Compounds based on isoindoline-substituted glutarimide skeletons and their applications

Abstract

The present disclosure relates to a compound of formula (I) or its salts, enantiomers, stereoisomers, solvates, and polymorphs, and applications thereof. The present disclosure further relates to a pharmaceutical composition comprising a compound of formula (I) or its salts, enantiomers, stereoisomers, solvates, and polymorphs as an active ingredient, and applications thereof. A series of compounds designed and synthesized in this disclosure can effectively prevent and / or treat diseases or conditions associated with cereblon protein. [Formula 1] JPEG2025528804000628.jpg2551 formula (I)

Description

[Technical Field]

[0001] The present disclosure relates to compounds of formula (I) or salts, enantiomers, non-enantiomers, isotopically enriched analogues, solvates, pharmaceutical precursors or polymorphs thereof and applications thereof, particularly for use in the prevention and / or treatment of diseases or conditions associated with the cereblon protein (CRBN). [ka] Formula (I) [Background technology]

[0002] Phthalimide immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, have shown remarkable efficacy in the treatment of multiple myeloma and autoimmune diseases. However, it was not until 2010 that their direct binding protein, the E3 ubiquitin ligase cereblon (CRBN), was identified. It was subsequently demonstrated that this class of drug acts as a molecular glue, inducing the interaction between the transcription factors IKZF1 / 3 and CRBN, leading to ubiquitination and degradation. Molecular glue proteolytic drugs have the advantage of a natural mechanism over traditional small molecule inhibitors: whereas the latter act by occupying the functional domain of target proteins and inhibiting their function, proteolytic drugs directly degrade the entire target protein, sometimes resulting in greater efficacy than traditional small molecule inhibitors and enabling them to target "non-druggable" targets. Furthermore, proteolytic drugs do not require high binding strength and require only low catalytic doses for their activity, overcoming the clinical drug resistance problem of traditional small molecule inhibitors. Furthermore, molecular glue degrading drugs generally have small molecular weights and are easy to develop, making their development highly valued. Based on the mechanism of CRBN E3 ubiquitin ligase and molecular glue degradation, a series of compounds have been developed, including the commercially available pomalidomide and Bristol-Myers Squibb (BMS) CC-122, CC-220, CC-90009, CC-99282, and CC-92480, Novartis DKY709, and C4 Therapeutics CFT7455. The degradation substrates of these molecular glues extend from the initially discovered transcription factor IKZF1 / 3 to include casein kinase 1α (CK1α), zinc finger protein 91 (ZFP91), and translation factor GSPT1. Through the degradation of these protein substrates, molecular glues exert pharmacodynamic activities such as immunomodulation, anti-inflammatory, and anti-tumor effects.Currently, only a very limited number of molecular glue candidate compounds have been discovered, and theoretically, there are a wide variety of pathogenic proteins for which molecular glues can be developed as degradation substrates. Therefore, it is necessary to develop more molecular glues through rationalization and diversification design, degrade and remove more pathogenic proteins, and apply them to the treatment of pathogenic protein-related diseases.

[0003] The present invention aims to develop a number of novel molecular glue decomposers with high efficiency, low toxicity, stable properties and low cost through rational design based on the benzopentadiimide skeleton to meet the needs of clinical applications. Summary of the Invention [Problem to be solved by the invention]

[0004] In view of the above, the present disclosure aims to provide novel molecular glue proteolytic drugs, their uses, and methods for using them. [Means for solving the problem]

[0005] To achieve the above and other related objects, in one aspect, the present disclosure provides a compound of formula (I) or a salt, stereoisomer (including enantiomers and non-enantiomers), isotopically enriched analogue, solvate, pharmaceutical precursor, or polymorph thereof: [ka] Formula (I) where: R b1 , R b2 , R b3 , R b4 , and R b5 are each independently H, D (deuterium), or C 1-3 represents alkyl; X represents C(O) or CH2; (R a ) n The benzene ring of formula (I) is optionally selected from n R awhere R a is deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy or halogenated C 1-6 alkyl, and n represents an integer of 0, 1, 2, or 3; and L1 is C(O), alkenylene, optionally substituted C 1-5 Alkylene, -CH=, optionally substituted C 6-10 Arylene-C 1-5 Alkylene-* or N(R c1 ), where R c1 is H or C 1-3 alkyl, and the symbol * represents the point of attachment to the group X1, or L1 is -C(R L1 R L2 )-, where R L1 , R L2 are optionally substituted C together with the carbon atoms connected to them. 3-8 forming a cycloalkylene, or L represents a bond; X1 represents an optionally substituted cycloalkylene, an optionally substituted heterocyclylene, or an optionally substituted heteroarylene; X2 is C(O), optionally substituted C 1-5 Alkylene, optionally substituted C 3-8 Cycloalkylene, optionally substituted C 1-2 Alkylene-N(R c2 )-, -N(R c2 )-Optionally substituted C 1-2 Alkylene, or N(R c3 ), where R c2 and R c3 are each independently H or C 1-3 represents alkyl, or X2 represents a bond; R a1 has the following structure: [ka] Formula (IA) where: Ring A represents heterocyclylene, cycloalkylene, arylene, or heteroarylene; (R d1 ) m1 ring A is optionally joined to m groups R d1 m1 represents an integer of 0 to 10, and each R d1 are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH- or NH2-C 1-6 represents alkylene-; and Ring B represents an aryl, cycloalkyl, heterocyclyl, or heteroaryl; (R d2 ) m2 Ring B may optionally contain m groups R d2 m2 represents an integer of 0 to 10, and each R d2 are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH- or NH2-C 1-6 represents alkylene; wherein when L1 represents a bond, X1 represents an optionally substituted nitrogen-containing bridged heterocyclylene; and when X2 represents a bond, L1 is not a bond.

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

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

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

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

[0010] In another aspect, the present disclosure further provides the use of a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer (including enantiomers and non-enantiomers), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, or a pharmaceutical composition according to the present disclosure, in the manufacture of a medicament for treating or preventing a disease or condition associated with a cereblon protein.

[0011] In another aspect, the present disclosure further provides a method for treating or preventing a disease or condition associated with a cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of the compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer (including enantiomers and non-enantiomers), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or said pharmaceutical composition. [Brief explanation of the drawings]

[0012] [Figure 1] This is a study on the degradation of IKZF1 / 3 protein and GSPT1 protein in human peripheral blood mononuclear cells (hPBMC) by the compounds of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0013] In order to help those skilled in the art understand and implement the contents of the present disclosure, the following detailed description is provided as an illustrative specific embodiment. However, such description is not intended to limit the scope of the present disclosure. On the premise that it does not deviate from the spirit and scope of the present disclosure, it should be recognized that the specific embodiments described in the present disclosure can be further modified and changed in various ways, and these modifications and improvements fall within the protection scope of the present disclosure.

[0014] I. Compound Compounds of formula (I) The present disclosure provides a compound of formula (I) or a salt (including a pharmaceutically acceptable salt), stereoisomer (including an enantiomer, a non-enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, [ka] Formula (I) where the group R b1 , R b2 , R b3 , R b4 , R b5 , (R a ) n , X, L1, X1, X2 and R a1 is as defined above for the compounds of formula (I) and in each embodiment.

[0015] The compounds of formula (I) or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, pharmaceutical precursors, or polymorphs thereof provided by the present disclosure possess binding ability to CRBN and contribute to the recruitment of substrate proteins. The compounds of formula (I) or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, pharmaceutical precursors, or polymorphs thereof provided by the present disclosure can also degrade substrate proteins (e.g., IKZF1 / 2 / 3 / 4 protein, WEE1 protein, CK1α protein, GSPT1 protein, ZFP91 protein, etc.). The compounds of formula (I) or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogs, pharmaceutical precursors, or polymorphs thereof provided by the present disclosure possess antitumor activity or excellent pharmacokinetic properties and can be used as therapeutic agents for tumor patients.

[0016] In some embodiments of the present disclosure, R b1 , R b2 , R b3 , R b4 and R b5 are the same or different and each independently represent H, D or C 1-3 In some subembodiments of the present disclosure, R b1 , R b2 , R b3 , R b4 and R b5 are the same or different and each independently represent H. In some subembodiments of the present disclosure, R b1 , R b2 , R b3 , R b4 and R b5 are the same or different and each independently represent D. In some sub-embodiments of the present disclosure, R b1 , R b2 , R b3 and R b4 each independently represents H, and R b5 is H, D or C 1-3 It represents alkyl (for example, methyl, ethyl, or propyl).

[0017] In some embodiments of the present disclosure, X represents C(O).

[0018] In some embodiments of the present disclosure, X represents CH2.

[0019] In some embodiments of the present disclosure, (R a ) n The benzene ring of formula (I) is optionally selected from n R a where R a is deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 Alkyl or optionally deuterated C 1-3 alkyl, for example methyl, CD, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy or optionally deuterated C 1-3 Alkoxy, such as methoxy, ethoxy, or propoxy), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, or CH2ClCH2-), and n represents an integer of 0, 1, 2, or 3. In some subembodiments of the present disclosure, n represents an integer of 0. In some subembodiments of the present disclosure, n represents an integer of 1. In some subembodiments of the present disclosure, n represents an integer of 2. In some subembodiments of the present disclosure, n represents an integer of 3.

[0020] In some embodiments of the present disclosure, (a) L is C(O), alkenylene (e.g., C 2-8 Alkenylene, C 2-6Alkenylene, C 2-4 Alkenylene or C 2-3 alkenylene), optionally substituted C 1-5 Alkylene (e.g., optionally substituted C 1-4 Alkylene or optionally substituted C 1-3 alkylene), -CH=, optionally substituted C 6-10 Arylene-C 1-5 Alkylene-* (e.g., optionally substituted C 6-10 Arylene-C 1-3 alkylene-*), or N(R c1 ), where R c1 is H or C 1-3 represents alkyl (e.g., methyl, ethyl, or propyl), the symbol * represents the point of attachment to the group X, or L is -C(R L1 R L2 )-, where R L1 , R L2 are optionally substituted C together with the carbon atoms connected to them. 3-8 Cycloalkylene (e.g., optionally substituted C 3-7 cycloalkylene); and / or (b) X is an optionally substituted cycloalkylene (e.g., an optionally substituted C 3-20 Cycloalkylene or optionally substituted C 3-15 cycloalkylene), optionally substituted heterocyclylene (for example, optionally substituted 4- to 20-membered heterocyclylene or optionally substituted 4- to 15-membered heterocyclylene), or optionally substituted heteroarylene (for example, optionally substituted 5- to 20-membered heteroarylene or optionally substituted 5- to 15-membered heteroarylene).

[0021] In some embodiments of the present disclosure, (a1) L1 is C(O), C 2-6 Alkenylene (e.g., C 2-5 Alkenylene, C 2-4 Alkenylene or C 2-3 alkenylene), optionally substituted C 1-5 Alkylene (e.g., optionally substituted C 1-4 Alkylene or optionally substituted C 1-3alkylene), -CH=, optionally substituted C 6-10 Arylene-C 1-5 Alkylene-* (e.g., optionally substituted C 6-10 Arylene-C 1-3 alkylene-*), or N(R c1 ), where R c1 is H or C 1-3 alkyl (e.g., methyl, ethyl, or propyl), and the symbol * represents the point of attachment to the group X1, where 1-5 Alkylene and the C 6-10 Arylene-C 1-5 Each alkylene is independently selected from D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene-(e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)- (e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3or L is optionally substituted with 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof; or L is -C(R L1 R L2 )-, where R L1 , R L2 are optionally substituted C together with the carbon atoms connected to them. 3-8 Cycloalkylene (e.g., optionally substituted C 3-7 cycloalkylene); and / or (b1) X1 is an arbitrarily substituted C 3-20 cycloalkylene, optionally substituted 4- to 20-membered heterocyclylene, or optionally substituted 5- to 20-membered heteroarylene, wherein 3-20 The cycloalkylene and the 4- to 20-membered heterocyclylene are each independently selected from D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, oxo group, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene (e.g., NH2-C 1-3alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 and optionally substituted with one or more (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof, wherein the 5- to 20-membered heteroarylene is selected from the group consisting of D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene-(e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 and optionally substituted with one or more (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof.

[0022] In some embodiments of the present disclosure, (a2) L1 is C(O), vinylene (i.e., —CH═CH—), optionally substituted C 1-5 Alkylene (e.g., optionally substituted -CH2-, -(CH2)2-, and -(CH2)3-, such as -CH(OH)-, -CH2-, -(CH2)2-, -(CH2)3-, -CHF2-, and -CH2F-), NH, -CH=, or optionally substituted C 6-10 Arylene-C 1-3 Alkylene-* (e.g., optionally substituted phenylene-C 1-3 Alkylene-* or optionally substituted naphthylene-C 1-3 alkylene-*, e.g., optionally substituted phenylene-CH2-*), where the symbol * represents the point of attachment to the group X1, and where the C 1-5 Alkylene and C 6-10 Arylene-C 1-3 Each alkylene is independently selected from D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 1-4 Alkyl-NH- (e.g., C1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene-(e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 or L is optionally substituted with 1-4 (e.g., 1-3 or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof; L1 R L2 )-, where R L1 , R L2 are optionally substituted C together with the carbon atoms connected to them. 3-8 forming cycloalkylenes (e.g., optionally substituted cyclopropylene, optionally substituted cyclobutylene, optionally substituted cyclopentylene, optionally substituted cyclohexylene, and optionally substituted cycloheptylene); and / or (b2) X1 is an optionally substituted C 3-20 cycloalkylene, optionally substituted 4- to 20-membered heterocyclylene, or optionally substituted 5- to 20-membered heteroarylene, wherein 3-20 The cycloalkylene and the 4- to 20-membered heterocyclylene are each independently selected from D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C1-3 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, oxo group, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene (e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 and optionally substituted with one or more (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof, wherein the 5- to 20-membered heteroarylene is selected from the group consisting of D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, C1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene-(e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 and optionally substituted with one or more (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof.

[0023] In the embodiments of the present disclosure, the number of substituents is not limited in principle or is automatically limited by the size of the constitutional unit.

[0024] In some embodiments of the present disclosure, (a3) ​​L1 is C(O), vinylene, optionally substituted C 1-5 Alkylene (e.g., optionally substituted C 1-4 Alkylene or optionally substituted C 1-3Alkylene, for example, —CH(OH)—, —CH—, —(CH)—, —(CH)—, —CHF—, and —CHF—, —CH═, optionally substituted phenylene, 1-5 Alkylene-* (e.g., optionally substituted phenylene-C 1-3 alkylene-*, e.g., optionally substituted phenylene-CH2-*), optionally substituted naphthylene-C 1-5 Alkylene-* (e.g., optionally substituted naphthylene-C 1-3 alkylene-*), or N(R c1 ), where R c1 is H or C 1-3 alkyl (e.g., methyl, ethyl, or propyl), and the symbol * represents the point of attachment to the group X1, where 1-5 alkylene, phenylene-C 1-5 Alkylene and the naphthylene-C 1-5 Each alkylene is independently selected from D, optionally deuterated C 1-4 Alkyl, hydroxy, amino, mercapto, halogen, cyano, C 1-4 Alkoxy, C 1-4 Alkyl-NH-, halogenated C 1-4 Alkyl, NH2-C 1-4 Alkylene-, C 1-4 Alkyl-NHC(O)-, C 1-4 L is optionally substituted with 1-10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof; or L is -C(R L1 R L2 )-, where R L1 , R L2 are optionally substituted C together with the carbon atoms connected to them. 3-8 forming a cycloalkylene (e.g., optionally substituted cyclopropylene, optionally substituted cyclobutylene, optionally substituted cyclopentylene, optionally substituted cyclohexylene, and optionally substituted cycloheptylene); and / or (b3) X1 is a divalent group: D, optionally deuterated C 1-4 Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C 1-4 Alkoxy, C 1-4 Alkyl-NH-, halogenated C 1-4 Alkyl, NH2-C 1-4 Alkylene-, C 1-4 Alkyl-NHC(O)-, C 1-4 cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydropentalenylene, octahy- drylene, octacyclopentan ... dro-1H-indenylene, spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, spiro[5.5]undecylene, p-menthanylene, m-menthanylene, quinuclidinylene, adamantanylene, noradamantanylene, norbornylene, bicyclo[2.2.1]heptylene, 2-oxobicyclo[2.2.1]heptylene or bicyclo[2.2.1]heptenylene; or D, optionally deuterated C 1-4 Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C 1-4 Alkoxy, C 1-4 Alkyl-NH-, halogenated C 1-4 Alkyl, NH2-C 1-4 Alkylene-, C 1-4 Alkyl-NHC(O)-, C 1-4Azetidinylene, pyrrolidinylene, imidazolidylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azacyclooctylene, diazacycloheptanylene, diazacyclooctylene, 3-azabicyclo[3.1.0]hexylene, 3-azabicyclo[3.1.0]heptanylene, 2-, optionally substituted with one or more (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof. azabicyclo[2.2.1]heptanylene, 6-azabicyclo[3.1.1]heptanylene, 2-azabicyclo[2.2.2]octylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octylene, 3,8-diazabicyclo[3.2.1]octylene, 2,5-diazabicyclo[2.2.2]octylene, 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonylene, 3-azaspiro[5.5]undecylene, 7-azaspiro[3.5]nonylene, or octahydropyrrolo[3,4-c]pyrrolylene; or D, optionally deuterated C 1-4 Alkyl, hydroxy, amino, mercapto, halogen, cyano, C 1-4 Alkoxy, C 1-4 Alkyl-NH-, halogenated C 1-4 Alkyl, NH2-C 1-4 Alkylene-, C 1-4 Alkyl-NHC(O)-, C 1-4furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, optionally substituted with one or more (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof; benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, 4H-fluoro[3,2-b]pyrrolylene, pyrrolo[2,1-b]thiazolylene, or imidazo[2,1-b]thiazolylene. Represents.

[0025] In some embodiments of the present disclosure, (a4) L1 is the following group: C(O), -CH2-, -(CH2)2-, -(CH2)3-, -CH(OH)-, -CHF2-, -CH2F-, NH, -CH=CH-, -CH=, or optionally substituted phenylene -CH2-*, where the symbol * represents the point of attachment to the group X1, and where the phenylene is D, optionally deuterated C 1-4 Alkyl, hydroxy, amino, mercapto, halogen, cyano, C 1-4 Alkoxy, C 1-4 Alkyl-NH-, halogenated C 1-4 Alkyl, NH2-C 1-4 Alkylene-, C1-4 Alkyl-NHC(O)-, C 1-4 L is optionally substituted with 1-4 (e.g., 1-3 or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof; or L is -C(R L1 R L2 )-, where R L1 , R L2 together with the carbon atoms connected thereto form cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, or cycloheptylene, and said cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, or cycloheptylene each independently represents D, optionally deuterated C 1-4 Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C 1-4 Alkoxy, C 1-4 Alkyl-NH-, halogenated C 1-4 Alkyl, NH2-C 1-4 Alkylene-, C 1-4 Alkyl-NHC(O)-, C 1-4 Optionally substituted with one or more (e.g., 1-10, 1-8, 1-6, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof.

[0026] In some embodiments of the present disclosure, (b4) X1 is a divalent group: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] represents Here, the symbol # represents the connection point with the group L1.

[0027] In some embodiments of the present disclosure, (c) L represents a bond and X represents an optionally substituted nitrogen-containing bridged heterocyclylene (e.g., an optionally substituted 5- to 20-membered nitrogen-containing bridged heterocyclylene or an optionally substituted 5- to 15-membered nitrogen-containing bridged heterocyclylene).

[0028] In some embodiments of the present disclosure, (c1) L represents a bond and X represents an optionally substituted 5- to 20-membered nitrogen-containing bridged heterocyclylene, wherein the 5- to 20-membered nitrogen-containing bridged heterocyclylene is selected from the group consisting of D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, oxo group, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene-(e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 and optionally substituted with one or more (e.g., 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof.

[0029] In some embodiments of the present disclosure, (c2) L1 represents a bond and X1 is a divalent group: 3-azabicyclo[3.1.0]hexylene, 3-azabicyclo[3.1.0]heptanylene, 2-azabicyclo[2.2.1]heptanylene, 6-azabicyclo[3.1.1]heptanylene, 2-azabicyclo[2.2.2]octylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octylene, 3,8-diazabicyclo[3.2.1]octylene, or 2,5-diazabicyclo[2.2.2]octylene, wherein the divalent group is selected from the group consisting of D, optionally deuterated C 1-4 Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C 1-4 Alkoxy, C 1-4 Alkyl-NH-, halogenated C 1-4 Alkyl, NH2-C 1-4 Alkylene-, C 1-4 Alkyl-NHC(O)-, C 1-4 Optionally substituted with one or more (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof. In some embodiments of the present disclosure, (c3) L1 represents a bond and X1 is a divalent group: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] represents Here, the symbol # represents the connection point with the group L1.

[0030] In some embodiments of the present disclosure, X2 represents a bond, and when X2 represents a bond, L1 is not a bond.

[0031] In some embodiments of the present disclosure, X2 is the following group: C(O), optionally substituted C 1-5 Alkylene (e.g., optionally substituted C 1-4 Alkylene or optionally substituted C 1-3 alkylene), optionally substituted C 3-8 Cycloalkylene, optionally substituted C 1-2 Alkylene-N(R c2 )-, -N(R c2 )-Optionally substituted C 1-2 Alkylene, or N(R c3 ), where R c2 and R c3 are each independently H or C 1-3 alkyl (e.g., methyl, ethyl, or propyl), wherein 1-5 Alkylene and the C 3-8 Each cycloalkylene is independently selected from D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, oxo group, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 3-8 Cycloalkyl (e.g., C 3-7 Cycloalkyl, C 3-6 Cycloalkyl or C 3-5 cycloalkyl), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene (e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 optionally substituted with 1 to 10 (e.g., 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof; and Said C 1-2 Alkylene is D, optionally deuterated C 1-4 Alkyl (e.g., optionally deuterated C 1-3alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), hydroxy, amino, mercapto, halogen (for example fluorine, chlorine, bromine or iodine), cyano, oxo group, C 1-4 Alkoxy (e.g., C 1-3 alkoxy, such as methoxy, ethoxy, or propoxy), C 3-8 Cycloalkyl (e.g., C 3-7 Cycloalkyl, C 3-6 Cycloalkyl or C 3-5 cycloalkyl), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-4 Alkyl (e.g., halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-4 Alkylene (e.g., NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 Optionally substituted with 1-4 (e.g., 1-3 or 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-), and any combination thereof.

[0032] In some embodiments of the present disclosure, X2 represents C(O), -CH2-, -(CH2)2-, -(CH2)3-, 1,1-cyclopropylene, NH, -CH2-NH-, -(CH2)2-NH-, -NH-(CH2)2-, or -NH-CH2-. In some embodiments of the present disclosure, R a1 has the following structure: [ka] Formula (IA) where: Ring A is heterocyclylene (e.g., 4- to 20-membered heterocyclylene or 4- to 15-membered heterocyclylene), cycloalkylene (e.g., C 3-20 Cycloalkylene, or C 3-15 cycloalkylene), arylene (e.g., C 6-20 Arylene or C 6-10 arylene), or heteroarylene (for example, 5- to 20-membered heteroarylene or 5- to 15-membered heteroarylene), (R d1 ) m1 ring A is optionally joined to m groups R d1 m1 represents an integer of 0 to 10 (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1), and each R d1 are independently selected from deuterium, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, oxo groups, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 Alkyl or optionally deuterated C 1-3 alkyl, for example methyl, CD, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-5 Alkoxy or optionally deuterated C 1-3Alkoxy, such as methoxy, ethoxy, or propoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 alkyl-C(O)NH-, such as CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-, or NH2-C 1-6 Alkylene-(e.g., NH2-C 1-4 Alkylene- or NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-); and Ring B is an aryl (e.g., C 6-20 Aryl or C 6-10 aryl), cycloalkyl (e.g., C 3-20 Cycloalkyl or C 3-15 cycloalkyl), heterocyclyl (for example, 4- to 20-membered heterocyclyl or 4- to 15-membered heterocyclyl), or heteroaryl (for example, 5- to 20-membered heteroaryl or 5- to 15-membered heteroaryl), (R d2 ) m2 Ring B may optionally contain m groups R d2 m2 represents an integer of 0 to 10 (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1), and each R d2are independently selected from deuterium, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, oxo groups, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 Alkyl or optionally deuterated C 1-3 alkyl, for example methyl, CD, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-5 Alkoxy or optionally deuterated C 1-3 Alkoxy, such as methoxy, ethoxy, or propoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl or halogenated C 1-3 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-4 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), C 1-4 Alkyl-NHC(O)-(e.g., C 1-3 alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, or CH3CH2CH2-NHC(O)-), C 1-4 Alkyl-C(O)NH- (e.g., C 1-3 alkyl-C(O)NH-, such as CH3-C(O)NH-, CH3CH2-C(O)NH-, or CH3CH2CH2-C(O)NH-, or NH2-C 1-6 Alkylene-(e.g., NH2-C 1-4 Alkylene- or NH2-C 1-3 alkylene-, for example NH2CH2-, NH2CH2CH2- or NH2CH2CH2CH2-).

[0033] In some embodiments of the present disclosure, R a1 has the following structure: [ka] Formula (IA) where: Ring A is a 4- to 20-membered heterocyclylene, C 3-20 Cycloalkylene, C 6-20 (R d1 ) m1 ring A is optionally joined to m groups R d1 m1 represents an integer of 0 to 10 (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1), and each R d1 are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH- or NH2-C 1-6 represents alkylene-; and / or Ring B is C 6-20 Aryl, C 3-20 cycloalkyl, 4- to 20-membered heterocyclyl, or 5- to 20-membered heteroaryl; (R d2 ) m2 Ring B may optionally contain m groups R d2 m2 represents an integer of 0 to 10 (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1), and each R d2 are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH- or NH2-C 1-6 Represents alkylene-.

[0034] In some embodiments of the present disclosure, ring A is a divalent group: D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6 cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydropentalenylene, octahydro-1, optionally substituted with one or more (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkylene-, and any combination thereof. H-indenylene, spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, spiro[5.5]undecylene, p-menthanylene, m-menthanylene, quinuclidinylene, adamantanylene, noradamantanylene, norbornylene, bicyclo[2.2.1]heptylene, 2-oxobicyclo[2.2.1]heptylene or bicyclo[2.2.1]heptenylene; D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6 phenylene or naphthylene optionally substituted with one or more (e.g., 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkylene-, and any combination thereof; D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6alkylene-, and any combination thereof, optionally substituted with one or more (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of azetidinylene, pyrrolidinylene, imidazolidylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azacyclooctylene, diazacycloheptanylene, diazacyclooctylene, 3-azabicyclo[3.1.0]hexylene, 3-azabicyclo[3.1.0]heptanylene, 2-azabicyclo[3.1.0]hexylene, 3-azabicyclo[3.1.0]heptanylene, 2-azabicyclo[3.1.0]hexylene, 2 ... 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonylene, 3-azaspiro[5.5]undecylene, 7-azaspiro[3.5]nonylene, or octahydropyrrolo[3,4-c]pyrrolylene; or D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6and any combination thereof, optionally substituted with one or more (e.g., 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzyl, benzoxazolylene, benzoisoxazolylene, benzo- ...

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[0231] In the embodiments of the present disclosure, the number of substituents is not limited in principle or is automatically limited by the size of the constitutional unit.

[0035] In some embodiments of the present disclosure, Ring B is one of the following groups: D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydropentanol ... 1H-indenyl, spiro[3.3]heptanyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[5.5]undecyl, p-menthanyl, m-menthanyl, quinuclidinyl, adamantanyl, noradamantanyl, bornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl or bicyclo[2.2.1]heptenyl; D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6 phenyl or naphthyl optionally substituted with one or more (e.g., 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of alkylene-, and any combination thereof; D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6alkylene-, and any combination thereof, optionally substituted with one or more (e.g., 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) substituents selected from the group consisting of azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl, diazacyclooctyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.1]heptanyl, 2-azabicyclo[3.1.2]hexyl, 3-azabicyclo[3.1.3]heptanyl, 3-azabicyclo[3.1.4]heptanyl, 3-azabicyclo[3.1.5]heptanyl, 3-azabicyclo[3.1.6]heptanyl, 3-azabicyclo[3.1.7]heptanyl, 3-azabicyclo[3.1.8]heptanyl, 3-azabicyclo[3.1.9]heptanyl, 3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.2 ... cyclo[2.2.1]heptanyl, 6-azabicyclo[3.1.1]heptanyl, 2-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonyl, 3-azaspiro[5.5]undecyl, 7-azaspiro[3.5]nonyl or octahydropyrrolo[3,4-c]pyrrolyl; or D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-4 Alkyl-NH-, C 1-4 Alkyl-NHC(O)-, C 1-4 Alkyl-C(O)NH-, NH2-C 1-6furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazol ... It represents azolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl. In an embodiment of the present disclosure, the number of substituents is not limited in principle or is automatically limited by the size of the structural unit.

[0036] In some embodiments of the present disclosure, ring A is a divalent group: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] represents Here, the symbol ** represents the connection point with ring B.

[0037] In some embodiments of the present disclosure, Ring B is one of the following groups: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Represents.

[0038] In some embodiments of the present disclosure, R a1 has the following structure: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Represents.

[0039] In some embodiments of the present disclosure, -X1-X2-R in the compound of formula (I) a1 has the following structure: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

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[0040] In some embodiments of the present disclosure, the compound of formula (I) can also be a compound of formula (II) or a compound of formula (III): [ka] But also, where the group R b1 , R b2 , R b3 , R b4 , R b5 , (R a ) n , X, L1, X1, X2 and R a1 is as defined above for compounds of formula (I) and each embodiment thereof. In some embodiments of the present disclosure, the compound of Formula (I) can also be a compound of Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (IIa), Formula (IIb), Formula (IIc), Formula (IId), Formula (IIIa), Formula (IIIb), Formula (IIIc), or Formula (IIId): [ka] [ka] [ka] [ka] But also, where the group R b1 , R b2 , R b3 , R b4 , R b5 , (R a ) n , X, L1, X1, X2 and R a1 is as defined above for compounds of formula (I) and each embodiment thereof.

[0041] In particular, the compounds in Table 1 of the present invention and their salts (especially pharmaceutically acceptable salts, such as their hydrochloride salts), enantiomers, non-enantiomers, solvates, polymorphs thereof are preferred.

[0042] Table 1. Compounds of the invention [Table 1] [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] [Table 9] [Table 10] [Table 11] [Table 12] [Table 13] [Table 14] [Table 15] [Table 16] [Table 17] Table 18 Table 19 Table 20 Table 21 Table 22 Table 23 Table 24 Table 25 Table 26 Table 27 Table 28 Table 29

Table 30

Table 50

Table 91

Table 99

Table 100

[0043] II. Other Aspects of the Compounds (Including Salts, Enantiomers, Stereoisomers, Solvates, Isotopically Enriched Analogues, Pharmaceutical Precursors, or Polymorphs of the Compounds) The compounds of the present disclosure have a structure of any of Formula (I), Formula (II), Formula (III), Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (IIa), Formula (IIb), Formula (IIc), Formula (IId), Formula (IIIa), Formula (IIIb), Formula (IIIc), Formula (IIId), Formula (IIId). Unless otherwise stated, reference to the compounds of the present disclosure includes any compound of Formula (I), Formula (II), Formula (III), Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (IIa), Formula (IIb), Formula (IIc), Formula (IId), Formula (IIIa), Formula (IIIb), Formula (IIIc), Formula (IIId), and specific compounds falling within the scope of these general formulas.

[0044] It should be recognized that compounds of the present disclosure (including compounds of Formula (I), Formula (II), Formula (III), Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (IIa), Formula (IIb), Formula (IIc), Formula (IId), Formula (IIIa), Formula (IIIb), Formula (IIIc), or Formula (IIId)) can have stereoisomeric configurations and therefore can exist in one or more stereoisomeric forms. The present disclosure also relates to compounds having a stereoisomeric configuration that is optically enriched (e.g., greater than about 90% ee, e.g., greater than about 95% ee, 97% ee, or 99% ee), and mixtures thereof (including racemates). As used herein, "optically enriched" means that a mixture of enantiomers is composed of a significantly greater proportion of enantiomers and can be expressed in terms of enantiomeric excess (ee%). Purification of isomers and separation of isomeric mixtures can be achieved by standard techniques known in the art, such as column chromatography, preparative TLC, preparative HPLC, asymmetric synthesis (e.g., synthesis using chiral intermediates) and / or chiral separation.

[0045] In some embodiments, polymorphic forms of the disclosed compounds or salts of the disclosed compounds are also provided. Salts of the disclosed compounds may be pharmaceutically acceptable salts, including, but not limited to, hydrochloride, sulfate, citrate, maleate, sulfonate, citrate, lactate, tartrate, fumarate, phosphate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, malonate, benzoate, mandelate, succinate, trifluoroacetate, hydroxyacetate, or p-toluenesulfonate. The disclosed compounds may exist in a nonsolvated or solvated form in a pharmaceutically acceptable solvent, such as water or ethanol. In some embodiments, the disclosed compounds can be prepared into precursor drugs or pharmaceutical precursors. The precursor drugs are converted to the parent drug in the body and function. In some embodiments, isotope-labeled compounds of the disclosed compounds are also provided, with examples of isotopes including deuterium (D or 2 H) is included.

[0046] III. Drug Compositions / Formulations In some embodiments, the present disclosure provides pharmaceutical compositions comprising a compound of the present disclosure or a pharmaceutically acceptable salt, solvate, isotopically enriched analogue, polymorph, pharmaceutical precursor, stereoisomer (including enantiomer), or mixture of stereoisomers thereof as an active ingredient, and at least one pharmaceutically acceptable carrier.

[0047] In some embodiments, pharmaceutically acceptable carriers include, but are not limited to, fillers, stabilizers, dispersing agents, suspending agents, diluents, excipients, thickeners, solvents, or sealants. A 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 substances 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, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as coa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; surfactant phosphate buffers; polyethylene oxide, polyvinylpyrrolidone, polyacrylamide, poloxamer; and other non-toxic compatible substances used in drug formulations.

[0048] The pharmaceutical compositions described herein further comprise at least one second therapeutic agent, such as an anti-cancer agent. The second therapeutic agent can be used in combination with the compound of Formula (I) of the present disclosure to treat the diseases or conditions described herein. Examples of second therapeutic agents include, but are not limited to, chemotherapeutic agents, immunotherapeutic agents, gene therapy agents, angiogenesis inhibitors, immunomodulators, etc.

[0049] The pharmaceutical composition described in the present disclosure, which comprises the compound of formula (I) according to the present disclosure or a pharmaceutically acceptable salt thereof as an active ingredient, can be administered in an appropriate dosage form, such as a spool, a patch, a tablet (e.g., a regular tablet, a dispersible tablet, an orally disintegrating tablet), a capsule (e.g., a medicament for treating a rheumatoid arthritis, ... For example, the compound of formula (I) can be prepared into a soft capsule, hard capsule, enteric-coated capsule, dragee, troche, powder, granule, powder injection, suppository, or liquid preparation (e.g., suspension (e.g., aqueous or oily suspension), solution, emulsion, or syrup), or into a conventional injection form such as an injectable solution (e.g., a sterile injection solution prepared using water, Ringer's solution, isotonic sodium chloride solution, or the like as a carrier or solvent by a method known in the art) or a freeze-dried composition. In addition, those skilled in the art can also prepare the compound of formula (I) into a conventional, dispersible, chewable, or oral fast-disintegrating or fast-dissolving preparation, or a sustained-release capsule or controlled-release capsule, as needed.

[0050] The compound of formula (I) of the present disclosure as an active ingredient is included in a pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver to the subject a therapeutically effective amount for the indication requiring treatment without causing serious toxic effects to the subject being treated. For all diseases or conditions mentioned herein, the dosage of the active compound is, for example, about 5 ng / kg of subject's body weight / day to 500 mg / kg of subject's body weight / day, about 10 ng / kg of subject's body weight / day to 300 mg / kg of subject's body weight / day, e.g., 0.1 to 100 mg / kg of subject's body weight / day, or 0.5 to about 25 mg / kg of subject's body weight / day.

[0051] The compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present disclosure can be conveniently administered in any suitable formulation, including, but not limited to, less than 1 mg, 1 mg to 3000 mg, 5 mg to 1000 mg, for example, 5 to 500 mg, 25 to 250 mg of active ingredient per unit dosage form.

[0052] IV. Kits / Packaged Products The compounds of formula (I) of the present disclosure, or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polymorphs, pharmaceutical precursors, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, are for use as pharmaceuticals. The pharmaceutical agents of the present disclosure or the pharmaceutical compositions of the present disclosure can be present in a kit / packaged product. The kit / packaged product can include packaging or containers. Examples of packaging or containers include, but are not limited to, ampoules, blister packs, pharmaceutical plastic bottles, vials, pharmaceutical glass bottles, containers, syringes, laminated soft packaging, co-extruded membrane infusion containers, test tubes, and dispenser devices. The kit / packaged product can include product instructions.

[0053] V. Methods and Uses The compounds of formula (I) of the present disclosure, or their pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polycrystalline forms, pharmaceutical precursors, stereoisomers (including enantiomers), or mixtures of stereoisomers, can further be used as pharmaceuticals. In particular, the compounds of formula (I) of the present disclosure, or their pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polycrystalline forms, pharmaceutical precursors, stereoisomers (including enantiomers), or mixtures of stereoisomers, can be used in the manufacture of medicaments for preventing and / or treating diseases or conditions associated with cereblon protein. Diseases or conditions associated with cereblon protein include tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, vascular heart disease, Richter syndrome (RS), acute liver failure, and diabetes. In some embodiments, the disease or condition associated with cereblon protein includes, but is not limited to, tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, vascular cardiopathy, Richter syndrome (RS), acute liver failure, or diabetes. In some embodiments, the disease or condition associated with cereblon protein includes myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, and smoldering multiple myeloma; myelofibrosis; bone marrow disorders; myelodysplastic syndromes (MDS); previously treated myelodysplastic syndromes; transplant-associated cancer; neutropenia; leukemia, including acute myeloid leukemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, leukemia-associated anemia, and acute myeloid leukemia (AML).Lymphomas, including diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, and refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma and lung squamous cell carcinoma; inflammatory myofibroblastic tumor Cancer; Colorectal cancer; Bowel cancer; Brain glioma; Astroblastoma; Ovarian cancer; Bronchogenic carcinoma; Prostate cancer; Breast cancer including triple-negative breast cancer, incidental breast cancer and Cowden's disease; Pancreatic cancer; Central nervous system cancer; Neuroblastoma; Glioma; Peripheral neuroepithelioma; Extramedullary plasmacytoma; Plasmacytoma; Gastric cancer; Gastrointestinal stromal tumor; Esophageal cancer; Colorectal adenocarcinoma; Esophageal squamous cell carcinoma; Liver cancer; Renal cell carcinoma; Bladder cancer; Endometrial cancer; Uterine cancer; Head and neck cancer; Brain cancer; Oral cancer; Sarcomas including rhabdomyosarcoma, various lipogenic tumors, Ewing's sarcoma / undifferentiated 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's syndrome syndrome, RS); pyometra 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, and atopic dermatitis; keratoconjunctivitis sicca; inflammatory diseases including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, and bronchitis; cerebral malaria; infectious diseases including viral pneumonia, AIDS, COVID-19, gram-negative bacterial infections, gram-positive bacterial infections, and tuberculosis; septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, and lung) or tissue transplant rejection; diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; childhood aplastic anemia;Vascular heart disorders (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure due to cachexia and septic shock; or acute liver failure, including, but not limited to:

[0054] The present disclosure provides methods for preventing and / or treating a disease or condition associated with a cereblon protein, comprising administering to a subject a therapeutically effective amount of a compound of formula (I) according to the present disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I) according to the present disclosure or a pharmaceutically acceptable salt thereof as an active ingredient. In some embodiments, the disease or condition associated with a cereblon protein comprises a tumor, an infectious disease, an inflammatory disease, an autoimmune disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, vascular cardiopathies, Richter syndrome (RS), acute liver failure, or diabetes. In some embodiments, the disease or condition associated with a cereblon protein comprises multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma, or smoldering multiple myeloma. Myeloma, including AML; myelofibrosis; bone marrow disorders; myelodysplastic syndromes (MDS); previously treated myelodysplastic syndromes; transplant-related cancer; neutropenia; leukemia, including acute myeloid leukemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, leukemia-related anemia, and acute myeloid leukemia (AML); diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin's lymphoma, relapsed diffuse large B-cell lymphoma, and relapsed mediastinal (thymic) large B-cell lymphoma. Lymphomas, including primary mediastinal (thymic) large B-cell lymphoma, recurrent 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, and refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma and squamous cell carcinoma; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and Cowden's disease; pancreatic cancer; central nervous system cancer; neuroblastoma; glioma; peripheral neuroepithelioma; extramedullary plasmacytoma;Plasmacytoma; Gastric cancer; Gastrointestinal stromal tumor; Esophageal cancer; Colorectal adenocarcinoma; Esophageal squamous cell carcinoma; Liver cancer; Renal cell carcinoma; Bladder cancer; Endometrial cancer; Uterine cancer; Head and neck cancer; Brain cancer; Oral cancer; Sarcomas including rhabdomyosarcoma, various lipogenic 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 syndrome, RS); pyometra; autoimmune diseases including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren's syndrome, and atopic dermatitis; keratoconjunctivitis sicca; inflammatory diseases including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, and bronchitis; cerebral malaria; viral pneumonia, AIDS, and COVID-19 (coronavirus). Infectious diseases, including infections, gram-negative infections, gram-positive infections, 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; vascular heart disorders (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure due to cachexia and septic shock; or acute liver failure;

[0055] In a method for preventing and / or treating a disease or condition associated with a cereblon protein, a therapeutically effective amount of a compound of formula (I) according to the present disclosure, or a pharmaceutical composition comprising a compound of formula (I) according to the present disclosure as an active ingredient, is administered to the subject by at least one administration route selected from the group consisting of nasal administration, inhalation administration, topical administration, oral administration, buccal administration, rectal administration, pleural administration, peritoneal administration, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration, and intravenous administration.

[0056] The term "treatment" or "treatment" refers to the slowing (alleviation) of unwanted disease or symptoms, such as the progression of tumors, by administering to a subject a compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present disclosure, or a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. Beneficial effects or desired clinical results of the present disclosure include, but are not limited to, alleviation of symptoms, reduction in disease severity, stabilization of the disease state, delay or slowing of disease progression, improvement or alleviation of disease condition, and remission of disease.

[0057] A "therapeutically effective amount" of a compound according to the present disclosure will depend on a variety of factors, including the activity of the particular compound used, the metabolic stability and duration of action of the compound, the age, sex, and weight of the patient, the overall medical condition of the patient, the mode and time of administration, excretion rate, concomitant medications, and the progression of the disease or condition in the patient being treated. Those skilled in the art will be able to determine the appropriate amount depending on these and other factors.

[0058] It should be understood that the use of one or more active compounds and / or compositions and the selection of their dosage will vary depending on the individual's basic condition (generally should be optimized for the individual's condition).Dosage and administration scheme should be within the scope of the ability of a person skilled in the art, and the appropriate dosage depends on many factors, including the level of knowledge and ability of a general technical physician, veterinarian, or researcher (see, for example, Li Jun, ed., "Clinical Pharmacology", 4th Edition, People's Health Publishing House (2008)).

[0059] The patient or subject to be treated refers to an animal, e.g., a mammal, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, guinea pigs, rats, mice, etc.

[0060] VI.Definition Unless otherwise specified, the following terms, phrases and symbols used herein generally have the following meanings:

[0061] Generally, the nomenclature used herein (e.g., IUPAC nomenclature) and the laboratory programs described below (including those used in cell culture, organic chemistry, analytical chemistry, and pharmacology) are those well known and commonly used in the art. Unless otherwise defined, in accordance with the context of the present disclosure, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Additionally, in the claims and / or specification, when the terms "a" and "an" are used in conjunction with the term "comprise" or a noun, the meaning may be "one," but is also consistent with the meanings of "one or more," "at least one," and "one or more than one." Similarly, the terms "another" or "other" can denote at least a second or more.

[0062] When embodiments are described herein using the terms "comprising" or "having," it should be understood that other embodiments similar to the statements "consisting of" and / or "consisting essentially of" are also provided.

[0063] The term "about," used alone or in combination, is used herein to mean approximately, in the region of, roughly, or on the order of... When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries to numerical values ​​greater than or less than the stated value. Generally, the term "about" can modify the value higher or lower than the stated value by a variance (increase or decrease) up or down, for example, by 10%, 5%, 2%, 1%, etc.

[0064] As used herein, the term "represents a bond," used alone or in combination, means a bond connector (i.e., represents absence). For example, the term "L represents a bond" means that L is a bond connector. In other words, when L is a bond, the group X in the structure of formula (I) is directly connected to the benzene ring in the structure of formula (I). For example, the term "X represents a bond" means that X is a bond connector. In other words, when X is a bond, the group R in the structure of formula (I) is directly connected to the benzene ring in the structure of formula (I).a1 is directly connected to the group X1 in the compound of formula (I).

[0065] As used herein, the term "optionally substituted," used alone or in combination, means that the indicated group may be unsubstituted or may be substituted with one or more substituents as defined herein. As used herein, the terms "optionally substituted" and "unsubstituted or substituted" may be used interchangeably. The term "substituted" generally refers to one or more hydrogen atoms in the referenced structure being replaced with the same or different specific substituents. The number of substituents is not limited in principle to any particular number, and is automatically limited by the size of the structural unit (i.e., the total number of hydrogen atoms that may be replaced in the structural unit), or as expressly defined herein.

[0066] As used herein, bonds broken by wavy lines indicate the point of attachment of the depicted group to the rest of the molecule. For example, the group R a1 [ka] represents the connection between ring A of the group and group X2. For example, the divalent group X1 shown below: [ka] In the formula (I), the symbol # represents the connection point between atom N and group L1, and the other atom N is connected to group X2. When the connection point of a group is not specified in this specification, for example, in the group -CH2-NH- represented by X2, either one end of the group (e.g., CH2) is connected to group X1 of the compound of formula (I), and the other end is connected to group R a1 is connected to.

[0067] As used herein, the terms "halogen atom" or "halogen", alone or in combination, refer to fluorine, chlorine, bromine or iodine.

[0068] As used herein, the term "alkyl," alone or in combination, refers to straight or branched chain alkyl.x -C y Alkyl" or "C x-y The term "alkyl" (x and y are each integers) refers to a straight or branched chain alkyl containing x to y carbon atoms. The term "C1-C6 alkyl" as used alone or in combination in this disclosure refers to a straight or branched chain alkyl containing 1 to 6 carbon atoms, examples of which include C1-C5 alkyl, C1-C4 alkyl, and C1-C3 alkyl. The term "C1-C4 alkyl" as used alone or in combination in this disclosure refers to a straight or branched chain alkyl containing 1 to 4 carbon atoms. Examples of the term "C1-C6 alkyl" include C1-C5 alkyl, C1-C4 alkyl, C1-C3 alkyl, C1-C2 alkyl, and methyl. Representative examples of the term "C1-C6 alkyl" include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl. The term "C 1-4 "Alkyl" refers to a straight or branched chain alkyl containing 1 to 4 carbon atoms. 1-4 An example of an alkyl is C 1-4 Alkyl, C 1-3 Alkyl, C 1-2 Contains alkyl and methyl. 1-4 Representative examples of "alkyl" include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl. 1-3 "Alkyl" or "C1-C3 alkyl" refers to an alkyl containing 1 to 3 carbon atoms, representative examples of which include methyl, ethyl, n-propyl, and isopropyl. In this disclosure, the "alkyl" is optionally substituted, and the substituents are optionally D (i.e., deuterium), halogen, hydroxy, cyano, C 1-3 Alkyl, C 1-3 One or more substituents selected from the group consisting of alkoxy, trifluoromethyl, heterocyclyl (eg, a 4- to 8-membered heterocycle), or combinations thereof.

[0069] As used herein, the term "halogenated alkyl," alone or in combination, refers to a straight or branched chain alkyl substituted with one or more halogens, wherein one or more hydrogens in said alkyl are replaced with halogens. x -C y Alkyl" or "halogenated C x-y The term "alkyl" (x and y are each integers) refers to a straight or branched chain alkyl containing x to y carbon atoms substituted with one or more halogens. The term "halogenated C 1-6 "Alkyl" refers to a straight or branched chain alkyl containing 1 to 6 carbon atoms substituted with one or more halogens. 1-6 Examples of alkyl halide are C 1-6 Alkyl, halogenated C 1-5 Alkyl, halogenated C 1-4 Alkyl, halogenated C 1-3 Alkyl, halogenated C 1-2 The term "halogenated C" includes alkyl and methyl halides. 1-6 Representative examples of "alkyl" include methyl halides, ethyl halides, n-propyl halides, isopropyl halides, n-butyl halides, isobutyl halides, sec-butyl halides, tert-butyl halides, pentyl halides, isopentyl halides, neopentyl halides, tert-pentyl halides, and hexyl halides, among others, including, for example, F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, and CH2ClCH2-. The term "halogenated C 1-3"Alkyl" or "halogenated C1-C3 alkyl" refers to an alkyl containing 1 to 3 carbon atoms substituted with one or more halogens, representative examples of which include halogenated methyl, halogenated ethyl, halogenated n-propyl, and halogenated isopropyl, among others, such as F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2-, and CH2ClCH2-.

[0070] The term "deuterated," as used herein, alone or in combination, refers to the replacement of one or more hydrogen atoms in the referenced group with deuterium atoms (ie, D).

[0071] As used herein, the term "deuterated C" used alone or in combination x -C y Alkyl" or "Deuterated C x-y The term "alkyl" (x and y are each integers) refers to a straight or branched chain alkyl containing x to y carbon atoms substituted with one or more deuterium atoms. The term "deuterated C 1-6 The term "alkyl" refers to a straight or branched chain alkyl containing 1 to 6 carbon atoms substituted with one or more deuterium atoms. 1-6 An example of an alkyl is deuterated C 1-5 Alkyl, e.g., deuterated C 1-4 Rukyru, deuterated C 2-5 Alkyl, deuterated C 1-3 Alkyl, deuterated C 1-2 The term "deuterated C" includes alkyl and deuterated methyl. 1-6 Representative examples of "alkyl" include perdeuterated methyl (CD3), perdeuterated ethyl (CD3CD2), perdeuterated n-propyl, perdeuterated isopropyl, perdeuterated n-butyl, perdeuterated isobutyl, perdeuterated sec-butyl, perdeuterated tert-butyl, perdeuterated pentyl, perdeuterated isopentyl, perdeuterated neopentyl, perdeuterated tert-pentyl, and perdeuterated hexyl.1-3 "Alkyl" or "deuterated C1-C3 alkyl" refers to an alkyl containing 1 to 3 carbon atoms substituted with one or more deuterium atoms, representative examples of which include fully deuterated methyl (CD3-) and fully deuterated ethyl (CD3CD2).

[0072] As used herein, the term "alkylene" (which may be used interchangeably with "alkylene chain"), alone or in combination, refers to a straight or branched chain divalent saturated hydrocarbon group consisting of carbon and hydrogen atoms. x -C y Alkylene" or "C x - y The term "alkylene" (x and y are each an integer) refers to a straight or branched chain alkylene containing x to y carbon atoms. The term "C1-C5 alkylene" used alone or in combination herein refers to a straight or branched chain alkylene containing 1 to 5 carbon atoms, examples of which include C2-C5 alkylene, C1-C4 alkylene, C1-C3 alkylene, C1-C2 alkylene, and methylene. Representative examples include, but are not limited to, methylene, ethylene, propylene, isopropylidene, butylene, isobutylene, sec-butylene, tert-butylene, n-pentylene, isopentylene, neopentylidene, and tert-pentylene. In the present disclosure, the "alkylene" is optionally substituted, and the substituents may be optionally substituted with D, optionally deuterated C 1-4 Alkyl, C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, C1-C4 alkoxy, C1-C4 alkylamino, halogenated C1-C4 alkyl, amino C 1-4 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 and one or more (eg, 1-10, 1-6, 1-5, 1-4, 1-3, 2-3, or 1) substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof.

[0073] The term "alkoxy," as used herein, alone or in combination, refers to a straight or branched chain alkoxy and has the structural formula alkyl-O-. Optionally, the alkyl portion of the alkoxy can contain 1-10 carbon atoms. Representative examples of "alkoxy" include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy, 2-pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, 2-hexyloxy, 3-hexyloxy, 3-methylpentyloxy, and the like. The terms "C1-C4 alkoxy" or "C 1-4 "Alkoxy" refers to a straight or branched chain alkoxy containing 1-4 carbon atoms. 1-4 Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy.

[0074] As used herein, the term "halogenated alkoxy," alone or in combination, refers to an alkoxy substituted with one or more halogens. Optionally, the alkyl portion of the alkoxy can contain 1 to 10 carbon atoms. Examples of "halogenated alkoxy" include halogenated C 1-6 Alkoxy or halogenated C 1-4 Representative examples include, but are not limited to, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, and CH2ClCH2-O-.

[0075] As used herein, the term "alkyl-NH-," alone or in combination, refers to a straight or branched chain alkyl-NH-, where alkyl is as defined above. Optionally, the alkyl portion of the alkyl-NH- can contain 1 to 6 carbon atoms, i.e., C 1-6Representative examples of "alkyl-NH-" include, but are not limited to, methyl-NH-, ethyl-NH-, propyl-NH-, isopropyl-NH-, n-butyl-NH-, isobutyl-NH-, tert-butyl-NH-, pentyl-NH-, hexyl-NH-, and the like. The terms "C1-C4 alkyl-NH-" or "C 1-4 "Alkyl-NH-" refers to a straight or branched chain alkyl-NH- containing 1 to 4 carbon atoms. 1-4 Representative examples of alkyl-NH- include, but are not limited to, methyl-NH-, ethyl-NH-, n-propyl-NH-, isopropyl-NH-, n-butyl-NH-, isobutyl-NH-, and tert-butyl-NH-.

[0076] As used herein, the term "NH2-alkylene," alone or in combination, refers to a straight or branched chain alkylene substituted with an amino, where alkylene is as defined above. Optionally, the alkylene portion of "NH2-alkylene" can contain 1 to 6 carbon atoms. The term "NH2-C 1-4 alkylene" or "amino-C 1-4 "Alkylene-" refers to a straight or branched chain alkylene containing 1 to 4 carbon atoms substituted with an amino. 1-4 Representative examples of alkylene include, but are not limited to, NH2-CH2-, NH2-CH2CH2-, and NH2-CH2CH2CH2-.

[0077] As used herein, the term "alkyl-NHC(O)-," alone or in combination, refers to a straight or branched chain alkyl-NHC(O)-, where alkyl is as defined above. Optionally, the alkyl portion of alkyl-NHC(O)- can contain 1 to 6 carbon atoms. The terms "C1-C4 alkyl-NHC(O)-" or "C 1-4 "Alkyl-NHC(O)-" refers to a straight or branched chain alkyl-NHC(O)- containing 1 to 4 carbon atoms. 1-4Representative examples of alkyl-NHC(O)- include, but are not limited to, CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-.

[0078] As used herein, the term "alkyl-C(O)NH-," alone or in combination, refers to a straight or branched chain alkyl-C(O)NH-, where alkyl is as defined above. Optionally, the alkyl portion of the alkyl-C(O)NH- can contain 1 to 6 carbon atoms. The terms "C1-C4 alkyl-C(O)NH-" or "C 1-4 "Alkyl-C(O)NH-" refers to a straight or branched chain alkyl-C(O)NH- containing 1 to 4 carbon atoms. 1-4 Representative examples of alkyl-C(O)NH- include, but are not limited to, CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-.

[0079] In the present invention, the term "heteroaryl," used alone or in combination, refers to a 5-20-membered (optionally 5-15-membered, 5-12-membered, 5-11-membered, 5-10-membered, 5-9-membered, 5-8-membered, 5-7-membered, 5-6-membered, 6-15-membered, or 6-9-membered) monocyclic, bicyclic, or polycyclic group having at least one aromatic ring containing one or more (e.g., 1-6, 1-5, 1-4, or 1-3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroaryl includes bicyclic, tricyclic, or tetracyclic heteroaryl, in which one ring is an aromatic ring containing one or more heteroatoms independently selected from the group consisting of O, S, and N, and the other rings may be saturated, partially unsaturated, or aromatic, and may be carbocyclic or contain one or more heteroatoms independently selected from the group consisting of O, S, and N. Examples of monocyclic heteroaryls include, but are not limited to, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, tetrazolyl, and triazinyl. Examples of bicyclic heteroaryls include indolyl, isoindolyl, isoindolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolinyl, isoquinolinyl, naphthyl, and the like. Including, but not limited to, dinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, oxazolopyridyl, furopyridyl, pteridyl, purinyl, pyridopyridyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl and imidazo[2,1-b]thiazolyl.Examples of tricyclic or polycyclic heteroaryl include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, and xanthyl. The heteroaryl may be substituted or unsubstituted. Substituted heteroaryl refers to heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, where the substituent is C1-C3 alkyl, C. 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino C 1-3 Alkylene, C 1-3 Alkyl-NHC(O)-, C 1-3 It is optionally selected from the group consisting of alkyl-C(O)NH-, cyano group, or any combination thereof.

[0080] In the present disclosure, the term "heteroarylene," as used alone or in combination, refers to a 5-20-membered (optionally 5-15-membered, 5-12-membered, 5-11-membered, 5-10-membered, 5-9-membered, 5-8-membered, 5-7-membered, 5-6-membered, 6-15-membered, or 6-9-membered) monocyclic, bicyclic, or polycyclic divalent aromatic ring group having at least one aromatic ring containing one or more (e.g., 1 to 6, 1 to 5, 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroarylene includes bicyclic, tricyclic, or tetracyclic heteroarylene, in which one ring is an aromatic ring containing one or more heteroatoms independently selected from the group consisting of O, S, and N, and the other rings may be saturated, partially unsaturated, or aromatic, and may be carbocyclic or contain one or more heteroatoms independently selected from the group consisting of O, S, and N. Examples of monocyclic heteroarylenes include, but are not limited to, furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, tetrazolylene, and triazinylene.Examples of bicyclic heteroarylenes include indolylene, isoindolinylene, isoindolinylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthylene, and the like. Examples of heteroarylenes include, but are not limited to, rhizinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, oxazolopyridylene, furopyridylene, pteridylene, prinylene, pyridopyridylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene, and imidazo[2,1-b]thiazolylene. Examples of tricyclic or polycyclic heteroarylenes include, but are not limited to, acridinylene, benzoindolylene, carbazolylene, dibenzofuranylene, and xantylene. The heteroarylene may be unsubstituted or substituted. Substituted heteroarylene refers to heteroarylene that is substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituent is C1-C3 alkyl, C. 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino-substituted C 1-3 Alkylene, C 1-3 Alkyl-NHC(O)-, C 1-3 It is optionally selected from the group consisting of alkyl-C(O)NH-, cyano group, or any combination thereof.

[0081] As used herein, the term "aryl," alone or in combination, refers to a monovalent aromatic hydrocarbon group (e.g., phenyl, naphthyl, or fluorenyl) containing 5 to 14 carbon atoms and optionally containing one or more fused rings. In the present disclosure, the term "aryl" refers to 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) with a substituent (e.g., an aryl mono-, di-, or tri-substituted with a substituent), where the substituent is, for example, an optionally deuterated C1-C6 alkyl, an optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH—, and any combination thereof.

[0082] In the present disclosure, the term "arylene," used alone or in combination, refers to a divalent aromatic hydrocarbon group (e.g., phenylene, naphthylene, or fluorenylene) containing 5 to 14 carbon atoms and optionally containing one or more fused rings. In the present disclosure, the term "arylene" refers to an optionally substituted arylene. Substituted arylene refers to an arylene substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent (e.g., an arylene mono-, di-, or tri-substituted with a substituent), where the substituent is, for example, deuterium, an optionally deuterated C1-C6 alkyl, an optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH—, and any combination thereof.

[0083] The term "cycloalkyl," as used herein, alone or in combination, refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) mono-, bi-, or polycyclic hydrocarbon group, and in some embodiments, has from 3 to 20 carbon atoms (i.e., C 3-20 cycloalkyl), or 3 to 15 carbon atoms (i.e., C 3-15 cycloalkyl), 3 to 12 carbon atoms (i.e., C 3-12 cycloalkyl), or 3 to 11 carbon atoms (i.e., C 3-11 cycloalkyl), or 3 to 10 carbon atoms (i.e., C 3-10 cycloalkyl), or 3 to 8 carbon atoms (i.e., C 3-8 cycloalkyl), or 3 to 7 carbon atoms (i.e., C 3-7 cycloalkyl), or 3 to 6 carbon atoms (i.e., C 3-6 The term "cycloalkyl" includes monocyclic, bicyclic, tricyclic, or polycyclic cycloalkyls, having from 3 to 20 carbon atoms. Representative examples of monocyclic cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Bicyclic, tricyclic, and polycyclic cycloalkyls include bridged cycloalkyls (e.g., C 5-20 Bridged cycloalkyl, C 5-15 Bridged cycloalkyl and C 7-15 bridged cycloalkyl), fused cycloalkyl (e.g., C 5-20 Fused cycloalkyl, C 5-15 Fused cycloalkyl, C 6-20 Fused cycloalkyl, C 6-15 Fused cycloalkyl, C 7-20 Fused cycloalkyl, C 7-15 Fused cycloalkyl and C 8-15 fused cycloalkyl) and spirocycloalkyl (e.g., C 5-20 Spirocycloalkyl, C 5-15 Spirocycloalkyl, C 6-20 Spirocycloalkyl, C 6-15 Spirocycloalkyl, C7-20 Spirocycloalkyl, C 7-15 Spirocycloalkyl and C 8-15 spirocycloalkyl), representative examples include decalinyl, octahydropentalenyl, octahydro-1H-indenyl, C 5-20 Spirocycloalkyl, C 5-15 Examples of "cycloalkyl" include, but are not limited to, spirocycloalkyl, adamantanyl, noradamantanyl, bornyl, and norbornyl (IUPAC systematic name: bicyclo[2.2.1]heptyl). As used herein, the "cycloalkyl" is optionally mono- or polysubstituted, such as, but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl. The substituents of the substituted "cycloalkyl" include deuterium, optionally deuterated C1-C6 alkyl, optionally deuterated C1-C6 alkyl, and optionally deuterated C1-C6 alkyl. 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino substituted C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 The term "C" refers to one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof. 3-6 Examples of "cycloalkyl" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, and cyclohexyl.

[0084] As used herein, the term "cycloalkylene," alone or in combination, refers to a saturated and partially unsaturated (e.g., containing one or more double bonds but not fully conjugated) mono-, bi-, tri-, or polycyclic hydrocarbon divalent radical having 3 to 20 carbon atoms (e.g., 3-15, 3-12, 3-11, 3-10, 3-8, 3-7, or 3-6 carbon atoms). The term "cycloalkylene" includes mono-, bi-, tri-, or polycyclic hydrocarbon divalent radicals having 3 to 20 (e.g., 3-15 or 3-12) carbon atoms. Representative examples of monocyclic cycloalkylenes include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, and cyclooctylene. Bicyclic, tricyclic and polycyclic cycloalkylenes include bridged cycloalkylenes (e.g., C 5-20 Bridged cycloalkylene, C 5-15 Bridged cycloalkylene and C 7-15 bridged cycloalkylene), fused cycloalkylene (e.g., C 5-20 Fused cycloalkylene, C 5-15 Fused cycloalkylene, C 6-20 Fused cycloalkylene, C 6-15 Fused cycloalkylene, C 7-20 Fused cycloalkylene, C 7-15 Fused cycloalkylene and C 8-15 fused cycloalkylenes), and spirocycloalkylenes (e.g., C 5-20 Spirocycloalkylene, C 5-15 Spirocycloalkylene, C 6-20 Spirocycloalkylene, C 6-15 Spirocycloalkylene, C 7-20 Spirocycloalkylene, C 7-15 Spirocycloalkylene and C 8-15 spirocycloalkylene), representative examples include decalinylene, octahydropentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H-indenylene, C 5-20 Spirocycloalkylene, C 5-15These include, but are not limited to, spirocycloalkylene, adamantanylene, noradamantanylene, and norbornylene (systematic name is bicyclo[2.2.1]heptylene). In the present disclosure, the "cycloalkylene" is optionally mono- or polysubstituted, such as, but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl. The substituents of the substituted "cycloalkylene" are optionally deuterium, optionally deuterated C1-C6 alkyl, optionally deuterated C1-C6 alkyl, and optionally deuterated C1-C6 alkyl. 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH-, and any combination thereof.

[0085] As used herein, the term "C" as used alone or in combination x-y The term "spirocycloalkylene" (where x and y are each integers) refers to a spirocycloalkylene containing x to y carbon atoms. 7-11 "Spirocycloalkylene" refers to a spirocycloalkylene containing 7 to 11 (e.g., 7-10, 7-9) carbon atoms. 5-20 Spirocycloalkylene is a 5-15 spirocycloalkylene," "C 7-15 Spirocycloalkylene" and "C 7-20 The term "C" includes "spirocycloalkylene." 7-11 Representative examples of "spirocycloalkylene" include, but are not limited to, spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene. 7-11"Spirocycloalkylene" can further include deuterium, optionally deuterated C1-C6 alkyl, optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 and optionally substituted with one or more substituents selected from the group consisting of alkyl, -C(O)NH-, or any combination thereof.

[0086] As used herein, the term "heterocyclyl" or "heterocyclic group," used alone or in combination, refers to a 3- to 20-membered monocyclic, bicyclic, tricyclic, or polycyclic, saturated or partially unsaturated (i.e., having one or more double bonds but not completely conjugated) cyclic hydrocarbon group containing one or more (e.g., including 1 to 5, or 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. In some embodiments, "heterocyclyl" refers to a 3-15-membered (optionally 3-14-membered, 3-12-membered, 3-11-membered, 3-10-membered, 3-9-membered, 3-8-membered, 3-7-membered, 3-6-membered, 3-5-membered, or 4-9-membered) monocyclic 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., 1-5, or 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. Examples of the term "heterocyclyl" include monocyclic heterocyclyl (e.g., 4- to 20-membered monocyclic heterocyclyl and 4- to 15-membered monocyclic heterocyclyl), bridged heterocyclyl (e.g., 5- to 20-membered bridged heterocyclyl, 5- to 15-membered bridged heterocyclyl, 7- to 20-membered bridged heterocyclyl, and 7- to 15-membered bridged heterocyclyl), fused heterocyclyl (e.g., 5- to 20-membered fused heterocyclyl and 5- to 15-membered fused heterocyclyl), spiroheterocyclyl (e.g., 5- to 20-membered spiroheterocyclyl and 5- to 15-membered spiroheterocyclyl), ), cyclic ester groups (i.e., lactones, for example, 4-15-membered, 4-14-membered, 4-13-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 5-15-membered, 5-10-membered, 5-8-membered, 6-15-membered, or 6-10-membered cyclic ester groups), and cyclic amide groups (i.e., lactam groups, for example, 4-15-membered, 4-14-membered, 4-13-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 5-15-membered, 5-10-membered, 5-8-membered, 6-15-membered, or 6-10-membered cyclic amide groups).Representative examples of single-ring heterocyclyls include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptan-1-yl), and diazacyclooctyl. Bicyclic, tricyclic, and polycyclic heterocyclyls include bridged heterocyclyls, fused heterocyclyls, and spiroheterocyclyls, and representative examples include, but are not limited to, 6-azabicyclo[3.1.1]heptan-3-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl, and azaspirocycloalkyl (e.g., 5- to 20-membered azaspirocycloalkyl, such as 3-azaspiro[5.5]undecan-3-yl). The heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri- or poly-substituted) as clearly defined, where the substituents are deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C. 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, C 1-4 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH— and any combination thereof.

[0087] As used herein, the term "nitrogen-containing monocyclic heterocyclyl," alone or in combination, refers to a 3- to 20-membered (optionally 3-15-membered, 3-14-membered, 3-12-membered, 3-11-membered, 3-10-membered, 3-9-membered, 3-8-membered, 3-7-membered, 3-6-membered, 3-5-membered, or 4-9-membered) monocyclic saturated or partially unsaturated (i.e., having one or more double bonds but not fully conjugated) monovalent cyclic hydrocarbon group containing one nitrogen atom and, optionally, one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. Representative examples of nitrogen-containing monocyclic heterocyclyls include, but are not limited to, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptan-1-yl), and diazacyclooctyl. The nitrogen-containing monocyclic heterocyclyls may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as specifically defined, where the substituents are deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, C 1-4 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH— and any combination thereof.

[0088] As used herein, the term "nitrogen-containing bridged heterocyclyl," as used alone or in combination, refers to a 3- to 20-membered (optionally 3- to 15-membered, 3- to 14-membered, 3- to 12-membered, 3- to 11-membered, 3- to 10-membered, 3- to 9-membered, 3- to 8-membered, 3- to 7-membered, 3- to 6-membered, 3- to 5-membered, or 4- to 9-membered) tricyclic saturated or partially unsaturated (i.e., having one or more double bonds but not completely conjugated) monovalent cyclic hydrocarbon group containing one nitrogen atom and optionally containing one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. Tricyclic heterocyclyl includes bridged heterocyclyl, such as, but not limited to, 6-azabicyclo[3.1.1]heptan-3-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, and 2,5-diazabicyclo[2.2.2]octan-2-yl. The nitrogen-containing bridged heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri- or poly-substituted) as clearly defined, where the substituents are deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo groups, optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, C 1-4 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH— and any combination thereof.

[0089] As used herein, the term "heterocyclylene," alone or in combination, refers to a 3- to 20-membered monocyclic, bicyclic, tricyclic, or polycyclic, saturated or partially unsaturated (i.e., having one or more double bonds but not completely 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 the group consisting of sulfur, oxygen, and nitrogen. In some embodiments, "heterocyclylene" may refer to a 3- to 15-membered (optionally 3- to 14-membered, 3- to 12-membered, 3- to 11-membered, 3- to 10-membered, 3- to 9-membered, 3- to 8-membered, 3- to 7-membered, 3- to 6-membered, 3- to 5-membered, or 4- to 9-membered) monocyclic 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., containing 1 to 5, or 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. Examples of the term "heterocyclylene" include monocyclic heterocyclylene (e.g., 4- to 20-membered monocyclic heterocyclylene and 4- to 15-membered monocyclic heterocyclylene), bridged heterocyclylene (e.g., 5- to 20-membered bridged heterocyclylene, 5- to 15-membered bridged heterocyclylene, 7- to 20-membered bridged heterocyclylene, and 7- to 15-membered bridged heterocyclylene), fused heterocyclylene (e.g., 5- to 20-membered fused heterocyclylene and 5- to 15-membered fused heterocyclylene), spiroheterocyclylene (e.g., 5- to 20-membered spiroheterocyclylene and 5- to 15-membered spiroheterocyclylene). divalent cyclic ester groups (i.e., lactones, for example, 4-15-membered, 4-14-membered, 4-13-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 5-15-membered, 5-10-membered, 5-8-membered, 6-15-membered, or 6-10-membered divalent cyclic ester groups), and divalent cyclic amide groups (i.e., divalent lactam groups, for example, 4-15-membered, 4-14-membered, 4-13-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 5-15-membered, 5-10-membered, 5-8-membered, 6-15-membered, or 6-10-membered divalent cyclic amide groups).Representative examples of monocyclic heterocyclylenes include, but are not limited to, azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclohexylene, and diazacycloheptanylene (e.g., 1,4-diazacycloheptanylene, 4,5-diazacycloheptanylene, 1,3-diazacycloheptanylene). Bicyclic heterocyclylene, tricyclic heterocyclylene, and polycyclic heterocyclylene include bridged heterocyclylene, fused heterocyclylene, and spiroheterocyclylene, and representative examples include, but are not limited to, 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene, and azaspirocycloalkylene (e.g., 5- to 20-membered azaspirocycloalkylene, such as 3-azaspiro[5.5]undecanylene). The heterocyclylene may be unsubstituted or substituted (e.g., mono-, di-, tri- or poly-substituted) as clearly defined, where the substituents are deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated C. 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, C 1-4 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH— and any combination thereof.

[0090] As used herein, the term "nitrogen-containing monocyclic heterocyclylene," used alone or in combination, refers to a 3- to 20-membered (optionally 3-15-membered, 3-14-membered, 3-12-membered, 3-11-membered, 3-10-membered, 3-9-membered, 3-8-membered, 3-7-membered, 3-6-membered, 3-5-membered, or 4-9-membered) monocyclic saturated or partially unsaturated (i.e., having one or more double bonds but not completely conjugated) divalent cyclic hydrocarbon group containing one nitrogen atom and, optionally, one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. Representative examples of nitrogen-containing monocyclic heterocyclylenes include, but are not limited to, piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azacycloheptylene, diazacycloheptanylene, azacyclooctylene, and diazacyclooctylene. The nitrogen-containing monocyclic heterocyclylenes may be unsubstituted or substituted as clearly defined (e.g., mono-, di-, tri-, or poly-substituted), where the substituents are deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, or optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, C 1-4 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH— and any combination thereof.

[0091] As used herein, the term "nitrogen-containing bridged heterocyclylene," used alone or in combination, refers to a 3- to 20-membered (optionally 3-15-membered, 3-14-membered, 3-12-membered, 3-11-membered, 3-10-membered, 3-9-membered, 3-8-membered, 3-7-membered, 3-6-membered, 3-5-membered, or 4-9-membered) tricyclic saturated or partially unsaturated (i.e., having one or more double bonds but not completely conjugated) divalent cyclic hydrocarbon group containing one nitrogen atom and, optionally, one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. Tricyclic heterocyclylenes include, but are not limited to, bridged heterocyclylenes such as 6-azabicyclo[3.1.1]heptanylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, 3,8-diazabicyclo[3.2.1]octanylene, and 2,5-diazabicyclo[2.2.2]octanylene. The nitrogen-containing bridged heterocyclylenes may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as specifically defined, where the substituents are deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, or optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, optionally deuterated C 1-6 Alkoxy, C 1-4 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-4 Alkyl-NHC(O)-, C 1-4 alkyl-C(O)NH— and any combination thereof.

[0092] As used herein, the term "alkenylene," alone or in combination, refers to a straight-chain or branched-chain divalent hydrocarbon group containing 2 to 8 (e.g., 2 to 6, 2 to 5, 2 to 4, preferably 2) carbon atoms and having one or more (e.g., 1 to 3, 1 to 2, or 1) carbon-carbon double bonds. Examples of alkenylene include, but are not limited to, vinylene (e.g., —CH═CH—), 1-propynylene, allylidene, 1-butenylene, 2-butenylene, 3-butenylene, isobutenylene, pentenylene, n-penta-2,4-dienylene, 1-methyl-but-1-enylene, 2-methyl-but-1-enylene, 3-methyl-but-1-enylene, 1-methyl-but-2-enylene, 2-methyl-but-2-enylene, 3-methyl-but-2-enylene, 1-methyl-but-3-enylene, 2-methyl-but-3-enylene, 3-methyl-but-3-enylene, and hexenylene.

[0093] As used herein, the term "bornane" (also referred to as 1,7,7-trimethylbicyclo[2.2.1]heptane; camphane; or bornylane) has the definition known to those skilled in the art. As used herein, "bornyl" refers to a monovalent radical of bornane, i.e., the radical remaining after one of the hydrogen atoms in bornane has been removed. Representative examples of "bornyl" include 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-3-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-4-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-5-yl, or 1,7,7-trimethylbicyclo[2.2.1]heptan-6-yl. [ka] or [ka] Including, but not limited to:

[0094] As used herein, the term "bicyclo[2.2.1]heptane" (also referred to as bicyclo[2.2.1]heptane) or "norbornane" has the definition known to those skilled in the art. As used herein, "bicyclo[2.2.1]heptyl" or "norbornyl" refers to the monovalent radical of bicyclo[2.2.1]heptane, i.e., the radical remaining after loss of one hydrogen atom from bicyclo[2.2.1]heptane. Representative examples of "bicyclo[2.2.1]heptyl" include, but are not limited to, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]heptan-3-yl, bicyclo[2.2.1]heptan-4-yl, bicyclo[2.2.1]heptan-5-yl, or bicyclo[2.2.1]heptan-6-yl.

[0095] As used herein, the term "bicyclo[2.2.1]heptene" (also referred to as bicyclo[2.2.1]heptene) has the definition known to those skilled in the art. As used herein, "bicyclo[2.2.1]heptenyl" refers to the monovalent radical of bicyclo[2.2.1]heptene, i.e., the radical remaining after removal of one hydrogen atom from bicyclo[2.2.1]heptene. Representative examples of "bicyclo[2.2.1]heptenyl" include, but are not limited to, bicyclo[2.2.1]hept-5-en-2-yl, bicyclo[2.2.1]hept-5-en-3-yl, or bicyclo[2.2.1]hept-5-en-7-yl.

[0096] In the text, "adamantane" (Tricyclo[3.3.1.1 3,7 ]decane) has a definition known to those skilled in the art, and its structural formula is, for example, [ka] As used herein, "adamantanyl" refers to a monovalent radical of adamantane, i.e., the radical remaining after any hydrogen atom in adamantane is removed. Representative examples of "adamantanyl" include, but are not limited to, 1-adamantanyl, 2-adamantanyl, 3-adamantanyl, 4-adamantanyl, 5-adamantanyl, 6-adamantanyl, 7-adamantanyl, 8-adamantanyl, 9-adamantanyl, or 10-adamantanyl.

[0097] As used herein, the term "noradamantane" (also referred to as octahydro-2,5-methanopentalene) has the definition known to those skilled in the art, and its structural formula is, for example: [ka] or [ka] As used herein, "noradamantanyl" refers to a monovalent group of noradamantane, i.e., the group remaining after any hydrogen atom in noradamantane is removed. Representative examples of "noradamantanyl" include, but are not limited to, 1-noradamantanyl, 2-noradamantanyl, 3-noradamantanyl, 4-noradamantanyl, 5-noradamantanyl, 6-noradamantanyl, 7-noradamantanyl, 8-noradamantanyl, or 9-noradamantanyl.

[0098] Salts or pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates, and polymorphs of the compounds of Formula (I), Formula (II), or Formula (III) according to the present disclosure are also included within the scope of the present disclosure.

[0099] In all embodiments of the present disclosure, the salts or pharmaceutically acceptable salts of the compounds of formula (I), formula (II) or formula (III) refer to non-toxic inorganic or organic acid and / or base addition salts. 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-gluceptate, glycolate, mucate, L-ascorbate, orotate, picrate, glycinate, alanine, arginine, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, methanesulfonate, ethanesulfonate, ethanedisulfonate, formate, acetate, 2,2-dichloroacetate, trimethylacetate, propionate, pentanoate, palmitate, triphenylacetate, 2-ethyl-succinate, Examples of the salt include iodate, nicotinate, L-pyroglutamate, L-proline salt, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecenoate, camphorate, camphorsulfonate, dodecylbenzenesulfonate, phosphate, thiocyanate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalenesulfonate, hydroxyacetate, and p-toluenesulfonate.

[0100] A "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, such as a filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickener, solvent, or sealant, that can carry or deliver a compound useful in the present disclosure into a patient's body to perform its desired function. Generally, such constructs are carried or delivered from one organ or part of the body to another organ or part of the body. A carrier must be "acceptable" in that it is compatible with the other ingredients of the formulation (including the compound useful in the present disclosure) and is not harmful to the patient. Some examples of substances used as pharmaceutically acceptable carriers include, but are not limited to, sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; surfactants, phosphate buffers; and other non-toxic compatible substances used in drug formulations.

[0101] In the present disclosure, the term "room temperature" refers to an ambient temperature, for example, a temperature of 20 to 30°C.

[0102] As used herein, "stereoisomers" refer to compounds that have the same chemical constitution but differ in the way the atoms or groups are arranged in space. Stereoisomers include enantiomers, non-enantiomers, conformational isomers (rotational isomers), geometric isomers (cis / trans) isomers, atropisomers, etc.

[0103] As used herein, the term "solvate" refers to an association or complex of one or more solvent molecules with a compound of the present invention. Examples of solvents include water, isopropanol, ethanol, methanol, DMSO, ethyl acrylate, acetic acid, and ethanolamine. The term "hydrate" refers to a complex where the solvent molecule is water.

[0104] As used herein, the term "chiral" refers to a molecule that has the property of not being superimposable on its mirror image, and "non-chiral" refers to a molecule that is superimposable on its mirror image.

[0105] As used herein, the term "enantiomers" refers to two isomers of a compound that are non-superimposable mirror images of one another.

[0106] As used herein, the term "non-enantiomer" refers to a stereoisomer that has two or more chiral centers and whose molecules are not mirror images of one another. Non-enantiomers have different physical properties, such as melting points, boiling points, spectral properties, and reactivities. Mixtures of non-enantiomers can be separated by high-resolution analytical procedures, such as electrophoresis and chromatography, e.g., HPLC.

[0107] The term "oxo" or "oxo group", as used herein, alone or in combination, refers to =O.

[0108] The terms "C(O)" or "C(=O)" or "C=O", used herein, alone or in combination, refer to carbonyl.

[0109] As used herein, the term "C" as used alone or in combination x-y The term "spirocycloalkyl" (where x and y are each integers) refers to a spirocycloalkyl containing x to y carbon atoms. 7-11 "Spirocycloalkyl" refers to a spirocycloalkylene containing 7 to 11 (e.g., 7-10, 7-9) carbon atoms. 5-15 "Spirocycloalkyl" is "C 7-11Representative examples of "spirocycloalkyl" include, but are not limited to, spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl. 7-11 "Spirocycloalkyl" can be further divided into C 1-3 Alkyl, halogenated C 1-3 Alkyl, C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 It is optionally substituted with one or more substituents selected from the group consisting of alkylamino, amino, oxo, halogen, hydroxy, cyano, or any combination thereof.

[0110] As used herein, the term "C" as used alone or in combination x-y The term "bridged cycloalkyl" (where x and y are each integers) refers to a bridged cycloalkyl containing x to y carbon atoms. 7-11 "Bridged cycloalkyl" refers to a bridged cycloalkyl containing 7 to 11 carbon atoms. 7-11 Representative examples of "bridged cycloalkyl" include, but are not limited to, adamantanyl, noradamantanyl, norbornyl (systematic name bicyclo[2.2.1]heptyl), and cubanyl. x-y "Bridged cycloalkyl" is C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 1-3 Alkoxy, halogen, halogenated C 1-3 Alkyl, C 1-3 It is optionally substituted with 1 to 10 substituents selected from the group consisting of alkylamino, amino, hydroxy, cyano, oxo groups, or any combination thereof.

[0111] As used herein, "p-menthane" (also referred to as p-methane) has the definition known to those skilled in the art, and its structural formula is, for example, [ka] As used herein, "p-menthanyl" refers to a monovalent radical of p-menthane, i.e., the radical remaining after any hydrogen atom on any carbon atom of p-menthane is removed. Representative examples include: [ka] , [ka] , [ka] , [ka] or [ka] Including, but not limited to:

[0112] As used herein, "m-menthane" (also referred to as m-methane) has the definition known to those skilled in the art, and its structural formula is, for example, [ka] As used herein, "m-menthanyl" refers to a monovalent radical of m-menthane, i.e., the radical remaining after any hydrogen atom on any carbon atom of m-menthane is removed. Representative examples include: [ka] , [ka] , [ka] , [ka] , [ka] , [ka] , [ka] or [ka] Including, but not limited to:

[0113] As used herein, "quinuclidine" (also referred to as "quinuclidine") has the chemical name 1-azabicyclo[2.2.2]octane, the definition known to those skilled in the art, and the structural formula thereof is, for example, [ka] As used herein, "quinuclidinyl" refers to a monovalent radical of quinuclidine, i.e., the radical remaining after any hydrogen atom on any carbon atom of quinuclidine is removed. Representative examples include: [ka] , [ka] , [ka] , [ka] , [ka] , [ka] , or [ka] Including, but not limited to:

[0114] Example In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure. The present disclosure may be practiced without some or all of these specific details. In other instances, well-known process operations will not be described in detail so as not to unnecessarily obscure the present disclosure. While the present disclosure will be described with reference to certain examples, it should be understood that the present disclosure is not intended to be limited by these examples.

[0115] The following abbreviations may be used throughout the specification and examples:

[0116] In the present invention, 1 The H NMR spectrum was measured using a Bruker 500 MHz nuclear magnetic resonance spectrometer. When CD3OD containing 0.1% TMS was used as the solvent, CD3OD (δ=3.31 ppm) was used as the internal standard, or when CDCl3 containing 0.1% TMS was used as the solvent, 1 H NMR spectra were obtained using CDCl3 (δ = 7.26 ppm) as an internal standard or DMSO-d6 containing 0.03% TMS as the solvent. 1H NMR spectra were measured using DMSO-d (δ = 2.50 ppm) as an internal standard. LC-MS spectra were measured using a Sciex API 2000 mass spectrometer equipped with an Agilent 1100 binary pump, DAD, and ELSD, or an Agilent 1260-6125B single quadrupole liquid chromatography mass spectrometer equipped with an Agilent 1260 quadrupole pump, DAD, and ELSD. Preparative HPLC was measured using a Shimadzu LC-20AP, and HPLC purity was measured using a Shimadzu LC-30AP or a Waters 1525. Unless otherwise specified, all reactions were performed under air and monitored by TLC or LC-MS.

[0117] The solvents and reagents are as follows:

[0118] The solvents used in the reaction, DCM, DMF, anhydrous EtOH, and anhydrous MeOH, were all purchased from Chinese Sinopharm Group. Preparative HPLC was performed using preparative-grade CH3CN and deionized water. Unless otherwise specified, other reaction substrates, reagents, and chemicals can be purchased directly from commercial channels or synthesized by methods known in the art.

[0119] Common synthesis methods The compounds of the present disclosure and / or pharmaceutically acceptable salts thereof can be synthesized using commercially available raw materials by synthetic techniques known in the art. The synthesis schemes described below illustrate the methods for preparing most of the compounds by way of examples. The starting materials or reagents used in each scheme are all commercially available or can be prepared by methods known to those skilled in the art. Those skilled in the art can prepare the compounds of formula (I) of the present disclosure in the form of salts, racemates, enantiomers, phosphates, sulfates, hydrochlorides, and pharmaceutical precursors using ordinary skill in the art.

[0120] Synthetic Scheme 1: [ka] Scheme 1

[0121] In Scheme 1, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 , (R a ) n and X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure, wherein ring A preferably represents cycloalkylene, heterocyclylene, heteroarylene, or arylene. The group U of substrate 1-1 represents a group capable of undergoing an amine alkylation reaction with an amino group, such as Br, Cl, I, -OMs, -OTs, or -ONs. Ring C of substrate 1-2 represents a nitrogen-containing heterocyclyl, and W in ring C represents CH, -CH=, or N.

[0122] The amine alkylation reaction in Scheme 1 may be carried out by conventional techniques and methods familiar to those skilled in the art. For example, the amine alkylation may be carried out in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at room temperature to 80°C.

[0123] For example, the procedure of Scheme 1 may be as follows: Substrate 1-1 (1.3 eq.) and substrate 1-2 (1.0 eq.) are dissolved in DMF, and then triethylamine (3.0 eq.) and sodium iodide (1.0 eq.) are added to the solution. The reaction mixture is stirred at 50°C for 0.5 to 24 hours. Completion of the reaction is detected by LCMS. The reaction mixture is filtered, and the filtrate is separated and purified by preparative high-performance liquid chromatography to obtain the target compound.

[0124] Synthetic Scheme 2: [ka] Scheme 2

[0125] In Scheme 2, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 , (R a ) n and X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure. Ring C of substrate 2-1 corresponds to the optionally substituted nitrogen-containing heterocyclyl represented by X1 in the compounds of formula (I) of the present disclosure. Group U of substrate 2-2 represents a group capable of undergoing an amine alkylation reaction with an amino, such as Br, Cl, I, OMs, OTs, or ONs.

[0126] The amine alkylation reaction in Scheme 2 may be carried out by conventional techniques and methods familiar to those skilled in the art. For example, the amine alkylation may be carried out in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at room temperature to 80°C.

[0127] For example, the procedure of Scheme 2 may be as follows. Substrate 2-2 (1.3 eq.) and substrate 2-1 (1.0 eq.) are dissolved in DMF, and then triethylamine (3.0 eq.) and sodium iodide (1.0 eq.) are added to the solution. The reaction mixture is stirred at 50°C for 0.5 to 24 hours. Completion of the reaction is detected by LCMS. The reaction mixture is filtered, and the filtrate is separated and purified by preparative high-performance liquid chromatography to obtain the target compound.

[0128] Synthetic Scheme 3: [ka] Scheme 3

[0129] In Scheme 3, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 , (R a ) nand X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure. Ring D of compound 2-1 is an optionally substituted C 6-10 The ring C corresponds to an arylene, and the ring C corresponds to an optionally substituted nitrogen-containing heterocyclyl represented by X1 in the compound of formula (I) of the present disclosure, and W in the ring C represents CH, -CH=, or N. The group W1 of the substrate 3-2 represents a group capable of undergoing an amine alkylation reaction with an amino, such as Br, Cl, I, OMs, OTs, or ONs.

[0130] The amine alkylation reaction in Scheme 3 may be carried out by conventional techniques and methods familiar to those skilled in the art. For example, the amine alkylation may be carried out in the presence of DIEA and sodium iodide, or triethylamine and sodium iodide, at room temperature to 80°C.

[0131] For example, the procedure of Scheme 3 may be as follows. Substrate 3-2 (1.3 eq.) and substrate 3-1 (1.0 eq.) were dissolved in DMF, and then triethylamine (3.0 eq.) and sodium iodide (1.0 eq.) were added to the solution. The reaction mixture was stirred at 50°C for 0.5 to 24 hours. Completion of the reaction was detected by LCMS. The reaction mixture was filtered, and the filtrate was separated and purified by preparative high-performance liquid chromatography to obtain the target compound.

[0132] Synthetic Scheme 4: [ka] Scheme 4

[0133] In Scheme 4, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 , (R a ) n and X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure. Ring D of compound 4-1 is an optionally substituted C 6-10Ring C corresponds to the optionally substituted nitrogen-containing heterocyclyl represented by X1 in the compound of formula (I) of the present disclosure, and W in ring C represents CH, -CH= or N.

[0134] Depending on the target compound, the required target compound can be obtained by appropriately modifying and adjusting the reaction substrates, reaction conditions (including reaction volume, temperature, time, etc.), post-treatment, etc. in Scheme 4 using techniques and methods well known to those skilled in the art. For example, depending on the target compound, ring D may not be present. The reductive amination reaction in Scheme 4 can be carried out using conventional techniques and methods well known to those skilled in the art. For example, the reductive amination reaction can be carried out in the presence of sodium triacetoxyborohydride and 1,2-dichloroethane, or sodium cyanoborohydride and 1,2-dichloroethane, at room temperature to 80°C.

[0135] For example, the procedure of Scheme 4 may be as follows.

[0136] Aldehyde substrate 4-2 (1.3 eq.) and substrate 4-1 (1.0 eq.) are dissolved in anhydrous 1,2-dichloroethane, and acetic acid (1 drop) is added to the solution. The reaction mixture is stirred at 50°C for 1 hour, after which sodium triacetoxyborohydride (2.0 eq.) is added to the solution, and the reaction mixture is stirred for 1 to 24 hours. Completion of the reaction is detected by LCMS. The reaction mixture is filtered, and the filtrate is separated and purified by preparative high-performance liquid chromatography to obtain the target compound.

[0137] Synthetic Scheme 5: [ka] Scheme 5

[0138] In Scheme 5, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 , (R a ) nX is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure, wherein ring A is preferably a cyclic hydrocarbon group having an unsaturated double bond, such as a heteroaryl, an aryl, or a cycloalkyl having an unsaturated double bond (e.g., cyclohexenylene). Ring C of substrate 5- corresponds to the heterocyclyl or cycloalkyl having an optionally substituted carbonyl represented by X1 in the compounds of formula (I) of the present disclosure.

[0139] The reductive amination reaction in Scheme 5 may be carried out by conventional techniques and methods familiar to those skilled in the art. For example, the reductive amination reaction may be carried out in the presence of sodium triacetoxyborohydride and 1,2-dichloroethane, or sodium cyanoborohydride and 1,2-dichloroethane, at room temperature to 80°C.

[0140] Synthetic Scheme 6: [ka] Scheme 6

[0141] In Scheme 6, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 , (R a ) n and X is as defined in the compound of formula (I) of the present disclosure and each subembodiment thereof, wherein ring A is preferably a cyclic hydrocarbon group having an unsaturated double bond, such as a heteroaryl, an aryl, or a cycloalkyl having an unsaturated double bond (e.g., cyclohexenylene). Ring C of substrate 6-2 corresponds to the optionally substituted nitrogen-containing heterocyclyl represented by X1 in the compound of formula (I) of the present disclosure, and W in ring C represents CH, -CH=, or N. Substrate 6-2 may be in the form of a free base or a salt thereof (e.g., hydrochloride, trifluoroacetate).

[0142] The amide condensation reaction in Scheme 6 may be carried out by conventional techniques and methods familiar to those skilled in the art. For example, the amide condensation reaction may be carried out in the presence of HATU, DIEA, and DMF, or HOAt, EDCI, TEA, and DCM, at room temperature to 80°C.

[0143] For example, the procedure of Scheme 6 may be as follows: Acid substrate 6-1 (1.05 eq.) and substrate 6-2 (1.0 eq.) are dissolved in DMF, and then HATU (1.5 eq.) and triethylamine (3.0 eq.) are added to the solution. The reaction mixture is stirred at 50°C for 1 to 24 hours. Completion of the reaction is detected by LCMS. The reaction mixture is filtered, and the filtrate is separated and purified by preparative high-performance liquid chromatography to obtain the target compound.

[0144] Synthetic Scheme 7: [ka] Scheme 7

[0145] In Scheme 7, Br may be located at the 4-, 5-, 6-, or 7-position on the benzene ring of the isoindolinyl, and the hydroxymethyl group of the resulting product is correspondingly located at the 4-, 5-, 6-, or 7-position on the benzene ring of the isoindolinyl. A is as defined herein for compounds of formula (I). (R a ) n is a group in which the benzene ring is n-number of R a Each R represents a substitution a are the same or different and each independently represent deuterium, fluorine, protected hydroxy, protected mercapto, nitro, protected amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, C 2-6 Alkenyl, or C 2-6n represents an integer of 0, 1, 2, or 3. X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure.

[0146] The coupling reaction in Step 1 of Scheme 7 may be carried out using conventional techniques and methods familiar to those skilled in the art. For example, the coupling reaction may be carried out in the presence of tetrakis(triphenylphosphine)palladium and DMF at 40°C to 100°C. The esterification reaction in Step 2 of Scheme 7 may be carried out using conventional techniques and methods familiar to those skilled in the art. Alternatively, if necessary, the reactant MsCl in Step 2 may be replaced with TsCl or NsCl, and compound 7-2 may be esterified with TsCl or NsCl to obtain the target compound having the corresponding OTs or ONs group.

[0147] For example, the procedure of Scheme 7 may be as follows: Step 1: Bromo substrate 7-1 (1.0 eq.) and (tributylstannyl)methanol (1.5 eq.) are dissolved in DMF, and tetrakis(triphenylphosphine)palladium (0.05 eq.) is added to the solution. Under N2 protection, the reaction mixture is heated to 100 °C and stirred for 48 h. Completion of the reaction is detected by thin-layer chromatography. The reaction mixture is cooled to 60 °C and filtered while hot to remove the black solid. The filtrate is concentrated under reduced pressure, and dichloromethane is added to the residue. Filtration affords the solid intermediate compound 7-2.

[0148] Step 2: Solid intermediate compound 7-2 (1.0 eq.) was dissolved in dimethyl sulfoxide / dichloromethane (1 / 9), and triethylamine (30 eq.) and methanesulfonyl chloride (1.5 eq.) were added to the reaction mixture in that order. The reaction mixture was stirred at room temperature for 1 hour. Completion of the reaction was detected by thin layer chromatography. Water was added to the reaction mixture, and the mixture was filtered. The solid was washed with water and dried to obtain the target compound.

[0149] Synthetic Scheme 8: [ka] Scheme 8

[0150] In Scheme 8, Br can be located at the 4-, 5-, 6-, or 7-position on the benzene ring of the isoindolinyl. (R a ) n is a group in which the benzene ring is n-number of R a Each R represents a substitution a are the same or different and each independently represent deuterium, fluorine, protected hydroxy, protected mercapto, nitro, protected amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, C 2-6 Alkenyl, or C 2-6 n represents an integer of 0, 1, 2, or 3. X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure.

[0151] The coupling reaction in Step 1 of Scheme 8 may be carried out using conventional techniques and methods familiar to those skilled in the art. For example, the coupling reaction may be carried out in the presence of a palladium catalyst and cesium carbonate at 40°C to 100°C.

[0152] For example, the procedure of Scheme 8 may be as follows: Step 1: Bromo substrate 8-1 (1.0 eq.) and substrate 8-2 (1.5 eq.) are dissolved in N,N-dimethylcarboxamide, and palladium catalyst (0.05 eq.) and cesium carbonate (2.0 eq.) are added to the solution. Under N2 protection, the reaction mixture is heated to 100 °C and stirred for 1 to 24 hours. Completion of the reaction is detected by thin-layer chromatography. The reaction mixture is cooled to room temperature, washed with water, extracted with dichloromethane, and the organic phases are combined, dried, filtered, and concentrated. The residue is purified by silica gel column chromatography to obtain intermediate product 8-3.

[0153] Step 2: Dissolve the intermediate product 8-3 obtained in the previous step in dichloromethane and add trifluoroacetic acid. Stir the reaction mixture at room temperature for 2 hours. Completion of the reaction is detected by LCMS, and the reaction mixture is concentrated under reduced pressure to give the desired product 8-4.

[0154] Synthetic Scheme 9: [ka] Scheme 9

[0155] In Scheme 9, Br can be located at the 4-, 5-, 6-, or 7-position on the benzene ring of the isoindolinyl. (R a ) n is a group in which the benzene ring is n-number of R a Each R represents a substitution a are the same or different and each independently represent deuterium, fluorine, protected hydroxy, protected mercapto, nitro, protected amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, C 2-6 Alkenyl, or C 2-6 n represents an integer of 0, 1, 2, or 3. X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure. The Suzuki coupling reaction and hydrogenation reduction reaction in steps 1-3 of scheme 9 may be carried out by conventional techniques and methods familiar to those skilled in the art.

[0156] For example, the procedure of Scheme 9 may be as follows: Step 1: Bromo substrate 9-1 (1.0 eq.) and substrate 9-2 (1.5 eq.) were dissolved in N,N-dimethylcarboxamide, and palladium catalyst (0.05 eq.) and cesium carbonate (2.0 eq.) were added to the solution. Under N2 protection, the reaction mixture was heated to 100 °C and stirred for 1-24 h. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was cooled to room temperature, washed with water, extracted with dichloromethane, and the combined organic phases were dried, filtered, and concentrated. The residue was purified by silica gel column chromatography to obtain intermediate product 9-3.

[0157] Route 9-1, Step 2: Dissolve the intermediate product 9-3 obtained in the previous step in tetrahydrofuran, add palladium on carbon, and flush the reaction vessel with hydrogen gas three times. Under a hydrogen gas atmosphere (1 atm), warm the reaction mixture to 50 °C and stir for 2 h. Completion of the reaction is detected by LCMS. The reaction mixture is filtered and concentrated under reduced pressure to give intermediate product 9-4.

[0158] Route 9-1, Step 3: Dissolve the intermediate product 9-4 obtained in the previous step in dichloromethane and add trifluoroacetic acid. Stir the reaction mixture at ambient temperature for 2 hours. Completion of the reaction is detected by LCMS, and the reaction mixture is concentrated under reduced pressure to give the desired product 9-5.

[0159] Route 9-2, Step 2: The intermediate product 9-3 obtained in the previous step is dissolved in dichloromethane and trifluoroacetic acid is added. The reaction is stirred at ambient temperature for 2 hours. Completion is detected by LCMS, and the reaction is concentrated under reduced pressure to give the desired product 9-6.

[0160] Synthetic Scheme 10: [ka] Scheme 10

[0161] In Scheme 10, (R a ) nand X are as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure. The group U of substrate 10-1 is a group capable of undergoing a Suzuki coupling reaction with the boronic acid (ester) substrate 10-2, such as Br, Cl, I, or OT. f The group Y of the boronic acid (ester) substrate 10-2 represents H or alkyl, and the ring D represents an optionally substituted C 6-10 The ring C corresponds to an arylene, and the ring C corresponds to an optionally substituted nitrogen-containing heterocyclyl represented by X1 in the compound of formula (I) of the present disclosure, and W on the ring C represents CH, -CH=, or N. The Suzuki coupling reaction may be carried out by conventional techniques and methods familiar to those skilled in the art, for example, in the presence of Pd(dppf)Cl2 and K2CO3 at 60°C to 80°C.

[0162] Synthetic Scheme 11: [ka] Scheme 11

[0163] Synthetic Scheme 12: [ka] Scheme 12

[0164] Synthetic Scheme 13: [ka] Scheme 13

[0165] Synthetic Scheme 14: [ka] Scheme 14

[0166] In Scheme 14, ring A, (R d1 ) m1 , ring B, (R d2 ) m2is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure, wherein ring A is preferably a cyclic hydrocarbon group having an unsaturated double bond, such as a heteroaryl, an aryl, or a cycloalkyl having an unsaturated double bond (e.g., cyclohexenylene). Group W of substrate 14-1 is a group capable of undergoing a Suzuki coupling reaction with boronic acid (ester) substrate 14-2, such as Br, Cl, I, or OT. f The group Y of the boronic acid (ester) substrate 14-2 represents H or alkyl.

[0167] Synthetic Scheme 15: [ka] Scheme 15

[0168] In Scheme 15, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure, wherein ring A is preferably a cyclic hydrocarbon group having an unsaturated double bond, such as a heteroaryl, an aryl, or a cycloalkyl having an unsaturated double bond (e.g., cyclohexenylene). The group W of the amine substrate 15-1 is a group capable of undergoing a Suzuki coupling reaction with the boronic acid (ester) substrate 15-2, such as Br, Cl, I, or OT. f The group Y of the boronic acid (ester) substrate 15-2 represents H or alkyl.

[0169] In some embodiments, the amino of the amine substrate 15-1 can be protected with a protecting group (e.g., Boc), and the resulting product 15-3 can be further deprotected using conditions such as HCl and ethyl acrylate, or TFA and DCM.

[0170] Synthetic Scheme 16: [ka] Scheme 16

[0171] In Scheme 16, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure, wherein ring A preferably represents cycloalkylene, heterocyclylene, heteroarylene, or arylene. The group W of substrate 16-1 is a group capable of undergoing a Suzuki coupling reaction with the boronic acid (ester) substrate 16-2, such as Br, Cl, I, or OT. f The group Y of the boronic acid (ester) substrate 16-2 represents H or alkyl. Ring C of the substrate 16-5 represents an optionally substituted nitrogen-containing heterocyclyl, which corresponds to the group X1 of the compound of formula (I) of the present disclosure.

[0172] Synthetic Scheme 17: [ka] Scheme 17

[0173] In Scheme 17, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure, wherein ring A preferably represents cycloalkylene, heterocyclylene, heteroarylene, or arylene. Ring C of substrate 17-3 represents an optionally substituted nitrogen-containing heterocyclyl and corresponds to group X1 of compounds of formula (I) of the present disclosure.

[0174] The reductive amination reaction in Step 1 and the deprotection reaction in Step 2 of Scheme 17 may be carried out using conventional techniques and methods familiar to those skilled in the art. For example, the reductive amination reaction may be carried out in the presence of sodium triacetoxyborohydride and 1,2-dichloroethane at room temperature to 80° C. The deprotection reaction may be carried out using TFA and DCM, or HCl and ethyl acrylate.

[0175] For example, the operation of Scheme 17 may be as follows: Step 1: Aldehyde substrate 17-1 (1.0 eq.) and the corresponding amine substrate 17-2 (1.0 eq.) were dissolved in 1,2-dichloroethane, followed by the addition of sodium triacetoxyborohydride (2.0 eq.). The reaction mixture was heated to 80°C and stirred for 2 hours. Completion of the reaction was confirmed by thin-layer chromatography. The reaction mixture was cooled to room temperature, quenched with water, and extracted with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography to obtain the product.

[0176] Step 2: Dissolve the product from the previous step in dichloromethane and add trifluoroacetic acid. Stir the reaction mixture at room temperature for 2 hours. Completion of the reaction is detected by LCMS. Concentrate the reaction mixture under reduced pressure to obtain the desired product.

[0177] Synthetic Scheme 18: [ka] Scheme 18

[0178] In Scheme 18, ring A, (R d1 ) m1 , ring B, (R d2 ) m2 is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure, wherein ring A preferably represents cycloalkylene, heterocyclylene, heteroarylene, or arylene. Ring C of substrate 18-3 represents an optionally substituted nitrogen-containing heterocyclyl and corresponds to group X1 of compounds of formula (I) of the present disclosure.

[0179] The oxidation reaction in Step 1 of Scheme 18 may be carried out using conventional techniques and methods familiar to those skilled in the art. For example, the oxidation reaction may be carried out using sodium hypochlorite, sodium dihydrogen phosphate dihydrate, and hydrogen peroxide. The amide condensation reaction and deprotection reaction in Step 2 of Scheme 18 may be carried out using conventional techniques and methods familiar to those skilled in the art. For example, the amide condensation reaction may be carried out in the presence of HATU and DIEA at room temperature to 80°C. The deprotection reaction may be carried out using TFA and DCM.

[0180] For example, the operation of Scheme 18 may be as follows: Step 1: Aldehyde substrate 18-1 (1.0 eq.) was dissolved in acetonitrile and water, followed by the addition of sodium hypochlorite (1.5 eq.), sodium dihydrogen phosphate dihydrate (0.2 eq.), and hydrogen peroxide (10 eq.). The reaction mixture was stirred at room temperature for 16 hours. Completion of the reaction was confirmed by thin-layer chromatography. Saturated sodium carbonate solution was added to the reaction mixture, which was then extracted with petroleum ether. The aqueous phase was adjusted to pH 6 with dilute hydrochloric acid and extracted with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to give the intermediate product acid 18-2.

[0181] Step 2 (1) Amide condensation reaction: Acid 18-2 (1.0 eq.) obtained in Step 1 and amine substrate 18-3 (1.2 eq.) are dissolved in N,N-dimethylcarboxamide, followed by the addition of triethylamine (3.0 eq.) and HATU (1.5 eq.). The reaction mixture is stirred at room temperature for 3 hours. Completion of the reaction is detected by thin-layer chromatography. The reaction mixture is washed with water and extracted with dichloromethane. The organic phases are combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the intermediate product.

[0182] Step 2(2) Deprotection: The product obtained in Step 2(1) is dissolved in dichloromethane and trifluoroacetic acid is added. The reaction mixture is stirred at room temperature for 2 hours. Completion of the reaction is detected by LCMS. The reaction mixture is concentrated under reduced pressure to obtain the desired product 18-4.

[0183] Synthetic Scheme 19: [ka] Scheme 19

[0184] In Scheme 19, Br may be located at the 4-, 5-, 6-, or 7-position on the benzene ring of the isoindolinyl. (R a ) n is a group in which the benzene ring is n-number of R a Each R represents a substitution a are the same or different and each independently represent deuterium, fluorine, protected hydroxy, protected mercapto, nitro, protected amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, optionally substituted C 3-6 Cycloalkyl, C 2-6 Alkenyl, or C 2-6 n represents an integer of 0, 1, 2, or 3. X is as defined in the compounds of formula (I) and each subembodiment thereof of the present disclosure. The coupling reaction and deprotection in Step 1-2 of Scheme 19 may be carried out by conventional techniques and methods familiar to those skilled in the art.

[0185] For example, the operation of Scheme 19 may be as follows: Step 1: Bromo substrate 19-1 (1.0 eq.) and tert-butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (1.5 eq.) were dissolved in N,N-dimethylcarboxamide, and palladium catalyst (0.05 eq.) and cesium carbonate (2.0 eq.) were added to the solution. Under N2 protection, the reaction mixture was heated to 100 °C and stirred for 1 to 24 hours. Completion of the reaction was confirmed by thin-layer chromatography. The reaction mixture was cooled to room temperature, washed with water, and extracted with dichloromethane. The organic phases were combined, dried, filtered, and concentrated. The residue was purified by silica gel column chromatography to give intermediate product 19-2.

[0186] Step 2: Dissolve the intermediate product 19-2 obtained in the previous step in dichloromethane and add trifluoroacetic acid. Stir the reaction mixture at room temperature for 2 hours. Completion of the reaction is detected by LCMS, and the reaction mixture is concentrated under reduced pressure to give the desired product 19-3.

[0187] Synthetic Scheme 20: [ka] Scheme 20

[0188] Synthetic Scheme 21: [ka] Scheme 21

[0189] Depending on the target compound, the required target compound can be obtained by appropriately modifying and adjusting each of the above schemes and their reaction substrates, reaction conditions (including reaction volume, temperature, time, etc.), post-treatment, etc. using techniques and methods well known to those skilled in the art. In addition, the obtained target compound can be further modified with substituents, etc. using methods well known to those skilled in the art to obtain other target compounds.

[0190] Example Intermediate Example 1: Preparation of 3-(5-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03234) [ka] The starting material, methyl 2,5-dimethylbenzoate (3.4 g, 20.6 mmol), was added to 100 mL of carbon tetrachloride, followed by N-bromosuccinimide (8.0 g, 45 mmol) and dibenzoyl peroxide (0.31 g, 1.26 mmol), in that order. The reaction mixture was refluxed at 80 °C for 12 h, cooled to room temperature, diluted with 100 mL of petroleum ether, and washed twice with water and once with saturated brine. The organic phase was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent (v / v): EA / PE = 0 / 1 to 1 / 20) to give the intermediate compound, methyl 2,5-bis(bromomethyl)benzoate (white solid, 5.0 g, yield: 76%).

[0191] Cesium carbonate (1.6 g, 5 mmol) was added to a mixture of 50 mL of 1,2-dichloroethane and 5 mL of hexafluoropropanol and stirred at 65 °C for 15 min. 3-Amino-2,6-piperidinedione hydrochloride (8.21 g, 5 mmol) and methyl 2,5-bis(bromomethyl)benzoate (1.6 g, 5 mmol) were added in this order and stirred at 65 °C for 12 h. After the reaction was completed, the reaction mixture was cooled to room temperature and washed with water. The organic phase was separated, and the solvent was evaporated under reduced pressure. The residue was separated by silica gel column chromatography (eluent (v / v): MeOH / DCM = 0 / 1-1 / 10). The resulting product was slurried in acetonitrile and further purified to give a white powder (455 mg, yield: 27%). 1H NMR (500 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.78 - 7.66 (m, 2H), 7.59 (dd, J = 7.9, 1.5 Hz, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.83 (s, 2H), 4.47 (d, J = 17.3 Hz, 1H), 4.34 (d, J = 17.4 Hz, 1H), 2.91 (ddd, J = 17.3, 13.6, 5.4 Hz, 1H), 2.68 - 2.55 (m, 1H), 2.39 (qd, J = 13.3, 4.5Hz, 1H), 2.01 (dtd, J = 12.7, 5.3, 4.7, 1.9 Hz, 1H). LCMS (ESI) m / z: C 14 H 14 BrN2O3 + [M+H] + , calculated value 337.0; measured value, 337.3.

[0192] Intermediate Example 2: Preparation of 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde (GTC00947) [ka] Step 1: Preparation of 2-chloro-4,4-dimethylcyclohex-1-ene-1-formaldehyde [ka] To a solution of DMF (4.9 mL, 63.4 mmol) in DCM (100 mL) was added POCl3 (5.5 mL, 59.4 mmol) dropwise at -10 °C. After the addition was complete, the reaction mixture was warmed to room temperature, and 3,3-dimethylcyclohexan-1-one (5.5 mL, 39.6 mmol) was added dropwise. The reaction mixture was refluxed for 18 hours. Completion of the reaction was detected by thin layer chromatography. The reaction mixture was cooled to room temperature and quenched with saturated NaHCO3 solution. The solution was washed with water (100 mL) and extracted with DCM (100 mL x 3). The combined organic phase was washed with saturated brine (50 mL x 1), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: petroleum ether / ethyl acrylate=50 / 1) to give a colorless oily compound, 2-chloro-4,4-dimethylcyclohex-1-ene-1-formaldehyde (5.9 g, yield: 86%). LCMS (ESI): CH 14 ClO + [M+H] + ,Calculated value,173.07, Measured value,173.3.

[0193] Step 2: Preparation of 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde 2-Chloro-4,4-dimethylcyclohex-1-ene-1-formaldehyde (1.5 g, 8.7 mmol) and p-fluorophenylboronic acid (1.8 g, 13.1 mmol) prepared in Step 1 were dissolved in dioxane (30 mL) and HO (3 mL). Pd(dppf)Cl (0.32 g, 0.43 mmol) and KCO (2.4 g, 17.4 mmol) were added to the solution in that order. The atmosphere in the reaction vessel was purged with N three times, and the reaction mixture was heated to 90 °C and stirred for 18 h. Completion of the reaction was confirmed by thin-layer chromatography (TLC). The reaction mixture was concentrated, and the residue was washed with water (100 mL) and extracted with ethyl acrylate (100 mL x 3). The combined organic phase was washed with saturated brine (50 mL x 1), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: petroleum ether) to give 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde (GTC00947) (1.2 g, yield: 59%) as a pale yellow oil. 1H NMR (400 MHz, DMSO) δ 9.39 (s, 1H), 7.39 - 7.31 (m, 2H), 7.25 (ddd, J = 8.8, 5.6, 2.4 Hz, 2H), 2.32 (d, J = 2.0 Hz, 2H), 2.30 - 2.23 (m, 2H), 1.44 (t, J = 6.4 Hz, 2H), 0.97 (s, 6H). LCMS (ESI): C 15 H 18 FO + [M+H] + ,Calculated value,233.13, Measured value,233.1.

[0194] Intermediate Example 3: Preparation of 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine [ka] Referring to the method of Scheme 16, Step 3, 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine was prepared.

[0195] Step 1: Preparation of tert-butyl 4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carboxylate [ka] To a solution of 2-(bromomethyl)-4'-chloro-1,1'-biphenyl (CAS number: 1001754-57-9) (0.8 g, 2.8 mmol) and N-Boc-piperazine (0.8 g, 4.3 mmol) in DCM (20 mL) was added TEA (1 mL, 5.7 mmol). The reaction mixture was stirred at room temperature for 2 hours. Completion of the reaction was confirmed by thin-layer chromatography (TLC). The reaction mixture was washed with water (50 mL) and extracted with DCM (50 mL x 3). The combined organic phase was washed with saturated brine (50 mL x 1), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: petroleum ether / ethyl acrylate = 4 / 1) to obtain the compound tert-butyl 4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carboxylate (780 mg, yield: 71%) as a white solid. LC / MS (ESI) m / z: C 22 H 28 ClN2O2 + [M+H] + , Calculated 387.2; Measured 387.2.

[0196] Step 2: Preparation of 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine To a solution of tert-butyl 4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carboxylate (780 mg, 2.0 mmol) obtained in Step 3 in dichloromethane (20 mL) was added HCl / dioxane (5 mL, 4M). The reaction mixture was stirred at room temperature for 2 hours. Completion of the reaction was detected by LCMS. The reaction mixture was concentrated under reduced pressure to give the compound 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine (650 mg, yield: 100%) as a white solid. LC / MS (ESI) m / z: C 17 H 20 ClN2 + [M+H] + , Calculated 287.2; Measured 287.2.

[0197] Intermediate Example 4: Preparation of 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione [ka] Referring to the method of Scheme 9, Step 1, 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione was prepared.

[0198] Step 1: Preparation of tert-butyl 4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)benzyl)piperazine-1-carboxylate 3-(5-Bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione (CAS No.: 1010100-26-1) (1 g, 3.1 mmol), (4-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)phenyl)boronic acid (CAS No.: 1190095-10-3) (1 g, 3.1 mmol) were dissolved in dioxane (20 mL). Pd(dppf)Cl (0.23 g, 0.31 mmol) and KCO (0.86 g, 6.2 mmol) were added to the solution in this order. The atmosphere in the reaction vessel was purged with N three times, and the reaction mixture was heated to 90 °C and stirred for 18 h. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was washed with water (100 mL) and extracted with DCM (100 mL x 3). The combined organic phase was washed with saturated brine (50 mL x 1), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: DCM / MeOH = 20 / 1) to obtain the compound tert-butyl 4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)benzyl)piperazine-1-carboxylate (810 mg, yield: 51%) as a pale yellow solid. LC / MS (ESI) m / z: C 29 H 35 N4O5 + [M+H] + , Calculated value 519.3; Measured value 519.3.

[0199] Step 2: Preparation of 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione To a solution of tert-butyl 4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)benzyl)piperazine-1-carboxylate (810 mg, 1.56 mmol) obtained in Step 1 in dichloromethane (20 mL) was added a solution of HCl in dioxane (4 mL, 4 M). The reaction mixture was stirred at room temperature for 2 hours. Completion of the reaction was detected by LCMS. The reaction mixture was concentrated under reduced pressure to give the compound 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione (740 mg, yield: 104%) as a white solid. LC / MS (ESI) m / z: C 24 H 27 N4O3 + [M+H] + , Calculated value 419.2; Measured value 419.2.

[0200] Intermediate Example 5: Preparation of (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate [ka] (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate (20.0 g, yield: 86%, off-white solid) was prepared by following the method of Scheme 7. LC / MS (ESI) m / z: C 15 H 17 N2O6S + [M+H] + , Calculated value 353.08; Measured value 353.1.

[0201] Intermediate Example 6: Preparation of (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate [ka] (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate (1.1 g, yield: 86%, pale yellow solid) was prepared by following the method of Scheme 7. LC / MS (ESI) m / z: C 15 H 16 FN2O6S + [M+H] + , Calculated value 371.07; Measured value 371.1.

[0202] Intermediate Example 7: Preparation of (2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate [ka] (2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate (1.1 g, yield: 86%, pale yellow solid) was prepared by following the method of Scheme 7. LC / MS (ESI) m / z: C 15 H 16 FN2O6S + [M+H] + , Calculated value 371.07; Measured value 371.1.

[0203] Intermediate Example 8: Preparation of (2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate [ka] (2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate (6.5 g, yield: 82%, off-white solid) was prepared by following the method of Scheme 7. LC / MS (ESI) m / z: C 15 H 16 FN2O6S + [M+H] + , Calculated value 371.07; Measured value 371.1.

[0204] Intermediate Example 9: Preparation of (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl methanesulfonate [ka] (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl methanesulfonate (4.5 g, yield: 85%, off-white solid) was prepared according to the method of Scheme 7. LC / MS (ESI) m / z: C 15 H 17 N2O6S + [M+H] + , Calculated value 353.08; Measured value 353.1.

[0205] Intermediate Example 10: Preparation of 3-(1-oxo-5-(piperidin-4-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione (GT-3423) [ka] 3-(1-oxo-5-(piperidin-4-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione (3.2 g, yield: 83%, brown solid) was prepared by referring to the method of Scheme 9. 1H NMR (400 MHz, DMSO) δ 10.98 (s, 1H), 9.01 - 8.55 (m, 2H), 7.73 - 7.60 (m, 1H), 7.51 - 7.41 (m, 1H), 7.35 (t, J = 7.4 Hz, 1H), 5.11 (dd, J = 13.2, 5.1 Hz, 1H), 4.38 (dt, J = 32.5, 16.6 Hz, 2H), 3.21 (d, J = 12.4 Hz, 2H), 2.92 (dt, J = 13.9, 6.4 Hz, 1H), 2.77 (dd, J = 22.7, 11.4 Hz, 2H), 2.64 (dd, LC / MS (ESI) m / z: C 19 H 23 N3O3 + [M+H] + , Calculated value 342.17; Measured value 342.2.

[0206] Intermediate Example 11: Preparation of 3-(1-oxo-5-(piperazin-1-ylamino)isoindolin-2-yl)piperidine-2,6-dione [ka] 3-(1-oxo-5-(piperazin-1-ylamino)isoindolin-2-yl)piperidine-2,6-dione (1.6 g, yield: 91%, light brown solid) was prepared by referring to the method of Scheme 8. 1H NMR (400 MHz, DMSO) δ 11.09 (s, 1H), 8.90 (s, 2H), 7.37 (d, J = 6.5 Hz, 2H), 5.09 (dd, J = 13.0, 5.3 Hz, 1H), 3.77 (s, 4H), 3.44 (s, LC / MS (ESI) m / z: cal. C 17 H 21 N5O3 + [M+H] + , Calculated 344.2; Measured 344.2.

[0207] Intermediate Example 12: Preparation of 3-(5-(azetidin-3-ylamino)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione [ka] 3-(5-(azetidin-3-ylamino)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (2.5 g, yield: 97%, light brown solid) was prepared by referring to the method of Scheme 8. 1H NMR (400 MHz, DMSO) δ 10.95 (s, 1H), 8.81 (d, J = 40.1 Hz, 2H), 7.39 (d, J = 10.5 Hz, 1H), 6.92 (d, J = 4.8 Hz, 1H), 6.79 (d, J = 7.5 Hz, 1H), 5.04 (dd, J = 13.3, 5.1 Hz, 1H), 4.48 (dd, J = 13.7, 6.9 Hz, 1H), 4.30 (dd, J = 10.0, 6.7 Hz, 3H), 4.18 (d, J = 16.9 Hz, 1H), 4.06 - 3.97 (m, 2H), 2.94 - 2.84 (m, 1H), 2.59 (d, J = 16.7 Hz, 1H), 2.36 (dt, J = 13.3, 8.8 Hz, 1H), 1.97 (dd, J = 10.4, 5.0 Hz, 1H). LC / MS (ESI) m / z: C 16 H 18 FN4O3 + [M+H] + , Calculated value 333.2; Measured value 333.1.

[0208] Intermediate Example 13: Preparation of 3-(5-(azetidin-3-ylidenemethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione [ka] 3-(5-(azetidin-3-ylidenemethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (730 mg, yield: 80%, brown solid) was prepared by referring to the method of Route 9-2 in Scheme 9. 1H NMR (400 MHz, DMSO) δ 10.99 (s, 1H), 9.08 (s, 2H), 7.72 (d, J = 7.9 Hz, 1H), 7.42 (s, 1H), 7.33 (d, J = 7.7 Hz, 1H), 6.56 (s, 1H), 5.11 (dd, J = 13.3, 5.0 Hz, 1H), 5.04 (s, 1H), 4.80 (s, 2H), 4.39 (dd, J = 48.0, 17.4 Hz, 2H), 2.92 (ddd, J = 18.6, 13.6, 5.4 Hz, 1H), 2.61 (dd, J = 32.9, 14.6 Hz, 2H), 2.46 - 2.28 (m, 1H), 2.06 - 1.95 (m, 1H). LC / MS (ESI) m / z: C 17 H 18 N3O3 + [M+H] + , Calculated value 312.13; Measured value 312.2.

[0209] Intermediate Example 14: Preparation of 3-(5-(azetidin-3-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione [ka] The method of Route 9-1 in Scheme 9 was carried out to prepare 3-(5-(azetidin-3-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (1.3 g, yield: 69%, brown solid). 1H NMR (400 MHz, DMSO) δ 10.98 (s, 1H), 8.60 (d, J = 36.3 Hz, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.44 (s, 1H), 7.35 (d, J = 8.1 Hz, 1H), 5.10 (dd, J = 13.3, 5.0 Hz, 1H), 4.47 - 4.26 (m, 2H), 3.96 (s, 2H), 3.74 (s, 2H), 3.10 (dd, J = 15.3, 7.4 Hz, 1H), 3.04 (d, J = 7.7 Hz, 2H), 2.98 - 2.84 (m, 1H), 2.60 (d, J = 17.8 Hz, 1H), 2.40 (dt, J = 13.6, 9.0 Hz, 2H), 2.01 (s, 1H). LC / MS (ESI) m / z: C 17 H 20 N3O3 + [M+H] + , Calculated value 314.15; Measured value 314.2.

[0210] Intermediate Example 15: Preparation of 3-(5-(hydroxy(3-hydroxyazetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione [ka] 3-(5-(hydroxy(3-hydroxyazetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione was prepared with reference to the method of Scheme 11.

[0211] Step 1: tert-Butyl 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methylene)azetidine-1-carboxylate (2 g, 4.86 mmol) was dissolved in THF (10 mL) and HO (10 mL). Potassium osmate (180 mg, 0.49 mmol) and N-methylmorpholine N-oxide (1.14 g, 9.72 mmol) were added to the solution. The reaction mixture was stirred at room temperature for 18 hours. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was quenched with saturated sodium metabisulfite (50 mL) and extracted with ethyl acrylate (50 mL x 3). The combined organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give a brown solid compound, tert-butyl 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)(hydroxy)methyl)-3-hydroxyazetidine-1-carboxylate (1.5 g, yield: 69%). LC / MS (ESI) m / z: C 22 H 28 N3O7 + [M+H] + , Calculated value 446.19; Measured value [M+H-56] + 390.2.

[0212] Step 2: To a solution of tert-butyl 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)(hydroxy)methyl)-3-hydroxyazetidine-1-carboxylate (1.5 g, 3.37 mmol) in dichloromethane (30 mL) was added TFA (10 mL). The reaction mixture was stirred at room temperature for 18 hours. Completion of the reaction was detected by LCMS. The reaction mixture was concentrated under reduced pressure, and ethyl acrylate / petroleum ether (20 mL, 1 / 1 volume ratio) was added to the residue, causing precipitation of a solid. The suspension was filtered and collected to give the desired compound (1 g, brown solid, yield: 67%). 1H NMR (400 MHz, DMSO) δ 10.99 (s, 1H), 8.66 (d, J = 68.6 Hz, 2H), 7.69 (d, J = 7.9 Hz, 1H), 7.60 (d, J = 6.5 Hz, 1H), 7.55 - 7.46 (m, 1H), 6.45 (s, 1H), 6.26 (s, 1H), 5.12 (dd, J = 8.6, 3.4 Hz, 1H), 4.38 (dd, J = 53.5, 17.2 Hz, 2H), 4.19 (d, J = 31.0 Hz, 2H), 3.79 (s, 1H), 3.57 (s, 1H), 2.91 (dd, J = LC / MS (ESI) m / z: C 17 H 20 N3O5 + [M+H] + , Calculated value 346.14; Measured value 346.2.

[0213] Intermediate Example 16: Preparation of 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione [ka] 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione (740 mg, yield: 104%, white solid) was prepared by following the method of Scheme 10. LC / MS (ESI) m / z: C 24 H 27 N4O3 + [M+H] + ,Calculated value 419.26; measured value 419.3.

[0214] Intermediate Example 17: Preparation of 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione [ka] Referring to the method of Scheme 19, 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.76 g, yield: 82%, light brown solid) was prepared. 1 H NMR (400 MHz, DMSO) δ 10.95 (s, 1H), 9.25 (d, J = 47.8 Hz, 2H), 7.58 (d, J = 8.3 Hz, 1H), 7.24 - 6.91 (m, 2H), 5.05 (dd, J = 13.0, 4.5 Hz, 1H), 4.54 (s, 2H), 4.27 (dt, J = 26.0, 13.0 Hz, 2H), 3.08 (s, 4H), 2.90 (t, J = 12.8 Hz, 1H), 2.59 (d, J = 17.0 Hz, 1H), 2.44 - 2.31 (m, 1H), 2.19 - 1.87 (m, 5H). LC / MS (ESI) m / z: C 19 H 22 N4O3 + [M+H] + , Calculated value 355.17; Measured value 355.2.

[0215] Intermediate Example 18: Preparation of 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione [ka] 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione was prepared with reference to the method in Scheme 12.

[0216] Step 1: (2-(2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate (1.0 g, 2.84 mmol) and N-Boc-piperazine (1.06 g, 5.68 mmol) were dissolved in anhydrous DCM (40 mL), and the reaction mixture was added with diisopropylethylamine (1.18 mL, 8.5 mmol) and sodium iodide (0.43 g, 2.84 mmol). The reaction mixture was stirred at room temperature for 18 hours. Completion of the reaction was detected by thin layer chromatography. The reaction mixture was washed with water (50 mL) and extracted with DCM (50 mL x 3). The combined organic phase was washed with saturated brine (50 mL x 1), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain a white solid compound, tert-butyl 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazine-1-carboxylate (780 mg, yield: 71%). LC / MS (ESI) m / z: C 23 H 31 N4O5 + [M+H] + , Calculated 443.2; Measured 443.2.

[0217] Step 2: tert-Butyl 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)piperazine-1-carboxylate (780 mg, 2.0 mmol) was dissolved in dichloromethane (20 mL), and a hydrochloric acid / dioxane solution (5.2 mL, 4M) was added to the solution. The reaction mixture was stirred at room temperature for 2 hours. Completion of the reaction was detected by LCMS. The reaction mixture was concentrated under reduced pressure to give the compound 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione (910 mg, yield: 105%) as a white solid. LC / MS (ESI) m / z: C 18 H 23 N4O3 + [M+H] + , Calculated value 343.2; Measured value 343.2.

[0218] Intermediate Example 19: Preparation of 3-(1-oxo-5-(piperidin-4-ylamino)isoindolin-2-yl)piperidine-2,6-dione [ka] 3-(1-oxo-5-(piperidin-4-ylamino)isoindolin-2-yl)piperidine-2,6-dione was prepared with reference to the method of Scheme 13.

[0219] Step 1: 3-(5-Amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (CAS number: 191732-70-4) (2 g, 7.71 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (3.1 g, 15.43 mmol) were dissolved in dichloromethane (30 mL) at 25 °C. Acetic acid (10 mL) was added to the reaction mixture. The reaction mixture was cooled to 0 °C and stirred for 2 hours. 2-Methylpyridine borane complex (1.64 g, 15.43 mmol) was added to the reaction mixture, followed by stirring for 48 hours. Completion of the reaction was confirmed by thin-layer chromatography. The reaction mixture was quenched with saturated sodium bicarbonate solution (30 mL) and adjusted to pH 8, resulting in the precipitation of a black solid. Filtration, washing of the filter cake with ethyl acrylate, and collection of the solid gave the intermediate product tert-butyl 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)amino)piperidine-1-carboxylate (2.4 g, black solid, yield: 70%). 1H NMR (400 MHz, DMSO) δ 10.93 (s, 1H), 7.39 (d, J = 8.2 Hz, 1H), 6.69 (s, 2H), 6.27 (d, J = 7.5 Hz, 1H), 5.02 (d, J = 8.8 Hz, 1H), 4.21 (dd, J = 51.6, 16.5 Hz, 2H), 3.89 (d, J = 11.4 Hz, 2H), 3.52 (s, 2H), 2.92 (d, J = 12.2 Hz, 4H), 2.59 (d, J = 17.2 Hz, 1H), 2.35 (d, J = 12.0Hz, 1H), 1.94 - 1.77 (m, 3H), 1.41 (s, 9H). LCMS (ESI)m / z: C 23 H 31 N4O5 + [M+H] + , Calculated value 443.22; Measured value 443.3.

[0220] Step 2: To a solution of tert-butyl 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)amino)piperidine-1-carboxylate (2.3 g, 3.64 mmol) in dichloromethane (30 mL) was added TFA (10 mL). The reaction mixture was stirred at room temperature for 1 hour. Completion of the reaction was detected by LCMS. The reaction mixture was concentrated under reduced pressure, and the residue was purified by reverse phase column to give 3-(1-oxo-5-(piperidin-4-ylamino)isoindolin-2-yl)piperidine-2,6-dione (229 mg, yield: 14%). 1 H NMR (400 MHz, DMSO) δ 10.93 (s, 1H), 8.70 - 8.32 (m, 2H), 7.48 - 7.33 (m, 1H), 6.80 - 6.61 (m, 2H), 5.02 (dd, J = 13.3, 5.1 Hz, 1H), 4.22 (d, J = 34.3 Hz, 2H), 3.64 (t, J = 9.9 Hz, 1H), 3.33 (d, J = 12.7 Hz, 2H), 3.03 (dd, J = 21.7, 11.5 Hz, 2H), 2.95 - 2.82 (m, 1H), 2.59 (d, J = 16.8 Hz, 1H), 2.35 (dt, J = 13.2, 8.8 Hz, 1H), 2.08 (d, J = 13.1 Hz, 2H), 1.99 - 1.90 (m, 1H), 1.57 (dd, J = 21.5, 10.5 Hz, 2H). LC / MS (ESI) m / z: C 18 H 23 N4O3 + [M+H] + , Calculated value 343.18; Measured value 343.10.

[0221] Intermediate Example 20: Preparation of 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxylic acid (GTC00260) [ka] To a 250 mL single-neck flask, 3-(5-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione (9.0 g, 27.851 mmol), palladium acetate (0.19 g, 0.836 mmol), the ligand Xantphos (16.12 g, 27.851 mmol), formic acid (3.85 g, 83.553 mmol), and N,N'-dicyclohexylenecarbodiimide (1.15 g, 5.570 mmol) were added in this order at room temperature. After stirring for 1 minute, triethylamine (7.764 mL, 55.702 mmol) was added. The atmosphere in the reaction vessel was purged with nitrogen gas three times, and the reaction mixture was heated to 100 °C and stirred for 3 hours. Completion of the reaction was detected by TLC. The reaction mixture was filtered to remove solids, and the filtrate was concentrated to give the crude product, which was slurried with dichloromethane, filtered, washed with water, and dried under vacuum to give GTC00260 (white solid, 5.96 g, 74.24% yield). 1 H NMR (400 MHz, DMSO) δ 13.33 (s, 1H), 11.01 (s, 1H), 8.17 (s, 1H), 8.08 (dd, J = 7.9, 1.2 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 5.15 (dd, J = 13.3, 5.1 Hz, 1H), 4.48 (dd, J = 50.2, 17.7 Hz, 2H), 3.01 - 2.89 (m, 1H), 2.61 (d, J = 16.6 Hz, 1H), 2.41 (qd, J = 13.2, 4.4 Hz, 1H), 2.03 (ddd, J = 10.2, 5.2, 3.1 Hz, 1H). LCMS (ESI): C 14 H 13 N2O5 + [M+H] + ,Calculated value: 289.07; Measured value: 289.1.

[0222] Intermediate Example 21: Preparation of 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid (GTC00923) [ka] At room temperature, 1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxylic acid (9.0 g, 46.843 mmol), 3-aminopiperidine-2,6-dione hydrochloride (6.00 g, 46.843 mmol), sodium acetate (11.53 g, 140.530 mmol), and 100 ml of acetic acid were added to a 250 mL single-neck flask in this order. The reaction mixture was heated to 90 °C and stirred for 4 hours. Completion of the reaction was detected by TLC. The reaction mixture was concentrated to obtain the crude product. The crude product was slurried with dichloromethane, and the solid was filtered, washed with water, and dried under vacuum to obtain GTC00923 (blue solid, 12.5 g, 88.29% yield). 1 H NMR (400 MHz, DMSO) δ 13.74 (s, 1H), 11.15 (s, 1H), 8.40 (dd, J = 7.8, 1.4 Hz, 1H), 8.27 (d, J = 0.5 Hz, 1H), 8.04 (d, J = 7.8 Hz, 1H), 5.20 (dd, J = 12.8, 5.4 Hz, 1H), 2.99 - 2.84 (m, 1H), 2.69 - 2.59 (m, 1H), 2.54 (dd, J = 13.3, 4.3 Hz, 1H), 2.15 - 2.03 (m, 1H). LCMS (ESI): C 14 H 11 N2O6 + [M+H] + ,Calculated value: 303.05; Measured value: 303.1.

[0223] Intermediate Example 22: Preparation of 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carboxylic acid (GTC00948) [ka] 4'-Fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carboxylic acid was prepared by following the method in Scheme 18, Step 1.

[0224] A solution of 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenylbiphenyl]-2-formaldehyde (GTC00947) (25 g, 107.619 mmol) in acetonitrile (100 mL), sodium dihydrogen phosphate (3.36 g, 27.981 mmol), water (140 mL), hydrogen peroxide (24.39 g, 215.239 mmol), and aqueous sodium hypochlorite (13.63 g, 150.667 mmol) was added to a 500 mL single-neck flask at room temperature, in that order, and the reaction mixture was stirred overnight at room temperature. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was washed with water (400 mL) and extracted with ethyl acrylate (500 mL x 3). The resulting organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give compound GTC00948 (white solid, 20 g, 74.84% yield). 1H NMR (400 MHz, DMSO) δ 12.03 (s, 1H), 7.34 - 7.00 (m, 4H), 2.35 (t, J = 6.4 Hz, 2H), 2.09 (s, 2H), 1.42 (t, J = 6.4 Hz, 2H), 0.96 (s, 6H). LCMS (ESI): C 17 H 21 FNO2 + [M+H+CH3CN] + ,Calculated value,290.12, Measured value,290.1. Intermediate Example 23: Preparation of (4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)(piperazin-1-yl)methanone (GTC00935) [ka] (4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)(piperazin-1-yl)methanone was prepared according to the method of Scheme 18, Step 2.

[0225] Step 2(1): To a 100 mL single-neck flask at room temperature, a solution of 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carboxylic acid (1.1 g, 4.16 mmol) and tert-butyl piperazine-1-carboxylate (0.85 g, 4.57 mmol) in N,N-dimethylcarboxamide (20 mL) was added, followed by the addition of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (2.37 g, 4.57 mmol) and N,N-diisopropylethylamine (1.61 g, 12.46 mmol). The air in the reaction vessel was purged with nitrogen gas three times, and the reaction mixture was stirred overnight at room temperature. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was washed with water (40 mL) and extracted with ethyl acrylate (100 mL x 3). The resulting organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / ethyl acrylate = 10 / 1 to 2 / 1) to give tert-butyl 4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazine-1-carboxylate (colorless oil, 1.4 g, yield 85.37%). LCMS (ESI): C 24 H 33 ClN2NaO3 + [M+Na] + ,Calculated value,455.21, Measured value,455.2.

[0226] Step 2(2): At room temperature, a 100 mL one-neck flask was charged with a solution of tert-butyl 4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazine-1-carboxylate (1.3 g, 3.00 mmol) in ethyl acrylate (20 mL) and a solution of hydrochloric acid in ethyl acrylate (40 mL, 3 M). The air in the reaction vessel was purged with nitrogen gas once, and the reaction mixture was stirred at room temperature for 3 hours. Completion of the reaction was detected by LC / MS. The reaction mixture was concentrated under reduced pressure to give compound GTC00935 (white solid, 956 mg, 95.7% yield).1 H NMR (400 MHz, DMSO) δ 7.38 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 3.25 (s, 1H), 3.11 (d, J = 38.0 Hz, 2H), 2.88 (s, 1H), 2.53 (s, 1H), 2.47 - 2.31 (m, 3H), 2.22 (s, 1H), 2.07 (d, J = 17.6 Hz, 1H), 1.90 (d, J = 17.2 Hz, 1H), 1.78 (s, 1H), 1.43 (dd, J = 14.0, 6.4 Hz, 2H), 0.98 (d, J = 10.4 Hz, 6H). LCMS (ESI) C 19 H 26 ClNO + [M+H] + : Calculated value 333.17, measured value 333.2.

[0227] Intermediate Examples 24-62 The following intermediate compounds were prepared by referring to the methods of Scheme 18, or Step 2 of Scheme 18, or Intermediate Examples 22-23.

[0228] Table 2. Compounds of Intermediate Examples 24-62 [Table 197] [Table 198] [Table 199] [Table 200] [Table 201] [Table 202] [Table 203] Table 204 Table 205 Table 206 Table 207 Table 208 Table 209 Table 210 Table 211 Table 212 Table 213 Table 214 Table 215 Table 216 Table 217 Table 218 Table 219 Table 220 [Table 221] [Table 222] [Table 223]

[0229] Intermediate Example 63: Preparation of N-(4'-chloro-[1,1'-biphenyl]-2-yl)piperidin-4-amine hydrochloride [ka] N-(4'-chloro-[1,1'-biphenyl]-2-yl)piperidin-4-amine hydrochloride was prepared with reference to the method of Scheme 20.

[0230] Step 1: 4'-Chloro-[1,1'-biphenyl]-2-amine (980 mg, 4.81 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (1150 mg, 5.77 mmol) were dissolved in 1,2-dichloroethane (10 mL) at room temperature. Acetic acid (0.5 mL) was added to the reaction mixture, and the mixture was stirred for 1 hour. Sodium triacetoxyborohydride (2039 mg, 9.62 mmol) was then added to the solution, and the mixture was stirred for 15 hours. Completion of the reaction was confirmed by LCMS. The reaction mixture was washed with water (50 mL) and extracted with DCM (50 mL x 3). The combined organic phase was washed with saturated brine (50 mL x 1), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was slurried with petroleum ether / ethyl acrylate (5:1, 100 mL) and filtered to give the intermediate product tert-butyl 4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidine-1-carboxylate (1.9 g, yield: 94%) as a yellow solid. LCMS (ESI): C 22 H 27 ClN2O2 + [M+H] +, Calculated value 387.18; Measured value 387.2.

[0231] Step 2: At room temperature, tert-butyl 4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidine-1-carboxylate (1.9 g, 3.83 mmol) was dissolved in dichloromethane, and a hydrochloric acid / dioxane solution (15 mL, 4 M) was added to the solution. The reaction mixture was stirred at room temperature for 1 hour. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was concentrated under reduced pressure, and the residue was slurried with petroleum ether / ethyl acrylate (5:1, 100 mL) and filtered to give the product N-(4'-chloro-[1,1'-biphenyl]-2-yl)piperidin-4-amine hydrochloride (500 mg, yield: 45%) as a white solid. 1 H NMR (400 MHz, DMSO) δ 9.35 - 8.75 (m, 2H), 7.47 (dd, J = 28.8, 8.3 Hz, 4H), 7.24 (t, J = 7.7 Hz, 1H), 7.04 (d, J = 7.4 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.81 (t, J = 7.3 Hz, 1H), 3.59 - 3.46 (m, 1H), 3.21 (d, J = 12.7 Hz, 2H), 2.92 (dd, J = 22.1, 11.4 Hz, 2H), 1.99 (d, J = 11.9 Hz, 2H), 1.59 (q, J = 10.0 Hz, 2H). LCMS (ESI): C 22 H 27 ClN2O2 + [M+H] + ,Calculated value 287.12; Measured value 287.2.

[0232] Intermediate Example 64: Preparation of 4-(chloromethyl)-3-(4-chlorophenyl)pyridine [ka] 4-(chloromethyl)-3-(4-chlorophenyl)pyridine was prepared according to the method of Scheme 21.

[0233] At room temperature, (3-(4-chlorophenyl)pyridin-4-yl)methanol (490 mg, 2.23 mmol) was dissolved in dichloromethane (10 mL). The reaction mixture was cooled to 0°C, and thionyl chloride (1.5 mL, 20.68 mmol) was added dropwise. After the addition, the mixture was gradually warmed to room temperature and stirred for 1.5 hours. Completion of the reaction was detected by LCMS. The reaction mixture was concentrated under reduced pressure to give 4-(chloromethyl)-3-(4-chlorophenyl)pyridine (415 mg, 78.1% yield, brown solid). 1 H NMR (400 MHz, DMSO) δ8.79(d,J = 4.8 Hz,1H),8.69(s,1H),7.92(s,1H),7.59(dd,J = 33.2,8.2 Hz,4H),4.78(s,2H). LCMS (ESI) C 12 H9Cl2N + , [M+H] + , Calculated value 238.01; Measured value 238.0.

[0234] Intermediate Example 65: Preparation of 1-(2-(5-chloropyridin-2-yl)benzyl)piperazine hydrochloride (GTC01002) [ka] 1-(2-(5-chloropyridin-2-yl)benzyl)piperazine hydrochloride was prepared with reference to the method in Scheme 15.

[0235] At room temperature, in a 30 mL sealed tube, (2-((4-(tert-butoxycarbonyl)piperazin-1-yl)methylphenyl)boronic acid (CAS: 1012785-48-6) (300 mg, 0.746 mmol) and 2-bromo-5-chloropyridine (250 mg, 1.299 mmol) were dissolved in ethanol (3 mL), toluene (3 mL), and water (3 mL), and tetrakis(triphenylphosphine)palladium (62.55 mg, 0.054 mmol) and sodium carbonate (229.49 mg, 2.165 mmol) were added to the solution. The air in the reaction bottle was purged with nitrogen gas. The reaction mixture was microwave-induced at 130°C for 15 minutes. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was repeated three times, and the combined reaction mixture was concentrated under reduced pressure, washed with water, extracted with ethyl acrylate, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by column chromatography (petroleum ether / ethyl acrylate = 1 / 0 to 10 / 1) to give tert-butyl 4-(2-(5-chloropyridin-2-yl)benzyl)piperazine-1-carboxylate (yellow solid, 110 mg, yield 12.1%). LCMS (ESI): C 21 H 26 ClN3O2 + [M+H] + ,Calculated value,388.17, Measured value,388.2.

[0236] To a 100 mL one-neck flask, tert-butyl 4-(2-(5-chloropyridin-2-yl)benzyl)piperazine-1-carboxylate (110 mg, 0.284 mmol) and a solution of hydrochloric acid in ethyl acrylate (5 mL, 3 M) were added at room temperature, and the reaction mixture was stirred at room temperature for 1 hour. Completion of the reaction was detected by LC / MS. The reaction mixture was filtered and dried to give compound GTC01002 (white solid, 68 mg, yield 73.84%). 1H NMR (400 MHz, MeOD-d4) δ 8.92 (d,J = 2.0 Hz, 1H), 8.15 (dd,J = 8.6, 2.4 Hz, 1H), 7.95 - 7.87 (m, 2H), 7.73 (ddd,J = 9.2, 8.0, 1.2 Hz, 2H), 7.64 (td,J = 7.6, 1.2 Hz, 1H), 4.55 (s, 2H), 3.75 (d,J = 5.2 Hz, 4H), 3.72 (d,J = 5.0 Hz, 4H), 2.02 (d,J = 3.6 Hz, 1H). LCMS (ESI) C 16 H 18 ClN3 + [M+H] + : Calculated value 288.12, measured value 288.2.

[0237] Intermediate Examples 66-79 The following intermediate compounds were prepared by reference to the methods of Scheme 15 or Intermediate Example 65.

[0238] Table 3. Compounds of Intermediate Examples 66-79 [Table 224] [Table 225] [Table 226] [Table 227] [Table 228] [Table 229] [Table 230] [Table 231]

[0239] Intermediate Example 80: Preparation of 1-((4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-en-1-yl)methyl)piperazine (GTC00924) [ka] Referring to Step 1 of Scheme 16 and the method of Scheme 17, 1-((4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-en-1-yl)methyl)piperazine was prepared.

[0240] 1, 4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-ene-1-formaldehyde was prepared by referring to the method in Step 1 of Scheme 16.

[0241] To a 100 mL single-neck flask, 2-bromo-4,4-dimethylcyclohex-1-ene-1-formaldehyde (1.0 g, 4.63 mmol), thiophen-2-ylboronic acid (712 mg, 5.56 mmol), potassium carbonate (1.6 g, 11.56 mmol), tetrabutylammonium bromide (75 mg, 0.232 mmol), and water / chloroform (12 mL, 5:1) were added in this order at room temperature. Then, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (170 mg, 0.232 mmol) was added to the reaction mixture. The air in the reaction vessel was purged with nitrogen gas three times, and the reaction mixture was gradually heated to 110 °C and stirred for 40 min. Completion of the reaction was confirmed by thin-layer chromatography. The reaction was quenched with water, extracted with ethyl acrylate, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / ethyl acrylate = 10 / 1 to 2 / 1) to give 4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-ene-1-formaldehyde (white solid, 660 mg, yield 65.8%). LCMS (ESI): C 13 H 16 OS + [M+H]+ ,Calculated value,221.09, Measured value,221.1.

[0242] 2, 1-((4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-en-1-yl)methyl)piperazine was prepared by referring to the method of Scheme 17.

[0243] To a 50 mL one-neck flask, 4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-ene-1-formaldehyde (560 mg, 2.55 mmol), tert-butyl piperazine-1-carboxylate (710 mg, 3.82 mmol), and dichloroethane (10 mL) were added in this order at room temperature. The reaction mixture was stirred at room temperature for 20 minutes, followed by the addition of sodium triacetoxyborohydride (1.08 g, 5.09 mmol). The reaction mixture was stirred at room temperature for 3 hours. Completion of the reaction was detected by thin-layer chromatography (TLC). Water was added to quench the reaction. The reaction mixture was extracted with ethyl acrylate, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / ethyl acrylate = 10 / 1 to 2 / 1) to give tert-butyl 4-((4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-en-1-yl)methyl)piperazine-1-carboxylate (white solid, 430 mg, yield 36.70%). LCMS (ESI): C 22 H 34 N2O2S + [M+H] + ,Calculated value,391.23, Measured value,391.5.

[0244] To a 50 mL one-neck flask was added a solution of tert-butyl 4-((4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-en-1-yl)methyl)piperazine-1-carboxylate (430 mg, 1.102 mmol) in ethyl acrylate (8 mL) at room temperature, followed by a solution of hydrochloric acid in ethyl acrylate (16 mL, 3 M). The reaction mixture was stirred at room temperature for 2 hours. Completion of the reaction was detected by LC / MS. The reaction mixture was concentrated under reduced pressure to give compound GTC00924 (white solid, 345 mg, 97% yield). 1 HNMR (400 MHz, D2O) δ 7.42 (d, J = 5.1 Hz, 1H), 7.06 - 7.01 (m, 1H), 6.87 (d, J = 3.4 Hz, 1H), 3.97 (s, 2H), 3.47 (d, J = 4.5 Hz, 4H), 3.36 (s, 4H), 2.24 - 2.14 (m, 4H), 1.45 (t, J = 6.2 Hz, 2H), 0.90 (s, 6H). LCMS (ESI) C 17 H 26 N2S + [M+H] + : Calculated value 291.18, measured value 291.2.

[0245] Intermediate Examples 81-91 The following intermediate compounds were prepared by reference to the method of Intermediate Example 80.

[0246] Table 4. Compounds of Intermediate Examples 81-91 [Table 232] [Table 233] [Table 234] [Table 235] [Table 236] [Table 237]

[0247] Intermediate Example 92: Preparation of 1-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazine hydrochloride (GTC01018) [ka] 1-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazine hydrochloride was prepared with reference to the method of Scheme 17.

[0248] In a 100 mL one-neck flask, 4'-chloro-[1,1'-biphenyl]-4-formaldehyde (1.1 g, 5.09 mmol) and tert-butyl piperazine-1-carboxylate (1.14 g, 6.11 mmol) were added to dichloroethane (16 mL) at room temperature, and sodium triacetoxyborohydride (1.62 g, 7.64 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 3 hours. Completion of the reaction was detected by thin-layer chromatography. The reaction mixture was quenched with water (20 mL), and ethyl acrylate (20 mL x 3) was extracted. The resulting organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / ethyl acrylate=10 / 1 to 2 / 1) to give tert-butyl 4-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazine-1-carboxylate (white solid, 1.4 g, yield 71.2%). LCMS (ESI): C 22 H 28 ClN2O2 + [M+H] + ,Calculated value: 387.18; Measured value: 387.3.

[0249] To a 100 mL one-neck flask was added a solution of tert-butyl 4-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazine-1-carboxylate (1.2 g, 3.11 mmol) in ethyl acrylate (10 mL) and a solution of hydrochloric acid in ethyl acrylate (10 mL, 3 M) at room temperature. The reaction mixture was stirred at room temperature for 2 hours. Completion of the reaction was detected by LC / MS. The reaction mixture was concentrated under reduced pressure to give compound GTC01018 (white solid, 1.09 g, 98.32% yield). 1 H NMR (400 MHz, D2O) δ 7.71 (d, J = 8.2 Hz, 2H), 7.60 (t, J = 8.3 Hz, 4H), 7.47 (d, J = 8.5 Hz, 2H), 4.52 (s, 2H), 3.65 (s, 8H). LCMS (ESI): [M+H] + ,Calculated value: 287.12; Measured value: 287.2.

[0250] Intermediate Examples 93-137 The following intermediate compounds were prepared by the methods of Scheme 17 or by reference to Intermediate Example 92.

[0251] Table 5. Compounds of Intermediate Examples 93-137 [Table 238] [Table 239] [Table 240] [Table 241] [Table 242] [Table 243] [Table 244] Table 245 Table 246 Table 247 Table 248 Table 249 Table 250 Table 251 Table 252 Table 253 Table 254 Table 255 Table 256 Table 257 Table 258 Table 259 Table 260 Table 261 [Table 262] [Table 263] [Table 264] [Table 265]

[0252] Example 1: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03355) The target product GT-03355 was prepared with reference to the synthesis method in Scheme 1.

[0253] To a solution of 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine (306 mg, 0.85 mmol) obtained in Intermediate Example 3 and 3-(5-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03234) (286 mg, 0.85 mmol) in DMF (8 mL) were added TEA (0.56 mL, 3.4 mmol) and NaI (128 mg, 0.85 mmol), and the reaction mixture was stirred at 50°C for 18 hours. Completion of the reaction was detected by LCMS. The reaction mixture was filtered, and the filtrate was purified by high-performance liquid chromatography to obtain compound GT-03355 (349 mg, yield: 75%) as a white solid. 1H NMR (400 MHz, DMSO) δ 10.94 (s, 1H), 7.73-7.68 (m, 2H), 7.65-7.55 (m, 2H), 7.45-7.43 (m, 2H), 7.38-7.30 (m, 4H), 7.24-7.20 (m, 1H), 5.08-5.04 (m, 1H), 4.41 (d, J = 17.6 Hz, 1H), 4.28 (d, J = 17.6 Hz, 1H), 3.26-3.15 (m, 6H), 3.03-2.81 (m, 5H), 2.56-2.50 (m, 2H), 2.37-2.33 (m, 2H), 1.95-1.92 (m, 1H). LC / MS (ESI) m / z: C 31 H 32 ClN4O3 + [M+H] + , Calculated value 543.22; Measured value 543.2.

[0254] Example 2: Preparation of 3-(5-(4-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03356) The target product GT-03356 was obtained by referring to the synthesis method in Scheme 3.

[0255] To a solution of 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione (30 mg, 0.066 mmol) obtained in Intermediate Example 16 and 2-(bromomethyl)-4'-chloro-1,1'-biphenyl (CAS number: 1001754-57-9) (19 mg, 0.066 mmol) in DMF (2 mL) was added TEA (33 μL, 0.2 mmol), and the reaction mixture was stirred at 50°C for 2 hours. Completion of the reaction was detected by LCMS. The reaction mixture was filtered, and the filtrate was purified by high-performance liquid chromatography to obtain compound GT-03356 (18 mg, yield: 44%) as a white solid. 1H NMR (400 MHz, MeOD) δ 7.81-7.77 (m, 1H), 7.74-7.70 (m, 1H), 7.56-7.49 (m, 2H), 7.39-7.34 (m, 4H), 7.26-7.18 (m, 5H), 6.78-6.74 (m, 2H), 5.11-5.06 (m, 1H), 4.67-4.56 (m, 2H), 4.55-4.48 (m, 1H), 4.24-4.21 (m, 1H), 4.12 (s, 2H), 3.95-3.79 (m, 2H), 3.43-3.30 (m, 5H), 2.99-2.65 (m, 4H), 2.63-2.34 (m, 2H). LC / MS (ESI) m / z: C 37 H 36 ClN4O3 + [M+H] + , Calculated value 619.25; Measured value 619.3.

[0256] Example 3: Preparation of 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03361) Referring to the method of Scheme 3, 3-(1-oxo-5-(piperidin-4-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione (GT-3423) and 2-(bromomethyl)-4'-chloro-1,1'-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target compound GT-03361 (17 mg, yield: 40%, white solid). 1 H NMR (400 MHz, MeOD) δ 7.86-7.71 (m, 2H), 7.58-7.51 (m, 4H), 7.46-7.32 (m, 5H), 5.17-5.13 (m, 1H), 4.53-4.41 (m, 3H), 4.34 (s, 2H), 3.44-3.37 (m, 1H), 3.35-3.30 (m, 1H), 3.08-2.88 (m, 2H), 2.82-2.78 (m, 1H), 2.71-2.60 (m, 3H), 2.52-2.49 (m, 1H), 2.19-2.16 (m, 1H), 1.92-1.77 (m, 2H), 1.54-1.47 (m, 1H), 1.41-1.38 (m, 1H). LC / MS (ESI) m / z: C 32 H 33 ClN3O3 + [M+H] + , Calculated value 542.22; Measured value 542.2.

[0257] Example 4 Preparation of 3-(5-(4-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03367) The target product GT-03367 was obtained by referring to the synthesis method in Scheme 4.

[0258] To a solution of 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione (30 mg, 66 μmol) obtained in Intermediate Example 16 and 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde (CAS number: 1228837-05-5) (20 mg, 79 μmol) in DMF (2 mL), AcOH (1d) was added, and the reaction mixture was stirred at 50°C for 17 hours. NaBHCN (9 mg, 0.13 mmol) was then added, followed by stirring for 2 hours. Completion of the reaction was detected by LCMS. The reaction mixture was filtered, and the filtrate was purified by high-performance liquid chromatography to obtain compound GT-03367 (18 mg, yield: 42%) as a white solid. 1H NMR (400 MHz, MeOD) δ 7.80-7.75 (m, 2H), 7.72-7.68 (m, 3H), 7.47 (d, J = 7.8 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 6.98 (d, J = 8.2 Hz, 2H), 5.11-5.07 (m, 1H), 4.53-4.42 (m, 2H), 4.16-3.98 (m, 2H), 3.38-3.26 (m, 3H), 3.17-2.86 (m, 5H), 2.86-2.59 (m, 4H), 2.45-2.40 (m, 1H), 2.23-2.17 (m, 2H), 2.14-2.08 (m, 1H), 2.00 (brs, 2H), 1.45 (t, J = 6.3 Hz, 2H), 0.91 (s, 6H). LC / MS (ESI) m / z: C 39 H 44 ClN4O3 + [M+H] + , Calculated 651.31; Measured 651.3.

[0259] Example 5 Preparation of 3-(5-((1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03368) Referring to the synthesis method of Scheme 4 or the method of Example 4, 3-(1-oxo-5-(piperidin-4-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione (GT-3423) and 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde were used as starting materials to obtain the target product GT-03368 (8 mg, yield: 16%, white solid). 1 H NMR (400 MHz, MeOD) δ 7.63 (d, J = 7.8 Hz, 1H), 7.33-7.27(m, 3H), 7.24 (d, J = 7.8 Hz, 1H), 7.02-6.97 (m, 2H), 5.07-5.02 (m, 1H), 4.41-4.31 (m, 2H), 3.54-3.49 (m, 2H), 3.30-3.26 (m, 2H), 3.03-2.98 (m, 1H), 2.81-2.77 (m, 1H), 2.71 (brs, 1H), 2.63 (d, J = 6.4 Hz, 2H), 2.50-2.36 (m, 3H), 2.20-2.13 (m, 3H), 2.12-1.99 (m, 4H), 1.76-1.72 (m, 2H), 1.48 (t, J = 6.2 Hz, 3H), 0.92 (s, 6H). LC / MS (ESI) m / z: C 34 H 41 ClN3O3 + [M+H] + , Calculated value 574.28; Measured value 574.3.

[0260] Example 6 Preparation of 3-(5-(4-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03453) The target product GT-03453 was obtained by referring to the synthesis method in Scheme 4.

[0261] To a solution of 3-(1-oxo-5-(4-(piperazin-1-ylmethyl)phenyl)isoindolin-2-yl)piperidine-2,6-dione (30 mg, 66 μmol) obtained based on Intermediate Example 16 and 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde (21 mg, 92 μmol) obtained in Intermediate Example 2 in DMF (2 mL) was added DIEA (22 μL, 0.13 mmol), and the reaction mixture was stirred at 50°C for 2 hours. NaBHCN (8 mg, 0.13 mmol) was then added to the reaction mixture, followed by stirring for 16 hours. Completion of the reaction was detected by LCMS. The reaction mixture was filtered, and the filtrate was purified by high-performance liquid chromatography to obtain compound GT-03453 (10 mg, yield: 14%) as a white solid. 1H NMR (400 MHz, MeOD) δ 7.80-7.75 (m, 2H), 7.72-7.68 (m, 3H), 7.49 -7.44 (m, 2H), 7.30-7.25 (m, 2H), 7.01 - 6.96 (m, 2H), 5.11-5.07 (m, 1H), 4.53-4.42 (m, 2H), 4.16-3.98 (m, 2H), 3.38-3.26 (m, 3H), 3.17-2.86 (m, 5H), 2.86-2.59 (m, 4H), 2.45-2.40 (m, 1H), 2.23-2.17 (m, 2H), 2.14-2.08 (m, 1H), 2.00 (brs, 2H), 1.45 (t, J = 6.3 Hz, 2H), 0.91 (s, 6H). LC / MS (ESI) m / z: C 39 H 44 FN4O3 + [M+H] + , Calculated value 635.34; Measured value 635.3.

[0262] Example 7 Preparation of 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03454) Referring to the synthesis method of Scheme 4 or the method of Example 4, 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 18 and 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde obtained in Intermediate Example 2 were used as starting materials to obtain the target product GT-03454 (6 mg, yield: 12%, white solid). 1 H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.87 - 7.77 (m, 2H), 7.75 - 7.66 (m, 1H), 7.21 - 7.12 (m, 4H), 5.14 (dd, J = 13.2, 5.1 Hz, 1H), 4.51 - 4.33 (m, 4H), 3.48 - 3.23 (m, 8H), 2.98 - 2.84 (m, 2H), 2.61 (d, J = 16.6 Hz, 2H), 2.43 (dd, J = 13.0, 4.3 Hz, 1H), 2.35 (brs, 2H), 2.02 (s, 3H), 1.44 (t, J = 6.0 Hz, 2H), 0.95 (s, 6H). LC / MS (ESI) m / z: C 33 H 40 FN4O3 + [M+H] + , Calculated value 559.31; Measured value 559.3.

[0263] Example 7 Preparation of 3-(5-((1-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03455) Referring to the synthesis method of Scheme 4 or the method of Example 4, 3-(1-oxo-5-(piperidin-4-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione and 4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde obtained based on Intermediate Example 2 were used as starting materials to obtain the target product GT-03455 (4 mg, yield: 10%, white solid). 1 H NMR (400 MHz, MeOD) δ 7.75 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.15-7.12 (m, 4H), 5.19-5.14 (m, 1H), 4.53-4.46 (m, 2H), 3.61 (s, 2H), 3.42 - 3.39 (m, 2H), 3.18 - 3.06 (m, 1H), 2.99 - 2.87 (m, 1H), 2.84 - 2.81 (m, 1H), 2.76 - 2.70 (m, 2H), 2.60 -2.48 (m, 3H), 2.34 - 2.23 (m, 2H), 2.23 - 2.10 (m, 3H), 1.94 - 1.79 (m, 2H), 1.66 -1.46 (m, 4H), 1.04 (s, 6H). LC / MS (ESI) m / z: C 34 H 41 FN3O3 + [M+H] + , Calculated value 558.31; Measured value 558.3.

[0264] Example 8 Preparation of 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03468) The target product GT-03468 was obtained by referring to the synthesis method in Scheme 1 or the method in Example 1.

[0265] To a solution of (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate (20 mg, 0.054 mmol) obtained based on Intermediate Example 6 and 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine (CAS number: 1228780-72-0) (17 mg, 0.054 mmol) in DMF (2 mL) was added TEA (18 μL, 0.11 mmol), and the reaction mixture was stirred at 50°C for 2 hours. Completion of the reaction was detected by LCMS. The reaction mixture was filtered, and the filtrate was purified by high-performance liquid chromatography to produce compound GT-03468 (20 mg, yield: 62%) as a white solid. 1H NMR (400 MHz, DMSO) δ 11.03 (s, 1H), 7.64 (brs, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 5.16-5.11 (m, 1H), 4.57 (d, J = 17.6 Hz, 1H), 4.41 (d, J = 17.6 Hz, 1H), 3.79 (brs, 2H), 3.69-3.49 (m, 4H), 3.31-3.19 (m, 4H), 2.96-2.88 (m, 3H), 2.69-2.59 (m, 3H), 2.50-2.40 (m, 1H), 2.30-2.22 (m, 2H), 2.05-1.98 (m, 3H), 1.51-1.42 (m, 2H), 0.96 (s, 6H). LC / MS (ESI) m / z: C 33 H 39 ClFN4O3 + [M+H] + , Calculated value 593.27; Measured value 593.3.

[0266] Example 9 Preparation of 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03469) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 8 and 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine (CAS number: 1228780-72-0) were used as starting materials to obtain the target product GT-03469 (18 mg, yield: 56%, white solid). 1 H NMR (400 MHz, MeOD) δ 7.42 (s, 1H), 7.31 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 10.0 Hz, 1H), 7.01 (d, J = 8.2 Hz, 2H), 5.06-5.01 (m, 1H), 4.48-4.37 (m, 2H), 4.06 (brs, 2H), 3.57 (brs, 2H), 3.17-3.06 (m, 5H), 2.86-2.67 (m, 4H), 2.44-2.33 (m, 1H), 2.26-2.23(m 3H), 2.09-2.03 (m, 4H), 1.50-1.47 (m, 2H), 0.92 (s, 6H). LC / MS (ESI) m / z: C 33 H 39 ClFN4O3 + [M+H] + , Calculated value 593.27; Measured value 593.3.

[0267] Example 10: Preparation of 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03492) With reference to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 5 and 3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane obtained based on Intermediate Example 13 were used as starting materials to obtain the target product GT-03492 (8 mg, yield: 24%, white solid). 1 H NMR (400 MHz, MeOD) δ 7.81 (d, J = 8.0Hz, 1H), 7.61 (s, 1H), 7.56-7.54 (m, 1H), 7.23-7.20 (m, 2H), 6.96-6.94 (m, 2H), 5.11-5.06 (m, 1H), 4.54-4.44 (m, 2H), 4.32-4.24 (m, 2H), 3.67-3.53 (m, 1H), 2.86-2.64 (m, 5H), 2.47-2.06 (m, 9H), 1.95-1.91 (m, 3H), 1.42 (d, J = 6.4 Hz, 2H), 0.91 (s, 6H). LC / MS (ESI) m / z: C 34 H 40 ClN4O3 + [M+H] + , Calculated value 587.28; Measured value 587.3.

[0268] Example 11 Preparation of 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03493) With reference to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 6 and 3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane obtained based on Intermediate Example 13 were used as starting materials to obtain the target product GT-03493 (8 mg, yield: 24%, white solid). 1 H NMR (400 MHz, MeOD) δ 7.66-762 (m, 2H), 7.24-7.22 (m, 2H), 6.97-6.95 (m, 2H), 5.11-5.06 (m, 1H), 4.59-4.47 (m, 2H), 4.38-4.25 (m, 2H), 3.67-3.54 (m, 1H), 3.06-3.03 (m, 1H), 2.93 (d, J = 11.9 Hz, 1H), 2.87 - 2.75 (m, 2H), 2.75 - 2.64 (m, 2H), 2.44 (dd, J = 27.1, 14.1 Hz, 2H), 2.25 (s, LC / MS (ESI) m / z: C 34 H 39 ClFN4O3 + [M+H] + , Calculated value 605.27; Measured value 605.3.

[0269] Example 12: Preparation of 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03578) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 7 and 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine (CAS number: 1228780-72-0) were used as starting materials to obtain the target product GT-03578 (36 mg, yield: 45%, white solid). 1 H NMR (400 MHz, DMSO) δ 11.02 (s, 1H), 7.73 (brs, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.43 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 5.16-5.11 (m, 1H), 4.44-4.31 (m, 2H), 4.14-3.75 (m, 2H), 3.69-3.49 (m, 4H), 3.33-3.16 (m, 4H), 2.96-2.88 (m, 2H), 2.68-2.59 (m, 2H), 2.46-2.40 (m, 1H), 2.27 (brs, 2H), 2.02 (brs, 3H), 1.47-1.44 (m, 2H), 1.30-1.23 (m, 1H), 0.96 (s, 6H). LC / MS (ESI) m / z: C 33 H 39 ClFN4O3 + [M+H] + , Calculated value 593.27; Measured value 593.3.

[0270] Example 13: Preparation of 3-(4-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03649) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl methanesulfonate obtained based on Intermediate Example 9 and 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine (CAS number: 1228780-72-0) were used as starting materials to obtain the target product GT-03649 (41 mg, yield: 45%, white solid). 1 H NMR (400 MHz, DMSO) δ 11.04 (s, 1H), 7.79-7.76 (m, 2H), 7.58 (t, J = 7.2 Hz, 1H), 7.42 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 5.18-5.13 (m, 1H), 4.81-4.68 (m, 1H), 4.47-4.40 (m, 1H), 3.67-3.47 (m, 4H), 3.33-3.17(m, 4H), 3.01-2.92 (m, 2H), 2.85-2.77 (m, 2H), 2.67-2.62 (m, 2H), 2.41-2.31 (m, 3H), 2.02-1.99 (m, 3H), 1.47-1.44 (m, 2H), 0.96 (s, 6H). LC / MS (ESI) m / z: C 33 H 40 ClN4O3 + [M+H] + , Calculated value 575.28; Measured value 575.3.

[0271] Example 14: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03694) With reference to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 6 and 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine (CAS number: 870812-97-8) obtained based on Intermediate Example 3 were used as starting materials to obtain the target product GT-03694 (40 mg, yield: 76%, white solid). 1 H NMR (400 MHz, DMSO) δ 11.02 (s, 1H), 7.80-7.75 (m, 1H), 7.65-7.63 (m, 1H), 7.52-7.47 (m, 5H), 7.40-7.38 (m, 2H), 7.30-7.28 (m, 1H), 5.16-5.11(m, 1H), 4.57 (d, J = 17.6 Hz, 1H), 4.41 (d, J = 17.6 Hz, 1H), 3.33-3.05 (m, 5H), 2.93-2.88 (m, 3H), 2.63-2.58 (m, 3H), 2.42-2.32 (m, 1H), 2.03-1.97 (m, 2H), 1.30-1.23 (m, 2H). LC / MS (ESI) m / z: C 31 H 31 ClFN4O3 + [M+H] + , Calculated value 561.21; Measured value 561.2.

[0272] Example 15: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03695) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 7 and 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine were used as starting materials to obtain the target product GT-03695 (39 mg, yield: 83%, white solid). 1 H NMR (400 MHz, DMSO) δ 11.02 (s, 1H), 7.86-7.71 (m, 1H), 7.66-7.58 (m, 1H), 7.56-7.47 (m, 5H), 7.43-7.37 (m, 2H), 7.34-7.25 (m, 1H), 5.14-5.11 (m, 1H), 4.45 (d, J = 17.2 Hz, 2H), 4.33 (d, J = 17.2 Hz, 1H), 3.31-3.04 (m, 3H), 2.96-2.88 (m, 2H), 2.74-2.58 (m, 3H), 2.44-2.33 (m, 2H), 2.07-1.94 (m, 2H), 1.33-1.23 (m, 4H). LC / MS (ESI) m / z: C 31 H 31 ClFN4O3 + [M+H] + , Calculated value 561.21; Measured value 561.2.

[0273] Example 16: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03696) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 8 and 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine were used as starting materials to obtain the target product GT-03696 (39 mg, yield: 74%, white solid). 1H NMR (400 MHz, DMSO) δ 11.01 (s, 1H), 7.98-7.71 (m, 1H), 7.62-7.49 (m, 4H), 7.48-7.43 (m, 2H), 7.41-7.35 (m, 2H), 7.30-7.27 (m, 1H), 5.11-5.07 (m, 1H), 4.49 (d, J = 17.6 Hz, 1H), 4.36 (d, J = 17.6 Hz, 1H), 4.30- 4.05 (m, 2H), 3.33-3.06 (m, 5H), 3.02-2.84 (m, 3H), 2.60-2.58 (m, 2H), 2.46-2.30 (m, 1H), 2.08-1.91 (m, 1H), 1.30-1.24 (m, 1H). LC / MS (ESI) m / z: C 31 H 31 ClFN4O3 + [M+H] + , Calculated value 561.21; Measured value 561.2.

[0274] Example 17: Preparation of 3-(4-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03876) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl methanesulfonate and 1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine obtained based on Intermediate Example 9 were used as starting materials to obtain the target product GT-03876 (16 mg, yield: 24%, white solid). 1H NMR (400 MHz, MeOD) δ 7.84 (d, J = 8.0 Hz, 1H), 7.76-7.70 (m, 1H), 7.68-7.66 (m, 1H), 7.61-7.57 (m, 1H), 7.56-7.51 (m, 4H), 7.42-7.32 (m, 3H), 5.21-5.17 (m, 1H), 4.66-4.53 (m, 2H), 4.27 (brs, 2H), 4.02 (brs, 2H), 3.22-2.88 (m, 8H), 2.87-2.73 (m, 2H), 2.57-2.46 (m, 1H), 2.29-2.12 (m, 1H). LC / MS (ESI) m / z: C 31 H 32 ClN4O3 + [M+H] + , Calculated value 543.22; Measured value 543.2.

[0275] Example 18: Preparation of 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03877) Referring to the synthesis method of Scheme 1, 3-(1-oxo-5-(piperidin-4-ylamino)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 19 and 2-(bromomethyl)-4′-chloro-1,1′-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target product GT-03877 (30 mg, yield: 52%, white solid). 1H NMR (400 MHz, MeOD) δ 7.78-7.76 (m, 1H), 7.64-7.48 (m, 5H), 7.44-7.43 (m, 1H), 7.40-7.38(m, 2H), 6.74-6.71 (m, 2H), 5.10-5.06 (m, 1H), 4.50-4.31 (m, 4H), 3.62-3.57 (m, 1H), 3.44-3.39 (m, 2H), 2.99-2.70 (m, 4H), 2.54-2.38 (m, 1H), 2.26-2.00 (m, 3H), 1.67-1.62 (m, 2H). LC / MS (ESI) m / z: C 31 H 32 ClN4O3 + [M+H] + , Calculated value 543.22; Measured value 543.2.

[0276] Example 19: Preparation of 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03878) Referring to the synthesis method of Scheme 1, 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 17 and 2-(bromomethyl)-4′-chloro-1,1′-biphenyl were used as starting materials to obtain the target product GT-03878 (22 mg, yield: 37%, white solid). 1H NMR (400 MHz, MeOD) δ 7.73-7.72 (m, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.53-7.44 (m, 2H), 7.42-7.40 (m, 2H), 7.36-7.34 (m, 1H), 7.26-7.24 (m, 2H), 6.92-6.87 (m, 2H), 5.18-5.14 (m, 1H), 4.48-4.41 (m, 4H), 4.33 (brs, 2H), 3.06-2.99 (m, 2H), 2.98-2.77 (m, 4H), 2.58-2.47 (m, 1H), 2.32-2.14 (m, 3H), 2.10-2.00 (m, 2H). LC / MS (ESI) m / z: C 32 H 32 ClN4O3 + [M+H] + , Calculated value 555.22; Measured value 555.2.

[0277] Example 20: Preparation of 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3-hydroxyazetidin-3-yl)(hydroxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03880) Referring to the synthesis method of Scheme 1, 3-(5-(hydroxy(3-hydroxyazetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 15 and 2-(bromomethyl)-4'-chloro-1,1'-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target product GT-03880 (13 mg, yield: 22%, white solid). 1H NMR (400 MHz, MeOD) δ 7.78 (dd, J = 8.0, 1.6 Hz, 1H), 7.67-7.52 (m, 6H), 7.46-7.34 (m, 4H), 5.20-5.15 (m, 1H), 4.77-4.68 (m, 1H), 4.59-4.42 (m, 5H), 4.37-4.21 (m, 1H), 4.09-3.85 (m, 1H), 3.60-3.46 (m, 1H), 3.01-2.86 (m, 1H), 2.83-2.73 (m, 1H), 2.52-2.50 (m, 1H), 2.28-2.08 (m, 1H). LC / MS (ESI) m / z: C 30 H 29 ClN3O5 + [M+H] + , Calculated value 546.18; Measured value 546.2.

[0278] Example 21: Preparation of 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-ylidene)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03881) Referring to the method of Scheme 1, 3-(5-(azetidin-3-ylidenemethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 13 and 2-(bromomethyl)-4′-chloro-1,1′-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target product GT-03881 (11 mg, yield: 20%, white solid). 1H NMR (400 MHz, MeOD) δ 7.81 (d, J = 8.0 Hz, 1H), 7.63-7.54 (m, 3H), 7.49 (d, J = 8.4 Hz, 2H), 7.45-7.42 (m, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.32 (s, 1H), 7.25 (d, J = 8.0 Hz, 1H), 6.60 (s, 1H), 5.20-5.16 (m, 1H), 4.95-4.88 (m, 2H), 4.64 (s, 2H), 4.57-4.47 (m, 2H), 2.99-2.88 (m, 1H), 2.84-2.78 (m, 1H), 2.59-2.45 (m, 1H), 2.24-2.17 (m, 1H). LC / MS (ESI) m / z: C 30 H 27 ClN3O3 + [M+H] + , Calculated value 512.17; Measured value 512.2.

[0279] Example 22: Preparation of 3-(5-(((1R,4R)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03887) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 5 and (1R,4R)-2-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane were used as starting materials to obtain the target product GT-03887 (42 mg, yield: 63%, white solid). 1H NMR (400 MHz, MeOD) δ 7.89 (d, J = 8.0 Hz, 1H), 7.82-7.75 (m, 1H), 7.70-7.63 (m, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 5.22-5.17 (m, 1H), 5.04-4.93 (m, 4H), 4.64-4.50 (m, 2H), 4.33-4.19 (m, 2H), 3.86-3.83 (m, 1H), 3.76-3.70 (m, 1H), 3.50-3.40 (m, 3H), 3.02-2.88 (m, LC / MS (ESI) m / z: C 34 H 40 ClN4O3 + [M+H] + , Calculated value 587.28; Measured value 587.3.

[0280] Example 23 Preparation of 3-(5-(((1R,4R)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03888) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 6 and (1R,4R)-2-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane were used as starting materials to obtain the target product GT-03888 (43 mg, yield: 66%, white solid). 1H NMR (400 MHz, MeOD) δ 7.83-7.71 (m, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 5.21-5.17 m, 1H), 5.04-4.97 (m, 2H), 4.67-4.49 (m, 2H), 4.34-4.27 (m, 3H), 4.16-4.05 (m, 1H), 3.86-3.83 (m, 1H), 3.76-3.70 (m, 1H), 3.51-3.36 (m, 3H), 3.00- 2.88 (m, 1H), 2.83-2.79 (m, 1H), 2.59-2.50 (m, 1H), 2.44-2.28 (m, 3H), 2.22-2.17 (m, 3H), 1.61 (t, J = 6.4 Hz, 2H), 1.05 (s, 6H). LC / MS (ESI) m / z: C 34 H 39 ClFN4O3 + [M+H] + , Calculated value 605.27; Measured value 605.3.

[0281] Example 24: Preparation of 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03889) With reference to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methylsulfonate obtained based on Intermediate Example 5 and 3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane obtained based on Intermediate Example 93 were used as starting materials to obtain the target product GT-03889 (26 mg, yield: 38%, white solid). 1H NMR (400 MHz, MeOD) δ 7.80 (d, J = 8.0 Hz, 1H), 7.66 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.25-7.19 (m, 2H), 6.97-6.92 (m, 2H), 5.11-5.06 (m, 1H), 4.57-4.35 (m, 2H), 4.22 (brs, 2H), 3.80 (brs, 2H), 2.87-2.64 (m, 6H), 2.52-2.35 (m, 1H), 2.30-2.18 (m, 9H), 1.93 (brs, 2H), 1.42-1.39 (m, 2H), 0.90 (s, 6H). LC / MS (ESI) m / z: C 35 H 42 ClN4O3 + [M+H] + , Calculated value 601.29; Measured value 601.3.

[0282] Example 25 Preparation of 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03890) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methylsulfonate obtained based on Intermediate Example 6 and 3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane obtained based on Intermediate Example 93 were used as starting materials to obtain the target product GT-03890 (21 mg, yield: 31%, white solid). 1H NMR (400 MHz, MeOD) δ 7.71-7.61 (m, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 5.10-5.06 (m, 1H), 4.52 (q, J = 17.6 Hz, 2H), 4.29 (brs, 2H), 3.92 (brs, 2H), 3.00-2.91 (m, 2H), 2.88-2.77 (m, 3H), 2.74-2.66 (m, 1H), 2.45-2.42 (m, 2H), 2.37-2.25 (m, 3H), 2.21-2.17 (m, 2H), 2.16-2.06 (m, 3H), 1.95 (brs, 2H), 1.42 (t, J = 6.6 Hz, 2H), 0.9 (s, 6H). LC / MS (ESI) m / z: C 35 H 41 ClFN4O3 + [M+H] + , Calculated value 619.28; Measured value 619.3.

[0283] Example 26: Preparation of 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03891) The target product GT-03891 was obtained by referring to the synthesis method in Scheme 6.

[0284] To a solution of 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione (45 mg, 0.13 mmol) obtained based on Intermediate Example 18 and 4'-chloro-[1,1'-biphenyl]-2-carboxylic acid (CAS number: 7079-15-4) (40 mg, 0.17 mmol) in DMF (2 mL) was added TEA (55 μL, 0.39 mmol) and HATU (75 mg, 0.19 mmol). The reaction mixture was stirred at 50°C for 2 hours. Completion of the reaction was detected by LCMS. The reaction mixture was filtered, and the filtrate was purified by high-performance liquid chromatography to produce compound GT-03891 (26 mg, yield: 35%) as a white solid. 1H NMR (400 MHz, MeOD) δ 7.92 (d, J = 7.6 Hz, 1H), 7.71 (s, 1H), 7.65-7.58 (m, 2H), 7.56-7.46 (m, 7H), 5.21-5.17 (m, 1H), 5.02-4.92 (m, 3H), 4.57 (q, J = 17.2 Hz, 2H), 4.39-4.35 (m, 2H), 3.51-3.40 (m, 4H), 3.13-3.03 (m, 1H), 2.97-2.92 (m, 1H), 2.86-2.77 (m, 1H), 2.61-2.47 (m, 1H), 2.29-2.14 (m, 1H). LC / MS (ESI) m / z: C 31 H 30 ClN4O4 + [M+H] + , Calculated value 557.20; Measured value 557.2.

[0285] Example 27: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03991) Referring to the synthesis method of Scheme 1 or the method of Example 1, 3-(5-(bromomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03234) and N-(4'-chloro-[1,1'-biphenyl]-2-yl)piperidin-4-amine hydrochloride obtained based on Intermediate Example 63 were used as starting materials to prepare the target product GT-03991 (17 mg, yield: 24%). 1H NMR (400 MHz, MeOD) δ 7.92 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.35-7.31 (m, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 7.00 (t, J = 8.0 Hz, 1H), 5.22-5.17 (m, 1H), 4.64-4.53 (m, 2H), 4.47 (s, 2H), 3.68-3.62 (m, 1H), 3.57-3.54 (m, 2H), 3.17 (t, J = 12.4 Hz, 2H), 2.94-2.89 (m, 1H), 2.86-2.73 (m, 1H), 2.59-2.51 (m, 1H), 2.25-2.19 (m, 3H), 1.75-1.67 (m, 2H). LC / MS (ESI) m / z: C 31 H 32 ClN4O3 + [M+H] + , Calculated value 543.22; Measured value 543.2.

[0286] Example 28: Preparation of 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03922) Referring to the synthesis method of Scheme 6, 3-(5-(azetidin-3-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 14 and 4′-chloro-[1,1′-biphenyl]-2-carboxylic acid (CAS number: 7079-15-4) were used as starting materials to obtain the target product GT-03922 (35 mg, yield: 57%, white solid). 1 H NMR (400 MHz, MeOD) δ 7.60 (d, J = 7.6 Hz, 1H), 7.47-7.26 (m, 8H), 7.17 (s, 1H), 7.11 (d, J = 7.6 Hz, 1H), 5.07-5.01 (m, 1H), 4.43-4.29 (m, 2H), 3.99-3.88 (m, 1H), 3.59-3.55 (m, 1H), 3.53-3.45 (m, 1H), 3.08-3.04 (m, 1H), 2.87-2.76 (m, 1H), 2.74-2.63 (m, 2H), 2.58-2.52 (m, 2H), 2.46-2.30 (m, 1H), 2.11-2.01 (m, 1H). LC / MS (ESI) m / z: C 30 H 27 ClN3O4 + [M+H] + , Calculated value 528.17; Measured value 528.2.

[0287] Example 29: Preparation of 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03923) Referring to the synthesis method of Scheme 2, 3-(5-(azetidin-3-ylmethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 14 and 2-(bromomethyl)-4′-chloro-1,1′-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target product GT-03923 (38 mg, yield: 63%, white solid). 1H NMR (400 MHz, MeOD) δ 7.65-7.63 (m, 1H), 7.47-7.39 (m, 5H), 7.31-7.18 (m, 3H), 7.12 (d, J = 7.6 Hz, 1H), 5.08-5.02 (m, 1H), 4.74-4.69 (m, 3H), 4.46-4.34 (m, 2H), 4.32 (s, 1H), 3.96-3.91 (m, 1H), 3.83-3.80 (m, 1H), 3.58-3.53 (m, 1H), 3.06-2.99 (m, 1H), 2.85-2.75 (m, 2H), 2.74-2.64 (m, 1H), 2.41-2.34 (m, 1H), 2.14-2.00 (m, 1H). LC / MS (ESI) m / z: C 30 H 29 ClN3O3 + [M+H] + , Calculated value 514.19; Measured value 514.2.

[0288] Example 30 Preparation of 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03995) With reference to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 5 and 6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane obtained based on Intermediate Example 14 were used as starting materials to obtain the target product GT-03995 (8 mg, yield: 12%, white solid). 1H NMR (400 MHz, MeOD) δ 7.82 (d, J = 8.0 Hz, 1H), 7.68 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.25-7.19 (m, 2H), 6.97-6.92 (m, 2H), 5.12-5.07 (m, 1H), 4.58-4.37 (m, 2H), 3.80 (brs, 2H), 2.88-2.65 (m, 6H), 2.54-2.37 (m, 1H), 2.31-2.19 (m, 9H), 1.95-1.90 (m, 2H), 1.42-1.39 (m, 2H), 0.90 (s, 6H). LC / MS (ESI) m / z: C 34 H 40 ClN4O3 + [M+H] + , Calculated value 587.28; Measured value 587.3.

[0289] Example 31 Preparation of 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03996) Referring to the synthesis method of Scheme 1 or the method of Example 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate and 8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane obtained based on Intermediate Example 94 were used as starting materials to obtain the target product GT-03996 (32 mg, yield: 42%, white solid). 1H NMR (400 MHz, MeOD) δ 7.67 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 5.08-5.03 (m, 1H), 4.47-4.27 (m, 2H), 3.67 (brs, 4H), 3.52 (brs, 2H), 2.89-2.73 (m, 3H), 2.72-2.70 (m, 1H), 2.69-2.55 (m, 2H), 2.43-2.35 (m, 1H), 2.25-2.20 (m, 2H), 2.13-2.02 (m, 3H), 1.90-1.84 (m, 2H), 1.49 (t, J = 8.0 Hz, 2H), 1.33-1.24 (m, 2H), 0.93 (s, 6H). LC / MS (ESI) m / z:C 35 H 42 ClN4O3 + [M+H] + , Calculated value 601.29; Measured value 601.3.

[0290] Example 32: Preparation of 3-(5-(((1R,5S)-6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-06194) The synthesis method of Scheme 1 or the method of Example 1 was followed to obtain the target product GT-06194 (8 mg, yield: 12%, white solid). 1H NMR (400 MHz, MeOD) δ 7.82 (d, J = 8.0 Hz, 1H), 7.68 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.25-7.19 (m, 2H), 6.97-6.92 (m, 2H), 5.12-5.07 (m, 1H), 4.58-4.37 (m, 2H), 3.80 (brs, 2H), 2.88-2.65 (m, 6H), 2.54-2.37 (m, 1H), 2.31-2.19 (m, 9H), 1.95-1.90 (m, 2H), 1.42-1.39 (m, 2H), 0.90 (s, 6H). LC / MS (ESI) m / z: C 34 H 40 ClN4O3 + [M+H] + , Calculated value 587.28; Measured value 587.3.

[0291] Example 33 Preparation of 3-(5-(((1S,4S)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-03997) The synthesis method of Scheme 1 or the method of Example 1 was followed to obtain the target product GT-03997 (36 mg, yield: 48%, white solid). 1H NMR (400 MHz, MeOD) δ 7.89 (d, J = 8.0 Hz, 1H), 7.82-7.77 (m, 1H), 7.72-7.64 (m, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 5.22-5.17 (m, 1H), 4.62-4.51 (m, 2H), 4.44-4.16 (m, 2H), 3.91-3.68 (m, 2H), 2.99-2.87 (m, 1H), 2.83-2.77 (m, 1H), 2.58-2.49 (m, 1H), 2.42-2.39 (m, 2H), 2.26-2.10 (m, 3H), 1.61 (t, J = 6.4 Hz, 2H), 1.05 (s, 6H). LC / MS (ESI) m / z: C 34 H 40 ClN4O3 + [M+H] + , Calculated value 587.28; Measured value 587.3.

[0292] Example 34: Preparation of 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-02785) Referring to the synthesis method of Scheme 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 5 and 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine (CAS number: 1228780-72-0) were used as starting materials to obtain the target product GT-02785 (20 mg, yield: 62%, white solid). 1H NMR (400 MHz, MeOD) δ 7.87 (d, J = 7.8 Hz, 1H), 7.73 (s, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 5.21-5.16 (m, 1H), 4.60-4.49 (m, 2H), 4.22 (brs, 2H), 3.61 (brs, 2H), 3.32 - 3.28 (m, 2H), 3.26 - 3,12 (m, 5H), 3.02 - 2.87 (m, 2H), 2.87 - 2.76 (m, 1H), 2.52 - 2.42 (m, 1H), 2.38 - 2.32 (m, 2H), 2.25 - 2.16 (m, 1H), 2.14 (s, 2H), 1.59 (t, J = 6.4 Hz, 2H), 1.04 (s, 6H). LC / MS (ESI) m / z: C 33 H 40 ClN4O3 + [M+H] + , Calculated value 575.28; Measured value 575.3.

[0293] Example 35: Preparation of 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04252) Referring to the synthesis method of Scheme 4, 3-(1-oxo-5-(piperazin-1-ylamino)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 11 and 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-formaldehyde (CAS number: 1228837-05-5) were used as starting materials to obtain the target product GT-04252 (15 mg, yield: 17%, white solid). 1H NMR (400 MHz, MeOD) δ 7.44 (d, J = 8.4 Hz, 1H), 7.39 - 7.33 (m, 2H), 7.09 - 7.02 (m, 2H), 6.90 (s, 1H), 6.81 (dd, J = 8.4, 1.8 Hz, 1H), 5.00 - 4.95 (m, 1H), 4.35 - 4.16 (m, 2H), 3.62 (s, 2H), 3.46 - 3.29 (m, 2H), 3.10 - 2.95 (m, 2H), 2.90 - 2.75 (m, 6H), 2.72 - 2.60 (m, 1H), 2.40 - 2.29 (m, 1H), 2.21 - 2.18 (m, 2H), 2.05 (brs, 3H), 1.51 (t, J = 6.4 Hz, 2H), 0.94 (s, 6H). LC / MS (ESI) m / z: C 32 H 39 ClN5O3 + [M+H] + , Calculated value 576.27; Measured value 576.3.

[0294] Example 36: Preparation of 3-(5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04167) Referring to the synthesis method of Scheme 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 5 and 2-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane (GTC00247) were used as starting materials to obtain the target product GT-04167 (29 mg, yield: 42%, white solid). 1H NMR (400 MHz, MeOD) δ 7.78 (d, J = 7.8 Hz, 1H), 7.69 - 7.45 (m, 2H), 7.34 (d, J = 7.4 Hz, 2H), 7.08 (d, J = 7.4 Hz, 2H), 5.11 - 5.05 (m, 1H), 4.53 - 4.37 (m, 2H), 4.21 - 4.01 (m, 4H), 3.88 - 3.72 (m, 2H), 3.61 - 3.32 (m, 2H), 2.87 - 2.78 (m, 1H), 2.75 - 2.61 (m, 1H), 2.48 - 2.37 (m, 1H), 2.32 - 2.18 (m, 3H), 2.15 - 1.96 (m, 3H), 1.96 - 1.62 (m, 2H), 1.49 (t, J = 6.4 Hz, 2H), 0.93 (s, 6H). LC / MS (ESI) m / z: C 35 H 42 ClFN4O3 + [M+H] + , Calculated value 601.29; Measured value 601.3.

[0295] Example 37: Preparation of 3-(5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04168) Referring to the synthesis method of Scheme 1, (2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 6 and 2-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane were used as starting materials to obtain the target product GT-04168 (26 mg, yield: 37%, white solid). 1H NMR (400 MHz, MeOD) δ 7.61 (d, J = 6.4 Hz, 1H), 7.56 - 7.49 (m, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 5.11 - 5.06 (m, 1H), 4.57 - 4.44 (m, 2H), 4.38 - 3.98 (m, 4H), 3.91 - 3.72 (m, 2H), 3.59 - 3.33 (m, 3H), 2.90 - 2.76 (m, 1H), 2.73 - 2.71 (m, 1H), 2.45 - 2.27 (m, 1H), 2.27 (brs, 2H), 2.21 - 1.96 (m, 6H), 1.94 - 1.6 (m, 2H), 1.49 (t, J = 6.5 Hz, 2H), 0.93 (s, 6H). LC / MS (ESI) m / z: C 35 H 41 ClFN4O3 + [M+H] + , Calculated value 619.28; Measured value 619.3.

[0296] Example 38: Preparation of 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04224) Referring to the synthesis method of Scheme 6, 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 18 and 4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carboxylic acid (CAS number: 2716235-85-5) were used as starting materials to obtain the target product GT-04224 (27 mg, yield: 43%, white solid). 1H NMR (400 MHz, MeOD) δ 7.93 (d, J = 7.8 Hz, 1H), 7.70 (s, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.47 - 7.34 (m, 2H), 7.27 - 7.21 (m, 2H), 5.22 - 5.18 (m, 1H), 4.69 - 4.50 (m, 2H), 4.36 (brs, 2H), 3.16 - 3.10 (m, 4H), 3.04 - 2.88 (m, 2H), 2.87 - 2.73 (m, 2H), 2.62 - 2.45 (m, 4H), 2.34 - 2.11 (m, 2H), 2.05 - 1.97 (m, 1H), 1.59 - 1.55 (m, 2H), 1.06 (s, 6H). LC / MS (ESI) m / z: C 33 H 38 ClN4O4 + [M+H] + , Calculated value 589.26; Measured value 589.3.

[0297] Example 39: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04196) Referring to the synthesis method of Scheme 2, 3-(1-oxo-5-(piperazin-1-ylamino)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 11 and 2-(bromomethyl)-4′-chloro-1,1′-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target product GT-04196 (34 mg, yield: 56%, white solid). 1H NMR (400 MHz, MeOD) δ 7.71 - 7.63 (m, 1H), 7.53 - 7.40 (m, 5H), 7.35 - 7.23 (m, 3H), 6.88 (s, 1H), 6.78 (dd, J = 8.4, 1.8 Hz, 1H), 5.02 - 4.95 (m, 1H), 4.36 (s, 2H), 4.31 - 4.16 (m, 2H), 3.31 - 3.27 (m, 2H), 3.08 - 2.86 (m, 4H), 2.86 - 2.60 (m, 4H), 2.40 - 2.21 (m, 1H), 2.09 - 1.92 (m, 1H). LC / MS (ESI) m / z: C 30 H 31 ClN5O3 + [M+H] + , Calculated value 544.21; Measured value 544.2.

[0298] Example 40: Preparation of 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)amino)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04204) Referring to the synthesis method of Scheme 2, 3-(5-(azetidin-3-ylamino)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 12 and 2-(bromomethyl)-4'-chloro-1,1'-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target product GT-04204 (10 mg, yield: 19%, white solid). 1H NMR (400 MHz, MeOD) δ 7.54 - 7.33 (m, 5H), 7.35 - 7.25 (m, 4H), 6.59 - 6.39 (m, 1H), 5.01 - 4.96 (m, 1H), 4.47 (s, 2H), 4.44 - 4.29 (m, 3H), 4.24 (t, J = 11.2 Hz, 2H), 3.87 - 3.59 (m, 2H), 2.84 - 2.76 (m, 1H), 2.70 - 2.64 (m, 1H), 2.40 -2.21 (m, 1H), 2.12 - 1.92 (m, 1H). LC / MS (ESI) m / z: C 29 H 27 ClFN4O3 + [M+H] + , Calculated value 533.18; Measured value 533.2.

[0299] Example 41: Preparation of 3-(5-((4-((3-(4-chlorophenyl)pyridin-4-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04275) Referring to the synthesis method of Scheme 2, 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione and 4-(chloromethyl)-3-(4-chlorophenyl)pyridine (Example 64) were used as starting materials to obtain the target product GT-04275 (36 mg, yield: 49%, white solid). 1H NMR (400 MHz, MeOD) δ 8.89 (d, J = 6.0 Hz, 1H), 8.81 (s, 1H), 8.47 (d, J = 6.0 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.88 (s, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.64 - 7.57 (m, 2H), 7.54 - 7.48 (m, 2H), 5.21 - 5.17 (m, 1H), 4.59 (d, J = 10.0 Hz, 2H), 4.55 (s, 2H), 3.93 (s, 2H), 3.40 (brs, 4H), 2.97 - 2.78 (m, 4H), 2.71 (brs, 1H), 2.59 - 2.48 (m, 1H), 2.27 - 2.11 (m, 1H). LC / MS (ESI) m / z: C 30 H 31 ClN5O3 + [M+H] + , Calculated value 544.21; Measured value 544.2.

[0300] Example 42: Preparation of 3-(5-((4-(3-(4-chlorophenyl)isonicotinoyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04222) Referring to the synthesis method of Scheme 6, 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 18 and 3-(4-chlorophenyl)isonicotinic acid (CAS number: 883107-39-9) were used as starting materials to obtain the target product GT-04222 (23 mg, yield: 36%, white solid). 1H NMR (400 MHz, MeOD) δ 8.75 (s, 1H), 8.69 (d, J = 5.6 Hz, 1H), 7.78 (d, J = 5.6 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.58 (s, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 5.01 - 4.95 (m, 1H), 4.37 (q, J = 17.2 Hz, 2H), 4.24 (s, 2H), 3.43 - 3.26 (m, 2H), 3.26 - 3.12 LC / MS (ESI) m / z: C 30 H 29 ClN5O4 + [M+H] + , Calculated value 558.19; Measured value 558.2.

[0301] Example 43: Preparation of 3-(5-((4-((4'-fluoro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04256) Referring to the synthesis method of Scheme 2, 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 18 and 2-(bromomethyl)-4′-chloro-1,1′-biphenyl (CAS number: 1001754-57-9) were used as starting materials to obtain the target product GT-04256 (28 mg, yield: 44%, white solid). 1H NMR (400 MHz, MeOD) δ 7.75 (d, J = 7.8 Hz, 1H), 7.58 - 7.54 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.39 - 7.36 (m, 2H), 7.29 - 7.22 (m, 3H), 7.11 (t, J = 8.8 Hz, 2H), 5.09 - 5.04 (m, 1H), 4.51 - 4.33 (m, 2H), 4.10 (brs, 2H), 3.97 (brs, 1H), 3.03 (brs, 4H), 2.92 - 2.64 (m, 6H), 2.46 - 2.35 (m, 1H), 2.16 - 1.97 (m, 1H). LC / MS (ESI) m / z: C 31 H 32 FN4O3 + [M+H] + , Calculated value 527.25; Measured value 527.3.

[0302] Example 44: Preparation of 3-(5-((4-(4'-fluoro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04194) Referring to the synthesis method of Scheme 6, 3-(1-oxo-5-(piperazin-1-ylmethyl)isoindolin-2-yl)piperidine-2,6-dione obtained based on Intermediate Example 18 and 4'-fluoro-[1,1'-biphenyl]-2-carboxylic acid (CAS number: 1841-57-2) were used as starting materials to obtain the target product GT-04194 (10 mg, yield: 16%, white solid). 1H NMR (400 MHz, MeOD) δ 7.92 (d, J = 7.8 Hz, 1H), 7.72 (s, 1H), 7.65 - 7.57 (m, 2H), 7.57 - 7.41 (m, 5H), 7.21 - 7.19 (m, 2H), 5.21 - 5.19 (m, 1H), 4.58 (q, J = 17.2 Hz, 2H), 4.41 (brs, 2H), 3.59 - 3.33 (m, 4H), 3.15 - 3.08 (m, 2H), 3.02 - 2.88 (m, 2H), 2.87 - 2.75 (m, 2H), 2.57 - 2.43 (m, 1H), 2.29 - 2.13 (m, 1H). LC / MS (ESI) m / z: C 31 H 30 FN4O4 + [M+H] + , Calculated value 541.22; Measured value 541.3.

[0303] Example 45: Preparation of 3-(5-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04193) Referring to the synthesis method of Scheme 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate and 1-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine obtained based on Intermediate Example 5 were used as starting materials to obtain the target product GT-04193 (30 mg, yield: 46%, white solid). 1H NMR (400 MHz, MeOD) δ 7.89 (d, J = 7.8 Hz, 1H), 7.78 (s, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.24 - 7.07 (m, 4H), 5.21 - 5.17 (m, 1H), 4.56 (q, J = 17.2 Hz, 2H), 4.36 (brs, 2H), 3.68 (brs, 2H), 3.39 (brs, 8H), 3.00 - 2.87 (m, 1H), 2.86 - 2.72 (m, 1H), 2.61 - 2.42 (m, 1H), 2.37-2.34 (m, 4H), 2.27 - 2.12 (m, 1H), 1.82 (s, 4H). LC / MS (ESI) m / z: C 31 H 36 FN4O3 + [M+H] + , Calculated value 531.28; Measured value 531.3.

[0304] Example 46: Preparation of 3-(5-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04170) Referring to the synthesis method of Scheme 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 5 and (4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)(piperazin-1-yl)methanone obtained based on Intermediate Example 24 were used as starting materials to obtain the target product GT-04170 (42 mg, yield: 63%, white solid). 1H NMR (400 MHz, MeOD) δ 7.91 (d, J = 7.6 Hz, 1H), 7.74 (brs, 1H), 7.63 (brs, 1H), 7.32 - 7.23 (m, 2H), 7.17 - 7.00 (m, 2H), 5.30 - 5.12 (m, 1H), 4.69 - 4.51 (m, 3H), 4.35 - 4.20 (m, 2H), 4.15 - 3.79 (m, 1H), 3.51 - 3.41 (m, 2H), 3.27 - 3.03 (m, 2H), 2.99 - 2.91 (m, 1H), 2.87 - 2.77 (m, 1H), 2.76 - 2.61 (m, 2H), 2.61 - 2.43 (m, 2H), 2.29 - 2.09 (m, 3H), 1.95 - 1.60 (m, 4H). LC / MS (ESI) m / z: C 31 H 34 FN4O4 + [M+H] + , Calculated value 545.26; Measured value 545.3.

[0305] Example 47: Preparation of 3-(5-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04169) Referring to the synthesis method of Scheme 1, (2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl methanesulfonate obtained based on Intermediate Example 5 and (3,6-diazabicyclo[3.1.1]heptan-3-yl)(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methanone obtained based on Intermediate Example 25 were used as starting materials to obtain the target product GT-04169 (37 mg, yield: 54%, white solid). 1H NMR (400 MHz, MeOD) δ 7.87 (d, J = 7.8 Hz, 1H), 7.79 (s, 1H), 7.70 - 7.65 (m, 1H), 7.41 - 7.23 (m, 2H), 7.12 - 7.05 (m, 2H), 5.21 - 5.16 (m, 1H), 4.71 (s, 1H), 4.66 - 4.50 (m, 2H), 4.46 - 4.37 (m, 1H), 4.35 - 4.18 (m, 1H), 4.02 - 3.96 (m, 1H), 3.80 - 3.71 (m, 2H), 3.23 - 3.04 (m, 1H), 3.02 - 2.87 (m, 1H), 2.87 - 2.76 (m, 1H), 2.71 - 2.65 (m, 1H), 2.57 - 2.52 (m, 3H), 2.41 - 2.09 (m, 4H), 1.89 - 1.84 (m, 4H). LC / MS (ESI) m / z:C 32 H 34 FN4O4 + [M+H] + , Calculated value 557.26; Measured value 557.3.

[0306] Example 48: Preparation of 3-(5-((4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05672) The target compound (GT-05672) (white solid, 15 mg, yield 20.85%) was prepared according to the method in Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.87 - 7.78 (m, 2H), 7.72 (dd, J = 16.4, 8.2 Hz, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.3 Hz, 2H), 5.14 (dd, J = 13.2, 5.1 Hz, 1H), 4.42 (dd, J = 51.5, 17.8 Hz, 6H), 3.42 - 3.12 (m, 10H), 2.95 - 2.87 (m, 1H), 2.61 (d, J = 17.2Hz, 1H), 2.46 - 2.36 (m, 1H), 2.20 (s, 2H), 2.01 (dd, J = 9.0, 3.6 Hz, 1H), 1.21 (s, 6H). LCMS (ESI) C 32 H 38 ClN4O4 + [M+H] + : Calculated value 577.26, measured value 577.3.

[0307] Example 49: Preparation of 3-(6-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05363) The target compound (GT-05363) (white solid, 10 mg, yield 10%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.96 - 7.81 (m, 1H), 7.74 - 7.67 (m, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.10 (d, J = 7.6 Hz, 2H), 5.12 (dd, J = 13.2, 5.0 Hz, 1H), 4.51 - 4.34 (m, 4H), 3.56 - 3.40 (m, 4H), 3.08 - 3.05 (m, 2H), 2.99 - 2.85 (m, 2H), 2.86 - 2.71 (m, 2H), 2.70 - 2.57 (m, LCMS (ESI) C 33 H 40 ClN4O3 + [M+H] + : Calculated value 575.28, measured value 575.3.

[0308] Example 50: Preparation of 3-(7-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05360) The target compound (GT-05360) (white solid, 31 mg, yield 30%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 7.69 (brs, 3H), 7.41 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 5.12 (dd, J = 13.1, 5.0 Hz, 1H), 4.94 - 4.88(m, 2H), 4.49 (d, J = 17.6 Hz, 1H), 4.38 (d, J = 17.9 Hz, 1H), 3.67 - 3.61 (m, 4H), 2.99 - 2.86 (m, 2H), 2.73 (s, 1H), 2.62 (d, J = 17.2 Hz, LCMS (ESI) C 33 H 40 ClN4O3 + [M+H] + : Calculated value 575.28, measured value 575.3.

[0309] Example 51: Preparation of 3-(5-(2-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05361) The target compound (GT-05361) (white solid, 28 mg, yield 26%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.50 (s, 1H), 7.44 - 7.40 (m, 3H), 7.12 (d, J = 6.5 Hz, 2H), 5.11 (dd, J = 13.4, 4.8 Hz, 1H), 4.37 (dd, J = 51.1, 17.5 Hz, 2H), 3.62 - 3.49 (m, 3H), 3.14 - 3.05 (m, 3H), 2.97 - 2.85 (m, 3H), 2.69 - 2.54 (m, 4H), 2.46 - 2.29 (m, 3H), 2.26 - 2.19 (m, 2H), 2.15 - 1.94 (m, 4H), 1.54 - 1.38 (m, 2H), 0.96 (s, 6H). LCMS (ESI) C 34 H 42 ClN4O3 + [M+H] + : Calculated value 589.29, measured value 589.3.

[0310] Example 52: Preparation of 3-(5-(3-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05362) The target compound (GT-05362) (white solid, 28 mg, yield 33%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.47 (s, 1H), 7.41 - 7.37 (m, 3H), 7.12 (d, J = 7.9 Hz, 2H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.43 (d, J = 17.3 Hz, 1H), 4.30 (d, J = 17.3 Hz, 1H), 3.77 - 3.55 (m, 4H), 3.39 -3.31 (m, 4H), 3.13 - 3.02 (m, 3H), 2.99 - 2.85 (m, 2H), 2.77 - 2.70 (m, 2H), 2.60 (d, J = 16.4 Hz, 1H), 2.42 - 2.38 (m, 1H), 2.35 - 2.23 (m, 2H), 2.09 - 1.91 (m, 5H), 1.45 - 1.41(m, 2H), 0.96 (s, 6H).LCMS (ESI) C 35 H 44 ClN4O3 + [M+H] + : Calculated value 603.31, measured value 603.3.

[0311] Example 53: Preparation of 3-(4-fluoro-5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05390) The target compound (GT-05390) (white solid, 29 mg, yield 32%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.71 - 7.63 (m, 2H), 7.21 - 7.11 (m, 4H), 5.13 (dd, J = 13.3, 5.0 Hz, 1H), 4.59 - 4.38(m, 2H), 4.16 - 3.90 (m, 2H), 3.43 - 3.28 (m, 5H), 3.15 - 3.03(m, 2H), 2.98 - 2.87 (m, 2H), 2.81 - 2.72 (m, 1H), 2.61 (d, J = 17.6 Hz, 2H), 2.45 (dd, J = 13.2, LCMS (ESI) C 33 H 39 F2N4O3 + [M+H] + : Calculated value 577.30, measured value 577.3.

[0312] Example 54: Preparation of 3-(6-fluoro-5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05391) The target compound (GT-05391) (white solid, 34 mg, yield 38%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.78 - 7.70 (m, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.19 (t, J = 8.8 Hz, 2H), 7.13 (t, J = 6.9 Hz, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.39 (dd, J = 49.9, 17.4 Hz, 2H), 4.10 - 3.98 (m, 1H), 3.30 - 3.20 (m, 5H), 2.94 - 2.87(m, 5H), 2.72 - 2.63 (m, 3H), 2.41 (dd, J = 13.3, 4.7 Hz, 1H), 2.29 (brs, 2H), 2.02 (brs, 3H), 1.45 (t, J = 6.2 Hz, 2H), 0.95 (s, 6H). LCMS (ESI) C 33 H 39 F2N4O3 + [M+H] + : Calculated value 577.30, measured value 577.3.

[0313] Example 55: Preparation of 3-(7-fluoro-5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05392) The target compound (GT-05392) (white solid, 7 mg, yield 8%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.62 - 7.35 (m, 2H), 7.24 - 7.09 (m, 4H), 5.09 (dd, J = 13.2, 5.1 Hz, 1H), 4.56 - 4.29 (m, 3H), 3.37 - 3.27 (m, 4H), 3.30 - 3.00 (m, 4H), 2.98 - 2.85 (m, 2H), 2.83 - 2.72 (m, 1H), 2.60 (d, J = 17.5 Hz, 2H), 2.39 (dd, J = 13.2, 4.7 Hz, 1H), 2.35 - 2.30 (m, 2H), 2.11 - 1.91 (m, 3H), 1.45 (t, J = 6.1 Hz, 2H), 0.95 (s, 6H). LCMS (ESI) C 33 H 39 F2N4O3 + [M+H] + : Calculated value 577.30, measured value 577.3.

[0314] Example 56: Preparation of 3-(4-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05393) The target compound (GT-05393) (white solid, 10 mg, yield 11%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.74 - 7.70 (m, 2H), 7.61 - 7.54 (m, 2H), 7.20 - 7.10 (m, 4H), 5.16 (dd, J = 13.3, 5.0 Hz, 2H), 4.91 (s, 2H), 4.69 - 4.26 (m, 5H), 3.00 - 2.87 (m, 3H), 2.71 - 2.56 (m, 4H), 2.49 - 2.44 (m, 2H), 2.25 - 2.21 (m, 2H), 2.07 - 2.02 (m, 4H), 1.46 (t, J = 6.1 Hz, 2H), 0.95 (s, 6H).LCMS (ESI) C 33 H 40 FN4O3 + [M+H] + : Calculated value 559.31, measured value 559.3.

[0315] Example 57: Preparation of 3-(6-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05394) The target compound (GT-05394) (white solid, 15 mg, yield 16%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.90 (brs, 1H), 7.83 - 7.54 (m, 3H), 7.19 - 7.12 (m, 3H), 5.12 (dd, J = 13.2, 4.9 Hz, 1H), 4.53 - 4.30 (m, 4H), 3.32 - 3.29 (m, 4H), 3.26 - 3.10 (m, 4H), 2.98 - 2.86 (m, 2H), 2.61 (d, J = 17.7 Hz, 2H), 2.46 - 2.37 (m, 1H), 2.33 - 2.27 (m, 2H), 2.01 (brs, 3H), 1.44 (t, J = 6.4 Hz, 2H), 0.95 (s, 6H). LCMS (ESI) C 33 H 40 FN4O3 + [M+H] + : Calculated value 559.31, measured value 559.3.

[0316] Example 58: Preparation of 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05396) The target compound (GT-05396) (white solid, 14 mg, yield 17%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.89 - 7.86 (m, 1H), 7.82 - 7.62 (m, 2H), 7.46 - 7.42 (m, 2H), 7.14 (d, J = 7.6 Hz, 2H), 5.14 (dd, J = 10.9, 2.6 Hz, 1H), 4.67 - 4.24 (m, 4H), 3.82 - 3.59 (m, 4H), 3.10 - 2.89 (m, 4H), 2.61 (d, J = 17.2 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.28 - 2.22 (m, 2H), 2.07 (s, 4H), 1.45 (t, J = 6.0 Hz, 2H), 0.95 (s, 6H). LCMS (ESI) C 34 H 42 ClN4O3 + [M+H] + : Calculated value 589.29, measured value 589.3.

[0317] Example 59: Preparation of 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05529) The target compound (GT-05529) (white solid, 23 mg, yield 26%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.59 - 7.55 (m, 2H), 7.49 - 7.46 (m, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.26 - 7.14 (m, 2H), 5.17 - 5.05 (m, 1H), 4.63 - 4.19 (m, 3H), 4.05 - 4.00 (m, 1H), 3.84 - 3.65 (m, 2H), 3.31 - 3.13 (m, 4H), 2.95 - 2.85 (m, 1H), 2.77 - 2.62 (m, 3H), 2.45 - 2.42 (m, 1H), 2.33 - 2.15 (m, 2H), 2.12 - 1.90 (m, 5H), 1.44 (t, J = 6.1 Hz, 2H), 0.94 (s, 6H). LCMS (ESI) C 34 H 39 ClFN4O3 + [M+H] + : Calculated value 605.27, measured value 605.3.

[0318] Example 60: Preparation of 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05534) The target compound (GT-05534) (white solid, 13 mg, yield 45%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.64 - 7.53 (m, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.55 (d, J = 17.5 Hz, 1H), 4.38 (d, J = 17.5 Hz, 1H), 3.75 (d, J = 21.7 Hz, 4H), 3.47 - 3.43(m, 2H), 3.00 - 2.79 (m, 3H), 2.73 - 2.68 (m, 2H), 2.61 (d, J = 17.2 Hz, 1H), 2.45 - 2.42 (m, 1H), 2.29 (s, 2H), 2.07 - 1.99 (m, 2H), 2.04 - 1.94 (m, 1H), 1.76 (d, J = 8.3 Hz, 2H), 1.46 (t, J = 6.1 Hz, 2H), 1.19 (t, J = 7.3 Hz, 2H), 0.96 (s, 6H). LCMS (ESI) C 35 H 41 ClFN4O3 + [M+H] + : Calculated value 619.28, measured value 619.3.

[0319] Example 61: Preparation of 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05367) The target compound (GT-05367) (white solid, 11 mg, yield 13%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.68 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 7.09 (d, J = 8.2 Hz, 2H), 5.17 - 5.12 (m, 2H), 4.52 - 4.47 (m, 2H), 4.38 - 4.32 (m, 3H), 2.95 - 2.87 (m, 4H), 2.63 - 2.57 (m, 2H), 2.45 - 2.36 (m, 2H), 2.35 - 2.14 (m, 4H), 2.08 - 2.00 (m, 5H), 1.44 - 1.41 (m, 2H), 0.96 (s, 6H). LCMS (ESI) C 34 H 39 ClFN4O3 + [M+H] + : Calculated value 605.27, measured value 605.3.

[0320] Example 62: Preparation of 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05530) The target compound (GT-05530) (white solid, 25 mg, yield 29%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.02 (brs, 1H), 7.72 (dd, J = 9.9, 6.1 Hz, 1H), 7.54 - 7.51 (m, 1H), 7.50 - 7.47 (m, 1H), 7.36 (t, J = 7.9 Hz, 1H), 7.28 - 7.12 (m, 2H), 5.18 - 5.08 (m, 1H), 4.44 - 4.42 (m, 1H), 4.38 - 4.22 (m, 1H), 4.12 - 3.92 (m, 1H), 3.79 - 3.68 (m, 2H), 3.52 - 3.40 (m, 3H), 3.32 - 3.15 (m, 2H), 3.08 - 2.83 (m, 2H), 2.77 - 2.56 (m, 3H), 2.46 - 2.35 (m, 1H), 2.30 - 2.13 (m, 3H), 2.11 - 2.02 (m, 4H), 1.46 - 1.43 (m, 2H), 0.95 (s, 6H). LCMS (ESI) C 34 H 39 ClFN4O3 + [M+H] + : Calculated value 605.27, measured value 605.3.

[0321] Example 63: Preparation of 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05535) The target compound (GT-05535) (white solid, 11 mg, yield 38%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.75 (s, 1H), 7.54 (d, J = 8.7 Hz, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.44 (d, J = 17.4 Hz, 1H), 4.31 (d, J = 17.4 Hz, 1H), 3.83 (brs, 2H), 3.75 (brs, 2H), 3.49 - 3.41 (m, 3H), 3.24 - 3.09 (m, 2H), 2.99 - 2.86 (m, 1H), 2.80 (brs, 1H), 2.61 (d, J = 16.9 Hz, 1H), 2.47 - 2.31 (m, 3H), 2.07 (s, 2H), 2.05 - 1.96 (m, 1H), 1.85 (brs, 2H), 1.46 (t, J = 6.2 Hz, 2H), 1.21 - 1.15 (m, 2H), 0.96 (s, 6H). LCMS (ESI) C 35 H 41 ClFN4O3 + [M+H] + : Calculated value 619.28, measured value 619.3.

[0322] Example 64: Preparation of 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05383) The target compound (GT-05383) (white solid, 30 mg, yield 30%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.59 - 7.55 (m, 1H), 7.53 - 7.49 (m, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.2 Hz, 2H), 5.15 - 5.06 (m, 1H), 4.64 - 4.25 (m, 6H), 2.95 - 2.83 (m, 4H), 2.67 - 2.57 (m, 2H), 2.33 - 2.23 (m, 5H), 2.02 - 1.91 (m, 5H), 1.42 (t, J = 6.7 Hz, 2H), 0.96 (d, J = 3.0 Hz, 6H). LCMS (ESI) C 34 H 39 ClFN4O3 + [M+H] + : Calculated value 605.27, measured value 605.3.

[0323] Example 65: Preparation of 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05531) The target compound (GT-05531) (white solid, 22 mg, yield 25%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.53 - 7.47 (m, 1H), 7.38 - 7.35 (m, 2H), 7.26 - 7.21 (m, 2H), 7.18 - 7.15 (m, 1H), 5.08 (dd, J = 13.3, 5.0 Hz, 1H), 4.53 - 4.50 (m, 1H), 4.49 - 4.45 (m, 1H), 4.41 - 4.29 (m, 1H), 3.84 - 3.79 (m, 1H), 3.63 (s, 1H), 3.31 - 3.14 (m, 3H), 3.12 - 3.01 (m, 1H), 2.98 - 2.78 (m, 2H), 2.62 - 2.51 (m, 3H), 2.46 - 2.35 (m, 1H), 2.30 - 2.19 (m, 2H), 2.13 - 1.89 (m, 5H), 1.45 (d, J = 5.8 Hz, 2H), 0.97 (s, 6H).LCMS (ESI) C 34 H 39 ClFN4O3 + [M+H] + : Calculated value 605.27, measured value 605.3.

[0324] Example 66: Preparation of 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05536) The target compound (GT-05536) (white solid, 12 mg, yield 42%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.39 (s, 1H), 7.27 - 7.23 (m, 1H), 7.21 (t, d = 7.5 Hz, 2H), 5.07 (dd, J = 13.3, 5.1 Hz, 1H), 4.45 (d, J = 17.8 Hz, 1H), 4.32 (d, J = 17.9 Hz, 1H), 3.72 (s, 4H), 3.49 - 3.47 (m, 2H), 2.99 - 2.82 (m, 3H), 2.73 - 2.62 (m, 2H), 2.60 (d, J = 16.7 Hz, 1H), 2.40 - 2.33 (m, 3H), 2.08 (s, 2H), 2.01 - 1.98 (m, 1H), 1.83 (brs, 2H), 1.47 (t, J = 6.2 Hz, 2H), 1.19 (t, J = 7.3 Hz, 2H), 0.96 (s, 6H). LCMS (ESI) C 35 H 41 ClFN4O3 + [M+H] + : Calculated value 619.29, measured value 619.3.

[0325] Example 67: Preparation of 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05525) The target compound (GT-05525) (white solid, 6 mg, yield 7%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 7.75 (s, 1H), 7.68 (s, 1H), 7.43 - 7.36 (m, 2H), 7.29 - 7.10 (m, 2H), 5.14 (dd, J = 13.2, 4.7 Hz, 1H), 4.60 - 4.41 (m, 4H), 3.78 - 3.54 (m, 1H), 3.29 - 3.18 (m, 3H), 3.15 - 2.85 (m, 4H), 2.61 (d, J = 16.8 Hz, 1H), 2.48 - 2.28 (m, 4H), 2.22 - 2.11 (m, 1H), 2.06 - 1.97 (m, 1H), 1.92 - 1.88 (m, 1H), 1.56 - 1.34 (m, 2H), 0.98 (s, 6H). LCMS (ESI) C 33 H 37 ClFN4O4 + [M+H] + : Calculated value 607.25, measured value 607.3.

[0326] Example 68: Preparation of 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05526) The target compound (GT-05526) (white solid, 11 mg, yield 13%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.87 (s, 1H), 7.65 (s, 1H), 7.38 (d, J = 8.5 Hz, 2H), 7.20 (s, 2H), 5.14 (dd, J = 13.2, 5.0 Hz, 1H), 4.49 - 4.32 (m, 4H), 3.65 (brs, 1H), 3.30 - 3.18 (m, 5H), 3.09 - 3.05 (m, 1H), 2.98 - 2.87 (m, 1H), 2.61 (d, J = 16.8 Hz, 1H), 2.48 - 2.27 (m, 4H), 2.22- 2.16 (m, 1H), 2.07 - 1.96 (m, 1H), 1.92 - 1.87 (m, 1H), 1.43 (brs, 2H), 0.96 (s, 6H). LCMS (ESI) C 33 H 37 ClFN4O4 + [M+H] + : Calculated value 607.25, measured value 607.3.

[0327] Example 69: Preparation of 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05527) The target compound (GT-05527) (white solid, 5 mg, yield 6%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.56 - 7.49 (m, 2H), 7.38 (d, J = 8.5 Hz, 2H), 7.29 - 7.10 (m, 2H), 5.10 (dd, J = 13.1, 4.9 Hz, 1H), 4.63 - 4.18 (m, 4H), 3.77 - 3.49 (m, 2H), 3.21 - 3.07 (m, 1H), 3.03 - 2.81 (m, 3H), 2.60 (d, J = 16.3 Hz, 2H), 2.47 - 2.26 (m, 4H), 2.20 - 2.09 (m, 2H), 2.05 - 1.96 (m, 1H), 1.96 - 1.82 (m, 1H), 1.50 - 1.44 (m, 2H), 0.97 (s, 6H).LCMS (ESI) C 33 H 37 ClFN4O4 + [M+H] + : Calculated value 607.25, measured value 607.3.

[0328] Example 70: Preparation of 3-(4-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05528) The target compound (GT-05528) (white solid, 9 mg, yield 11%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.06 (s, 1H), 7.97 - 7.69 (m, 2H), 7.65 - 7.59 (m, 1H), 7.43 - 7.38 (m, 2H), 7.29 - 7.15 (m, 2H), 5.26 - 5.09 (m, 1H), 4.74 - 4.62 (m, 1H), 4.54 - 4.20 (m, 3H), 3.74 - 3.63 (m, 1H), 3.33 - 3.18 (m, 4H), 3.07 - 3.88 (m, 3H), 2.64 (d, J = 17.8 Hz, 1H), 2.41 - 2.27 (m, 4H), 2.27 - 2.11 (m, 1H), 2.09 - 2.01 (m, 2H), 1.92 - 1.88 (m, 1H), 1.60 - 1.36 (m, 2H), 0.97 (s, 6H). LCMS (ESI) C 33 H 38 ClN4O4 + [M+H] + : Calculated value 589.26, measured value 589.3.

[0329] Example 71: Preparation of 3-(5-(4-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05359) The target compound (GT-05359) (white solid, 11 mg, yield 16%) was prepared according to the method of Synthesis Scheme 6. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.93 (s, 1H), 7.87 - 7.83 (m, 1H), 7.57 - 7.50 (m, 2H), 7.44 - 7.38 (m, 2H), 7.23 - 7.15 (m, 4H), 6.81 (d, J = 7.9 Hz, 1H), 5.15 (dd, J = 13.2, 5.1 Hz, 1H), 4.53 (d, J = 17.5 Hz, 1H), 4.40 (d, J = 17.5 Hz, 1H), 4.36 - 4.22 (m, 1H), 4.13 - 4.08 (m, 1H), 3.14 - 3.02 (m, 4H), 2.95 - 2.89 (m, 2H), 2.67 - 2.58 (m, 1H), 2.43 - 2.30 (m, 4H), 2.22 - 2.08 (m, 2H), 2.07 - 2.00 (m, 1H), 1.95 - 1.87 (m, 1H), 1.51 - 1.40 (m, 3H), 0.97 (s, 6H). LCMS (ESI) C 39 H 42 ClN4O4 + [M+H] + : Calculated value 665.29, measured value 665.3.

[0330] Example 72: Preparation of 3-(5-((3-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05521) The target compound (GT-05521) (white solid, 10 mg, yield 12%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.86 - 7.73 (m, 1H), 7.72 - 7.61 (m, 1H), 7.50 - 7.33 (m, 3H), 7.28 - 7.16 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.62 - 4.58 (m, 1H), 4.51 - 4.43 (m, 1H), 4.37 - 4.19 (m, 2H), 4.17 - 4.10 (m, 1H), 3.80 - 3.63 (m, 1H), 3.50 - 3.39 (m, 1H), 3.25 - 3.13 (m, 2H), 2.95 - 2.89 (m, 1H), 2.61 (d, J = 17.6 Hz, 2H), 2.49 - 2.33 (m, 3H), 2.26 - 2.17 (m, 1H), 2.12 - 1.96 (m, 2H), 1.93 - 1.89 (m, 1H), 1.59 - 1.33 (m, 2H), 0.99 (d, J = 6.6 Hz, 6H). LCMS (ESI) C 34 H 38 ClN4O4 + [M+H] + : Calculated value 601.26, measured value 601.3.

[0331] Example 73: Preparation of 3-(5-((3-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05522) The target compound (GT-05522) (white solid, 12 mg, yield 15%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.97 - 7.64 (m, 3H), 7.45 - 7.36 (m, 3H), 7.15 (d, J = 7.7 Hz, 1H), 5.14 (dd, J = 12.7, 4.7 Hz, 1H), 4.51 - 4.46 (m, 2H), 4.26 - 4.16 (m, 2H), 4.16 - 4.04 (m, 1H), 3.93 - 3.80 (m, 1H), 3.76 (brs, 1H), 3.69 - 3.52 (m, 1H), 3.27 - 3.18 (m, 2H), 3.00 - 2.85 (m, 1H), 2.75 - 2.68 (m, 1H), 2.61 (d, J = 17.4 Hz, 1H), 2.47 - 2.21 (m, 4H), 2.16 - 2.10 (m, 1H), 2.02 - 1.99 (m, 2H), 1.90 - 1.88 (m, 1H), 1.65 - 1.63 (m, 1H), 1.52 - 1.43 (m, 2H), 0.95 (s, 6H). LCMS (ESI) C 35 H 40 ClN4O4 + [M+H] + : Calculated value 615.27, measured value 615.3.

[0332] Example 74: Preparation of 3-(5-((8-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05523) The target compound (GT-05523) (white solid, 12 mg, yield 15%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.90 - 7.86 (m, 1H), 7.79 - 7.69 (m, 2H), 7.41 (d, J = 7.7 Hz, 2H), 7.26 (d, J = 7.7 Hz, 2H), 5.20 - 5.04 (m, 1H), 4.62 - 4.13 (m, 4H), 3.91 (brs, 1H), 3.41 - 3.28 (m, 4H), 3.21 - 3.07 (m, 2H), 3.03 - 2.82 (m, 2H), 2.63 (t, J = 17.3 Hz, 2H), 2.47 - 2.21 (m, 4H), 2.07 - 1.94 (m, 2H), 1.91 - 1.76 (m, 2H), 1.56 - 1.37 (m, 2H), 0.97 (s, 6H). LCMS (ESI) C 35 H 40 ClN4O4 + [M+H] + : Calculated value 615.27, measured value 615.3.

[0333] Example 75: Preparation of 3-(5-((5-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05524) The target compound (GT-05524) (white solid, 10 mg, yield 12%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.85 - 7.75 (m, 2H), 7.74 - 7.65 (m, 1H), 7.51 - 7.33 (m, 2H), 7.32 - 7.18 (m, 2H), 5.14 (dd, J = 13.1, 5.1 Hz, 1H), 4.66 - 4.09 (m, 6H), 3.73 - 3.60 (m, 1H), 3.27 - 3.22 (m, 2H), 3.15 - 3.13 (m, 1H), 3.05 - 2.84 (m, 2H), 2.61 (d, J = 16.1 Hz, 1H), 2.43 (dd, J = 13.1, 3.8 Hz, 1H), 2.39 - 2.10 (m, 4H), 2.03 - 1.99 (m, 2H), 1.53 - 1.34 (m, 2H), 0.97 (s, 6H). LCMS (ESI) C 34 H 38 ClN4O4 + [M+H] + : Calculated value 601.26, measured value 601.3.

[0334] Example 76: Preparation of 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05541) Referring to the method of Synthesis Scheme 6, the raw materials 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxylic acid and 2-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane were subjected to an amide condensation reaction to produce the target compound (GT-05541) (white solid, 51 mg, yield 60%). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.80 - 7.74 (m, 1H), 7.64 (d, J = 29.1 Hz, 1H), 7.57 - 7.52 (m, 1H), 7.42 - 7.35 (m, 1H), 7.34 - 7.15 (m, 3H), 5.14 (dt, J = 11.3, 5.6 Hz, 1H), 4.71 - 4.67 (m, 1H), 4.55 - 4.36 (m, 2H), 4.17 (t, J = 28.0 Hz, 1H), 3.47 - 3.41 (m, 1H), 3.27 - 3.00 (m, 2H), 3.00 - 2.85 (m, 2H), 2.61 (d, J = 16.9 Hz, 1H), 2.46 - 2.35 (m, 1H), 2.30 - 2.23 (m, 3H), 2.07 - 2.00 (m, 2H), 1.83 - 1.75 (m, 1H), 1.63 - 1.60 (m, 1H), 1.47 - 1.42 (m, 2H), 0.97 (s, 6H). LCMS (ESI) C 34 H 36 ClN4O5 + [M+H] + : Calculated value 615.24, measured value 615.3.

[0335] Example 77: Preparation of 3-(5-(2-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05876) The target compound (GT-05876) (white solid, 37 mg, yield 50%) was obtained by referring to the method in Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.58 - 7.51 (m, 3H), 7.49 - 7.47(m, 2H), 7.45 - 7.38 (m, 3H), 7.35 - 7.26 (m, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.48 - 4.37 (m, 2H), 4.09 - 3.82 (m, 2H), 3.37 - 3.25 (m, 7H), 3.24 - 3.04 (m, 4H), 3.00 - 2.84 (m, 2H), 2.60 (d, J = 16.2 Hz, 1H), 2.48 - 2.32 (m, 1H), 2.11 - 1.91 (m, 1H). LCMS (ESI) C 32 H 34 ClN4O3 + [M+H] + : Calculated value 557.23, measured value 557.3.

[0336] Example 78: Preparation of 3-(5-(3-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05893) The target compound (GT-05893) (white solid, 38 mg, yield 48%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.79 (brs, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.49 - 7.35 (m, 6H), 7.34 - 7.26 (m, 1H), 5.10 (dd, J = 13.3, 5.0 Hz, 1H), 4.45 - 4.27 (m, 3H), 3.45 - 3.30 (m, 4H), 3.18 - 3.06 (m, 4H), 2.98 - 2.85 (m, 2H), 2.77 - 2.73 (m, 3H), 2.60 (d, J = 17.0 Hz, 2H), 2.46 - 2.32 (m, 1H), 2.05 - 1.97 (m, 3H). LCMS (ESI) C 33 H 36 ClN4O3 + [M+H] + : Calculated value 571.25, measured value 571.3.

[0337] Example 79: Preparation of 3-(4-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05861) The target compound (GT-05861) (white solid, 41 mg, yield 45%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 7.75 (brs, 2H), 7.57 (brs, 1H), 7.29 - 7.03 (m, 4H), 5.15 (dd, J = 13.2, 4.9 Hz, 1H), 4.71 (brs, 1H), 4.44 - 4.40 (m, 1H), 3.39 - 3.33 (m, 4H), 3.30 - 3.10 (m, 4H), 3.03 - 2.85 (m, 3H), 2.73 (brs, 1H), 2.63 (d, J = 17.0 Hz, 2H), 2.43 - 2.15 (m, 5H), 2.08 - 1.94 (m, 1H), 1.68 (s, 4H). LCMS (ESI) C 31 H 36 FN4O3 + [M+H] + : Calculated value 531.28, measured value 531.3.

[0338] Example 80: Preparation of 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05382) The target compound (GT-05382) (white solid, 12 mg, yield 19%) was obtained by referring to the method in Synthesis Scheme 2. 1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 7.73 - 7.62 (m, 1H), 7.58 - 7.56(m, 1H), 7.53 - 7.47 (m, 3H), 7.46 - 7.43 (m, 2H), 7.41 - 4.37 (m, 1H), 7.37 - 7.27 (m, 1H), 6.60 (brs, 1H), 6.58 (brs, 1H), 5.02 (dd, J = 13.3, 5.1 Hz, 1H), 4.56 - 4.38 (m, 3H), 4.28 (d, J = 17.0 Hz, 2H), 4.16 (d, J = 16.9 Hz, 2H), 4.05 - 3.96 (m, 1H), 3.78 - 3.71 (m, 1H), 2.98 - 2.93 (m, 1H), 2.60 - 2.51 (m, 1H), 2.39 - 2.33 (m, 1H), 1.98 - 1.90 (m, 1H). LCMS (ESI) C 29 H 28 ClN4O3 + [M+H] + : Calculated value 515.18, measured value 515.2.

[0339] Example 81: Preparation of 3-(4-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04947) The target compound (GT-04947) (white solid, 39 mg, yield 49%) was obtained by referring to the method in Synthesis Scheme 1. 1H NMR (400 MHz, DMSO) δ 11.07 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 7.7 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.53 - 7.45 (m, 3H), 7.40 (d, J = 8.5 Hz, 1H), 7.22 - 7.17 (m, 1H), 7.01 - 6.93 (m, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.73 (t, J = 7.4 Hz, 1H), 5.19 (dd, J = 12.8, 4.7 Hz, 1H), 4.73 - 4.68 (m, 1H), 4.56 - 4.44 (m, 2H), 4.35 (d, J = 4.5 Hz, 2H), 3.23 - 3.04 (m, 2H), 3.04 - 2.88 (m, 2H), 2.65 (d, J = 15.8 Hz, 1H), 2.36 - 2.32 (m, 1H), 2.17 - 1.94 (m, 4H), 1.67 - 1.59 (m, 1H). LCMS (ESI) C 31 H 32 ClN4O3 + [M+H] + : Calculated value 543.22, measured value 543.3.

[0340] Example 82: Preparation of 3-(5-((8-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05618) The target compound (GT-05618) (white solid, 54 mg, yield 62%) was obtained by referring to the method in Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 8.04 (brs, 1H), 7.71 - 7.68 (m, 1H), 7.64 - 7.49 (m, 4H), 7.46 - 7.41 (m, 3H), 7.37 - 7.31 (m, 1H), 5.10 (dd, J = 13.3, 5.2 Hz, 1H), 4.36 (dd, J = 51.8, 17.7 Hz, 2H), 4.19 (brs, 1H), 3.84 - 3.54 (m, 4H), 3.54 - 3.47 (m, 4H), 2.96 - 2.89 (m, 2H), 2.80 - 2.54 (m, 3H), 2.46 - 2.28 (m, 1H), 2.08 - 1.94 (m, 1H), 1.94 - 1.76 (m, 1H), 1.35 - 1.26 (m, 1H). LCMS (ESI) C 33 H 34 ClN4O3 + [M+H] + : Calculated value 569.23, measured value 569.3.

[0341] Example 83: Preparation of 3-(5-((5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05619) The target compound (GT-05619) (white solid, 40 mg, yield 46%) was obtained by referring to the method in Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 8.17 (brs, 1H), 7.90 (brs, 1H), 7.80 (d, J = 4.8 Hz, 2H), 7.64 - 7.36 (m, 6H), 7.29 (brs, 1H), 5.14 (dd, J = 12.9, 5.0 Hz, 1H), 4.70 - 4.22 (m, 5H), 4.01 - 3.55 (m, 3H), 3.78 - 3.56 (m, 2H), 3.32 - 3.14 (m, 3H), 3.00 - 2.87 (m, 1H), 2.68 - 2.57 (m, 1H), 2.49 - 2.46 (m, 1H), 2.33 - 2.09 (m, 1H), 2.07 - 1.95 (m, 1H), 1.90 - 1.43 (m, 2H). LCMS (ESI) C 33 H 34 ClN4O3 + [M+H] + : Calculated value 569.23, measured value 569.2.

[0342] Example 84: Preparation of 3-(5-((4-(2-(5-chloropyridin-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05860) The target compound (GT-05860) (white solid, 32 mg, yield 59%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 8.90 (s, 1H), 8.15 (d, J = 7.5 Hz, 1H), 7.96 - 7.67 (m, 6H), 7.65 - 7.53 (m, 2H), 5.14 (dd, J = 13.2, 5.1 Hz, 1H), 4.69 - 4.06 (m, 7H), 3.30 - 3.01 (m, 5H), 2.98 - 2.83 (m, 2H), 2.61 (d, J = 16.7 Hz, 2H), 2.43 (dd, J = 13.0, 4.6 Hz, 1H), 2.03 - 1.99 (m, 1H). LCMS (ESI) C 30 H 31 ClN5O3 + [M+H] + : Calculated value 544.21, measured value 544.3.

[0343] Example 85: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05629) The target compound (GT-05629) (white solid, 33 mg, yield 37%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.93 (s, 1H), 7.81 - 7.67 (m, 5H), 7.59 - 7.49 (m, 5H), 5.12 (dd, J = 13.4, 5.0 Hz, 1H), 4.48 - 4.31 (m, 4H), 3.90 - 3.62 (m, 2H), 3.57 - 3.41 (m, 4H), 3.16 - 3.09 (m, 2H), 3.00 - 2.81 (m, 2H), 2.67 - 2.51 (m, 2H), 2.45 - 2.33 (m, 1H), 2.09 - 1.88 (m, 1H). LCMS (ESI) C 31 H 32 ClN4O3 + [M+H] +: Calculated value 543.22, measured value 543.3.

[0344] Example 86: Preparation of 3-(5-((4-(3-(5-chloropyridin-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05596) The target compound (GT-05596) (white solid, 9 mg, yield 10%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 8.73 (t, J = 1.6 Hz, 1H), 8.33 (s, 1H), 8.15 (d, J = 7.2 Hz, 1H), 8.08 (d, J = 1.5 Hz, 2H), 7.79 (d, J = 7.9 Hz, 2H), 7.74 - 7.64 (m, 2H), 7.61 - 7.57 (m, 1H), 5.21 - 5.11 (m, 1H), 4.69 - 4.17 (m, 8H), 3.38 - 3.19 (m, 5H), 2.95 - 2.89 (m, 2H), 2.60 (d, J = 17.1 Hz, 1H), 2.46 - 2.38 (m, 1H), 2.05 - 1.95 (m, 1H).LCMS (ESI) 30 H 31 ClN5O3 + [M+H] + : Calculated value 544.21, measured value 544.2.

[0345] Example 87: Preparation of 3-(1-oxo-5-((4-(3-(thiophen-2-yl)benzyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05597) The target compound (GT-05597) (white solid, 52 mg, yield 56%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.97 - 7.90 (m, 1H), 7.85 - 7.75 (m, 2H), 7.74 - 7.64 (m, 2H), 7.59 (d, J = 5.1 Hz, 1H), 7.56 (d, J = 3.5 Hz, 1H), 7.48 (d, J = 4.0 Hz, 2H), 7.17 (dd, J = 5.0, 3.7 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.50 - 4.33 (m, 5H), 3.62 - 3.54 (m, 4H), 3.34 - LCMS (ESI) C 29 H 31 N4O3S + [M+H] + : Calculated value 515.21, measured value 515.2.

[0346] Example 88: Preparation of 3-(5-((4-(3-(furan-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05692) The target compound (GT-05692) (white solid, 34 mg, yield 36%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.93 (t, J = 11.8 Hz, 1H), 7.83 - 7.71 (m, 4H), 7.71 - 7.58 (m, 1H), 7.51 - 7.44 (m, 2H), 6.98 (d, J = 3.3 Hz, 1H), 6.63 (dd, J = 3.3, 1.7 Hz, 1H), 5.13 (dd, J = 13.3, 4.7 Hz, 1H), 4.59 - 4.16 (m, 7H), 3.31 - 3.20 (m, 4H), 2.95 - 2.89 (m, 2H), 2.67 - 2.57 (m, 3H), 2.41 (dd, J = 12.5, 4.2 Hz, 1H), 2.04 - 1.99 (m, 1H). LCMS (ESI) C 29 H 31 N4O4 + [M+H] + : Calculated value 499.23, measured value 499.2.

[0347] Example 89: Preparation of 3-(5-((4-(3-(1H-pyrrol-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05733) The target compound (GT-05733) (white solid, 31 mg, yield 32%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 11.00 (s, 1H), 7.92 - 7.76 (m, 3H), 7.66 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.7 Hz, 1H), 7.32 - 7.29 (m, 1H), 6.88 (d, J = 1.3 Hz, 1H), 6.54 (s, 1H), 6.13 (dd, J = 5.6, 2.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.0 Hz, 1H), 4.61 - 4.16 (m, 7H), 3.22 - 3.06 (m, LCMS (ESI) C 29 H 32 N5O3 + [M+H] + : Calculated value 498.25, measured value 498.3.

[0348] Example 90: Preparation of 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05598) The target compound (GT-05598) (white solid, 45 mg, yield 50%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.80 - 7.70 (m, 9H), 7.58 - 7.48 (m, 2H), 5.13 (dd, J = 13.3, 5.0 Hz, 1H), 4.50 - 4.33 (m, 5H), 3.76- 3.59 (m, 4H), 3.37 - 3.13 (m, 5H), 2.99 - 2.85 (m, 1H), 2.61 (d, J = 16.7 Hz, 1H), 2.42 (dd, J = 13.2, 4.5 Hz, 1H), 2.07 - 1.91 (m, 1H).LCMS (ESI) C 31 H 32 ClN4O3 + [M+H] + : Calculated value 543.22, measured value 543.2.

[0349] Example 91: Preparation of 3-(5-((4-(4-(5-chloropyridin-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05872) The target compound (GT-05872) (white solid, 39 mg, yield 44%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 8.73 (dd, J = 2.3, 0.8 Hz, 1H), 8.15 (d, J = 8.2 Hz, 2H), 8.10 - 8.01 (m, 2H), 7.79 (d, J = 7.8 Hz, 2H), 7.70 (d, J = 5.7 Hz, 3H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.58 - 4.20 (m, 6H), 3.41 - 3.32 (m, 4H), 3.33 - 3.08 (m, 4H), 2.98 - 2.86 (m, 1H), 2.61 (d, J = 16.7 Hz, 1H), 2.42 (dd, J = 13.1, 4.4 Hz, 1H), 2.06 - 1.95 (m, 1H). LCMS (ESI) C 30 H 31 ClN5O3 + [M+H] + : Calculated value 544.21, measured value 544.2.

[0350] Example 92: Preparation of 3-(1-oxo-5-((4-(4-(thiophen-2-yl)benzyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05640) The target compound (GT-05640) (white solid, 9 mg, yield 10%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.81 - 7.66 (m, 4H), 7.65 - 7.43 (m, 5H), 7.16 (dd, J = 5.0, 3.7 Hz, 1H), 5.13 (dd, J = 13.4, 4.8 Hz, 1H), 4.49 - 4.43 (m, 5H), 3.42 - 3.35 (m, 4H), 3.24 - 3.04 (m, 4H), 2.94 - 2.88 (m, 1H), 2.69 - 2.57 (m, 2H), 2.41 (dd, J = 15.2, 2.4 Hz, 1H), 2.08 - 1.94 (m, 1H). LCMS (ESI) C 29 H 31 N4O3S + [M+H] + : Calculated value 515.21, measured value 515.2.

[0351] Example 93: Preparation of 3-(5-((4-(4-(furan-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05693) The target compound (GT-05693) (white solid, 58 mg, yield 61%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.79 - 7.75 (m, 5H), 7.72 - 7.66 (m, 1H), 7.63 - 7.61 (m, 2H), 7.04 (d, J = 3.3 Hz, 1H), 6.62 (dd, J = 3.4, 1.8 Hz, 1H), 5.13 (dd, J = 13.3, 5.0 Hz, 1H), 4.60 - 4.07 (m, 7H), 3.29 - 3.14 (m, 4H), 3.07 - 2.95 (m, 1H), 2.99 - 2.84 (m, 2H), 2.68 - 2.56 (m, 2H), 2.44 - 2.40 (m, 1H), 2.04 - 1.99 (m, 1H). LCMS (ESI) C 29 H 31N4O4 + [M+H] + : Calculated value 499.23, measured value 499.3.

[0352] Example 94: Preparation of 3-(5-((4-(4-(1H-pyrrol-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05734) The target compound (GT-05734) (white solid, 32 mg, yield 33%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 11.00 (s, 1H), 7.83 - 7.73 (m, 2H), 7.69 - 7.64 (m, 3H), 7.53 - 7.51 (m, 2H), 6.88 (s, 1H), 6.59 (s, 1H), 6.13 (dd, J = 5.6, 2.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.64 - 4.04 (m, 7H), 3.25 - 3.06 (m, 5H), 2.99 - 2.86 (m, 2H), 2.60 (d, J = 16.8 Hz, 2H), 2.45 - 2.34 (m, 1H), 2.06 - 1.90 (m, 1H). LCMS (ESI) C 29 H 32 N5O3 + [M+H] + : Calculated value 498.25, measured value 498.2.

[0353] Example 95: Preparation of 3-(5-((4-((6-(4-chlorophenyl)pyridin-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05632) The target compound (GT-05632) (white solid, 49 mg, yield 55%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 8.81 (s, 1H), 8.15 (d, J = 8.6 Hz, 2H), 8.10 (d, J = 7.7 Hz, 2H), 7.80 (d, J = 7.8 Hz, 2H), 7.72 - 7.69(m, 1H), 7.58 (d, J = 8.7 Hz, 2H), 5.13 (dd, J = 13.2, 5.0 Hz, 1H), 4.51 - 4.34 (m, 6H), 3.49 - 3.42 (m, 4H), 3.39 - 3.32 (m, 4H), 2.99 - 2.84 (m, 2H), 2.66 - 2.54 (m, 1H), 2.44 - 2.40 (m, 1H), 2.07 - 1.89 (m, 1H). LCMS (ESI) C 30 H 31 ClN5O3 + [M+H] + : Calculated value 544.21, measured value 544.2.

[0354] Example 96: Preparation of 3-(5-((4-([2,4'-bipyridin]-5-ylmethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05633) The target compound (GT-05633) (white solid, 32 mg, yield 34%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.09 (s, 1H), 9.04 (d, J = 6.6 Hz, 2H), 8.71 (d, J = 6.7 Hz, 2H), 8.51 (d, J = 8.2 Hz, 1H), 8.42 (d, J = 8.3 Hz, 1H), 7.94 (s, 1H), 7.81 (q, J = 8.1 Hz, 2H), 5.14 (dd, J = 13.2, 5.1 Hz, 1H), 4.71 - 4.33 (m, 10H), 3.94 - 3.83 (m, 4H), 2.99 - 2.87 (m, 1H), 2.61 (d, J = 16.9 Hz, 1H), 2.43 (dd, J = 13.2, 4.6 Hz, 1H), 2.03 - 2.00 (m, 1H). LCMS (ESI) C 29 H 31 N6O3 + [M+H] + : Calculated value 511.25, measured value 511.2.

[0355] Example 97: Preparation of 3-(1-oxo-5-((4-((5-phenylpyrazin-2-yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05544) The target compound (GT-05544) (white solid, 32 mg, yield 34%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.30 (s, 1H), 8.90 (s, 1H), 8.18 (dd, J = 7.9, 1.6 Hz, 2H), 7.90 - 7.70 (m, 3H), 7.64 - 7.51 (m, 3H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.60 - 4.29 (m, 6H), 3.45 - 3.41 (m, 4H), 3.33 - 3.23 (m, 4H), 2.99 - 2.85 (m, 1H), 2.61 (d, J = 16.6 Hz, 1H), 2.45 - 2.40 (m, 1H), 2.06 - 1.93 (m, 1H).LCMS (ESI) C 29 H 31 N6O3 + [M+H] + : Calculated value 511.25, measured value 511.2.

[0356] Example 98: Preparation of 3-(5-((4-((5-(4-chlorophenyl)thiophen-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05625) The target compound (GT-05625) (white solid, 24 mg, yield 27%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.80 (d, J = 7.7 Hz, 2H), 7.70 - 7.62 (m, 3H), 7.49 (d, J = 8.6 Hz, 3H), 7.24 (brs, 1H), 5.13 (dd, J = 13.2, 5.2 Hz, 1H), 4.60 - 4.17 (m, 6H), 3.35 - 3.26 (m, 4H), 3.17 - 3.00 (m, 4H), 2.91 - 2.88 (m, 2H), 2.61 (d, J = 16.7 Hz, 1H), 2.44 - 2.39 (m, 1H), 2.04 - 1.95 (m, 1H). LCMS (ESI) C 29 H30 ClN4O3S + [M+H] + : Calculated value 549.17, measured value 549.2.

[0357] Example 99: Preparation of 3-(5-((4-([2,2'-bithiophene]-5-ylmethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05624) The target compound (GT-05624) (white solid, 29 mg, yield 31%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.80 (d, J = 7.7 Hz, 2H), 7.70 (d, J = 6.9 Hz, 1H), 7.54 (d, J = 4.5 Hz, 1H), 7.31 (d, J = 3.0 Hz, 1H), 7.25 (brs, 1H), 7.21 (brs, 1H), 7.10 (dd, J = 5.1, 3.6 Hz, 1H), 5.13 (dd, J = 13.2, 5.1 Hz, 1H), 4.51 - 4.34 (m, 6H), 3.40 - 3.32 (m, 4H), 3.24 - 2.96 (m, LCMS (ESI) C 27 H 29 N4O3S2 + [M+H] + : Calculated value 521.17, measured value 521.2.

[0358] Example 100: Preparation of 3-(5-((4-((5-(4-chlorophenyl)furan-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05694) The target compound (GT-05694) (white solid, 34 mg, yield 37%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.84 - 7.66 (m, 5H), 7.51 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 3.2 Hz, 1H), 6.75 (s, 1H), 5.13 (dd, J = 13.1, 5.1 Hz, 1H), 4.64 - 4.21 (m, 7H), 3.27 - 3.14 (m, 5H), 2.99 - 2.83 (m, 2H), 2.63 (t, J = 18.5 Hz, 2H), 2.42 (dd, J = 13.2, 4.5Hz, 1H), 2.02 - 1.91 (m, 1H). LCMS (ESI) C 29 H 30 ClN4O4 + [M+H] + : Calculated value 533.20, measured value 533.3.

[0359] Example 101: Preparation of 3-(1-oxo-5-((4-((5-(thiophen-2-yl)furan-2-yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione (GT-05627) The target compound (GT-05627) (white solid, 27 mg, yield 28%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.87 - 7.76 (m, 2H), 7.71 (d, J = 7.1 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.13 (dd, J = 4.9, 3.7 Hz, 1H), 6.79 (d, J = 3.2 Hz, 1H), 6.74 (s, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.61 - 4.17 (m, 6H), 3.39 - 3.28 (m, 4H), 3.24 - 3.02 (m, 4H), 2.97 - 2.87 (m, 1H), 2.60 (d, J = 16.9 Hz, 1H), 2.46 - 2.32 (m, 1H), 2.07 - 1.95 (m, 1H). 27 H 29 N4O4S + [M+H] + : Calculated value 505.19, measured value 505.2.

[0360] Example 102: Preparation of 3-(5-((4-([2,2'-bifuran]-5-ylmethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05695) The target compound (GT-05695) (white solid, 37 mg, yield 38%) was prepared according to the method of Synthesis Scheme 1. 1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.85 - 7.66 (m, 4H), 6.73 (brs, 3H), 6.64 - 6.59 (m, 1H), 5.13 (dd, J = 13.2, 5.1 Hz, 1H), 4.61 - 4.17 (m, 7H), 3.29 - 3.01 (m, 5H), 2.99 - 2.86 (m, 2H), 2.63 (t, J = 16.7 Hz, 2H), 2.42 (dd, J = 13.1, 4.5 Hz, 1H), 2.09 - 1.88 (m, 1H). LCMS (ESI) C27 H 29 N4O5 + [M+H] + : Calculated value 489.21, measured value 489.2.

[0361] Example 103: Preparation of 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-04397) The target compound (GT-04397) (white solid, 24 mg, yield 36%) was prepared according to the method of Synthesis Scheme 6. 1 H NMR (400 MHz, MeOD) δ 7.49 - 7.33 (m, 9H), 6.51 - 6.44 (m, 1H), 6.39 (s, 1H), 4.97 (dd, J = 13.3, 5.2 Hz, 1H), 4.30 - 4.19 (m, 3H), 4.06 - 4.01 (m, 1H), 3.94 - 3.85 (m, 1H), 3.69 (dd, J = 10.8, 4.7 Hz, 1H), 3.33 - 3.26 (m, 1H), 2.86 - 2.73 (m, 1H), 2.69 - 2.63 (m, 1H), 2.31 - 2.21 (m, 1H), 2.07 - 1.97 (m, 1H). LCMS (ESI) C 29 H 26 ClN4O4 + [M+H] + : Calculated value 529.16, measured value 529.2.

[0362] Example 104: Preparation of 3-(5-(4-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05874) The target compound (GT-05874) (white solid, 16 mg, yield 27%) was prepared according to the method of Synthesis Scheme 6. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.93 (s, 1H), 7.83 (brs, 4H), 7.72 - 7.36 (m, 10H), 5.15 (dd, J = 13.2, 5.1 Hz, 1H), 4.55 - 4.38 (m, 4H), 4.32 (brs, 1H), 3.30 - 3.23 (m, 4H), 3.07 (brs, 2H), 3.02 - 2.86 (m, 2H), 2.62 (d, J = 16.4 Hz, 2H), 2.44 (dd, J = 13.3, 4.4 Hz, 1H), 2.04 - 1.97 (m, 1H). LCMS (ESI) C 37 H 34 ClN4O4 + [M+H] + : Calculated value 633.23, measured value 633.3.

[0363] Example 105: Preparation of 3-(5-((7-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05620) The target compound (GT-05620) (white solid, 52 mg, yield 62%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.43 - 11.20 (m, 1H), 11.00 (s, 1H), 7.78 (d, J = 7.7 Hz, 2H), 7.67 (d, J = 7.4 Hz, 1H), 7.53 - 7.39 (m, 7H), 7.36 - 7.26 (m, 1H), 5.13 (dd, J = 13.3, 5.3 Hz, 1H), 4.50 - 4.32 (m, 4H), 3.88 - 3.74 (m, 4H), 3.66 - 3.54 (m, 2H), 3.06 - 2.86 (m, 2H), 2.85 - 2.70 (m, 1H), 2.61 (d, J = 17.4 Hz, 1H), 2.46 - 2.34 (m, 1H), 2.08 - 1.93 (m, 1H), 1.94 - 1.71 (m, 1H), 1.70 - 1.43 (m, 2H), 1.06 - 0.94 (m, 1H). LCMS (ESI) C 34 H 34 ClN4O4 + [M+H] + : Calculated value 597.23, measured value 597.3.

[0364] Example 106: Preparation of 3-(5-(3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05875) The target compound (GT-05875) (white solid, 34 mg, yield 52%) was prepared according to the method of Synthesis Scheme 6. 1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 7.58 (s, 2H), 7.54 - 7.41 (m, 4H), 7.36 - 7.33 (m, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.24 (dd, J = 7.6, 2.3 Hz, 1H), 6.98 - 6.89 (m, 1H), 6.87 - 6.81 (m, 1H), 5.10 - 4.94 (m, 1H), 4.45 - 4.41 (m, 1H), 4.35 - 4.23 (m, 1H), 4.23 - 4.08 (m, 2H), 3.92 (d, J = 13.2 Hz, 1H), 3.12 (dd, J = 50.6, 12.2 Hz, 2H), 2.99 - 2.84 (m, 1H), 2.71 - 2.54 (m, 3H), 2.40 - 2.34 (m, 1H), 2.05 - 1.83 (m, 2H), 1.83 - 1.68 (m, 1H), 1.65 - 1.42 (m, 1H), 1.17 - 1.12 (m, 1H). LCMS (ESI) C 32 H 30 ClN4O4 + [M+H] + : Calculated value 569.20, measured value 569.2.

[0365] Example 107: Preparation of 3-(5-((8-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05542) The target compound (GT-05542) (white solid, 60 mg, yield 70%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 7.95 - 7.91 (m, 1H), 7.82 - 7.69 (m, 2H), 7.59 - 7.48 (m, 6H), 7.41 - 7.36 (m, 2H), 5.12 (dd, J = 12.9, 3.5 Hz, 1H), 4.69 - 4.59 (m, 1H), 4.55 - 4.21 (m, 3H), 3.67 - 3.61 (m, 1H), 3.56 - 3.41(m, 4H), 3.24 - 3.09 (m, 1H), 3.13 - 2.99 (m, 1H), 2.96 LCMS (ESI) C 33 H 32 ClN4O4 + [M+H] + : Calculated value 583.21, measured value 583.2.

[0366] Example 108: Preparation of 3-(5-((5-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05543) The target compound (GT-05543) (white solid, 51 mg, yield 60%) was prepared according to the method of Synthesis Scheme 1. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 8.02 - 7.88 (m, 1H), 7.85 - 7.76 (m, 1H), 7.68 - 7.34 (m, 9H), 5.14 (dd, J = 12.9, 4.7 Hz, 1H), 4.71 - 4.42 (m, 3H), 4.42 - 4.28 (m, 1H), 4.25 - 4.16 (m, 1H), 3.97 - 3.56 (m, 2H), 3.45 - 3.41 (m, 2H), 3.27 - 3.08 (m, 1H), 2.96 - 2.89 (m, 2H), 2.61 LCMS (ESI)C 33 H 32 ClN4O4 + [M+H] + : Calculated value 583.21, measured value 583.2.

[0367] Example 109: Preparation of 3-(5-(6-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05637) The target compound (GT-05637) (white solid, 21 mg, yield 29%) was prepared according to the methods of Synthesis Scheme 6 and Example 76. 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.85 - 7.79 (m, 2H), 7.74 - 7.63 (m, 1H), 7.64 - 7.45 (m, 5H), 7.45 - 7.36 (m, 2H), 7.36 - 7.29 (m, 1H), 5.13 (dd, J = 13.3, 5.2 Hz, 1H), 4.52 - 4.35 (m, 4H), 4.24 (brs, 3H), 4.04 (brs, 3H), 3.64 - 3.47 (m, 2H), 3.00 - 2.82 (m, 1H), 2.63 (t, J = 16.6 Hz, 2H), 2.46 - 2.28 (m, 1H), 2.13 - 1.93 (m, 1H). LCMS (ESI) C 32 H 30 ClN4O4 + [M+H] + : Calculated value 569.20, measured value 569.3.

[0368] Example 110: Preparation of 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (GT-05638) The ...

Claims

1. A compound of formula (I) or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, comprising: 【Chemistry 3】 Formula (I) In formula (I), R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ , and R ｂ５ are each independently H, D or C １－３ represents alkyl; X is C(O) or CH ２ represents; (R ａ ) ｎ The benzene ring of formula (I) may optionally be a group consisting of n R ａ where R ａ is deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy or halogenated C １－６ alkyl, and n represents an integer of 0, 1, 2, or 3; and L １ is C(O), alkenylene, optionally substituted C １－５ Alkylene, -CH=, optionally substituted C ６－１０ Arylene-C １－５ Alkylene-*, or N(R ｃ１ ), where R ｃ１ is H or C １－３ represents alkyl, and the symbol * represents the group X １ represents the connection point with １ Ha-C(R Ｌ１ R Ｌ２ )-, where R Ｌ１ , R Ｌ２ are optionally substituted C together with the carbon atoms connected thereto. ３－８ forming a cycloalkylene, or L １ represents a bond; X １ represents an optionally substituted cycloalkylene, an optionally substituted heterocyclylene, or an optionally substituted heteroarylene; X ２ is C(O), optionally substituted C １－５ Alkylene, optionally substituted C ３－８ Cycloalkylene, optionally substituted C １－２ Alkylene-N(R ｃ２ ) -, -N(R ｃ２ )-optionally substituted C １－２ alkylene, or N(R ｃ３ ), where R ｃ２ and R ｃ３ are each independently H or C １－３ represents alkyl, or X ２ represents a bond; R ａ１ has the following structure: 【Chemistry 2】 Formula (IA) In formula (IA), Ring A represents heterocyclylene, cycloalkylene, arylene, or heteroarylene; (R ｄ１ ) ｍ１ Ring A may optionally contain m groups R ｄ１ m1 represents an integer of 0 to 10, and each R ｄ１ are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH- or NH ２ -C １－６ represents alkylene-; and Ring B represents an aryl, cycloalkyl, heterocyclyl, or heteroaryl; (R ｄ２ ) ｍ２ Ring B may optionally contain m groups R ｄ２ m2 represents an integer of 0 to 10, and each R ｄ２ are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH- or NH ２ -C １－６ represents alkylene-; Here, L １ When represents a bond, X １ represents an optionally substituted nitrogen-containing bridged heterocyclylene; and X ２ When represents a bond, L １ is not a bond, a compound of formula (I) or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof.

2. It is also a compound of formula (II) or a compound of formula (III), 【Chemistry 115】 where the group R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ , R ｂ５ , (R ａ ) ｎ , X, L １ , X １ , X ２ and R ａ１ 2. The compound of formula (I) according to claim 1, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, wherein:

3. It is also a compound of formula (Ia), formula (Ib), formula (Ic), formula (Id), formula (IIa), formula (IIb), formula (IIc), formula (IId), formula (IIIa), formula (IIIb), formula (IIIc), or formula (IIId), 【Chemistry 116】 【Chemistry 117】 【Chemistry 118】 【Chemistry 119】 where the group R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ , R ｂ５ , (R ａ ) ｎ , X, L １ , X １ , X ２ and R ａ１ 2. The compound of formula (I) according to claim 1, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, wherein:

4. R ｂ１ , R ｂ２ , R ｂ３ and R ｂ４ each independently represents H; R ｂ５ A compound of formula (I) or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof according to any one of claims 1 to 3, wherein represents H or D.

5. 5. The compound of formula (I) or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof according to any one of claims 1 to 4, wherein X represents C(O).

6. X is CH ２ or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, of formula (I) according to any one of claims 1 to 4, which represents:

7. L １ is C(O), C ２－６ Alkenylene, optionally substituted C １－５ Alkylene, -CH=, optionally substituted C ６－１０ Arylene-C １－５ Alkylene-*, or N(R ｃ１ ), where R ｃ１ is H or C １－３ represents alkyl, and the symbol * represents the group X １ where C represents a connection point with １－５ Alkylene and the C ６－１０ Arylene-C １－５ Each alkylene is independently selected from D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ optionally substituted with 1 to 10 substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof; or L １ Ha-C(R Ｌ１ R Ｌ２ )-, where R Ｌ１ , R Ｌ２ are optionally substituted C together with the carbon atoms connected thereto. ３－８ forming a cycloalkylene, and / or X １ is an optionally substituted C ３－２０ represents a cycloalkylene, an optionally substituted 4- to 20-membered heterocyclylene, or an optionally substituted 5- to 20-membered heteroarylene, wherein ３－２０ The cycloalkylene and the 4- to 20-membered heterocyclylene are each independently selected from D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene, C １－４ Alkyl-NHC(O)-, C １－４ and any combination thereof, wherein the 5- to 20-membered heteroarylene is selected from the group consisting of D, optionally deuterated C(O)NH—, １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ 7. A compound of formula (I) according to any one of claims 1 to 6, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof.

8. L １ is C(O), vinylene, optionally substituted C １－５ alkylene, -CH=, optionally substituted phenylene-C １－５ Alkylene-*, optionally substituted naphthylene-C １－５ Alkylene-*, or N(R ｃ１ ), where R ｃ１ is H or C １－３ represents alkyl, and the symbol * represents the group X １ where C represents a connection point with １－５ alkylene, the phenylene-C １－５ Alkylene and the naphthylene-C １－５ Each alkylene is independently selected from D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ optionally substituted with 1 to 10 substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof; or L １ Ha-C(R Ｌ１ R Ｌ２ )-, where R Ｌ１ , R Ｌ２ are optionally substituted C together with the carbon atoms connected thereto. ３－８ Forms a cycloalkylene, wherein said C ３－８ Cycloalkylene is D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ and / or optionally substituted with 1 to 10 substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof; X １ is the following divalent radical: D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydropentalenylene, octahydro-1H-indenylene, spiro[3.3]heptylene, optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof; , spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, spiro[5.5]undecylene, p-menthanylene, m-menthanylene, quinuclidinylene, adamantanylene, noradamantanylene, norbornylene, bicyclo[2.2.1]heptylene, 2-oxobicyclo[2.2.1]heptylene or bicyclo[2.2.1]heptenylene; or D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ Azatidinylene, pyrrolidinylene, imidazolidylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, azepanylene, azacyclooctylene, diazacycloheptanylene, diazacyclooctylene, 3-azabicyclo[3.1.0]hexylene, 3-azabicyclo[3.1.0]heptanylene, 2-azabicyclo[2.2.1]heptanylene, 6-azabicyclo[3.1.0 ... chloro[3.1.1]heptanylene, 2-azabicyclo[2.2.2]octylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octylene, 3,8-diazabicyclo[3.2.1]octylene, 2,5-diazabicyclo[2.2.2]octylene, 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonylene, 3-azaspiro[5.5]undecylene, 7-azaspiro[3.5]nonylene, or octahydropyrrolo[3,4-c]pyrrolylene; or D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzyl, benzophenyl, benzophenyl, benzothiazole, benzophenyl ... benzoisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, 4H-fluoro[3,2-b]pyrrolylene, pyrrolo[2,1-b]thiazolylene, or imidazo[2,1-b]thiazolylene.

8. The compound of formula (I) of claim 7, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents:

9. X １ is the following divalent radical: 【Chemistry 4】 【Chemistry 5】 【Chemistry 6】 【Chemistry 7】 【Chemistry 8】 【Chemistry 9】 【Chemistry 10】 【Chemistry 11】 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 200】 【Chemistry 16】 【Chemistry 17】 【Chemistry 18】 【Chemistry 19】 【Chemistry 20】 【Chemical 21】 ​ 【Chemical 23】 where the symbol # represents the group L １ 8. A compound of formula (I) according to claim 7, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents a junction point with

10. L １ is the following group: C(O), —CH ２ -, -(CH ２ ) ２ -, -(CH ２ ) ３ -, -CH(OH)-, -CHF ２ -, -CH ２ F—, NH, —CH═CH—, —CH═, or optionally substituted phenylene —CH ２ -*, where the symbol * represents the group X １ and the phenylene is selected from the group consisting of D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ optionally substituted with 1 to 4 substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof; L １ Ha-C(R Ｌ１ R Ｌ２ )-, where R Ｌ１ , R Ｌ２ together with the carbon atoms connected thereto form an optionally substituted cyclopropylene, an optionally substituted cyclobutylene, an optionally substituted cyclopentylene, an optionally substituted cyclohexylene, an optionally substituted cycloheptylene, or an optionally substituted cyclooctylene, wherein said cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, or cyclooctylene is selected from the group consisting of D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ 8. The compound of formula (I) of claim 7, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, optionally substituted with 1 to 10 substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof.

11. L １ represents a bond, and X １ represents an optionally substituted 5- to 20-membered nitrogen-containing bridged heterocyclylene, wherein the 5- to 20-membered nitrogen-containing bridged heterocyclylene is selected from the group consisting of D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ 7. A compound of formula (I) according to any one of claims 1 to 6, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof.

12. X １ is the following divalent radical: 3-azabicyclo[3.1.0]hexylene, 3-azabicyclo[3.1.0]heptanylene, 2-azabicyclo[2.2.1]heptanylene, 6-azabicyclo[3.1.1]heptanylene, 2-azabicyclo[2.2.2]octylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octylene, 3,8-diazabicyclo[3.2.1]octylene, or 2,5-diazabicyclo[2.2.2]octylene, wherein the divalent group is selected from the group consisting of D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C １－４ Alkoxy, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene-, C １－４ Alkyl-NHC(O)-, C １－４ 12. The compound of formula (I) according to claim 11, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof.

13. X １ is the following divalent radical: 【Chemistry 4】 【Chemistry 5】 【Chemistry 6】 【Chemistry 7】 【Chemistry 8】 【Chemistry 9】 【Chemistry 10】 【Chemistry 24】 【Chemical 22】 【Chemical 23】 represents where the symbol # represents the group L １ 12. The compound of formula (I) of claim 11, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents a junction point with

14. X ２ is C(O), optionally substituted C １－５ Alkylene, optionally substituted C ３－８ Cycloalkylene, optionally substituted C １－２ Alkylene-N(R ｃ２ ) -, -N(R ｃ２ )-optionally substituted C １－２ alkylene, or N(R ｃ３ ), where R ｃ２ and R ｃ３ are each independently H or C １－３ alkyl, wherein the C １－５ Alkylene and C ３－８ Each cycloalkylene is independently selected from D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C １－４ Alkoxy, C ３－８ Cycloalkyl, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene, C １－４ Alkyl-NHC(O)-, C １－４ and any combination thereof, wherein the C is optionally substituted with 1 to 10 substituents selected from the group consisting of alkyl-C(O)NH—, and any combination thereof; １－２ Alkylene is D, optionally deuterated C １－４ Alkyl, hydroxy, amino, mercapto, halogen, cyano, oxo group, C １－４ Alkoxy, C ３－８ Cycloalkyl, C １－４ Alkyl-NH-, halogenated C １－４ Alkyl, NH ２ -C １－４ Alkylene, C １－４ Alkyl-NHC(O)-, C １－４ 14. The compound of formula (I) according to any one of claims 1 to 13, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, optionally substituted with 1 to 4 substituents selected from the group consisting of alkyl-C(O)NH-, and any combination thereof.

15. X ２ is C(O), -CH ２ -, -(CH ２ ) ２ -, -(CH ２ ) ３ -, NH, -CH ２ -NH-, -(CH ２ ) ２ -NH-, -NH-(CH ２ ) ２ -, or -NH-CH ２ 15. The compound of formula (I) of claim 14, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents -.

16. X ２ represents a bond, and X ２ When represents a bond, L １ is not a bond, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof.

17. R ａ１ has the following structure: 【Chemistry 2】 Formula (IA) where: Ring A is a 4- to 20-membered heterocyclylene, C ３－２０ Cycloalkylene, C ６－２０ arylene, or 5- to 20-membered heteroarylene, (R ｄ１ ) ｍ１ Ring A is m groups R ｄ１ m1 represents an integer of 0 to 10, and each R ｄ１ are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH- or NH ２ -C １－６ represents alkylene-; and / or Ring B is C ６－２０ Aryl, C ３－２０ cycloalkyl, 4- to 20-membered heterocyclyl, or 5- to 20-membered heteroaryl; (R ｄ２ ) ｍ２ Ring B is m groups R ｄ２ m2 represents an integer of 0 to 10, and each R ｄ２ are independently deuterium, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH- or NH ２ -C １－６ 17. A compound of formula (I) according to any one of claims 1 to 16, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, wherein R represents alkylene-.

18. Ring A is a divalent group as follows: D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cycloheptenylene, cyclooctylene, decalinylene, octahydropentalenylene, octahydro-1H-indenylene, spiro[3.3]he, optionally substituted with one or more substituents selected from the group consisting of alkylene-, and any combination thereof; butylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, spiro[5.5]undecylene, p-menthanylene, m-menthanylene, quinuclidinylene, adamantanylene, noradamantanylene, norbornylene, bicyclo[2.2.1]heptylene, 2-oxobicyclo[2.2.1]heptylene or bicyclo[2.2.1]heptenylene; D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ phenylene or naphthylene, optionally substituted with one or more substituents selected from the group consisting of alkylene-, and any combination thereof; D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ azetidinylene, pyrrolidinylene, imidazolidylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, pyranylene, dihydropyranylene, azepanylene, azacyclooctylene, diazacycloheptanylene, diazacyclooctylene, 3-azabicyclo[3.1.0]hexylene, 3-azabicyclo[3.1.0]heptanylene, 2-azabicyclo[2.2.1]heptanylene, optionally substituted with one or more substituents selected from the group consisting of alkylene-, and any combination thereof; 6-azabicyclo[3.1.1]heptanylene, 2-azabicyclo[2.2.2]octylene, 2,5-diazabicyclo[2.2.1]heptanylene, 3,6-diazabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.1]octylene, 3,8-diazabicyclo[3.2.1]octylene, 2,5-diazabicyclo[2.2.2]octylene, 2,6-diazaspiro[3.3]heptanylene, 2,7-diazaspiro[3.5]nonylene, 3-azaspiro[5.5]undecylene, 7-azaspiro[3.5]nonylene or octahydropyrrolo[3,4-c]pyrrolylene; or D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benziso Thiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, 4H-fluoro[3,2-b]pyrrolylene, pyrrolo[2,1-b]thiazolylene, or imidazo[2,1-b]thiazolylene. represents; and / or Ring B is the following group: D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spiro[3.3]heptanyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[5.5]undecyl, p-menthanyl, m-menthanyl, quinuclidinyl, adamantanyl, noradamantanyl, bornyl, bicyclo[2.2.1]heptanyl, 2-oxobicyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl, optionally substituted with one or more substituents selected from the group consisting of alkylene-, and any combination thereof; D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ phenyl or naphthyl optionally substituted with one or more substituents selected from the group consisting of alkylene-, and any combination thereof; D, hydroxy, amino, mercapto, halogen, cyano, oxo group, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azacycloheptyl, azacyclooctyl, diazacycloheptanyl, diazacyclooctyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.1]heptanyl, 2-azabicyclo[2.2.1]heptanyl, 6-azabicyclo, optionally substituted with one or more substituents selected from the group consisting of alkylene-, and any combination thereof [3.1.1]heptanyl, 2-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonyl, 3-azaspiro[5.5]undecyl, 7-azaspiro[3.5]nonyl or octahydropyrrolo[3,4-c]pyrrolyl; or D, hydroxy, amino, mercapto, halogen, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C １－４ Alkyl-NH-, C １－４ Alkyl-NHC(O)-, C １－４ Alkyl-C(O)NH-, NH ２ -C １－６ furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, and benzoisothiazolyl are optionally substituted with one or more substituents selected from the group consisting of alkylene- and any combination thereof. allyl, benzotriazolyl, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolyl, pyrrolo[2,1-b]thiazolyl or imidazo[2,1-b]thiazolyl 18. The compound of formula (I) of claim 17, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents:

19. Ring A is a divalent group as follows: 【Chemistry 25】 【Chemical 26】 【Chemical 27】 【Chemical Formula 28】 【Chemical 29】 【Chemistry 30】 【Chemical 31】 【Chemical 32】 【Chemical 33】 ​ 【Chemical 35】 【Chemical 36】 【Chemical 37】 【Chemical 38】 【Chemical 39】 【Chemistry 40】 【Chemistry 41】 【Chemistry 42】 where the symbol ** represents the connection point with ring B; and / or Ring B is the following group: 【Chemistry 43】 【Chemical 44】 【Chemistry 45】 【Chemistry 46】 【Chemistry 47】 【Chemistry 48】 【Chemistry 49】 【Chemistry 50】 【Chemistry 51】 【Chemistry 52】 【Chemistry 53】 【Chemical 54】 【Chemistry 55】 【Chemical Formula 56】 【Chemical 57】 【Chemistry 58】 【Chemical Formula 59】 【Chemistry 60】 【Hua 61】 18. The compound of formula (I) of claim 17, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents:

20. R ａ１ has the following structure: 【Hua 62】 【Chemistry 201】 【Hua 64】 【Chemistry 65】 【Hua 66】 【Hua 67】 【Chemistry 68】 【Chemical 69】 18. A compound of formula (I) according to any one of claims 1 to 17, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents:

21. -X １ -X ２ -R ａ１ has the following structure: 【Chemistry 70】 【Chemical 71】 【Chemical 72】 【Chemical 73】 【Chemical 74】 【Chemistry 75】 【Chemical 76】 【Chemical 77】 【Chemical 78】 【Chemical 79】 【Chemistry 80】 【Chemistry 81】 【Chemistry 82】 【Chemistry 83】 【Chemistry 84】 【Chemistry 85】 【Chemistry 86】 【Hua 87】 【Hua 88】 【Chemistry 89】 【Chemistry 90】 【Chemistry 91】 【Chemistry 92】 【Chemistry 93】 【Chemistry 94】 【Chemistry 95】 【Chemistry 96】 【Chemistry 97】 【Chemistry 98】 【Hua99】 【Chemistry 100】 【Chemistry 101】 【Chemistry 102】 【Chemistry 103】 【Chemistry 104】 【Chemistry 105】 【Chemistry 106】 【Chemistry 107】 【Chemistry 108】 【Chemistry 109】 【Chemistry 110】 【Chemistry 111】 【Chemistry 112】 【Chemistry 113】 【Chemistry 114】 18. A compound of formula (I) according to any one of claims 1 to 17, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, which represents:

22. The following: 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)fluoromethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)difluoromethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(1-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)cyclopropyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(1-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)cyclobutyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(1-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)cyclopentyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-chlorophenyl)cyclopent-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-chlorophenyl)cyclopropyl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-chlorophenyl)cyclobutyl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4,4-dimethyl-2-(thiophen-2-yl)cyclohex-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(furan-2-yl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4,4-dimethyl-2-(thiazol-5-yl)cyclohex-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4,4-dimethyl-2-(oxazol-5-yl)cyclohex-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)amino)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-ylidene)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3-hydroxyazetidin-3-yl)(hydroxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxopiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,5S)-6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-ylidene)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3-hydroxyazetidin-3-yl)(hydroxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)imidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,3-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepane-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(7-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1R,4R)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidine-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepane-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(7-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepane-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(7-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepane-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(7-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)ethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)propyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-((4'-fluoro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-((4'-fluoro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-((4'-fluoro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4'-fluoro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-((4'-fluoro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-fluoro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)fluoromethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)difluoromethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(1-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)cyclopropyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(1-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)cyclobutyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(1-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)cyclopentyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-bromophenyl)cyclopent-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-bromophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-bromophenyl)cyclopropyl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((2-(4-bromophenyl)cyclobutyl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(2-(thiophen-2-yl)benzyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-(furan-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-(1H-pyrrol-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-(1-methyl-1H-pyrrol-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-(1-methyl-1H-pyrazol-5-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(2-(thiazol-5-yl)benzyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-(oxazol-5-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3-hydroxyazetidin-3-yl)(hydroxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-ylidene)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)amino)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)-3,3-difluoropiperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)imidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-oxopiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,3-difluoropiperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((3-(4-chlorophenyl)pyridin-4-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-(4-chlorophenyl)pyridin-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((3-(4-chlorophenyl)pyridin-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(2-(5-chloropyridin-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(5-chloropyridin-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(3-(thiophen-2-yl)benzyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(furan-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(1H-pyrrol-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(5-chloropyridin-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(4-(thiophen-2-yl)benzyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(furan-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4-(1H-pyrrol-2-yl)benzyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((6-(4-chlorophenyl)pyridin-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-([2,4'-bipyridin]-5-ylmethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-((5-phenylpyrazin-2-yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-(2-phenylpyrimidine-5-carbonyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((5-(4-chlorophenyl)thiophen-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-([2,2'-bithiophene]-5-ylmethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((5-(furan-2-yl)thiophen-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((5-(4-chlorophenyl)furan-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-((5-(thiophen-2-yl)furan-2-yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-([2,2'-bifuran]-5-ylmethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(3-(4-chlorophenyl)isonicotinoyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3-hydroxyazetidin-3-yl)(hydroxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-ylidene)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)imidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-3,3-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)imidazolidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepane-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(7-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1R,4R)-5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)azetidin-3-ylidene)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3-hydroxyazetidin-3-yl)(hydroxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)phenyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperidin-4-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)azetidin-3-ylidene)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3-hydroxyazetidin-3-yl)(hydroxy)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperidin-4-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1R,4R)-5-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,5-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,3-dimethylpiperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepane-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(7-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1R,4R)-5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(8-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(8-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-((4',5,5-trimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-amino-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-(4-chlorophenyl)-5,6-dihydro-2H-pyran-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4-(4-fluorophenyl)-5,6-dihydro-2H-pyran-3-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-4,4-difluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-chloro-4-methoxy-4-methyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((8-(4-chlorophenyl)spiro[4.5]dec-7-en-7-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((6-(4-chlorophenyl)spiro[3.5]non-6-en-7-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-amino-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-pyran-3-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-(4-fluorophenyl)-5,6-dihydro-2H-pyran-3-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-4,4-difluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4'-chloro-4-methoxy-4-methyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((8-(4-chlorophenyl)spiro[4.5]dec-7-en-7-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-((6-(4-chlorophenyl)spiro[3.5]non-6-en-7-yl)methyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 4-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)amino)piperidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxopiperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepan-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((7-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((1R,4R)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-oxoimidazolidin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-[1,1'-biphenyl]-3-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((3-(4-chlorophenyl)pyridin-4-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-([2,4'-bipyridin]-5-ylmethyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-((5-phenylpyrazin-2-yl)methyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-((5-(4-chlorophenyl)thiophen-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-((5-(thiophen-2-yl)furan-2-yl)methyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-((4',5,5-trimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-((4'-amino-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((4-((4-(4-chlorophenyl)-5,6-dihydro-2H-pyran-3-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-4,4-difluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4'-chloro-4-methoxy-4-methyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((8-(4-chlorophenyl)spiro[4.5]dec-7-en-7-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((4-((6-(4-chlorophenyl)spiro[3.5]nona-6-en-7-yl)methyl)piperazin-1-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)imidazolidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepane-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(7-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octane-2-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(fluoromethyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1R,4R)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,5-dimethylpiperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,3-dimethylpiperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2-(trifluoromethyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)isoindoline-1,3-dione; 5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-[1,1'-biphenyl]-3-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-[1,1'-biphenyl]-4-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((3-(4-chlorophenyl)pyridin-4-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-((4',5,5-trimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)isoindoline-1,3-dione; 5-(4-((4'-amino-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)isoindoline-1,3-dione; 5-(4-((4-(4-chlorophenyl)-5,6-dihydro-2H-pyran-3-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-4,4-difluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4'-chloro-4-methoxy-4-methyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((8-(4-chlorophenyl)spiro[4.5]dec-7-en-7-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((6-(4-chlorophenyl)spiro[3.5]non-6-en-7-yl)methyl)piperazine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(8-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(8-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(3-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(6-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)isoindoline-1,3-dione; 3-(6-((3-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-5-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-5-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-5-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((5-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazine-1-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-((4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 5-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)isoindoline-1,3-dione; 5-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)amino)piperidine-1-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazine-1-carbonyl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)isoindoline-1,3-dione; 3-(5-(((1S,4S)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1S,4S)-5-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1S,4S)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(7-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,7-diazaspiro[3.5]nonane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,6-diazaspiro[3.3]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(5-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1S,4S)-5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-((2-phenylpyrimidin-5-yl)methyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1S,4S)-5-(4'-chloro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1S,4S)-5-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1S,4S)-5-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((1S,4S)-5-(4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-(((1S,4S)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1S,4S)-5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(6-fluoro-5-((3-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-((4'-fluoro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-1,4-diazepan-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((5-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-((4-(4'-fluoro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)piperazin-1-yl)methyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptane-6-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbonyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 2. The compound of formula (I) according to claim 1, or a salt, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph thereof, selected from 3-(1-oxo-5-((4-(5-phenylpyrazine-2-carbonyl)piperazin-1-yl)methyl)isoindolin-2-yl)piperidine-2,6-dione.

23. 23. The compound of formula (I) or a salt thereof, enantiomer, non-enantiomer, isotopically enriched analogue, solvate, pharmaceutical precursor or polymorph according to any one of claims 1 to 22, which is the hydrochloride, sulfate, citrate, maleate, methanesulfonate, citrate, lactate, tartrate, fumarate, phosphate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, malonate, benzoate, mandelate, succinate, trifluoroacetate, hydroxyacetate or p-toluenesulfonate salt of the compound of formula (I).

24. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 23 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

25. 25. The pharmaceutical composition of claim 24, further comprising a second therapeutic agent, such as an anti-cancer agent.

26. Use of a compound of formula (I) according to any one of claims 1 to 23 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 24 or 25, for the manufacture of a medicament for the prevention and / or treatment of a disease or condition associated with cereblon protein.

27. 27. The use of claim 26, wherein the disease or condition associated with the cereblon protein is selected from the group consisting of tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, vascular heart disease, Richter syndrome (RS), acute liver failure, or diabetes.

28. The diseases or conditions associated with the cereblon protein include myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, and smoldering multiple myeloma; myelofibrosis; bone marrow disorders; myelodysplastic syndromes (MDS); previously treated myelodysplastic syndromes; transplant-associated cancers; neutropenia; leukemia, including acute myeloid leukemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, leukemia-associated anemia, and acute myeloid leukemia (AML); diffuse large B-cell lymphoma; Non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell Lymphoma, including refractory primary mediastinal (thymic) large B-cell lymphoma, and refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma and squamous cell carcinoma; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and Cowden's disease; pancreatic cancer; central nervous system cancer; neuroblastoma; glioma; peripheral neuroepithelioma ; Extramedullary plasmacytoma; Plasmacytoma; Gastric cancer; Gastrointestinal stromal tumor; Esophageal cancer; Colorectal adenocarcinoma; Esophageal squamous cell carcinoma; Liver cancer; Renal cell carcinoma; Bladder cancer; Endometrial cancer; Uterine cancer; Head and neck cancer; Brain cancer; Oral cancer; Sarcomas including rhabdomyosarcoma, various lipogenic 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's syndrome autoimmune diseases including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren's syndrome, and atopic dermatitis; keratoconjunctivitis sicca; inflammatory diseases including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, and bronchitis;27. The use of claim 26, wherein the therapeutic agent is selected from the group consisting of cerebral malaria, infectious diseases including viral pneumonia, AIDS, COVID-19, gram-negative bacterial infections, gram-positive bacterial infections, tuberculosis, and the like; 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; vascular heart disorders (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure due to cachexia and septic shock; or acute liver failure.

29. 24. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 23, for use in preventing and / or treating a disease or condition associated with a cereblon protein.

30. 30. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 29, wherein the disease or condition associated with the cereblon protein is selected from the group consisting of tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, vascular heart disease, Richter syndrome (RS), acute liver failure, or diabetes.

31. The diseases or conditions associated with the cereblon protein include myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, and smoldering multiple myeloma; myelofibrosis; bone marrow disorders; myelodysplastic syndromes (MDS); previously treated myelodysplastic syndromes; transplant-associated cancers; neutropenia; leukemia, including acute myeloid leukemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, leukemia-associated anemia, and acute myeloid leukemia (AML); diffuse large B-cell lymphoma; Non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell Lymphoma, including refractory primary mediastinal (thymic) large B-cell lymphoma, and refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma and squamous cell carcinoma; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and Cowden's disease; pancreatic cancer; central nervous system cancer; neuroblastoma; glioma; peripheral neuroepithelioma ; Extramedullary plasmacytoma; Plasmacytoma; Gastric cancer; Gastrointestinal stromal tumor; Esophageal cancer; Colorectal adenocarcinoma; Esophageal squamous cell carcinoma; Liver cancer; Renal cell carcinoma; Bladder cancer; Endometrial cancer; Uterine cancer; Head and neck cancer; Brain cancer; Oral cancer; Sarcomas including rhabdomyosarcoma, various lipogenic 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's syndrome autoimmune diseases including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren's syndrome, and atopic dermatitis; keratoconjunctivitis sicca; inflammatory diseases including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, and bronchitis;30. The compound of formula (I) according to claim 29 or a pharmaceutically acceptable salt thereof, selected from the group consisting of cerebral malaria; infectious diseases including viral pneumonia, AIDS, COVID-19 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; vascular heart disorders (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure due to cachexia and septic shock; or acute liver failure.

32. A method for treating or preventing a disease or condition associated with cereblon protein, comprising administering to a subject a therapeutically effective amount of a compound of formula (I) according to any one of claims 1 to 23 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 24 or 25.

33. 33. The method of claim 32, wherein the disease or condition associated with cereblon protein is selected from the group consisting of tumors, infectious diseases, inflammatory diseases, autoimmune diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, vascular heart disease, Richter syndrome (RS), acute liver failure, or diabetes.

34. The diseases or conditions associated with the cereblon protein include myeloma, including multiple myeloma, plasma cell myeloma, smoldering myeloma, and smoldering multiple myeloma; myelofibrosis; bone marrow disorders; myelodysplastic syndromes (MDS); previously treated myelodysplastic syndromes; transplant-associated cancers; neutropenia; leukemia, including acute myeloid leukemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, leukemia-associated anemia, and acute myeloid leukemia (AML); diffuse large B-cell lymphoma; Non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell Lymphoma, including refractory primary mediastinal (thymic) large B-cell lymphoma, and refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer, including lung adenocarcinoma and squamous cell carcinoma; inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and Cowden's disease; pancreatic cancer; central nervous system cancer; neuroblastoma; glioma; peripheral neuroepithelioma ; Extramedullary plasmacytoma; Plasmacytoma; Gastric cancer; Gastrointestinal stromal tumor; Esophageal cancer; Colorectal adenocarcinoma; Esophageal squamous cell carcinoma; Liver cancer; Renal cell carcinoma; Bladder cancer; Endometrial cancer; Uterine cancer; Head and neck cancer; Brain cancer; Oral cancer; Sarcomas including rhabdomyosarcoma, various lipogenic 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's syndrome autoimmune diseases including rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren's syndrome, and atopic dermatitis; keratoconjunctivitis sicca; inflammatory diseases including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, and bronchitis;33. The method of claim 32, wherein the disease is selected from the group consisting of cerebral malaria, infectious diseases including viral pneumonia, AIDS, COVID-19 infection, gram-negative bacterial infections, gram-positive bacterial infections, tuberculosis, and the like; 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; vascular heart disorders (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure due to cachexia and septic shock; or acute liver failure.

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