, spiro[4.4]nonylidene, spiro[4.5]decylidene, spiro[5.5]undecylidene), p-menthylidene, m-menthylidene, or bridged cycloalkylidene (e.g., C6-C 20 bridged cycloalkylidene, e.g., adamantylidene, noradamantylidene, bornylidene, norbornylidene, bicyclo[2.2.1]heptylidene, 2-oxabicyclo 2.2.1]heptylidene or bicyclo[2.2.1]heptenylidene), which is optionally substituted by one or more (e.g., 1 - 20) substituents selected from deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, oxo, C 1-6 alkyl, halo - C 1-6 alkyl, deuterated - C 1-6 alkyl, hydroxyl - substituted C 1-6 alkyl, amino - substituted C 1-6 alkyl, C 1-6 alkoxy, deuterated - C 1-6 alkoxy, halo - C 1-6 alkoxy, C 2-6 alkenyl and C 2-6 alkynyl; or Azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxanyl, azepanyl, azocanyl, diazepanediyl (e.g., 1,4-diazepanediyl, 4,5-diazepanediyl, 1,3-diazepanediyl), diazocanediyl, bridged heterocyclic group (e.g., 6- to 20-membered bridged heterocyclic group, e.g., 6-azabicyclo[3.1.1]heptanediyl, 2,5-diazabicyclo[2.2.1]heptanediyl, 3,6-diazabicyclo[3.1.1]heptanediyl, 3-azabicyclo[3.2.1]octanediyl, 3,8-diazabicyclo[3.2.1]octanediyl, 3,8-diazabicyclo[3.2.1]octanediyl, 2,5-diazabicyclo[2.2.2]octanediyl and quinuclidinyl), azaspiro group (e.g., 5- to 20-membered azaspiro group, e.g., 2,6-diazaspiro[3.3]heptanediyl, 2,7-diazaspiro[3.5]nonanediyl, 2,8-diazaspiro[4.5]decadiyl, 3,9-diazaspiro[5.5]undecanediyl, 3-azaspiro[5.5]undecanediyl and 7-azaspiro[3.5]nonanediyl), or octahydropyrrolo[3,4-c]pyrrolyl, which is optionally substituted by one or more (e.g., 1-20) substituents selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, oxo, C 1-6 alkyl, halo-C 1-6 alkyl, deutero-C 1-6 alkyl, hydroxy-substituted C 1-6 alkyl, amino-substituted C 1-6 alkyl, C 1-6 alkoxy, deutero-C 1-6 alkoxy, halo-C 1-6 alkoxy, C 2-6 alkenyl and C 2-6 alkynyl; or A phenylene or naphthylene group, optionally substituted by one or more (e.g., 1-6) substituents selected from deuterium, halogen, hydroxyl, mercapto, nitro, amino, cyano, C 1-6 alkyl, halo-C 1-6 alkyl, deuterated C 1-6 alkyl, hydroxyl-substituted C 1-6 alkyl, amino-substituted C 1-6 alkyl, C 1-6 alkoxy, deuterated C 1-6 alkoxy, halo-C 1-6 alkoxy, C 2-6 alkenyl and C 2-6 alkynyl; or Furylidene, oxazolylidene, isoxazolylidene, oxadiazolylidene, thienylidene, thiazolylidene, isothiazolylidene, thiadiazolylidene, pyrrolylidene, imidazolylidene, pyrazolylidene, triazolylidene, pyridinylidene, pyrimidinylidene, pyridazinylidene, pyrazinylidene, triazinylidene, indolylidene, isoindolylidene, indolinylidene, benzofurylidene, chromanyl, isobenzofurylidene, benzothienylidene, indazolylidene, benzimidazolylidene, benzoxazolylidene, benzisoxazolylidene, benzothiazolylidene, benzisothiazolylidene, benzotriazolylidene, benzo[2,1,3]oxadiazolylidene, benzo[2,1,3]thiadiazolylidene, benzo[1,2,3]thiadiazolylidene, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolylidene, benzo[b][1,4]oxazinylidene, 3,4-dihydro-2H-benzo[b][1,4]oxazinylidene, quinolinylidene, isoquinolinylidene, 1,2,3,4-tetrahydroquinolinylidene, naphthyridinylidene, cinnolinylidene, quinazolinylidene, quinoxalinylidene, 1,2,3,4-tetrahydroquinoxalinylidene, phthalazinylidene, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinylidene, 4,5,6,7-tetrahydrothieno[3,2-c]pyridinylidene, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinylidene, thieno[2,3-d]pyrimidinylidene, thieno[3,2-d]pyrimidinylidene, isoxazolo[4,5-c]pyridinylidene, isoxazolo[4,5-c]pyrimidinylidene, isoxazolo[4,5-d]pyrimidinylidene, pyrazolo[1,5-a]pyridinylidene, pyrazolo[1,5-a]pyrimidinylidene, imidazo[1,2-a]pyridinylidene, 1H-pyrrolo[3,2-b]pyridinylidene, 1H-pyrrolo[2,3-b]pyridinylidene, pyrrolo[2,1-b]thiazolylidene, imidazo[2,1-b]thiazolylidene, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinylidene, or 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinylidene, which is optionally substituted by one or more (e.g., 1-20) substituents selected from deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 alkyl, halo-C 1-6 alkyl, deuterated C 1-6 alkyl, hydroxy-substituted C 1-6 alkyl, amino-substituted C 1-6 alkyl, C 1-6 alkoxy, deuterated C 1-6 alkoxy, halo-C 1-6 alkoxy, C 2-6 alkenyl and C 2-6 alkynyl substituents; and / or (v) the ring D represents: Cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydro-s-indacenyl, octahydro-1H-indenyl, spiroalkyl (e.g., C5-C 20 spiro group, e.g., spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[5.5]undecyl), p-menthanyl, m-menthanyl, or bridged cycloalkyl (e.g., C6-C 20 bridged group, e.g., adamantyl, noradamantyl, borneol, norborneol, bicyclo[2.2.1]heptyl, 2-oxabicyclo 2.2.1]heptyl or bicyclo[2.2.1]heptenyl), which is optionally substituted with one or more (e.g., 1 - 20) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl and C 2-6 alkenyl; or Azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, tetrahydropyridyl, dihydroxypiperidinyl, difluoropiperidinyl, morpholinyl, thiomorpholinyl, azepanyl, azocanyl, dioxanyl, azepanyl, azocanyl, diazepanyl (e.g., 1,4-diazepanyl, 4,5-diazepanyl, 1,3-diazepanyl), diazocanyl, bridged heterocyclic group (e.g., 6- to 20-membered bridged heterocyclic group, e.g., 6-azabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2.2.2]octanyl and quinuclidinyl), and azaspiro group (e.g., 5- to 20-membered azaspiro group, e.g., 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, 2,8-diazaspiro[4.5]decanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azaspiro[5.5]undecanyl and 7-azaspiro[3.5]nonanyl), or octahydropyrrolo[3,4-c]pyrrolyl, which is optionally substituted with one or more (e.g., 1-20) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl and C 2-6 alkenyl; or phenyl or naphthyl, optionally substituted by one or more (e.g., 1-7) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C 2-6 alkynyl and C 2-6 alkenyl; or furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, benzofuranyl, chromanyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, 2-oxo-2,3-dihydro-1H-benzo[d]imidazolyl, benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, phthalazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydrothieno[3,2-c]pyridyl, 5-oxo-6,7-dihydrothieno[3,2-d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, isoxazolo[4,5-c]pyridyl, isoxazolo[4,5-c]pyrimidinyl, isoxazolo[4,5-d]pyrimidinyl, 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, imidazo[2,1-b]thiazolyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, or 6,7-dihydro-5H-cyclopenta[f]thieno[2,3-d]pyrimidinyl, which is optionally substituted by one or more (e.g., 1 - 20) substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, C 2-6 alkynyl and C 2-6 substituted by substituents of alkenyl.

5. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof according to any one of claims 1 - 4, wherein R represents: -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4- or -(CH2)5-; wherein the above groups are optionally substituted with substituents selected from deuterium, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, halogen, amino, hydroxy, mercapto, cyano, oxo, C 2-6 alkynyl and C 2-6 alkenyl.

6. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof according to any one of claims 1-5, wherein X represents:

7. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof according to claim 1, which is selected from: 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-(4'-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4'-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluor-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluor-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluor-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-Dioxopiperidin-3-yl)-4-((4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-Dioxopiperidin-3-yl)-5-((4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 3-(5-((3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(4-Diphenylmethylpiperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)isoindoline-1,3-dione; 3-(5-(3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3,3-Difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3′,3′-Difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidine]-1′-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-Diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(2,3-Dichlorophenyl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(2,3-Dichlorophenyl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(2,3-Dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(2,3-Dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-thioisoindolin-2-yl)piperidine-2,6-dione; 1-(5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-diphenylmethylpiperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(4-diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-Diphenylmethylpiperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((3,3-Difluoro-4-(4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-(4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbonyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-((4′-Chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)dihydropyrimidine-2,4(1H,3H)-dione; 5-((4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)pyrimidine-2,4(1H,3H)-dione; 5-((4-(4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)-3,3-difluoropiperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)pyrimidine-2,4(1H,3H)-dione; 2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-5-((4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 1-(5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)pyrimidine-2,4(1H,3H)-dione; 5-((3,3-difluoro-4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)piperidin-1-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione; 1-(5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-1-oxoisoindolin-2-yl)pyrimidine-2,4(1H,3H)-dione; and 5-((3′,3′-difluoro-4-(6-fluorobenzo[d]isoxazol-3-yl)-[1,4′-bipiperidin]-1′-yl)methyl)-2-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)isoindoline-1,3-dione.

8. The compound of formula (I) or a salt, enantiomer, stereoisomer, solvate or polymorph thereof as claimed in any one of claims 1 to 7, which is a sulfate, hydrohalide (including hydrochloride, hydrobromide), maleate, sulfonate, citrate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, α-ketoglutarate, hippurate, D-glucuronate, D-gluconate, α-D-glucoheptonate, glycolate, mucate, L-ascorbate, orotate, picrate, glycinate, alaninate, arginate, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, mesylate, esylate, ethanedisulfonate, formate, acetate, 2,2-dichloroacetate, trimethylacetate, propionate, valerate, palmitate, triphenylacetate, 2-ethyl-succinate, iodate, nicotinate, L-pyroglutamate, L-prolinate, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecylenate, camphorate, camphorsulfonate, dodecylsulfonate, phosphate, thiocyanate, dihydrogenphosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalenesulfonate, glycolate, trifluoroacetate, terephthalate and p-toluenesulfonate of the compound of formula (I).

9. A pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 8, and at least one pharmaceutically acceptable carrier or excipient.

10. The pharmaceutical composition as claimed in claim 9, further comprising a second therapeutic agent, such as an anti-cancer agent.

11. The compound of formula (I) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 8, which is used for preventing or treating a disease or disorder related to cereblon protein.

12. The compound of formula (I) or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 8, which is used for preventing or treating a disease or disorder selected from the following: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure and diabetes.

13. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 11 or 12, wherein the disease or disorder is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; myelodysplastic diseases; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancers; neutropenia; leukemia, including acute myeloid leukemia, chronic myelogenous leukemia (CML), chronic granulocytic leukemia, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, anemia associated with leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (including acute B-lymphoblastic leukemia, T-lymphocytic leukemia, acute T-lymphocytic leukemia, chronic lymphocytic leukemia, lymphoblastic leukemia, T-lymphocytic leukemia, monocytic leukemia, myelomonocytic leukemia); lymphoma, including diffuse large B-cell lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, immunoblastic T-cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin lymphoma, refractory B-cell non-Hodgkin lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin lymphoma; Burkitt lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, squamous cell lung cancer, non-small cell lung cancer, small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; bowel cancer; glioma; astrocytoma; ovarian cancer; bronchial cancer; prostate cancer; breast cancer, including triple-negative breast cancer, sporadic breast cancer, ductal carcinoma of the breast, and patients with Cowden disease; pancreatic cancer; central nervous system cancer; neuroblastoma; glioma; Peripheral neuroepithelioma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumor; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcoma, including rhabdomyosarcoma, various fat-derived tumors, Ewing sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial cancer; basal cell carcinoma; oral squamous cell carcinoma; cholangiocarcinoma; bone cancer; cervical cancer; skin cancer; Richter syndrome (RS); septic syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent aphthous ulcer, Kawasaki disease, polymyositis / dermatomyositis, Sjogren's syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type I diabetes, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, acquired immunodeficiency syndrome (AIDS), COVID-19 novel coronavirus infection, Gram-negative bacterial infection, Gram-positive bacterial infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular diseases (such as coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure caused by cachexia and septic shock; and acute liver failure.

14. Use of a compound of formula (I) as claimed in any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as claimed in claim 9 or 10 for the manufacture of a medicament for the prevention or treatment of a disease or disorder associated with cereblon protein.

15. Use of a compound of formula (I) as claimed in any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as claimed in claim 9 or 10 for the manufacture of a medicament for the prevention or treatment of a disease or disorder selected from the group consisting of: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure and diabetes.

16. A method for treating or preventing a disease or disorder associated with cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described in any one of claims 1-8, or a pharmaceutical composition as described in claim 9 or 10.

17. A method for treating or preventing a disease or disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as described in any one of claims 1-8, or a pharmaceutical composition as described in claim 9 or 10, wherein the disease or disorder is selected from: tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure, and diabetes.

18. The use according to claim 14 or 15 or the method according to claim 16 or 17, wherein the disease or disorder is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; myelodysplastic diseases; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancers; neutropenia; leukemia, including acute myeloid leukemia, chronic myelogenous leukemia (CML), chronic granulocytic leukemia, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, anemia associated with leukemia, acute B-lymphoblastic leukemia, T-lymphocytic leukemia, acute T-lymphocytic leukemia, lymphoblastic leukemia, monocytic leukemia, myelomonocytic leukemia; lymphoma, including diffuse large B-cell lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, immunoblastic T-cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin lymphoma, refractory B-cell non-Hodgkin lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin lymphoma; Burkitt lymphoma (Burkitt's lymphoma); thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, squamous cell carcinoma of the lung, non-small cell lung cancer, small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; bowel cancer; glioma; astrocytoma; ovarian cancer; bronchial cancer; prostate cancer; breast cancer, including triple-negative breast cancer, sporadic breast cancer, ductal carcinoma of the breast, and patients with Cowden disease; pancreatic cancer; central nervous system cancer; neuroblastoma; glioma; Peripheral neuroepithelioma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumor; esophageal cancer; adenocarcinoma of the large intestine; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcoma, including rhabdomyosarcoma, various adipose-derived tumors, Ewing's sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; cholangiocarcinoma; Bone cancer; cervical cancer; skin cancer; Richter syndrome (RS); septic syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis, recurrent aphthous ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren's syndrome, atopic dermatitis, hidradenitis suppurativa, gout, type I diabetes, urticaria, inflammatory bowel disease (including Crohn's disease and ulcerative colitis); keratoconjunctivitis sicca; inflammatory diseases, including pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, acquired immunodeficiency syndrome (AIDS), COVID-19 novel coronavirus infection, Gram-negative bacterial infection, Gram-positive bacterial infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular diseases (such as coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure caused by cachexia and septic shock; and acute liver failure.

19. A process for preparing a compound of formula (I) as claimed in claim 1, which comprises reacting a compound of formula (M1) with a compound of formula (M2) to prepare a compound of formula (I): wherein the group R a1 、R a2 、R a3 、R a4 、(R a5 ) m 、Z1, Z2, Z3, Z4, Z5, (R d1 ) n1 、ring B, (R d2 ) n2 、R c 、ring C, m1, (R d3 ) n3 、ring D, and (R d4 ) n4 as defined in claim 1; The nitrogen-containing heterocycle A represents a 4- to 30-membered nitrogen-containing heterocycle (preferably, a 4- to 20-membered nitrogen-containing heterocycle; more preferably, a 4- to 15-membered nitrogen-containing heterocycle); R represents an optionally substituted straight-chain or branched C 1-5 alkylene group; LE represents Cl, Br, I, methanesulfonyloxy, p-toluenesulfonyloxy, o-nitrobenzenesulfonyl, C(O)Cl or COOH; and X of the compound of formula (I) a correspondingly represents a structure represented by the following general formula: wherein the nitrogen-containing heterocyclic group A is a divalent group obtained by removing the hydrogen atom on N from the nitrogen-containing heterocycle A, the nitrogen-containing heterocyclic group A represents a 4- to 30-membered nitrogen-containing heterocyclic group (preferably, a 4- to 20-membered nitrogen-containing heterocyclic group; more preferably, a 4- to 15-membered nitrogen-containing heterocyclic group), and (R d1 ) n1 , ring B, (R d2 ) n2 , R c , ring C, m1, (R d3 ) n3 , ring D, and (R d4 ) n4 as defined in any one of claims 1 - 8.

20. The method according to claim 19, wherein (1) when the group LE represents mesyloxy, the compound of formula (M1) is prepared by reacting the compound of formula (M3) with methanesulfonic anhydride or methanesulfonyl chloride: wherein the group R a1 、R a2 、R a3 、R a4 、(R a5 ) m 、Z1, Z2, Z3, Z4, Z5 and R are as defined in claim 19; or wherein (2) when the group LE represents Cl, Br or I, the compound of formula (M1) is prepared by subjecting the compound of formula (M3) to a halogenation reaction with a hydrohalic acid.

21. The method according to claim 20 or 21, wherein R of the compound of formula (M1), the compound of formula (I) and the compound of formula (M3) represents CH2.

22. The method according to claim 21, wherein the compound of formula (M3) is prepared by subjecting the compound of formula (M4) to a coupling reaction with (tributylstannyl)methanol under the catalysis of a palladium catalyst: wherein the group R a1 、R a2 、R a3 、R a4 、(R a5 ) m 、Z1, Z2, Z3, Z4 and Z5 are as defined in claim 19.

23. The method according to claim 22, wherein when Z5 in the compound of formula (M4) represents N, and Z1 represents C(O), CH2 or CD2, and Z2, Z3 and Z4 each independently represent C(O), the compound of formula (M4) is prepared by subjecting the compound of formula (M5) to a transaminolysis reaction with the compound of formula (M6): wherein the group R a1 、R a2 、R a3 、R a4 and (R a5 ) m are as defined in claim 19.

24. The method according to claim 22, wherein when Z1 in the compound of formula (M4) represents C(O), C(S), CH2 or CD2, Z2, Z3 and Z4 each independently represent C(O) or C(S), and at least one of Z1, Z2, Z3 and Z4 represents C(S), the compound of formula (M4) is prepared by subjecting the compound of formula (M7) to a sulfidation reaction with a sulfiding reagent: wherein Z6 of the compound of formula (M7) represents C(O), CH2 or CD2; and Group R a1 、R a2 、R a3 、R a4 and (R a5 ) m as defined in claim 19.

25. The method according to claim 24, wherein the sulfurizing reagent comprises carbon disulfide, hexamethyldisilathiane, sulfur, thiourea, hydrogen sulfide, phosphorus pentasulfide, Lawesson's Reagent, Belleau's reagent, and Davy's reagent.

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