Compound with glutarimido isoindolinone skeleton

Abstract

The invention discloses a compound which is based on a glutarimido isoindolinone skeleton and is shown in a formula (I) or a salt, an enantiomer, a stereoisomer, a solvate, an isotope-enriched analogue, a prodrug or a polymorphic substance of the compound and application of the compound to treatment and prevention of cerebron protein related diseases or symptoms including tumors or cancers.

Description

Compounds with glutarimidoisoindolinone skeleton Technical Field

[0001] The present invention relates to a compound represented by formula (I) or its salt, enantiomer, stereoisomer, solvate, isotope-enriched analog, prodrug or polymorph, and to its use in treating diseases or disorders associated with cereblon protein. Background Art

[0002] Phthalimide immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, are highly effective in treating hematologic malignancies 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 extremely challenging. 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 CC-122, CC-220, CC-90009, CC-99282, and CC-92480 from Bristol-Myers Squibb (BMS), DKY709 from Novartis, and CFT7455 from C4 Therapeutics, all currently undergoing clinical trials. The 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), and translation factor GSPT1. The degradation of these protein substrates enables the molecular glue to exert pharmacological activities such as immunomodulatory, anti-inflammatory, and anti-tumor activities. The structural novelty of the molecular glue candidates currently designed and developed is very limited, so the design and development of molecular glue compounds with novel and diverse scaffolds has become a research hotspot in this field.

[0003] Therefore, there is an urgent need for a series of novel CRBN E3 ubiquitin ligase ligand scaffolds and their application in the development of effective molecular glue degraders for the treatment and / or prevention of diseases or conditions mediated by or associated with degraded proteins.

[0004] Summary of the Invention

[0005] In view of the shortcomings of the prior art, one of the objectives of the present invention is to provide a series of novel compounds based on the glutarimidoisoindolinone skeleton or their salts, enantiomers, stereoisomers, solvates, isotopically enriched analogs, prodrugs or polymorphs, which can effectively treat diseases including tumors, autoimmune diseases, etc., thereby addressing unmet clinical needs.

[0006] In some embodiments, the present invention provides a compound represented by formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof:

[0007]

[0008] in,

[0009] Indicates a single bond or a double bond;

[0010] X represents CH2 or C(=O);

[0011] (Y) m represents that the benzene ring is optionally substituted by m Y groups, Y represents deuterium, C1-C4 alkyl, halogen or halogenated C1-C2 alkyl, and m represents an integer of 0, 1, 2 or 3;

[0012] L represents a methylene group, or a linear or branched C2-C6 alkylene group, wherein the methylene group or the linear or branched C2-C6 alkylene group may be optionally substituted by one or more of the following groups: deuterium, halogen, C 1- C3 alkyl, C1-C3 alkoxy or C1-C3 haloalkyl;

[0013] R 1 Indicates bond, O, N(R a )、N(R a )S(O)2、S(O)2N(R a ), a nitrogen-containing heterocyclic group or a nitrogen-containing heterocyclic group subunit, R a represents hydrogen, deuterium or C1-C6 alkyl, and the nitrogen-containing heterocyclylene group or nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy;

[0014] R 2 represents heteroarylene, heteroarylene, heterocyclylene, (CH2) n -arylene or (CH2) n-cycloalkylene, wherein n represents an integer of 0, 1 or 2, and the heteroarylene group, the heteroarylene group, the heterocyclylene group, the arylene group or the cycloalkylene group is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy;

[0015] R 3 Represents hydrogen, deuterium, and SR b 、R b , C1-C6 haloalkyl, cycloalkyl or nitrogen-containing heterocyclic group, R b represents an aryl group, wherein the aryl group, the cycloalkyl group or the nitrogen-containing heterocyclic group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy;

[0016] Among them, when When it represents a double bond, R 1 Represents a nitrogen-containing heterocyclic subunit, R 2 represents a heteroaryl subunit;

[0017] when When it represents a single bond, R 1 Indicates bond, O, N(R a )、N(R a )S(O)2、S(O)2N(R a ) or a nitrogen-containing heterocyclic group, R 2 represents heteroarylene, heterocyclylene, (CH2) n -arylene or (CH2) n -cycloalkylene.

[0018] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein examples of the methylene or linear or branched C2-C6 alkylene represented by L include but are not limited to: -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5- or -(CH2)6-, wherein the methylene or the linear or branched C2-C6 alkylene may be optionally substituted by one or more of the following groups: deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), C 1-C3 alkyl (e.g. methyl, ethyl or propyl), C1-C3 alkoxy (e.g. methoxy, ethoxy or propoxy) or C1-C3 haloalkyl (e.g. F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- and CH2ClCH2-).

[0019] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, has the following structure:

[0020] in, X, Y, L, m, R 1 、R 2 and R 3 As defined above.

[0021] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, has the following structure:

[0022] in, X, Y, L, m, R 2 and R 3 As defined above;

[0023] R c represents deuterium, hydrogen or C1-C6 alkyl;

[0024] Ring A represents a nitrogen-containing heterocyclylene group or a nitrogen-containing heterocyclyl subunit, and the nitrogen-containing heterocyclylene group or the nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0025] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, has the following structure:

[0026] in, Y, L, m, R 2 and R3 As defined above;

[0027] R c represents deuterium, hydrogen or C1-C6 alkyl;

[0028] Ring A represents a nitrogen-containing heterocyclylene group or a nitrogen-containing heterocyclyl subunit, and the nitrogen-containing heterocyclylene group or the nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0029] In some embodiments, the compound of formula (I) disclosed herein or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein Y represents D, F, Cl, Br, I, CF3, CH2F, CHF2, CH2Cl, CHCl2, CF2CF3, CHFCF3, CF2CHF2, CHFCHF2, CH2CF3 or CH2CH2Cl.

[0030] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 1 is Ring A, which represents a nitrogen-containing heterocyclylene group or a nitrogen-containing heterocyclyl subunit, wherein the nitrogen-containing heterocyclylene group or the nitrogen-containing heterocyclyl subunit is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0031] In some embodiments, the compounds of formula (I) disclosed herein, or their salts, enantiomers, stereoisomers, solvates, isotopically enriched analogs, prodrugs or polymorphs, wherein examples of the nitrogen-containing heterocyclic group represented by ring A include, but are not limited to, 4- to 30-membered nitrogen-containing heterocyclic groups, 4- to 20-membered nitrogen-containing heterocyclic groups, 4- to 15-membered nitrogen-containing heterocyclic groups, 5- to 30-membered nitrogen-containing heterocyclic groups, 5- to 20-membered nitrogen-containing heterocyclic groups or 5- to 15-membered nitrogen-containing heterocyclic groups, wherein the nitrogen-containing heterocyclic group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0032] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein examples of the nitrogen-containing heterocyclic group represented by ring A include, but are not limited to, piperazinyl, piperidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, morpholinyl, thiomorpholinyl, diazacycloheptyl, diazabicyclo[3.1.1]heptyl, diazabicyclo[2.2.1]heptyl , diazabicyclo[2.2.2]octanyl, diazabicyclo[3.2.1]octanyl, or azaspirocyclyl (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered azaspirocyclyl), wherein the nitrogen-containing heterocyclyl is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0033] In some embodiments, the compounds of formula (I) disclosed herein or their salts, enantiomers, stereoisomers, solvates, isotopically enriched analogs, prodrugs or polymorphs, wherein examples of the nitrogen-containing heterocyclyl subunit represented by ring A include but are not limited to: a 4- to 30-membered nitrogen-containing heterocyclyl subunit, a 4- to 20-membered nitrogen-containing heterocyclyl subunit, a 4- to 15-membered nitrogen-containing heterocyclyl subunit, a 5- to 30-membered nitrogen-containing heterocyclyl subunit, a 5- to 20-membered nitrogen-containing heterocyclyl subunit or a 5- to 15-membered nitrogen-containing heterocyclyl subunit, wherein the nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0034] In some embodiments, the compound of formula (I) disclosed herein or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein examples of the nitrogen-containing heterocyclic subunit represented by ring A include but are not limited to: piperazinyl subunit, piperidinyl subunit, pyrrolidinyl subunit, imidazolidinyl subunit, pyrazolidinyl subunit, oxazolidinyl subunit, thiazolidinyl subunit, morpholinyl subunit, thiomorpholinyl subunit, diazepanyl subunit, diazepanyl subunit, Heterobicyclo[3.1.1]heptanyl subunit, diazabicyclo[2.2.1]heptanyl subunit, diazabicyclo[2.2.2]octanyl subunit, diazabicyclo[3.2.1]octanyl subunit or azaspiro subunit, wherein the nitrogen-containing heterocyclyl subunit is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, sulfhydryl, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0035] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 1 Examples of the ring A include but are not limited to:

[0036] The symbol * indicates the connection point with L.

[0037] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2 represents a heteroaryl group, a heteroarylene group, a heterocyclylene group, an arylene group, a cycloalkylene group, -CH2-arylene group, -CH2-cycloalkylene group, -(CH2)2-arylene group or -(CH2)2-cycloalkylene group, wherein the heteroaryl group, the heteroarylene group, the heterocyclylene group, the arylene group or the cycloalkylene group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0038] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2represents a heteroaryl subunit, examples of which are not limited to a 7- to 30-membered heteroaryl subunit, a 7- to 25-membered heteroaryl subunit, a 7- to 20-membered heteroaryl subunit, a 7- to 15-membered heteroaryl subunit, an 8- to 30-membered heteroaryl subunit, an 8- to 25-membered heteroaryl subunit, an 8- to 20-membered heteroaryl subunit, an 8- to 15-membered heteroaryl subunit, a 9- to 30-membered heteroaryl subunit, a 9- to 25-membered heteroaryl subunit, a 9- to 20-membered heteroaryl subunit, a 9- to 15-membered heteroaryl subunit, a 10- to 30-membered heteroaryl subunit, a 10- to 25-membered heteroaryl subunit, a 10- to 20-membered heteroaryl subunit, or a 10- to 15-membered heteroaryl subunit, which is optionally substituted with one or more of deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0039] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2 Examples of heteroaryl subunits include, but are not limited to, chromanyl subunits or 2,3-dihydroquinolin-4(1H)-yl subunits, which are optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0040] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2 Examples of heteroarylene groups include, but are not limited to, a 5- to 30-membered heteroarylene, a 5- to 25-membered heteroarylene, a 5- to 20-membered heteroarylene, a 5- to 15-membered heteroarylene, a 6- to 30-membered heteroarylene, a 6- to 25-membered heteroarylene, a 6- to 20-membered heteroarylene, a 6- to 15-membered heteroarylene, a 7- to 30-membered heteroarylene, a 7- to 25-membered heteroarylene, a 7- to 20-membered heteroarylene, a 7- to 15-membered heteroarylene, an 8- to 30-membered heteroarylene, an 8- to 25-membered heteroarylene, an 8- to 20-membered heteroarylene, or an 8- to 15-membered heteroarylene, optionally substituted with one or more of deuterium, hydroxy, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0041] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2Examples of heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, indazolylene, quinolylene, isoquinolylene, quinazolinylene, triazinylene, isoxazolo[4,5-c]pyridylene, pyrrolo[2,3-b]pyridylene pyrimidine, benzothiazolylene, benzofuranylene, isobenzofuranylene, benzothiophenylene, benzoimidazolylene, 2,3-dihydro-1H-benzo[d]imidazolylene, pyrrolo[2,3-b]pyridinylene, chromanylene, 6,7-dihydrothieno[3,2-d]pyrimidinylene, acridinylene, benzoindolylene, carbazolylene, dibenzofuranylene, xanthenylene, 3,4-dihydroquinolinylene, 2,3-dihydro-4H-benzo[b] [1,4]oxazinediyl, benzodihydropyranyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, dihydrothieno[3,2-d]pyrimidinyl, 5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazinyl, dihydrothieno[3 [1,5-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]thiazolylene or benzo[2,1-b]thiazolylene. The heteroarylene group is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0042] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2Examples of heterocyclylene include, but are not limited to, 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 20-membered, or 7- to 15-membered heterocyclylene. In some embodiments, examples of heterocyclylene include 4- to 30-membered monocyclic heterocyclylene, 4- to 25-membered monocyclic heterocyclylene, 4- to 20-membered monocyclic heterocyclylene, 4- to 15-membered monocyclic heterocyclylene, 5- to 30-membered subbridged heterocyclylene, 5- to 20-membered subbridged heterocyclylene, 5- to 15-membered subbridged heterocyclylene, 6- to 20-membered subbridged heterocyclylene, 6- to 15-membered subbridged heterocyclylene, 7- to 30-membered subbridged heterocyclylene, 7- to 20-membered subbridged heterocyclylene, 7- to 15-membered subbridged heterocyclylene, 5- to 30-membered subbridged heterocyclylene, , 5- to 20-membered fused heterocyclyl, 5- to 15-membered fused heterocyclyl, 6- to 20-membered fused heterocyclyl, 6- to 15-membered fused heterocyclyl, 7- to 30-membered fused heterocyclyl, 7- to 20-membered fused heterocyclyl, 7- to 15-membered fused heterocyclyl, 5- to 30-membered spiro heterocyclyl, 5- to 20-membered spiro heterocyclyl, 5- to 15-membered spiro heterocyclyl, 6- to 20-membered spiro heterocyclyl, 6- to 15-membered spiro heterocyclyl, 7- to 30-membered spiro heterocyclyl, 7- to 20-membered spiro heterocyclyl, or 7- to 15-membered spiro heterocyclyl. The heterocyclylene radical is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, sulfhydryl, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0043] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2Examples of heterocyclylene groups include, but are not limited to, azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, piperidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, tetrahydrothiophenylene, thiomorpholinylene, dioxanylene, azetidin-1-ylidene, 3,6-dihydropyridin-1(2H)-ylidene, 1,4-diazacycloheptane-1-ylidene, 3,6-diazabicyclo[3.1.1]heptane-6-ylidene, 3,6-diazabicyclo[3.1.1]heptane-3-ylidene, 2,5-diazabicyclo [2.2.1]heptane-2-ylidene, 2,5-diazabicyclo[2.2.2]octane-2-ylidene, 3,8-diazabicyclo[3.2.1]octane-3-ylidene, 3,8-diazabicyclo[3.2.1]octane-8-ylidene and azaspirocyclyl (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered azaspirocyclyl) which is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0044] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2 Indicates (CH2) n -arylene, n represents an integer of 0, 1 or 2. Examples of arylene include, but are not limited to: C 5-30 Arylene, C 5-20 Arylene, C 5-15 Arylene, C 6-30 Arylene, C 6-20 Arylene or C 6-15 In some embodiments, (CH2) n Examples of -arylene groups include, but are not limited to: C 5-30 Arylene, C 5-20 Arylene, C 5-15 Arylene, C 6-30 Arylene, C 6-20 Arylene, C 6-15 Arylene, C 7-30 Arylene, C 7-20 Arylene, C 7-15 Arylene, C 8-30 Arylene, C 8-20 Arylene, C 8-15 Arylene, CH2-(C 5-30arylene), CH2-(C 5-20 arylene), CH2-(C 5-15 arylene), CH2-(C 6-30 arylene), CH2-(C 6-20 arylene), CH2-(C 6-15 arylene), CH2-(C 7-30 arylene), CH2-(C 7-20 arylene), CH2-(C 7-15 arylene), CH2-(C 8-30 arylene), CH2-(C 8-20 arylene), CH2-(C 8-15 arylene), CH2-CH2-(C 5-30 arylene), CH2-CH2-(C 5-20 arylene), CH2-CH2-(C 5-15 arylene), CH2-CH2-(C 6-30 arylene), CH2-CH2-(C 6-20 arylene), CH2-CH2-(C 6-15 arylene), CH2-CH2-(C 7-30 arylene), CH2-CH2-(C 7-20 arylene), CH2-CH2-(C 7-15 arylene), CH2-CH2-(C 8-30 arylene), CH2-CH2-(C 8-20 Arylene) or CH2-CH2-(C 8-15 The arylene group is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0045] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2 Indicates (CH2) n -arylene, n represents an integer of 0, 1 or 2, examples of which include but are not limited to phenylene, naphthylene, CH2-phenylene, CH2-naphthylene, CH2-CH2-phenylene or CH2-CH2-naphthylene, wherein the phenylene or naphthylene is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0046] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2 Indicates (CH2) n -cycloalkylene, n represents an integer of 0, 1 or 2. Examples of cycloalkylene include, but are not limited to: C3-C 30 Cycloalkylene, C3-C 20 Cycloalkylene, C3-C 15 Cycloalkylene, C4-C 30 Cycloalkylene, C4-C 20 Cycloalkylene, C4-C 15 Cycloalkylene and C3-C 12 Cycloalkylene. (CH2) n Examples of -cycloalkylene include, but are not limited to: 3-30 Monocyclic cycloalkylene, C 3-20 Monocyclic cycloalkylene, C 3-15 Monocyclic cycloalkylene, C 4-15 Monocyclic cycloalkylene, C5-C 15 Monocyclic cycloalkylene, C7-C 30 Monocyclic cycloalkylene, C7-C 20 Monocyclic cycloalkylene, C7-C 15 Monocyclic cycloalkylene, C5-C 30 Sub-bridged cycloalkyl, C5-C 20 Sub-bridged cycloalkyl, C5-C 15 Sub-bridged cycloalkyl, C6-C 30 Sub-bridged cycloalkyl, C6-C 20 Sub-bridged cycloalkyl, C6-C 15 Sub-bridged cycloalkyl, C7-C 30 Sub-bridged cycloalkyl, C7-C 20 Sub-bridged cycloalkyl, C7-C 15 Sub-bridged cycloalkyl, C5-C 30 Fused cycloalkyl, C5-C 20 Fused cycloalkyl, C5-C 15 Fused cycloalkyl, C6-C 30 Fused cycloalkyl, C6-C 20 Fused cycloalkyl, C6-C 15 Fused cycloalkyl, C7-C 30 Fused cycloalkyl, C7-C 20 Fused cycloalkyl, C7-C 15 Fused cycloalkyl, C5-C 20 Spirocycloalkylene, C5-C 20 Spirocycloalkylene, C5-C 15 Spirocycloalkylene, C6-C 30Spirocycloalkylene, C6-C 20 Spirocycloalkylene, C6-C 15 Spirocycloalkylene, C7-C 30 Spirocycloalkylene, C7-C 20 Spirocycloalkylene, C7-C 15 Spirocycloalkylene, CH2-(C 3-30 monocyclic cycloalkylene), CH2-(C 3-20 monocyclic cycloalkylene), CH2-(C 3-15 monocyclic cycloalkylene), CH2-(C 4-15 monocyclic cycloalkylene), CH2-(C 5-15 monocyclic cycloalkylene), CH2-(C 7-30 monocyclic cycloalkylene), CH2-(C 7-20 monocyclic cycloalkylene), CH2-(C 7-15 monocyclic cycloalkylene), CH2-(C 5-30 cycloalkylene), CH2-(C 5-20 cycloalkylene), CH2-(C 5-15 cycloalkylene), CH2-(C 6-30 cycloalkylene), CH2-(C 6-20 cycloalkylene), CH2-(C 6-15 cycloalkylene), CH2-(C 7-30 cycloalkylene), CH2-(C 7-20 cycloalkylene), CH2-(C 7-15 cycloalkylene), CH2-(C 5-30 fused cycloalkylene), CH2-(C 5-20 fused cycloalkylene), CH2-(C 5-15 fused cycloalkylene), CH2-(C 6-30 fused cycloalkylene), CH2-(C 6-20 fused cycloalkylene), CH2-(C 6-15 fused cycloalkylene), CH2-(C 7-30 fused cycloalkylene), CH2-(C 7-20 fused cycloalkylene), CH2-(C 7-15 fused cycloalkylene), CH2-(C 5-30 Spirocycloalkylene), CH2-(C 5-20 Spirocycloalkylene), CH2-(C 5-15 Spirocycloalkylene), CH2-(C 6-30 Spirocycloalkylene), CH2-(C 6-20 Spirocycloalkylene), CH2-(C 6-15 Spirocycloalkylene), CH2-(C 7-30 Spirocycloalkylene), CH2-(C7-20 Spirocycloalkylene), CH2-(C 7-15 Spirocycloalkylene), CH2-CH2-(C 3-30 monocyclic cycloalkylene), CH2-CH2-(C 3-20 monocyclic cycloalkylene), CH2-CH2-(C 3-15 monocyclic cycloalkylene), CH2-CH2-(C 4-15 monocyclic cycloalkylene), CH2-CH2-(C 5-15 monocyclic cycloalkylene), CH2-CH2-(C 7-30 monocyclic cycloalkylene), CH2-CH2-(C 7-20 monocyclic cycloalkylene), CH2-CH2-(C 7-15 monocyclic cycloalkylene), CH2-CH2-(C 5-30 bridged cycloalkyl), CH2-CH2-(C 5-20 bridged cycloalkyl), CH2-CH2-(C 5-15 bridged cycloalkyl), CH2-CH2-(C 6-30 (C-( ... 6-20 bridged cycloalkyl), CH2-CH2-(C 6-15 bridged cycloalkyl), CH2-CH2-(C 7-30 (C-( ... 7-20 bridged cycloalkyl), CH2-CH2-(C 7-15 bridged cycloalkyl), CH2-CH2-(C 5-30 fused cycloalkylene), CH2-CH2-(C 5-20 fused cycloalkylene), CH2-CH2-(C 5-15 fused cycloalkylene), CH2-CH2-(C 6-30 fused cycloalkylene), CH2-CH2-(C 6-20 fused cycloalkylene), CH2-CH2-(C 6-15 fused cycloalkylene), CH2-CH2-(C 7-30 fused cycloalkylene), CH2-CH2-(C 7-20 fused cycloalkylene), CH2-CH2-(C 7-15 fused cycloalkylene), CH2-CH2-(C 5-30 Spirocycloalkylene), CH2-CH2-(C 5-20 Spirocycloalkylene), CH2-CH2-(C 5-15 Spirocycloalkylene), CH2-CH2-(C 6-30 Spirocycloalkylene), CH2-CH2-(C 6-20 Spirocycloalkylene), CH2-CH2-(C6-15 Spirocycloalkylene), CH2-CH2-(C 7-30 Spirocycloalkylene), CH2-CH2-(C 7-20 Spirocycloalkylene) or CH2-CH2-(C 7-15 Spirocycloalkylene), which is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0047] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 2 Indicates (CH2) n -cycloalkylene, n represents an integer of 0, 1 or 2, examples of which include but are not limited to: cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, C5-C 15 Spirocyclylene, adamantylene, noradamantylene, bornylene, bicyclo[2,2,1]heptanylene, bicyclo[2,2,1]heptenylene, CH2-cyclopropylene, CH2-cyclobutylene, CH2-cyclopentylene, CH2-cyclopentenylene, CH2-cyclohexylene, CH2-cyclohexenylene, CH2-cycloheptylene, CH2-cyclooctylene, CH2-decalinylene, CH2-(octahydropentalenylene), CH2-(octahydro-1H-indenylene), CH2-(C5-C 15 spirocyclylene), CH2-adamantylene, CH2-noradamantylene, CH2-bornylene, CH2-(bicyclo[2,2,1]heptanylene), CH2-(bicyclo[2,2,1]heptenylene), CH2-CH2-cyclopropylene, CH2-CH2-cyclobutylene, CH2-CH2-cyclopentylene, CH2-CH2-cyclopentenylene, CH2-CH2-cyclohexylene, CH2-CH2-cyclohexenylene, CH2-CH2-cycloheptylene, CH2-CH2-cyclooctylene, CH2-CH2-decalinylene, CH2-CH2-(octahydropentalenylene), CH2-CH2-(octahydro-1H-indenylene), CH2-CH2-(C5-C 15spirocyclylene), CH2-CH2-adamantylene, CH2-CH2-noradamantylene, CH2-CH2-bornylene, CH2-CH2-(bicyclo[2,2,1]heptanylene) or CH2-CH2-(bicyclo[2,2,1]heptenylene), the cycloalkylene group being optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0048] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 3 Indicates SR b or R b , where R b represents an aryl group, examples of which include but are not limited to: C 5-30 Aryl, C 5-20 Aryl, C 5-15 Aryl, C 6-30 Aryl, C 6-20 Aryl, C 6-15 Aryl, C 7-30 Aryl, C 7-20 Aryl, C 7-15 Aryl, C 8-30 Aryl, C 8-20 Aryl and C 8-15 Aryl. SR b Examples include, but are not limited to: S-(C 5-30 aryl), S-(C 5-20 Aryl), S-(C 5-15 Aryl), S-(C 6-30 Aryl), S-(C 6-20 Aryl), S-(C 6-15 Aryl), S-(C 7-30 Aryl), S-(C 7-20 Aryl), S-(C 7-15 Aryl), S-(C 8-30 aryl), S-(C 8-20 Aryl) or S-(C 8-15 aryl), which may be optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0049] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R3 Indicates SR b or R b , where R b represents an aryl group, R 3 Examples include, but are not limited to, phenyl, naphthyl, S-phenyl or S-naphthyl, wherein the aryl group is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0050] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 3 Examples of C1-C6 haloalkyl groups include, but are not limited to, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-.

[0051] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 3 Examples of cycloalkyl groups include, but are not limited to: C 3-30 Monocyclic cycloalkyl, C 3-20 Monocyclic cycloalkyl, C 3-15 Monocyclic cycloalkyl, C 4-15 Monocyclic cycloalkyl, C 5-15 Monocyclic cycloalkyl, C 7-30 Monocyclic cycloalkyl, C 7-20 Monocyclic cycloalkyl, C 7-15 Monocyclic cycloalkyl, C 5-30 Bridged cycloalkyl, C 5-20 Bridged cycloalkyl, C 5-15 Bridged cycloalkyl, C 6-30 Bridged cycloalkyl, C 6-20 Bridged cycloalkyl, C 6-15 Bridged cycloalkyl, C 7-30 Bridged cycloalkyl, C 7-20 Bridged cycloalkyl, C 7-15 Bridged cycloalkyl, 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, C7-15 Condensed cycloalkyl, 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 or C 7-15 Spirocycloalkyl, the cycloalkyl being optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0052] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 3 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, C5-C 15 Spirocyclyl, adamantyl, noradamantyl, bornyl, bicyclo[2,2,1]heptyl, bicyclo[2,2,1]heptenyl, the cycloalkyl group being optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0053] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 3 Examples of nitrogen-containing heterocyclic groups include, but are not limited to, a 4- to 20-membered nitrogen-containing heterocyclic group, a 4- to 15-membered nitrogen-containing heterocyclic group, a 5- to 20-membered nitrogen-containing heterocyclic group, or a 5- to 15-membered nitrogen-containing heterocyclic group, wherein the nitrogen-containing heterocyclic group is optionally substituted with one or more of the following groups: hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0054] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein R 3Examples of nitrogen-containing heterocyclic groups include, but are not limited to, piperazinyl, piperidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, morpholinyl, thiomorpholinyl, diazacycloheptyl, diazabicyclo[3.1.1]heptyl, diazabicyclo[2.2.1]heptyl, diazabicyclo[2.2.2]octyl, diazabicyclo[3.2.1]octyl, or azaspirocyclic groups, which are optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy.

[0055] In some embodiments, the compound of formula (I) disclosed herein, or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, when R 1 When it is O, NH, NHS(O)2 or S(O)2NH, R 2 Indicates -(CH2) n -cycloalkylene, R 3 Represents hydrogen, the cycloalkylene group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy, and the cycloalkylene group is as defined above and is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

[0056] In some embodiments, the compound of formula (I) disclosed herein or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, when When it represents a double bond, R 1 is a piperidinyl subunit or an azetidinyl subunit, R 2 is a chromanyl subunit, R 3 For hydrogen.

[0057] In some embodiments, the compound of formula (I) disclosed herein or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, when When it represents a double bond, -R 1 -R 2 - represents the following structure:

[0058] Those skilled in the art should understand that the present invention covers compounds obtained by any combination of the various embodiments, and embodiments obtained by combining the technical features or preferred technical features in one embodiment with the technical features or preferred technical features of another embodiment are also included in the scope of the present invention.

[0059] In some embodiments, provided are compounds of the following Table 1 and their salts (including pharmaceutically acceptable salts, such as their hydrochloride salts), enantiomers, stereoisomers, solvates, isotopically enriched analogs, prodrugs, or polymorphs:

[0060] Table 1 Compounds disclosed in the present invention

[0061] In some embodiments, the present invention also provides polymorphic forms of the disclosed compounds or salts of the disclosed compounds of the present invention. The salts of the disclosed compounds of the present invention can be pharmaceutically acceptable salts, including but not limited to hydrochloride, hydrobromide, sulfate, citrate, maleate, sulfonate, methanesulfonate, ethanesulfonate, edisylate, formate, acetate, 2,2-dichloroacetate, pivalate, propionate, valerate, 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, glycine The compounds disclosed herein may be present in pharmaceutically acceptable solvents such as water, ethanol, or the like, and may be present in the form of unsolvated or solvated compounds.

[0062] In some embodiments, the compounds disclosed herein can be made into prodrugs or prodrugs. Prodrugs can be converted into parent drugs in the body and exert their effects. In some embodiments, isotope-labeled compounds disclosed herein are also provided. Examples of isotopes include deuterium (D or 2 H).

[0063] In some embodiments, the present invention provides a pharmaceutical composition comprising as an active ingredient a compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, and at least one pharmaceutically acceptable carrier.

[0064] 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 glycols; esters, such as ethyl oleate and ethyl laurate; agar; buffers, such as magnesium hydroxide and aluminum hydroxide; phosphate buffers, surfactants; polyethylene oxide, polyvinyl pyrrolidone, polyacrylamide, poloxamers; and other nontoxic, compatible substances used in pharmaceutical formulations.

[0065] The pharmaceutical composition disclosed in the present invention further comprises at least one second therapeutic agent for treating tumors or cancer. The second therapeutic agent can be used in combination with the compound of formula (I) disclosed in the present invention to treat tumors or cancer, including but not limited to chemotherapeutic agents, immunotherapeutic agents, gene therapy agents, etc.

[0066] In some embodiments, the tumor or cancer 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 (AML), chronic myeloid leukemia (CML), chronic myeloid leukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, and leukemia. Related anemia, monocytic leukemia, myelomonocytic leukemia, T-lymphocytic leukemia, acute T-lymphocytic 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; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung cancer, small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; glioblastoma astrocytoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, sporadic breast cancer, Patients with ductal carcinoma and Cowden disease; pancreatic cancer; central nervous system cancers; neuroblastoma; glioma; peripheral neuroepithelial tumor; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumor; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcomas, including rhabdomyosarcoma, various adipose tumors, Ewing sarcoma / primitive neuroectodermal tumors (Ewing / PNETs), and leiomyosarcoma; urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; bile duct cancer; bone cancer; cervical cancer; skin cancer; or Richter syndrome (RS).

[0067] In some embodiments, the pharmaceutical composition disclosed in the present invention comprising the 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 conventional, dispersible, chewable, orally rapidly disintegrating or rapidly dissolving preparations, or sustained-release capsules or controlled-release capsules according to needs using the compound represented by formula (I).

[0068] In some embodiments, the present invention provides a test kit or medicine box comprising a compound represented by formula (I) of the present invention or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, or a pharmaceutical composition of the present invention. The test kit or medicine box may include packaging or containers. The packaging or containers include, but are 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 test kit or medicine box may include product instructions for use.

[0069] In some embodiments, the present invention provides a compound represented by the formula (I) or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, which is used to prepare a medicament for treating a disease or condition. In some embodiments, the disease or condition includes a disease or condition associated with cereblon protein. In some embodiments, the disease or condition includes but is not limited to: tumor or cancer, 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 or diabetes.

[0070] In some embodiments, the present invention further provides a method for treating a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) disclosed herein or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, or the pharmaceutical composition disclosed herein. In some embodiments, the disease or condition includes a disease or condition associated with cereblon protein. In some embodiments, the disease or condition includes, but is not limited to, tumors or cancer, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure or diabetes.

[0071] 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 (AML), chronic myeloid leukemia (CML), chronic myeloid leukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, anemia associated with leukemia, monocytic leukemia, myelomonocytic leukemia, T-lymphocytic leukemia, acute T-lymphocytic 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 Patients with thyroid cancer (including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer) are eligible for this treatment. Patients with thyroid cancer (including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer) are eligible for this treatment. Patients with thyroid cancer (including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer) are eligible for this treatment. Patients with thyroid cancer (including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer) are eligible for this treatment. Patients with thyroid cancer (including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer) are eligible for this treatment. Patients with thyroid cancer (including adenocarcinoma, squamous cell carcinoma, non-small cell lung cancer, and small cell lung cancer) are eligible for this treatment. 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 (Richter syndrome) syndrome, RS); sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjögren's syndrome, atopic dermatitis; keratoconjunctivitis sicca;Inflammatory diseases, including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, HIV / 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 (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure caused by cachexia and septic shock; and acute liver failure.

[0072] In the method for treating a disease or condition in a subject, a therapeutically effective amount of the compound of formula (I) disclosed in the present invention or the pharmaceutical composition disclosed in the present invention is administered to the subject by at least one administration method selected from 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.

[0073] 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 down (mitigate) the development of an undesirable disease or condition (e.g., a tumor). The beneficial or desired clinical results disclosed herein 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.

[0074] A "therapeutically effective amount" of a compound disclosed herein depends on a variety of factors, including the activity of the particular compound employed, 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, co-administration of medications, and the progression of the disease or condition being treated in the patient. Those skilled in the art will be able to determine an appropriate dosage based on these and other factors.

[0075] The patients or subjects for treatment mentioned above refer to animals, such as mammals, including but not limited to primates (such as humans), cows, sheep, goats, horses, dogs, cats, rabbits, guinea pigs, rats, mice, etc.

[0076] Terminology and Definitions

[0077] Unless stated otherwise, the following words, phrases and symbols used in this specification and claims shall generally have the following meanings.

[0078] In the present invention, the term "compound" includes all stereoisomers, geometric isomers, tautomers and isotopes.

[0079] The compounds of the present invention may be asymmetric, for example, having one or more stereoisomers. Unless otherwise indicated, all stereoisomers are included, such as enantiomers and diastereomers. Compounds of the present invention containing asymmetric carbon atoms can be isolated in optically pure or racemic forms. Optically pure forms can be resolved from racemic mixtures or synthesized by using chiral starting materials or chiral reagents.

[0080] The compounds of the present invention also include tautomeric forms, which result from the exchange of a single bond with an adjacent double bond accompanied by the migration of a proton.

[0081] Isotopes in the present invention refer to two or more atoms of the same chemical element with the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium.

[0082] In the present invention, the term "stereoisomer" refers to a compound having the same chemical structure but different arrangements of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers, (cis / trans) isomers, atropisomers, and the like. Among them, enantiomers refer to two isomers of a compound that cannot be superimposed but are mirror images of each other, and diastereomers refer to stereoisomers with two or more chiral centers and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting points, boiling points, spectral properties and reactivity. Diastereomeric mixtures can be separated by high-resolution analytical operations such as electrophoresis and chromatography, for example HPLC.

[0083] 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.

[0084] In the present invention, the nomenclature used (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 in conjunction with the disclosure described in the present invention have the same meanings as those skilled in the art generally understand. 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 represent at least a second or more.

[0085] It should be understood that whenever the present disclosure uses the terms "including" or "comprising" to describe various aspects, other similar aspects described by "consisting of" and / or "consisting essentially of" are also provided.

[0086] In the present invention, the term "represents a bond" means that it is a bond linker (ie, it does not exist). For example, the term "R 1 "Represents a key" means R 1 is a bond linker. In other words, when R 1 When the group R of the formula (I) represents a bond, 2 Directly connected to the L group in the structure of formula (I).

[0087] In the present invention, a bond broken by a wavy line shows the point of attachment of the depicted group to the rest of the molecule.

[0088] In the present invention, the terms "optionally substituted with" and "unsubstituted or substituted" are used interchangeably. The term "substituted" generally means that one or more hydrogen atoms in the referenced structure are replaced with the same or different substituents of the specified substituent.

[0089] In the present invention, the term "halogen" used alone or in combination refers to fluorine, chlorine, bromine or iodine.

[0090] In the present invention, the term "hydroxyl" refers to -OH.

[0091] In the present invention, the term "sulfonyl" refers to -SO2-.

[0092] In the present invention, the term "oxo" or "oxo group" refers to =O.

[0093] In the present invention, the term "alkyl" used alone or in combination refers to a straight-chain or branched saturated aliphatic hydrocarbon group consisting of carbon atoms and hydrogen atoms. x -C y"C1-C6 alkyl" (x and y are each an integer) refers to a straight-chain or branched saturated aliphatic hydrocarbon group containing x to y carbon atoms. The term "C1-C6 alkyl" used alone or in combination in the present invention refers to a straight-chain or branched alkyl group containing 1 to 6 carbon atoms. The C1-C6 alkyl disclosed in the present invention includes C1-C5 alkyl, C1-C4 alkyl, C1-C3 alkyl, representative examples of which include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, etc. The "alkyl" or "C1-C6 alkyl" may be unsubstituted or substituted with one or more substituents selected from deuterium, hydroxyl, halogen, cyano, amino, thiol, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, or a combination thereof.

[0094] In the present invention, the term "haloalkyl" used alone or in combination refers to a straight or branched chain alkyl group substituted by one or more halogens, wherein one or more hydrogens in the alkyl group are replaced by halogens. x -C y "Haloalkyl" (x and y are each an integer) refers to a straight-chain or branched-chain alkyl group containing x to y carbon atoms substituted by one or more halogens. The term "C1-C6 haloalkyl" used alone or in combination in the present invention refers to a straight-chain or branched-chain alkyl group containing 1 to 6 carbon atoms substituted by one or more halogens. The C1-C6 haloalkyl disclosed in the present invention includes, for example, C1-C5 haloalkyl, C1-C4 haloalkyl or C1-C3 haloalkyl, and representative examples include halomethyl, haloethyl, halo-n-propyl, halo-isopropyl, halo-n-butyl, halo-isobutyl, halo-sec-butyl, halo-tert-butyl, halopentyl, halo-isopentyl, halo-neopentyl, halo-tert-pentyl and halohexyl, etc.

[0095] In the present invention, the term "alkoxy" used alone or in combination refers to a straight or branched alkoxy group, the structural formula of which is alkyl-O-. The term "C1-C6 alkoxy" used alone or in combination in the present invention refers to a straight or branched alkoxy group containing 1 to 6 carbon atoms. The C1-C6 alkoxy group disclosed in the present invention includes C1-C5 alkoxy, C1-C4 alkoxy, and C1-C3 alkoxy. Representative examples include methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, 2-pentyloxy, neopentyloxy, hexyloxy, 2-hexyloxy, 3-hexyloxy, 3-methylpentyloxy, etc.

[0096] In the present invention, the term "haloalkoxy" used alone or in combination refers to a straight or branched alkoxy group substituted by one or more halogens, wherein one or more hydrogens in the alkoxy group are replaced by halogens. x -C y"Haloalkoxy" (x and y are each an integer) refers to a straight-chain or branched alkoxy group containing x to y carbon atoms substituted by one or more halogens. The term "C1-C6 haloalkoxy" used alone or in combination in the present invention refers to a straight-chain or branched alkoxy group containing 1 to 6 carbon atoms substituted by one or more halogens. The C1-C6 haloalkoxy group disclosed in the present invention includes, for example, a C1-C5 haloalkoxy group, a C1-C4 haloalkoxy group or a C1-C3 haloalkoxy group, and representative examples include halogenated methoxy, halogenated ethoxy, halogenated n-propoxy, halogenated isopropoxy, halogenated n-butoxy, halogenated isobutoxy, halogenated sec-butoxy, halogenated tert-butoxy, halogenated pentoxy, halogenated isopentoxy, halogenated neopentoxy, halogenated tert-pentoxy and halogenated hexyloxy, etc.

[0097] In the present invention, the term "alkylene" used alone or in combination refers to a straight-chain or branched divalent saturated hydrocarbon group consisting of carbon atoms and hydrogen atoms. x -C y "Alkylene" (x and y are each an integer) refers to a straight or branched alkylene group containing x to y carbon atoms. The C1-C6 alkylene disclosed in the present invention includes, for example, C1-C5 alkylene, C1-C4 alkylene or C1-C3 alkylene, representative examples of which include but are not limited to methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, pentylene, isopentylene, neopentylene, tert-pentylene and hexylene. The "alkylene" or "C1-C6 alkylene" may be unsubstituted or substituted with one or more substituents selected from deuterium, hydroxyl, halogen, cyano, amino, thiol, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy or a combination thereof.

[0098] In the present invention, the term "aryl" used alone or in combination refers to a monovalent aromatic hydrocarbon group containing 5 to 30 (e.g., 5 to 20, 5 to 15, 6 to 20, 6 to 15, 7 to 20, 7 to 15, 8 to 20, 8 to 15, 9 to 20, 9 to 15, 10 to 20, 10 to 15) carbon atoms and optionally containing one or more fused rings, such as phenyl or naphthyl or fluorenyl. In the present invention, the "aryl" is an optionally substituted aryl. Substituted aryl refers to an aryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) by a substituent, for example, an aryl is monosubstituted, disubstituted, or trisubstituted by a substituent, wherein the substituent is optionally selected from, for example, deuterium, halogen, hydroxyl, cyano, amino, thiol, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or any combination thereof.

[0099] In the present invention, the term "arylene", used alone or in combination, refers to a divalent aromatic hydrocarbon group containing 5 to 30 (e.g., 5 to 20, 5 to 15, 6 to 20, 6 to 15, 7 to 20, 7 to 15, 8 to 20, 8 to 15, 9 to 20, 9 to 15, 10 to 20, 10 to 15) carbon atoms and optionally containing one or more fused rings, such as phenylene, naphthylene, or fluorenylene. In the present invention, the "arylene" is an optionally substituted arylene. Substituted arylene refers to an arylene group substituted one or more times (e.g., 1 to 4, 1 to 3, or 1 to 2 times) with a substituent, for example, the arylene group is monosubstituted, disubstituted, or trisubstituted with a substituent, wherein the substituent is optionally selected from, for example, deuterium, halogen, hydroxyl, cyano, amino, mercapto, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or any combination thereof.

[0100] In the present invention, the term "cycloalkyl" used alone or in combination refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) monocyclic or bicyclic or polycyclic hydrocarbon radical, which in some embodiments has 3 to 30 carbon atoms (i.e., C3-C 30 Cycloalkyl), 3 to 20 carbon atoms (i.e. C3-C 20 cycloalkyl), or 3 to 15 carbon atoms (i.e. C3-C 15 cycloalkyl), or 3 to 12 carbon atoms (i.e. C3-C 12 cycloalkyl), or 3 to 11 carbon atoms (i.e. C3-C 11 cycloalkyl), or 3 to 10 carbon atoms (i.e. C3-C 10 cycloalkyl), or 3 to 9 carbon atoms (i.e., C3-C9 cycloalkyl), or 3 to 8 carbon atoms (i.e., C3-C8 cycloalkyl), or 3 to 7 carbon atoms (i.e., C3-C7 cycloalkyl), 3 to 6 carbon atoms (i.e., C3-C6 cycloalkyl), 4 to 20 carbon atoms (i.e., C4-C 20 Cycloalkyl) or 4 to 15 carbon atoms (ie C4-C 15 The term "cycloalkyl" includes monocyclic, bicyclic, tricyclic or polycyclic cycloalkyl groups having 3 to 30 carbon atoms. Examples of the term cycloalkyl include, but are not limited to, monocyclic cycloalkyl groups (e.g., C3-C 30 Monocyclic cycloalkyl, C3-C 20 Monocyclic cycloalkyl, C3-C 15 Monocyclic cycloalkyl, C4-C 15 Monocyclic cycloalkyl, C5-C 15 Monocyclic cycloalkyl, C7-C 30 Monocyclic cycloalkyl, C7-C 20 Monocyclic cycloalkyl, C7-C 15Monocyclic cycloalkyl), bridged cycloalkyl (e.g. C5-C 30 Bridged cycloalkyl, C5-C 20 Bridged cycloalkyl, C5-C 15 Bridged cycloalkyl, C6-C 30 Bridged cycloalkyl, C6-C 20 Bridged cycloalkyl, C6-C 15 Bridged cycloalkyl, C7-C 30 Bridged cycloalkyl, C7-C 20 Bridged cycloalkyl, C7-C 15 Bridged cycloalkyl), fused cycloalkyl (e.g. C5-C 30 Condensed cycloalkyl, C5-C 20 Condensed cycloalkyl, C5-C 15 Condensed cycloalkyl, C6-C 30 Condensed cycloalkyl, C6-C 20 Condensed cycloalkyl, C6-C 15 Condensed cycloalkyl, C7-C 30 Condensed cycloalkyl, C7-C 20 Condensed cycloalkyl, C7-C 15 Condensed cycloalkyl) and spirocycloalkyl (e.g. C5-C 30 Spiroalkyl, C5-C 20 Spiroalkyl, C5-C 15 Spiroalkyl, C6-C 30 Spiroalkyl, C6-C 20 Spiroalkyl, C6-C 15 Spiroalkyl, C7-C 30 Spiroalkyl, C7-C 20 Spiroalkyl, C7-C 15 Representative examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Examples of bridged cycloalkyl groups, fused cycloalkyl groups, and spirocycloalkyl groups include, but are not limited to, decahydronaphthyl, octahydropentalenyl, C5-C 20 Spirocycloalkyl, adamantyl, noradamantyl, bornyl, norbornyl (IUPAC system named bicyclo[2,2,1]heptanyl). In the present invention, 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 to 5, 1 to 4, 1 to 3, 1 to 2 or 1) selected from: deuterium, =0, halogen, hydroxyl, cyano, amino, thiol, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy or any combination thereof.

[0101] 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 fully conjugated) monocyclic or bicyclic or polycyclic hydrocarbon divalent group having 3 to 30 carbon atoms (e.g., 3 to 25, 3 to 20, 3 to 15, 3 to 12, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 4 to 20, 4 to 15, 4 to 12, 4 to 10, 4 to 9, 4 to 8, 4 to 7 or 4 to 6 carbon atoms). The term "cycloalkylene" includes monocyclic, bicyclic, tricyclic or polycyclic cycloalkylene groups having 3 to 30 carbon atoms. Examples of the term cycloalkylene include, but are not limited to, submonocyclic cycloalkylene groups (e.g., C3-C 30 Monocyclic cycloalkylene, C3-C 20 Monocyclic cycloalkylene, C3-C 15 Monocyclic cycloalkylene, C4-C 15 Monocyclic cycloalkylene, C5-C 15 Monocyclic cycloalkylene, C7-C 30 Monocyclic cycloalkylene, C7-C 20 Monocyclic cycloalkylene, C7-C 15 monocyclic cycloalkylene), bridged cycloalkylene (e.g. C5-C 30 Sub-bridged cycloalkyl, C5-C 20 Sub-bridged cycloalkyl, C5-C 15 Sub-bridged cycloalkyl, C6-C 30 Sub-bridged cycloalkyl, C6-C 20 Sub-bridged cycloalkyl, C6-C 15 Sub-bridged cycloalkyl, C7-C 30 Sub-bridged cycloalkyl, C7-C 20 Sub-bridged cycloalkyl, C7-C 15 bridged cycloalkylene), fused cycloalkylene (e.g. C5-C 30 Fused cycloalkyl, C5-C 20 Fused cycloalkyl, C5-C 15 Fused cycloalkyl, C6-C 30 Fused cycloalkyl, C6-C 20 Fused cycloalkyl, C6-C 15 Fused cycloalkyl, C7-C 30 Fused cycloalkyl, C7-C 20 Fused cycloalkyl, C7-C 15 fused cycloalkylene) and spirocycloalkylene (e.g. C5-C 30 Spirocycloalkylene, C5-C 20 Spirocycloalkylene, C5-C 15 Spirocycloalkylene, C6-C 30 Spirocycloalkylene, C6-C 20 Spirocycloalkylene, C6-C15 Spirocycloalkylene, C7-C 30 Spirocycloalkylene, C7-C 20 Spirocycloalkylene, C7-C 15 Representative examples of monocyclic cycloalkylene include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, and cyclooctylene. Examples of bridged cycloalkylene, fused cycloalkylene, and spirocycloalkylene include, but are not limited to, decahydronaphthylene, octahydropentalenylene, C5-C 20 Spirocyclylene, adamantylene, noradamantylene, norbornylene (systematically named bicyclo[2.2.1]heptanylene). In the present invention, 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 cyclohexylene. The substituents of the substituted "cycloalkylene" are optionally one or more (for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2 or 1) selected from: deuterium, =0, halogen, hydroxyl, cyano, amino, thiol, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy or any combination thereof.

[0102] In the present invention, the term "heteroaryl" used alone or in combination refers to a 5- to 30-membered (optionally 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, or 6- to 9-membered) monocyclic or bicyclic or polycyclic monovalent cyclic hydrocarbon group containing at least one aromatic ring having one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroaryl groups include bicyclic, tricyclic, or tetracyclic or polycyclic heteroaryl groups, one of which is an aromatic ring having one or more heteroatoms independently selected from O, S, and N, and the other rings may be saturated, partially unsaturated, and / or aromatic rings and may be carbocyclic or contain one or more heteroatoms independently selected from O, S, and N.Representative examples of such heteroaryl groups include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, triazinyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, indolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, chromanyl, benzo[2,1,3 ]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, benzo[b]thien-4-yl, quinolyl, isoquinolyl, dihydroquinolyl, isoxazolo[4,5-c]pyridinyl, 2,3-dihydro-1H-benzo[d]imidazol-1-yl, 3,4-dihydroquinolin-1(2H)-yl, dihydro-4H-benzo[b][1,4]oxazin-4-yl, chroman-4-yl, thieno[2,3-d]pyrimidin-4-yl, 5,6,7,8-tetrahydrobenzo[4,5 ]thieno[2,3-d]pyrimidin-4-yl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl, 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl, thieno[2,3-d]pyrimidin-4-yl, thieno[2,3-d]pyrimidin-2-yl, 5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl, pyrazolo[1,5]thiadiazolyl, 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, 6,7-dihydrothieno[3,2-d]pyrimidinyl, 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" may be unsubstituted or substituted. A substituted heteroaryl refers to a heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) by a substituent, wherein the substituent is optionally selected from: deuterium, =O, halogen, hydroxyl, cyano, amino, thiol, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or any combination thereof.

[0103] In the present invention, the term "heteroarylene" used alone or in combination refers to a 5- to 30-membered (optionally 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, or 6- to 9-membered) monocyclic or bicyclic or polycyclic divalent cyclic hydrocarbon group containing at least one aromatic ring having one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroarylene groups include bicyclic, tricyclic, tetracyclic, or polycyclic heteroarylene groups, one of which is an aromatic ring having one or more heteroatoms independently selected from O, S, and N, and the other rings contained may be saturated, partially unsaturated, and / or aromatic rings and may be carbocyclic or contain one or more heteroatoms independently selected from O, S, and N. Representative examples of heteroarylene groups include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, indazolylene, quinolinylene, isoquinolinylene, quinazolinylene, triazinylene, isoxazolo[4,5-c]pyridinylene, pyrrolo[2,3-b]pyridinylene, ]pyridinylene, indolinylene, benzothiazolylene, benzofuranylene, isobenzofuranylene, benzothienylene, benzimidazolylene, 2,3-dihydro-1H-benzo[d]imidazolylene, pyrrolo[2,3-b]pyridinylene, chromanylene, 6,7-dihydrothieno[3,2-d]pyrimidinylene, acridinylene, benzoindolylene, carbazolylene, dibenzofuranylene, xanthenylene, 3,4-dihydroquinolinylene, 2,3-dihydro-4H-benzo[ b][1,4]oxazinediyl, benzodihydropyranyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, dihydrothieno[3,2-d]pyrimidinyl, 5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazinyl, dihydrothieno[ 3,2-c]pyridinylene, benzoxazolylene, benzoisoxazolylene, benzoisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, pyrazolo[1,5-a]pyridinylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridinylene, 1H-pyrrolo[3,2-b]thiazolylene or benzo[2,1-b]thiazolylene. The “heteroarylene” 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 a substituent, wherein the substituent is optionally selected from: deuterium, =0, halogen, hydroxyl, cyano, amino, thiol, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or any combination thereof.

[0104] In the present invention, the term "heterocyclyl" used alone or in combination refers to a 4-30 membered (optionally 4-25 membered, 4-20 membered, 4-15 membered, 5-20 membered, 5-15 membered, 6-20 membered, 6-15 membered, 7-20 membered or 7-15 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. Representative examples of the heterocyclyl group include, but are not limited to, monocyclic heterocyclyl (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, or 4- to 15-membered monocyclic heterocyclyl), bridged heterocyclyl (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered bridged heterocyclyl), fused heterocyclyl (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered fused heterocyclyl), and spiro heterocyclyl (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered spiro heterocyclyl). Representative examples of heterocyclyl include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, azetidin-1-yl, 3,6-dihydropyridin-1(2H)-yl, 1,4-diazepan-1-yl , 3,6-diazabicyclo[3.1.1]heptane-6-yl, 3,6-diazabicyclo[3.1.1]heptane-3-yl, 2,5-diazabicyclo[2.2.1]heptane-2-yl, 2,5-diazabicyclo[2.2.2]octane-2-yl, 3,8-diazabicyclo[3.2.1]octane-3-yl, 3,8-diazabicyclo[3.2.1]octane-8-yl and azaspirocyclyl. The “heterocyclyl” may be unsubstituted or substituted. A substituted heterocyclyl group refers to a heterocyclyl group substituted one or more times (e.g., 1 to 4, 1 to 3, or 1 to 2 times) with substituents, wherein the substituents are optionally selected from: deuterium, =0, halogen, hydroxyl, cyano, amino, mercapto, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or any combination thereof.

[0105] In the present invention, the term "heterocyclylene" used alone or in combination refers to a 4-30 membered (optionally 4-25 membered, 4-20 membered, 4-15 membered, 5-20 membered, 5-15 membered, 6-20 membered, 6-15 membered, 7-20 membered or 7-15 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 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. Representative examples of the heterocyclylene group include, but are not limited to, monocyclic heterocyclylene (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, or 4- to 15-membered monocyclic heterocyclylene), bridged heterocyclylene (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered bridged heterocyclylene), fused heterocyclylene (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered fused heterocyclylene), and spiroheterocyclylene (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 6- to 20-membered, 6- to 15-membered, 7- to 30-membered, 7- to 20-membered, or 7- to 15-membered spiroheterocyclylene). Representative examples of heterocyclylene include, but are not limited to, azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, piperidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothiophenylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, tetrahydrothiophenylene, thiomorpholinylene, dioxanylene, azetidin-1-ylidene, 3,6-dihydropyridin-1(2H)-ylidene, 1,4-dihydropyridin-1(2H)-ylidene, Azacycloheptan-1-ylidene, 3,6-diazabicyclo[3.1.1]heptane-6-ylidene, 3,6-diazabicyclo[3.1.1]heptane-3-ylidene, 2,5-diazabicyclo[2.2.1]heptane-2-ylidene, 2,5-diazabicyclo[2.2.2]octane-2-ylidene, 3,8-diazabicyclo[3.2.1]octane-3-ylidene, 3,8-diazabicyclo[3.2.1]octane-8-ylidene and azaspirocyclylene. The “heterocyclylene” may be unsubstituted or substituted. Substituted heterocyclylene refers to a heterocyclylene group substituted one or more times (e.g., 1 to 4, 1 to 3, or 1 to 2 times) with a substituent, wherein the substituent is optionally selected from: deuterium, =0, halogen, hydroxyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or any combination thereof.

[0106] In the present invention, the suffix "group" in the name of a group means that the group is connected to the rest of the molecule through one single bond and one double bond in the molecule and is a trivalent group.

[0107] In the present invention, the term "heterocyclylene group" used alone or in combination refers to a 4-30 membered (optionally selected as 4-25 membered, 4-20 membered, 4-15 membered, 5-20 membered, 5-15 membered, 6-20 membered, 6-15 membered, 7-20 membered or 7-15 membered) monocyclic, bicyclic, tricyclic or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds but not fully conjugated) trivalent cyclic hydrocarbon group 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. Representative examples of the heterocyclyl subunit include, but are not limited to, monocyclic heterocyclyl subunits (e.g., 4- to 30-membered, 4- to 25-membered, 4- to 20-membered, 4- to 15-membered monocyclic heterocyclyl subunits), bridged heterocyclyl subunits (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 7- to 30-membered, 7- to 20-membered, 7- to 15-membered bridged heterocyclyl subunits), fused heterocyclyl subunits (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 7- to 30-membered, 7- to 20-membered, 7- to 15-membered fused heterocyclyl subunits), and spiroheterocyclyl subunits (e.g., 5- to 30-membered, 5- to 20-membered, 5- to 15-membered, 7- to 30-membered, 7- to 20-membered, 7- to 15-membered spiroheterocyclyl subunits). Representative examples of heterocyclyl subunits include, but are not limited to, azetidinyl subunits, oxetanyl subunits, pyrrolidinyl subunits, imidazolidinyl subunits, pyrazolidinyl subunits, piperidinyl subunits, tetrahydrofuranyl subunits, tetrahydropyranyl subunits, tetrahydrothiophenyl subunits, tetrahydrothiopyranyl subunits, oxazolidinyl subunits, thiazolidinyl subunits, piperidinyl subunits, piperazinyl subunits, morpholinyl subunits, tetrahydrothiophenyl subunits, thiomorpholinyl subunits, dioxanyl subunits, azetidin-1-yl subunits, 3,6-dihydropyridin-1(2H)-yl subunits, The “heterocyclyl subunit” may be unsubstituted or substituted. A substituted heterocyclyl substituent refers to a heterocyclyl substituent substituted one or more times (e.g., 1 to 4, 1 to 3, or 1 to 2 times) with a substituent, wherein the substituent is optionally selected from: deuterium, =0, halogen, hydroxyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or any combination thereof.

[0108] In the present invention, the term "heteroaryl group" used alone or in combination refers to a 7- to 30-membered (optionally 7- to 30-membered, 7- to 20-membered, 7- to 15-membered, 7- to 12-membered, 7- to 11-membered, 7- to 10-membered, 8- to 15-membered, 8 ...) aromatic ring containing at least one heteroatom (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) independently The invention also includes a (1- to 30-membered, 8- to 20-membered, 8- to 15-membered, 8- to 12-membered, 8- to 11-membered, 8- to 10-membered, 9- to 30-membered, 9- to 20-membered, 9- to 15-membered, 10- to 30-membered, 10- to 20-membered, 10- to 15-membered, 11- to 30-membered, 11- to 20-membered, 11- to 15-membered, 12- to 30-membered, 12- to 20-membered, 15- to 30-membered, or 15- to 20-membered) bicyclic or polycyclic trivalent cyclic hydrocarbon group. The bicyclic or polycyclic heteroaryl subunit includes a bicyclic, tricyclic, or tetracyclic or polycyclic heteroaryl subunit, one of which is an aromatic ring having one or more heteroatoms independently selected from O, S, and N, and the other rings may be saturated and / or partially unsaturated rings and may be carbocyclic or contain one or more heteroatoms independently selected from O, S, and N. Representative examples of the heteroaryl substituent groups include, but are not limited to, chromanyl substituents (e.g. ) or 2,3-dihydroquinolin-4(1H)-yl subunit (e.g. ). The "heteroaryl substituent" may be unsubstituted or substituted. A substituted heteroaryl substituent refers to a heteroaryl substituent substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituent is optionally selected from: deuterium, =0, halogen, hydroxyl, cyano, amino, thiol, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or any combination thereof.

[0109] 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,

[0110] In the present invention, the term "bicyclo[2,2,1]heptane" (also known as bicyclo[2.2.1]heptane) or "norbornane" has the definition known to those skilled in the art. In the present invention, "bicyclo[2,2,1]heptane" refers to a monovalent radical of bicyclo[2,2,1]heptane, that is, 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-1-yl, 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, or bicyclo[2,2,1]heptane-6-yl.

[0111] The term "adamantan" 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.

[0112] In this document, 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.

[0113] In the embodiments disclosed herein, the compound of formula (I) or a pharmaceutically acceptable salt thereof refers to a non-toxic inorganic 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, 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 or p-toluenesulfonate, etc.

[0114] As used herein, the term "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 the useful compounds disclosed herein into or to a patient so that they can perform their intended function. Typically, such constructs carry or transport from one organ or part of the body to another. The carrier must be "acceptable" in that it is compatible with the other ingredients of the formulation (including the compounds useful in the present disclosure) and not injurious 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 glycols; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; phosphate buffers, which are surfactants; and other nontoxic, compatible substances used in pharmaceutical formulations.

[0115] In the present invention, the term "room temperature" refers to ambient temperature, for example, a temperature of 20-30°C.

[0116] The compounds disclosed in the present invention have a strong binding affinity to CRBN and can significantly inhibit the proliferation of tumor cells, with an inhibitory effect far superior to that of the positive control drugs lenalidomide and pomalidomide. In protein immunoblotting experiments, the compounds disclosed in the present invention exhibit the ability to degrade substrate proteins (such as IKZF 1 / 2 / 3 / 4 protein, WEE1 protein, CK1α protein, GSPT1 protein, ZFP91 protein, etc.). The results of pharmacokinetic testing experiments show that the novel compounds of the present invention have good pharmacokinetic (DMPK) properties when administered orally and can be used as therapeutic drugs for cancer patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0117] FIG1 shows the Western Blot experimental results of the compounds of the present invention on the degradation of target substrate proteins in cells. DETAILED DESCRIPTION

[0118] To better illustrate this application and facilitate understanding of the technical solutions of this application, the application is described in further detail below. It should be understood that the embodiments described herein are merely some, and not all, of the present invention. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of this invention without inventive effort are intended to fall within the scope of protection of this invention.

[0119] The terms used in the embodiments of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The singular forms "a", "an", "the" and "the" used in the embodiments of the present invention and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise.

[0120] The following abbreviations are used throughout the specification and examples: DIEA N,N-diisopropylethylamine DMF N,N-dimethylformamide Eq Equivalent OMs Methanesulfonate OTs Toluenesulfonate ONs m-Nitrobenzenesulfonate 1 H NMR nuclear magnetic resonance spectroscopy

[0121] Synthesis method

[0122] The compounds and / or 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, enantiomers, stereoisomers, solvates, isotopically enriched analogs, prodrugs or polymorphs of the compounds of formula (I) disclosed herein can be prepared by those skilled in the art according to conventional techniques in the art.

[0123] Synthesis Scheme 1

[0124] In Synthesis Scheme 1, the group X in substrate 1 represents CH2 or C(=O), Y represents fluorine or hydrogen, and the group LE represents Cl, Br, I, OMs, OTs or ONs. The group R in substrate 2 b1 represents hydrogen, group R b2 represents an optionally substituted heterocyclic or cycloalkyl group, or a group R b1 and group R b2 Together with the nitrogen atom to which they are attached, they form an optionally substituted nitrogen-containing heterocycle.

[0125] The amine alkylation reaction in Synthesis Scheme 1 can be carried out under conventional conditions familiar to those skilled in the art. For example, the amine alkylation can be carried out in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at a temperature between room temperature and 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 to 2:1, 1.1 to 1.5:1, 1:1.1 to 2, 1:1.1 to 1.5, 1:1.1 to 1.2, or 1:1.2 to 1.3. For example, mesylate substrate 1 (1.1 eq.) and substrate 2 (1.0 eq.) are dissolved in 3 mL of anhydrous DMF, and triethylamine (3.0 eq.) and sodium iodide (1.0 eq.) are then added to the solution, and the reaction mixture is stirred at room temperature for 18 hours. The reaction was completed by LCMS detection, the reaction solution was filtered, and the filtrate was purified by high performance liquid chromatography to obtain the target compound.

[0126] Depending on the target compound, the above scheme and its 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.

[0127] Examples of compounds of the present invention

[0128] Example 1: Preparation of 3-(1-oxo-5-((4-(thiophen-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04545)

[0129] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04545) (white solid, 57 mg, yield 51%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),9.64(s,1H),7.91(s,1H),7.87–7.75(m,4H),6.13(t,J=3.8Hz,1H),5.14(dd,J=13.3,5.0Hz,1H),4.66–4.34( m,4H),3.45–3.39(m,5H),3.27(brs,2H),2.99–2.81(m,2H),2.61(d,J=16.8Hz,1H),2.43(dd,J=12.9,4.3Hz,1H),2.06–1.96(m,1H).LCMS(ESI)C 22 H 25 N4O3S + [M+H] + :Calculated value 425.16, measured value 425.2.

[0130] Example 2: Preparation of 3-(5-((4-(5-methylthiophen-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04546)

[0131] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04546) (white solid, 43 mg, yield 40%) was prepared. 1 H NMR(400MHz,DMSO)δ11.01(s,1H),9.65(s,1H),7.91(s,1H),7.87–7.74(m, 3H),5.14(dd,J=13.3,5.1Hz,1H),4.53–4.36(m,4H),3.39–3.27(m,5H),3.2 8–3.04(m,2H),2.93-2.88(m,1H),2.84–2.72(m,1H),2.61(d,J=16.6Hz,1H ),2.50(s,3H),2.44(dd,J=13.1,4.5Hz,1H),2.05–2.01(m,1H).LCMS(ESI)C 23 H 27 N4O3S +[M+H] + :Calculated value 439.18, measured value 439.2.

[0132] Example 3: Preparation of 3-(5-((4-(3-methylthiophen-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04582)

[0133] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04582) (white solid, 39 mg, yield 36%) was prepared. 1 H NMR(400MHz,MeOD)δ7.97(d,J=7.8Hz,1H),7.82(s,1H),7.75(d,J=7.8Hz,1H),7.02(d ,J=5.6Hz,1H),6.77(d,J=5.6Hz,1H),5.21(dd,J=13.3,5.2Hz,1H),4.70–4.52(m,4H), 3.56(brs,2H),3.50–3.45(m,2H),3.32-3.20(m,2H),3.03–2.96(m,2H),3.00–2.88(m, 1H),2.84–2.80(m,1H),2.60-2.49(m,1H),2.30–2.19(m,1H),2.19(s,3H).LCMS(ESI)C 23 H 27 N4O3S + [M+H] + :Calculated value 439.18, measured value 439.2.

[0134] Example 4: Preparation of 3-(1-oxo-5-((4-(thiophen-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04547)

[0135] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04547) (white solid, 39 mg, yield 35%) was prepared. 1H NMR(400MHz,DMSO)δ11.39(s,1H),11.01(s,1H),9.71(s,1H),7.92(s,1H),7.87–7.75 (m,2H),7.50–7.38(m,1H),7.00-6.96(m,1H),5.14(dd,J=13.4,4.8Hz,1H),4.65–4.32 (m,4H),3.48–3.42(m,3H),3.37(d,J=10.3Hz,2H),3.29–3.08(m,3H),3.00–2.84(m,1H ),2.61(d,J=17.5Hz,1H),2.43(dd,J=13.1,4.4Hz,1H),2.08–1.97(m,1H).LCMS(ESI)C 22 H 25 N4O3S + [M+H] + :Calculated value 425.16, measured value 425.2.

[0136] Example 5: Preparation of 3-(5-((4-(4-methylthiophen-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04548)

[0137] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04548) (white solid, 77 mg, yield 71%) was prepared. 1 H NMR (400MHz, DMSO) δ11.21(s,1H),11.01(s,1H),7.91(s,1H),7.82(q,J=7.8Hz,2H),7.16–7.09 (m,1H),6.80(d,J=3.2Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.54–4.37(m,4H),3.38(d,J=11.7 Hz,2H),3.29(d,J=13.6Hz,2H),3.23(d,J=10.8Hz,2H),3.05–2.97(m,2H),2.95–2.86(m,1H),2 .61(d,J=16.6Hz,1H),2.43(dd,J=13.2,4.4Hz,1H),2.10(s,3H),2.06–1.95(m,1H).LCMS(ESI)C 23 H 27 N4O3S + [M+H] + :Calculated value 439.18, measured value 439.2.

[0138] Example 6: Preparation of 3-(5-((4-(5-methylthiophen-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04549)

[0139] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04549) (white solid, 73 mg, yield 67%) was prepared. 1 H NMR(400MHz,DMSO)δ11.00(s,1H),7.91(d,J=7.3Hz,1H),7.87–7.73(m,2H),6.68(s,1H), 6.19(s,1H),5.14(dd,J=13.2,5.1Hz,1H),4.59–4.33(m,3H),3.61-3.59(m,2H),3.47–3. 42(m,2H),3.35(d,J=10.3Hz,2H),3.17(s,3H),3.11–3.08(m,2H),2.94–2.90(m,1H),2.6 1(d,J=16.8Hz,1H),2.46–2.41(m,1H),2.38–2.32(m,1H),2.06–1.95(m,1H).LCMS(ESI)C 23 H 27 N4O3S + [M+H] + :Calculated value 439.18, measured value 439.2.

[0140] Example 7: Preparation of 3-(1-oxo-5-((4-(thiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04494)

[0141] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04494) (white solid, 26 mg, yield 23%) was prepared. 1H NMR (400MHz, DMSO) δ11.01(s,1H),10.58(s,1H),7.85(d,J=7.2Hz,2H),7.74(d,J=7.7Hz,1H) ,7.49(d,J=4.8Hz,1H),7.17(s,1H),7.10–7.01(m,1H),6.06(s,1H),5.15(dd,J=13.2,5.0Hz, 1H),4.56–4.37(m,4H),3.88–3.68(m,2H),3.65–3.61(m,1H),3.27–3.22(m,1H),2.96–2.88(m ,1H),2.82(brs,2H),2.67–2.59(m,1H),2.43(d,J=8.7Hz,1H),2.10–1.94(m,1H).LCMS(ESI)C 23 H 24 N3O3S + [M+H] + :Calculated value 422.15, measured value 422.2.

[0142] Example 8: Preparation of 3-(5-((4-(5-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04572)

[0143] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04572) (white solid, 53 mg, yield 48%) was prepared. 1 H NMR (400MHz, DMSO) δ11.00(s,1H),10.82(s,1H),7.93–7.81(m,2H),7.76(d,J=7 .3Hz,1H),6.94(s,1H),6.74(s,1H),5.90(s,1H),5.14(dd,J=13.2,4.0Hz,1H),4 .54–4.36(m,4H),3.82–3.69(m,2H),3.63–3.46(m,1H),3.46–3.43(m,2H),2.82– 2.71(m,2H),2.61(d,J=16.4Hz,2H),2.41(s,sH),2.07–1.99(m,1H).LCMS(ESI)C 24 H 26 N3O3S + [M+H] + :Calculated value 436.17, measured value 436.2.

[0144] Example 9: Preparation of 3-(5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04495)

[0145] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04495) (white solid, 25 mg, yield 23%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.67(s,1H),7.85(d,J=6.4Hz,2H),7.75(d,J=8. 0Hz,1H),7.39(d,J=5.1Hz,1H),6.91(d,J=5.1Hz,1H),5.84(s,1H),5.15(dd,J=13.2, 5.0Hz,1H),4.54–4.37(m,4H),3.92–3.69(m,2H),3.64–3.59(m,1H),3.02–2.73(m,2 H),2.72–2.55(m,2H),2.45–2.39(m,2H),2.22(s,3H),2.05–2.01(m,1H).LCMS(ESI)C 24 H 26 N3O3S + [M+H] + :Calculated value 436.17, measured value 436.3.

[0146] Example 10: Preparation of 3-(1-oxo-5-((4-(thiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04585)

[0147] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04585) (white solid, 55 mg, yield 48%) was prepared. 1H NMR(400MHz,MeOD)δ7.97(d,J=7.8Hz,1H),7.82(s,1H),7.75(d,J=7.8Hz,1H),7.02(d ,J=5.6Hz,1H),6.77(d,J=5.6Hz,1H),5.21(dd,J=13.3,5.2Hz,1H),4.70–4.52(m,4H), 3.56(brs,2H),3.50–3.45(m,2H),3.32-3.20(m,2H),3.03–2.96(m,2H),3.00–2.88(m, 1H),2.84–2.80(m,1H),2.60-2.49(m,1H),2.30–2.19(m,1H),2.19(s,3H).LCMS(ESI)C 23 H 24 N3O3S + [M+H] + :Calculated value 422.15, measured value 422.2.

[0148] Example 11: Preparation of 3-(5-((4-(4-methylthiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04503)

[0149] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04503) (white solid, 20 mg, yield 18%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.77(s,1H),7.91–7.82(m,2H),7.77(d,J=7.7Hz,1H),7.42 (d,J=3.0Hz,1H),7.20(d,J=2.9Hz,1H),5.79(s,1H),5.15(dd,J=13.3,5.0Hz,1H),4.54–4.50(m ,3H),4.39(d,J=17.4Hz,1H),3.87–3.66(m,2H),3.63–3.59(m,1H),3.28–3.19(m,1H),2.94–2.8 8(m,2H),2.62(d,J=16.8Hz,2H),2.46–2.37(m,1H),2.23(s,3H),2.09–1.94(m,1H).LCMS(ESI)C 24 H 26 N3O3S + [M+H] + :Calculated value 436.17, measured value 436.2.

[0150] Example 12: Preparation of 3-(5-((4-(5-methylthiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04587)

[0151] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04587) (white solid, 66 mg, yield 60%) was prepared. 1 H NMR (400MHz, MeOD) δ8.34(d,J=5.2Hz,1H),7.94(dd,J=17.5,7.5Hz,1H),7.84–7.51(m,2H),7.20–7.01(m,1H),6.00(d,J=76.8Hz,1H),5.22( d,J=7.9Hz,1H),4.77–4.36(m,4H),3.87(d,J=31.1Hz,2H),3.53–3.35(m,2H),3.00–2.70(m,4H),2.63–2.44(m,4H),2.21(s,1H).LCMS(ESI)C 24 H 26 N3O3S + [M+H] + :Calculated value 436.17, measured value 436.2.

[0152] Example 13: Preparation of 3-(5-((4-(furan-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04617)

[0153] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04617) (white solid, 44 mg, yield 46%) was prepared. 1 H NMR(400MHz,MeOD)δ7.95(t,J=9.2Hz,1H),7.80(d,J=10.6Hz,1H),7.74(d,J =8.2Hz,1H),7.52(s,1H),6.89–5.86(m,3H),5.21(dd,J=13.3,5.2Hz,1H),4 .67–4.47(m,4H),3.86(d,J=63.6Hz,2H),3.52–3.34(m,2H),3.00–2.89(m,1 H),2.82(d,J=12.8Hz,3H),2.62–2.45(m,1H),2.30–2.15(m,1H).LCMS(ESI)C23 H 24 N3O4 + [M+H] + :Calculated value 406.18, measured value 406.2.

[0154] Example 14: Preparation of 3-(5-((4-(furan-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04589)

[0155] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04589) (white solid, 67 mg, yield 56%) was prepared. 1 H NMR(400MHz,MeOD)δ7.96(d,J=7.8Hz,1H),7.81(s,1H),7.74(d,J=7.8Hz,1H),7.68(s,1H),7.5 2(t,J=1.6Hz,1H),6.68(s,1H),5.96(d,J=39.6Hz,1H),5.21(dd,J=13.3,5.2Hz,1H),4.68–4.5 0(m,4H),3.94(d,J=23.1Hz,2H),3.76(s,1H),3.39(d,J=18.9Hz,1H),3.01–2.88(m,1H),2.83( dd,J=11.0,8.7Hz,3H),2.54(qd,J=13.5,4.9Hz,1H),2.22(dd,J=10.1,4.9Hz,1H).LCMS(ESI)C 23 H 24 N3O4 + [M+H] + :Calculated value 406.18, measured value 406.2.

[0156] Example 15: Preparation of 3-(1-oxo-5-((4-(thiophen-2-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04571)

[0157] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04571) (white solid, 51 mg, yield 45%) was prepared. 1H NMR (400MHz, DMSO) δ11.02(s,1H),10.80(s,1H),7.88(s,1H),7.83(t,J=6.5Hz,1H),7.76(d,J =7.9Hz,1H),7.38(dd,J=5.1,1.2Hz,1H),6.97(dd,J=5.1,3.5Hz,1H),6.90(d,J=3.4Hz,1H),5 .15(dd,J=13.3,5.1Hz,1H),4.65–4.39(m,4H),3.49–3.39(m,2H),3.11–3.05(m,3H),2.94–2. 89(m,1H),2.61(d,J=17.6Hz,1H),2.43(dd,J=13.0,4.4Hz,1H),2.17–1.97(m,5H).LCMS(ESI)C 23 H 26 N3O3S + [M+H] + :Calculated value 424.17, measured value 424.2.

[0158] Example 16: Preparation of 3-(5-((4-(5-methylthiophen-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04573)

[0159] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04573) (white solid, 59 mg, yield 54%) was prepared. 1H NMR (400 MHz, MeOD) δ 7.83 (d, J = 7.8 Hz, 1H), 7.68 (s, 1H), 7.60 (d, J = 7.8 Hz, 1H), 6.56 (s, 1H), 6.49 (s, 1H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.48 (q, J = 17.4 Hz, 2H), 4.38 (s, 2H), 3.49 (d, J = 11.3 Hz, 2H), 3.16–2.95 (m, 3H), 2.92–2.75 (m, 1H), 2.75–2.64 (m, 1H), 2.42 (qd, J=13.2, 4.6 Hz, 1H), 2.31 (s, 3H), 2.24–2.02 (m, 3H), 1.91–1.69 (m, 2H). LCMS (ESI) C24H28N3O3S+[M+H]+: calculated value 438.18, found value 438.2.

[0160] Example 17: Preparation of 3-(5-((4-(3-methylthiophen-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04502)

[0161] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04502) (white solid, 31 mg, yield 28%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.42(s,1H),7.85(d,J=7.3Hz,2H),7.73(d,J=8.1H z,1H),7.26(d,J=5.1Hz,1H),6.82(d,J=5.0Hz,1H),5.15(dd,J=13.2,5.1Hz,1H),4.54 –4.37(m,4H),3.44(d,J=11.4Hz,2H),3.20–3.06(m,3H),3.02–2.85(m,1H),2.61(d,J= 18.0Hz,1H),2.43(dd,J=13.0,4.3Hz,1H),2.14(s,3H),2.08–1.87(m,5H).LCMS(ESI)C 24 H 28 N3O3S + [M+H] + :Calculated value 438.18, measured value 438.2.

[0162] Example 18: Preparation of 3-(1-oxo-5-((4-(thiophen-3-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04586)

[0163] Referring to the method of Synthesis Scheme 1, under appropriate conditions known in the art, the target compound (GT-04586) (white solid, 62 mg, yield 55%) was prepared. 1H NMR(400MHz,MeOD)δ7.96(d,J=7.8Hz,1H),7.82(s,1H),7.74(d,J=7.8Hz,1H),7.40(dd,J=5.0,2 .9Hz,1H),7.17(d,J=2.6Hz,1H),7.07(dd,J=5.0,1.1Hz,1H),5.21(dd,J=13.4,5.2Hz,1H),4.69– 4.55(m,2H),4.52(s,2H),3.63(d,J=12.6Hz,2H),3.26–3.20(m,2H),3.11–2.98(m,1H),2.98–2.8 7(m,1H),2.86–2.77(m,1H),2.60–2.49(m,1H),2.32–2.16(m,3H),1.99–1.88(m,2H).LCMS(ESI)C 23 H 26 N3O3S + [M+H] + :Calculated value 424.17, measured value 424.2.

[0164] Example 19: Preparation of 3-(5-((4-(5-methylthiophen-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04588)

[0165] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04588) (white solid, 52 mg, yield 48%) was prepared. 1 H NMR(400MHz,MeOD)δ7.95(d,J=7.8Hz,1H),7.81(s,1H),7.73(d,J=7.8Hz,1H),6.87( s,1H),6.73(s,1H),5.21(dd,J=13.3,5.2Hz,1H),4.69–4.46(m,4H),3.54(dd,J=57.9 ,21.8Hz,2H),3.28–3.12(m,2H),3.02–2.76(m,3H),2.54(ddd,J=26.4,13.2,4.6Hz, 1H),2.52–2.40(m,3H),2.28–2.06(m,3H),1.89(dd,J=24.9,11.7Hz,2H).LCMS(ESI)C 24 H 28 N3O3S + [M+H] + :Calculated value 438.18, measured value 438.2.

[0166] Example 20: Preparation of 3-(5-((4-(4-methylthiophen-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04504)

[0167] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04504) (white solid, 27 mg, yield 25%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.81(s,1H),7.89(s,1H),7.83(d,J=7.7Hz,1H),7.7 7(d,J=7.8Hz,1H),7.11(d,J=4.9Hz,2H),5.15(dd,J=13.2,5.0Hz,1H),4.54–4.37(m,4H ),3.50–3.46(m,2H),3.11–3.05(m,2H),3.00–2.85(m,1H),2.85–2.72(m,1H),2.61(d,J =17.2Hz,1H),2.43(dd,J=13.2,4.4Hz,1H),2.17(s,3H),2.08–1.87(m,5H).LCMS(ESI)C 24 H 28 N3O3S + [M+H] + :Calculated value 438.18, measured value 438.2.

[0168] Example 21: Preparation of 3-(5-((4-(furan-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04618)

[0169] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04618) (white solid, 49 mg, yield 52%) was prepared. 1H NMR(400MHz,MeOD)δ7.95(d,J=7.7Hz,1H),7.80(s,1H),7.72(d,J=7.9Hz,1H),7.42(s ,1H),6.35(s,1H),6.15(s,1H),5.21(dd,J=13.4,5.1Hz,1H),4.66–4.46(m,4H),3.58 (t,J=27.2Hz,2H),3.20(dd,J=23.8,12.1Hz,2H),3.09–2.87(m,2H),2.87–2.75(m,1H ),2.54(qd,J=13.4,4.7Hz,1H),2.39–2.15(m,3H),1.93(t,J=11.8Hz,2H).LCMS(ESI)C 23 H 26 N3O4 + [M+H] + :Calculated value 408.19, measured value 408.3.

[0170] Example 22: Preparation of 3-(5-((4-(furan-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04590)

[0171] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04590) (white solid, 59 mg, yield 50%) was prepared. 1 H NMR(400MHz,MeOD)δ7.94(t,J=7.4Hz,1H),7.86–7.78(m,1H),7.72(t,J=7.6Hz,1H),7.48(dd, J=16.2,14.6Hz,1H),7.40(s,1H),6.46(d,J=35.8Hz,1H),5.20(dt,J=19.1,9.6Hz,1H),4.67– 4.54(m,2H),4.51(s,2H),3.61(d,J=11.8Hz,2H),3.28–3.13(m,2H),2.98–2.75(m,3H),2.54( qd,J=13.3,4.7Hz,1H),2.22(dd,J=10.1,4.7Hz,3H),1.85(td,J=16.5,3.6Hz,2H).LCMS(ESI)C 23 H 26 N3O4 + [M+H] + :Calculated value 408.19, measured value 408.3.

[0172] Example 23: Preparation of 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04201)

[0173] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04201) (white solid, 22 mg, yield 30%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ7.95(d,J=7.8Hz,1H),7.81(s,1H),7.74(d,J=7.9Hz,1H),7.32–7.27(m,2H),7.18–7.11(m,1H),5.19(dd,J=13.4,5.1Hz,1H ),4.66–4.51(m,4H),3.62–3.43(m,6H),3.17–3.07(m,2H),3.02–2.85(m, 1H),2.82–2.77(m,1H),2.60–2.44(m,1H),2.27–2.12(m,1H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0174] Example 24: Preparation of 3-(1-oxo-5-((4-phenylpiperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04446)

[0175] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04446) (white solid, 91 mg, yield 65%) was prepared. 1 H NMR (400MHz, DMSO) δ11.63(s,1H),11.02(s,1H),7.95(s,1H),7.83(s,2H),7.26(dd,J= 8.7,7.3Hz,2H),6.98(d,J=7.9Hz,2H),6.86(t,J=7.3Hz,1H),5.15(dd,J=13.3,5.1Hz,1 H),4.52–4.37(m,4H),3.82-3.78(m,2H),3.39(d,J=8.9Hz,2H),3.29–3.09(m,4H),2.93 –2.89(m,1H),2.62(d,J=16.5Hz,1H),2.46–2.38(m,1H),2.05–2.01(m,1H).LCMS(ESI)C24 H 27 N4O3 + [M+H] + :Calculated value 419.21, measured value 419.3.

[0176] Example 25: Preparation of 3-(5-((4-(2-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04490)

[0177] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04490) (white solid, 46 mg, yield 36%) was prepared. 1 H NMR(400MHz,DMSO)δ11.02(s,1H),7.90(s,1H),7.85-7.78(m,2H),7.04–6.98(m,2H) ,6.95-6.85(m,2H),5.15(dd,J=13.2,5.2Hz,1H),4.54–4.37(m,4H),3.78(s,3H),3.4 7(d,J=12.8Hz,2H),3.39(d,J=12.8Hz,2H),3.25–5.22(m,2H),3.08–3.02(m,2H),2. 99-2.85(m,1H),2.64–2.59(m,1H),2.49–2.41(m,1H),2.07-1.95(m,1H).LCMS(ESI)C 25 H 29 N4O4 + [M+H] + :Calculated value 449.22, measured value 449.3.

[0178] Example 26: Preparation of 3-(5-((4-(3-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04448)

[0179] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04448) (white solid, 105 mg, yield 83%) was prepared. 1H NMR (400MHz, DMSO) δ11.16(s,1H),11.02(s,1H),7.90(s,1H),7.85(d,J=7.8Hz,1H),7.78(d,J=7.8Hz,1H),7.16(t,J=8.2Hz,1H),6.56(dd,J=8.2,1. 9Hz,1H),6.50(t,J=2.2Hz,1H),6.45(dd,J=8.0,2.0Hz,1H),5.15(dd,J=13 .3,5.1Hz,1H),4.59–4.33(m,4H),3.81(d,J=9.2Hz,2H),3.72(s,3H),3.41 -3.38(m,2H),3.15(d,J=8.8Hz,4H),3.02–2.85(m,1H),2.62(d,J=16.7Hz,1H),2.48–2.39(m,1H),2.07–1.93(m,1H).LCMS(ESI)C 25 H 29 N4O4 + [M+H] + :Calculated value 449.22, measured value 449.3.

[0180] Example 27: Preparation of 3-(5-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04447)

[0181] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04447) (white solid, 81 mg, yield 64%) was prepared. 1 H NMR (400MHz, DMSO) δ11.13(s,1H),11.02(s,1H),7.91(s,1H),7.85(d,J=7.8Hz,1H),7.79(d,J=7.9 Hz,1H),6.94(d,J=9.1Hz,2H),6.90–6.83(m,2H),5.15(dd,J=13.3,5.1Hz,1H),4.59–4.35(m,4H), 3.70(s,3H),3.62–3.60(m,2H),3.40(d,J=10.8Hz,2H),3.23-3.19(m,2H),3.08(t,J=11.9Hz,2H), 3.01–2.87(m,1H),2.65(dd,J=23.9,9.3Hz,1H),2.48–2.38(m,1H),2.10–1.94(m,1H).LCMS(ESI)C 25 H 29N4O4 + [M+H] + :Calculated value 449.22, measured value 449.3.

[0182] Example 28: Preparation of 3-(1-oxo-5-((4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04451)

[0183] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04451) (white solid, 63 mg, yield 56%) was prepared. 1 H NMR (400MHz, DMSO) δ11.03(s,1H),10.79(s,1H),7.86(d,J=9.2Hz,2H),7.74(d,J=7.1Hz,1H),7.58( d,J=8.5Hz,2H),7.13(d,J=8.8Hz,2H),5.16(dd,J=13.3,5.2Hz,1H),4.55–4.50(m,2H),4.40(d,J=17 .4Hz,1H),4.00(s,1H),3.49–3.38(m,2H),3.30–3.26(m,1H),3.22(d,J=11.5Hz,4H),2.93(dd,J=21 .7,9.0Hz,1H),2.62(d,J=16.2Hz,1H),2.40(dd,J=31.1,17.5Hz,2H),2.11–1.98(m,1H).LCMS(ESI)C 25 H 26 F3N4O3 + [M+H] + :Calculated value 487.20, measured value 487.2.

[0184] Example 29: Preparation of 3-(5-((4-(3-fluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04452)

[0185] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04452) (white solid, 71 mg, yield 54%) was prepared. 1H NMR (400MHz, DMSO) δ11.03(s,1H),10.86(s,1H),7.86(d,J=7.2Hz,2H),7.75(d,J=7.6Hz,1H),7.27(dd, J=16.0,7.9Hz,1H),6.82(t,J=10.1Hz,2H),6.64(t,J=8.3Hz,1H),5.16(dd,J=13.3,5.1Hz,1H),4.63–4 .44(m,3H),4.40(d,J=17.6Hz,1H),3.88(d,J=9.4Hz,2H),3.16(d,J=8.9Hz,4H),2.93(dd,J=21.8,9.5H z,1H),2.64(t,J=15.9Hz,1H),2.42(dd,J=13.1,8.8Hz,1H),2.04(dd,J=16.7,11.2Hz,1H).LCMS(ESI)C 24 H 26 FN4O3 + [M+H] + :Calculated value 437.20, measured value 437.2.

[0186] Example 30: Preparation of 3-(5-((4-(4-fluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04453)

[0187] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04453) (white solid, 85 mg, yield 65%) was prepared. 1 H NMR (400MHz, DMSO) δ11.36(s,1H),11.03(s,1H),7.92(s,1H),7.82(dd,J=17.3,7.8Hz,2H) ,7.11(t,J=8.9Hz,2H),7.06–6.93(m,2H),5.16(dd,J=13.2,5.0Hz,1H),4.62–4.46(m,3H), 4.39(d,J=17.6Hz,1H),3.71(d,J=10.5Hz,2H),3.40(d,J=9.6Hz,2H),3.25–3.07(m,4H),2 .99–2.85(m,1H),2.62(d,J=16.9Hz,1H),2.47–2.31(m,1H),2.08–1.94(m,1H).LCMS(ESI)C 24 H 26 FN4O3 + [M+H] +:Calculated value 437.20, measured value 437.2.

[0188] Example 31: Preparation of 3-(5-((4-(2-chlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04454)

[0189] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04454) (white solid, 48 mg, yield 39%) was prepared. 1 H NMR (400MHz, DMSO) δ11.03(s,1H),10.69(s,1H),7.86(d,J=7.6Hz,2H),7.77(d,J=7.3 Hz,1H),7.46(d,J=6.7Hz,1H),7.35(t,J=7.1Hz,1H),7.21(d,J=8.0Hz,1H),7.12(t,J =7.5Hz,1H),5.16(dd,J=13.3,5.1Hz,1H),4.53(d,J=18.2Hz,3H),4.40(d,J=17.6Hz, 1H),3.43(d,J=12.6Hz,4H),3.28(d,J=12.3Hz,2H),3.12(t,J=11.4Hz,2H),2.98–2.87 (m,1H),2.62(d,J=18.1Hz,1H),2.43(dd,J=17.7,9.1Hz,1H),2.07–1.98(m,1H).LCMS(ESI)C 24 H 26 ClN4O3 + [M+H] + :Calculated value 453.17, measured value 453.2.

[0190] Example 32: Preparation of 3-(5-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04455)

[0191] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04455) (white solid, 64 mg, yield 51%) was prepared. 1H NMR (400MHz, DMSO) δ11.20(s,1H),11.03(s,1H),7.92–7.81(m,2H),7.78(d,J=7.7Hz,1H) ,7.29(d,J=9.0Hz,2H),7.00(d,J=9.1Hz,2H),5.16(dd,J=13.3,5.1Hz,1H),4.66–4.45(m, 3H),4.39(d,J=17.6Hz,1H),3.81(d,J=9.1Hz,2H),3.39(s,2H),3.16(d,J=8.6Hz,4H),3. 01–2.85(m,1H),2.64(t,J=16.0Hz,1H),2.48–2.34(m,1H),2.07–1.97(m,1H).LCMS(ESI)C 24 H 26 ClN4O3 + [M+H] + :Calculated value 453.17, measured value 453.2.

[0192] Example 33: Preparation of 3-(5-((4-(2-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04456)

[0193] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04456) (white solid, 59 mg, yield 53%) was prepared. 1 H NMR (400MHz, DMSO) δ11.03(s,1H),10.61(s,1H),7.86(d,J=6.3Hz,2H),7.77(d,J=7.7Hz,1H),7 .64(d,J=7.8Hz,1H),7.39(t,J=7.3Hz,1H),7.22(d,J=6.9Hz,1H),7.06(t,J=7.6Hz,1H),5.16( dd,J=13.4,5.1Hz,1H),4.71–4.46(m,3H),4.40(d,J=17.8Hz,1H),3.50–3.38(m,4H),3.28(s,3 H),3.11(t,J=11.8Hz,2H),2.99–2.89(m,1H),2.68–2.60(m,1H),2.11–1.95(m,1H).LCMS(ESI)C 24 H 26 BrN4O3 + [M+H] + :Calculated value 497.12, measured value 497.1.

[0194] Example 34: Preparation of 3-(5-((4-(3-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04467)

[0195] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04467) (white solid, 58 mg, yield 52%) was prepared. 1 H NMR (400MHz, DMSO) δ11.05(s,1H),11.01(s,1H),7.96–7.79(m,2H),7.76(d,J=7.8Hz,1H),7.19 (dd,J=17.0,8.9Hz,2H),6.98(dd,J=14.5,5.7Hz,2H),5.15(dd,J=13.3,5.1Hz,1H),4.69–4.45( m,3H),4.39(d,J=17.6Hz,1H),3.87(d,J=9.4Hz,2H),3.38(d,J=9.0Hz,2H),3.18(d,J=9.6Hz,4 H),2.97–2.85(m,1H),2.63(t,J=15.4Hz,1H),2.46–2.36(m,1H),2.06–1.97(m,1H).LCMS(ESI)C 24 H 26 BrN4O3 + [M+H] + :Calculated value 497.12, measured value 497.1.

[0196] Example 35: Preparation of 3-(5-((4-(3-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04485)

[0197] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04485) (white solid, 59 mg, yield 53%) was prepared. 1H NMR (400MHz, DMSO) δ11.39(s,1H),11.01(s,1H),7.91(s,1H),7.81(dd,J=19.6,7.8Hz,2H),7.40(d,J=8.9Hz,2H),6.94(d,J= 9.0Hz,2H),5.15(dd,J=13.2,5.0Hz,1H),4.45(dd,J=52.4,17.4Hz,4H),3.80(d,J=10.3Hz,2H),3.38(d,J=8.1Hz,2H),3.25– 3.09(m,4H),3.01–2.84(m,1H),2.61(d,J=16.7Hz,1H),2.43(dd,J=13.1,4.4Hz,1H),2.08–1.93(m,1H).LCMS(ESI)C 24 H 26 BrN4O3 + [M+H] + :Calculated value 497.12, measured value 497.1.

[0198] Example 36: Preparation of 3-(1-oxo-5-((4-(o-tolyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04461)

[0199] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04461) (white solid, 77 mg, yield 58%) was prepared. 1 H NMR (400MHz, DMSO) δ11.03(s,1H),10.81(s,1H),7.92–7.83(m,2H),7.79(d,J=8.0Hz,1H),7.19(t,J= 8.1Hz,2H),7.03(dd,J=12.4,5.0Hz,2H),5.16(dd,J=13.3,5.2Hz,1H),4.53(d,J=17.6Hz,3H),4.40(d ,J=17.6Hz,1H),3.26(d,J=11.4Hz,2H),3.19(d,J=13.0Hz,2H),3.08(t,J=12.1Hz,2H),2.98–2.88(m, 1H),2.64(t,J=15.5Hz,1H),2.44(dd,J=13.3,4.5Hz,1H),2.26(s,3H),2.06–1.98(m,1H).LCMS(ESI)C 25 H 29 N4O3 + [M+H] +:Calculated value 433.2, measured value 433.3.

[0200] Example 37: Preparation of 3-(1-oxo-5-((4-(m-tolyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04462)

[0201] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04462) (white solid, 71 mg, yield 53%) was prepared. 1 H NMR (400MHz, DMSO) δ11.12(s,1H),11.01(s,1H),7.95–7.82(m,2H),7.78(d,J=7.9Hz,1H),7.14(t,J =7.8Hz,1H),6.82–6.73(m,2H),6.68(d,J=7.4Hz,1H),5.15(dd,J=13.3,5.0Hz,1H),4.61–4.46(m,3 H),4.40(d,J=17.6Hz,1H),3.79(d,J=10.4Hz,2H),3.40(d,J=10.1Hz,2H),3.23–3.07(m,4H),2.98– 2.88(m,1H),2.64(t,J=15.6Hz,1H),2.47–2.38(m,1H),2.26(s,3H),2.07–1.99(m,1H).LCMS(ESI)C 25 H 29 N4O3 + [M+H] + :Calculated value 433.2, measured value 433.3.

[0202] Example 38: Preparation of 3-(1-oxo-5-((4-(p-tolyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04463)

[0203] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04463) (white solid, 74 mg, yield 56%) was prepared. 1H NMR (400MHz, DMSO) δ11.16(s,1H),11.01(s,1H),7.90(s,1H),7.84(d,J=7.8Hz,1H),7.79(d,J=7.9Hz,1 H),7.07(d,J=8.4Hz,2H),6.88(d,J=8.5Hz,2H),5.15(dd,J=13.3,5.1Hz,1H),4.52(d,J=17.2Hz,3H),4 .39(d,J=17.6Hz,1H),3.72(d,J=12.0Hz,2H),3.39(d,J=12.4Hz,2H),3.12(dd,J=25.6,13.1Hz,3H),3. 00–2.87(m,1H),2.62(d,J=16.9Hz,1H),2.47–2.36(m,1H),2.21(s,3H),2.06–1.98(m,1H).LCMS(ESI)C 25 H 29 N4O3 + [M+H] + :Calculated value 433.2, measured value 433.3.

[0204] Example 39: Preparation of 3-(5-((4-(2,4-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04464)

[0205] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04464) (white solid, 44 mg, yield 39%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.96(s,1H),7.92–7.80(m,2H),7.77(d,J=7.6Hz,1H),7.60(d,J =2.3Hz,1H),7.41(dd,J=8.6,2.3Hz,1H),7.22(t,J=7.3Hz,1H),5.15(dd,J=13.2,5.1Hz,1H),4.52( d,J=18.0Hz,3H),4.39(d,J=17.4Hz,1H),3.42(t,J=12.6Hz,4H),3.25(d,J=10.5Hz,2H),3.19–3.10 (m,2H),2.98–2.87(m,1H),2.63(t,J=15.9Hz,1H),2.46–2.37(m,1H),2.08–1.95(m,1H).LCMS(ESI)C 24 H 25Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0206] Example 40: Preparation of 3-(5-((4-(2,5-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04487)

[0207] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04487) (white solid, 51 mg, yield 52%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.83(s,1H),7.85(d,J=10.7Hz,2H),7.77(d,J=8. 1Hz,1H),7.48(d,J=8.5Hz,1H),7.23(s,1H),7.18(d,J=8.3Hz,1H),5.15(dd,J=13.4, 5.0Hz,1H),4.46(dd,J=51.6,17.7Hz,4H),3.53–3.37(m,4H),3.15(s,2H),3.01–2.86 (m,2H),2.63(t,J=16.1Hz,1H),2.37(d,J=30.0Hz,2H),2.09–1.93(m,1H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0208] Example 41: Preparation of 3-(5-((4-(2,6-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04613)

[0209] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04613) (white solid, 57 mg, yield 58%) was prepared. 1H NMR(400MHz,MeOD)δ7.94(d,J=7.8Hz,1H),7.81(s,1H),7.74(d,J=8.1Hz,1H),7 .40(d,J=32.2Hz,2H),7.18(t,J=8.1Hz,1H),5.19(dd,J=13.3,5.1Hz,1H),4.66– 4.48(m,4H),3.79(s,2H),3.44(d,J=33.6Hz,4H),3.13(s,2H),2.98–2.84(m,1H) ,2.84–2.72(m,1H),2.52(qd,J=13.2,4.8Hz,1H),2.28–2.13(m,1H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0210] Example 42: Preparation of 3-(5-((4-(3,4-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04437)

[0211] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04437) (white solid, 72 mg, yield 64%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),11.00–10.89(m,1H),7.85(d,J=7.8Hz,2H),7.75(d,J=7.6Hz,1H) ,7.47(d,J=9.0Hz,1H),7.23(d,J=2.6Hz,1H),6.98(dd,J=9.0,2.7Hz,1H),5.15(dd,J=13.3,5.1Hz, 1H),4.52(d,J=17.3Hz,3H),4.40(d,J=17.6Hz,1H),3.90(d,J=10.2Hz,2H),3.37(s,2H),3.26–3.08 (m,4H),3.00–2.89(m,1H),2.62(d,J=17.7Hz,1H),2.47–2.33(m,1H),2.07–1.98(m,1H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0212] Example 43: Preparation of 3-(5-((4-(3,5-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04614)

[0213] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04614) (white solid, 77 mg, yield 68%) was prepared. 1 H NMR(400MHz,MeOD)δ7.94(d,J=7.9Hz,1H),7.78(s,1H),7.71(d,J=7.9Hz,1H ),6.98(s,2H),6.93(s,1H),5.19(dd,J=13.3,5.2Hz,1H),4.58(q,J=17.1Hz, 4H),3.91(s,2H),3.40(dd,J=48.0,7.4Hz,4H),3.13(s,2H),2.98–2.86(m,1 H),2.79(d,J=15.3Hz,1H),2.58–2.42(m,1H),2.26–2.12(m,1H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0214] Example 44: Preparation of 3-(5-((4-(2,3-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04515)

[0215] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04515) (white solid, 55 mg, yield 53%) was prepared. 1H NMR (400MHz, DMSO) δ11.01(s,1H),10.97(s,1H),7.94–7.80(m,2H),7.76(d,J=7.9Hz,1H),7.10(dq, J=16.6,7.9Hz,2H),6.92(t,J=7.8Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.46(dd,J=51.1,17.5Hz,4H ),3.53(d,J=10.1Hz,2H),3.41(s,2H),3.22(d,J=11.8Hz,3H),2.94(dd,J=23.1,10.3Hz,1H),2.62( d,J=17.4Hz,1H),2.43(dd,J=13.3,4.4Hz,1H),2.10–1.92(m,1H),1.19(t,J=7.2Hz,1H).LCMS(ESI)C 24 H 25 F2N4O3 + [M+H] + :Calculated value 455.19, measured value 455.2.

[0216] Example 45: Preparation of 3-(5-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04438)

[0217] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04438) (white solid, 77 mg, yield 62%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,2H),7.92–7.83(m,2H),7.78(d,J=7.8Hz,1H),7.26(ddd,J=12.1,9.0 ,2.8Hz,1H),7.14(td,J=9.4,5.9Hz,1H),7.05(dd,J=11.4,5.3Hz,1H),5.15(dd,J=13.3,5.1Hz,1H ),4.60–4.47(m,3H),4.40(d,J=17.5Hz,1H),3.39(s,4H),3.26(d,J=9.9Hz,2H),3.16(t,J=11.2Hz ,2H),3.00–2.88(m,1H),2.64(t,J=15.6Hz,1H),2.47–2.31(m,1H),2.07–1.97(m,1H).LCMS(ESI)C 24 H 25 F2N4O3 +[M+H] + :Calculated value 455.19, measured value 455.2.

[0218] Example 46: Preparation of 3-(5-((4-(2,5-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04539)

[0219] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04539) (white solid, 37 mg, yield 35%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.85(s,1H),7.85(d,J=7.7Hz,2H),7.75(d,J=7. 0Hz,1H),7.27–7.15(m,1H),7.01–6.95(m,1H),6.85–6.82(m,1H),5.15(dd,J=13.3,5 .1Hz,1H),4.51–4.37(m,4H),3.54(d,J=11.0Hz,2H),3.43–3.40(m,2H),3.31-3.25(m ,2H),3.19–3.15(m,2H),3.00–2.82(m,1H),2.61(d,J=18.4Hz,1H),2.43(dd,J=13.3, 4.5Hz,1H),2.12–1.89(m,1H).LCMS(ESI)C 24 H 25 F2N4O3 + [M+H] + :Calculated value 455.19, measured value 455.2.

[0220] Example 47: Preparation of 3-(5-((4-(2,6-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04540)

[0221] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04540) (white solid, 47 mg, yield 45%) was prepared. 1H NMR (400MHz, DMSO) δ11.01 (s, 1H), 10.87 (s, 1H), 7.93–7.81 (m, 2H), 7.76 (d, J = 8.0Hz, 1H), 7.19–7.15(m,1H),7.10–7.05(m,2H),5.15(dd,J=13.2,5.1Hz,1H),4.54–4.37(m,4H),3.5 2(t,J=11.7Hz,2H),3.41–3.37(m,2H),3.33–3.29(m,2H),3.21–3.17(m,2H),3.01–2.83(m ,1H),2.61(d,J=17.9Hz,1H),2.43(dd,J=13.1,4.5Hz,1H),2.09–1.92(m,1H).LCMS(ESI)C 24 H 25 F2N4O3 + [M+H] + :Calculated value 455.19, measured value 455.2.

[0222] Example 48: Preparation of 3-(5-((4-(3,4-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04529)

[0223] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04529) (white solid, 51 mg, yield 49%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.72(s,1H),7.85(d,J=7.9Hz,2H),7.73(d,J=7.7Hz,1H), 7.31(dd,J=19.7,9.5Hz,1H),7.08(ddd,J=13.8,6.9,2.8Hz,1H),6.80–6.76(m,1H),5.15(dd, J=13.2,5.0Hz,1H),4.60–4.33(m,4H),3.80(d,J=11.4Hz,2H),3.51–3.39(m,2H),3.22–3.07( m,4H),3.01–2.82(m,1H),2.67–2.60(m,1H),2.46–2.36(m,1H),2.09–1.86(m,1H).LCMS(ESI)C 24 H 25 F2N4O3 + [M+H] + :Calculated value 455.19, measured value 455.2.

[0224] Example 49: Preparation of 3-(5-((4-(3,5-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04496)

[0225] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04496) (white solid, 68 mg, yield 55%) was prepared. 1 H NMR (400MHz, DMSO) δ11.11(s,1H),11.02(s,1H),7.92–7.80(m,2H),7.75(d,J=7.8Hz,1 H),6.70(d,J=9.1Hz,2H),6.58(t,J=9.2Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.54–4.3 7(m,4H),3.93(d,J=12.9Hz,2H),3.41-3.38(m,2H),3.27–3.15(m,4H),3.02–2.85(m,1 H),2.61(d,J=16.4Hz,1H),2.43(dd,J=13.0,4.5Hz,1H),2.05–2.01(m,1H).LCMS(ESI)C 24 H 25 F2N4O3 + [M+H] + :Calculated value 455.19, measured value 455.2.

[0226] Example 50: Preparation of 3-(5-((4-(2,4-dimethylphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04439)

[0227] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04439) (white solid, 87 mg, yield 68%) was prepared. 1H NMR (400MHz, DMSO) δ11.13(s,1H),11.01(s,1H),7.93(s,1H),7.83(q,J=7.9Hz,2H),7.04–6.95(m,2H),6.92(d,J=8.0Hz,1H) ,5.15(dd,J=13.3,5.0Hz,1H),4.58–4.48(m,3H),4.40(d,J=17.6Hz,1H),3.38(d,J=11.2Hz,2H),3.23(d,J=7.8Hz,2H),3.11 (s,4H),3.00–2.87(m,1H),2.64(t,J=16.0Hz,1H),2.47–2.33(m,1H),2.21(s,6H),2.07–1.98(m,1H).LCMS(ESI)C 26 H 31 N4O3 + [M+H] + :Calculated value 447.24, measured value 447.3.

[0228] Example 51: Preparation of 3-(5-((4-(5-chloro-2-methylphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04440)

[0229] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04440) (white solid, 58 mg, yield 49%) was prepared. 1 H NMR (400MHz, DMSO) δ11.02(s,1H),10.78(s,1H),7.92–7.81(m,2H),7.78(d,J=7.9Hz,1H),7.22(d ,J=8.2Hz,1H),7.06(dd,J=14.2,5.0Hz,2H),5.16(dd,J=13.2,5.1Hz,1H),4.53(d,J=17.4Hz,3H), 4.40(d,J=17.7Hz,1H),3.41(d,J=11.8Hz,2H),3.31–3.19(m,4H),3.08(t,J=11.7Hz,2H),2.99–2 .86(m,1H),2.64(t,J=15.5Hz,1H),2.47–2.37(m,1H),2.23(s,3H),2.07–1.99(m,1H).LCMS(ESI)C 25 H 28 ClN4O3 + [M+H] +:Calculated value 467.18, measured value 467.2.

[0230] Example 52: Preparation of 3-(1-oxo-5-((4-phenylpiperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04465)

[0231] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04465) (white solid, 60 mg, yield 46%) was prepared. 1 H NMR(400MHz,DMSO)δ11.01(s,1H),10.49(s,1H),7.89–7.81(m,2H),7.75(d,J=8.0Hz,1H), 7.37–7.30(m,2H),7.23(t,J=6.3Hz,3H),5.15(dd,J=13.2,5.1Hz,1H),4.46(dt,J=32.3,17 .6Hz,4H),3.46(d,J=12.3Hz,2H),3.15–3.01(m,2H),2.98–2.89(m,1H),2.80(t,J=11.4Hz ,1H),2.63(t,J=15.3Hz,1H),2.46–2.37(m,1H),1.99(dd,J=26.0,12.6Hz,4H).LCMS(ESI)C 25 H 28 N3O3 + [M+H] + :Calculated value 418.21, measured value 418.3.

[0232] Example 53: Preparation of 3-(5-((4-(3-bromophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04466)

[0233] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04466) (white solid, 34 mg, yield 31%) was prepared. 1H NMR (400MHz, DMSO) δ11.01 (s, 1H), 10.43 (s, 1H), 7.85 (d, J = 7.4Hz, 2H), 7.77–7.69 (m, 1H),7.47–7.39(m,2H),7.31(t,J=7.8Hz,1H),7.24(d,J=7.8Hz,1H),5.15(dd,J=13.3, 5.0Hz,1H),4.46(dt,J=34.1,17.6Hz,4H),3.46(d,J=12.4Hz,2H),3.06(s,2H),2.97– 2.80(m,2H),2.63(t,J=15.1Hz,1H),2.46–2.36(m,1H),2.08–1.93(m,5H).LCMS(ESI)C 25 H 27 BrN3O3 + [M+H] + :Calculated value 496.12, measured value 496.1.

[0234] Example 54: Preparation of 3-(5-((4-(4-bromophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04493)

[0235] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04493) (white solid, 45 mg, yield 41%) was prepared. 1 H NMR (400MHz, DMSO) δ11.02(s,1H),10.54(s,1H),7.85(d,J=10.2Hz,2H),7.75(d,J=7.8Hz,1H),7.53(d,J=8.4Hz,2H),7.19(d,J=8.5Hz,2H),5.15(dd,J= 13.3,5.1Hz,1H),4.54–4.37(m,4H),3.46(d,J=10.8Hz,2H),3.05(d,J=11.1Hz,2H),2.99–2.87(m ,1H),2.85–2.78(m,1H),2.63(t,J=15.5Hz,1H),2.46–2.39(m,1H),2.05–2.01(m,5H).LCMS(ESI)C 25 H 27 BrN3O3 + [M+H] + :Calculated value 496.12, measured value 496.1.

[0236] Example 55: Preparation of 3-(5-((4-(2-chlorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04468)

[0237] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04468) (white solid, 51 mg, yield 41%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.70(s,1H),7.91–7.79(m,2H),7.76(d,J=7.9Hz,1H),7.45(d,J= 7.9Hz,1H),7.37(t,J=7.0Hz,1H),7.33–7.22(m,2H),5.15(dd,J=13.3,5.1Hz,1H),4.46(dt,J=31.1,1 7.6Hz,4H),3.47(d,J=11.6Hz,2H),3.19(dt,J=31.7,10.8Hz,3H),2.98–2.88(m,1H),2.61(d,J=17.3H z,1H),2.43(dd,J=13.0,4.4Hz,1H),2.04(dd,J=21.3,8.7Hz,3H),1.95(d,J=12.8Hz,2H).LCMS(ESI)C 25 H 27 ClN3O3 + [M+H] + :Calculated value 452.17, measured value 452.2.

[0238] Example 56: Preparation of 3-(5-((4-(4-chlorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04469)

[0239] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04469) (white solid, 73 mg, yield 58%) was prepared. 1H NMR (400MHz, DMSO) δ11.01(s,1H),10.46(s,1H),7.85(d,J=7.6Hz,2H),7.74(d,J=8.0H z,1H),7.39(d,J=8.4Hz,2H),7.25(d,J=8.5Hz,2H),5.15(dd,J=13.3,5.2Hz,1H),4.55– 4.38(m,4H),3.46(d,J=11.4Hz,2H),3.06(d,J=9.1Hz,2H),2.96–2.88(m,1H),2.82(s,1 H),2.63(t,J=15.5Hz,1H),2.43(dd,J=13.0,4.3Hz,1H),2.06–1.94(m,5H).LCMS(ESI)C 25 H 27 ClN3O3 + [M+H] + :Calculated value 452.17, measured value 452.2.

[0240] Example 57: Preparation of 3-(5-((4-(2-fluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04470)

[0241] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04470) (white solid, 35 mg, yield 27%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.48(s,1H),7.85(d,J=7.3Hz,2H),7.74(d,J=8.1Hz,1H) ,7.29(dd,J=17.0,7.6Hz,2H),7.23–7.15(m,2H),5.15(dd,J=13.3,5.0Hz,1H),4.46(dt,J=29 .3,17.6Hz,4H),3.46(d,J=11.2Hz,2H),3.20–3.06(m,3H),2.97–2.87(m,1H),2.61(d,J=16. 8Hz,1H),2.43(dd,J=13.1,4.1Hz,1H),2.14–1.99(m,3H),1.93(d,J=13.4Hz,2H).LCMS(ESI)C 25 H 27 FN3O3 + [M+H] + :Calculated value 436.20, measured value 436.2.

[0242] Example 58: Preparation of 3-(5-((4-(4-fluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04471)

[0243] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04471) (white solid, 57 mg, yield 43%) was prepared. 1 H NMR(400MHz,DMSO)δ11.01(s,1H),10.61(s,1H),7.88–7.80(m, 2H),7.76(d,J=7.8Hz,1H),7.26(dd,J=8.6,5.6Hz,2H),7.16(t,J=8.9Hz,2H) ,5.15(dd,J=13.2,5.1Hz,1H),4.46(dt,J=31.7,17.6Hz,4H),3.45(d,J=11.8 Hz,2H),3.11–2.99(m,2H),2.98–2.89(m,1H),2.82(t,J=11.7Hz,1H),2.63(t ,J=15.4Hz,1H),2.47–2.38(m,1H),1.98(dd,J=27.8,12.4Hz,5H).LCMS(ESI)C 25 H 27 FN3O3 + [M+H] + :Calculated value 436.20, measured value 436.2.

[0244] Example 59: Preparation of 3-(1-oxo-5-((4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04488)

[0245] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04488) (white solid, 46 mg, yield 40%) was prepared. 1H NMR (400MHz, DMSO) δ11.01(s,1H),10.48(s,1H),7.85(d,J=8.3Hz,2H),7.72(t,J=8.9Hz,3H) ,7.53(d,J=8.2Hz,1H),7.46(t,J=7.7Hz,1H),5.15(dd,J=13.2,5.0Hz,1H),4.46(dt,J=32.0, 17.6Hz,4H),3.46(d,J=11.8Hz,2H),3.26–3.09(m,3H),3.00–2.85(m,1H),2.70–2.57(m,1H) ,2.46–2.38(m,1H),2.24–2.09(m,2H),2.09–1.96(m,1H),1.88(d,J=13.3Hz,2H).LCMS(ESI)C 26 H 27 F3N3O3 + [M+H] + :Calculated value 486.20, measured value 486.2.

[0246] Example 60: Preparation of 3-(1-oxo-5-((4-(3-trifluoromethyl)phenyl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04472)

[0247] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04472) (white solid, 52 mg, yield 46%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01 (s, 1H), 10.60 (s, 1H), 7.89–7.82 (m, 2H), 7.76 (d, J = 8. 1Hz,1H),7.63–7.54(m,4H),5.15(dd,J=13.3,5.1Hz,1H),4.47(dt,J=38.7,17.6H z,4H),3.48(d,J=11.0Hz,2H),3.07(dd,J=21.7,9.6Hz,2H),2.99–2.89(m,2H),2. 61(d,J=17.6Hz,1H),2.43(dd,J=12.9,4.1Hz,1H),2.11–1.97(m,5H).LCMS(ESI)C 26 H 27 F3N3O3 + [M+H] + :Calculated value 486.20, measured value 486.2.

[0248] Example 61: Preparation of 3-(5-((4-(2,3-dichlorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04551)

[0249] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04551) (white solid, 59 mg, yield 60%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.18(s,1H),7.86(d,J=7.8Hz,1H),7.82(s,1H) ,7.72(d,J=7.6Hz,1H),7.56(d,J=7.9Hz,1H),7.40(t,J=8.0Hz,1H),7.29(d,J=7.5H z,1H),5.15(dd,J=13.2,5.3Hz,1H),4.54–4.38(m,5H),4.19–3.98(m,4H),3.03–2. 84(m,2H),2.73–2.58(m,2H),2.44(d,J=13.1Hz,1H),2.04–1.93(m,4H).LCMS(ESI)C 25 H 26 Cl2N3O3 + [M+H] + :Calculated value 486.13, measured value 486.1.

[0250] Example 62: Preparation of 3-(5-((4-(2-chloro-3-fluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04553)

[0251] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04553) (white solid, 60 mg, yield 59%) was prepared. 1H NMR(400MHz,DMSO)δ11.01(s,1H),10.00(s,1H),7.87–7.84(m, 2H),7.74(d,J=7.8Hz,1H),7.47–7.38(m,1H),7.34–7.30(m,1H),7.18–7.12(m,1H),5.15(dd,J=13.3,5.0Hz,1H),4.55–4.46(m,5H),3.5 2–3.47(m,2H),3.24–3.20(m,3H),3.00–2.84(m,2H),2.63(t,J=15.2Hz,1H),2.43(dd,J=13.2,4.5Hz,1H),2.05–2.01(m,5H).LCMS(ESI)C 25 H 26 ClFN3O3 + [M+H] + :Calculated value 470.16, measured value 470.2.

[0252] Example 63: Preparation of 3-(5-((4-(2,3-difluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04552)

[0253] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04552) (white solid, 59 mg, yield 56%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.28(s,1H),7.89–7.81(m,2H),7.73(d,J=8 .0Hz,1H),7.35–7.31(m,1H),7.24–7.19(m,1H),7.11–7.08(m,1H),5.15(dd,J=1 3.2,4.9Hz,1H),4.52–4.42(m,5H),3.52–3.48(m,2H),3.15–3.12(m,3H),3.02–2 .85(m,2H),2.70–2.57(m,2H),2.46–2.38(m,1H),2.10–1.90(m,5H).LCMS(ESI)C 25 H 26 F2N3O3 + [M+H] + :Calculated value 454.19, measured value 454.2.

[0254] Example 64: Preparation of 3-(5-((4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04550)

[0255] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04550) (white solid, 57 mg, yield 58%) was prepared. 1 H NMR(400MHz,DMSO)δ11.01(s,1H),10.85(s,1H),7.94–7.82(m,2H),7.78(d,J=7.5Hz,1H),7 .63(dd,J=8.1,1.3Hz,1H),7.40(t,J=7.9Hz,1H),7.25(dd,J=7.7,1.5Hz,1H),5.75(s,1H),5 .15(dd,J=13.3,5.1Hz,1H),4.66–4.34(m,4H),3.91–3.71(m,2H),3.69–3.56(m,1H),3.01– 2.75(m,2H),2.69–2.53(m,3H),2.43(dd,J=13.4,4.5Hz,1H),2.09–1.92(m,1H).LCMS(ESI)C 25 H 24 Cl2N3O3 + [M+H] + :Calculated value 484.12, measured value 484.1.

[0256] Example 65: Preparation of 3-(5-((4-(2-chloro-3-fluorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04554)

[0257] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04554) (white solid, 57 mg, yield 56%) was prepared. 1H NMR (400MHz, DMSO) δ11.01(s,1H),10.61(s,1H),7.86(d,J=8.1Hz,2H),7.76(d,J= 7.0Hz,1H),7.43–7.40(m,2H),7.18–7.10(m,1H),5.79(s,1H),5.15(dd,J=13.2,5. 1Hz,1H),4.64–4.35(m,5H),3.87–3.78(m,2H),3.65–3.60(m,1H),2.97–2.79(m,2 H),2.72–2.58(m,2H),2.43(dd,J=13.2,4.6Hz,1H),2.10–1.92(m,1H).LCMS(ESI)C 25 H 24 ClFN3O3 + [M+H] + :Calculated value 468.15, measured value 468.2.

[0258] Example 66: Preparation of 3-(1-oxo-5-((4-(pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04449)

[0259] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04449) (white solid, 75 mg, yield 54%) was prepared. 1 H NMR (400MHz, DMSO) δ12.06 (s, 1H), 11.02 (s, 1H), 8.12 (dd, J= 5.8,1.4Hz,1H),7.97(t,J=7.9Hz,1H),7.93(s,1H),7.86–7.76(m,2H),7.30(d,J= 9.0Hz,1H),6.98(t,J=6.4Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.54–4.50(m,4H) ,4.39(d,J=17.6Hz,3H),3.6br6(s,2H),3.44(brs,2H),3.22(brs,2H),2.94–2.89 (m,1H),2.62(d,J=16.8Hz,1H),2.47–2.39(m,1H),2.08–1.93(m,1H).LCMS(ESI)C 23 H 26 N5O3 + [M+H] + :Calculated value 420.20, measured value 420.2.

[0260] Example 67: Preparation of 3-(5-((4-(6-methylpyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04530)

[0261] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04530) (white solid, 20 mg, yield 19%) was prepared. 1 H NMR(400MHz,DMSO)δ12.05(s,1H),11.01(s,1H),7.93(s,1H),7.91–7.76(m,3H),7.0 9(d,J=8.7Hz,1H),6.85(d,J=7.2Hz,1H),5.14(dd,J=13.3,5.1Hz,1H),4.62–4.35(m ,6H),3.71–3.60(m,2H),3.50–3.37(m,3H),3.31–3.12(m,2H),2.93–2.89(m,1H),2. 61(d,J=17.6Hz,1H),2.53(s,3H),2.48–2.41(m,1H),2.04–2.01(m,1H).LCMS(ESI)C 24 H 28 N5O3 + [M+H] + :Calculated value 434.22, measured value 434.2.

[0262] Example 68: Preparation of 3-(5-((4-(6-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04497)

[0263] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04497) (white solid, 31 mg, yield 30%) was prepared. 1H NMR (400MHz, DMSO) δ11.59(s,1H),11.02(s,1H),7.90(s,1H),7.83(d,J=7.8Hz,1H),7.78(d, J=7.8Hz,1H),7.64(dd,J=8.3,7.6Hz,1H),6.89(d,J=8.4Hz,1H),6.78(d,J=7.5Hz,1H),5.15 (dd,J=13.3,5.1Hz,1H),4.54–4.31(m,6H),3.44–3.36(m,4H),3.13–3.08(m,2H),3.00–2.85 (m,1H),2.61(d,J=16.5Hz,1H),2.43(dd,J=13.1,4.5Hz,1H),2.09–1.91(m,1H).LCMS(ESI)C 23 H 25 ClN5O3 + [M+H] + :Calculated value 454.16, measured value 454.2.

[0264] Example 69: Preparation of 3-(5-((4-(5-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04431)

[0265] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04431) (white solid, 91 mg, yield 73%) was prepared. 1 H NMR (400MHz, DMSO) δ11.37(s,1H),11.02(s,1H),8.18(d,J=2.6Hz,1H),7.89(s,1H),7.84(d,J=7 .8Hz,1H),7.77(d,J=8.0Hz,1H),7.71(dd,J=9.1,2.7Hz,1H),6.98(d,J=9.1Hz,1H),5.15(dd,J=1 3.3,5.1Hz,1H),4.43(dt,J=33.2,16.6Hz,6H),3.35(dd,J=25.9,12.5Hz,4H),3.10(d,J=11.2Hz, 2H),3.00–2.86(m,1H),2.62(d,J=16.6Hz,1H),2.47–2.37(m,1H),2.07–1.98(m,1H).LCMS(ESI)C 23 H 25 ClN5O3 + [M+H] +:Calculated value 454.16, measured value 454.

[0266] Example 70: Preparation of 3-(5-((4-(4-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04430)

[0267] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04430) (white solid, 89 mg, yield 72%) was prepared. 1 H NMR (400MHz, DMSO) δ11.86(s,1H),11.02(s,1H),8.12(d,J=5.6Hz,1H),7.92(s,1H),7.81( q,J=8.1Hz,2H),7.15(d,J=1.3Hz,1H),6.87(dd,J=5.6,1.6Hz,1H),5.15(dd,J=13.3,5.1Hz ,1H),4.44(dt,J=24.4,17.8Hz,6H),3.57–3.28(m,4H),3.11(s,2H),2.99–2.86(m,1H),2. 61(d,J=17.3Hz,1H),2.44(dd,J=13.1,4.4Hz,1H),2.02(dd,J=9.0,3.6Hz,1H).LCMS(ESI)C 23 H 25 ClN5O3 + [M+H] + :Calculated value 454.16, measured value 454.2.

[0268] Example 71: Preparation of 3-(5-((4-(3-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04428)

[0269] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04428) (white solid, 82 mg, yield 66%) was prepared. 1H NMR (400MHz, DMSO) δ11.70(s,1H),11.02(s,1H),8.26(dd,J=4.7,1.6Hz,1H),7.95(s,1H),7.87( dd,J=7.8,1.6Hz,1H),7.83(s,2H),7.10(dd,J=7.8,4.7Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4. 54–4.36(m,4H),3.83(d,J=13.5Hz,2H),3.39(t,J=13.9Hz,4H),3.29–3.16(m,2H),2.93(ddd,J= 17.3,9.5,4.1Hz,1H),2.62(d,J=16.6Hz,1H),2.49–2.38(m,1H),2.10–1.94(m,1H).LCMS(ESI)C 23 H 25 ClN5O3 + [M+H] + :Calculated value 454.16, measured value 454.2.

[0270] Example 72: Preparation of 3-(5-((4-(3-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04578)

[0271] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04578) (white solid, 33 mg, yield 30%) was prepared. 1 H NMR(400MHz,MeOD)δ8.07(dd,J=5.4,1.3Hz,1H),7.95(d,J=7.8Hz,1H),7.90(s,1H),7.81–7.73(m,2H),7.20–7.09(m,1H),5.20(dd,J=13.3,5.2H z,1H),4.80–4.54(m,4H),4.27(s,2H),3.77–3.40(m,6H),2.99–2.90(m, 1H),2.85–2.74(m,1H),2.60–2.49(m,1H),2.25–2.19(m,1H).LCMS(ESI)C 23 H 25 FN5O3 + [M+H] + :Calculated value 438.19, measured value 438.3.

[0272] Example 73: Preparation of 3-(5-((4-(6-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04498)

[0273] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04498) (white solid, 23 mg, yield 21%) was prepared. 1 H NMR (400MHz, DMSO) δ11.47(s,1H),11.01(s,1H),7.89(s,1H),7.83(d,J=7.8Hz,1H),7.76(dt,J=11 .8,6.7Hz,2H),6.79(dd,J=8.2,2.3Hz,1H),6.40(dd,J=7.7,2.5Hz,1H),5.15(dd,J=13.3,5.0Hz,1 H),4.45(q,J=17.7Hz,4H),4.31(d,J=13.4Hz,2H),3.37(t,J=13.1Hz,4H),3.13–3.09(m,2H),3.01 –2.85(m,1H),2.61(d,J=17.2Hz,1H),2.43(dd,J=13.1,4.4Hz,1H),2.09–1.92(m,1H).LCMS(ESI)C 23 H 25 FN5O3 + [M+H] + :Calculated value 438.19, measured value 438.3.

[0274] Example 74: Preparation of 3-(5-((4-(5-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04531)

[0275] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04531) (white solid, 40 mg, yield 37%) was prepared. 1H NMR (400MHz, DMSO) δ11.68 (s, 1H), 11.01 (s, 1H), 8.15 (d, J = 3.0 Hz,1H),7.93(s,1H),7.86–7.76(m,2H),7.66–7.57(m,1H),6.99(dd,J=9 .3,3.4Hz,1H),5.14(dd,J=13.3,5.1Hz,1H),4.70–4.34(m,5H),4.28(d, J=13.2Hz,2H),3.39–3.32(m,4H),3.12–3.05(m,2H),3.01–2.82(m,1H), 2.61(d,J=17.3Hz,1H),2.47–2.35(m,1H),2.05–2.01(m,1H).LCMS(ESI)C 23 H 25 FN5O3 + [M+H] + :Calculated value 438.19, measured value 438.3.

[0276] Example 75: Preparation of 3-(1-oxo-5-((4-(3-trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04434)

[0277] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04434) (white solid, 59 mg, yield 52%) was prepared. 1 H NMR (400MHz, DMSO) δ11.29(s,1H),11.02(s,1H),8.60(d,J=3.5Hz,1H),8.15(dd,J=7.9,1 .6Hz,1H),7.93(s,1H),7.82(q,J=8.0Hz,2H),7.33(dd,J=7.5,5.1Hz,1H),5.15(dd,J=13. 2,5.1Hz,1H),4.63–4.39(m,4H),3.54–3.35(m,6H),3.21(d,J=10.9Hz,2H),2.99–2.87(m ,1H),2.62(d,J=17.2Hz,1H),2.44(dd,J=13.1,4.4Hz,1H),2.11–1.92(m,1H).LCMS(ESI)C 24 H 25 F3N5O3 + [M+H] + :Calculated value 488.19, measured value 488.2.

[0278] Example 76: Preparation of 3-(1-oxo-5-((4-(6-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04432)

[0279] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04432) (white solid, 60 mg, yield 53%) was prepared. 1 H NMR (400MHz, DMSO) δ11.02(s,1H),10.93(s,1H),7.84(s,3H),7.73(d,J=7.8Hz,1H) ,7.20(dd,J=24.1,8.0Hz,2H),5.16(dd,J=13.1,5.1Hz,1H),4.60–4.34(m,6H),3.45 (d,J=12.6Hz,2H),3.37(s,1H),3.33–3.29(m,1H),3.15(s,2H),3.00–2.89(m,1H), 2.62(d,J=15.6Hz,1H),2.44(dd,J=13.6,4.2Hz,1H),2.08–1.99(m,1H).LCMS(ESI)C 24 H 25 F3N5O3 + [M+H] + :Calculated value 488.19, measured value 488.2.

[0280] Example 77: Preparation of 3-(1-oxo-5-((4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04433)

[0281] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04433) (white solid, 86 mg, yield 76%) was prepared. 1H NMR (400MHz, DMSO) δ11.18(s,1H),11.02(s,1H),8.48(s,1H),7.93(dd,J=9.2,2.4Hz,1 H),7.85(d,J=8.0Hz,2H),7.74(d,J=8.4Hz,1H),7.08(d,J=9.1Hz,1H),5.15(dd,J=13. 3,5.1Hz,1H),4.46(dd,J=51.1,17.7Hz,6H),3.42(d,J=11.4Hz,4H),3.13(s,2H),3.00 –2.85(m,1H),2.66(d,J=14.8Hz,1H),2.47–2.39(m,1H),2.12–1.97(m,1H).LCMS(ESI)C 24 H 25 F3N5O3 + [M+H] + :Calculated value 488.19, measured value 488.2.

[0282] Example 78: Preparation of 3-(5-((4-(3,4-dichloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04532)

[0283] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04532) (white solid, 19 mg, yield 19%) was prepared. 1 H NMR (400MHz, DMSO) δ11.38 (s, 1H), 11.01 (s, 1H), 8.21 (d, J = 5.3 Hz,1H),7.91(s,1H),7.81(q,J=7.9Hz,2H),7.38(d,J=5.3Hz,1H),5.14(d d,J=13.3,5.1Hz,1H),4.60–4.33(m,4H),3.86(d,J=13.3Hz,2H),3.39(dd, J=25.0,12.5Hz,5H),3.23(d,J=10.2Hz,2H),3.00–2.85(m,1H),2.61(d,J =17.0Hz,1H),2.43(dd,J=13.1,4.4Hz,1H),2.05–2.01(m,1H).LCMS(ESI)C 23 H 24 Cl2N5O3 + [M+H] + :Calculated value 488.13, measured value 488.2.

[0284] Example 79: Preparation of 3-(5-((4-(3,5-dichloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04479)

[0285] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04479) (white solid, 54 mg, yield 48%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.95(s,1H),8.33(d,J=2.1Hz,1H),8.13(d,J=1.9Hz,1H) ,7.89–7.79(m,2H),7.76(d,J=7.8Hz,1H),5.14(dd,J=13.2,5.0Hz,1H),4.52(d,J=17.2Hz,3 H),4.39(d,J=17.6Hz,1H),3.85(d,J=11.8Hz,2H),3.43(d,J=9.6Hz,2H),3.31–3.17(m,4H), 3.00–2.87(m,1H),2.63(t,J=15.8Hz,1H),2.46–2.36(m,1H),2.05–1.97(m,1H).LCMS(ESI)C 23 H 24 Cl2N5O3 + [M+H] + :Calculated value 488.13, measured value 488.2.

[0286] Example 80: Preparation of 3-(5-((4-(4,5-dichloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04533)

[0287] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04533) (white solid, 19 mg, yield 19%) was prepared. 1H NMR (400MHz, DMSO) δ11.44(s,1H),11.01(s,1H),8.30(s,1H),7.88(s,1H),7. 79(dd,J=29.5,7.8Hz,2H),7.29(s,1H),5.14(dd,J=13.3,5.1Hz,1H),4.60–4. 31(m,6H),3.38(t,J=12.5Hz,4H),3.15–3.01(m,2H),3.00–2.85(m,1H),2.61( d,J=17.5Hz,1H),2.43(dd,J=13.2,4.5Hz,1H),2.08–1.86(m,1H).LCMS(ESI)C 23 H 24 Cl2N5O3 + [M+H] + :Calculated value 488.13, measured value 488.2.

[0288] Example 81: Preparation of 3-(5-((4-(3,4-difluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04579)

[0289] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04579) (white solid, 37 mg, yield 35%) was prepared. 1 H NMR(400MHz,MeOD)δ8.03(t,J=6.4Hz,1H),7.95(d,J=7.9Hz,1H),7.88(s,1H) ,7.77(d,J=7.9Hz,1H),7.01-6.96(m,1H),5.20(dd,J=13.2,5.2Hz,1H),4.69 –4.52(m,4H),4.40–4.18(m,2H),3.60(brs,2H),3.51–3.38(m,4H),2.99–2.9 0(m,1H),2.85–2.79(m,1H),2.60–2.49(m,1H),2.24–2.19(m,1H).LCMS(ESI)C 23 H 24 F2N5O3 + [M+H] + :Calculated value 456.18, measured value 456.2.

[0290] Example 82: Preparation of 3-(5-((4-(4-chloro-3-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04610)

[0291] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04610) (white solid, 45 mg, yield 45%) was prepared. 1 H NMR(400MHz,MeOD)δ8.03(d,J=5.3Hz,1H),7.97(d,J=7.8Hz, 1H),7.88(s,1H),7.79(d,J=7.8Hz,1H),7.14(t,J=5.0Hz,1H),5.23(dd, J=13.3,5.1Hz,1H),4.57(d,J=13.5Hz,4H),4.26(d,J=11.4Hz,2H),3.57 (s,2H),3.39(dd,J=23.5,11.0Hz,4H),2.98(ddd,J=18.7,11.8,5.0Hz,1H),2.88–2.76(m,1H),2.61–2.50(m,1H),2.30–2.15(m,1H).LCMS(ESI)C 23 H 24 ClFN5O3 + [M+H] + :Calculated value 472.15, measured value 472.2.

[0292] Example 83: Preparation of 3-(5-((4-(3-fluoro-4-iodopyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04557)

[0293] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04557) (white solid, 42 mg, yield 48%) was prepared. 1 H NMR (400MHz, DMSO) δ11.53(s,1H),11.01(s,1H),7.91(s,1H),7.80(dd,J=16.9,7.9Hz ,2H),7.72(d,J=5.1Hz,1H),7.39(dd,J=5.0,3.7Hz,1H),5.14(dd,J=13.3,5.1Hz,1H), 4.51–4.36(m,4H),4.04(d,J=14.0Hz,3H),3.53–3.33(m,4H),3.21–3.17(m,2H),3.00– 2.84(m,1H),2.61(d,J=17.2Hz,1H),2.48–2.38(m,1H),2.10–1.91(m,1H).LCMS(ESI)C 23 H24 FIN5O3 + [M+H] + :Calculated value 564.09, measured value 564.1.

[0294] Example 84: Preparation of 3-(5-((4-(3-bromo-4-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04615)

[0295] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04615) (white solid, 47 mg, yield 52%) was prepared. 1 H NMR (400MHz, MeOD) δ8.23(d,J=5.3Hz,1H),7.97(d,J=7.8Hz,1H),7.86(s,1H),7.78(d,J =8.1Hz,1H),7.32(d,J=5.2Hz,1H),5.22(dd,J=13.4,5.1Hz,1H),4.67–4.51(m,4H),3.99 (d,J=13.9Hz,2H),3.61(d,J=11.9Hz,2H),3.44(t,J=11.2Hz,2H),3.28(s,2H),3.04–2.9 0(m,1H),2.85–2.74(m,1H),2.55(qd,J=13.4,4.9Hz,1H),2.28–2.11(m,1H).LCMS(ESI)C 23 H 24 BrClN5O3 + [M+H] + :Calculated value 532.07, measured value 532.1.

[0296] Example 85: Preparation of 3-(5-((4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04480)

[0297] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04480) (white solid, 54 mg, yield 51%) was prepared. 1H NMR (400MHz, DMSO) δ11.17(s,1H),11.01(s,1H),8.62(s,1H),8.29(s,1H),7.90–7.80( m,2H),7.76(d,J=7.5Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.52(d,J=17.2Hz,3H),4.3 9(d,J=17.5Hz,1H),4.11(d,J=13.2Hz,2H),3.43(t,J=12.2Hz,4H),3.25(s,2H),2.99– 2.87(m,1H),2.61(d,J=17.6Hz,1H),2.48–2.35(m,1H),2.06–1.98(m,1H).LCMS(ESI)C 24 H 24 ClF3N5O3 + [M+H] + :Calculated value 522.15, measured value 522.2.

[0298] Example 86: Preparation of 3-(5-((4-(4-chloro-6-methylpyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04491)

[0299] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04491) (white solid, 69 mg, yield 62%) was prepared. 1 H NMR(400MHz,DMSO)δ11.67(s,1H),11.01(s,1H),7.90(s,1H), 7.82(d,J=7.8Hz,1H),7.78(d,J=7.9Hz,1H),6.91(s,1H),6.75(s,1H),5.15(dd,J=13.3,5.1Hz,1H),4.57–4.38(m,6H),3.43–3.35(m,4H) ),3.11–3.04(m,2H),3.01–2.85(m,1H),2.61(d,J=16.9Hz,1H),2.43(dd,J=13.0,4.5Hz,1H),2.34(s,3H),2.05–2.01(m,1H).LCMS(ESI)C 24 H 27 ClN5O3 + [M+H] + :Calculated value 468.18, measured value 468.2.

[0300] Example 87: Preparation of 3-(1-oxo-5-((4-(pyridin-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04508)

[0301] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04508) (white solid, 45 mg, yield 22%) was prepared. 1 H NMR (400MHz, DMSO) δ11.97(s,1H),11.01(s,1H),8.53(d,J=2.6Hz,1H),8.26(d,J=5.3Hz,1H), 8.08(dd,J=8.9,2.3Hz,1H),7.93(s,1H),7.90–7.76(m,3H),5.15(dd,J=13.2,5.0Hz,1H),4.5 8–4.34(m,4H),4.10(brs,2H),3.66–3.57(m,2H),3.23(brs,2H),3.18–3.06(m,2H),2.99–2.8 6(m,1H),2.62(d,J=16.7Hz,1H),2.44(dd,J=13.1,4.4Hz,1H),2.08–1.95(m,1H).LCMS(ESI)C 23 H 26 N5O3 + [M+H] + :Calculated value 420.20, measured value 420.3.

[0302] Example 88: Preparation of 3-(5-((4-(6-chloropyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04537)

[0303] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04537) (white solid, 25 mg, yield 24%) was prepared. 1H NMR (400MHz, DMSO) δ11.44(s,1H),11.01(s,1H),8.13(d,J=3.1Hz,1H),7.90(s,1H),7.81(dd,J=22 .9,7.9Hz,2H),7.48(dd,J=8.9,3.2Hz,1H),7.36(d,J=8.8Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4. 68–4.34(m,4H),3.89(d,J=12.7Hz,2H),3.39(d,J=11.3Hz,2H),3.22(dt,J=19.7,12.6Hz,4H),3.0 1–2.85(m,1H),2.61(d,J=17.1Hz,1H),2.43(dd,J=13.2,4.6Hz,1H),2.05–2.01(m,1H).LCMS(ESI)C 23 H 25 ClN5O3 + [M+H] + :Calculated value 454.16, measured value 454.2.

[0304] Example 89: Preparation of 3-(5-((4-(4,5-dichloropyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04538)

[0305] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04538) (white solid, 50 mg, yield 51%) was prepared. 1 H NMR (400MHz, DMSO) δ11.87(s,1H),11.01(s,1H),8.52(s,1H),8.40(s,1H),7. 97(s,1H),7.84(q,J=7.9Hz,2H),5.15(dd,J=13.2,5.1Hz,1H),4.61–4.48(m,4 H),3.55(d,J=12.4Hz,2H),3.42(t,J=10.7Hz,4H),3.26(s,2H),3.00–2.85(m, 1H),2.62(d,J=17.3Hz,1H),2.47–2.39(m,1H),2.10–1.92(m,1H).LCMS(ESI)C 23 H 24 Cl2N5O3 + [M+H] + :Calculated value 488.13, measured value 488.1.

[0306] Example 90: Preparation of 3-(5-((4-(2,4-dichloropyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04896)

[0307] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04896) (white solid, 30 mg, yield 40%) was prepared. 1 H NMR (400MHz, DMSO) δ7.36(s,1H),7.13(d,J=8.3Hz,1H),7.05(s,1H),6.97(s,1H),6.73(s,1H),4.41–4.29(m,2H),3.92–3.76(m,4H) ,3.02-2.99(m,2H),2.77(d,J=12.0Hz,2H),2.69–2.60(m,2H),2.21–1.98(m,1H),1.78–1.56(m,2H),1.51–1.39(m,1H).LCMS(ESI)C 23 H 24 Cl2N5O3 + [M+H] + :Calculated value 488.13, measured value 488.1.

[0308] Example 91: Preparation of 3-(1-oxo-5-((4-(pyridin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04450)

[0309] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04450) (white solid, 36 mg, yield 29%) was prepared. 1 H NMR (400MHz, CDCl3) δ11.01(s,1H),8.35(d,J=7.3Hz,2H),7.90(s,1H),7.82(d,J =7.7Hz,1H),7.76(d,J=7.5Hz,1H),7.25(d,J=7.6Hz,2H),5.14(dd,J=13.3,5.1Hz ,1H),4.54–4.35(m,6H),3.71(brs,2H),3.44(brs,2H),3.16(brs,2H),3.01–2.89 (m,1H),2.61(d,J=17.3Hz,1H),2.48–2.40(m,1H),2.05–2.01(m,1H).LCMS(ESI)C 23 H 26 N5O3 +[M+H] + :Calculated value 420.20, measured value 420.2.

[0310] Example 92: Preparation of 3-(5-((4-(2-methylpyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04541)

[0311] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04541) (white solid, 20 mg, yield 18%) was prepared. 1 H NMR (400MHz, DMSO) δ14.23 (s, 1H), 12.36 (s, 1H), 11.01 (s, 1H), 8.23 ​​(d, J = 7.1Hz, 1H), 7.92(s,1H),7.80(dd,J=13.9,7.3Hz,2H),7.19(s,1H),7.13(d,J=7.4Hz,1H),5.14(d d,J=13.2,4.9Hz,1H),4.44(dd,J=52.6,17.4Hz,7H),3.72(s,4H),3.20(s,2H),3.02– 2.83(m,2H),2.61(d,J=16.9Hz,2H),2.46–2.37(m,1H),2.09–1.90(m,1H).LCMS(ESI)C 24 H 28 N5O3 + [M+H] + :Calculated value 434.22, measured value 434.3.

[0312] Example 93: Preparation of 3-(5-((4-(3-bromopyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04580)

[0313] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04580) (white solid, 20 mg, yield 21%) was prepared. 1H NMR (400MHz, MeOD) δ8.86(d,J=1.1Hz,1H),8.54(dd,J=6.9,1.2Hz,1H),8.00–7.91(m,2H),7.80(d,J=7.8Hz,1H),7.54(d,J=6.9Hz,1H),5.21(dd,J=13. 3,5.2Hz,1H),4.70–4.52(m,4H),4.36(brs,2H),3.62(brs,6H),3.02-2.83( m,1H),2.83–2.79(m,1H),2.60–2.49(m,1H),2.24-2.19(m,1H).LCMS(ESI)C 23 H 25 BrN5O3 + [M+H] + :Calculated value 498.11, measured value 498.1.

[0314] Example 94: Preparation of 3-(5-((4-(3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04581)

[0315] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04581) (white solid, 21 mg, yield 19%) was prepared. 1 H NMR (400MHz, MeOD) δ8.62 (dd, J=8.5, 1.1Hz, 1H), 8.32 (dd, J= 7.1,1.1Hz,1H),7.96(d,J=7.8Hz,1H),7.92(s,1H),7.78(d,J=8.9Hz,1H),7.49(dd,J=8.7,7.1Hz,1H),5.21(dd,J=13.3,5.1Hz,1H),4. 70–4.51(m,4H),4.16-3.83(m,4H),3.59(s,4H),3.02–2.85(m,1H),2.84–2.79(m,1H),2.60–2.49(m,1H),2.22–2.19(m,1H).LCMS(ESI)C 23 H 25 FN5O3 + [M+H] + :Calculated value 438.19, measured value 438.2.

[0316] Example 95: Preparation of 3-(5-((4-(3-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04481)

[0317] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04481) (white solid, 30 mg, yield 24%) was prepared. 1 H NMR (400MHz, DMSO) δ12.41(s,1H),11.01(s,1H),8.81(s,1H),8.53(d,J=6.8Hz,1H),7.97(s, 1H),7.88–7.72(m,2H),7.51(d,J=6.8Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.56(s,2H),4.49 (s,1H),4.38(d,J=17.6Hz,1H),4.18(s,2H),3.77(s,2H),3.44(s,2H),3.31(s,2H),2.99–2.8 8(m,1H),2.61(d,J=16.9Hz,1H),2.43(tt,J=13.2,6.7Hz,1H),2.07–1.98(m,1H).LCMS(ESI)C 23 H 25 ClN5O3 + [M+H] + :Calculated value 454.16, measured value 454.1.

[0318] Example 96: Preparation of 3-(5-((4-(2-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04435)

[0319] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04435) (white solid, 72 mg, yield 58%) was prepared. 1H NMR (400MHz, DMSO) δ12.12(s,1H),11.02(s,1H),8.12(d,J=6.5Hz,1H),7.92(s,1H),7.81(q,J=7.8H z,2H),7.15(d,J=2.3Hz,1H),7.02(dd,J=6.6,2.4Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.50(s,2H), 4.40(s,2H),4.24(d,J=12.6Hz,2H),3.56(s,2H),3.36(s,2H),3.27–3.09(m,2H),2.93(ddd,J=17.4 ,9.5,4.2Hz,1H),2.61(d,J=16.7Hz,1H),2.47–2.34(m,1H),2.02(dd,J=9.0,3.5Hz,1H).LCMS(ESI)C 23 H 25 ClN5O3 + [M+H] + :Calculated value 454.16, measured value 454.2.

[0320] Example 97: Preparation of 3-(5-((4-(2-chloro-3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04612)

[0321] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04612) (white solid, 47 mg, yield 47%) was prepared. 1 H NMR(400MHz,MeOD)δ8.02(d,J=5.8Hz,1H),7.92(t,J=8.4Hz,1H),7.86(s,1H),7. 76(d,J=7.9Hz,1H),7.09(t,J=6.2Hz,1H),5.18(dd,J=13.3,5.1Hz,1H),4.66–4.4 8(m,4H),4.01(s,2H),3.44(t,J=47.5Hz,6H),2.92(ddd,J=18.5,13.5,5.3Hz,1H ),2.84–2.69(m,1H),2.51(tt,J=13.3,6.5Hz,1H),2.23–2.11(m,1H).LCMS(ESI)C 23 H 24 ClFN5O3 + [M+H] + :Calculated value 472.15, measured value 472.1.

[0322] Example 98: Preparation of 3-(5-((4-(2-bromo-3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04928)

[0323] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04928) (white solid, 24 mg, yield 31%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ8.07(d,J=6.2Hz,1H),7.92(t,J=7.8Hz,1H),7.87(s,1H),7.75(d,J=6.7Hz,1H),7.19(t,J=6.6Hz,1H),5.18(dd,J=13.3,5.1 Hz,1H),4.68–4.52(m,4H),4.15(brs,2H),3.75–3.37(m,6H),2.97–2.88(m ,1H),2.85–2.73(m,1H),2.58–2.47(m,1H),2.26–2.12(m,1H).LCMS(ESI)C 23 H 24 BrFN5O3 + [M+H] + :Calculated value 516.10, measured value 516.1.

[0324] Example 99: Preparation of 3-(5-((4-(3-bromo-2-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04616)

[0325] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04616) (white solid, 46 mg, yield 51%) was prepared. 1H NMR (400MHz, MeOD) δ8.25(d,J=5.5Hz,1H),7.96(d,J=7.8Hz,1H),7.88(s,1H),7.78(d,J=7.9Hz ,1H),7.13(d,J=5.5Hz,1H),5.21(dd,J=13.3,5.1Hz,1H),4.71–4.51(m,4H),3.84(d,J=13.2Hz, 2H),3.66(d,J=11.5Hz,2H),3.47(t,J=11.0Hz,2H),3.28(d,J=12.0Hz,2H),2.94(ddd,J=18.4,1 3.4,5.3Hz,1H),2.88–2.76(m,1H),2.55(qd,J=13.2,4.7Hz,1H),2.29–2.15(m,1H).LCMS(ESI)C 23 H 24 BrClN5O3 + [M+H] + :Calculated value 532.07, measured value 532.1.

[0326] Example 100: Preparation of 3-(5-((4-(2,3-dichloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04542)

[0327] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04542) (white solid, 65 mg, yield 67%) was prepared. 1 H NMR (400MHz, DMSO) δ11.93 (s, 1H), 11.01 (s, 1H), 8.22 (d, J = 5.5Hz, 1H), 7.96 (s, 1H) ),7.83(s,2H),7.20(d,J=5.5Hz,1H),5.15(dd,J=13.2,5.1Hz,1H),4.54–4.37(m, 4H),3.71(d,J=12.4Hz,2H),3.41(t,J=12.5Hz,4H),3.27–3.22(m,2H),2.98–2.92 (m,1H),2.62(d,J=16.7Hz,1H),2.48–2.35(m,1H),2.05–2.01(m,1H).LCMS(ESI)C 23 H 24 Cl2N5O3 + [M+H] + :Calculated value 488.13, measured value 488.1.

[0328] Example 101: Preparation of 3-(5-((4-(2,3-difluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04543)

[0329] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04543) (white solid, 62 mg, yield 59%) was prepared. 1 H NMR(400MHz,DMSO)δ11.90(s,1H),11.02(s,1H),7.94(s,1H),7.82(s,2H),7.80(d ,J=5.7Hz,1H),7.03(t,J=6.0Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.66–4.35(m,4 H),4.01–3.84(m,2H),3.65–3.46(m,2H),3.38(brs,2H),3.25(brs,2H),3.01–2.8 2(m,1H),2.62(d,J=17.1Hz,1H),2.48–2.40(m,1H),2.09–1.90(m,1H).LCMS(ESI)C 23 H 24 F2N5O3 + [M+H] + :Calculated value 456.18, measured value 456.2.

[0330] Example 102: Preparation of 3-(5-((4-(3-fluoro-2-hydroxypyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04929)

[0331] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04929) (white solid, 14 mg, yield 20%) was prepared. 1 H NMR (400 MHz, MeOD) LCMS (ESI) C 23 H 25 FN5O4 + [M+H] + :Calculated value 454.19, measured value 454.2.

[0332] Example 103: Preparation of 3-(5-((4-(3-bromo-5-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04600)

[0333] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04600) (white solid, 40 mg, yield 44%) was prepared. 1 H NMR (400MHz, MeOD) δ8.78(s,1H),8.68(s,1H),7.94(d,J=7.9Hz,1H),7.89(s,1H),7.78(d,J=8.1Hz,1H),5.19(dd,J=13.2,5.2Hz,1H),4.69–4.55(m, 4H),3.89–3.76(m,4H),3.64–3.61(m,2H),3.51–3.43(m,2H),3.02–2.85(m ,1H),2.84–2.74(m,1H),2.58–2.48(m,1H),2.29–2.09(m,1H).LCMS(ESI)C 23 H 24 BrClN5O3 + [M+H] + :Calculated value 532.07, measured value 532.1.

[0334] Example 104: Preparation of 3-(5-((4-(3-chloro-5-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04611)

[0335] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04611) (white solid, 25 mg, yield 25%) was prepared. 1 H NMR (400MHz, MeOD) δ8.77–8.58(m,2H),7.94(q,J=8.2Hz,2H),7.79(d,J=8.0Hz,1H),5.20(dt,J=13.4,6.7Hz,1H),4.67–4.53(m,4H),4.09(s,2H), 3.85(s,2H),3.65(s,2H),3.49(d,J=9.3Hz,2H),3.02–2.88(m,1H),2.88– 2.74(m,1H),2.55(dt,J=13.2,8.5Hz,1H),2.28–2.14(m,1H).LCMS(ESI)C 23 H 24 ClFN5O3 + [M+H] + :Calculated value 472.15, measured value 472.1.

[0336] Example 105: Preparation of 3-(5-((4-(3,5-dichloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04436)

[0337] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04436) (white solid, 45 mg, yield 40%) was prepared. 1 H NMR (400MHz, DMSO) δ11.81 (s, 1H), 10.99 (d, J = 12.5Hz, 1H), 8.52 (s, 2H), 7.98 (s, 1H), 7.8 4(q,J=8.0Hz,2H),5.15(dd,J=13.3,5.1Hz,1H),4.53(d,J=20.8Hz,3H),4.40(t,J=12.1H z,1H),3.84(t,J=12.3Hz,2H),3.43(dd,J=26.7,12.2Hz,4H),3.20(d,J=10.2Hz,2H),2.9 6–2.88(m,1H),2.61(d,J=17.1Hz,1H),2.47–2.37(m,1H),2.05–1.98(m,1H).LCMS(ESI)C 23 H 24 Cl2N5O3 + [M+H] + :Calculated value 488.13, measured value 488.1.

[0338] Example 106: Preparation of 3-(5-((4-(2,6-dimethylpyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04492)

[0339] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04492) (white solid, 43 mg, yield 34%) was prepared. 1H NMR (400MHz, DMSO) δ13.92(s,1H),12.29(s,1H),11.01(s,1H),7.92(s,1H),7.82(d,J=7.7Hz,1H),7.79–7.71(m,1H),7.05(s,2H) ,5.15(dd,J=13.3,5.1Hz,1H),4.57–4.31(m,6H),3.71(brs,2H),3.42(brs,2H),3.16(brs,2H),3.00–2.81(m,1H),2.61(d,J=17.1 Hz,1H),2.48(s,6H),2.45–2.41(m,1H),2.08–1.91(m,1H).LCMS(ESI)C 25 H 30 N5O3 + [M+H] + :Calculated value 448.23, measured value 448.3.

[0340] Example 107: Preparation of 3-(1-oxo-5-((4-(perfluoropyridin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04499)

[0341] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04499) (white solid, 41 mg, yield 42%) was prepared. 1 H NMR (400MHz, DMSO) δ11.80(s,1H),11.01(s,1H),7.92(s,1H),7.81(q,J=7.9Hz,2H),5.14(dd,J=13.3,5.1Hz,1H),4.60–4.33(m,4H),3.87–3.76(m, 4H),3.41(d,J=10.9Hz,2H),3.23(brs,2H),3.01–2.83(m,1H),2.61(d,J= 17.7Hz,1H),2.44(dd,J=13.1,4.4Hz,1H),2.10–1.91(m,1H).LCMS(ESI)C 23 H 22 F4N5O3 + [M+H] + :Calculated value 492.17, measured value 492.2.

[0342] Example 108: Preparation of 3-(1-oxo-5-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04473)

[0343] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04473) (white solid, 6 mg, yield 4%) was prepared. 1 H NMR (400MHz, DMSO) δ11.67 (s, 1H), 11.01 (s, 1H), 8.80 (d, J = 4.5Hz, 1H), 7.89 (s, 1H) ,7.87–7.79(m,2H),7.76(t,J=8.8Hz,2H),5.15(dd,J=13.2,5.1Hz,1H),4.52(d,J= 14.8Hz,5H),4.39(d,J=17.6Hz,1H),3.50(d,J=36.9Hz,4H),3.18(s,2H),2.97–2.8 8(m,1H),2.61(d,J=17.4Hz,1H),2.47–2.32(m,1H),2.06–1.98(m,1H).LCMS(ESI)C 22 H 25 N6O3 + [M+H] + :Calculated value 421.20, measured value 421.2.

[0344] Example 109: Preparation of 3-(5-((4-(6-chloropyridazin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04482)

[0345] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04482) (white solid, 53 mg, yield 43%) was prepared. 1 H NMR(400MHz,DMSO)δ11.37(s,1H),10.99(d,J=13.7Hz,1H),7.89–7.82(m,2H),7 .75(d,J=7.8Hz,1H),7.66(d,J=9.6Hz,1H),7.48(d,J=9.6Hz,1H),5.15(dd,J=1 3.2,5.1Hz,1H),4.55–4.34(m,6H),3.50–3.38(m,4H),3.16(s,2H),2.99–2.85( m,1H),2.63(t,J=15.5Hz,1H),2.47–2.36(m,1H),2.07–1.98(m,1H).LCMS(ESI)C 22 H 24 ClN6O3 + [M+H] +:Calculated value 455.16, measured value 455.2.

[0346] Example 110: Preparation of 3-(1-oxo-5-((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04484)

[0347] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04484) (white solid, 57 mg, yield 41%) was prepared. 1 H NMR (400MHz, DMSO) δ11.65(s,1H),11.01(s,1H),8.44(d,J=4.8Hz,2H),7.91(s,1H),7 .80(dd,J=17.4,7.9Hz,2H),6.77(t,J=4.8Hz,1H),5.14(dd,J=13.3,5.1Hz,1H),4.69 (d,J=13.9Hz,2H),4.48(dd,J=29.4,22.4Hz,4H),3.43(dd,J=24.5,12.2Hz,4H),3.08 (d,J=10.1Hz,2H),3.00–2.83(m,1H),2.61(d,J=17.3Hz,1H),2.44(dd,J=13.2,4.4Hz, 1H),2.09–1.94(m,1H).LCMS(ESI)C 22 H 25 N6O3 + [M+H] + :Calculated value 421.20, measured value 421.2.

[0348] Example 111: Preparation of 3-(1-oxo-5-((4-(pyrazin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04483)

[0349] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04483) (white solid, 75 mg, yield 54%) was prepared. 1H NMR (400MHz, DMSO) δ11.99(s,1H),11.01(s,1H),8.43(s,1H),8.20(d,J=1.3Hz,1H),7.99 –7.87(m,2H),7.80(d,J=8.0Hz,2H),5.13(d,J=5.1Hz,1H),4.50(t,J=14.5Hz,4H),4.40(t ,J=13.4Hz,2H),3.49(t,J=12.7Hz,2H),3.40(d,J=11.8Hz,2H),3.13(d,J=9.3Hz,2H),2. 99–2.87(m,1H),2.61(d,J=17.1Hz,1H),2.48–2.35(m,1H),2.08–1.94(m,1H).LCMS(ESI)C 22 H 25 N6O3 + [M+H] + :Calculated value 421.20, measured value 421.2.

[0350] Example 112: Preparation of 3-(5-((4-(5,6-dichloropyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04501)

[0351] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04501) (white solid, 41 mg, yield 42%) was prepared. 1 H NMR(400MHz,DMSO)δ11.65(s,1H),11.01(s,1H),8.52(s,1H),7.89(s,1H),7.83(d ,J=7.8Hz,1H),7.77(d,J=7.9Hz,1H),5.14(dd,J=13.3,5.1Hz,1H),4.53–4.36(m,6 H),3.57(t,J=12.9Hz,2H),3.44–3.39(m,2H),3.20(brs,2H),3.03–2.82(m,1H),2 .61(d,J=16.8Hz,1H),2.43(dd,J=13.1,4.4Hz,1H),2.10–1.91(m,1H).LCMS(ESI)C 22 H 23 Cl2N6O3 + [M+H] + :Calculated value 489.12, measured value 489.2.

[0352] Example 113: Preparation of 3-(5-((4-(3,6-dichloropyridazin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04500)

[0353] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04500) (white solid, 41 mg, yield 42%) was prepared. 1 H NMR(400MHz,DMSO)δ11.92(s,1H),11.01(s,1H),7.93(s,1H),7.82(s,2H),7.5 8(s,1H),5.15(dd,J=13.3,5.0Hz,1H),4.56–4.39(m,4H),3.96–3.86(m,2H),3. 51(t,J=11.8Hz,2H),3.43–3.34(m,2H),3.25(brs,2H),3.00–2.83(m,1H),2.61 (d,J=17.4Hz,1H),2.44(dd,J=13.0,4.3Hz,1H),2.10–1.93(m,1H).LCMS(ESI)C 22 H 23 Cl2N6O3 + [M+H] + :Calculated value 489.12, measured value 489.2.

[0354] Example 114: Preparation of 3-(5-((4-(1,3,5-triazin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04486)

[0355] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04486) (white solid, 45 mg, yield 32%) was prepared. 1H NMR(400MHz,DMSO)δ11.53(s,1H),11.01(s,1H),8.70(s,2H),7.87(s,1H),7.83(d ,J=7.8Hz,1H),7.75(d,J=7.7Hz,1H),5.14(dd,J=13.2,5.0Hz,1H),4.72(d,J=13. 4Hz,2H),4.56–4.34(m,4H),3.56–3.37(m,4H),3.12(s,2H),3.01–2.85(m,1H),2. 61(d,J=17.0Hz,1H),2.43(dd,J=13.0,4.4Hz,1H),2.09–1.93(m,1H).LCMS(ESI)C 21 H 24 N7O3 + [M+H] + : Calculated value 422.19, measured value 422.2.

[0356] Example 115: Preparation of 3-(5-((4-(3,4-dichloropyridin-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04690)

[0357] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04690) was prepared (white solid, 22 mg, yield 22%). 1 H NMR (400MHz, MeOD) δ8.30(d,J=5.2Hz,1H),7.83(d,J=7.8Hz,1H),7.75(s,1H),7.64(d,J=7.8Hz,1H),7.42(d,J=5.2Hz,1H),5.09(dd,J=13.3,5.1Hz,1H ),4.55–4.43(m,5H),3.56(d,J=14.0Hz,3H),3.19–3.07(m,1H),2.83–2.79( m,1H),2.75–2.64(m,1H),2.43–2.38(m,1H),2.14–2.03(m,5H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0358] Example 116: Preparation of 3-(5-((4-(2,3-dichloropyridin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04560)

[0359] Referring to the method of synthesis scheme 1, under appropriate conditions understood in the art, the target compound (GT-04560) was prepared (white solid, 36 mg, yield 37%). 1 H NMR (400MHz, DMSO) δ11.12(s,1H),11.00(s,1H),8.39(d,J=5.0Hz,1H),7.89(s,1H), 7.84–7.76(m,2H),7.37(d,J=5.1Hz,1H),5.14(dd,J=13.2,5.1Hz,1H),4.54–4.37(m ,4H),3.40–3.37(m,1H),3.33–3.27(m,1H),3.20–3.12(m,2H),3.02–2.83(m,1H),2. 64–2.59(m,1H),2.46–2.41(m,1H),2.23–2.07(m,2H),2.03–1.97(m,3H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0360] Example 117: Preparation of 3-(5-((4-(2,3-difluoropyridin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04556)

[0361] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04556) (white solid, 72 mg, yield 69%) was prepared. 1H NMR (400MHz, DMSO) δ11.18(s,1H),11.01(s,1H),8.04(d,J=5.0Hz,1H),7.91(s,1H),7 .81(dd,J=19.0,7.9Hz,2H),7.29(t,J=4.8Hz,1H),5.15(dd,J=13.3,5.0Hz,1H),4.54– 4.37(m,5H),3.53–3.40(m,3H),3.28–3.21(m,1H),3.16–3.04(m,2H),2.99–2.85(m,1H ),2.61(d,J=16.6Hz,1H),2.44(dd,J=13.1,4.4Hz,1H),2.05–2.01(m,3H).LCMS(ESI)C 24 H 25 F2N4O3 + [M+H] + :Calculated value 455.19, measured value 455.2.

[0362] Example 118: Preparation of 3-(5-([3,4'-bipiperidinyl]-1-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04591)

[0363] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04591) (white solid, 34 mg, yield 72%) was prepared. 1 H NMR(400MHz,MeOD)δ7.98–7.84(m,2H),7.76(d,J=7.9Hz,1H),5.20(dd,J=13.3 ,5.1Hz,1H),4.69–4.40(m,4H),3.57(d,J=12.4Hz,1H),3.45(t,J=13.1Hz,3H) ,3.09–2.76(m,6H),2.55(qd,J=13.3,4.7Hz,1H),2.30–2.15(m,1H),1.90(ddd ,J=40.7,32.6,15.1Hz,6H),1.71–1.41(m,3H),1.41–1.27(m,1H).LCMS(ESI)C 24 H 33 N4O3 + [M+H] + :Calculated value 425.25, measured value 425.3.

[0364] Example 119: Preparation of 3-(5-((3,4-dichloro-3',6'-dihydro-[2,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04570)

[0365] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04570) (white solid, 44 mg, yield 45%) was prepared. 1 H NMR (400MHz, DMSO) δ11.19(s,1H),11.00(s,1H),8.49(d,J=5.2Hz,1H),7.92(s,1H), 7.83(q,J=7.9Hz,2H),7.71(d,J=5.2Hz,1H),6.20(s,1H),5.15(dd,J=13.3,5.0Hz,1H ),4.66–4.33(m,4H),3.87–3.79(m,3H),3.28–3.17(m,1H),3.03–2.86(m,2H),2.66( dd,J=35.3,19.1Hz,2H),2.44(dd,J=13.1,4.5Hz,1H),2.10–1.92(m,1H).LCMS(ESI)C 24 H 23 Cl2N4O3 + [M+H] + :Calculated value 485.11, measured value 485.2.

[0366] Example 120: Preparation of 3-(5-((4,5-dichloro-3',6'-dihydro-[3,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04558)

[0367] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04558) (white solid, 24 mg, yield 24%) was prepared. 1H NMR(400MHz,DMSO)δ11.56(s,1H),11.01(s,1H),8.75(s,1H),8.39(s,1H),7.96(s ,1H),7.84(s,2H),5.91(s,1H),5.15(dd,J=13.3,5.1Hz,1H),4.51(dd,J=41.0,23. 4Hz,4H),3.88-3.78(m,2H),3.65–3.56(m,1H),3.32-3.24(m,1H),2.99–2.90(m,2 H),2.64–2.57(m,2H),2.44(dd,J=13.1,4.5Hz,1H),2.10–1.94(m,1H).LCMS(ESI)C 24 H 23 Cl2N4O3 + [M+H] + :Calculated value 485.11, measured value 485.2.

[0368] Example 121: Preparation of 3-(5-((5-chloro-3',6'-dihydro-[3,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04620)

[0369] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04620) (white solid, 29 mg, yield 28%) was prepared. 1 H NMR(400MHz,MeOD)δ8.89(dt,J=6.3,3.1Hz,2H),8.62–8.57(m,1H),7.97(d,J=7.9Hz,1H),7. 90(d,J=6.5Hz,1H),7.78(dd,J=17.6,13.8Hz,1H),6.52(s,1H),5.21(dd,J=13.4,5.2Hz,1H), 4.72–4.58(m,4H),4.04(d,J=2.5Hz,2H),3.91–3.86(m,1H),3.56–3.42(m,1H),3.07–2.96(m ,2H),2.97–2.87(m,1H),2.85–2.79(m,1H),2.64–2.46(m,1H),2.29–2.15(m,1H).LCMS(ESI)C 24 H 24 ClN4O3 + [M+H] + :Calculated value 451.15, measured value 451.2.

[0370] Example 122: Preparation of 3-(5-((2',3'-dichloro-3,6-dihydro-[4,4'-bipyridyl]-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04559)

[0371] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04559) (white solid, 52 mg, yield 53%) was prepared. 1 H NMR (400MHz, DMSO) δ11.59 (s, 1H), 11.00 (s, 1H), 8.40 (d, J = 4.9Hz, 1H), 7.95 (s, 1H) ),7.84(s,2H),7.35(d,J=4.9Hz,1H),5.91(s,1H),5.15(dd,J=13.2,5.1Hz,1H),4 .56(d,J=10.8Hz,2H),4.55–4.34(m,2H),3.86–3.79(m,2H),3.28(brs,1H),3.06– 2.85(m,2H),2.64–2.55(m,2H),2.46–2.42(m,1H),2.12–1.88(m,1H).LCMS(ESI)C 24 H 23 Cl2N4O3 + [M+H] + : Calculated value 485.11, measured value 485.1.

[0372] Example 123: Preparation of 3-(5-((3-fluoro-3',6'-dihydro-[2,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04689)

[0373] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04689) (white solid, 17 mg, yield 25%) was prepared. 1H NMR (400MHz, MeOD) δ8.47(d,J=4.0Hz,1H),7.97(d,J=7.8Hz,1H),7.88(s,1H),7.79(d,J=7.8H z,1H),7.73(dd,J=11.7,8.4Hz,1H),7.47(dt,J=8.4,4.2Hz,1H),6.63(s,1H),5.22(dd,J=13. 4,5.1Hz,1H),4.67–4.60(m,4H),4.04(s,2H),3.84(brs,1H),3.50–3.43(m,1H),3.13–2.96(m ,2H),2.94–2.84(m,1H),2.87–2.76(m,1H),2.62–2.49(m,1H),2.28–2.16(m,1H).LCMS(ESI)C 24 H 24 FN4O3 + [M+H] + :Calculated value 435.18, measured value 435.2.

[0374] Example 124: Preparation of 3-(5-((2',3'-difluoro-3,6-dihydro-[4,4'-bipyridyl]-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04555)

[0375] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04555) (white solid, 75 mg, yield 71%) was prepared. 1 H NMR (400MHz, DMSO) δ11.01(s,1H),10.85(s,1H),8.05(d,J=5.0Hz,1H),7.85(d,J=7.8Hz,2H),7. 76(d,J=7.4Hz,1H),7.42(t,J=5.1Hz,1H),6.34(s,1H),5.15(dd,J=13.2,5.1Hz,1H),4.62–4.37 (m,4H),3.98–3.77(m,2H),3.67–3.62(m,1H),3.30–3.19(m,1H),3.02–2.86(m,2H),2.70(d,J=2 4.2Hz,1H),2.62(d,J=16.9Hz,1H),2.43(dd,J=13.3,4.6Hz,1H),2.09–1.92(m,1H).LCMS(ESI)C 24 H 23 F2N4O3 + [M+H]+ :Calculated value 453.17, measured value 453.2.

[0376] Example 125: Preparation of 3-(5-((3-(2,3-dichlorophenyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04712)

[0377] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04712) (white solid, 29 mg, yield 30%) was prepared. 1 H NMR(400MHz,MeOD)δ7.93(d,J=14.0Hz,1H),7.76(dd,J=39.9,18.4Hz,2H), 7.47–7.12(m,3H),5.20(dd,J=13.4,5.1Hz,1H),4.90(s,2H),4.85–4.81(m, 2H),4.69–4.48(m,5H),3.98–3.74(m,3H),2.99–2.89(m,1H),2.86–2.78(m ,1H),2.53(dd,J=13.2,4.7Hz,1H),2.21(dd,J=8.8,3.8Hz,1H).LCMS(ESI)C 25 H 25 Cl2N4O3 + [M+H] + :Calculated value 499.13, measured value 499.1.

[0378] Example 126: Preparation of 3-(5-((6-(2,3-dichlorophenyl)-3,6-diazabicyclo[3.1.1]heptane-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04897)

[0379] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04897) (white solid, 48 mg, yield 63%) was prepared. 1H NMR(400MHz,DMSO)δ6.97(d,J=7.7Hz,1H),6.83–6.77(m,2H),6.27(t,J=8.2Hz,1H), 6.14(d,J=7.6Hz,1H),5.69(d,J=7.6Hz,1H),4.44(dd,J=13.3,4.7Hz,1H),4.01–3.9 3(m,1H),3.89–3.85(m,1H),3.70(brs,2H),3.58(brs,2H),3.07–2.81(m,4H),2.26– 2.10(m,2H),2.03(d,J=13.9Hz,1H),1.77(dd,J=13.2,4.6Hz,1H),1.50–1.32(m,2H). LCMS(ESI)C 25 H 25 Cl2N4O3 + [M+H] + :Calculated value 499.13, measured value 499.1.

[0380] Example 127: Preparation of 3-(5-(((1R,4R)-5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04724)

[0381] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04724) (white solid, 47 mg, yield 49%) was prepared. 1 H NMR (400MHz, MeOD) δ7.93(d,J=7.8Hz,1H),7.86(s,1H),7.77(d,J=7.9Hz,1H),7.20(t,J=8.0Hz,1H),7.14(s,1H),6 .99(d,J=7.5Hz,1H),5.20(dd,J=13.3,5.2Hz,1H),4.71(d,J=13.1Hz,1H),4.61(t,J=12.6Hz,3H),4.52(d,J=13.1Hz ,2H),3.88(dd,J=30.8,11.0Hz,2H),3.65(d,J=10.5Hz,1H),3.49(d,J=12.7Hz,1H),2.94(ddd,J=18.5,13.4,5.3Hz ,1H),2.86–2.76(m,1H),2.54(ddd,J=26.6,13.2,4.7Hz,2H),2.33(d,J=11.3Hz,1H),2.27–2.13(m,1H).LCMS(ESI)C25 H 25 Cl2N4O3 + [M+H] + :Calculated value 499.13, measured value 499.1.

[0382] Example 128: Preparation of 3-(5-(((1S,4S)-5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04898)

[0383] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04898) (white solid, 42 mg, yield 55%) was prepared. 1 H NMR (400MHz, DMSO) δ7.20–6.79(m,3H),6.51–6.08(m,3H),4.46–4.26(m,1H),3.82–3.64(m,5H),3.18–2.88(m,2H),2.84 –2.77(m,1H),2.69–2.61(m,1H),2.19–1.87(m,2H),1.83–1.60(m,2H),1.57–1.45(m,1H),1.42–1.28(m,2H).LCMS(ESI)C 25 H 25 Cl2N4O3 + [M+H] + :Calculated value 499.13, measured value 499.1.

[0384] Example 129: Preparation of 3-(5-((5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04930)

[0385] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04930) (white solid, 26 mg, yield 33%) was prepared. 1H NMR(400MHz,MeOD-d4)δ7.93(d,J=7.8Hz,1H),7.86(s,1H),7.78(d,J=7.6Hz,1 H),7.31–7.22(m,3H),5.19(dd,J=13.2,5.0Hz,1H),4.90–4.70(m,2H),4.65–4 .49(m,2H),3.90–3.55(m,5H),2.97–2.91(m,1H),2.85–2.74(m,1H),2.57–2.4 7(m,2H),2.38–2.29(m,1H),2.21–2.11(m,3H),1.95–1.87(m,1H).LCMS(ESI)C 26 H 27 Cl2N4O3 + [M+H] + :Calculated value 513.15, measured value 513.2.

[0386] Example 130: Preparation of 3-(5-((8-(2,3-dichlorophenyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04899)

[0387] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04899) (white solid, 41 mg, yield 53%) was prepared. 1 H NMR (400MHz, DMSO) δ7.19–7.11(m,1H),7.07–7.00(m,1H),7.00–6.92(m,1H),6 .45–6.39(m,2H),6.26–6.21(m,1H),4.44–4.39(m,1H),3.84–3.75(m,3H),3.47 –3.35(m,2H),2.87–2.79(m,2H),2.73-2.69(m,2H),2.21–2.11(m,1H),2.02–1. 98(m,1H),1.77–1.71(m,1H),1.51–1.39(m,3H),1.26–1.21(m,3H).LCMS(ESI)C 26 H 27 Cl2N4O3 + [M+H] + : Calculated value 513.15, measured value 513.2.

[0388] Example 131: Preparation of 3-(5-((3-(2,3-dichlorophenyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04855)

[0389] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04855) (white solid, 21 mg, yield 22%) was prepared. 1 H NMR(400MHz,MeOD)δ7.97(d,J=7.8Hz,1H),7.87(s,1H),7.79(d,J=7.7Hz,1H), 7.32(dt,J=12.4,8.0Hz,2H),7.18(d,J=6.8Hz,1H),5.24–5.19(m,2H),4.61(d ,J=6.9Hz,4H),4.47(s,2H),4.13(s,2H),3.39(s,2H),2.92(dd,J=13.5,5.3Hz ,1H),2.82(d,J=18.0Hz,1H),2.58–2.45(m,4H),2.26–2.15(m,1H).LCMS(ESI)C 26 H 27 Cl2N4O3 + [M+H] + :Calculated value 513.15, measured value 513.2.

[0390] Example 132: Preparation of 3-(5-((4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04856)

[0391] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04856) (white solid, 23 mg, yield 24%) was prepared. 1 H NMR(400MHz,MeOD)δ7.96(d,J=7.8Hz,1H),7.83(s,1H),7.76(d,J=7.7Hz,1H),7.33–7.22(m,3H),5.21(dd,J=13.2,5.1Hz,2H),4.65–4.59(m, 4H),3.64(s,4H),3.51(s,3H),3.35(s,1H),2.92(dd,J=13.2,5.2Hz,1H),2.84(s,1H),2.54(dd,J=13.3,4.8Hz,1H),2.23(s,2H).LCMS(ESI)C 25H 27 Cl2N4O3 + [M+H] + :Calculated value 501.15, measured value 501.2.

[0392] Example 133: Preparation of 3-(5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04254)

[0393] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04254) (white solid, 28 mg, yield 38%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ7.94(d,J=7.8Hz,1H),7.89(dd,J=8.8,5.1Hz,1H),7.80(s,1H), 7.72(d,J=7.8Hz,1H),7.43(d,J=6.8Hz,1H),7.21(td,J=9.0,2.1Hz,1H),5.19(dd,J=13. 5,5.2Hz,1H),4.62–4.49(m,4H),3.73–3.63(m,2H),3.61–3.42(m,2H),2.99–2.86(m,1H) ,2.82–2.76(m,1H),2.61–2.47(m,1H),2.46–2.38(m,2H),2.25–2.16(m,3H).LCMS(ESI)C 26 H 26 FN4O4 + [M+H] + :Calculated value 477.19, measured value 477.2.

[0394] Example 134: Preparation of 3-(5-((4-(Benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04907)

[0395] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04907) (white solid, 27 mg, yield 38%) was prepared. 1H NMR(400MHz,MeOD-d4)δ7.93(dd,J=7.9,2.0Hz,2H),7.84(s,1H),7.76(d,J=7.7Hz,1H),7.6 5(d,J=3.0Hz,2H),7.40(ddd,J=8.0,4.9,3.0Hz,1H),5.18(dd,J=13.3,5.1Hz,1H),4.55–4. 51(m,4H),3.67(d,J=11.7Hz,2H),3.57-3.44(m,2H),3.00–2.86(m,1H),2.81–2.70(m,1H), 2.53–2.47(m,1H),2.40(d,J=14.4Hz,3H),2.30–2.23(m,2H),2.21–2.13(m,1H).LCMS(ESI)C 26 H 27 N4O4 + [M+H] + :Calculated value 459.20, measured value 459.2.

[0396] Example 135: Preparation of 3-(5-((4-(isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04715)

[0397] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04715) (white solid, 21 mg, yield 25%) was prepared. 1 H NMR(400MHz,MeOD)δ8.65(t,J=11.6Hz,1H),7.95(t,J=8.2Hz,1H),7.82(s,1H),7.73(d,J=8.3Hz ,1H),6.51(t,J=13.1Hz,1H),5.21(dd,J=13.3,5.2Hz,1H),4.61–4.52(m,5H),3.66(d,J=12.0Hz, 2H),3.28–3.20(m,2H),2.94(dd,J=15.3,10.5Hz,1H),2.82(d,J=15.4Hz,1H),2.53(dt,J=13.5, 6.8Hz,1H),2.34(d,J=14.4Hz,2H),2.25–2.19(m,1H),2.00(dd,J=25.1,11.7Hz,2H).LCMS(ESI)C 22 H 25 N4O4 + [M+H] + :Calculated value 409.19, measured value 409.3.

[0398] Example 136: Preparation of 3-(5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04667)

[0399] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04667) (white solid, 62 mg, yield 62%) was prepared. 1 H NMR (400MHz, MeOD) δ8.01–7.91(m,2H),7.84(s,1H),7.77(d,J=7.8Hz,1H),7.38(d,J=8.8Hz,1H),7.18(t,J=8.1Hz,1H),5.22(dd,J=13.4,5.1Hz,1H), 4.77(s,1H),4.68–4.53(m,4H),4.24(s,1H),3.50(s,6H),3.03–2.90(m,1H ),2.81(d,J=17.8Hz,1H),2.62–2.47(m,1H),2.27–2.15(m,1H).LCMS(ESI)C 25 H 25 FN5O4 + [M+H] + :Calculated value 478.19, measured value 478.2.

[0400] Example 137: Preparation of 3-(5-((4-(isoxazolo[4,5-c]pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04904)

[0401] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04904) (white solid, 27 mg, yield 38%) was prepared. 1H NMR(400MHz,MeOD)δ9.80(s,1H),8.87(d,J=6.9Hz,1H),8.20(d,J=6.9Hz,1H),7 .93(d,J=8.4Hz,2H),7.78(d,J=7.9Hz,1H),5.18(dd,J=13.3,5.1Hz,1H),4.69– 4.53(m,4H),4.43–4.32(m,2H),3.89–3.44(m,6H),3.00–2.86(m,1H),2.79(dd, J=15.3,2.3Hz,1H),2.53(qd,J=13.2,4.6Hz,1H),2.29–2.10(m,1H).LCMS(ESI)C 24 H 25 N6O4 + [M+H] + :Calculated value 461.19, measured value 461.2.

[0402] Example 138: Preparation of 3-(5-((4-(6-fluorobenzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05332)

[0403] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05332) (white solid, 18 mg, yield 20%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ8.10–8.03(m,1H),7.95(d,J=7.8Hz,1H),7.83(s,1H ),7.77–7.69(m,2H),7.25(td,J=8.8,2.3Hz,1H),5.19(dd,J=13.4,5.2Hz,1 H),4.66–4.54(m,4H),4.17(d,J=12.5Hz,2H),3.63–3.41(m,6H),2.99–2.85 (m,2H),2.85–2.74(m,1H),2.61–2.44(m,1H),2.25–2.14(m,1H).LCMS(ESI)C 25 H 25 FN5O3S + [M+H] + :Calculated value 494.17, measured value 494.1.

[0404] Example 139: Preparation of 3-(5-((4-(6-fluoro-1H-indazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05264)

[0405] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05264) (white solid, 37 mg, yield 42%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ7.94 (d, J = 7.9 Hz, 1H), 7.85 (s, 1H), 7.81–7.73 (m, 2H), 7.08 (dd, J = 9. 5,2.1Hz,1H),6.88(td,J=9.1,2.2Hz,1H),5.19(dd,J=13.4,5.2Hz,1H),4.66–4.50(m,4H),4 .05(d,J=11.4Hz,2H),3.63–3.57(m,2H),3.47–3.44(m,2H),3.38–3.35(m,1H),2.92–2.88(m ,1H),2.84–2.73(m,1H),2.62–2.61(m,1H),2.52–2.37(m,1H),2.25–2.13(m,1H).LCMS(ESI)C 25 H 26 FN6O3 + [M+H] + :Calculated value 477.20, measured value 477.3.

[0406] Example 140: Preparation of 3-(5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04601)

[0407] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04601) (white solid, 10 mg, yield 10%) was prepared. 1H NMR (400MHz, MeOD) δ8.78(s,1H),8.68(s,1H),7.94(d,J=7.9Hz,1H),7.89(s,1H),7.78(d,J=8.1Hz,1H),5.19(dd,J=13.2,5.2Hz,1H),4.69–4.55(m, 4H),3.89–3.76(m,4H),3.64–3.61(m,2H),3.51–3.43(m,2H),3.02–2.85(m ,1H),2.84–2.74(m,1H),2.58–2.48(m,1H),2.29–2.09(m,1H).LCMS(ESI)C 25 H 27 N6O3 + [M+H] + :Calculated value 459.21, measured value 459.3.

[0408] Example 141: Preparation of 3-(5-((4-(6-fluoro-1H-indol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04713)

[0409] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04713) (white solid, 60 mg, yield 60%) was prepared. 1 H NMR (400MHz, MeOD) δ7.97(d,J=7.8Hz,1H),7.83(s,1H),7.75(d,J=7.9Hz,1H),7.57(dd,J=8.7,5.3Hz,1H),7.0 6(d,J=10.6Hz,2H),6.83(dd,J=12.9,5.6Hz,1H),5.21(dd,J=13.3,5.1Hz,1H),4.91–4.89(m,1H),4.63(t,J=1 2.2Hz,2H),4.54(s,2H),3.65(d,J=11.5Hz,2H),3.32–3.13(m,3H),2.94(ddd,J=21.8,13.4,6.8Hz,1H),2.86– 2.77(m,1H),2.62–2.47(m,1H),2.33(d,J=13.7Hz,2H),2.26–2.16(m,1H),2.03(d,J=14.0Hz,2H).LCMS(ESI)C 27 H 28FN4O3 + [M+H] + :Calculated value 475.21, measured value 475.2.

[0410] Example 142: Preparation of 3-(5-((4-(6-fluoro-1-methyl-1H-indol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04858)

[0411] Referring to the method of synthesis scheme 1, under appropriate conditions understood in the art, the target compound (GT-04858) was prepared (white solid, 41 mg, yield 42%). 1 H NMR (400MHz, MeOD) δ7.97(d,J=7.8Hz,1H),7.82(s,1H),7.75(d,J=7.8Hz,1H),7.57(d d,J=8.8,5.1Hz,1H),7.09(d,J=10.0Hz,1H),7.03(d,J=6.6Hz,1H),6.84(dd,J=14.8, 5.6Hz, 1H), 5.21 (dd, J=13.3, 5.2Hz, 1H), 4.60 (dd, J=28.2, 21.1Hz, 4H), 3.70 (t, J=22 .0Hz,5H),3.30–3.15(m,3H),2.92(dd,J=13.4,5.4Hz,1H),2.83(d,J=2.5Hz,1H),2.54 (dd,J=13.1,4.6Hz,1H),2.32(d,J=14.8Hz,2H),2.22(dd,J=10.2,4.8Hz,1H),2.01(d,J=12.8Hz,2H).LCMS(ESI)C 28 H 30 FN4O3 + [M+H] + :Calculated value 489.23, measured value 489.3.

[0412] Example 143: Preparation of 3-(5-((4-(5-fluoroindolin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04650)

[0413] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04650) (white solid, 33 mg, yield 33%) was prepared. 1H NMR(400MHz,MeOD)δ8.00–7.86(m,2H),7.79–7.70(m,1H),7.43(dd,J=8.8,4.2Hz,1H),7.19(ddd ,J=12.7,11.2,5.3Hz,2H),5.19(dd,J=13.3,5.2Hz,1H),4.59(dd,J=28.0,18.6Hz,4H),4.26–4. 12(m,1H),3.95(t,J=7.7Hz,2H),3.67(d,J=12.4Hz,2H),3.33–3.25(m,4H),2.94(ddd,J=18.5,1 3.5,5.4Hz,1H),2.86–2.73(m,1H),2.54(qd,J=13.3,4.7Hz,1H),2.41–2.07(m,5H).LCMS(ESI)C 27 H 30 FN4O3 + [M+H] + :Calculated value 477.23, measured value 477.3.

[0414] Example 144: Preparation of 3-(5-((4-(5-fluoro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04905)

[0415] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04905) (white solid, 9 mg, yield 12%) was prepared. 1 H NMR(400MHz,MeOD)δ9.63(s,1H),8.20(dd,J=9.3,4.0Hz,1H),7.98–7.90(m,2H),7.80 (d,J=9.0Hz,1H),7.65(dd,J=7.9,2.1Hz,1H),7.52(td,J=9.2,2.4Hz,1H),5.21–5.15( m,2H),4.69–4.52(m,4H),3.78(d,J=12.7Hz,2H),3.56–3.41(m,2H),3.00–2.86(m,1H) ,2.79(ddd,J=17.6,4.6,2.4Hz,1H),2.74–2.46(m,5H),2.27–2.10(m,1H).LCMS(ESI)C 26 H 27 FN5O3 + [M+H] + :Calculated value 476.21, measured value 476.2.

[0416] Example 145: Preparation of 3-(5-((4-(5-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04714)

[0417] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04714) (white solid, 5 mg, yield 5%) was prepared. 1 H NMR(400MHz,MeOD)δ7.97(d,J=7.8Hz,1H),7.85(s,1H),7.76(d,J=8.1Hz,1H),7.27(dd, J=8.7,4.4Hz,1H),6.86(t,J=8.9Hz,2H),5.21(dd,J=13.3,5.1Hz,1H),4.92–4.88(m,1H) ,4.61(dd,J=26.9,19.7Hz,5H),3.70(d,J=12.2Hz,2H),3.31–3.19(m,1H),3.00–2.78(m, 4H),2.55(qd,J=13.2,4.7Hz,1H),2.27–2.17(m,1H),2.09(t,J=13.4Hz,2H).LCMS(ESI)C 26 H 27 FN5O4 + [M+H] + :Calculated value 492.20, measured value 492.2.

[0418] Example 146: Preparation of 3-(5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04603)

[0419] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04603) (white solid, 12 mg, yield 12%) was prepared. 1H NMR (400MHz, MeOD) δ8.78(s,1H),8.68(s,1H),7.94(d,J=7.9Hz,1H),7.89(s,1H),7.78(d,J=8.1Hz,1H),5.19(dd,J=13.2,5 .2Hz,1H),4.69–4.55(m,4H),3.89–3.76(m,4H),3.64–3.61(m,2H),3.51–3.43(m,2H),3.02–2.85(m,1H),2.84–2.74(m,1H), 2.58–2.48(m,1H),2.29–2.09(m,1H).LCMS(ESI)C 26 H 28 N5O3 + [M+H] + :Calculated value 458.22, measured value 458.3.

[0420] Example 147: Preparation of 3-(5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04602)

[0421] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04602) (white solid, 22 mg, yield 21%) was prepared. 1 H NMR (400MHz, MeOD) δ8.78(s,1H),8.68(s,1H),7.94(d,J=7.9Hz,1H),7.89(s,1H),7.78(d,J=8.1Hz,1H),5.19(dd,J=13.2,5.2Hz,1H),4.69–4.55(m, 4H),3.89–3.76(m,4H),3.64–3.61(m,2H),3.51–3.43(m,2H),3.02–2.85(m ,1H),2.84–2.74(m,1H),2.58–2.48(m,1H),2.29–2.09(m,1H).LCMS(ESI)C 26 H 26 N5O3 + [M+H] + :Calculated value 456.20, measured value 456.2.

[0422] Example 148: Preparation of 3-(5-((4-(6-fluoro-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04722)

[0423] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04722) (white solid, 45 mg, yield 45%) was prepared. 1 H NMR(400MHz,MeOD)δ7.98–7.75(m,4H),7.30–7.10(m,2H),6.69(t,J=9.2Hz,1H),5.29–5.13(m,2H) ,4.59(d,J=17.0Hz,4H),2.94(s,3H),2.82(d,J=17.2Hz,3H),2.55(s,2H),2.22(s,2H).LCMS(ESI)C 27 H 26 FN4O3 + [M+H] + :Calculated value 473.20, measured value 473.2.

[0424] Example 149: Preparation of 3-(5-((4-(6-fluoro-1-methyl-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04723)

[0425] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04723) (white solid, 45 mg, yield 46%) was prepared. 1 H NMR(400MHz,MeOD)δ7.98(d,J=7.9Hz,1H),7.81(dd,J=16.9,8.6Hz,3H),7.18(t,J=8.8H z,1H),6.96(dd,J=19.8,8.4Hz,1H),6.23(d,J=34.2Hz,1H),5.21(dd,J=13.3,5.1Hz,2H) ,5.01(d,J=12.8Hz,1H),4.75(s,1H),4.61(d,J=4.6Hz,3H),3.79(d,J=7.4Hz,3H),2.92( d,J=12.9Hz,2H),2.81(d,J=16.5Hz,2H),2.53(d,J=7.2Hz,2H),2.22(s,2H).LCMS(ESI)C 28 H 28 FN4O3+ [M+H] + :Calculated value 487.21, measured value 487.2.

[0426] Example 150: Preparation of 3-(5-((4-(6-fluoro-3,4-dihydroquinolin-1(2H)-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04691)

[0427] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04691) (white solid, 42 mg, yield 43%) was prepared. 1 H NMR(400MHz,MeOD)δ7.93(d,J=7.8Hz,1H),7.86(s,1H),7.74(d,J=7.7Hz,1H),7.31–7 .21(m,1H),7.04(t,J=8.3Hz,2H),5.20(dd,J=13.3,5.1Hz,1H),4.59(q,J=17.5Hz,2H ),4.51(s,2H),4.11–4.05(m,1H),3.66(d,J=12.1Hz,2H),3.58–3.47(m,2H),3.23(t, J=12.0Hz,2H),3.03–2.87(m,3H),2.87–2.76(m,1H),2.58–2.50(m,1H),2.33–2.05(m, 7H).LCMS(ESI)C 28 H 32 FN4O3 + [M+H] + :Calculated value 491.25, measured value 491.2.

[0428] Example 151: Preparation of 3-(5-((4-(7-fluoro-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04859)

[0429] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04859) (white solid, 40 mg, yield 41%) was prepared. 1H NMR (400MHz, DMSO) δ11.16(s,1H),11.01(s,1H),7.89(s,1H),7.83(d,J=7.8Hz,1H),7.77(d,J=7.8Hz,1H),6.86 –6.79(m,1H),6.62–6.57(m,2H),5.14(dd,J=13.3,5.0Hz,1H),4.45(q,J=17.7Hz,4H),4.22–4.12(m,2H),3.91( t,J=11.7Hz,2H),3.46(d,J=9.4Hz,2H),3.19–3.12(m,2H),3.11–3.02(m,2H),2.98–2.84(m,1H),2.61(d,J=17. 2Hz,1H),2.44(dd,J=13.2,4.3Hz,1H),2.22-2.16(m,2H),2.09–1.96(m,1H),1.78(d,J=11.9Hz,2H).LCMS(ESI)C 27 H 30 FN4O4 + [M+H] + :Calculated value 493.22, measured value 493.2.

[0430] Example 152: Preparation of 3-(5-((4-(7-fluoro-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04860)

[0431] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04860) (white solid, 46 mg, yield 49%) was prepared. 1H NMR (400MHz, DMSO) δ11.01(s,1H),10.14(s,1H),7.86(d,J=7.7Hz,1H),7.80(s,1H),7.70(d,J=7.7Hz,1H ),7.47(dd,J=9.0,5.5Hz,1H),7.00(dd,J=9.2,2.9Hz,1H),6.96–6.89(m,1H),5.15(dd,J=13.1,5.0Hz,1H ),4.57(s,2H),4.46(dd,J=48.7,17.8Hz,5H),3.50(d,J=11.6Hz,2H),3.15(d,J=11.4Hz,2H),2.97–2.79 (m,3H),2.66(d,J=12.4Hz,1H),2.45–2.42(m,1H),2.06–1.98(m,1H),1.94(d,J=13.2Hz,2H).LCMS(ESI)C 27 H 28 FN4O5 + [M+H] + :Calculated value 507.20, measured value 507.3.

[0432] Example 153: Preparation of 3-(5-((4-(7-fluorochroman-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04901)

[0433] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04901) (white solid, 24 mg, yield 32%) was prepared. 1H NMR (400MHz, MeOD) δ7.91(d,J=7.8Hz,1H),7.76(s,1H),7.68(d,J=7.9Hz,1H),7.11(dd,J=8.4,6.7Hz,1H),6.58(td,J =8.4,2.7Hz,1H),6.48(dd,J=10.4,2.7Hz,1H),5.18(dd,J=13.3,5.2Hz,1H),4.64–4.50(m,2H),4.43(s,2H),4.27–4. 21(m,1H),4.19–4.08(m,1H),3.54(t,J=14.0Hz,2H),3.08–3.01(m,2H),2.97–2.84(m,1H),2.84–2.74(m,2H),2.66–2 .47(m,1H),2.22–2.17(m,1H),2.13–2.01(m,1H),2.00–1.84(m,4H),1.82–1.70(m,1H),1.61–1.49(m,1H).LCMS(ESI)C 28 H 31 FN3O4 + [M+H] + :Calculated value 492.23, measured value 492.3.

[0434] Example 154: Preparation of 3-(5-((4-(7-fluorochroman-4-ylidene)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04649)

[0435] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04649) (white solid, 28 mg, yield 29%) was prepared. 1 H NMR (400MHz, MeOD) δ7.94 (t, J = 8.8 Hz, 1H), 7.79 (d, J = 10.6 Hz,1H),7.71(t,J=9.1Hz,1H),7.19(dd,J=8.6,6.5Hz,1H),6.70–6.46(m, 2H),5.21(dd,J=13.4,5.2Hz,1H),4.67–4.44(m,4H),4.41–4.19(m,2H),3 .56(d,J=46.1Hz,2H),3.35(s,2H),3.12(t,J=13.9Hz,2H),3.02–2.89(m, 1H),2.87–2.73(m,2H),2.73–2.30(m,4H),2.27–2.14(m,1H).LCMS(ESI)C 28 H29 FN3O4 + [M+H] + :Calculated value 490.21, measured value 490.2.

[0436] Example 155: Preparation of 3-(5-((4-(5-fluoronaphthalen-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04664)

[0437] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04664) (white solid, 51 mg, yield 52%) was prepared. 1 H NMR (400MHz, MeOD) δ8.10–7.93(m,3H),7.85(s,1H),7.77(d,J=7.9Hz,1H),7.55(dt,J= 17.5,7.6Hz,3H),7.25(dd,J=10.5,7.8Hz,1H),5.22(dd,J=13.4,5.2Hz,1H),4.74–4.49 (m,4H),3.70(dd,J=49.6,37.0Hz,3H),3.41(dd,J=23.7,11.0Hz,2H),2.95(ddd,J=18.5 ,13.5,5.4Hz,1H),2.87–2.76(m,1H),2.61–2.46(m,1H),2.34–2.00(m,5H).LCMS(ESI)C 29 H 29 FN3O3 + [M+H] + :Calculated value 486.22, measured value 486.2.

[0438] Example 156: Preparation of 3-(5-((4-(7-fluoroquinolin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04648)

[0439] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04648) (white solid, 24 mg, yield 25%) was prepared. 1H NMR(400MHz,MeOD)δ9.21(d,J=5.9Hz,1H),8.83(dd,J=9.5,5.3Hz,1H),8.04(d,J=6.0Hz,1H) ,8.00–7.85(m,4H),7.81(d,J=8.1Hz,1H),5.19(dd,J=13.3,5.1Hz,1H),4.69–4.52(m,4H),4. 18(t,J=11.9Hz,1H),3.74(d,J=12.6Hz,2H),3.48(t,J=11.2Hz,2H),2.98–2.87(m,1H),2.84 –2.74(m,1H),2.53(qd,J=13.3,4.7Hz,1H),2.45–2.25(m,4H),2.24–2.14(m,1H).LCMS(ESI)C 28 H 28 FN4O3 + [M+H] + :Calculated value 487.21, measured value 487.2.

[0440] Example 157: Preparation of 3-(5-((4-(isoquinolin-5-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04665)

[0441] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04665) (white solid, 22 mg, yield 22%) was prepared. 1 H NMR(400MHz,MeOD)δ9.83(s,1H),8.88(d,J=6.9Hz,1H),8.66(t,J=12.4Hz,1H),8.47(d,J=8.2Hz,1H),8 .28–8.17(m,1H),8.09(q,J=7.7Hz,1H),8.00–7.90(m,2H),7.82(d,J=7.1Hz,1H),5.19(td,J=13.0,4.9H z,1H),4.71–4.51(m,4H),4.02–3.86(m,1H),3.74(d,J=12.4Hz,2H),3.49(dt,J=20.1,10.4Hz,2H),2.95 (tt,J=12.5,8.5Hz,1H),2.86–2.76(m,1H),2.56(qd,J=13.1,4.7Hz,1H),2.42–2.08(m,5H).LCMS(ESI)C 28 H 29 N4O3 + [M+H]+ :Calculated value 469.22, measured value 469.2.

[0442] Example 158: Preparation of 3-(5-((4-(5-fluoronaphthalen-1-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04902)

[0443] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04902) (white solid, 38 mg, yield 52%) was prepared. 1 H NMR(400MHz,MeOD)δ8.08(d,J=8.4Hz,1H),7.98(d,J=7.9Hz,1H),7.85(s,1H),7.83–7.78(m, 2H),7.57(t,J=7.8Hz,1H),7.53–7.41(m,3H),7.23(dd,J=10.8,7.3Hz,1H),5.83(s,1H),5.2 0(dd,J=13.3,5.2Hz,1H),4.68–4.59(m,4H),4.01(brs,2H),3.88–3.83(m,1H),3.58–3.55(m ,1H),2.94–2.88(m,1H),2.81–2.76(m,3H),2.55–2.51(m,1H),2.23–2.17(m,1H).LCMS(ESI)C 29 H 27 FN3O3 + [M+H] + :Calculated value 484.20, measured value 484.2.

[0444] Example 159: Preparation of 3-(5-((4-(isoquinolin-5-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04666)

[0445] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04666) (white solid, 21 mg, yield 21%) was prepared. 1H NMR (400MHz, MeOD) δ9.84(s,1H),8.80(d,J=6.8Hz,1H),8.62(d,J=6.8Hz,1H),8.53(d,J=8.3Hz,1H),8.18(d,J=7. 2Hz,1H),8.09(t,J=7.8Hz,1H),8.03–7.95(m,2H),7.88(d,J=7.7Hz,1H),5.96(s,1H),5.21(dd,J=13.3,5.1Hz,1H) ,4.94–4.88(m,1H)4.71(t,J=9.6Hz,2H),4.61(t,J=12.8Hz,2H),4.07(s,2H),3.88(s,1H),3.63(d,J=8.9Hz,1H), 3.15(s,1H),3.01–2.88(m,1H),2.84(d,J=2.3Hz,1H),2.56(qd,J=13.1,4.6Hz,1H),2.29–2.18(m,1H).LCMS(ESI)C 28 H 27 N4O3 + [M+H] + :Calculated value 467.21, measured value 467.2.

[0446] Example 160: Preparation of 3-(5-((3-(7-fluorochroman-4-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04700)

[0447] Referring to the method of Synthesis Scheme 1, under appropriate conditions known in the art, the target compound (GT-04700) (white solid, 24 mg, yield 25%) was prepared. 1 H NMR(400MHz,MeOD)δ7.93(d,J=7.8Hz,1H),7.73(s,1H),7.66(d,J=7.5Hz,1H),7.02(t,J=7.4H z,1H),6.59(d,J=8.5Hz,1H),6.54(dd,J=10.3,2.7Hz,1H),5.20(dd,J=13.0,4.8Hz,1H),4.56 (t,J=12.7Hz,5H),4.42–4.31(m,1H),4.21(s,5H),3.15(s,2H),2.94(dd,J=29.9,16.6Hz,2H) ,2.81(d,J=15.2Hz,2H),2.63–2.45(m,1H),2.25–2.19(m,1H),2.10–2.04(m,1H).LCMS(ESI)C26 H 27 FN3O4 + [M+H] + :Calculated value 464.20, measured value 464.2.

[0448] Example 161: Preparation of 3-(5-((3-(7-fluoroazetidin-4-ylidene)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04701)

[0449] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04701) (white solid, 32 mg, yield 33%) was prepared. 1 H NMR(400MHz,MeOD)δ7.95(d,J=7.8Hz,1H),7.79(s,1H),7.72(d,J=7.6Hz,1H),7.0 1(dd,J=8.7,6.3Hz,1H),6.72(td,J=8.5,2.7Hz,1H),6.65(dd,J=10.1,2.6Hz,1H), 5.21(dd,J=13.1,5.3Hz,4H),4.72(s,2H),4.59(d,J=7.1Hz,3H),4.24(s,2H),3.01 –2.90(m,1H),2.86–2.75(m,1H),2.61–2.49(m,3H),2.27–2.15(m,1H).LCMS(ESI)C 26 H 25 FN3O4 + [M+H] + :Calculated value 462.18, measured value 462.2.

[0450] Example 162: Preparation of 3-(5-((3-(7-fluoroquinolin-4-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04651)

[0451] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04651) (white solid, 25 mg, yield 24%) was prepared. 1H NMR(400MHz,MeOD)δ9.30(t,J=7.7Hz,1H),8.40–8.07(m,2H),8.00(dd,J=8.6,2.5Hz,1H),7.85(dt,J=51.8,25.7Hz,4H),5.42–5.05(m,2H),4.6 1(dt,J=26.7,24.7Hz,8H),2.92(ddd,J=18.5,13.5,5.4Hz,1H),2.85–2.72(m,1H),2.52(qd,J=13.1,4.5Hz,1H),2.27–2.12(m,1H).LCMS(ESI)C 26 H 24 FN4O3 + [M+H] + :Calculated value 459.18, measured value 459.2.

[0452] Example 163: Preparation of 3-(5-((3-(5-fluoroindolin-1-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04677)

[0453] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04677) (white solid, 33 mg, yield 26%) was prepared. 1 H NMR (400MHz, MeOD) δ7.92(d,J=7.8Hz,1H),7.75(s,1H),7.67(d,J=7.9Hz,1H),6.89(d,J= 8.3Hz,1H),6.75(t,J=8.5Hz,1H),6.40–6.29(m,1H),5.18(dd,J=13.3,5.2Hz,1H),4.67–4 .53(m,4H),4.44–4.31(m,4H),4.30–4.28(m,1H),3.43(t,J=8.1Hz,2H),3.01-2.99(m,2H ),2.95–2.86(m,1H),2.84–2.74(m,1H),2.56–2.46(m,1H),2.23–2.13(m,1H).LCMS(ESI)C 25 H 26 FN4O3 + [M+H] + :Calculated value 449.20, measured value 449.2.

[0454] Example 164: Preparation of 3-(5-((3-(5-fluoro-1H-benzo[d]imidazol-1-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04716)

[0455] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04716) (white solid, 79 mg, yield 78%) was prepared. 1 H NMR(400MHz,MeOD)δ9.80(d,J=80.3Hz,1H),7.96–7.89(m,2H),7.81(dd,J=23.1,6.2Hz,1H ),7.72–7.65(m,1H),7.51(td,J=9.2,2.3Hz,1H),5.91(s,1H),5.19(dt,J=13.6,6.8Hz,1H ),4.97(dd,J=23.4,16.2Hz,3H),4.83(s,3H),4.68–4.47(m,2H),2.94(ddd,J=18.6,13.6, 5.3Hz,1H),2.85–2.76(m,1H),2.54(qd,J=13.1,4.7Hz,1H),2.27–2.13(m,1H).LCMS(ESI)C 24 H 23 FN5O3 + [M+H] + :Calculated value 448.18, measured value 448.2.

[0456] Example 165: Preparation of 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04678)

[0457] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04678) (white solid, 37 mg, yield 48%) was prepared. 1H NMR(400MHz,DMSO)δ11.84(s,1H),11.02(s,1H),8.57(s,1H),7.92(s,1H),7.86–7.7 4(m,3H),7.70(d,J=6.2Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.70(d,J=12.7Hz,2H), 4.65–4.29(m,5H),3.85–3.80(m,2H),3.46(d,J=11.0Hz,2H),3.24(brs,2H),3.01–2 .82(m,1H),2.62(d,J=17.7Hz,1H),2.48–2.39(m,1H),2.11–1.90(m,1H).LCMS(ESI)C 24 H 25 N6O3S + [M+H] + :Calculated value 477.17, measured value 477.2.

[0458] Example 166: Preparation of 3-(5-((4-(5-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04679)

[0459] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04679) (white solid, 50 mg, yield 51%) was prepared. 1 H NMR(400MHz,MeOD)δ8.70(s,1H),7.94(d,J=8.1Hz,1H),7.83(s,1H),7.73(d,J=8.5 Hz,1H),7.44(d,J=1.1Hz,1H),5.19(dd,J=13.3,5.1Hz,1H),4.57(d,J=4.8Hz,4H), 4.39–4.31(m,1H),3.72-3.59(m,5H),3.39–3.34(m,3H),2.98–2.85(m,1H),2.79(d ,J=15.6Hz,1H),2.61(s,3H),2.52(d,J=14.5Hz,1H),2.23–2.17(m,1H).LCMS(ESI)C 25 H 27 N6O3S + [M+H] + :Calculated value 491.19, measured value 491.2.

[0460] Example 167: Preparation of 3-(5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04680)

[0461] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04680) (white solid, 67 mg, yield 69%) was prepared. 1 H NMR(400MHz,MeOD)δ8.70(s,1H),7.96(d,J=7.9Hz,1H),7.91(s,1H),7.78(d,J=7.8Hz,1H ),7.50(d,J=1.3Hz,1H),5.21(dd,J=13.4,5.2Hz,1H),4.69–4.54(m,4H),3.91–3.84(m,1 H),3.75–3.45(m,4H),3.35–3.32(m,3H),2.99–2.90(m,1H),2.82(ddd,J=17.6,4.6,2.4H z,1H),2.69(d,J=1.2Hz,3H),2.55(qd,J=13.3,4.7Hz,1H),2.25–2.19(m,1H).LCMS(ESI)C 25 H 27 N6O3S + [M+H] + :Calculated value 491.19, measured value 491.2.

[0462] Example 168: Preparation of 3-(5-((4-(6-isopropylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04705)

[0463] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04705) (white solid, 22 mg, yield 30%) was prepared. 1H NMR(400MHz,MeOD)δ8.76(s,1H),7.98–7.91(m,2H),7.80(d,J=7.9Hz,1H),7.53 (s,1H),5.21(dd,J=13.2,5.2Hz,1H),5.03–4.97(m,1H),4.74–4.47(m,5H),4.1 3-3.99(m,2H),3.59(brs,4H),3.46–3.39(m,1H),2.95–2.90(m,1H),2.86–2.75 (m,1H),2.57–2.51(m,1H),2.28–2.15(m,1H),1.45(d,J=6.9Hz,6H).LCMS(ESI)C 27 H 31 N6O3S + [M+H] + :Calculated value 519.22, measured value 519.2.

[0464] Example 169: Preparation of 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04706)

[0465] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04706) (white solid, 26 mg, yield 34%) was prepared. 1 H NMR(400MHz,MeOD)δ8.63(s,1H),7.84(d,J=7.7Hz,1H),7.77(s,1H),7.64(d,J =7.6Hz,1H),5.09(dd,J=13.6,5.1Hz,1H),4.49(d,J=6.5Hz,4H),4.36–4.31(m ,2H),3.74-3.69(m,2H),3.56–3.47(m,3H),3.39–3.31(m,3H),2.88–2.75(m,1 H),2.75–2.62(m,1H),2.45(s,3H),2.37(s,3H),2.13–2.07(m,1H).LCMS(ESI)C 26 H 29 N6O3S + [M+H] + :Calculated value 505.20, measured value 505.3.

[0466] Example 170: Preparation of 3-(1-oxo-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04862)

[0467] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04862) (white solid, 49 mg, yield 55%) was prepared. 1 H NMR(400MHz,DMSO)δ11.01(s,1H),10.97(s,1H),8.52(s,1H),8.00(s,1H),7.88–7.83(m,4H),7 .76(d,J=8.0Hz,1H),7.51(t,J=7.6Hz,2H),7.43(t,J=7.4Hz,1H),5.15(dd,J=13.2,5.1Hz,1H), 4.74(d,J=14.2Hz,2H),4.55–4.36(m,4H),3.66–3.58(m,2H),3.51–3.43(m,2H),3.30–3.22(m,2 H),2.96–2.89(m,1H),2.62(d,J=17.1Hz,1H),2.51–2.43(m,1H),2.05–2.01(m,1H).LCMS(ESI)C 30 H 29 N6O3S + [M+H] + :Calculated value 553.20, measured value 553.2.

[0468] Example 171: Preparation of 3-(5-((4-(6-bromothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04861)

[0469] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04861) (white solid, 28 mg, yield 32%) was prepared. 1H NMR (400MHz, DMSO) δ11.40(s,1H),11.01(s,1H),8.49(s,1H),7.93(s,1H),7.89–7. 82(m,2H),7.76(d,J=7.9Hz,1H),5.15(dd,J=13.2,5.0Hz,1H),4.65–4.57(m,2H),4 .55–4.35(m,4H),3.67–3.58(m,2H),3.46–3.43(m,2H),3.27–3.18(m,2H),3.00–2. 86(m,1H),2.63(t,J=16.0Hz,1H),2.47–2.39(m,1H),2.11–1.95(m,1H).LCMS(ESI)C 24 H 24 BrN6O3S + [M+H] + :Calculated value 555.08, measured value 552.2.

[0470] Example 172: Preparation of 3-(1-oxo-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04709)

[0471] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04709) (white solid, 22 mg, yield 31%) was prepared. 1 H NMR(400MHz,MeOD)δ8.79(s,1H),7.93(d,J=7.8Hz,1H),7.73(d,J=5.2Hz,2H ),7.62(d,J=7.8Hz,1H),7.51–7.48(m,5H),5.21(dd,J=13.2,5.2Hz,1H),4. 68–4.52(m,2H),4.41(s,2H),4.15(brs,2H),3.32–3.06(m,4H),2.99–2.90( m,3H),2.75–2.64(m,1H),2.60-2.49(m,1H),2.27-2.16(m,1H).LCMS(ESI)C 30 H 29 N6O3S + [M+H] + :Calculated value 553.20, measured value 553.3.

[0472] Example 173: Preparation of 3-(1-oxo-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05209)

[0473] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05209) (white solid, 35 mg, yield 43%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ8.63(s,1H),7.94(d,J=7.8Hz,1H),7.84(s,1H),7.7 4(d,J=7.8Hz,1H),5.19(dd,J=13.3,5.2Hz,1H),4.66–4.51(m,4H),4.32–4.2 1(m,2H),3.63–3.43(m,6H),3.04–2.86(m,5H),2.82–2.77(m,1H),2.56–2.47 (m,1H),2.25–2.14(m,1H),2.03–1.97(m,2H),1.88–1.83(m,2H).LCMS(ESI)C 28 H 31 N6O3S + [M+H] + :Calculated value 531.22, measured value 531.3.

[0474] Example 174: Preparation of 3-(5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04996)

[0475] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04996) (white solid, 44 mg, yield 56%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ8.63(s,1H),7.95(d,J=7.9Hz,1H),7.84(s,1H),7.74(d,J=6.8Hz,1H),5.19(dd,J=13.2,5.1Hz,1H),4.66–4.4 7(m,6H),3.78–3.48(m,5H),3.16–3.07(m,5H),2.98–2.86(m,1H),2.81–2.77(m,1H),2.55–2.50(m,3H),2.23–2.16(m,1H).LCMS(ESI)C27 H 29 N6O3S + [M+H] + :Calculated value 517.20, measured value 517.3.

[0476] Example 175: Preparation of 3-(5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05100)

[0477] Referring to the method of Synthesis Scheme 1, under appropriate conditions known in the art, the target compound (GT-05100) (white solid, 50 mg, yield 58%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ7.91(d,J=7.8Hz,1H),7.71(s,1H),7.64(s,1H),7.59 (d,J=7.8Hz,1H),7.51–7.45(m,5H),5.19(dd,J=13.3,5.2Hz,1H),4.64–4.49( m,2H),4.39(s,2H),4.18(brs,2H),3.29–3.08(m,4H),2.93–2.88(m,2H),2.8 3–2.74(m,2H),2.74(s,3H),2.58–2.47(m,1H),2.25–2.15(m,1H).LCMS(ESI)C 31 H 31 N6O3S + [M+H] + :Calculated value 567.22, measured value 567.3.

[0478] Example 176: Preparation of 3-(5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04900)

[0479] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04900) (white solid, 60 mg, yield 73%) was prepared. 1H NMR(400MHz,MeOD)δ7.93(d,J=7.8Hz,1H),7.87(s,1H),7.75(d,J=7.9Hz,1H ),5.18(dd,J=13.3,5.2Hz,1H),4.66–4.52(m,4H),4.47–4.40(m,1H),3.84– 3.32(m,7H),3.00–2.86(m,5H),2.82–2.76(m,1H),2.69(s,3H),2.58–2.48( m,1H),2.22–2.17(m,1H),2.02–1.97(m,2H),1.87–1.81(m,2H).LCMS(ESI)C 29 H 33 N6O3S + [M+H] + :Calculated value 545.23, measured value 545.3.

[0480] Example 177: Preparation of 3-(5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05157)

[0481] Referring to the method of synthesis scheme 1, under appropriate conditions understood in the art, the target compound (GT-05157) was prepared (white solid, 46 mg, yield 57%). 1 H NMR (400MHz, MeOD-d4) δ7.94(d,J=7.9Hz,1H),7.88(s,1H),7.76(d,J=7.9Hz,1H),5.19(dd,J=13.4,5.2Hz,1H),4.65–4.53(m,5H),3.94–3.76(m ,2H),3.69–3.47(m,4H),3.16–3.07(m,5H),2.95–2.86(m,1H),2.84–2.7 4(m,1H),2.70(s,3H),2.57–2.50(m,3H),2.21–2.18(m,1H).LCMS(ESI)C 28 H 31 N6O3S + [M+H] + :Calculated value 531.22, measured value 531.2.

[0482] Example 178: Preparation of 3-(5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04693)

[0483] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04693) (white solid, 24 mg, yield 25%) was prepared. 1 H NMR(400MHz,MeOD)δ7.95(d,J=8.1Hz,2H),7.85–7.78(m,3H),5.39–4.94(m, 3H),4.72–4.55(m,4H),4.11–4.38(m,1H),3.70-3.56(m,4H),3.01–2.88(m, 1H),2.87–2.77(m,1H),2.74(s,3H),2.55(qd,J=13.1,4.5Hz,1H),2.28–2.14(m,1H).LCMS(ESI)C 25 H 27 N6O3S + [M+H] + :Calculated value 491.19, measured value 491.2.

[0484] Example 179: Preparation of 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04725)

[0485] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04725) (white solid, 43 mg, yield 43%) was prepared. 1 H NMR(400MHz,MeOD)δ8.96(s,1H),7.98(d,J=7.8Hz,1H),7.87(s,1H),7.80(d,J=7 .8Hz,1H),7.36(dd,J=23.1,6.0Hz,2H),5.24(dd,J=13.2,5.2Hz,1H),5.01(d,J=1 1.8Hz,2H),4.58(s,4H),3.61(s,2H),3.52–3.40(m,2H),3.32–3.21(m,2H),3.02– 2.93(m,1H),2.86–2.76(m,1H),2.61–2.45(m,1H),2.25–2.17(m,1H).LCMS(ESI)C 24 H 25 N6O3S+ [M+H] + :Calculated value 477.14, measured value 477.2.

[0486] Example 180: Preparation of 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04707)

[0487] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04707) (white solid, 32 mg, yield 43%) was prepared. 1 H NMR(400MHz,MeOD)δ8.65(s,1H),7.95–7.89(m,2H),7.76(d,J=8.0Hz,1H),5.20(dd,J=1 3.2,5.2Hz,1H),4.68–4.53(m,5H),4.28(brs,1H),4.14(brs,1H),3.96(brs,1H),3.74( brs,2H),3.62(brs,1H),3.01–2.87(m,1H),2.87–2.76(m,1H),2.61–2.51(m,2H),2,54( s,3H),2.50–2.41(m,1H),2.45(s,3H),2.37-2.32(m,1H),2.26–2.15(m,1H).LCMS(ESI)C 27 H 31 N6O3S + [M+H] + :Calculated value 519.22, measured value 519.2.

[0488] Example 181: Preparation of 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04702)

[0489] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04702) (white solid, 25 mg, yield 31%) was prepared. 1H NMR(400MHz,MeOD)δ9.00(s,1H),7.97(d,J=7.8Hz,1H),7.88(d,J=6.1Hz,1H),7.85(s,1H), 7.76(d,J=7.8Hz,1H),7.73(d,J=6.1Hz,1H),5.22(dd,J=13.3,5.1Hz,1H),4.82(s,1H),4.68 –4.54(m,4H),3.74(t,J=13.9Hz,3H),2.95(ddd,J=18.7,13.5,5.4Hz,1H),2.88–2.76(m,1H) ,2.55(qd,J=13.1,4.6Hz,1H),2.36(dd,J=24.2,11.7Hz,2H),2.28–2.14(m,3H).LCMS(ESI)C 25 H 26 N5O3S + [M+H] + :Calculated value 476.18, measured value 476.2.

[0490] Example 182: Preparation of 3-(5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04717)

[0491] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04717) (white solid, 28 mg, yield 29%) was prepared. 1 H NMR (400MHz, MeOD) δ9.00(d,J=10.8Hz,1H),7.96(d,J=7.8Hz,1H),7.90(s,1H),7.79(d,J=7.3Hz,1H),7.57(s,1H),5.21(dd,J =13.3,5.1Hz,1H),4.71–4.48(m,5H),3.72(d,J=12.2Hz,2H),3.40(s,2H),2.99–2.90(m,1H),2.86–2.79(m,1H),2.74(s,3H), 2.55(dd,J=13.0,4.5Hz,1H),2.40(t,J=12.4Hz,2H),2.25(d,J=14.7Hz,3H).LCMS(ESI)C 26 H 28 N5O3S + [M+H] + :Calculated value 490.19, measured value 490.3.

[0492] Example 183: Preparation of 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05034)

[0493] Referring to the method of synthesis scheme 1, under appropriate conditions understood in the art, the target compound (GT-05034) was prepared (white solid, 39 mg, yield 51%). 1 H NMR(400MHz,MeOD-d4)δ8.93(s,1H),7.93(t,J=8.1Hz,1H),7.86(s,1H),7.76(d ,J=7.9Hz,1H),5.18(dd,J=13.3,5.2Hz,1H),4.64–4.51(m,4H),4.07–4.00(m,1 H),3.68(d,J=12.2Hz,2H),3.42–3.35(m,2H),2.99–2.85(m,1H),2.82–2.78(m, 1H),2.62(s,3H),2.59(s,3H),2.47–2.35(m,3H),2.24–2.18(m,3H).LCMS(ESI)C 27 H 30 N5O3S + [M+H] + :Calculated value 504.21, measured value 504.2.

[0494] Example 184: Preparation of 3-(1-oxo-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05159)

[0495] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05159) (white solid, 31 mg, yield 37%) was prepared. 1H NMR(400MHz,MeOD-d4)δ8.93(s,1H),8.00(s,1H),7.96(d,J=7.9Hz,1H),7.8 8–7.81(m,3H),7.75(d,J=7.8Hz,1H),7.56–7.44(m,3H),5.19(dd,J=13.3,5. 2Hz,1H),4.67–4.54(m,4H),3.77–3.70(m,3H),3.37–3.33(m,2H),2.99–2.87 (m,1H),2.83–2.77(m,1H),2.60–2.45(m,1H),2.36–2.19(m,5H).LCMS(ESI)C 31 H 30 N5O3S + [M+H] + :Calculated value 552.21, measured value 552.2.

[0496] Example 185: Preparation of 3-(1-oxo-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04995)

[0497] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04995) was prepared (white solid, 48 mg, yield 58%). 1 H NMR (400MHz, MeOD-d4) δ8.99 (s, 1H), 7.92 (d, J = 7.8Hz, 1H), 7.72 (s, 1H), 7.66–7. 62(m,2H),7.56–7.46(m,5H),5.20(dd,J=13.4,5.2Hz,1H),4.64–4.55(m,2H),4.3 9(s,2H),3.49(d,J=11.8Hz,2H),3.00–2.88(m,2H),2.84–2.75(m,1H),2.59–2.48 (m,1H),2.42–2.36(m,2H),2.24–2.14(m,3H),1.91(d,J=13.9Hz,2H).LCMS(ESI)C 31 H 30 N5O3S + [M+H] + :Calculated value 552.21, measured value 552.2.

[0498] Example 186: Preparation of 3-(1-oxo-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05265)

[0499] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05265) (white solid, 34 mg, yield 35%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ8.91(s,1H),7.93(d,J=7.8Hz,1H),7.87(s,1H),7.76(d,J=7.8Hz,1H),5.18(dd,J=13.3,5.1Hz,1H) ,4.64–4.52(m,4H),3.90(t,J=12.0Hz,1H),3.67(d,J=12.4Hz,2H),3.39(dd,J=12.9,10.5Hz,2H),3.13–3.09(m,2H),2.98– 2.95(m,2H),2.94–2.85(m,1H),2.82–2.79(m,1H),2.55–2.51(m,1H),2.47–2.36(m,2H),2.25–2.17(m,3H),2.01–1.96(m,5H).LCMS(ESI)C 29 H 32 N5O3S + [M+H] + :Calculated value 530.22, measured value 530.2.

[0500] Example 187: Preparation of 3-(5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04994)

[0501] Referring to the method of Synthesis Scheme 1, under appropriate conditions known in the art, the target compound (GT-04994) (white solid, 40 mg, yield 51%) was prepared. 1H NMR(400MHz,MeOD-d4)δ8.94(s,1H),7.92(d,J=7.8Hz,1H),7.89(s,1H),7.77(d, J=7.8Hz,1H),5.18(dd,J=13.3,5.1Hz,1H),4.67–4.52(m,4H),3.72–3.67(m,3H), 3.43–3.37(m,2H),3.26–3.22(m,2H),3.17–3.13(m,3H),2.97–2.87(m,1H),2.82– 2.77(m,1H),2.66–2.59(m,2H),2.42–2.38(m,2H),2.30–2.14(m,4H).LCMS(ESI)C 28 H 30 N5O3S + [M+H] + :Calculated value 516.21, measured value 516.3.

[0502] Example 188: Preparation of 3-(5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05158)

[0503] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05158) (white solid, 52 mg, yield 61%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ7.92(d,J=7.8Hz,1H),7.75(s,1H),7.64(d,J=8.1Hz,2 H),7.52–7.45(m,5H),5.20(dd,J=13.3,5.1Hz,1H),4.59(q,J=17.6Hz,2H),4.3 9(s,2H),3.50(d,J=11.7Hz,2H),3.02–2.91(m,2H),2.91–2.85(m,1H),2.81(s ,3H),2.59–3.52(m,1H),2.38–2.19(m,5H),1.92(d,J=14.1Hz,2H).LCMS(ESI)C 32 H 32 N5O3S + [M+H] + :Calculated value 566.22, measured value 566.3.

[0504] Example 189: Preparation of 3-(5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04993)

[0505] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04993) (white solid, 15 mg, yield 18%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ7.93(d,J=7.8Hz,1H),7.88(s,1H),7.76(d,J=7.2Hz,1H),5. 18(dd,J=13.3,5.2Hz,1H),4.64–4.55(m,4H),3.92(t,J=12.0Hz,1H),3.67(d,J=12.4 Hz,2H),3.37(t,J=11.8Hz,2H),3.12–3.05(m,2H),2.97–2.92(m,3H),2.89–2.84(m,1 H),2.81(s,3H),2.55–2.43(m,3H),2.25–2.18(m,3H),2.02–1.95(m,4H).LCMS(ESI)C 30 H 34 N5O3S + [M+H] + :Calculated value 544.24, measured value 544.3.

[0506] Example 190: Preparation of 3-(5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05210)

[0507] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05210) (white solid, 31 mg, yield 39%) was prepared. 1H NMR(400MHz,MeOD-d4)δ7.94–7.90(m,2H),7.78(d,J=7.7Hz,1H),5.18(dd,J =13.3,5.2Hz,1H),4.64–4.51(m,4H),3.83–3.67(m,3H),3.43–3.37(m,2H), 3.27–3.23(m,2H),3.16–3.13(m,2H),2.95–2.90(m,1H),2.87(s,3H),2.84–2.74(m,1H) ,2.67–2.59(m,2H),2.56–2.46(m,3H),2.41–2.38(m,1H),2.25–2.18(m,2H).LCMS(ESI)C 29 H 32 N5O3S + [M+H] + :Calculated value 530.22, measured value 530.3.

[0508] Example 191: Preparation of 3-(5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04726)

[0509] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04726) (white solid, 19 mg, yield 20%) was prepared. 1 H NMR (400MHz, MeOD) δ7.99–7.87(m,4H),7.77(dd,J=20.5,6.9Hz,1H),5.21(dd,J=13.3,5.1Hz,1H),4.68–4.50(m,4H),3.77(dd,J=31.8, 12.4Hz,3H),3.39(d,J=13.0Hz,2H),3.02–2.89(m,1H),2.89–2.79(m,4H),2.61–2.43(m,3H),2.24(dd,J=18.5,10.7Hz,3H).LCMS(ESI)C 26 H 28 N5O3S + [M+H] + :Calculated value 490.19, measured value 490.2.

[0510] Example 192: Preparation of 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-2-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04933)

[0511] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04933) (white solid, 16 mg, yield 22%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ9.36 (s, 1H), 7.96–7.93 (m, 2H), 7.85 (s, 1H), 7.75 (d, J = 7. 5Hz,1H),7.61(d,J=6.0Hz,1H),5.19(dd,J=13.3,5.1Hz,1H),4.60–4.54(m,4H),3. 70(d,J=12.4Hz,2H),3.54–3.39(m,2H),3.01–2.86(m,1H),2.85–2.74(m,1H),2.59 –2.48(m,1H),2.41–2.33(m,3H),2.35–2.24(m,2H),2.21–2.18(m,1H).LCMS(ESI)C 25 H 26 N5O3S + [M+H] + :Calculated value 476.18, measured value 476.2.

[0512] Example 193: Preparation of 3-(5-((4-(5-ethylpyrimidin-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04936)

[0513] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04936) (white solid, 25 mg, yield 36%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ8.95(s,2H),7.91(t,J=7.5Hz,1H),7.87(s,1H),7.75(d,J=7.4Hz,1H),5.18(dd,J=13.1,4.9Hz,1H),4.64–4.49(m,4H),3.67 (d,J=11.6Hz,2H),3.48–3.34(M,2H),2.98–2.85(m,1H),2.84–2.78(m,3H ),2.60–2.45(m,1H),2.44–2.13(m,6H),1.32(t,J=7.5Hz,3H).LCMS(ESI)C 25 H 30 N5O3S + [M+H] + :Calculated value 448.23, measured value 448.3.

[0514] Example 194: Preparation of 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04692)

[0515] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04692) (white solid, 23 mg, yield 23%) was prepared. 1 H NMR(400MHz,MeOD)δ9.08(s,1H),7.97(dd,J=15.6,7.0Hz,2H),7.92(s,1H),7.84(d,J=8.3Hz,1H),7.79(d,J=6.1Hz,1H),6.71 (s,1H),5.22(dd,J=17.8,8.9Hz,1H),4.59–4.51(m,4H),4.11(s,2H),3.96–3.90(m,1H),3.59–3.50(m,1H),3.22-3.18(m,3H), 3.00–2.90(m,1H),2.84(d,J=2.3Hz,1H),2.57(dd,J=13.2,4.4Hz,1H),2.26–2.18(m,1H).LCMS(ESI)C 25 H 24 N5O3S + [M+H] + :Calculated value 474.16, measured value 474.1.

[0516] Example 195: Preparation of 3-(5-((4-(5-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04703)

[0517] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04703) (white solid, 31 mg, yield 40%) was prepared. 1H NMR(400MHz,MeOD)δ9.04(s,1H),7.98(d,J=7.8Hz,1H),7.91(s,1H),7.82(d,J=8.1Hz,1 H),7.59(s,1H),6.01(s,1H),5.22(dd,J=13.3,5.2Hz,1H),4.71(d,J=3.7Hz,2H),4.62( q,J=17.5Hz,2H),4.08(s,2H),3.89(s,1H),3.57(s,1H),3.19–3.01(m,2H),3.00–2.88( m,1H),2.88–2.76(m,1H),2.61–2.53(m,1H),2.52(s,3H),2.28–2.16(m,1H).LCMS(ESI)C 26 H 26 N5O3S + [M+H] + :Calculated value 488.18, measured value 488.2.

[0518] Example 196: Preparation of 3-(5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04704)

[0519] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04704) (white solid, 32 mg, yield 41%) was prepared. 1 H NMR(400MHz,MeOD)δ8.95(s,1H),7.99(d,J=7.8Hz,1H),7.88(s,1H),7.80(d,J=8.3H z,1H),7.43(s,1H),6.65(s,1H),5.22(dd,J=13.3,5.2Hz,1H),4.69(s,2H),4.62(d,J =7.3Hz,2H),4.10(s,2H),3.90(s,1H),3.15(s,2H),3.00–2.89(m,1H),2.84(s,1H),2 .79(d,J=11.7Hz,1H),2.70(s,3H),2.62–2.50(m,1H),2.26–2.20(m,1H).LCMS(ESI)C 26 H 26 N5O3S + [M+H] + :Calculated value 488.18, measured value 488.2.

[0520] Example 197: Preparation of 3-(5-((4-(6-isopropylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04935)

[0521] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04935) (white solid, 38 mg, yield 49%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ8.99(s,1H),7.99–7.88(m,2H),7.80(d,J=6.6Hz,1H),7.49(s,1H),6.63(s, 1H),5.19(dd,J=13.3,5.1Hz,1H),4.68(s,2H),4.58(q,J=12.9Hz,2H),4.11(d,J=2.4Hz,2H),3.92– 3.85(m,1H),3.57–3.50(m,1H),3.44–3.35(m,1H),3.15(brs,2H),3.02–2.85(m,1H),2.85–2.73(m, 1H),2.59–2.51(m,2H),2.46–2.35(m,1H),2.26–2.15(m,1H),1.44(s,3H),1.43(s,3H).LCMS(ESI)C 28 H 30 N5O3S + [M+H] + :Calculated value 516.21, measured value 516.2.

[0522] Example 198: Preparation of 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04727)

[0523] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04727) (white solid, 34 mg, yield 36%) was prepared. 1H NMR(400MHz,MeOD)δ8.95(s,1H),7.97(t,J=9.5Hz,1H),7.89(s,1H),7.82(t,J =7.9Hz,2H),7.70(s,1H),7.62(d,J=8.0Hz,1H),5.96(s,1H),5.52(s,1H),5.20 (td,J=14.0,5.1Hz,2H),4.69(d,J=11.7Hz,2H),4.61(t,J=9.0Hz,2H),4.51(t,J=12.6Hz,2H),4.06(s,2H),2 .94(ddd,J=23.8,12.7,6.0Hz,3H),2.87–2.77(m,2H),2.39(s,3H),2.21(dd,J=12.9,5.1Hz,2H).LCMS(ESI)C 27 H 28 N5O3S + [M+H] + :Calculated value 502.19, measured value 502.2.

[0524] Example 199: Preparation of 3-(1-oxo-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05101)

[0525] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05101) (white solid, 51 mg, yield 61%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ8.99(s,1H),7.96(d,J=6.9Hz,2H),7.85(d,J=7.0Hz,3H),7.8 0(d,J=7.6Hz,1H),7.53–7.48(m,3H),6.74(s,1H),5.20(dd,J=13.3,5.2Hz,1H),4.64 –4.53(m,4H),4.09(s,2H),3.93–3.84(m,1H),3.56–3.46(m,1H),3.23–3.07(m,2H),3 .01–2.86(m,1H),2.80–2.79(m,1H),2.54–2.51(m,1H),2.20–2.17(m,1H).LCMS(ESI)C 31 H 28 N5O3S + [M+H] + :Calculated value 550.19, measured value 550.2.

[0526] Example 200: Preparation of 3-(1-oxo-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04908)

[0527] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04908) (white solid, 26 mg, yield 31%) was prepared. 1 H NMR(400MHz,MeOD)δ9.07(s,1H),7.96(d,J=7.8Hz,1H),7.80(s,1H),7.75(d,J=5.9Hz,1H), 7.67(d,J=7.9Hz,1H),7.44–7.33(m,4H),7.24(t,J=7.1Hz,1H),5.48(s,1H),5.22(dd,J=13 .4,5.3Hz,1H),4.69–4.53(m,2H),4.46(s,2H),3.52–3.47(m,2H),3.07–2.87(m,3H),2.85– 2.77(m,1H),2.74–2.66(m,2H),2.54(qd,J=13.2,4.7Hz,1H),2.29–2.13(m,1H).LCMS(ESI)C 31 H 28 N5O3S + [M+H] + :Calculated value 550.19, measured value 550.2.

[0528] Example 201: Preparation of 3-(1-oxo-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05266)

[0529] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05266) (white solid, 49 mg, yield 51%) was prepared. 1H NMR(400MHz,MeOD-d4)δ9.12(s,1H),7.97(s,1H),7.94(d,J=7.8Hz,1H),7.84(d,J= 7.3Hz,1H),6.18(s,1H),5.19(dd,J=13.3,5.1Hz,1H),4.71(s,2H),4.60(q,J=17.5 Hz,2H),4.10(s,2H),3.96–3.78(m,1H),3.62–3.54(m,1H),3.05–3.01(m,3H),2.98 –2.70(m,5H),2.58–2.49(m,1H),2.26–2.15(m,1H),2.03–1.87(m,4H).LCMS(ESI)C 29 H 30 N5O3S + [M+H] + :Calculated value 528.21, measured value 528.3.

[0530] Example 202: Preparation of 3-(5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04934)

[0531] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04934) (white solid, 45 mg, yield 58%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ8.95(s,1H),7.95(d,J=7.9Hz,1H),7.91(d,J=7.0Hz, 1H),7.80(d,J=7.3Hz,1H),6.20(s,1H),5.19(dd,J=13.3,5.1Hz,1H),4.68(s, 2H),4.65–4.52(m,2H),4.08(s,2H),3.95–3.77(m,1H),3.65–3.43(m,1H),3.15–3.09(m,4H),2.98 (brs,2H),2.95–2.85(m,1H),2.86–2.74(m,1H),2.63–2.46(m,3H),2.27–2.13(m,1H).LCMS(ESI)C 28 H 28 N5O3S + [M+H] + :Calculated value 514.19, measured value 514.2.

[0532] Example 203: Preparation of 3-(5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05102)

[0533] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05102) (white solid, 53 mg, yield 62%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ7.96(d,J=7.8Hz,1H),7.77(s,1H),7.73(s,1H),7.68(d,J=7.8Hz,1 H),7.43–7.33(m,4H),7.24(t,J=7.2Hz,1H),5.60(s,1H),5.22(dd,J=13.3,5.1Hz,1H),4.68 –4.54(m,2H),4.47(s,2H),3.61–3.51(m,1H),3.49–3.38(m,1H),3.17–3.02(m,1H),3.00–2. 88(m,2H),2.85(s,3H),2.83–2.75(m,1H),2.60–2.49(m,3H),2.27–2.17(m,1H).LCMS(ESI)C 32 H 30 N5O3S + [M+H] + :Calculated value 564.21, measured value 564.2.

[0534] Example 204: Preparation of 3-(5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04863)

[0535] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04863) (white solid, 24 mg, yield 33%) was prepared. 1H NMR(400MHz,DMSO)δ11.50(s,1H),11.01(s,1H),7.97(s,1H),7.86(s,2H),5.84(s,1 H),5.15(dd,J=13.2,5.1Hz,1H),4.66–4.38(m,4H),3.82–3.73(m,2H),3.69–3.66(m ,1H),3.45–3.39(m,1H),3.10–2.95(m,1H),2.95–2.74(m,6H),2.68(s,3H),2.62(d, J=15.5Hz,2H),2.46–2.41(m,1H),2.08–1.99(m,1H),1.89–1.70(m,4H).LCMS(ESI)C 30 H 32 N5O3S + [M+H] + :Calculated value 542.22, measured value 542.3.

[0536] Example 205: Preparation of 3-(5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05211)

[0537] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-05211) (white solid, 26 mg, yield 32%) was prepared. 1 H NMR(400MHz,MeOD-d4)δ7.97–7.92(m,2H),7.83(d,J=7.9Hz,1H),6.32(s,1H), 5.19(dd,J=13.3,5.1Hz,1H),4.76–4.67(m,2H),4.66–4.52(m,2H),4.11(s,2H) ,3.93–3.78(m,1H),3.64–3.46(m,1H),3.21–2.97(m,6H),2.91(s,3H),2.84–2. 74(m,1H),2.61–2.46(m,3H),2.45–2.36(m,1H),2.26–2.13(m,1H).LCMS(ESI)C 29 H 30 N5O3S + [M+H] + :Calculated value 528.21, measured value 528.3.

[0538] Example 206: Preparation of 3-(5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04718)

[0539] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04718) (white solid, 3 mg, yield 3%) was prepared. 1 H NMR(400MHz,MeOD)δ7.99(d,J=7.7Hz,1H),7.87(s,1H),7.82–7.76(m,2H),7.66 (d,J=6.1Hz,1H),6.64(s,1H),5.22(dd,J=13.3,5.3Hz,1H),4.89(s,2H),4.85– 4.85(m,2H),4.71–4.57(m,4H),4.10(s,2H),2.94(d,J=12.5Hz,1H),2.84(s,1H),2.79(s,3H),2.55(d,J=8.9Hz,1H),2.22(s,1H).LCMS(ESI)C 26 H 26 N5O3S + [M+H] + :Calculated value 488.18, measured value 488.3.

[0540] Example 207: Preparation of 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04708)

[0541] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04708) (white solid, 17 mg, yield 21%) was prepared. 1H NMR (400MHz, MeOD) δ9.29(s,1H),7.98(d,J=7.9Hz,1H),7.87(d,J=6.4Hz,2H),7.79(d,J=8.0Hz,1H),7.56(d,J=6. 1Hz,1H),7.30(s,1H),5.21(dd,J=13.6,5.3Hz,1H),4.68(d,J=5.2Hz,2H),4.62(d,J=7.6Hz,2H),4.11(s,2H),3.96 -3.87(m,1H),3.50-3.48(m,1H),3.15–3.08(m,1H),3.00–2.89(m,1H),2.81(d,J=15.7 Hz,1H),2.55(dd,J=13.2,5.0Hz,1H),2.25–2.19(m,1H),1.35-1.31(m,1H).LCMS(ESI)C 25 H 24 N5O3S + [M+H] + :Calculated value 474.16, measured value 474.1.

[0542] Example 208: Preparation of 3-(5-((4-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04683)

[0543] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04683) (white solid, 40 mg, yield 43%) was prepared. 1 H NMR (400MHz, MeOD) δ7.98(d,J=7.7Hz,1H),7.81(s,1H),7.75(d,J=8.1Hz,1H),5.23(dd,J=13.2,5.1Hz,1H),4.66–4.57(m,6H),4.55(s,2H),3.63–3 .56(m,2H),3.47–3.43(m,4H),3.29–3.22(m,2H),3.03–2.90(m,1H),2.85 –2.83(m,1H),2.55(dd,J=13.3,4.5Hz,1H),2.24–2.19(m,1H).LCMS(ESI)C 24 H 26 ClN6O3S + [M+H] + :Calculated value 513.15, measured value 513.2.

[0544] Example 209: Preparation of 3-(5-((4-(2-morpholino-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04710)

[0545] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04710) (white solid, 31 mg, yield 45%) was prepared. 1 H NMR(400MHz,MeOD)δ7.95(d,J=7.8Hz,1H),7.90(s,1H),7.76(d,J=7.6Hz,1H),5.20(dd,J=13.42 5.2Hz,1H),4.98–4.88(m,4H),4.61–4.56(m,4H),4.53-4.51(m,1H),3.82–3.76(m,9 H),3.56–3.52(m,3H),3.44–3.40(m,3H),2.94–2.90(m,1H),2.86–2.74(m,1H),2.57 -2.52(m,1H),2.23–2.19(m,1H).LCMS(ESI)C 28 H 34 N7O4S + [M+H] + :Calculated value 564.24, measured value 564.3.

[0546] Example 210: Preparation of 3-(1-oxo-5-((4-(4-(piperazin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04720)

[0547] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04720) (white solid, 25 mg, yield 93%) was prepared. 1H NMR (400MHz, MeOD) δ7.94 (s, 2H), 7.80 (d, J = 7.4Hz, 1H), 5.20 (dd,J=13.2,4.9Hz,1H),4.61(dd,J=17.9,6.9Hz,6H),4.43(s,1H),4.22(t,J=15.2Hz,4H),3.69(d,J=5.2Hz,2H),3.62(s,1H),3. 53(d,J=7.4Hz,4H),3.43(d,J=14.5Hz,5H),3.01–2.88(m,1H),2.82(d,J=15.5Hz,1H),2.62–2.37(m,2H),2.23(s,1H).LCMS(ESI)C 28 H 35 N8O4S + [M+H] + :Calculated value 563.25, measured value 563.3.

[0548] Example 211: Preparation of 3-(5-((4-(4-morpholino-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04694)

[0549] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04694) (white solid, 41 mg, yield 47%) was prepared. 1 H NMR(400MHz,MeOD)δ7.98–7.90(m,2H),7.78(d,J=7.8Hz,1H),5.21(dd,J=13.4,5.1Hz,1H),4.8 3(d,J=5.0Hz,2H),4.69–4.49(m,5H),4.06–3.94(m,4H),3.86–3.75(m,4H),3.73–3.53(m,3H),3 .51(dd,J=12.9,4.8Hz,3H),3.39(dd,J=12.7,4.6Hz,3H),2.95(ddd,J=18.5,13.5,5.3Hz,1H), 2.87–2.76(m,1H),2.55(qd,J=13.2,4.7Hz,1H),2.22(ddd,J=10.5,5.3,3.1Hz,1H).LCMS(ESI)C 28 H 34 N7O4S + [M+H] + :Calculated value 564.24, measured value 564.3.

[0550] Example 212: Preparation of 3-(1-oxo-5-((4-(thieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04681)

[0551] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04681) (white solid, 36 mg, yield 47%) was prepared. 1 H NMR(400MHz,MeOD)δ8.92(s,1H),8.64(d,J=5.6Hz,1H),7.99(d,J=7.8Hz,1H),7. 91(s,1H),7.82(d,J=7.7Hz,1H),7.68(d,J=5.6Hz,1H),5.24(dd,J=13.3,5.1Hz,1 H),4.63–4.53(m,4H),3.57–3.51(m,4H),3.36–3.32(m,4H),3.04–2.91(m,1H),2. 82(d,J=15.5Hz,1H),2.57(dd,J=13.1,4.5Hz,1H),2.29–2.14(m,1H).LCMS(ESI)C 24 H 25 N6O3S + [M+H] + :Calculated value 477.17, measured value 477.2.

[0552] Example 213: Preparation of 3-(5-((4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04682)

[0553] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04682) (white solid, 60 mg, yield 64%) was prepared. 1H NMR(400MHz,MeOD)δ8.29(d,J=5.5Hz,1H),7.99(d,J=7.8Hz,1H),7.85(s,1H),7.7 9(d,J=7.8Hz,1H),7.48(d,J=5.5Hz,1H),5.24(dd,J=13.4,5.1Hz,1H),5.01–4.83 (m,2H),4.71–4.59(m,5H),3.79–3.60(m,3H),3.48–3.41(m,2H),3.06–2.93(m,1H ),2.88–2.77(m,1H),2.57(dd,J=13.3,4.3Hz,1H),2.30–2.14(m,1H).LCMS(ESI)C 24 H 24 ClN6O3S + [M+H] + :Calculated value 511.13, measured value 511.1.

[0554] Example 214: Preparation of 3-(5-((4-(2-morpholinothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04903)

[0555] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04903) (white solid, 30 mg, yield 35%) was prepared. 1 H NMR(400MHz,MeOD)δ8.30(d,J=5.6Hz,1H),7.93(d,J=8.0Hz, 2H),7.81–7.74(m,1H),7.41(d,J=5.6Hz,1H),5.18(dd,J=13.3,5.2Hz,1H),5.13–4.89(m,2H),4.68–4.50(m,4H),3.84(brs ,10H),3.75–3.40(m,4H),3.01–2.85(m,1H),2.82–2.76(m,1H),2.52(qd,J=13.2,4.7Hz,1H),2.27–2.12(m,1H).LCMS(ESI)C 28 H 32 N7O4S + [M+H] + :Calculated value 562.22, measured value 562.3.

[0556] Example 215: Preparation of 3-(1-oxo-5-((4-(4-(piperazin-1-yl)thieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04698)

[0557] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04698) (white solid, 43 mg, yield 62%) was prepared. 1 H NMR (400MHz, MeOD) δ8.35(d,J=5.6Hz,1H),7.97(d,J=7.8Hz,1H),7.92(s,1H),7.79(d,J=7.3Hz,1 H),7.46(d,J=5.6Hz,1H),5.21(dd,J=13.4,5.2Hz,1H),4.63(dd,J=14.9,11.0Hz,4H),4.45–4.38 (m,4H),4.34(d,J=7.0Hz,1H),3.69(d,J=5.2Hz,3H),3.61(d,J=5.9Hz,4H),3.53(d,J=5.0Hz,4H) ,3.03–2.89(m,1H),2.82(d,J=15.7Hz,1H),2.63–2.47(m,1H),2.22(d,J=10.2Hz,1H).LCMS(ESI)C 28 H 33 N8O3S + [M+H] + :Calculated value 561.24, measured value 561.3.

[0558] Example 216: Preparation of 3-(5-((4-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04906)

[0559] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04906) (white solid, 27 mg, yield 32%) was prepared. 1H NMR(400MHz,MeOD)δ8.28(d,J=5.6Hz,1H),7.94(d,J=7.9Hz,1H),7.86(s,1H), 7.74(d,J=7.5Hz,1H),7.39(d,J=5.6Hz,1H),5.19(dd,J=13.3,5.1Hz,1H),4.66 –4.52(m,5H),4.20–4.09(m,4H),3.90–3.82(m,5H),3.60–3.36(m,7H),3.00–2. 87(m,1H),2.84–2.78(m,1H),2.60–2.45(m,1H),2.23–2.16(m,1H).LCMS(ESI)C 28 H 32 N7O4S + [M+H] + :Calculated value 562.22, measured value 562.3.

[0560] Example 217: Preparation of 3-(5-((4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04202)

[0561] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04202) (white solid, 30 mg, yield 41%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ7.95(d,J=7.8Hz,1H),7.84(s,1H),7.77(d,J=7.9Hz,1H),7.66(d,J=8.1Hz, 1H),7.62(d,J=5.5Hz,1H),7.49(dd,J=5.6,0.7Hz,1H),7.32(t,J=7.9Hz,1H),7.01(d,J=7.6Hz,1H) ,5.19(dd,J=13.4,5.2Hz,1H),4.60(q,J=10.0Hz,4H),3.71–3.58(m,4H),3.57–3.51(m,2H),3.20–3 .11(m,2H),3.00–2.85(m,1H),2.84–2.72(m,1H),2.56–2.46(m,1H),2.21–2.11(m,1H).LCMS(ESI)C 26 H 27 N4O3S + [M+H] + :Calculated value 475.18, measured value 475.2.

[0562] Example 218: Preparation of 3-(1-oxo-5-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04199)

[0563] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04199) (white solid, 16 mg, yield 23%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ7.88(d,J=7.8Hz,1H),7.76(s,1H),7.68(d,J=7.9Hz,1H),5.17(dd,J=13.4,5.2Hz,1H),4.55(q,J=17.3Hz,2 H),4.45–4.32(m,6H),3.48(t,J=5.5Hz,2H),2.99–2.86(m,1H),2.85–2.74(m,1H),2.56–2.45(m,1H),2.26–2.13(m,1H).LCMS(ESI)C 20 H 20 F3N6O3S + [M+H] + :Calculated value 449.15, measured value 449.2.

[0564] Example 219: Preparation of 3-(5-((4-(2-((2,4-dimethylphenyl)thio)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04203)

[0565] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04203) (white solid, 27 mg, yield 40%) was prepared. 1H NMR (400MHz, MeOD-d4) δ7.95(d,J=7.8Hz,1H),7.81(s,1H),7.73(d,J=7.8Hz,1H),7.28(d,J=7.9Hz,1 H),7.21–7.10(m,3H),7.06(d,J=6.6Hz,1H),6.99–6.91(m,1H),6.57–6.49(m,1H),5.20(dd,J=13.4, 5.1Hz,1H),4.67–4.52(m,4H),3.68–3.45(m,4H),3.42-3.36(m,2H),3.23–3.08(m,2H),2.94–2.88(m ,1H),2.85–2.75(m,1H),2.57-2.51(m,1H),2.33(s,3H),2.27(s,3H),2.24–2.13(m,1H).LCMS(ESI)C 32 H 35 N4O3S + [M+H] + :Calculated value 555.24, measured value 555.3.

[0566] Example 220: Preparation of 3-(5-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04200)

[0567] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04200) (white solid, 17 mg, yield 28%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ7.94(d,J=7.8Hz,1H),7.80(s,1H),7.73(d,J=7.8Hz,1H),7.40( d,J=5.2Hz,1H),6.86(d,J=5.2Hz,1H),5.19(dd,J=13.4,5.2Hz,1H),4.65(s,2H),4.5(q, J=12.2Hz,2H),4.36(s,2H),3.97–3.77(m,1H),3.57–3.46(m,1H),3.25(t,J=6.1Hz,2H) ,3.01–2.86(m,1H),2.82–2.77(m,1H),2.56–2.47(m,1H),2.23–2.16(m,1H).LCMS(ESI)C 21 H 22 N3O3S + [M+H] +:Calculated value 396.14, measured value 396.2.

[0568] Example 221: Preparation of 3-(5-((4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04255)

[0569] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04255) (white solid, 33 mg, yield 47%) was prepared. 1 H NMR (400MHz, MeOD-d4) δ8.04(d,J=8.2Hz,1H),7.95(d,J=8.0Hz,2H),7.82(s,1H),7.75(d,J=7.6Hz,1H),7.57(t,J=7.3Hz,1H),7.47(t,J=7 .4Hz,1H),5.19(dd,J=13.3,5.2Hz,1H),4.68–4.50(m,4H),4.33–4.09(m,2H),3.69–3.38(m,6H),3.03–2.86(m,1H),2.86–2.72(m,1H),2.58 -2.47(m,1H),2.24–2.18(m,1H).LCMS(ESI)C 25 H 26 N5O3S + [M+H] + :Calculated value 476.18, measured value 476.2.

[0570] Example 222: Preparation of 3-(5-((4-(4-((3r,5r,7r)-adamantan-1-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03026)

[0571] Referring to the method of Synthesis Scheme 1, under appropriate conditions known in the art, the target compound (GT-03026) (white solid, 20 mg, yield 37%) was prepared. LCMS (ESI) C 35 H 43 N4O3S + [M+H] + :Calculated value 567.33, measured value 567.3.

[0572] Example 223: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione (GT-04732)

[0573] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04732) (white solid, 28 mg, yield 41%) was prepared. 1 H NMR (400MHz, MeOD) δ8.15(s,1H),8.06(s,2H),7.28(d,J=5.1Hz,1H),6.90(d,J=5.1Hz,1H),5.90(s,1H),5.21(dd,J=1 2.5,5.4Hz,1H),4.86(s,2H),4.67(s,2H),3.96(s,2H),2.99–2.74(m,5H),2.32(s,3H),2.24–2.12(m,1H).LCMS(ESI)C 24 H 24 N3O4S + [M+H] + :Calculated value 450.15, measured value 450.1.

[0574] Example 224: Preparation of 3-(4-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04728)

[0575] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04728) (white solid, 24 mg, yield 37%) was prepared. 1 H NMR(400MHz,MeOD)δ8.00(d,J=7.6Hz,1H),7.89(d,J=7.6Hz,1H),7.76–7.71(m,1H),7.28(d, J=5.1Hz,1H),6.90(d,J=5.1Hz,1H),5.91(s,1H),5.25(dd,J=17.2,8.2Hz,2H),4.88(d,J=3. 4Hz,1H),4.84–4.81(m,1H),4.59(s,2H),4.01(s,2H),8.89–1.79(m,197H),2.85(s,2H),2.6 1(d,J=8.1Hz,2H),2.53(dd,J=13.0,4.5Hz,1H),2.32(s,3H),2.30–2.19(m,2H).LCMS(ESI)C 24 H 26 N3O3S + [M+H] + :Calculated value 436.17, measured value 436.2.

[0576] Example 225: Preparation of 3-(4-fluoro-5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04729)

[0577] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04729) (white solid, 21 mg, yield 31%) was prepared. 1 H NMR (400MHz, MeOD) δ7.86–7.79(m,2H),7.28(d,J=5.1Hz,1H),6.90(d,J=5.1Hz,1H),5.91(s,1H),5.21(dd,J=13.4,5.1Hz,1H),4.78–4 .54(m,5H),4.03(s,2H),2.92(dd,J=13.2,5.4Hz,2H),2.84(s,2H),2.60–2.51(m,1H),2.32(s,3H),2.23(d,J=5.2Hz,1H).LCMS(ESI)C 24 H 25 FN3O3S + [M+H] + :Calculated value 454.16, measured value 454.2.

[0578] Example 226: Preparation of 3-(7-fluoro-5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04730)

[0579] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04730) (white solid, 35 mg, yield 51%) was prepared. 1H NMR (400MHz, MeOD) δ7.63(s,1H),7.48(d,J=9.8Hz,1H),7.28(d,J=5.1Hz,1H),6.90( d,J=5.1Hz,1H),5.90(s,1H),5.18(dd,J=13.3,5.2Hz,1H),4.87(s,1H),4.59(t,J=1 2.5Hz,4H),3.96(s,2H),3.78(s,1H),3.00–2.89(m,2H),2.82(dd,J=9.9,7.7Hz,2H) ,2.52(dd,J=13.2,4.8Hz,1H),2.32(s,3H),2.22(dd,J=9.1,3.7Hz,1H).LCMS(ESI)C 24 H 25 FN3O3S + [M+H] + :Calculated value 454.16, measured value 454.2.

[0580] Example 227: Preparation of 2-(2,6-dioxopiperidin-3-yl)-4-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione (GT-04731)

[0581] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04731) (white solid, 22 mg, yield 33%) was prepared. 1 H NMR (400MHz, MeOD) δ8.10(dd,J=6.1,2.3Hz,1H),8.04–7.98(m,2H),7.28(d,J=5.1Hz,1H),6.90(d,J=5.1Hz,1H),5.92(s,1H),5.24( dd,J=12.6,5.5Hz,1H),4.92(d,J=3.0Hz,4H),4.09(s,2H),2.93–2.72(m,5H),2.31(d,J=11.7Hz,3H),2.25–2.15(m,1H).LCMS(ESI)C 24 H 24 N3O4S + [M+H] + :Calculated value 450.15, measured value 450.2.

[0582] Example 228: Preparation of 3-(4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04528)

[0583] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04528) (white solid, 62 mg, yield 79%) was prepared. 1 H NMR (400MHz, DMSO) δ11.07(s,1H),10.93(s,1H),8.00(d,J=6.4Hz,1H),7.85(d,J=7.0Hz,1 H),7.67(d,J=7.2Hz,1H),7.43–7.29(m,2H),7.20(d,J=6.5Hz,1H),5.19(dd,J=13.2,5.0H z,1H),4.84(d,J=17.6Hz,1H),4.63–4.41(m,3H),3.59–3.39(m,5H),3.16–3.26(m,3H),3. 04–2.88(m,1H),2.66(d,J=16.2Hz,1H),2.44–2.23(m,1H),2.13–1.94(m,1H).LCMS(ESI)C 24 H 25 Cl2N4O3 + [M+H] + :Calculated value 487.13, measured value 487.1.

[0584] Example 229: Preparation of 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04526)

[0585] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04526) (white solid, 30 mg, yield 30%) was prepared. 1 H NMR (400MHz, DMSO) δ11.03(s,1H),7.88(s,1H),7.73(d,J=7.8Hz,1H),7.60(dd ,J=7.1,3.5Hz,1H),7.36(q,J=7.8Hz,2H),7.20(dd,J=7.3,2.2Hz,1H),5.17–5 .13(m,1H),4.69–4.37(m,5H),3.65–3.52(m,2H),3.21–3.06(m,3H),2.99–2.8 4(m,2H),2.70–2.57(m,2H),2.57–2.42(m,1H),2.06–1.95(m,1H).LCMS(ESI)C 24 H 24 Cl2FN4O3+ [M+H] + :Calculated value 505.12, measured value 505.1.

[0586] Example 230: Preparation of 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04527)

[0587] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04527) (white solid, 48 mg, yield 47%) was prepared. 1 H NMR (400MHz, DMSO) δ11.02(s,1H),8.02(s,1H),7.70(d,J=8.0Hz,1H),7.41–7.3 1(m,2H),7.19(dd,J=7.2,2.2Hz,1H),5.15(dd,J=13.2,5.1Hz,1H),4.56(brs,2 H),4.45(dd,J=50.2,17.4Hz,3H),3.61–3.39(m,4H),3.21–3.12(m,3H),3.01–2 .87(m,1H),2.64–2.56(m,1H),2.51–2.41(m,1H),2.11–1.90(m,1H).LCMS(ESI)C 24 H 24 Cl2FN4O3 + [M+H] + :Calculated value 505.12, measured value 505.1.

[0588] Example 231: Preparation of 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04445)

[0589] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04445) (white solid, 3.3 g, yield 81%) was prepared. 1H NMR (400MHz, DMSO) δ11.43(s,1H),11.03(s,1H),7.76–7.66(m,2H),7.42–7.32(m,2H),7.20(dd,J=7.3,2.3Hz,1H),5.12(dd,J=13.3,5.1Hz,1H),4. 61–4.36(m,4H),3.51–3.45(m,4H),3.33–3.15(m,4H),3.01–2.84(m,1H), 2.61(d,J=17.9Hz,1H),2.47-2.40(m,1H),2.05–2.01(m,1H).LCMS(ESI)C 24 H 24 Cl2FN4O3 + [M+H] + :Calculated value 505.12, measured value 505.1.

[0590] Example 232: Preparation of 3-(5-((4-(5,6-dichloropyridazin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04544)

[0591] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04544) (white solid, 60 mg, yield 62%) was prepared. 1 H NMR (400MHz, DMSO) δ11.02 (s, 1H), 9.06 (s, 1H), 7.85 (d, J = 7.4Hz, 2H), 7.74 (d,J=8.3Hz,1H),5.15(dd,J=13.3,5.1Hz,1H),4.62–4.37(m,4H),4.10–3.8 4(m,2H),3.54–3.36(m,4H),3.25–3.21(m,2H),2.92–2.90(m,2H),2.62(d, J=17.5Hz,1H),2.43(dd,J=13.2,4.6Hz,1H),2.10–1.92(m,1H).LCMS(ESI)C 22 H 23 Cl2N6O3 + [M+H] + :Calculated value 489.12, measured value 489.1.

[0592] Example 233: Preparation of 3-(4-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04764)

[0593] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04764) (white solid, 71 mg, yield 61%) was prepared. 1 H NMR (400MHz, DMSO) δ11.08(s,1H),10.99(d,J=45.5Hz,1H),8.30–8.16(m,1H),7.99(d,J=6.8Hz,1H),7.86(d,J=7 .5Hz,1H),7.77–7.68(m,1H),7.66(d,J=7.4Hz,1H),7.35(d,J=9.1Hz,1H),5.21(dd,J=13.2,5.1Hz,1H),4.85(s,1 H),4.55(d,J=17.5Hz,1H),4.45(s,2H),3.56(dd,J=25.5,11.2Hz,2H),3.49–3.39(m,2H),3.26(d,J=8.8Hz,2H), 2.96(s,1H),2.66(d,J=15.2Hz,1H),2.42–2.34(m,2H),2.21(d,J=12.3Hz,2H),2.07(d,J=5.7Hz,1H).LCMS(ESI)C 26 H 26 FN4O4 + [M+H] + :Calculated value 477.19, measured value 477.3.

[0594] Example 234: Preparation of 3-(6-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04768)

[0595] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04768) (white solid, 34 mg, yield 29%) was prepared. 1H NMR(400MHz,DMSO)δ11.02(s,1H),10.74(s,1H),8.21–8.09(m,1H),8.02(d,J=12.1Hz,1H), 7.90(d,J=7.6Hz,1H),7.79–7.64(m,2H),7.34(td,J=9.1,2.1Hz,1H),5.14(dd,J=13.3,5.2 Hz,1H),4.53(d,J=17.6Hz,3H),3.54(d,J=10.7Hz,2H),3.45(s,1H),3.13(s,2H),2.99–2.8 6(m,1H),2.72–2.57(m,2H),2.47–2.37(m,1H),2.25(s,4H),2.06–1.96(m,1H).LCMS(ESI)C 26 H 26 FN4O4 + [M+H] + :Calculated value 477.19, measured value 477.3.

[0596] Example 235: Preparation of 3-(4-fluoro-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04765)

[0597] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04765) (white solid, 77 mg, yield 64%) was prepared. 1 H NMR (400MHz, DMSO) δ11.04(s,1H),10.84(s,1H),8.14(d,J=3.7Hz,1H),7.93(s,1H),7.79 –7.68(m,2H),7.34(td,J=9.1,2.0Hz,1H),5.16(dd,J=13.3,5.1Hz,1H),4.53(dt,J=50.5 ,13.7Hz,4H),3.62(s,2H),3.46(s,1H),3.25(s,2H),3.02–2.82(m,1H),2.64(dd,J=20.5 ,9.6Hz,1H),2.48–2.40(m,1H),2.33(s,2H),2.25(s,2H),2.07–1.96(m,1H).LCMS(ESI)C 26 H 25 F2N4O4 + [M+H] + :Calculated value 495.18, measured value 495.2.

[0598] Example 236: Preparation of 3-(6-fluoro-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04766)

[0599] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04766) (white solid, 66 mg, yield 55%) was prepared. 1 H NMR (400MHz, DMSO) δ11.03(s,1H),11.03–10.80(m,1H),8.23–8.09(m,1H),8.03(d,J=16.1Hz,1H),7 .71(dd,J=11.9,10.4Hz,2H),7.34(t,J=9.1Hz,1H),5.16(dd,J=13.2,5.0Hz,1H),4.64–4.47(m,3H), 4.39(d,J=17.6Hz,1H),3.59(d,J=11.6Hz,2H),3.45(d,J=12.7Hz,2H),3.24(d,J=10.2Hz,2H),3.03 –2.85(m,1H),2.72–2.56(m,2H),2.33(s,2H),2.22(d,J=13.7Hz,2H),2.09–1.96(m,1H).LCMS(ESI)C 26 H 25 F2N4O4 + [M+H] + :Calculated value 495.18, measured value 495.3.

[0600] Example 237: Preparation of 3-(7-fluoro-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04767)

[0601] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04767) (white solid, 82 mg, yield 68%) was prepared. 1H NMR (400MHz, DMSO) δ11.03(s,2H),8.17(dd,J=8.8,5.3Hz,1H),7.75(t,J=6.7Hz,1H),7.72(s, 1H),7.67(d,J=10.0Hz,1H),7.34(td,J=9.1,2.2Hz,1H),5.12(dd,J=13.3,5.1Hz,1H),4.55–4 .40(m,4H),3.55(d,J=11.6Hz,2H),3.46(s,1H),3.14(d,J=11.9Hz,2H),2.96–2.86(m,1H),2. 61(d,J=16.8Hz,2H),2.37–2.29(m,2H),2.22(d,J=12.3Hz,2H),2.05–1.96(m,1H).LCMS(ESI)C 26 H 25 F2N4O4 + [M+H] + :Calculated value 495.18, measured value 495.2.

[0602] Example 238: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-04771)

[0603] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04771) (white solid, 50 mg, yield 42%) was prepared. 1 H NMR (400MHz, DMSO) δ11.16(s,1H),11.01(s,1H),8.27(s,1H),8.15(dd,J=8.6,5.3Hz,2 H),8.05(dd,J=15.9,7.6Hz,1H),7.72(dd,J=9.1,2.0Hz,1H),7.34(td,J=9.2,2.1Hz,1 H),5.20(dd,J=12.9,5.4Hz,1H),4.60(s,2H),3.55(d,J=11.3Hz,2H),3.47–3.42(m,1H ),3.15(d,J=11.5Hz,2H),2.90(dd,J=15.7,9.9Hz,1H),2.62(dd,J=29.8,12.4Hz,3H), 2.32(d,J=6.9Hz,1H),2.27(d,J=11.9Hz,2H),2.13–2.03(m,1H).LCMS(ESI)C 26 H 24FN4O5 + [M+H] + :Calculated value 491.17, measured value 491.2.

[0604] Example 239: Preparation of 2-(2,6-dioxopiperidin-3-yl)-4-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-04770)

[0605] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04770) (white solid, 29 mg, yield 24%) was prepared. 1 H NMR (400MHz, DMSO) δ11.17(s,1H),10.74(s,1H),8.22(d,J=7.5Hz,1H),8.15(dd,J=8.4,5. 4Hz,1H),8.07–7.95(m,2H),7.72(d,J=7.3Hz,1H),7.34(t,J=8.1Hz,1H),5.20(dd,J=12.8, 5.3Hz,1H),4.80(s,2H),3.63(s,2H),3.54(s,1H),2.97–2.83(m,1H),2.60(dd,J=26.0,12 .6Hz,2H),2.51(s,2H),2.31(d,J=16.1Hz,2H),2.24(s,2H),2.14–2.02(m,1H).LCMS(ESI)C 26 H 24 FN4O5 + [M+H] + :Calculated value 491.17, measured value 491.2.

[0606] Example 240: Preparation of 3-(4-((4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04914)

[0607] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04914) (white solid, 51 mg, yield 73%) was prepared. 1H NMR (400MHz, DMSO) δ11.08(s,2H),8.04(d,J=7.5Hz,1H),7.86(d,J=7.3Hz,1H),7.77(d,J=5.5Hz,1H),7. 68(dd,J=15.0,7.8Hz,2H),7.50(d,J=5.5Hz,1H),7.32(t,J=7.9Hz,1H),6.96(d,J=7.5Hz,1H),5.20(dd,J =13.2,5.1Hz,1H),4.89(d,J=17.7Hz,1H),4.58(d,J=17.6Hz,1H),4.51(s,2H),3.57(s,2H),3.50(s,4H), 3.28(s,2H),3.03–2.91(m,1H),2.66(d,J=17.2Hz,1H),2.42–2.31(m,1H),2.10–2.02(m,1H).LCMS(ESI)C 26 H 27 N4O3S + [M+H] + :Calculated value 475.18, measured value 475.2.

[0608] Example 241: Preparation of 5-((4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-04915)

[0609] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04915) (white solid, 46 mg, yield 38%) was prepared. 1H NMR (400MHz, DMSO) δ11.32(s,1H),11.16(s,1H),8.29(s,1H),8.17(d,J=7.7Hz,1H),8.07(d,J=7.6Hz,1H),7 .76(d,J=5.5Hz,1H),7.70(d,J=8.1Hz,1H),7.49(d,J=5.5Hz,1H),7.31(t,J=7.9Hz,1H),6.96(d,J=7.6Hz,1H ),5.20(dd,J=12.9,5.3Hz,1H),4.66(s,2H),3.55(d,J=12.2Hz,2H),3.47(s,2H),3.22(t,J=11.4Hz,2H),2. 91(ddd,J=13.8,12.2,5.2Hz,1H),2.62(dd,J=28.3,10.8Hz,2H),2.54(s,2H),2.14–2.03(m,1H).LCMS(ESI)C 26 H 25 N4O4S + [M+H] + :Calculated value 489.16, measured value 489.2.

[0610] Example 242: Preparation of 3-(1-oxo-4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-04920)

[0611] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04920) (white solid, 14 mg, yield 19%) was prepared. 1H NMR (400MHz, DMSO) δ13.05 (s, 1H), 11.13 (d, J = 7.7Hz, 1H), 8.50(d,J=7.8Hz,1H),8.45(s,1H),8.03(s,1H),7.97–7.91(m,2H),7.84–7.77(m,1H),7.75(d,J= 8.3Hz,1H),7.70(d,J=7.6Hz,2H),7.50(s,1H),5.21–5.12(m,1H),4.75(s,1H),4.42(s,2H),3.69( d,J=7.5Hz,3H),3.32–3.25(m,2H),3.24–3.10(m,3H),2.96–2.85(m,2H),2.68–2.58(m,3H),2.55 (s,2H),2.07(d,J=4.6Hz,1H),1.95(d,J=12.9Hz,2H),1.86(s,1H),1.77–1.53(m,4H).LCMS(ESI)C 20 H 20 F3N6O3 + [M+H] + :Calculated value 449.15, measured value 449.2.

[0612] Example 243: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)isoindoline-1,3-dione (GT-04921)

[0613] Referring to the method of Synthesis Scheme 1, under appropriate conditions understood in the art, the target compound (GT-04921) (white solid, 33 mg, yield 25%) was prepared. 1 H NMR (400MHz, DMSO) δ11.13(s,1H),7.98(s,1H),7.96–7.90(m,2H),5.16(dd,J=12.9,5.4Hz,1H),4.21(t,J=5.4Hz,2H),4.04(d,J=25.0Hz,4 H),3.07(t,J=5.3Hz,2H),2.90(d,J=6.6Hz,1H),2.64–2.55(m,2H),2.53(s,1H),2.11–2.02(m,1H),1.27(dt,J=7.4,4.9Hz,1H).LCMS(ESI)C 20 H 18 F3N6O4 + [M+H] +:Calculated value 463.13, measured value 463.1.

[0614] Example 244: Preparation of 3-(1-oxo-5-((4-(2-(piperidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05380)

[0615] Referring to the method of Synthesis Scheme 1, the target compound (GT-05380) (white solid, 24 mg, yield 27%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.34(s,1H),11.01(s,1H),7.85(s,1H),7.83(d,J=7.9Hz,1H),7.7 4(d,J=7.6Hz,1H),5.15(dd,J=13.2,5.1Hz,1H),4.59–4.33(m,6H),3.70–3.65(m,4H),3.62 –3.58(m,3H),3.34–3.26(m,3H),3.24–3.07(m,4H),2.99–2.86(m,1H),2.61(d,J=17.1Hz,1 H),2.47–2.37(m,1H),2.09–1.96(m,1H),1.67–1.61(m,2H),1.56–1.48(m,4H).LCMS(ESI)C 29 H 36 N7O3S + [M+H] + :Calculated value 562.26, measured value 562.3.

[0616] Example 245: Preparation of 3-(1-oxo-5-((4-(2-(pyrrolidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05389)

[0617] Referring to the method of Synthesis Scheme 1, the target compound (GT-05389) (white solid, 12 mg, yield 13%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.02(s,1H),7.89(s,1H),7.82(d,J=7.7Hz,1H),7.76(d,J=7.7Hz,1H),5.15(dd,J=13.2,5.0Hz,1H),4.85–4.75(m,1H),4. 57–4.35(m,6H),3.45–3.27(m,7H),3.24–3.08(m,3H),3.01–2.86(m,2H), 2.61(d,J=16.6Hz,2H),2.46–2.36(m,1H),2.05–1.91(m,6H).LCMS(ESI)C 28 H 34 N7O3S + [M+H] + :Calculated value 548.24, measured value 548.3.

[0618] Example 246: Preparation of 3-(5-((4-(2-(azetidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05900)

[0619] Referring to the method of Synthesis Scheme 1, the target compound (GT-05900) (white solid, 45 mg, yield 50%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ12.33(s,1H),11.01(s,1H),7.93(s,1H), 7.83–7.77(m,2H),5.14(dd,J=13.3,5.0Hz,1H),4.63–4.39(m,6H),4.05(t,J=5.6Hz,1H),3.81–3.67(m,4H),3.52–3.38(m,6H),3 .39–3.28(m,2H),3.26–3.17(m,2H),3.02–2.84(m,1H),2.61(d,J=16.5Hz,1H),2.48–2.38(m,1H),2.03–1.99(m,2H).LCMS(ESI)C 27 H 32 N7O3S + [M+H] + :Calculated value 534.23, measured value 534.3.

[0620] Example 247: Preparation of 3-(5-((((3s,5s,7s)-adamantan-1-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-06913)

[0621] Referring to the method of Synthesis Scheme 1, the target compound (GT-06913) (white solid, 14 mg, yield 18%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.00(s,1H),9.01(s,2H),7.81(d,J=7.6Hz,2H),7.71(d ,J=8.3Hz,1H),5.14(dd,J=13.4,5.2Hz,1H),4.50(d,J=17.6Hz,1H),4.36(d,J=1 7.6Hz,1H),4.24(s,2H),3.01–2.83(m,1H),2.61(d,J=17.6Hz,1H),2.47–2.35(m ,1H),2.16(s,3H),2.05–2.01(m,1H),1.98(s,6H),1.71–1.61(m,6H).LCMS(ESI)C 24 H 30 N3O3 + [M+H] + :Calculated value 408.23, measured value 408.3.

[0622] Example 248: Preparation of (1-((1R,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-yl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)methanesulfonamide (GT-06927)

[0623] Referring to the method of Synthesis Scheme 1, the target compound (GT-06927) (white solid, 9 mg, yield 26%) was prepared under appropriate conditions understood in the art. 1H NMR(400MHz,DMSO-d6)δ10.98(s,1H),7.74(s,1H),7.71(d,J=7.8Hz,1H),7.59(s,1H) ,7.50(d,J=7.9Hz,1H),5.11(dd,J=13.3,5.1Hz,1H),4.53–4.27(m,4H),3.02–2.82(m ,2H),2.60(d,J=16.1Hz,1H),2.53–2.48(m,1H),2.47–2.28(m,3H),2.11–1.85(m,4H) ,1.58–1.51(m,1H),1.48–1.33(m,1H),0.99(s,3H),0.75(d,J=1.3Hz,3H).LCMS(ESI)C 24 H 30 N3O6S + [M+H] + :Calculated value 488.18, measured value 488.2.

[0624] Example 249: Preparation of 5-((4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-07842)

[0625] Referring to the method of Synthesis Scheme 1, the target compound (GT-07842) (white solid, 60 mg, yield 74%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.22(s,1H),11.16(s,1H),8.28(s,1H),8.16(d,J=7.3Hz,1H),8.0 6(d,J=7.6Hz,1H),7.68–7.60(m,1H),7.40(t,J=7.9Hz,1H),7.25(dd,J=7.6,1.4Hz,1H),5.7 4(s,1H),5.20(dd,J=12.9,5.3Hz,1H),4.79–4.55(m,2H),3.93–3.70(m,2H),3.69–3.54(m, 1H),3.31–3.22(m,2H),2.94–2.82(m,2H),2.65–2.54(m,2H),2.10–2.05(m,1H).LCMS(ESI)C 25 H 22 Cl2N3O4 + [M+H] + :Calculated value 498.10, measured value 498.1

[0626] Example 250: Preparation of 5-((4-(3-chloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-07843)

[0627] Referring to the method of Synthesis Scheme 1, the target compound (GT-07843) (white solid, 34 mg, yield 54%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.73(s,1H),11.15(s,1H),8.29(s,1H), 8.26(dd,J=4.7,1.6Hz,1H),8.18(dd,J=7.7,1.2Hz,1H),8.04(d,J=7.6Hz,1H),7.87 (dd,J=7.8,1.6Hz,1H),7.10(dd,J=7.8,4.7Hz,1H),5.19(dd,J=12.9,5.4Hz,1H),4.7 5–4.71(m,2H),3.84(d,J=12.9Hz,2H),3.44–3.33(m,4H),3.31–3.13(m,2H),2.95–2 .86(m,1H),2.62(d,J=17.7Hz,1H),2.58–2.53(m,1H),2.15–2.00(m,1H).LCMS(ESI)C 23 H 23 ClN5O4 + [M+H] + :Calculated value 468.14, measured value 468.1.

[0628] Example 251: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-07844)

[0629] Referring to the method of Synthesis Scheme 1, the target compound (GT-07844) (white solid, 40 mg, yield 56%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ12.39 (s, 1H), 11.16 (s, 1H), 8.86 (dd, J = 3.9, 1.7Hz, 1H), 8.3 0(s,1H),8.18(dd,J=7.7,1.2Hz,1H),8.04(d,J=7.7Hz,1H),7.99–7.96(m,2H),5.19 (dd,J=12.8,5.4Hz,1H),4.61(s,2H),4.51–4.45(m,3H),3.53–3.08(m,5H),2.91–2. 88(m,1H),2.62(d,J=18.0Hz,1H),2.58–2.52(m,1H),2.14–2.00(m,1H).LCMS(ESI)C 22 H 23 N6O4 + [M+H] + :Calculated value 435.18, measured value 435.1.

[0630] Example 252: Preparation of 5-((4-(4-chloro-3-fluoropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-08135)

[0631] Referring to the method of Synthesis Scheme 1, the target compound (GT-08135) (white solid, 41 mg, yield 66%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.88(s,1H),11.22(s,1H),8.33(s,1H),8.25–8.18(m,1H ),8.13–8.05(m,2H),7.25(t,J=4.9Hz,1H),5.25(dd,J=12.9,5.3Hz,1H),4.64(s,2 H),4.15(d,J=13.4Hz,2H),3.51(dd,J=32.1,12.6Hz,4H),3.37–3.17(m,2H),3.08 –2.88(m,1H),2.74–2.65(m,1H),2.64–2.58(m,1H),2.20–2.05(m,1H).LCMS(ESI)C 23 H 22 ClFN5O4 + [M+H] + :Calculated value 486.13, measured value 486.1.

[0632] Example 253: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoro-3,4-dihydroquinolin-1(2H)-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06234)

[0633] Referring to the method of Synthesis Scheme 1, the target compound (GT-06234) (white solid, 48 mg, yield 60%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.16(s,1H),8.27(s,1H),8.16(d,J=7.8Hz,1H),8.04(d,J=7.7 Hz,1H),6.86–6.67(m,3H),5.20(dd,J=12.8,5.3Hz,1H),4.50(d,J=3.4Hz,2H),3.97–3.8 1(m,3H),3.46(d,J=11.3Hz,2H),3.18–3.03(m,3H),2.98–2.84(m,1H),2.71–2.61(m,2H) ,2.62–2.55(m,1H),2.29–2.21(m,2H),2.10–2.03(m,1H),1.83–1.77(m,4H).LCMS(ESI)C 28 H 30 FN4O4 + [M+H] + :Calculated value 505.22, measured value 505.3.

[0634] Example 254: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoro-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06235)

[0635] Referring to the method of Synthesis Scheme 1, the target compound (GT-06235) (white solid, 42 mg, yield 53%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.43(s,1H),11.16(s,1H),8.26(s,1H),8.15(d,J=7.6Hz,1H),8.04(d,J=7.6Hz ,1H),6.88–6.79(m,1H),6.62–6.57(m,2H),5.20(dd,J=12.9,5.3Hz,1H),4.50(d,J=3.9Hz,2H),3.91(t,J =11.5Hz,2H),3.48(d,J=11.1Hz,2H),3.21–3.13(m,2H),3.11–3.00(m,2H),2.99–2.82(m,1H),2.62(d,J= 17.9Hz,1H),2.58–2.53(m,1H),2.21–2.14(m,3H),2.09–2.05(m,1H),1.79(d,J=12.3Hz,2H).LCMS(ESI)C 27 H 28 FN4O5 + [M+H] + :Calculated value 507.20, measured value 507.2.

[0636] Example 255: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoro-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06236)

[0637] Referring to the method of Synthesis Scheme 1, the target compound (GT-06236) (white solid, 53 mg, yield 68%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.16(s,1H),10.83(s,1H),8.23(s,1H),8.08(dd,J=18.3,7.7Hz,2H),7.57–7.5 3(m,1H),6.99(dd,J=9.2,2.9Hz,1H),6.91(td,J=8.7,2.9Hz,1H),5.20(dd,J=12.9,5.3Hz,1H),4.52(d,J =8.2Hz,2H),4.46–4.40(m,1H),3.51(d,J=11.0Hz,2H),3.42–3.38(m,2H),3.20–3.11(m,2H),3.02–2.80 (m,3H),2.62(d,J=17.7Hz,1H),2.58–2.52(m,1H),2.15–2.01(m,1H),1.91(d,J=12.4Hz,2H).LCMS(ESI)C 27 H 26 FN4O6 + [M+H] + :Calculated value 521.18, measured value 521.2.

[0638] Example 256: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluorochroman-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06237)

[0639] Referring to the method of Synthesis Scheme 1, the target compound (GT-06237) (white solid, 39 mg, yield 49%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.15(s,1H),10.72(s,1H),8.21(s,1H),8.08(d,J=7.8Hz,1H),8.03(d,J=7.6Hz,1H),7 .17–7.08(m,1H),6.67(td,J=8.5,2.6Hz,1H),6.59(dd,J=10.5,2.6Hz,1H),5.19(dd,J=12.8,5.4Hz,1H),4.47(d ,J=4.4Hz,2H),4.29–4.05(m,2H),3.47–3.31(m,2H),3.00–2.79(m,3H),2.76–2.66(m,1H),2.61(d,J=18.3Hz,1H ),2.56(d,J=4.4Hz,1H),2.11–2.06(m,1H),1.99–1.93(m,1H),1.88–1.84(m,3H),1.76–1.52(m,3H).LCMS(ESI)C 28 H 29 FN3O5 + [M+H] + :Calculated value 506.21, measured value 506.2.

[0640] Example 257: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluorochroman-4-methylene)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06238)

[0641] Referring to the method of Synthesis Scheme 1, the target compound (GT-06238) (white solid, 40 mg, yield 50%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.15(s,1H),10.80(s,1H),8.19(s,1H),8.06(s,2H),7.25 –7.16(m,1H),6.73–6.65(m,2H),5.19(dd,J=12.7,5.3Hz,1H),4.54(d,J=4.8Hz,2H ),4.34–4.29(m,1H),4.24–4.19(m,1H),3.53–3.39(m,2H),3.11–2.85(m,4H),2.70 –2.64(m,2H),2.61–2.53(m,2H),2.49–2.37(m,3H),2.12–2.03(m,1H).LCMS(ESI)C 28 H 27 FN3O5 +[M+H] + :Calculated value 504.19, measured value 504.2.

[0642] Example 258: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoronaphthalen-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06263)

[0643] Referring to the method of Synthesis Scheme 1, the target compound (GT-06263) (white solid, 51 mg, yield 63%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.21(s,1H),11.16(s,1H),8.30(s,1H),8.18(d,J=7.7Hz,1H),8.07(t,J=8.0Hz,2H),7.98 (d,J=8.3Hz,1H),7.66–7.59(m,1H),7.59–7.52(m,1H),7.48(d,J=7.2Hz,1H),7.36(dd,J=10.7,7.7Hz,1H),5.21(dd ,J=12.9,5.3Hz,1H),4.59(d,J=4.1Hz,2H),3.67(t,J=11.8Hz,1H),3.56(d,J=11.4Hz,2H),3.27–3.21(m,2H),2.95– 2.87(m,1H),2.62(d,J=16.8Hz,1H),2.56(dd,J=13.4,4.4Hz,1H),2.27-2.18(m,2H),2.10–2.05(m,3H).LCMS(ESI)C 29 H 27 FN3O4 + [M+H] + :Calculated value 500.20, measured value 500.2.

[0644] Example 259: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoroquinolin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06265)

[0645] Referring to the method of Synthesis Scheme 1, the target compound (GT-06265) (white solid, 61 mg, yield 76%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.89(s,1H),11.17(s,1H),9.13(d,J=5.2Hz,1H),8.61(dd,J=9.5,5.8Hz,1H),8.34(s,1 H),8.23(d,J=7.8Hz,1H),8.07(d,J=7.9Hz,1H),8.06–8.00(m,1H),7.82–7.77(m,1H),7.64(d,J=5.3Hz,1H),5.2 1(dd,J=12.9,5.3Hz,1H),4.60(d,J=3.0Hz,2H),3.90(t,J=12.0Hz,1H),3.59(d,J=11.4Hz,2H),3.29–3.20(m,2H ),2.98–2.85(m,1H),2.66–2.61(m,1H),2.58–2.52(m,1H),2.42–2.33(m,2H),2.07(d,J=12.7Hz,3H).LCMS(ESI)C 28 H 26 FN4O4 + [M+H] + :Calculated value 501.19, measured value 501.2.

[0646] Example 260: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(isoquinolin-5-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione (GT-06266)

[0647] Referring to the method of Synthesis Scheme 1, the target compound (GT-06266) (white solid, 51 mg, yield 61%) was prepared under appropriate conditions understood in the art. 1H NMR(400MHz,DMSO-d6)δ11.96(s,1H),11.17(s,1H),9.89(s,1H),8.76–8.68(m,2H),8.47–8.41(m,1H ),8.36(s,1H),8.25(d,J=7.7Hz,1H),8.07(d,J=7.6Hz,1H),8.01(d,J=4.8Hz,2H),5.21(dd,J=12.9, 5.3Hz,1H),4.62(s,2H),3.79(t,J=11.8Hz,2H),3.58(d,J=11.1Hz,2H),3.33–3.20(m,3H),2.98–2.8 5(m,1H),2.63(d,J=17.2Hz,1H),2.60–2.54(m,1H),2.45–2.35(m,2H),2.11–2.04(m,3H).LCMS(ESI)C 28 H 27 N4O4 + [M+H] + :Calculated value 483.20, measured value 483.2.

[0648] Example 261: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoronaphthalen-1-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione (GT-06264)

[0649] Referring to the method of Synthesis Scheme 1, the target compound (GT-06264) (white solid, 55 mg, yield 68%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.53(s,1H),11.16(s,1H),8.35(s,1H),8.23(d,J=7 .5Hz,1H),8.08(d,J=7.6Hz,1H),8.03(d,J=8.4Hz,1H),7.99(d,J=8.6Hz,1H), 7.68–7.59(m,1H),7.53–7.48(m,1H),7.46(d,J=5.0Hz,1H),7.37(dd,J=10.8,7.7 Hz,1H),5.75(s,1H),5.21(dd,J=12.9,5.3Hz,1H),4.83–4.57(m,2H),3.99–3.76(m ,2H),3.76–3.62(m,1H),3.49–3.38(m,1H),3.12–2.95(m,1H),2.97–2.83(m,1H),2 .62(d,J=14.2Hz,2H),2.56(dd,J=13.3,4.4Hz,1H),2.19–2.00(m,1H).LCMS(ESI)C 29 H 25 FN3O4 + [M+H] + :Calculated value 498.18, measured value 498.2.

[0650] Example 262: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoroquinolin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione (GT-06267)

[0651] Referring to the method of Synthesis Scheme 1, the target compound (GT-06267) (white solid, 65 mg, yield 80%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ12.18(s,1H),11.16(s,1H),9.12(d,J=5.0Hz,1H),8.54(dd,J=9.4,6.0Hz,1H),8.39(s,1H),8.28(d,J= 7.7Hz,1H),8.07(d,J=7.7Hz,1H),8.01(dd,J=9.7,2.6Hz,1H),7.70(td,J=9.0,2.6Hz,1H),7.65(d,J=5.0Hz,1H),5.94(s,1H),5 .21(dd,J=12.9,5.3Hz,1H),4.73(q,J=14.3Hz,2H),3.92–3.73(m,3H),3.80–3.67(m,1H),3.51–3.32(m,1H),3.19–3.07(m,1H) ,2.95–2.87(m,1H),2.71(d,J=17.3Hz,1H),2.63(d,J=16.8Hz,1H),2.56(dd,J=13.5,4.5Hz,1H),2.12–2.07(m,1H).LCMS(ESI)C 28 H 24 FN4O4 + [M+H] + :Calculated value 499.18, measured value 499.2.

[0652] Example 263: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(isoquinolin-5-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione (GT-06268)

[0653] Referring to the method of Synthesis Scheme 1, the target compound (GT-06268) (white solid, 60 mg, yield 72%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ12.25(s,1H),11.17(s,1H),9.87(s,1H),8.67(dd,J=15.3,6.6Hz,2H),8.48(dd,J=7 .3,2.0Hz,1H),8.41(s,1H),8.29(dd,J=7.7,1.1Hz,1H),8.07(d,J=7.7Hz,1H),8.03–7.98(m,2H),5.83(s,1 H),5.21(dd,J=12.9,5.3Hz,1H),4.74(d,J=9.7Hz,2H),3.72(brs,2H),3.43(brs,2H),3.15-3.09(m,1H),2. 95–2.91(m,1H),2.72–2.68(m,1H),2.63(d,J=17.1Hz,1H),2.57–2.52(m,1H),2.16–2.03(m,1H).LCMS(ESI)C 28 H 25 N4O4 + [M+H] + :Calculated value 481.19, measured value 481.2.

[0654] Example 264: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((3-(7-fluorochroman-4-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione (GT-06269)

[0655] Referring to the method of Synthesis Scheme 1, the target compound (GT-06269) (white solid, 17 mg, yield 17%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.22(s,1H),11.15(s,1H),8.17(d,J=9.0Hz,1H),8.07–8.02(m,2H),7 .10–7.01(m,1H),6.88–6.61(m,2H),5.18(dd,J=12.8,5.3Hz,1H),4.62–4.58(m,2H),4.45–4.37 (m,1H),4.23–4.10(m,2H),4.10–3.98(m,2H),3.25–3.17(m,2H),2.99–2.81(m,2H),2.67–2.58 (m,1H),2.59–2.53(m,1H),2.15–2.02(m,1H),2.01–1.87(m,1H),1.74–1.65(m,1H).LCMS(ESI)C 26 H25 FN3O5 + [M+H] + :Calculated value 478.18, measured value 478.2.

[0656] Example 265: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((3-(7-fluorochroman-4-methylene)azetidin-1-yl)methyl)isoindoline-1,3-dione (GT-08134)

[0657] Referring to the method of Synthesis Scheme 1, the target compound (GT-08134) (white solid, 25 mg, yield 33%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.44(s,1H),11.09(s,1H),8.15(s,1H),8.05(d,J=7.7Hz,1H), 7.98(d,J=7.7Hz,1H),6.99–6.94(m,1H),6.73–6.68(m,2H),5.12(dd,J=12.9,5.3Hz,1H ),5.04(brs,2H),4.94–4.75(m,2H),4.66(s,2H),4.22–4.08(m,2H),3.35–3.32(m,2H), 2.88–2.73(m,1H),2.61–2.52(m,1H),2.52–2.46(m,1H),2.08–1.96(m,1H).LCMS(ESI)C 26 H 23 FN3O5 + [M+H] + :Calculated value 476.16, measured value 476.1.

[0658] Example 266: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((3-(7-fluoroquinolin-4-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione (GT-06270)

[0659] Referring to the method of Synthesis Scheme 1, the target compound (GT-06270) (white solid, 54 mg, yield 63%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.16(s,1H),9.13(d,J=4.7Hz,1H),8.21(d,J=7.2Hz,1H),8.13–8.08(m,1H),8.03( d,J=7.5Hz,1H),8.01–7.95(m,1H),7.93–7.83(m,1H),7.74(d,J=5.0Hz,1H),7.65(t,J=7.6Hz,1H),5.18(dd ,J=10.6,5.3Hz,1H),4.96–4.84(m,1H),4.82–4.75(m,1H),4.64(s,2H),4.54–4.47(m,1H),4.40–4.35(m,1H ),3.62–3.41(m,1H),2.95–2.88(m,1H),2.68–2.59(m,1H),2.53–2.48(m,1H),2.10–2.04(m,1H).LCMS(ESI)C 26 H 22 FN4O4 + [M+H] + :Calculated value 473.16, measured value 473.1.

[0660] Example 267: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((3-(5-fluoroindoline-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione (GT-06271)

[0661] Referring to the method of Synthesis Scheme 1, the target compound (GT-06271) (white solid, 38 mg, yield 37%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.15(s,1H),8.21(d,J=6.5Hz,1H),8.11(d,J=7.7Hz,1H),8.03(dd,J= 8.0,3.0Hz,1H),6.97(d,J=8.5Hz,1H),6.84–6.78(m,1H),6.47–6.36(m,1H),5.18(dd,J=12.8, 5.4Hz,1H),4.71(d,J=6.0Hz,1H),4.62(d,J=4.6Hz,2H),4.40–4.20(m,4H),3.48(t,J=8.2Hz,2 H),3.00–2.83(m,3H),2.61(d,J=17.7Hz,1H),2.58–2.52(m,1H),2.15–2.00(m,1H).LCMS(ESI)C 25 H 24FN4O4 + [M+H] + :Calculated value 463.18, measured value 463.2.

[0662] Example 268: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((3-(5-fluoro-1H-benzo[d]imidazol-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione (GT-06272)

[0663] Referring to the method of Synthesis Scheme 1, the target compound (GT-06272) (white solid, 26 mg, yield 25%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.14(s,1H),8.71(s,1H),8.14(s,1H),8.00(d,J=6.8Hz,2H), 7.86(dd,J=9.0,4.6Hz,1H),7.55(dd,J=9.4,2.5Hz,1H),7.23(td,J=9.3,2.4Hz,1H),5. 53–5.42(m,1H),5.17(dd,J=12.8,5.4Hz,1H),4.47–4.37(m,2H),4.30–4.18(m,2H),3. 89–3.74(m,2H),2.94–2.87(m,2H),2.61(d,J=17.8Hz,1H),2.54(d,J=14.5Hz,1H),2.14 –1.99(m,1H).LCMS(ESI)C 24 H 21 FN5O4 + [M+H] + :Calculated value 462.16, measured value 462.1.

[0664] Example 269: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06303)

[0665] Referring to the method of Synthesis Scheme 1, the target compound (GT-06303) (white solid, 39 mg, yield 62%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ12.10(s,1H),11.16(s,1H),8.56(s,1H),8.27(s,1H),8.15(d,J=7.8H z,1H),8.05(d,J=7.6Hz,1H),7.77(d,J=6.1Hz,1H),7.70(d,J=6.2Hz,1H),5.19(dd,J=12.9,5. 4Hz,1H),4.70(d,J=10.4Hz,2H),4.60(s,2H),3.84–3.63(m,2H),3.45(brs,2H),3.26(brs,2H ),2.99–2.81(m,1H),2.62(d,J=17.7Hz,1H),2.58–2.53(m,1H),2.15–1.98(m,1H).LCMS(ESI)C 24 H 23 N6O4S + [M+H] + :Calculated value 491.15, measured value 491.2.

[0666] Example 270: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06304)

[0667] Referring to the method of Synthesis Scheme 1, the target compound (GT-06304) (white solid, 48 mg, yield 60%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.49(s,1H),11.15(s,1H),8.63(s,1H),8.27(s,1H),8.14(d,J=7. 7Hz,1H),8.06(d,J=7.5Hz,1H),7.48(s,1H),5.18(dd,J=12.2,6.1Hz,1H),4.62(s,1H),3.92 (d,J=13.5Hz,1H),3.83–3.72(m,4H),3.52(d,J=13.2Hz,1H),3.42(d,J=9.7Hz,1H),3.39–3. 22(m,2H),2.99–2.83(m,1H),2.69–2.59(m,2H),2.55(s,3H),2.10–2.07(m,1H).LCMS(ESI)C 25 H 25 N6O4S + [M+H] +:Calculated value 505.17, measured value 505.2.

[0668] Example 271: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06305)

[0669] Referring to the method of Synthesis Scheme 1, the target compound (GT-06305) (white solid, 63 mg, yield 79%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ12.18(s,1H),11.16(s,1H),8.52(s,1H),8.28(s,1H),8.17( dd,J=7.7,1.1Hz,1H),8.05(d,J=7.6Hz,1H),7.43(d,J=1.1Hz,1H),5.20(dd,J=12.9, 5.4Hz,1H),4.65(s,1H),4.61(s,3H),3.71(brs,2H),3.45(brs,2H),3.24(brs,2H),2 .95–2.87(m,1H),2.62(d,J=17.7Hz,1H),2.57(s,3H),2.14–2.00(m,1H).LCMS(ESI)C 25 H 25 N6O4S + [M+H] + :Calculated value 505.17, measured value 505.2.

[0670] Example 272: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-isopropylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06306)

[0671] Referring to the method of Synthesis Scheme 1, the target compound (GT-06306) (white solid, 56 mg, yield 73%) was prepared under appropriate conditions understood in the art. 1H NMR(400MHz,DMSO-d6)δ11.94(s,1H),11.16(s,1H),8.49(s,1H),8.27(s,1H),8.16(d ,J=7.8Hz,1H),8.05(d,J=7.6Hz,1H),7.36(s,1H),5.20(dd,J=12.9,5.3Hz,1H),4.61 (s,4H),3.67(brs,2H),3.44(brs,2H),3.31–3.24(m,3H),3.01–2.82(m,1H),2.62(d, J=17.5Hz,1H),2.58–2.53(m,1H),2.17–1.96(m,1H),1.34(d,J=6.8Hz,6H).LCMS(ESI) C 27 H 29 N6O4S + [M+H] + :Calculated value 533.20, measured value 533.2.

[0672] Example 273: Preparation of 5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-06307)

[0673] Referring to the method of Synthesis Scheme 1, the target compound (GT-06307) (white solid, 62 mg, yield 80%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.72(s,1H),11.15(s,1H),8.57(s,1H),8.28(s,1H),8.20–8.11(m, 1H),8.05(d,J=7.7Hz,1H),5.19(dd,J=12.8,5.4Hz,1H),4.61(s,2H),3.88(d,J=13.7Hz,2H) ,3.50(t,J=12.1Hz,2H),3.41(d,J=10.4Hz,2H),3.34–3.29(m,2H),2.98–2.81(m,1H),2.62( d,J=17.7Hz,1H),2.57–2.53(m,1H),2.46(s,3H),2.42(s,3H),2.13–2.01(m,1H).LCMS(ESI)C 26 H 27 N6O4S + [M+H] + :Calculated value 519.18, measured value 519.2.

[0674] Example 274: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06310)

[0675] Referring to the method of Synthesis Scheme 1, the target compound (GT-06310) (white solid, 58 mg, yield 80%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.60(s,1H),11.16(s,1H),8.52(s,1H),8.26(s,1H),8.14(d,J=7.5Hz,1H),8.0 7(d,J=7.6Hz,1H),8.01(s,1H),7.91–7.82(m,2H),7.51(t,J=7.5Hz,2H),7.43(t,J=7.3Hz,1H),5.20(dd ,J=12.9,5.4Hz,1H),4.73(d,J=13.7Hz,2H),4.62(s,2H),3.68(t,J=10.4Hz,2H),3.57–3.54(m,2H),3.2 8(brs,2H),3.01–2.82(m,1H),2.62(d,J=17.3Hz,1H),2.59–2.54(m,1H),2.16–1.94(m,1H).LCMS(ESI)C 30 H 27 N6O4S + [M+H] + :Calculated value 567.18, measured value 567.2.

[0676] Example 275: Preparation of 5-((4-(6-bromothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-06309)

[0677] Referring to the method of Synthesis Scheme 1, the target compound (GT-06309) (white solid, 64 mg, yield 89%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.84(s,1H),11.16(s,1H),8.49(s,1H),8.26(s,1H),8. 14(d,J=7.8Hz,1H),8.06(d,J=7.6Hz,1H),7.94(s,1H),5.20(dd,J=12.9,5.4Hz, 1H),4.60(s,4H),3.70–3.56(m,2H),3.53–3.36(m,2H),3.23(s,2H),2.99–2.81( m,1H),2.62(d,J=17.6Hz,1H),2.59–2.53(m,1H),2.17–1.97(m,1H).LCMS(ESI)C 24 H 22 BrN6O4S + [M+H] + :Calculated value 569.06, measured value 569.1.

[0678] Example 276: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06345)

[0679] Referring to the method of Synthesis Scheme 1, the target compound (GT-06345) (white solid, 59 mg, yield 82%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.75(s,1H),11.16(s,1H),8.68(s,1H),8.13(s,1H),8.06–7.98(m,2H),7.78(s,1H),7.49–7.43(m,2H) ,7.41(dd,J=7.5,2.9Hz,3H),5.20(dd,J=12.9,5.3Hz,1H),4.39(s,2H),3.86–3.72(m,4H),3.23–3.07(m,4H),2.98–2.84(m,1H), 2.62(d,J=17.2Hz,1H),2.55(dd,J=13.2,4.3Hz,1H),2.11–2.07(m,1H).LCMS(ESI)C 30 H 27 N6O4S + [M+H] + :Calculated value 567.18, measured value 567.2.

[0680] Example 277: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06564)

[0681] Referring to the method of Synthesis Scheme 1, the target compound (GT-06564) (white solid, 52 mg, yield 79%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.56(s,1H),11.16(s,1H),8.57(s,1H),8.28(s,1H),8.16( d,J=7.7Hz,1H),8.06(d,J=7.6Hz,1H),5.19(dd,J=12.9,5.3Hz,1H),4.62(s,2H),3.8 7(d,J=12.8Hz,2H),3.45–3.34(m,7H),2.92–2.87(m,4H),2.62(d,J=17.8Hz,1H),2. 58–2.52(m,1H),2.13–2.01(m,1H),1.90–1.85(m,2H),1.84–1.68(m,2H).LCMS(ESI)C 28 H 29 N6O4S + [M+H] + :Calculated value 545.20, measured value 545.2.

[0682] Example 278: Preparation of 5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (GT-06565)

[0683] Referring to the method of Synthesis Scheme 1, the target compound (GT-06565) (white solid, 48 mg, yield 74%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ12.05(s,1H),11.16(s,1H),8.52(s,1H),8.30(s,1H),8.18(dd,J=7.7,1. 0Hz,1H),8.04(d,J=7.6Hz,1H),5.19(dd,J=12.9,5.3Hz,1H),4.60(s,2H),4.15(d,J=13.2Hz,2H) ,3.61(t,J=11.9Hz,2H),3.43(d,J=10.4Hz,2H),3.29(brs,2H),3.14–2.97(m,4H),2.91–2.87(m, 1H),2.62(d,J=17.5Hz,1H),2.58–2.53(m,1H),2.47–2.33(m,2H),2.11–2.07(m,1H).LCMS(ESI)C 27 H 27 N6O4S + [M+H] + :Calculated value 531.18, measured value 531.2.

[0684] Example 279: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06346)

[0685] Referring to the method of Synthesis Scheme 1, the target compound (GT-06346) (white solid, 36 mg, yield 51%) was prepared under appropriate conditions understood in the art. 1 H NMR(400MHz,DMSO-d6)δ11.93(s,1H),11.16(s,1H),8.13(s,1H),8.07–7.98(m,2H), 7.68(s,1H),7.45–7.43(m,2H),7.41–7.36(m,3H),5.20(dd,J=12.9,5.3Hz,1H),4.38 (s,2H),3.79(d,J=12.2Hz,2H),3.26–3.03(m,4H),2.99–2.83(m,1H),2.63(s,3H),2. 60–2.58(m,1H),2.55–2.52(m,1H),2.50–2.43(m,2H),2.15–2.00(m,1H).LCMS(ESI)C 31 H 29 N6O4S + [M+H] +:Calculated value 581.20, measured value 581.2.

[0686] Example 280: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06348)

[0687] Referring to the method of Synthesis Scheme 1, the target compound (GT-06348) (white solid, 49 mg, yield 72%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ11.80(s,1H),11.16(s,1H),8.30(s,1H),8.18(d,J=8.0 Hz,1H),8.05(d,J=7.7Hz,1H),5.19(dd,J=12.9,5.3Hz,1H),4.61(s,2H),3.87– 3.83(m,4H),3.50–3.40(m,4H),3.32–3.25(m,2H),2.95–2.87(m,4H),2.62(d,J=17.3Hz ,1H),2.55(s,3H),2.09–2.05(m,1H),1.92–1.86(m,2H),1.77–1.65(m,2H).LCMS(ESI)C 29 H 31 N6O4S + [M+H] + :Calculated value 559.21, measured value 559.3.

[0688] Example 281: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06566)

[0689] Referring to the method of Synthesis Scheme 1, the target compound (GT-06566) (white solid, 46 mg, yield 69%) was prepared under appropriate conditions understood in the art. 1H NMR (400MHz, DMSO-d6) δ11.94(s,1H),11.16(s,1H),8.29(s,1H),8.17(d,J=7.7Hz,1H),8.05(d ,J=7.6Hz,1H),5.19(dd,J=12.9,5.3Hz,1H),4.60(s,2H),4.16(d,J=12.7Hz,2H),3.59(t,J=12. 5Hz,2H),3.44(d,J=11.0Hz,2H),3.27(brs,2H),3.12–2.94(m,4H),2.91–2.85(m,1H),2.66–2. 61(m,1H),2.58(d,J=9.8Hz,1H),2.54(s,3H),2.42–2.33(m,2H),2.11–1.99(m,1H).LCMS(ESI)C 28 H 29 N6O4S + [M+H] + :Calculated value 545.20, measured value 545.2.

[0690] Example 282: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione (GT-06347)

[0691] Referring to the method of Synthesis Scheme 1, the target compound (GT-06347) (white solid, 68 mg, yield 85%) was prepared under appropriate conditions understood in the art. 1 H NMR (400MHz, DMSO-d6) δ12.29(s,1H),11.16(s,1H),8.28(s,1H),8.17(d,J=7.8Hz, 1H),8.05(d,J=7.6Hz,1H),7.71(s,2H),5.20(dd,J=12.9,5.3Hz,1H),4.77(br...

Claims

1. A compound represented by formula (I) or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph: in, represents a single or double bond; X represents CH2 or C(=O); (Y) m represents that the benzene ring is optionally substituted by m Y groups, Y represents deuterium, C1-C4 alkyl, halogen or halogenated C1-C2 alkyl, and m represents an integer of 0, 1, 2 or 3; L represents a methylene group, or a linear or branched C2-C6 alkylene group, wherein the methylene group or the linear or branched C2-C6 alkylene group may be optionally substituted by one or more of the following groups: deuterium, halogen, C 1- C3 alkyl, C1-C3 alkoxy or C1-C3 haloalkyl; R 1 Indicates a bond, O, N(R a )、N(R a )S(O)2、S(O)2N(R a ), a nitrogen-containing heterocyclic group or a nitrogen-containing heterocyclic group subunit, R a represents hydrogen, deuterium or C1-C6 alkyl, the nitrogen-containing heterocyclylene or nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; R 2 represents heteroarylene, heteroarylene, heterocyclylene, (CH2) n -Arylene or (CH2) n -cycloalkylene, wherein n represents an integer of 0, 1 or 2, and the heteroarylene group, the heteroarylene group, the heterocyclylene group, the arylene group or the cycloalkylene group may be optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; R 3 Indicates hydrogen, deuterium, SR b , R b , C1-C6 haloalkyl, cycloalkyl or nitrogen-containing heterocyclic group, R b represents an aryl group, wherein the aryl group, the cycloalkyl group or the nitrogen-containing heterocyclic group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; Among them, when When it represents a double bond, R 1 Represents a nitrogen-containing heterocyclic subunit, R 2 represents a heteroaryl subunit; when When it represents a single bond, R 1 Indicates a bond, O, N(R a )、N(R a )S(O)2、S(O)2N(R a ) or a nitrogen-containing heterocyclic group, R 2 represents heteroarylene, heterocyclylene, (CH2) n -Arylene or (CH2) n -cycloalkylene.

2. The compound of formula (I) according to claim 1 or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein: The structure of formula (I) is also the structure of the following formula: in, X, Y, L, m, R 1 , R 2 and R 3 As defined in claim 1.

3. The compound of formula (I) according to claim 1 or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein: The structure of formula (I) is also the structure of the following formula: in, X, Y, L, m, R 2 and R 3 As defined in claim 1; R c represents hydrogen, deuterium or C1-C6 alkyl; Ring A represents a nitrogen-containing heterocyclylene group or a nitrogen-containing heterocyclyl subunit, and the nitrogen-containing heterocyclylene group or the nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

4. The compound of formula (I) according to claim 1 or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph, wherein: The structure of formula (I) is also the structure of the following formula: in, Y, L, m, R 2 and R 3 As defined in claim 1; R c represents hydrogen, deuterium or C1-C6 alkyl; Ring A represents a nitrogen-containing heterocyclylene group or a nitrogen-containing heterocyclyl subunit, and the nitrogen-containing heterocyclylene group or the nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

5. A compound of formula (I) according to any one of claims 1 to 4, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: Y represents D, F, Cl, Br, I, CF3, CH2F, CHF2, CH2Cl, CHCl2, CF2CF3, CHFCF3, CF2CHF2, CHFCHF2, CH2CF3 or CH2CH2Cl.

6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: The nitrogen-containing heterocyclic radical includes: a 4- to 30-membered nitrogen-containing heterocyclic radical, a 4- to 20-membered nitrogen-containing heterocyclic radical, a 4- to 15-membered nitrogen-containing heterocyclic radical, a 5- to 30-membered nitrogen-containing heterocyclic radical, a 5- to 20-membered nitrogen-containing heterocyclic radical or a 5- to 15-membered nitrogen-containing heterocyclic radical, and the nitrogen-containing heterocyclic radical is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

7. A compound of formula (I) according to any one of claims 1 to 6, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: The nitrogen-containing heterocyclyl subunit includes: a 4- to 30-membered nitrogen-containing heterocyclyl subunit, a 4- to 20-membered nitrogen-containing heterocyclyl subunit, a 4- to 15-membered nitrogen-containing heterocyclyl subunit, a 5- to 30-membered nitrogen-containing heterocyclyl subunit, a 5- to 20-membered nitrogen-containing heterocyclyl subunit or a 5- to 15-membered nitrogen-containing heterocyclyl subunit, and the nitrogen-containing heterocyclyl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

8. A compound of formula (I) according to any one of claims 1 to 7, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: The structure of the nitrogen-containing heterocyclic group includes: The symbol * indicates the connection point with L.

9. A compound of formula (I) according to any one of claims 1 to 8, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: R 2 represents a heteroaryl subunit, an arylene group, a heteroarylene group, a heterocyclyl group, a cycloalkylene group, a -CH2-arylene group, a -CH2-cycloalkylene group, a -(CH2)2-arylene group or a -(CH2)2-cycloalkylene group, wherein the heteroaryl subunit, the arylene group, the heteroarylene group, the heterocyclyl group or the cycloalkylene group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

10. A compound of formula (I) according to any one of claims 1 to 8, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: R 2 represents a 7- to 30-membered heteroarylene group, an arylene group, a 5- to 30-membered heteroarylene group, a 4- to 30-membered heterocyclylene group, a cycloalkylene group, a -CH2-arylene group, a -CH2-cycloalkylene group, a -(CH2)2-arylene group or a -(CH2)2-cycloalkylene group, wherein the arylene group includes C 5-30 Arylene, the cycloalkylene includes C 3-30 The heteroaryl group, the arylene group, the heteroarylene group, the heterocyclyl group or the cycloalkylene group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

11. A compound of formula (I) according to any one of claims 1 to 10, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: The heteroaryl subunit is a chromanyl subunit or a 2,3-dihydroquinolin-4(1H)-yl subunit, and the heteroaryl subunit is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; The arylene group is selected from the following groups: phenylene or naphthylene, and the arylene group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; The heteroarylene group is selected from the following groups: furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, quinazolinyl, triazine, isoxazolo[4,5-c]pyridinyl, pyrrolo[2,3-b]pyridinyl, indolyl, benzothiazolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, benzimidazolyl, 2,3-dihydro-1H-benzo[d]imidazolyl, pyrrolo[2,3-b]pyridinyl, 3,4-dihydroquinolinyl, 2,3-dihydro-4H-benzo benzo[b][1,4]oxazine, benzodihydropyranyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, dihydrothieno[3,2-d]pyrimidinyl, 5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazinediyl, dihydrothieno[3,2-c]pyridinyl, benzoxazolylene, benzoisoxazolylene, benzoisothiazolylene, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-c]pyridinyl, pyrazolo[1,5-d ... 5-a] pyrimidinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-b]thiazolyl or benzo[2,1-b]thiazolyl, wherein the heteroaryl group is optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; The heterocyclylene group is selected from the following groups: azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl or diazepanyl, and the heterocyclylene group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; The cycloalkylene group is selected from the following groups: cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decahydronaphthylene, octahydropentalenylene, octahydro-1H-indenylene, C5-C 15 A spirocycloalkylene, adamantylene, noradamantylene, bornylene, bicyclo[2,2,1]heptanylene or bicyclo[2,2,1]heptenylene, wherein the cycloalkylene is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

12. A compound of formula (I) according to any one of claims 1 to 11, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, wherein: The aryl group is selected from the following groups: phenyl or naphthyl, and the aryl group is optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, thiol, =O, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; The cycloalkyl group is selected from the following groups: cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decahydronaphthyl, octahydropentalenyl, octahydro-1H-indenyl, C5-C 15 Spirocyclyl, adamantyl, noradamantyl, bornyl, bicyclo[2,2,1]heptyl or bicyclo[2,2,1]heptenyl, the cycloalkyl being optionally substituted with one or more of the following groups: deuterium, hydroxyl, amino, thiol, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; The nitrogen-containing heterocyclic group is selected from the following groups: azetidinyl, pyrrolidinyl, imidazolidinyl, diazepanyl, morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl or azetidinyl, and the nitrogen-containing heterocyclic group is optionally replaced by one or more of the following groups: Substituted: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

13. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph according to claim 1, characterized in that: When R 1 When it is O, NH, NHS(O)2 or S(O)2NH, R 2 Represents -(CH2) n -cycloalkylene, R 3 represents hydrogen, and the cycloalkylene group may be optionally substituted by one or more of the following groups: deuterium, hydroxyl, amino, mercapto, =0, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy.

14. The compound of formula (I) or its salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph according to claim 1, characterized in that: when When it represents a double bond, R 1 is a piperidinyl subunit or an azetidinyl subunit, R 2 is a chromanyl subunit, R 3 For hydrogen.

15. A compound of formula (I) according to any one of claims 1 to 12, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug or polymorph thereof, selected from: 3-(1-oxo-5-((4-(thiophen-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthiophen-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-methylthiophen-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thiophen-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-methylthiophen-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthiophen-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-methylthiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(Furan-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(Furan-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thiophen-2-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthiophen-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-methylthiophen-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thiophen-3-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthiophen-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-methylthiophen-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(Furan-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(Furan-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-phenylpiperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-fluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-fluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-bromophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(o-tolyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(m-tolyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(p-tolyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,4-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,5-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,6-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,4-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,5-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,5-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,6-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,4-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,5-difluorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,4-dimethylphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-chloro-2-methylphenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-phenylpiperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-bromophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-bromophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chlorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-chlorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-fluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-fluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichlorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chloro-3-fluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-difluorophenyl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chloro-3-fluorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-methylpyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(3-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(6-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,4-dichloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,5-dichloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4,5-dichloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,4-difluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-chloro-3-fluoropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-fluoro-4-iodopyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-bromo-4-chloropyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-chloro-6-methylpyridin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(pyridin-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-chloropyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4,5-dichloropyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,4-dichloropyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(pyridin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methylpyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-bromopyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chloro-3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-bromo-3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-bromo-2-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-difluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-fluoro-2-hydroxypyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-bromo-5-chloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-chloro-5-fluoropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,5-dichloropyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,6-dimethylpyridin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(perfluoropyridin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-chloropyridazin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(pyrazin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5,6-dichloropyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,6-dichloropyridazin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1,3,5-triazine-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3,4-dichloropyridin-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichloropyridin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-difluoropyridin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-([3,4'-bipiperidinyl]-1-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,4-dichloro-3',6'-dihydro-[2,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4,5-dichloro-3',6'-dihydro-[3,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-chloro-3',6'-dihydro-[3,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2',3'-dichloro-3,6-dihydro-[4,4'-bipyridyl]-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-fluoro-3',6'-dihydro-[2,4'-bipyridyl]-1'(2'H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((2',3'-difluoro-3,6-dihydro-[4,4'-bipyridyl]-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(2,3-dichlorophenyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-(2,3-dichlorophenyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1S,4S)-5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(2,3-dichlorophenyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(2,3-dichlorophenyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(Benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(isoxazolo[4,5-c]pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluorobenzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluoro-1H-indazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluoro-1H-indol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluoro-1-methyl-1H-indol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-fluoroindolin-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-fluoro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluoro-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluoro-1-methyl-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-fluoro-3,4-dihydroquinolin-1(2H)-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(7-fluoro-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(7-fluoro-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(7-fluorochroman-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(7-fluorochroman-4-ylidene)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-fluoronaphthalen-1-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(7-fluoroquinolin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(isoquinolin-5-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-fluoronaphthalen-1-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(isoquinolin-5-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(7-fluorochroman-4-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(7-fluorochroman-4-ylidene)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidin-2,6-diol ketone; 3-(5-((3-(7-fluoroquinolin-4-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(5-fluoroindolin-1-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(5-fluoro-1H-benzo[d]imidazol-1-yl)azetidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-isopropylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-bromothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindoline-2- 1-(2-(4-piperidin-2,6-dione); 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-2-yl)piperidin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-ethylpyrimidin-2-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6-isopropylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thieno[2,3-d]pyrimidin-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-morpholino-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(4-(piperazin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-morpholino-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(2-(piperidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(2-(pyrrolidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-(azetidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(thieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-morpholinothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(4-(piperazin-1-yl)thieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-((2,4-dimethylphenyl)thio)phenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-((3r,5r,7r)-adamantan-1-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((((3s,5s,7s)-adamantan-1-yl)amino)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (1-((1R,4R)-7,7-dimethyl-2-oxobicyclo[ 2.2.1]heptane-1-yl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)methylsulfonamide; 3-(5-((((1R,4S)-bicyclo[2.2.1]heptan-2-yl)oxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thiophen-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthiophen-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-methylthiophen-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thiophen-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-methylthiophen-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthiophen-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-methylthiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthiophen-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(furan-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(furan-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thiophen-2-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthiophen-2-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-methylthien-2-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thiophen-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthien-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-methylthiophen-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(furan-2-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(furan-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-phenylpiperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methoxyphenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-methoxyphenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-fluorophenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-fluorophenyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(2-chlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2-bromophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3-bromophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-bromophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(o-tolyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(m-tolyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(p-tolyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(2,4-dichlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,5-dichlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,6-dichlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,4-dichlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,5-dichlorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-difluorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,5-difluorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,6-difluorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,4-difluorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,5-difluorophenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,4-dimethylphenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(5-chloro-2-methylphenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-phenylpiperidin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(3-bromophenyl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-bromophenyl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2-chlorophenyl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-chlorophenyl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-fluorophenyl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-fluorophenyl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(2,3-dichlorophenyl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2-chloro-3-fluorophenyl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-difluorophenyl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-dichlorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2-chloro-3-fluorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-methylpyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(6-chloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(5-chloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-chloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3-chloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-fluoropyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoropyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoropyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(3,4-dichloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,5-dichloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4,5-dichloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,4-difluoropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-chloro-3-fluoropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-fluoro-4-iodopyridin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(3-bromo-4-chloropyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-chloro-6-methylpyridin-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyridin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(6-chloropyridin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4,5-dichloropyridin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,4-dichloropyridin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyridin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methylpyridin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(3-bromopyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-fluoropyridin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(3-chloropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2-chloropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2-chloro-3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2-bromo-3-fluoropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3-bromo-2-chloropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-dichloropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-difluoropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(3-fluoro-2-hydroxypyridin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(3-bromo-5-chloropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3-chloro-5-fluoropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,5-dichloropyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,6-dimethylpyridin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(perfluoropyridin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyridazin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(6-chloropyridazin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(pyrazin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(5,6-dichloropyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,6-dichloropyridazin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(1,3,5-triazine-2-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(3,4-dichloropyridin-2-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-dichloropyridin-4-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-difluoropyridin-4-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-([3,4'-bipiperidinyl]-1-ylmethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3,4-dichloro-3',6'-dihydro-[2,4'-bipyridyl]-1'(2'H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4,5-dichloro-3',6'-dihydro-[3,4'-bipyridyl]-1'(2'H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((5-chloro-3',6'-dihydro-[3,4'-bipyridyl]-1'(2'H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((2',3'-dichloro-3,6-dihydro-[4,4'-bipyridyl]-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-fluoro-3',6'-dihydro-[2,4'-bipyridyl]-1'(2'H)-yl)methyl)isoindoline-1,3-dione; 5-((2',3'-difluoro-3,6-dihydro-[4,4'-bipyridyl]-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3-(2,3-dichlorophenyl)-3,6-diazabicyclo[3.1.1]heptane-6-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((6-(2,3-dichlorophenyl)-3,6-diazabicyclo[3.1.1]heptane-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((1R,4R)-5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((1S,4S)-5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((5-(2,3-dichlorophenyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((8-(2,3-dichlorophenyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3-(2,3-dichlorophenyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(Benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(isoxazol-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(isoxazolo[4,5-c]pyridin-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluorobenzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoro-1H-indazol-3-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoro-1H-indol-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoro-1-methyl-1H-indol-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoroindolin-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methyl) Isoindoline-1,3-dione; 5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoro-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoro-1-methyl-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-fluoro-3,4-dihydroquinolin-1(2H)-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoro-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoro-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluorochroman-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluorochroman-4-methylene)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoronaphthalen-1-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoroquinolin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(isoquinolin-5-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-fluoronaphthalen-1-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(isoquinolin-5-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(7-fluorochroman-4-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(7-fluorochroman-4-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(7-fluoroquinolin-4-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(5-fluoroindolin-1-yl)azetidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(5-fluoro-1H-benzo[d]imidazol-1-yl)azetidin-1-yl)methyl)isoindoline-1,3- diketone; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-isopropylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(6-bromothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[2,3-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)-1,4-diazepan-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[2,3-d]pyrimidin-2-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-ethylpyrimidin-2-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-isopropylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 5-((4-(5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(6-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 5-((4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-methylthieno[2,3-d]pyrimidin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[2,3-d]pyrimidin-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 5-((4-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-morpholino-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-(piperazin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-morpholino-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-(piperidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-(pyrrolidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(2-(azetidin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(thieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(2-morpholinothieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-(piperazin-1-yl)thieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)isoindoline-1,3-dione; 5-((4-(2-((2,4-dimethylphenyl)thio)phenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((((3s,5s,7s)-adamantan-1-yl)amino)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 1-((1R,4R)-7,7-dimethyl-2-oxobicyclo[ 2.2.1]heptane-1-yl)-N-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)methylxanthamide; 5-((((1R,4S)-bicyclo[2.2.1]heptane-2-yl)oxy)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(4-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(3-methylthiophen-2-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 3-(4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)isoindoline-1,3-dione; 3-(4-((4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(5,6-dichloropyridazin-4-yl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 2-(2,6-dioxopiperidin-3-yl)-5-((4-(7-fluoroquinolin-4-yl)-3,6-dihydropyridin-1(2H)-yl)methyl)isoindoline-1,3-dione; 5-((4-(5,6-dichloropyridazin-4-yl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

16. A compound or salt thereof, enantiomer, stereoisomer, solvate, isotope-enriched analog, prodrug or polymorph as described in any one of claims 1 to 15, which is a hydrohalide (including hydrochloride, hydrobromide), sulfate, citrate, maleate, sulfonate, methanesulfonate, ethanesulfonate, edisylate, formate, acetate, 2,2-dichloroacetate, trimethylacetate, propionate, valerate, citrate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, α-ketoglutarate, hippurate, D-glucuronate, D-gluconate, α-D-glucoheptonate, glycolate, mucate, L-ascorbate, lactate succinate, pyrophosphate, thiocyanate, dihydrogenphosphate, pyrophosphate, metaphosphate, oxalate, malonate, carbonate, malonate, benzoate, mandelate, succinate, trifluoroacetate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalene disulfonate, 3-hydroxy-2-naphthalene disulfonate, 1-hydroxy-2-naphthalene disulfonate, 2-naphthalenesulfonate, glycolate, or p-toluenesulfonate.

17. A pharmaceutical composition comprising as an active ingredient a compound represented by formula (I) according to any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

18. The pharmaceutical composition of claim 17, further comprising at least one additional therapeutic agent.

19. The pharmaceutical composition according to claim 18, further comprising at least one additional therapeutic agent, such as a therapeutic agent for treating a tumor or cancer.

20. A medicine box or a test kit comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 16 or a pharmaceutical composition according to claim 17.

21. Use of a compound of formula (I) according to any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition according to any one of claims 17 to 19 for preparing a medicament for treating a disease or condition selected from the following: tumor or cancer, 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 or diabetes.

22. A method for treating a disease or condition in a patient, comprising administering to the patient a therapeutically effective amount of a compound shown in formula (I) according to any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 17, wherein the disease or condition is selected from tumors or cancer, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, cardiovascular disease, Richter syndrome (RS), acute liver failure and diabetes.

23. The use according to claim 21 or the method according to claim 22, wherein the disease or condition is selected from the group consisting of: myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma; myelofibrosis; bone marrow disease; myelodysplastic syndrome (MDS); previously treated myelodysplastic syndrome; transplant-related cancer; neutropenia; leukemia, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myeloid leukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), B-cell chronic lymphocytic leukemia, anemia associated with leukemia, monocytic leukemia, myelomonocytic leukemia, T-lymphocytic leukemia, acute T-lymphocytic leukemia; lymphomas, including diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, immunoblastic T-cell lymphoma, CD2 0-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, marginal zone lymphoma (MZL), primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin's lymphoma, relapsed diffuse large B-cell lymphoma, relapsed mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, relapsed transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory Primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung cancer, small cell lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; astrocytoblastoma; ovarian cancer; bronchial cancer; prostate cancer; breast cancer, including triple-negative breast cancer, sporadic breast cancer, ductal carcinoma and Cowden's disease patients; 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; Cholangiocarcinoma; Bone cancer; cervical cancer; skin cancer; Richter syndrome (RS); sepsis syndrome; autoimmune diseases, including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjögren's syndrome, atopic dermatitis; keratoconjunctivitis sicca; inflammatory diseases, including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis; cerebral malaria; infectious diseases, including viral pneumonia, AIDS ), COVID-19 novel coronavirus infection, Gram-negative bacterial infection, Gram-positive bacterial infection, tuberculosis, etc.; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; aplastic anemia in children; 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.

24. The method of claim 22, wherein the compound shown in the formula (I) or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of any one of claims 17 to 19 is administered to the subject by at least one administration method selected from 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 space administration, intrathecal administration, and intravenous administration.

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