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

Abstract

The present disclosure relates to compounds of formula (I), formula (II) and formula (III) or their salts, enantiomers, stereoisomers, solvates, isotopically enriched analogues, pharmaceutical precursors or polymorphs and applications thereof. The present disclosure further relates to pharmaceutical compositions comprising compounds of formula (I), formula (II) and formula (III) or their salts, enantiomers, stereoisomers, solvates, isotopically enriched analogues, pharmaceutical precursors or polymorphs as active ingredients and applications thereof. TIFF2024539269000184.tif1784

Description

[Technical Field]

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

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

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

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

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

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

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

[0008] In some embodiments, the novel CRBN ligands of the present disclosure may be compounds of formula (I) or salts, stereoisomers (including enantiomers), solvates, isotopically enriched analogs, pharmaceutical precursors, or polymorphs thereof: [ka] Formula (I) where: A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent, for example, hydrogen, deuterium, halogen, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy or halogenated C 1-6 represents alkyl; R5, R6, R7 and R8 are the same or different and each independently represent, for example, R9, hydrogen, deuterium, halogen, hydroxy, mercapto group, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 alkynyl, wherein 1 to 3 of R5, R6, R7, and R8 represent R9; R9 represents the group RU-, where U represents a bond, or U represents N(R 10 ) or O, where R 10 is, for example, H or optionally deuterated C 1-6 represents alkyl; R represents an optionally substituted nitrogen-containing heterocyclyl, said optionally substituted nitrogen-containing heterocyclyl being an optionally substituted nitrogen-containing monocyclic heterocyclyl or an optionally substituted nitrogen-containing bridged heterocyclyl; where: When two to four of R5, R6, R7 and R8 independently represent R9, the compound of formula (I) is optionally partially or fully deuterated, or When only one of R5, R6, R7 and R8 represents R9, the compound of formula (I) is optionally partially or fully deuterated; wherein only one of R5, R6, R7 and R8 represents R9, and the compound of formula (I) is not deuterated. When R represents said optionally substituted nitrogen-containing bridged heterocyclyl, the compound of formula (I) is the following compound: 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-azabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and does not contain 3-(5-(9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonan-7-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; or A represents CO, and one of R6 and R7 represents R9, where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R6 and R7, R5 and R8 are each independently hydrogen, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 When the alkynyl is represented, one of R6 and R7 and one to three of R5 and R8 represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, NH2-C 1-6 Alkylene, C 1-6 Alkyl-NH-, C 1-6 Alkyl-NHC(O)-, C 1-6 substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof; A represents CO, one of R6 and R7 represents R9, and when the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, the other of R6 and R7 is hydrogen, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 alkynyl, and R5 and R8 each independently represent halogen; A represents CO, one of R5 and R8 represents R9, where R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R5 and R8, R6 and R7 are each independently hydrogen, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 When the alkynyl is represented, one of R5 and R8 and one to three of R6 and R7 represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen, cyano, CHO, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-6 Alkyl-NHC(O)-, C 1-6 substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof; A represents CO, one of R5 and R8 represents R9, and when the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, the other of R5 and R8 and / or R7 each independently represents a halogen, and R6 is hydrogen, a halogen, a hydroxyl, a mercapto group, a nitro, an amino, a cyano, a C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 represents alkynyl; A represents CH2, one of R6 and R7 represents R9, where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R6 and R7, R5 and R8 are each independently hydrogen, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 When the alkynyl is represented, one of R6 and R7 and one to three of R5 and R8 represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-6 Alkyl-NHC(O)-, C 1-6 substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof; A represents CH2, one of R6 and R7 represents R9, and when the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, R5 represents halogen, and the other of R6 and R7 and / or R8 each independently represents halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 represents alkynyl; A represents CH2, one of R5 and R8 represents R9, where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R5 and R8, R6 and R7 each independently represent hydrogen, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6Alkenyl, or C 2-6 When the alkynyl is represented, another of R5 and R8 and one to three of R6 and R7 represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen, cyano, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, C 1-6 Alkyl-NHC(O)-, C 1-6 or substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof; A represents CH2, one of R5 and R8 represents R9, where the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, and the other of R5 and R8, R6 and R7 are each independently hydrogen, halogen, hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 When representing alkynyl, the three of R5 and another of R8, R6 and R7 cannot be hydrogen at the same time, and when R6 is halogen, the other of R5 and R8 and R7 cannot be hydrogen at the same time.

[0009] In one aspect, the CRBN ligand of the present disclosure may be a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof: [ka] Formula (II) where: A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent, for example, hydrogen, deuterium, halogen, optionally deuterated C1-6 Alkyl, optionally deuterated C 1-6 Alkoxy or halogenated C 1-6 represents alkyl, (R b ) n is a group consisting of n benzene rings b Each R represents a substitution b are the same or different and each independently represent, for example, hydrogen, deuterium, halogen, hydroxy, mercapto group, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 represents alkynyl; (R a ) m The benzene ring has m R a Each R represents a substitution a are the same or different and each independently represent the following structure: W-LIN-U2-R c -U1- where: U1 and U2 are the same or different and each independently represent, for example, a bond, N(R d ) or O, where R d is, for example, H or optionally deuterated C 1-6 represents alkyl, R c represents an optionally substituted nitrogen-containing monocyclic heterocyclylene or an optionally substituted nitrogen-containing bridged heterocyclylene; W is hydrogen, optionally substituted nitrogen-containing monocyclic heterocyclyl, optionally substituted nitrogen-containing bridged heterocyclyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, C 2-6 Alkenyl, C 2-6 represents an alkynyl, a leaving group, a CHO, COOH, NH2, hydroxy or mercapto group; and where: When the compound of formula (II) is partially or fully deuterated, When W represents an optionally substituted nitrogen-containing monocyclic heterocyclyl, an optionally substituted nitrogen-containing bridged heterocyclyl, an optionally substituted cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted aryl, LIN represents a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may optionally contain one or more groups R e and / or one or more groups R f or one or more groups R e and R f Any combination of the groups R e , R f or group R e and R f The combination of R e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 represents alkyl, and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R e are not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, may further comprise, for example, deuterium, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6Cycloalkyl, hydroxy, amino, mercapto groups, halogen, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof; or W is hydrogen, C 2-6 Alkenyl, C 2-6 When representing an alkynyl, leaving group, CHO, COOH, NH2, hydroxy or mercapto group, LIN is an optionally substituted methylene or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may optionally contain one or more groups R e and / or one or more groups R f or one or more groups R e and R f Any combination of the groups R e , R f or group R e and R f The combination of R e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 represents alkyl, and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R e are not directly connected to each other;f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, may further be selected from the group consisting of, for example, deuterium, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto groups, halogen, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof; or When the compound of formula (II) is non-deuterated, L-In represents optionally substituted methylene, and W represents optionally substituted nitrogen-containing monocyclic heterocyclyl or optionally substituted nitrogen-containing bridged heterocyclyl; and M represents an integer of 1, 2, 3, or 4, N represents an integer of 0, 1, 2, or 3, and the sum of m and n represents an integer of 1, 2, 3, or 4; The proviso is that when the compound of formula (II) is not deuterated, the compound of formula (II) is the following compound: 3-(4,6-difluoro-1-oxo-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl)isoindoline-1,3-dione; 3-(4-chloro-1-oxo-5-(4-(piperidin-4-ylmethyl)piperidin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and 2-(2,6-dioxopiperidin-3-yl)-5-(3-(piperazin-1-ylmethyl)azetidin-1-yl)isoindoline-1,3-dione isn't it.

[0010] In one aspect, the proteolytic molecule of the present disclosure is a compound of formula (III) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, PBM-R 1 -W 1 -LIN-ULM Formula (III) Here, PBM-R 1 -W 1 - represents a targeting moiety capable of binding to a protein, ULM represents a ligand moiety capable of binding to an E3 ubiquitin ligase, LIN is a connecting moiety, and PBM-R 1 -W 1 is covalently linked to ULM by the group LIN; ULM represents a structure of the following formula (ULM): [ka] Formula (ULM) where: A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent, for example, hydrogen, deuterium, halogen, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy or halogenated C 1-6 represents alkyl; (R b ) n The benzene ring is optionally connected to n R b Each R represents a substitution bare the same or different and each independently represent, for example, hydrogen, deuterium, halogen, hydroxy, mercapto group, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 represents alkynyl; n represents an integer of 0, 1, 2, or 3; U1 and U2 are the same or different and each independently represent, for example, a bond, N(R d ) or O, where R d is, for example, H or optionally deuterated C 1-6 represents alkyl; R c represents an optionally substituted nitrogen-containing monocyclic heterocyclylene or an optionally substituted nitrogen-containing bridged heterocyclylene; LIN is a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may optionally contain one or more groups R e and / or one or more groups R f or one or more groups R e and R f Any combination of the groups R e , R f or group R e and R f The combination of R e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6represents alkyl, and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R e are not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently be further optionally substituted with, for example, deuterium, optionally deuterated C 1-6 Alkyl, optionally deuterated C 3-6 Cycloalkyl, hydroxy, amino, mercapto groups, halogen, optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof; W 1 is a ring W with t rings represented by the following structural formula: 2 is concatenated as: [ka] Each ring W 2 are the same or different and each independently an optionally substituted nitrogen-containing monocyclic heterocyclylene, an optionally substituted nitrogen-containing bridged heterocyclylene, or an optionally substituted cycloalkylene; and t represents an integer of 1 or 2; and R 1 teeth: Bond, -O-, optionally substituted C 1-6 alkylene (e.g., methylene); [ka] or C 6-10 aryl or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein 6-10 The aryl and the heteroaryl each optionally contain one or more R 3a and each R 3a are the same or different and each independently represent, for example, a halogen, a hydroxy, a cyano, an amino, a nitro group, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 is alkoxy; wherein one or more hydrogen atoms of the compound of formula (III) are optionally replaced with deuterium atoms; wherein when the compound of formula (III) is not substituted with deuterium, the compound of formula (III) is the following compound: [ka] Formula (IV-1) In formula (IV-1), R 1 represents a bond, and W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents fluorine, n represents an integer of 1, 2, or 3, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-1), R 1 represents a bond, and W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R brepresents fluorine, n represents an integer of 1, 2, or 3, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; [ka] Formula (IV-2) In formula (IV-2), R 1 represents a bond, and W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents fluorine, n represents an integer of 1, 2, or 3, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-2), R 1 represents a bond, and W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents fluorine, n represents an integer of 1, 2, or 3, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; [ka] Formula (IV-3) In formula (IV-3), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R brepresents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-3), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; and [ka] Formula (IV-4) Not including, In formula (IV-4), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-4), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O.

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

[0012] In one aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (II) or a salt thereof, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph, and at least one pharmaceutically acceptable carrier.

[0013] In one aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (III) or a salt thereof, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph, and at least one pharmaceutically acceptable carrier.

[0014] In one aspect, the present disclosure further comprises: a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the same; or a compound of formula (II) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same; or A compound of formula (III) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the same; A pharmaceutical kit or reagent kit comprising:

[0015] In one aspect, the present disclosure provides a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, or a pharmaceutical composition comprising same as an active ingredient, for use as a medicament.

[0016] In one aspect, the present disclosure further provides a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use in treating or preventing a disease or condition mediated by cereblon protein.

[0017] In some embodiments, the disease or condition mediated by cereblon protein includes, but is not limited to, a tumor, an infectious disease, an autoinflammatory disease, an inflammatory disease, an autoimmune disease, a neurological disease, a respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, congestive heart failure, myocardial infarction, Onwell-Richter syndrome, Richter syndrome (RS), acute liver failure, or diabetes.

[0018] In one aspect, the present disclosure provides a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use as a medicament.

[0019] In one aspect, the present disclosure further provides a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use in treating or preventing a disease or condition mediated by cereblon protein.

[0020] In one aspect, the present disclosure provides a compound of formula (III) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, or a pharmaceutical composition comprising the same as an active ingredient, for use as a medicament.

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

[0022] In one aspect, the present disclosure provides the use of a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof in the preparation of a compound of formula (III) of the present disclosure or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

[0023] In one aspect, the present disclosure further provides a method of preparing a compound of formula (III) of the present disclosure, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, pharmaceutical precursor, or polymorph thereof, using a compound of formula (I), or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, pharmaceutical precursor, or polymorph thereof.

[0024] In one aspect, the present disclosure provides the use of a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof in the preparation of a compound of formula (III) of the present disclosure or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

[0025] In one aspect, the present disclosure further provides a method of preparing a compound of formula (III) of the present disclosure, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, pharmaceutical precursor, or polymorph thereof, using a compound of formula (II), or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analog, pharmaceutical precursor, or polymorph thereof.

[0026] In one aspect, the present disclosure further provides the use of a compound of formula (I) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof in the manufacture of a medicament for treating or preventing a disease or condition mediated by cereblon protein.

[0027] In one aspect, the present disclosure further provides the use of a compound of formula (II) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof in the manufacture of a medicament for treating or preventing a disease or condition mediated by cereblon protein.

[0028] In one aspect, the disclosure further provides the use of a compound of formula (III) or a salt, stereoisomer (including enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof in the manufacture of a medicament for the treatment and / or prevention of a disease or condition selected from the group consisting of: tumor, infectious disease, autoinflammatory disease, inflammatory disease, autoimmune disease, neurological disease, respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, acute respiratory distress syndrome, congestive heart failure, myocardial infarction, Williams syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin disease, cardiovascular disease, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, or thyroid disease.

[0029] In one aspect, the present disclosure further provides a method for treating or preventing a disease or condition mediated by cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I), or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising the same.

[0030] In one aspect, the present disclosure further provides a method for treating or preventing a disease or condition mediated by cereblon protein in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (II), or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising the same.

[0031] In one aspect, the present disclosure further provides a method of treating or preventing a disease or condition in a subject, wherein the disease or condition comprises tumor, infectious disease, autoinflammatory disease, inflammatory disease, autoimmune disease, neurological disease, respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, acute respiratory distress syndrome, congestive heart failure, myocardial infarction, Williams syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin disease, cardiovascular disease, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, and thyroid disease, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (III) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, or a pharmaceutical composition comprising the same. [Brief explanation of the drawings]

[0032] [Figure 1] It shows that the compounds of the present invention can efficiently inhibit the proliferation of tumor cell line DU-145, and the inhibitory effect is superior to that of the positive control drug enzalutamide.

[0033] [Figure 2] 1 shows the ability of the compounds of the present invention to degrade full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) proteins in human prostate cancer cells 22RV1 measured using Western blot.

[0034] [Figure 3] 1 shows how the ability of the compounds of the present invention to degrade the full-length androgen receptor (AR-FL) protein in human prostate cancer cells C4-2 is measured using Western blot. DETAILED DESCRIPTION OF THE INVENTION

[0035] In order to facilitate understanding and implementation of the contents of the present disclosure, the following detailed description is provided as an illustrative specific embodiment. However, such description is not intended to limit the scope of the present disclosure. 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. I. Compound Compounds of formula (I)

[0036] The present disclosure provides a compound of formula (I) or a salt (including a pharmaceutically acceptable salt), stereoisomer (including an enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof, [ka] Formula (I) wherein A, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined above for compounds of formula (I).

[0037] In some embodiments, R, R, R, and R of the compound of Formula (I) are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butyloxy or tert-butyloxy), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0038] In some embodiments, R 1 , R 2 , R 3 , and R 4 of the compound of Formula (I) are the same or different and each independently represent hydrogen or deuterium.

[0039] In some embodiments, R1, R2, R3, and R4 of the compound of Formula (I) represent hydrogen.

[0040] In some embodiments, A in the compound of Formula (I) represents CO.

[0041] In some embodiments, A in the compound of Formula (I) represents CH2.

[0042] In some embodiments, A in the compound of Formula (I) represents CD2.

[0043] In some embodiments, when 2 to 4 (e.g., 2, 3, or 4) of R5, R6, R7, and R8 of a compound of Formula (I) independently represent R9, the compound of Formula (I) is optionally partially deuterated, for example, having 1 to 20 (e.g., 1-15, 1-10, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) deuterium atoms, or the compound of Formula (I) is optionally fully deuterated. The number of deuterium atoms is not limited in principle and is automatically limited by the size of the building block.

[0044] In some embodiments, when only one of R5, R6, R7, and R8 of the compound of formula (I) represents R9, the compound of formula (I) is partially deuterated, for example, having 1 to 15 (e.g., 1-10, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) deuterium atoms, or the compound of formula (I) is fully deuterated. The number of deuterium atoms is not limited in principle, or is automatically limited by the size of the building block. In one subembodiment, when R5 of the compound of formula (I) represents R9, R6, R7, and R8 are the same or different and each independently represent hydrogen, deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 In one subembodiment, when R6 in a compound of formula (I) represents R9, R5, R7 and R8 are the same or different and each independently represent hydrogen, deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6In one subembodiment, when R7 in a compound of formula (I) represents R9, R5, R6 and R8 are the same or different and each independently represent hydrogen, deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 In one subembodiment, when R8 in a compound of formula (I) represents R9, R5, R6 and R7 are the same or different and each independently represent hydrogen, deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl, optionally deuterated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 2-6 Alkenyl, or C 2-6 It represents alkynyl.

[0045] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of formula (I) represents R9, and said compound of formula (I) is not deuterated, when R represents said optionally substituted nitrogen-containing bridged heterocyclyl, the compound of formula (I) is the following compound: 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-azabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 3-(5-(9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonan-7-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione Does not include.

[0046] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CO, and one of R6 and R7 represents R9, where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R6 and R7, R5, and R8, each independently, is hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 When representing alkynyl (e.g., ethynyl, propynyl, or butynyl), one of R6 and R7, and one to three (e.g., one, two, or three) of R5 and R8 represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkyl (e.g., C 1-4alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 Alkyl-NH- (e.g., C 1-3 alkylNH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), C 1-6 Alkyl-NHC(O)- (e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-), C 1-6 It is substituted with one or more (e.g., 1 to 6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-) or any combination thereof. The number of substituents is not limited in principle, or is automatically limited by the size of the constituent unit.

[0047] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CO, and one of R6 and R7 represents R9, where the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, the other of R6 and R7 is hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 R5 and R8 each independently represent a halogen atom (for example, fluorine, chlorine, bromine, or iodine).

[0048] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CO, and one of R5 and R8 represents R9, where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R5 and R8, R6, and R7, each independently represents hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 When representing alkynyl (e.g., ethynyl, propynyl, or butynyl), one of R5 and R8, and one to three (e.g., one, two, or three) of R6 and R7 represent halogen (e.g., fluorine, chlorine, bromine, or iodine), and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, CHO, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 3-6 cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl-NH- (e.g., C 1-3 alkylNH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 alkyl-NHC(O)- (e.g., CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), C 1-6It is substituted with one or more (e.g., 1 to 6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-) or any combination thereof. The number of substituents is not limited in principle, or is automatically limited by the size of the constituent unit.

[0049] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CO, and one of R5 and R8 represents R9, where the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, the other of R5 and R8 and / or R7 each independently represent a halogen, and R6 is hydrogen, a halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, a mercapto group, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 It represents alkynyl (for example ethynyl, propynyl or butynyl).

[0050] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CH2, and one of R6 and R7 represents R9, where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R6 and R7, R5, and R8, each independently, is hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 When representing alkynyl (e.g., ethynyl, propynyl, or butynyl), one of R6 and R7, and one to three (e.g., one, two, or three) of R5 and R8 represent halogen (e.g., fluorine, chlorine, bromine, or iodine), and the nitrogen-containing monocyclic heterocyclyl is selected from hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), CHO, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C3-6 cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl-NH- (e.g., C 1-3 alkylNH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 alkyl-NHC(O)- (e.g., CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), C 1-6 It is substituted with one or more (e.g., 1 to 6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-) or any combination thereof. The number of substituents is not limited in principle, or is automatically limited by the size of the constituent unit.

[0051] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CH2 and one of R6 and R7 represents R9, where R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, R5 represents a halogen (e.g., fluorine, chlorine, bromine, or iodine), and the other of R6 and R7 and / or R8 each independently represents a halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 It represents alkynyl (for example ethynyl, propynyl or butynyl).

[0052] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CH2 and one of R5 and R8 represents R9, where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl, and the other of R5 and R8, R6, and R7, each independently represents hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6When representing alkynyl (e.g., ethynyl, propynyl, or butynyl), another of R5 and R8, and one to three (e.g., one, two, or three) of R6 and R7 represent halogen (e.g., fluorine, chlorine, bromine, or iodine), and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), CHO, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 3-6 cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl-NH- (e.g., C 1-3 alkylNH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 alkyl-NHC(O)- (e.g., CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), C 1-6 It is substituted with one or more (e.g., 1 to 6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-) or any combination thereof. The number of substituents is not limited in principle, or is automatically limited by the size of the constituent unit.

[0053] In some embodiments, when only one of R5, R6, R7, and R8 of a compound of Formula (I) represents R9, and the compound of Formula (I) is not deuterated, A represents CH2 and one of R5 and R8 represents R9, where the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, and the other of R5 and R8, R6, and R7, each independently, is hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 When R represents alkynyl (e.g., ethynyl, propynyl, or butynyl), the other of R and R, R, and R cannot simultaneously be hydrogen; and when R is halogen (e.g., fluorine, chlorine, bromine, or iodine), the other of R and R and R cannot simultaneously be hydrogen.

[0054] In some embodiments, the group R of the group R of the compound of Formula (I) represents an optionally substituted nitrogen-containing heterocyclyl, which is an optionally substituted nitrogen-containing monocyclic heterocyclyl or an optionally substituted nitrogen-containing bridged heterocyclyl. In one subembodiment, the nitrogen-containing monocyclic heterocyclyl is a 4- to 10-membered monocyclic heterocyclyl containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur, including, but not limited to, the following groups: piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, or diazacyclooctyl. In one subembodiment, the nitrogen-containing bridged heterocyclyl is a C 1 -C 2 -C 3 -C 4 -C 5 -C 6 -C 7 -C 8 -C 9 -C 10 -C 11 -C 12 -C 13 -C 14 -C 15 -C 16 -C 17 -C 18 -C 19 -C 20 -C 21 -C 22 -C 23 -C 2 5-20 and bridged heterocyclyl, including, but not limited to, the following groups: azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl, or diazabicyclo[2.2.2]octanyl, for example, the following groups: [ka] represents; wherein the nitrogen-containing monocyclic heterocyclyl and the nitrogen-containing bridged heterocyclyl are optionally substituted. In one subembodiment, the nitrogen-containing monocyclic heterocyclyl and the nitrogen-containing bridged heterocyclyl are optionally substituted with deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, CHO, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., C 1-3 alkylNH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 alkyl-NHC(O)- (e.g., CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-), C 1-6 Optionally substituted with one or more (e.g., 1-10, 1-8 or 1-6, e.g., 1, 2, 3, 4, 5 or 6) substituents selected from the group consisting of alkyl-C(O)NH- (e.g., CH3-C(O)NH-, CH3CH2-C(O)NH- and CH3CH2CH2-C(O)NH-), or any combination thereof.

[0055] In some embodiments, the group R9 of the compound of formula (I) is: [ka] Represents.

[0056] In some embodiments, the compound of Formula (I) is also a compound of Formula (I-1) or Formula (I-2): [ka] wherein A, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined above for compounds of formula (I).

[0057] In some embodiments, the compound of Formula (I) is also a compound of Formula (I-3), Formula (I-4), or Formula (I-5): [ka] wherein A, R5, R6, R7 and R8 are as defined above for compounds of formula (I).

[0058] In some embodiments, specific compounds of Formula (II) in Table 1 below and salts (including pharmaceutically acceptable salts, e.g., hydrochloride salts thereof), pharmaceutical precursors, solvates, isotopically enriched analogs, polycrystalline forms, stereoisomers (including enantiomers and non-enantiomers), or mixtures of stereoisomers thereof are provided. Table 1. Compounds of the present disclosure Compound of formula (II)

[0059] The present disclosure provides a compound of formula (II) or a salt (including a pharmaceutically acceptable salt), stereoisomer (including an enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof: [ka] Here, A, R1, R2, R3, R4, (R b ) n and (R a ) m is as defined above for compounds of formula (II).

[0060] In some embodiments, R, R, R, and R of the compound of Formula (II) are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0061] In some embodiments, R 1 , R 2 , R 3 , and R 4 of the compound of Formula (II) are the same or different and each independently represent hydrogen or deuterium.

[0062] In some embodiments, R1, R2, R3, and R4 of the compound of Formula (II) represent hydrogen.

[0063] In some embodiments, A in the compound of Formula (II) represents CO.

[0064] In some embodiments, A in the compound of Formula (II) represents CH2.

[0065] In some embodiments, A in the compound of Formula (II) represents CD2.

[0066] In some embodiments, m represents an integer of 1 and n represents an integer of 0, 1, 2, or 3 in the compound of Formula (II).

[0067] In some embodiments, m represents an integer of 2 and n represents an integer of 0, 1, or 2 in the compound of Formula (II).

[0068] In some embodiments, when the compound of formula (II) is partially or fully deuterated, when W represents an optionally substituted nitrogen-containing monocyclic heterocyclyl, an optionally substituted nitrogen-containing bridged heterocyclyl, an optionally substituted cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted aryl, L-In is a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may contain one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and / or one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5 or 6) groups R f or one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and R f and the group R e , R f or group R e and R f the combination of which cleaves one or more pairs (e.g., 1-10 pairs, 1-8 pairs, or 1-6 pairs, e.g., 1, 2, 3, 4, 5, or 6 pairs) of carbon-carbon bonds between adjacent carbon atoms in the carbon backbone; e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R eare not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkylNH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof.

[0069] In some embodiments, when the compound of Formula (II) is partially deuterated (e.g., having 1 to 20 deuterium atoms) or fully deuterated, and W represents an optionally substituted nitrogen-containing monocyclic heterocyclyl, an optionally substituted nitrogen-containing bridged heterocyclyl, an optionally substituted cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted aryl, L-In is a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may contain one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and / or one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5 or 6) groups R f or one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and R f and any combination of the groups R e , R f or group R e and R f the combination of which cleaves one or more pairs (e.g., 1-10 pairs, 1-8 pairs, or 1-6 pairs, e.g., 1, 2, 3, 4, 5, or 6 pairs) of carbon-carbon bonds between adjacent carbon atoms in the carbon backbone; e is O, N(R g), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R e are not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, amino, mercapto, halogen, optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3alkylNH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; wherein the methylene and the linear or branched C 2-30 Alkylene can be substituted with deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, or optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with one or more (e.g., 1-10, 1-8 or 1-6, e.g., 1, 2, 3, 4, 5 or 6) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH- and CH3CH2CH2-C(O)NH-), or any combination thereof.

[0070] In some embodiments, when the compound of formula (II) is partially or fully deuterated, W is hydrogen, C 2-6 Alkenyl, C 2-6 When representing an alkynyl, leaving group, CHO, COOH, NH2, hydroxy or mercapto group, LIN is an optionally substituted methylene or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C2-30 The alkylene carbon backbone may contain one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and / or one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5 or 6) groups R f or one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and R f and any combination of the groups R e , R f or group R e and R f the combination of which cleaves one or more pairs (e.g., 1-10 pairs, 1-8 pairs, or 1-6 pairs, e.g., 1, 2, 3, 4, 5, or 6 pairs) of carbon-carbon bonds between adjacent carbon atoms in the carbon backbone; e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R e are not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, may further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof.

[0071] In some embodiments, the compound of Formula (II) is partially deuterated (e.g., having 1 to 20 deuterium atoms) or fully deuterated, and W is hydrogen, C 2-6 Alkenyl, C 2-6 When representing an alkynyl, leaving group, CHO, COOH, NH2, hydroxy or mercapto group, LIN is an optionally substituted methylene or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may contain one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and / or one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5 or 6) groups R f or one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and R f and any combination of the groups R e , R f or group R e and R f the combination of which cleaves one or more pairs (e.g., 1-10 pairs, 1-8 pairs, or 1-6 pairs, e.g., 1, 2, 3, 4, 5, or 6 pairs) of carbon-carbon bonds between adjacent carbon atoms in the carbon backbone; e is O, N(R g ), C(O), C(O)O, S(O), S(O)2, S(O)2NH, NHS(O)2, OC(O), C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group Re are not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, may further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; wherein the methylene and the linear or branched C 2-30 Alkylene can be substituted with deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, or optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with one or more (e.g., 1-10, 1-8 or 1-6, e.g., 1, 2, 3, 4, 5 or 6) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH- and CH3CH2CH2-C(O)NH-), or any combination thereof.

[0072] In some embodiments, when the compound of Formula (II) is non-deuterated, L-In represents optionally substituted methylene and W represents optionally substituted nitrogen-containing monocyclic heterocyclyl or optionally substituted nitrogen-containing bridged heterocyclyl; wherein the methylene is optionally substituted with deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 It is substituted with one or more (e.g., 1 or 2) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), or any combination thereof.

[0073] In some embodiments, when the compound of Formula (II) is non-deuterated, L represents optionally substituted methylene and R c When R represents piperazinyl and W represents an optionally substituted nitrogen-containing monocyclic heterocyclyl, the piperazinyl is substituted. c The piperazinyl represented by the formula: 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 In some embodiments, the methylene represented by L-I is substituted with 1-4 (e.g., 1-3 or 1-2, e.g., 1, 2, 3, or 4) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), or any combination thereof. In some embodiments, the methylene represented by L-I is substituted with deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4

[0023] In some embodiments, the nitrogen-containing monocyclic heterocyclyl represented by W is optionally substituted with one or more (e.g., 1 or 2) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-, or any combination thereof. In some embodiments, the nitrogen-containing monocyclic heterocyclyl represented by W is optionally substituted with one or more (e.g., 1 or 2) substituents selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, CHO, COOH, N3, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally substituted C 3-8 cycloalkyl (e.g., substituted with one or more, for example, 1-6, for example, 1, 2, 3, 4, 5, or 6, substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, mercapto, cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy); optionally substituted 4- to 9-membered heterocyclyl (e.g., substituted with one or more, for example, 1-6, for example, 1, 2, 3, 4, 5, or 6, substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, mercapto, cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy); 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), deuterated C 1-6 Alkyl-O- (e.g., fully deuterated C 1-4 Alkoxy, such as CD3-O-, fully deuterated ethoxy, fully deuterated propoxy, fully deuterated isopropoxy, fully deuterated butoxy, fully deuterated sec-butoxy or fully deuterated tert-butoxy), C 1-6 Alkyl-NH- (e.g., C 1-3alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), deuterated C 1-6 Alkyl-NH- (e.g., fully deuterated C 1-3 Alkyl-NH-, such as CD3NH-, CD3CD2NH- or CD3CD2CD2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 Alkyl-NHC(O)- (e.g., C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-), deuterated C 1-6 Alkyl-NHC(O)- (e.g., fully deuterated C 1-4 Alkyl-NHC(O)-, such as CD3-NHC(O)-, CD3CD2-NHC(O)-, and CD3CD2CD2-NHC(O)-), C 1-6 Alkyl-C(O)NH- (e.g., C 1-4 Alkyl-C(O)NH-, such as CH3-C(O)NH-, CH3CH2-C(O)NH- and CH3CH2CH2-C(O)NH-), deuterated C 1-6 Alkyl-C(O)NH- (e.g., fully deuterated C 1-4 and optionally substituted with one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CD3-C(O)NH-, CD3CD2-C(O)NH-, and CD3CD2CD2-C(O)NH-), or any combination thereof.

[0074] In some embodiments, R of the compound of formula (II) c is the following group: A monocyclic ring C containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur. 3-10heterocyclylene (e.g., piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene, or diazacyclooctylene); or C containing one nitrogen atom and optionally containing heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur 5-20 Bridged heterocyclylene (e.g., azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene or diazabicyclo[2.2.2]octanylene, such as the group [ka] represents where the symbol * represents the connection point with the group U1, Here, the monocyclic ring C 3-10 Heterocyclylene and C 5-20 The bridged heterocyclylenes each independently contain deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, CHO, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with one or more (e.g., 1-10, 1-8 or 1-6, e.g., 1, 2, 3, 4, 5 or 6) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH- and CH3CH2CH2-C(O)NH-), or any combination thereof.

[0075] In some embodiments, R of the compound of formula (II) c is the following group: [ka] [ka] represents Here, the symbol * represents the connection point with the base U1.

[0076] In some embodiments, W of the compound of Formula (II) is the following group: A monocyclic ring C containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur. 3-10 heterocyclyl (e.g., piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl, or diazacyclooctyl); or C containing one nitrogen atom and optionally containing heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur 5-20 Bridged heterocyclyl (e.g., azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl or diazabicyclo[2.2.2]octanyl, such as the group [ka] ;or, Saturated or partially unsaturated monocyclic, bicyclic or polycyclic C 3-20 Cyclic hydrocarbon groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, C 7-11 spirocycloalkyl, adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl or biscyclo[2.2.1]heptenyl); or Heteroaryl, for example, a 5- to 20-membered monocyclic or bicyclic C ring containing one or more (e.g., 1-4, e.g., 1, 2, 3, or 4) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. 5-20Aromatic ring groups (e.g., furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxazolyl, thiadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl); or C optionally containing one or more (e.g., 1-3, e.g., 1, 2, or 3) fused rings 5-14 aryl (e.g., phenyl, or naphthyl or fluorenyl); represents wherein the monocyclic ring C 3-10 Heterocyclyl, said C 5-20 Bridged heterocyclyl, 3-20 The cyclic hydrocarbon group, the heteroaryl and the C 5-14 Aryl is independently selected from deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl, optionally substituted C 3-8cycloalkyl (e.g., substituted with one or more (e.g., 1-6, for example, 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, mercapto, cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy); optionally substituted 4- to 9-membered heterocyclyl (e.g., substituted with one or more (e.g., 1-6, for example, 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, mercapto, cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy); 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), deuterated C 1-6 Alkyl-O- (e.g., fully deuterated C 1-4 Alkoxy, such as CD3-O-, fully deuterated ethoxy, fully deuterated propoxy, fully deuterated isopropoxy, fully deuterated butoxy, fully deuterated sec-butoxy or fully deuterated tert-butoxy), C 1-6 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), deuterated C 1-6 Alkyl-NH- (e.g., fully deuterated C 1-3 Alkyl-NH-, such as CD3NH-, CD3CD2NH- or CD3CD2CD2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 Alkyl-NHC(O)-(e.g., C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-), deuterated C 1-6Alkyl-NHC(O)- (e.g., fully deuterated C 1-4 Alkyl-NHC(O)-, such as CD3-NHC(O)-, CD3CD2-NHC(O)-, and CD3CD2CD2-NHC(O)-), C 1-6 Alkyl-C(O)NH- (e.g., C 1-4 Alkyl-C(O)NH-, such as CH3-C(O)NH-, CH3CH2-C(O)NH- and CH3CH2CH2-C(O)NH-), deuterated C 1-6 Alkyl-C(O)NH- (e.g., fully deuterated C 1-4 and optionally substituted with one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CD3-C(O)NH-, CD3CD2-C(O)NH-, and CD3CD2CD2-C(O)NH-), or any combination thereof.

[0077] In some embodiments, the L I of the compound of formula (II) has the structure of the following formula: #-C 1-30 Alkylene-; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(Ra4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -(R e (C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -(R f (C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(R e -R f -(C(R a3 )(R a4 ))n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R f -R e -(C(R a3 )(R a4 )) n2 ) m1 -or #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 represents -; where each group R e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 represents alkyl; each group R fis selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene, independently of one another, may further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; Said C 1-30 One or more (e.g., 1-30) CH hydrogens in the alkylene may further be replaced by deuterium, hydroxy, amino, mercapto groups, nitro groups, halogens (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 alkyl-C(O)NH-, such as CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-, or any combination thereof; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 and R a8 are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 alkyl-C(O)NH-, such as CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-, or any combination thereof; The symbol # represents the point of attachment to the group U2; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

[0078] In some embodiments, the L I of the compound of formula (II) has the structure of the following formula: #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -(O(C(Ra5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -(O(C(R a5 )(R a6 )) n3 ) m2 -(O(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -(N(R g )(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -(N(R g )(C(R a5 )(R a6 )) n3 ) m2 -(N(R g )(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(C(O)N(R g )-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(C(O)N(R g )-(C(R a5 )(R a6 )) n3 ) m2 -(C(O)N(R g )-(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -C(O)N(Rg )-(C(R a3 )(R a4 )) n2 -(O(C(R a5 )(R a6 )) n3 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -(O-(C(R g )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -N(R g )C(O)-(C(R a3 )(R a4 )) n2 -(O(C(R a5 )(R a6 )) n3 ) m1 -; #-(C(Ra1 )(R a2 )) n1 -N(R g )C(O)N(R g )-(C(R a3 )(R a4 )) n2 -; #-(C(R a1 )(R a2 )) n1 -C(O)-(C(R a3 )(R a4 )) n2 -; #-(C(R a1 )(R a2 )) n1 -(arylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(arylene-(C(R a3 )(R a4 )) n2 ) m1 -Arylene-(C(R a5 )(R a6 )) n3 -; #-(C(R a1 )(R a2 )) n1 -(heterocyclylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(heterocyclylene-(C(R a3 )(R a4 )) n2 ) m1 -(heterocyclylene-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1-(heteroarylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(heteroarylene-(C(R a3 )(R a4 )) n2 ) m1 -(heteroarylene-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(cycloalkylene-(C(R a3 )(R a4 )) n2 ) m1 -or #-(C(R a1 )(R a2 )) n1 -(cycloalkylene-(C(R a3 )(R a4 )) n2 ) m1 -(cycloalkylene-(C(R a5 )(R a6 )) n3 ) m2 represents -; Here, each R g are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl; The cycloalkylene, the arylene, the heterocyclylene and the heteroarylene may each independently further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , Ra7 and R a8 are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4alkyl-C(O)NH-, such as CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-, or any combination thereof; The symbol # represents the point of attachment to the group U2; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15.

[0079] In some embodiments, L I of the compound of Formula (II) is a group: #-CH2-, #-(CH2)2-, #-(CH2)3-, #-(CH2)4-, #-(CH2)5-, #-(CH2)6-, #-(CH2)7-, #-(CH2)8-, #-(CH2)9-, #-(CH2) 10 -, #-(CH2) 11 -, #-(CH2) 12 -, #-(CH2) 13 -, #-(CH2) 14 -, #-(CH2) 15 -, #-(CH2) 16 -, #-(CH2) 17 -, #-(CH2) 18 -, #-(CH2) 19 -, #-(CH2) 20 -, #-(CH2) 21 -, #-(CH2) 22 -, #-(CH2) 25 - or #-(CH2) 30 -;#-CH2-O-CH2-, #-CH2-O-(CH2)2-, #-(CH2)1-O-(CH2)3-, #-(CH2)1-O-(CH2)4-, #-(CH2)1-O-(CH2)5-, #- (CH2)1-O-(CH2)6-, #-(CH2)1-O-(CH2)7-, #-(CH2)1-O-(CH2)8-, #-(CH2)1-O-(CH2)9-, #-(CH2)1-O-(CH2) 10-、#-(CH2)2-O-(CH2)1-、#-(CH2)2-O-(CH2)2-、#-(CH2)2-O-(CH2)3-、#-(CH2)2-O-(CH2)4-、#-(CH2)2-O-(CH2)5-、#-(CH2)2-O-(CH2)6-、#-(CH2)2-O-(CH2)7-、#-(CH2)2-O-(CH2)8-、#-(CH2)2-O-(CH2)9-、#-(CH2)2-O-(CH2) 10 -、#-(CH2)2-O-(CH2) 11 -、#-(CH2)2-O-(CH2) 12 -、#-(CH2)3-O-(CH2)1-、#-(CH2)3-O-(CH2)2-、#-(CH2)3-O-(CH2)3-、#-(CH2)3-O-(CH2)4-、#-(CH2)3-O-(CH2)5-、#-(CH2)3-O-(CH2)6-、#-(CH2)3-O-(CH2)7-、#-(CH2)4-O-(CH2)1-、#-(CH2)4-O-(CH2)2-、#-(CH 2)4-O-(CH2)3-、#-(CH2)4-O-(CH2)4-、#-(CH2)4-O-(CH2)5-、#-(CH2)4-O-(CH2)6-、#-(CH2)5-O-(CH2)1-、#-(CH2)5-O-(CH2)2-、#-(CH2)5-O-(CH2)3-、#-(CH2)5-O-(CH2)4-、#-(CH2)5-O-(CH2)5-、#-(CH2)6-O-( CH2)1-、#-(CH2)6-O-(CH2)2-、#-(CH2)6-O-(CH2)3-、#-(CH2)6-O-(CH2)4-、#-(CH2)7-O-(CH2)1-、#-(CH2)7-O-(CH2)2-、#-(CH2)7-O-(CH2)3-、#-(CH2)8-O-(CH2)1-、#-(CH2)8-O-(CH2)2-、#-CH(CH3)-O-(CH2)1- 、#-CH(CH3)-O-(CH2)2-、#-CH(CH3)-O-(CH2)3-、#-CH(CH3)-O-(CH2)4-、#-CH(CH3)-O-(CH2)5-、#-CH(CH3)-O-(CH2)6-、#-CH(CH3)-O-(CH2)7-、#-CH(CH3)-O-(CH2)8-、#-CH(CH3)-O-(CH2)9-、#-CH(CH3)-O-(CH2) 10-、#-CH2-(O(CH2)2)2-、#-CH2-(O(CH2)2)3-、#-CH2-(O(CH2)2)4-、#-CH2-(O(CH2)2)5-、#-CH2-(O(CH2)2)6-、#-CH2-(O(CH2)2)7-、#-CH2-(O(CH2)2)8-、#-CH2-(O(CH2)2)9-、#-CH2-(O(CH2)2) 10 -、#-CH2-(O(CH2)2)1-OCH2-、#-CH2-(O(CH2)2)2-OCH2-、#-CH2-(O(CH2)2)3-OCH2-、#-CH2-(O(CH2)2)4-OCH2-、#-CH2-(O(CH2)2)5-OCH2-、#-CH2-(O(CH2)2)6-OCH2-、#-CH2-(O(CH2)2)7-OCH2-、#-CH2-(O(CH2)2)8-OCH2-、#-CH2-(O(CH2)2)9-OCH2-、#-CH2-(O(CH2)2) 10 -OCH2-、#-(CH2)2-(O(CH2)2)2-、#-(CH2)2-(O(CH2)2)3-、#-(CH2)2-(O(CH2)2)4-、#-(CH2)2-(O(CH2)2)5-、#-(CH2)2-(O(CH2)2)6-、#-(CH2)2-(O(CH2)2)7-、#-(CH2)2-(O(CH2)2)8-、#-(CH2)2-(O(CH2)2)9-、#-(CH2)2-(O(CH2)2) 10 -、#-(CH2)3-(O(CH2)2)2-、#-(CH2)3-(O(CH2)2)3-、#-(CH2)3-(O(CH2)2)4-、#-(CH2)3-(O(CH2)2)5-、#-(CH2)3-(O(CH2)2)6-、#-(CH2)3-(O(CH2)2)7-、#-(CH2)3-(O(CH2)2)8-、#-(CH2)3-(O(CH2)2)9-、#-(CH2)3-(O(CH2)2) 10-、#-(CH2)4-(O(CH2)2)2-、#-(CH2)4-(O(CH2)2)3-、#-(CH2)4-(O(CH2)2)4-、#-(CH2)4-(O(CH2)2)5-、#-(CH2)4-(O(CH2)2)6-、#-(CH2)4-(O(CH2)2)7-、#-(CH2)4-(O(CH2)2)8-、#-(CH2)4-(O(CH2)2)9-、#-(CH2)4-(O(CH2)2) 10 -、#-CH2-(O(CH2)3)2-、#-CH2-(O(CH2)3) 3-、#-CH2-(O(CH2)3)4-、#-CH2-(O(CH2)3)5-、#-CH2-(O(CH2)3)6-、#-CH2-(O(CH2)3)7-、#-CH2-(O(CH2)3)8-、#-CH2-(O(CH2)3)9-、#-CH2-(O(CH2)3) 10 -、#-(CH2)2-(O(CH2)3)2-、#-(CH2)2-(O(CH2)3)3-、#-(CH2)2-(O(CH2)3)4-、#-(CH2)2-(O(CH2)3)5-、#-(CH2)2-(O(CH2)3)6-、#-(CH2)2-(O(CH2)3)7-、#-(CH2)2-(O(CH2)3)8-、#-(CH2)2-(O(CH2)3)9-、#-(CH2)2-(O(CH2)3) 10 -、#-(CH2)3-(O(CH2)3)2-、#-(CH2)3-(O(CH2)3)3-、#-(CH2)3-(O(CH2)3)4-、#-(CH2)3-(O(CH2)3)5-、#-(CH2)3-(O(CH2)3)6-、#-(CH2)3-(O(CH2)3)7-、#-(CH2)3-(O(CH2)3)8-、#-(CH2)3-(O(CH2)3)9-、#-(CH2)3-(O(CH2)3) 10-、#-CH2-O-(CH2)2-O-(CH2)3-、#-CH2-(O(CH2)2)2-(O(CH2)3)2-、#-CH2-(O(CH2)2)3-(O(CH2)3)3-、#-CH2-(O(CH2)2)4-(O(CH2)3)4-、#-CH2-(O(CH2)2)5-(O(CH2)3)5-、#-CH2-(O(CH2)2)6-(O(CH2)3)6-、#-(CH2)2-O-(CH2)2-O-(CH2)3-、#-(CH2)2-(O(CH2)2)2-(O(CH2)3)2-、#-(CH2)2-(O(CH2)2 )3-(O(CH2)3)3-、#-(CH2)2-(O(CH2)2)4-(O(CH2)3)4-、#-(CH2)2-(O(CH2)2)5-(O(CH2)3)5-、#-(CH2)2-(O(CH2)2)6-(O(CH2)3)6-、#-(CH2)3-O-(CH2)2-O-(CH2)3-、#-(CH2)3-(O(CH2)2)2-(O(CH2)3)2-、#-(CH2)3-(O(CH2)2)3-(O(CH2)3)3-、#-(CH2)3-(O(CH2)2)4-(O(CH2)3)4-、#-(CH2)3-(O(CH2 )2)5-(O(CH2)3)5-、#-(CH2)3-(O(CH2)2)6-(O(CH2)3)6-、#-CH2-O-(CH2)3-O-(CH2)2-、#-CH2-(O(CH2)3)2-(O(CH2)2)2-、#-CH2-(O(CH2)3)3-(O(CH2)2)3-、#-CH2-(O(CH2)3)4-(O(CH2)2)4-、#-CH2-(O(CH2)3)5-(O(CH2)2)5-、#-CH2-(O(CH2)3)6-(O(CH2)2)6-、#-(CH2)2-O-(CH2)3-O-(CH2)2-、#- (CH2)2-(O(CH2)3)2-(O(CH2)2)2-、#-(CH2)2-(O(CH2)3)3-(O(CH2)2)3-、#-(CH2)2-(O(CH2)3)4-(O(CH2)2)4-、#-(CH2)2-(O(CH2)3)5-(O(CH2)2)5-、#-(CH2)2-(O(CH2)3)6-(O(CH2)2)6-、#-(CH2)3-O-(CH2)3-O-(CH2)2-、#-(CH2)3-(O(CH2)3)2-(O(CH2)2)2-、#-(CH2)3-(O(CH2)3)3-(O(CH2)2)3-、#-(CH2)3-(O(CH2)3)4-(O(CH2)2)4-、#-(CH2)3-(O(CH2)3)5-(O(CH2)2)5-、#-(CH2)3-(O(CH2)3)6-(O(CH2)2)6-、#-CH2-O-(CH2)2-O-CH2-、#-(CH2)2-O-(CH2)2-O-CH2-、#-(CH2)2-(O(CH2)2)2-O-(CH2)3-、#-(CH2)2-(O(CH2)2)3-O-(CH2)3-、#-(CH2)2-(O(CH2)2)4-O-(CH2)3-、#-(CH2)5-(O(CH2)2)2-O-(CH2)5-、#-(CH2)5-(O(CH2)2)2-O-(CH2)6-、#-(CH2)1-N(R、 g )-(CH2)1-、#-(CH2)1-N(R g )-(CH2)2-、#-(CH2)1-N(R g )-(CH2)3-、#-(CH2)1-N(R g )-(CH2)4-、#-(CH2)1-N(R g )-(CH2)5-、#-(CH2)1-N(R g )-(CH2)6-、#-(CH2)1-N(R g )-(CH2)7-、#-(CH2)1-N(R g )-(CH2)8-、#-(CH2)1-N(R g )-(CH2)9-、#-(CH2)1-N(R g )-(CH2) 10 -、#-(CH2)2-N(R g )-(CH2)1-、#-(CH2)2-N(R g )-(CH2)2-、#-(CH2)2-N(R g )-(CH2)3-、#-(CH2)2-N(R g )-(CH2)4-、#-(CH2)2-N(R g )-(CH2)5-、#-(CH2)2-N(R g )-(CH2)6-、#-(CH2)2-N(R g )-(CH2)7-、#-(CH2)2-N(R g )-(CH2)8-、#-(CH2)2-N(R g )-(CH2)9-、#-(CH2) 2-N(Rg )-(CH2) 10 -、#-(CH2)2-N(R g )-(CH2) 11 -、#-(CH2)2-N(R g )-(CH2) 12 -、#-(CH2)3-N(R g )-(CH2)1-、#-(CH2)3-N(R g )-(CH2)2-、#-(CH2)3-N(R g )-(CH2)3-、#-(CH2)4-N(R g )-(CH2)1-、#-(CH2)4-N(R g )-(CH2)2-、#-(CH2)4-N(R g )-(CH2)3-、#-(CH2)4-N(R g )-(CH2)4-、#-(CH2)5-N(R g )-(CH2)1-、#-(CH2)5-N(R g )-(CH2)2-、#-(CH2)5-N(R g )-(CH2)3-、#-(CH2)5-N(R g )-(CH2)4-、#-(CH2)5-N(R g )-(CH2)5-、#-(CH2)6-N(R g )-(CH2)1-、#-(CH2)6-N(R g )-(CH2)2-、#-(CH2)6-N(R g )-(CH2)3-、#-(CH2)7-N(R g )-(CH2)1-、#-(CH2)7-N(R g )-(CH2)2-、#-(CH2)7-N(R g )-(CH2)3-、#-(CH2)8-N(R g )-(CH2)1-、#-(CH2)8-N(R g )-(CH2)2-、#-(CH2)8-N(R g )-(CH2)3-、#-CH(CH3)-N(R g )-(CH2)1-、#-CH(CH3)-N(R g )-(CH2)2-、#-CH(CH3)-N(R g )-(CH2)3-、#-CH(CH3)-N(R g)-(CH2)4-、#-CH(CH3)-N(R g )-(CH2)5-、#-CH(CH3)-N(R g )-(CH2)6-、#-CH(CH3)-N(R g )-(CH2)7-、#-CH(CH3)-N(R g )-(CH2)8-、#-CH(CH3)-N(R g )-(CH2)9-、#-CH(CH3)-N(R g )-(CH2) 10 -、#-CH2C(O)NHCH2-、#-(CH2)2C(O)NH(CH2)2-、#-(CH2)2C(O)NH(CH2)3-、#-(CH2)2C(O)NH(CH2)4-、#-(CH2)2C(O)NH(CH2)5-、#-(CH2)3C(O)NH(CH2)3-、#-(CH2)3C(O)NH(CH2)4-、#-(CH 2)4C(O)NH(CH2)4-、#-(CH2)5C(O)NH(CH2)5-、#-(CH2)6C(O)NH(CH2)7-、#-(CH2)6C(O)NH(CH2)6-、#-(CH2)7C(O)NH(CH2)7-、#-(CH2)8C(O)NH(CH2)8、U-(CH2)9C(O)NH(CH2)9-、#-(CH2) 10 C(O)NH(CH2) 10 -、#-(CH2)2C(O)NH(CH2)2-O-(CH2)2-、#-CH2NHC(O)CH2-、#-(CH2)2NHC(O)(CH2)2-、#-(CH2)2NHC(O) (CH2)3-、#-(CH2)2NHC(O)(CH2)4-、#-(CH2)2NHC(O)(CH2)5-、#-(CH2)3NHC(O)(CH2)3-、#-(CH2)3NHC (O)(CH2)4-、#-(CH2)4NHC(O)(CH2)4-、#-(CH2)5NHC(O)(CH2)5-、#-(CH2)6NHC(O)(CH2)7-、#-(CH2)6 NHC(O)(CH2)6-、#-(CH2)7NHC(O)(CH2)7-、#-(CH2)8NHC(O)(CH2)8、#-(CH2)9NHC(O)(CH2)9-、#-(CH2) 10 NHC(O)(CH2) 10-, #-(CH2)4NHC(O)(CH2)8-, #-(CH2)2NHC(O)(CH2)2-O-(CH2)2-, #-(CH2)4NHC(O)CH2-, #-CH2-piperidinylene-CH2-, #-CH2-piperidinylene-(CH2)2-, #-CH2-piperidinylene-(CH2)3-, #-CH2-piperidinylene-(CH2)4-, #-CH2-piperidinylene-(CH2)5-, #-CH2-piperidinylene-(CH2)6-, #-CH2-piperidinylene-(CH2)7-, #-CH2-piperidinylene-(CH2)8-, #-(CH2)2-piperidinylene-(CH2)1-, #-(CH2)2-piperidinylene-(CH2)2-, #-(CH2)2-piperidinylene-(CH2)3-, #-(CH2)2-piperidinylene-(CH2)4-, #-(CH2)2-piperidinylene-(CH2)5-, #-(CH2)2-piperidinylene-(CH2)6-, #-(CH2)2-piperidinylene-(CH2)7-, #-(CH2)2-piperidinylene-(CH2)8-, #-(CH2)3-piperidinylene-CH2-, #-(CH2)3-piperidinylene-(CH2)2-, # -(CH2)3-piperidinylene-(CH2)3-, #-(CH2)3-piperidinylene-(CH2)4-, #-(CH2)3-piperidinylene-(CH2)5-, #-(CH2)3-piperidinylene-(CH2)6-, #-(CH2)3-piperidinylene-(CH2)7-, #-(CH2)3-piperidinylene-(CH2)8-, #-(CH2)4-piperidinylene-CH2-, #-(CH2)4-piperidinylene-(CH2)2-, #-(CH2)4-piperidinylene-(CH2)3-, #-(CH2)4-piperidinylene-(CH2)4-, #- (CH2)4-piperidinylene-(CH2)5-, #-(CH2)4-piperidinylene-(CH2)6-, #-(CH2)4-piperidinylene-(CH2)7-, #-(CH2)4-piperidinylene-(CH2)8-, #-(CH2)5-piperidinylene-(CH2)1-, #-(CH2)5-piperidinylene-(CH2)2-, #-(CH2)5-piperidinylene-(CH2)3-, #-(CH2)5-piperidinylene-(CH2)4-, #-(CH2)5-piperidinylene-(CH2)5-, #-(CH2)5-piperidinylene-(CH2)6-,#-(CH2)5-piperidinylene-(CH2)7-, #-(CH2)5-piperidinylene-(CH2)8-, #-(CH2)6-piperidinylene-(CH2)1-, #-(CH2)6-piperidinylene-(CH2)2-, #-(CH2)6-piperidinylene-(CH2)3-, #-(CH2)6-piperidinylene-(CH2, )4-, #-(CH2)6-piperidinylene-(CH2)5-, #-(CH2)6-piperidinylene-(CH2)6-, #-(CH2)6-piperidinylene-(CH2)7-, #-(CH2)6-piperidinylene-(CH2)8-, #-(CH2)7-piperidinylene-(CH2)1-, #-(CH2)7-piperidinylene-(CH2)2-, #-(CH2)7-piperidinylene-(CH2)3-, #-(CH2)7-piperidinylene-(CH2)4-, #-(CH2)7-piperidinylene Nylene-(CH2)8-, #-(CH2)8-piperidinylene-CH2-, #-(CH2)8-piperidinylene-(CH2)2-, #-(CH2)8-piperidinylene-(CH2)3-, #-(CH2)8-piperidinylene-(CH2)4-, #-(CH2)8-piperidinylene-(CH2)5-, #-(CH2)8-piperidinylene-(CH2)6-, #-(CH2)8-piperidinylene-(CH2)7-, #-(CH2)8-piperidinylene-(CH2)8-, #-CH2-N(R g )-CH2-piperidinylene-CH2-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)2-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)3-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)4-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)5-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)6-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)7-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)8-, #-CH2-N(R g )-(CH2)2-piperidinylene-CH2-, #-CH2-N(R g)-(CH2)2-piperidinylene-(CH2)2-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)3-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)4-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)5-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)6-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)7-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)8-, #-(CH2)2-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)4-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)5-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)6-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)7-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)3-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)3-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)3-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)3-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)4-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)4-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)4-N(R g)-CH2-piperidinylene-(CH2)3-, #-(CH2)4-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)5-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)5-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)6-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)6-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)7-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)7-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)8-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)4-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)5-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)6-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)7-, #-(CH2)8-N(R g)-CH2-piperidinylene-(CH2)8-, #-CH2-piperazinylene-CH2-, #-CH2-piperazinylene-(CH2)2-, #-CH2-piperazinylene-(CH2)3-, #-CH2-piperazinylene-(CH2)4-, #-CH2-piperazinylene-(CH2)5-, #-CH2-piperazinylene-(CH2)6-, #-CH2-piperazinylene-(CH2)7-, #-CH2-piperazinylene ylene-(CH2)8-, #-(CH2)2-piperazinylene-(CH2)1-, #-(CH2)2-piperazinylene-(CH2)2-, #-(CH2)2-piperazinylene-(CH2)3-, #-(CH2)2-piperazinylene-(CH2)4-, #-(CH2)2-piperazinylene-(CH2)5-, #-(CH2)2-piperazinylene-(CH2)6-, #-(CH2)2-piperazinylene-(CH2)7 -, #-(CH2)2-piperazinylene-(CH2)8-, #-(CH2)3-piperazinylene-CH2-, #-(CH2)3-piperazinylene-(CH2)2-, #-(CH2)3-piperazinylene-(CH2)3-, #-(CH2)3-piperazinylene-(CH2)4-, #-(CH2)3-piperazinylene-(CH2)5-, #-(CH2)3-piperazinylene-(CH2)6-, #-(CH2)3-piperazinylene Perazinylene-(CH2)7-, #-(CH2)3-piperazinylene-(CH2)8-, #-(CH2)4-piperazinylene-CH2-, #-(CH2)4-piperazinylene-(CH2)2-, #-(CH2)4-piperazinylene-(CH2)3-, #-(CH2)4-piperazinylene-(CH2)4-, #-(CH2)4-piperazinylene-(CH2)5-, #-(CH2)4-piperazinylene-(CH2)6 -, #-(CH2)4-piperazinylene-(CH2)7-, #-(CH2)4-piperazinylene-(CH2)8-, #-(CH2)5-piperazinylene-(CH2)1-, #-(CH2)5-piperazinylene-(CH2)2-, #-(CH2)5-piperazinylene-(CH2)3-, #-(CH2)5-piperazinylene-(CH2)4-, #-(CH2)5-piperazinylene-(CH2)5-, #-(CH2)5-piperazinylene- (CH2)6-, #-(CH2)5-piperazinylene-(CH2)7-, #-(CH2)5-piperazinylene-(CH2)8-, #-(CH2)6-piperazinylene-(CH2)1-, #-(CH2)6-piperazinylene-(CH2)2-, #-(CH2)6-piperazinylene-(CH2)3-, #-(CH2)6-piperazinylene-(CH2)4-, #-(CH2)6-piperazinylene-(CH2)5-, #-(CH2)6-pipera Dinylene-(CH2)6-, #-(CH2)6-piperazinylene-(CH2)7-, #-(CH2)6-piperazinylene-(CH2)8-, #-(CH2)7-piperazinylene-(CH2)1-, #-(CH2)7-piperazinylene-(CH2)2-, #-(CH2)7-piperazinylene-(CH2)3-, #-(CH2)7-piperazinylene-(CH2)4-, #-(CH2)7-piperazinylene-(CH2)8-, #-(CH2) 8-piperazinylene-CH2-, #-(CH2)8-piperazinylene-(CH2)2-, #-(CH2)8-piperazinylene-(CH2)3-, #-(CH2)8-piperazinylene-(CH2)4-, #-(CH2)8-piperazinylene-(CH2)5-, #-(CH2)8-piperazinylene-(CH2)6-, #-(CH2)8-piperazinylene-(CH2)7-, or #-(CH2)8-piperazinylene-(CH2)8-; wherein the piperidinylene and the piperazinylene may each independently further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; Each R g are independently H or C 1-6 Alkyl (e.g., C 1-4alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl; The symbol # represents the point of attachment to the group U2; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15.

[0080] In some embodiments, R of the compound of formula (II) a is the following group: [ka] represents; wherein said groups are optionally partially or fully deuterated.

[0081] In some embodiments, the compound of Formula (II) is also a compound of Formula (II-1) or Formula (II-2): [ka] Here, A, R1, R2, R3, R4, (R b ) n and (R a ) m is as defined above for compounds of formula (II) and each embodiment thereof.

[0082] In some embodiments, the compound of formula (II) is also a compound of formula (II-3) or (II-4): [ka] where A, (R b ) n and (R a ) m is as defined above for compounds of formula (II) and each embodiment thereof.

[0083] In some embodiments, the compound of formula (II) is also a compound of formula (II-5), (II-6), (II-7), or (II-8): [ka] Here, A, R1, R2, R3, R4, (R b ) n and R a is as defined above for compounds of formula (II) and each embodiment thereof.

[0084] In some embodiments, the compound of Formula (II-5), Formula (II-6), Formula (II-7), or Formula (II-8): A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); (R b ) n is a group consisting of n benzene rings b Each R represents a substitution b are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 alkynyl (e.g. ethynyl, propynyl or butynyl); where n represents an integer of 0, 1, 2, or 3; R a is a structure of the formula: W-LIN-U2-R c -U1- represents where: U1 and U2 are the same or different and each independently represent a bond, N(R d ) or O, where R d is H or optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl; R c represents an optionally substituted nitrogen-containing monocyclic heterocyclylene or an optionally substituted nitrogen-containing bridged heterocyclylene; W is hydrogen, optionally substituted nitrogen-containing monocyclic heterocyclyl, optionally substituted nitrogen-containing bridged heterocyclyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, C 2-6alkenyl (e.g. vinyl, propenyl or butenyl), C 2-6 represents an alkynyl (e.g., ethynyl, propynyl, or butynyl), a leaving group, a CHO, COOH, NH2, hydroxy, or mercapto group; and where: When the compound is partially or fully deuterated, When W represents an optionally substituted nitrogen-containing monocyclic heterocyclyl, an optionally substituted nitrogen-containing bridged heterocyclyl, an optionally substituted cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted aryl, LIN represents a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may contain one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and / or one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5 or 6) groups R f or one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and R f and any combination of the groups R e , R f or group R e and R f the combination of which cleaves one or more pairs (e.g., 1-10 pairs, 1-8 pairs, or 1-6 pairs, e.g., 1, 2, 3, 4, 5, or 6 pairs) of carbon-carbon bonds between adjacent carbon atoms in the carbon backbone; e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 Alkyl (e.g., C 1-4alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), and the linear or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R e are not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; or W is hydrogen, C 2-6 Alkenyl, C 2-6 When representing an alkynyl, leaving group, CHO, COOH, NH2, hydroxy or mercapto group, LIN is an optionally substituted methylene or an optionally substituted straight or branched chain C 2-30 alkylene, wherein the straight or branched chain C 2-30 The alkylene carbon backbone may optionally contain one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and / or one or more (e.g. 1-10, 1-8 or 1-6, e.g. 1, 2, 3, 4, 5 or 6) groups R f or one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) groups R e and R f and any combination of the groups R e , R f or group R e and R f the combination of which cleaves one or more pairs (e.g., 1-10 pairs, 1-8 pairs, or 1-6 pairs, e.g., 1, 2, 3, 4, 5, or 6 pairs) of carbon-carbon bonds between adjacent carbon atoms in the carbon backbone; e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(Rg ), N(R g )C(O), or N(R g )C(O)N(R g ) wherein each R g are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example, methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), and the straight or branched C 2-30 Two or more groups R in the main carbon chain of the alkylene e When inserted, each group R e are not directly connected to each other; f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally fully deuterated cyclopropyl, optionally fully deuterated cyclobutyl, optionally fully deuterated cyclopentyl, or optionally fully deuterated cyclohexyl), hydroxy, amino, mercapto group, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH- (e.g., optionally deuterated C 1-3 alkyl-NH-, for example CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, e.g., NHCH-, NHCHCHCH-, and NHCHCHCHCH-), optionally deuterated C 1-6 Alkyl-NHC(O)- (e.g., optionally deuterated C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)- and CH3CH2CH2-NHC(O)-), optionally deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH-, and CH3CH2CH2-C(O)NH-), cyano, or any combination thereof; or When the compound is non-deuterated, L-In represents optionally substituted methylene, and W represents optionally substituted nitrogen-containing monocyclic heterocyclyl or optionally substituted nitrogen-containing bridged heterocyclyl; and wherein the nitrogen-containing monocyclic heterocyclylene, the nitrogen-containing bridged heterocyclylene, the nitrogen-containing monocyclic heterocyclyl, the nitrogen-containing bridged heterocyclyl, the cycloalkyl, the heteroaryl, and the aryl each independently represent deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-4Alkyl, such as CD3, fully deuterated ethyl, fully deuterated propyl, fully deuterated isopropyl, fully deuterated butyl, fully deuterated sec-butyl or fully deuterated tert-butyl), halogenated C 1-6 Alkyl, optionally substituted C 3-8 Cycloalkyl (e.g., substituted with one or more (e.g., 1-10, 1-8, or 1-6, e.g., 1, 2, 3, 4, 5, or 6) substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, mercapto, cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy), optionally substituted 4- to 9-membered heterocyclyl (e.g., substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, mercapto, cyano, CHO, COOH, N, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), deuterated C 1-6 Alkyl-O-, C 1-6 Alkyl-NH- (e.g., C 1-3 alkyl-NH-, such as CH3NH-, CH3CH2NH- or CH3CH2CH2NH-), deuterated C 1-6 Alkyl-NH- (e.g., fully deuterated C 1-3 Alkyl-NH-, such as CD3NH-, CD3CD2NH- or CD3CD2CD2NH-), NH2-C 1-6 Alkylene (e.g., NH2-C 1-3 alkylene-, such as NH2CH2-, NH2CH2CH2- and NH2CH2CH2CH2-), C 1-6 Alkyl-NHC(O)-(e.g., C 1-4 Alkyl-NHC(O)-, such as CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-), deuterated C 1-6Alkyl-NHC(O)- (e.g., fully deuterated C 1-4 Alkyl-NHC(O)-, such as CD3-NHC(O)-, CD3CD2-NHC(O)-, and CD3CD2CD2-NHC(O)-), C 1-6 Alkyl-C(O)NH-, deuterated C 1-6 Alkyl-C(O)NH- (e.g., optionally deuterated C 1-4 Optionally substituted with one or more (e.g., 1-10, 1-8 or 1-6, e.g., 1, 2, 3, 4, 5 or 6) substituents selected from the group consisting of alkyl-C(O)NH-, e.g., CH3-C(O)NH-, CH3CH2-C(O)NH- and CH3CH2CH2-C(O)NH-), or any combination thereof.

[0085] In some embodiments, specific compounds of Formula (II) in Table 2 below and salts (including pharmaceutically acceptable salts, e.g., hydrochloride salts thereof), pharmaceutical precursors, solvates, isotopically enriched analogs, polycrystalline forms, stereoisomers (including enantiomers and non-enantiomers), or mixtures of stereoisomers thereof are provided. Table 2. Compounds of the present disclosure Compound of formula (III)

[0086] The present disclosure provides a compound of formula (III) or a salt (including a pharmaceutically acceptable salt), stereoisomer (including an enantiomer), solvate, isotopically enriched analogue, pharmaceutical precursor, or polymorph thereof: PBM-R 1 -W 1 -LIN-ULM Formula (III) Here, PBM, R 1 , W 1 , LIN and ULM are as defined above for the compound of formula (III).

[0087] When the compound of formula (III) of the present disclosure is not substituted with deuterium, the compound of formula (III) is not a compound of formula (IV-1) below: [ka] Formula (IV-1) In formula (IV-1), R 1 represents a bond, and W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents fluorine, n represents an integer of 1, 2, or 3, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-1), R 1 represents a bond, and W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents fluorine; n represents an integer of 1, 2, or 3; and U1 and U2 are the same or different and each independently represent a bond, NH, or O.

[0088] When the compound of formula (III) of the present disclosure is not substituted with deuterium, the compound of formula (III) does not include the compound of formula (IV-2) below: [ka] Formula (IV-2) In formula (IV-2), R 1 represents a bond, and W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents fluorine, and n represents an integer of 1, 2, or 3, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-2), R 1 represents a bond, and W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents fluorine; n represents an integer of 1, 2, or 3; U1 and U2 are the same or different and each independently represents a bond, NH, or O.

[0089] When the compound of formula (III) of the present disclosure is not substituted with deuterium, the compound of formula (III) does not include the compound of formula (IV-3) below: [ka] Formula (IV-3) In formula (IV-3), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-3), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O.

[0090] When the compounds of formula (III) of the present disclosure are not substituted with deuterium, the compounds of formula (III) do not include compounds of formula (IV-4): [ka] Formula (IV-4) In formula (IV-4), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperidinylene, LIN represents methylene, and R c represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O; or In formula (IV-4), R 1 represents a bond or -O-CH2-CH2-, W 1 represents piperazinylene, LIN represents methylene, and R c represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R b represents hydrogen, and U1 and U2 are the same or different and each independently represent a bond, NH, or O.

[0091] The compounds of formula (III) of the present disclosure, or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), solvates, isotopically enriched analogues, pharmaceutical precursors, or polymorphs thereof, are capable of binding to target proteins and recruiting the target proteins to E3 ubiquitin ligases for ubiquitination tagging and degradation. The compounds of formula (III) of the present disclosure specifically target particular target protein types or families and exhibit broad pharmacological activity by degradation / inhibition of a variety of different target protein types or families.

[0092] In some embodiments, specific target proteins include, but are not limited to, the target proteins in Table 3 below. Table 3. Applicable specific target proteins

[0093] In some embodiments, the PBM is a small molecule ligand that targets a specific target protein, including, but not limited to, a small molecule ligand that targets EGFR, a small molecule ligand that targets CDK4 / 6, a small molecule ligand that targets ALK, a small molecule ligand that targets RET, a small molecule ligand that targets FAK, a small molecule ligand that targets BCR-ABL, a small molecule ligand that targets BTK, a small molecule ligand that targets AR, a small molecule ligand that targets ER, or a small molecule ligand that targets BET.

[0094] In some embodiments, the PBM has the formula: [ka] and where: (R 2 ) p1 The benzene ring of formula (PBM-1) is p1 R 2 Each R represents a substitution 2 are the same or different and each independently represent a halogen or halogenated C 1-6 represents alkyl; (R 3 ) p2 The quinazoline ring of formula (PBM-1) has p2 R 3 Each R represents a substitution 3 are the same or different and each independently represents C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Alkoxy, heterocyclyloxy, or -NHC(O)R 4 where R 4 is C 1-10 Alkyl or C 2-10 alkenyl, e.g., R 3 is methyl, methoxy, [ka] and; p1 represents an integer of 1, 2, 3, 4, or 5; p2 represents an integer of 1, 2, or 3; (R 5 ) p3 The benzene ring of formula (PBM-2) is p3 R 5 Each R represents a substitution 5 are the same or different and each independently represents C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Alkoxy or -NHC(O)R 4 where R 4 is C 1-10 Alkyl, deuterated C 1-10 Alkyl or C 2-10 alkenyl, e.g., R 5 is methyl, methoxy or [ka] represents; p3 represents an integer of 1, 2, 3, or 4; (R 6 ) p4 The 1H-indole ring of formula (PBM-2) is 6 Each R represents a substitution 6 are the same or different and each independently represents C 1-10 Alkyl or deuterated C 1-10 represents alkyl; p4 represents an integer of 0, 1, 2 or 3; (R 7 ) p5 The benzene ring of formula (PBM-3) has p5 R 7 Each R represents a substitution 7 are the same or different and each independently represent a halogen, a hydroxyl, or C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 represents an alkyl, NO2, NH2, or cyano group; p5 represents an integer of 2, 3, 4 or 5; R 8 is C 6-10 aryl, or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the C 6-10 The aryl and the heteroaryl each optionally contain one or more R 4a and each R 4a are the same or different and each independently represent a halogen, a hydroxyl, a cyano, an amino, a nitro group, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 is alkoxy; R 9 is C 1-10 Alkyl (for example) or deuterated C 1-10 represents alkyl; R 10 teeth [ka] where (R 5a ) p6 The piperidine ring has p6 R 5a Each R represents a substitution 5a are the same or different and each independently represent deuterium, halogen, hydroxy, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 represents an alkoxy, NO2, NH2, or cyano group, and p6 represents an integer of 1, 2, 3, 4, or 5; (R 11 ) p7 The benzene ring and the pyridine ring of formula (PBM-5) each optionally have p7 R 11 Each R represents a substitution 11 are the same or different and each independently represent a halogen, C 1-6 Alkyl, halogenated C1-6 Alkyl or deuterated C 1-6 alkyl, and p7 represents an integer of 0, 1, 2, or 3; Ring A of formula (PBM-6) is C 6-10 represents an aryl or a heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and the ring A optionally contains one or more R 6a and each R 6a are the same or different and each independently represent deuterium, halogen, hydroxy, cyano, amino, nitro group, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 2-6 Alkenyl, or C 2-6 is alkynyl; Ring B of formula (PBM-6) is C 3-15 cycloalkyl, or heterocyclyl containing one or two 3- to 7-membered rings and 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring B optionally contains one or more R 7a and each R 7a are the same or different and each independently represent deuterium, halogen, or C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 is alkoxy; Ring C in formula (PBM-6) represents a heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and the ring C optionally contains one or more R 8a and each R 8a are the same or different and each independently represent deuterium, halogen, hydroxy, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6Alkoxy or halogenated C 1-6 is alkoxy; X1 in formula (PBM-7) is N or CR 12 where R 12 is hydrogen or represents a bond, and X2 represents CH or N; R 13 is hydrogen or represents a bond, where R 13 represents a bond, X1 represents N or CH, and R 13 The ring atom N connected to R 1 Connect directly to R 13 is hydrogen, X1 is CR 12 where R 12 represents a bond, and R 12 The ring constituent atom C connected to 1 and connect; R 14 represents -O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, wherein the aryl and heteroaryl are each independently optionally selected from one or more R 9a and each R 9a are the same or different and each independently represent deuterium, halogen, hydroxy, cyano, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 is alkoxy; R 15 are deuterium, hydrogen, halogens, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl or -NHC(O)R 17 where R 17 is C 1-10 Alkyl or C 2-10 alkenyl, e.g., R 15 is hydrogen, methyl, or [ka] represents; R 16 represents hydrogen, a cyano group, or an amino group; X3 in formula (PBM-8) is CR 21 or fragment [ka] where ## denotes the connection point of X3 and the adjacent N, ### denotes the connection point of X4, and R 21 are deuterium, hydrogen, halogens, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-deuterated C 1-6 Alkyl or -C(O)NR 22 R 23 where R 22 , R 23 are the same or different and each independently represent hydrogen, C 1-6 Alkyl or deuterated C 1-6 represents alkyl, and R 22 , R 23 is not simultaneously hydrogen; X4 in formula (PBM-8) is N or CR 24 where R 24 are hydrogen, deuterium, halogens, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; X5 and X6 each independently represent CH or N; R 18 represents a bond or an optionally substituted heteroarylene (e.g., halogen-substituted heteroarylene); R 19 is hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl or optionally substituted C 3-7 represents cycloalkyl; R20 and R 25 are the same or different and each independently represent hydrogen, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 26 is hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; R 27 is hydrogen, cyano, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; (R 28 ) p8 The benzene ring of formula (PBM-10) has p8 R 28 Each R represents a substitution 28 are the same or different and each independently represent a halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 represents alkyl; p8 represents an integer of 1, 2, 3 or 4; R 29 is NR 30 R 31 where R 30 , R 31 are the same or different and each independently represent hydrogen, C 1-6 Alkyl or deuterated C 1-6 represents alkyl; In formula (PBM-11), X7, X8, and X9 are the same or different and each independently represent N or CH; (R 32 ) p9 The six-membered ring containing X8 and X9 in formula (PBM-11) is optionally divided into p9 R 32 Each R represents a substitution 32 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C1-6 Alkyl or halogenated C 1-6 represents alkyl; p9 represents an integer of 0, 1, 2, 3 or 4; R 33 is halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; R 34 -C(O)NHR 35 , -NHC(O)-R 35 , -S(O)2NHR 35 , -S(O)2R 35 or -P(O)(R 35 )2, where each R 35 are the same or different and each independently represents C 1-6 Alkyl or deuterated C 1-6 represents alkyl; (R 36 ) p10 The benzene ring of formula (PBM-12) is optionally selected from p10 R 36 Each R represents a substitution 36 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p10 represents an integer of 0, 1, 2, 3 or 4; (R 37 ) p11 The benzene ring of formula (PBM-13) has p11 R 37 Each R represents a substitution 37 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p11 represents an integer of 0, 1, 2, 3, or 4; (R 38 ) p12The benzene ring of formula (PBM-14) has p12 R 38 Each R represents a substitution 38 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p12 represents an integer of 0, 1, 2, 3 or 4; (R 39 ) p13 The 4-oxo-3,4-dihydroquinazoline ring of formula (PBM-14) is 39 Each R represents a substitution 39 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p13 represents an integer of 1, 2, 3 or 4; (R 40 ) p14 The benzene ring of formula (PBM-15) has p14 R 40 Each R represents a substitution 40 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p14 represents an integer of 1, 2, 3 or 4; R 41 is halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; (R 42 ) p15 The quinoline ring of formula (PBM-16) is 42 Each R represents a substitution 42 are the same or different and each independently represent a halogen, a cyano, or C 1-6 Alkoxy, C1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p15 represents an integer of 2, 3, or 4; (R 43 ) p16 The benzene ring of formula (PBM-16) has p16 R 43 Each R represents a substitution 43 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p16 represents an integer of 3 or 4; (R 44 ) p17 The benzene ring, pyrimidine ring, and pyridine ring of formula (PBM-17) each have p17 R 44 Each R represents a substitution 44 are the same or different and each independently represent a halogen, C 1-6 Alkoxy, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p17 represents an integer of 0, 1, 2, 3 or 4; R 45 , R 46 , R 47 and R 48 one of them represents a bond, and the remaining three are the same or different and each independently represent hydrogen, halogen, or hydroxy, where R 45 , R 46 , R 47 and R 48 When one of them represents a bond, the benzene ring or methylene in formula (PBM-18) connected by the bond is directly connected to R 1 and connected; Symbol connecting double bonds in formula (PBM-18) [ka] represents a bond that may be in any spatial configuration (cis or trans); (R 49 ) p18 The formula (PBM-19) has 18 1,2,3,4-tetrahydronaphthalene rings. 49 Each R represents a substitution 49 are the same or different and each independently represent hydrogen, hydroxy, halogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl; p18 represents an integer of 0, 1, 2, 3 or 4; and R 50 and R 51 One of them represents a bond, and the other represents hydrogen, halogen, or C. 1-6 Alkyl, deuterated C 1-6 Alkyl or halogenated C 1-6 represents alkyl, where R 50 and R 51 When one of them represents a bond, the benzene ring in formula (PBM-19) connected by the bond is directly connected to R 1 and is connected.

[0095] In some embodiments, PBM represents a small molecule ligand that targets EGFR, including, but not limited to, representing a structure of the following formula: (PBM-1-1A), (PBM-1-1B), (PBM-1-1C), or (PBM-1-1D). [ka] where: (R 2 ) p1 The benzene ring of formula (PBM-1-1A), formula (PBM-1-1B), formula (PBM-1-1C), or formula (PBM-1-1D) is a group having p1 R 2 Each R represents a substitution 2 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine) or a halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); (R 3 ) p2 The quinazoline ring of formula (PBM-1-1A), formula (PBM-1-1B), formula (PBM-1-1C) or formula (PBM-1-1D) has p R 3 Each R represents a substitution 3 are the same or different and each independently represents C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-10 Alkoxy (e.g., C 1-8 Alkoxy, C 1-6 Alkoxy or C 1-4 alkoxy, e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, or tert-butoxy), heterocyclyloxy (wherein heterocyclyl is, for example, a 4- to 20-membered monocyclic or bicyclic heterocyclyl containing one or more (e.g., 1-4 or 1, 2, 3, or 4) heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), or —NHC(O)R 4 where R 4 is C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl) or C 2-10Alkenyl (e.g., C 2-6 Alkenyl or C 2-4 alkenyl, such as vinyl, propenyl, butenyl or pentenyl), such as R 3 is methyl, methoxy, or [ka] and; p1 represents an integer of 1, 2, 3, 4, or 5; and p2 represents an integer of 1, 2 or 3.

[0096] In some embodiments, R 3 represents heterocyclyl-O—, wherein the heterocyclyl is a 4- to 20-membered (e.g., 4-15-membered, 4-12-membered, 4-10-membered, 4-7-membered, or 4-6-membered) monocyclic or bicyclic heterocyclyl containing one or more (e.g., 1 to 4 or 1, 2, 3, or 4) heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, diazacyclooctyl, , diazacycloheptanyl (e.g., 1,4-diazacycloheptan-1-yl), azacyclooctyl, diazacyclooctyl, azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl (e.g., 3,8-diazabicyclo[3.2.1]octan-3-yl), diazabicyclo[2.2.2]octanyl (e.g., 2,5-diazabicyclo[2.2.2]octan-2-yl).

[0097] In some embodiments, R 3 teeth, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl; methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy; -NHC(O)-C 2-10 alkenyl (e.g., -NHC(O)-vinyl, -NHC(O)-propenyl, or -NHC(O)-butenyl); or [ka] Represents.

[0098] In some embodiments, the PBM has the structure of formula (PBM-1-1), (PBM-1-2), (PBM-1-3), or (PBM-1-4): [ka] Represents.

[0099] In some embodiments, PBM represents a small molecule ligand that targets EGFR and has the structure of formula (PBM-2-1A), (PBM-2-1B), (PBM-2-1C) or (PBM-2-1D): [ka] Including, but not limited to, representing where: (R 5 ) p3 The benzene ring of formula (PBM-2-1A), formula (PBM-2-1B), formula (PBM-2-1C), or formula (PBM-2-1D) has p3 R 5 Each R represents a substitution 5 are the same or different and each independently represents C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-10 Alkoxy (e.g., C 1-8 Alkoxy, C 1-6 Alkoxy or C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy) or —NHC(O)R 4 where R 4 is C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.) or C 2-10 Alkenyl (e.g., C 2-6 Alkenyl or C 2-4 alkenyl, for example vinyl, propenyl, butenyl or pentenyl), for example R 5 is methyl, methoxy or [ka] represents; p3 represents an integer of 1, 2, 3, or 4; (R 6 ) p4 The 1H-indole ring of formula (PBM-2-1A), formula (PBM-2-1B), formula (PBM-2-1C), or formula (PBM-2-1D) has p4 R6で Each R represents a substitution. 6 are the same or different and each independently represents C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl) or deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); and p4 represents an integer of 0, 1, 2 or 3.

[0100] In some embodiments, the PBM has a structure of the following formula (PBM-2-1): [ka]

[0101] In some embodiments, PBM represents a small molecule ligand that targets EGFR and has the structure of formula (PBM-3-1A), (PBM-3-1B), (PBM-3-1C), or (PBM-3-1D): [ka] Including, but not limited to, representing where: (R 7 ) p5 The benzene ring of formula (PBM-3-1A), formula (PBM-3-1B), formula (PBM-3-1C), or formula (PBM-3-1D) has p5 R 7 Each R represents a substitution 7 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, C 1-6 Alkyl (e.g., C 1-8 Alkyl, C1-6 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 represents an alkyl group (e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), NO2, NH2, or cyano group; p5 represents an integer of 2, 3, 4, or 5; and R 8 is C 6-10 aryl, or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the C 6-10 The aryl and the heteroaryl each may be one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R 4a and each R 4a are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), a hydroxy, cyano, amino, or nitro group, C 1-6 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0102] In some embodiments, R 8 is C 6-10 aryl, such as, but not limited to, phenyl or naphthyl, each of which may be one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R 4a is optionally replaced by

[0103] In some embodiments, R 8 represents a heteroaryl containing one or two 5- to 7-membered rings and 1-4 heteroatoms selected from the group consisting of N, O, and S. In one subembodiment, R 8represents a 5- to 14-membered monocyclic or bicyclic aromatic ring group containing one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, examples of heteroaryl include furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzisothiazolyl, benzotriazolyl, and benzotriazolyl. Heteroaryl includes, but is not limited to, benzo[2,1,3]oxadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl. Heteroaryl includes one or more (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R as defined above. 4a is optionally replaced by

[0104] In some embodiments, PBM represents a structure of the following formula (PBM-3-1): [ka]

[0105] In some embodiments, PBM represents a small molecule ligand that targets EGFR, including, but not limited to, representing the structure of formula (PBM-4): [ka] where: R 9is C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 Alkyl, such as methyl, ethyl, propyl, isopropyl (), butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl) or deuterated C 1-10 Alkyl (e.g., fully deuterated C 1-8 Alkyl, fully deuterated C 1-6 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); and R 10 teeth [ka] where (R 5a ) p6 The piperidine ring has p6 R 5a Each R represents a substitution 5a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, C 1-6 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl), halogenated C 1-6 Alkyl, deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), deuterated C 1-6 Alkoxy (e.g., fully deuterated C 1-4represents an alkoxy (e.g., CD3-O-, CD3CD2-O-, or CD3CD2CD2-O-), NO2, NH2, or cyano group; and p6 represents an integer of 1, 2, 3, 4, or 5.

[0106] In some embodiments, the PBM has a structure of formula (PBM-4-1) or formula (PBM-4-2): [ka]

[0107] In some embodiments, PBM represents a small molecule ligand that targets EGFR, including, but not limited to, representing a structure of the following formula: (PBM-5-1A), (PBM-5-1B), (PBM-5-1C) or (PBM-5-1D): [ka] where: (R 11 ) p7 The benzene ring and the pyridine ring of Formula (PBM-5-1A), Formula (PBM-5-1B), Formula (PBM-5-1C), or Formula (PBM-5-1D) each have p7 R 11 represents an arbitrary substitution by 11 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and p7 represents an integer of 0, 1, 2 or 3.

[0108] In some embodiments, the PBM has the structure of the following formula (PBM-5-1): [ka]

[0109] In some embodiments, PBM represents a small molecule ligand that targets AR, including, but not limited to, representing the structure of the following formula (PBM-6-1A): [ka] where: Ring A of formula (PBM-6-1A) is C 6-10 aryl, or a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring A optionally contains t1 (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R 6a and each R 6a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro group, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 alkynyl (e.g., ethynyl, propynyl, or butynyl); Ring B of formula (PBM-6-1A) is C 3-15 cycloalkyl, or a 3- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring B optionally contains t2 (e.g., 1-6, e.g., 1, 2, 3, 4, 5, or 6) R 7a and each R 7a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-); Ring C of formula (PBM-6-1A) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and said ring C optionally contains t3 (e.g., 1 to 6, e.g., 1, 2, 3, 4, 5, or 6) R 8a and each R 8a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-); t1 represents an integer of 1, 2, 3, 4, 5, or 6; t2 represents an integer of 1, 2, 3, 4, 5, or 6; and t3 represents an integer of 1, 2, 3, 4, 5 or 6.

[0110] In some embodiments, the PBM represents a structure of the following formula (PBM-6-1A-1): [ka] where: (R 6a ) t1 The benzene ring of formula (PBM-6-1A-1) is optionally selected from t1 R 6a Each R represents a substitution 6a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, nitro group, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), C 2-6 alkenyl (e.g., vinyl, propenyl, or butenyl), or C 2-6 alkynyl (e.g., ethynyl, propynyl, or butynyl); Ring B of formula (PBM-6-1A-1) is C 3-15 cycloalkyl, or 3- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring B optionally contains t2 R 7a and each R 7a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-); Q1 represents N or CH; and (R 8a ) t3 is a nitrogen-containing heteroaryl of formula (PBM-6-1A-1) optionally containing t3 R 8a Each R represents a substitution 8a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-); t1 represents an integer of 1, 2, 3, 4, 5, or 6; t2 represents an integer of 1, 2, 3, 4, 5, or 6; and t3 represents an integer of 1 or 2.

[0111] In some embodiments, Q1 represents N. In some embodiments, Q1 represents CH.

[0112] In some embodiments, the PBM has the structure of formula (PBM-6-1), (PBM-6-2), or (PBM-6-3): [ka] Represents.

[0113] In some embodiments, PBM represents a small molecule ligand that targets BTK, including, but not limited to, representing a structure of formula (PBM-7-1A), formula (PBM-7-1B), or formula (PBM-7-1C): [ka] where: X2 represents CH or N; R 14 -O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, wherein the aryl and heteroaryl are each independently selected from one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R9a and each R 9a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-); R 15 is deuterium, hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or -NHC(O)R 17 where R 17 is C 1-10 Alkyl (e.g., C 1-8 Alkyl, C 1-6 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl) or C 2-10 Alkenyl (e.g., C 2-6 Alkenyl or C 2-4 alkenyl, such as vinyl, propenyl, butenyl or pentenyl), such as R 15 is hydrogen, methyl, or [ka] represents; and R 16 represents hydrogen, a cyano group, or an amino group.

[0114] In some embodiments, R 14 represents -O-aryl, -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where aryl is an optionally substituted C 6-10It may be aryl, including, but not limited to, phenyl or naphthyl, and heteroaryl may be an optionally substituted 5- to 14-membered monocyclic or bicyclic aromatic ring group containing one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. In one subembodiment, R 14 represents -O-phenyl or -O-naphthyl, and the phenyl or naphthyl may be joined by one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R 9a and each R 9a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4Alkoxy, for example, F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-). In one subembodiment, R 14 is -O-heteroaryl, -C 1-3 alkylene-NHC(O)-heteroaryl, or -C 1-3 alkylene-C(O)NH-heteroaryl, where heteroaryl optionally includes one or more (e.g., 1-5, e.g., 1, 2, 3, 4, or 5) R 9a and each R 9a are the same or different and each independently represent deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-).

[0115] In some embodiments, the PBM has the structure of formula (PBM-7-1) or formula (PBM-7-2): [ka] Represents.

[0116] In some embodiments, PBM represents a small molecule ligand that targets CDK4 / 6 and has the structure of formula (PBM-8-1A), (PBM-8-1B), (PBM-8-1C) or (PBM-8-1D): [ka] Including, but not limited to, representing where: R 21 is deuterium, hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), -C(O)-C1-6 Alkyl, -C(O)-deuterated C 1-6 Alkyl or -C(O)NR 22 R 23 where R 22 , R 23 are the same or different and each independently represent hydrogen, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.), and R 22 , R 23 is not simultaneously hydrogen; X4 is N or CR 24 where R 24 is hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); X5 and X6 each independently represent CH or N; Ring D represents an optionally substituted heteroarylene (e.g., heteroarylene substituted with halogen); R 19 is hydrogen, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), or optionally substituted C 3-7 Cycloalkyl (e.g., optionally halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, or cycloheptyl substituted with a substituent selected from the group consisting of alkyl; and R 20 and R 25 are the same or different and each independently represent hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0117] In some embodiments, Ring D represents an optionally substituted heteroarylene, for example, an optionally substituted 5- to 20-membered monocyclic or bicyclic heteroarylene containing one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Examples of heteroarylenes include furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]ox ... Heteroarylene includes, but is not limited to, sadiazolylene, 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, and imidazo[2,1-b]thiazolylene. Heteroarylene is selected from the group consisting of halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, cyano, amino, C 1-6 Alkyl (e.g., C 1-6Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, e.g., F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O-, or CH2ClCH2-O-).

[0118] In some embodiments, the PBM has the structure of formula (PBM-8-1), formula (PBM-8-2), or formula (PBM-8-3): [ka] Represents.

[0119] In some embodiments, PBM represents a small molecule ligand that targets ALK and has the structure of formula (PBM-9-1A), (PBM-9-1B), (PBM-9-1C), or (PBM-9-1D): [ka] Including, but not limited to, representing where: R 26 is hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.); and R 27 is hydrogen, cyano, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0120] In some embodiments, the PBM has the structure of the following formula (PBM-9-1): [ka] Represents.

[0121] In some embodiments, PBM represents a small molecule ligand that targets ALK and has the structure of the following formula (PBM-10): [ka] This includes, but is not limited to, representing where: (R 28 ) p8 is the benzene ring of formula (PBM-10) and p8 R 28 Each R represents a substitution 28 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-, etc.); p8 represents an integer of 1, 2, 3, or 4; or R29 is NR 30 R 31 where R 30 , R 31 are the same or different and each independently represent hydrogen, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0122] In some embodiments, the PBM has the structure of the following formula (PBM-10-1): [ka] Represents.

[0123] In some embodiments, the PBM has the structure of formula (PBM-11-1A), formula (PBM-11-1B), or formula (PBM-11-1C): [ka] represents where: X7, X8, and X9 are the same or different and each independently represent N or CH; (R 32 ) p9 The six-membered ring containing X8 and X9 is optionally divided into p9 R 32 Each R represents a substitution 32 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p9 represents an integer of 0, 1, 2, 3 or 4; R 33 is a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and R34 is -C(O)NHR 35 , -NHC(O)-R 35 , -S(O)2NHR 35 , -S(O)2R 35 or - P(O)(R 35 )2, where each R 35 are the same or different and each independently: C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0124] In some embodiments, PBM represents a small molecule ligand that targets ALK and has the structure of formula (PBM-11-1D), formula (PBM-11-1E), or formula (PBM-11-1F): [ka] Including, but not limited to, representing where: X8 and X9 are the same or different and each independently represent N or CH; (R 32 ) p9 The six-membered ring containing X8 and X9 is optionally divided into p9 R 32 Each R represents a substitution 32 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p9 represents an integer of 0, 1, 2, 3, or 4; and R 34 -C(O)NHR 35 , -NHC(O)-R 35 , -S(O)2NHR 35 , -S(O)2R 35 or -P(O)(R 35 )2, where each R 35 are the same or different and each independently: C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0125] In some embodiments, PBM represents a small molecule ligand that targets ALK and has the structure of formula (PBM-11-1) or formula (PBM-11-2): [ka] This includes, but is not limited to, representing

[0126] In some embodiments, PBM represents a small molecule ligand that targets FAK and has the structure of formula (PBM-11-1G), formula (PBM-11-1H), or formula (PBM-11-1I): [ka] Including, but not limited to, representing where: X8 and X9 are the same or different and each independently represent N or CH; (R 32 ) p9 The six-membered ring containing X8 and X9 is optionally divided into p9 R 32 Each R represents a substitution. 32 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p9 represents an integer of 0, 1, 2, 3, or 4; and R 34 -C(O)NHR 35 , -NHC(O)-R 35 , -S(O)2NHR 35 , -S(O)2R 35 or -P(O)(R 35 )2, where each R 35 are the same or different and each independently represents C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0127] In some embodiments, PBM represents a small molecule ligand that targets FAK and has the structure of formula (PBM-11-1G), formula (PBM-11-1H), or formula (PBM-11-1I): [ka] This includes, but is not limited to, representing

[0128] In some embodiments, PBM represents a small molecule ligand that targets RET and has the structure of formula (PBM-11-1J), formula (PBM-11-1K), or formula (PBM-11-1L): [ka] Including, but not limited to, representing where: X8 and X9 are the same or different and each independently represent N or CH; (R 32 ) p9 The six-membered ring containing X8 and X9 is optionally divided into p9 R 32 Each R represents a substitution 32 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p9 represents an integer of 0, 1, 2, 3, or 4; and R 34 -C(O)NHR 35 , -NHC(O)-R 35 , -S(O)2NHR 35 , -S(O)2R 35 or -P(O)(R 35 )2, where each R 35 are the same or different and each independently: C 1-6 Alkyl (e.g., C 1-6Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl) or deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.

[0129] In some embodiments, PBM represents a small molecule ligand that targets RET and has the structure of formula (PBM-11-4) or formula (PBM-11-5): [ka] This includes, but is not limited to, representing

[0130] In some embodiments, PBM represents a small molecule ligand that targets RET and has the structure of formula (PBM-12-1A), (PBM-12-1B), (PBM-12-1C), (PBM-12-1D) or (PBM-12-1E): [ka] Including, but not limited to, representing where: (R 36 ) p10 The benzene ring of formula (PBM-12-1A), formula (PBM-12-1B), formula (PBM-12-1C), formula (PBM-12-1D), or formula (PBM-12-1E) is optionally selected from p R 36 Each R represents a substitution 36 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p10 represents an integer of 0, 1, 2, 3 or 4.

[0131] In some embodiments, PBM represents a small molecule ligand that targets RET and has the structure of the following formula (PBM-12-1): [ka] This includes, but is not limited to, representing

[0132] In some embodiments, PBM represents a small molecule ligand that targets BET and has the structure of the following formula (PBM-13): [ka] This includes, but is not limited to, representing (R 37 ) p11 The benzene ring of formula (PBM-13) has p11 R 37 Each R represents a substitution 37 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p1 represents an integer of 10, 1, 2, 3 or 4.

[0133] In some embodiments, PBM represents a small molecule ligand that targets BET and has the structure of the following formula (PBM-13): [ka] This includes, but is not limited to, representing

[0134] In some embodiments, PBM represents a small molecule ligand that targets BET and has the structure of formula (PBM-14-1A), (PBM-14-1B), (PBM-14-1C), (PBM-14-1D) or (PBM-14-1E): [ka] Including, but not limited to, representing where: (R 38 ) p12The benzene ring of formula (PBM-14-1A), formula (PBM-14-1B), formula (PBM-14-1C), formula (PBM-14-1D), or formula (PBM-14-1E) has p R 38 Each R represents a substitution 38 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p12 represents an integer of 0, 1, 2, 3 or 4; (R 39 ) p13 The 4-oxo-3,4-dihydroquinazoline ring of formula (PBM-14-1A), formula (PBM-14-1B), formula (PBM-14-1C), formula (PBM-14-1D) or formula (PBM-14-1E) has p13 R 39 Each R represents a substitution 39 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p13 represents an integer of 1, 2, 3 or 4.

[0135] In some embodiments, PBM represents a small molecule ligand that targets BET and has the structure of the following formula (PBM-14-1): [ka] This includes, but is not limited to, representing

[0136] In some embodiments, PBM represents a small molecule ligand that targets BCR-ABL and has the structure of formula (PBM-15-1A) or formula (PBM-15-1B): [ka] This includes, but is not limited to, representing where: (R 40 ) p14 The benzene ring of formula (PBM-15-1A) or formula (PBM-15-1B) has p14 R 40Each R represents a substitution 40 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p14 represents an integer of 1, 2, 3, or 4; and R 41 is a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0137] In some embodiments, PBM represents a small molecule ligand that targets BCR-ABL and has the structure of the following formula (PBM-15-1): [ka] This includes, but is not limited to, representing

[0138] In some embodiments, PBM represents a small molecule ligand that targets BCR-ABL and has the structure of formula (PBM-16-1A), (PBM-16-1B), (PBM-16-1C) or (PBM-16-1D): [ka] Including, but not limited to, representing where: (R 42 ) p15 wherein the quinoline ring of formula (PBM-16-1A), formula (PBM-16-1B), formula (PBM-16-1C), or formula (PBM-16-1D) has p15 R 42 Each R represents a substitution 42 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p15 represents an integer of 2, 3, or 4; (R 43 ) p16 The benzene ring of formula (PBM-16-1A), formula (PBM-16-1B), formula (PBM-16-1C), or formula (PBM-16-1D) has p16 R 43 Each R represents a substitution 43 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p16 represents an integer of 3 or 4.

[0139] In some embodiments, PBM represents a small molecule ligand that targets BCR-ABL and has the structure of the following formula (PBM-16-1): [ka] This includes, but is not limited to, representing

[0140] In some embodiments, PBM represents a small molecule ligand that targets BCR-ABL and has the structure of formula (PBM-17-1A), (PBM-17-1B), (PBM-17-1C), (PBM-17-1D) or (PBM-17-1E): [ka] Including, but not limited to, representing where: (R 44 ) p17 The benzene ring, pyrimidine ring, and pyridine ring of formula (PBM-17-1A), formula (PBM-17-1B), formula (PBM-17-1C), formula (PBM-17-1D), or formula (PBM-17-1E) each optionally have p17 R 44 Each R represents a substitution 44 are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); and p17 represents an integer of 0, 1, 2, 3 or 4.

[0141] In some embodiments, PBM represents a small molecule ligand that targets BCR-ABL and has the structure of the following formula (PBM-17-1): [ka] This includes, but is not limited to, representing

[0142] In some embodiments, PBM represents a small molecule ligand that targets the ER and has the structure of formula (PBM-18-1A), (PBM-18-1B), (PBM-18-1C) or (PBM-18-1D): [ka] Including, but not limited to, representing where: R 45 , R 46 , R 47 and R 48 are the same or different and each independently represent hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), or hydroxy; and Symbol connecting double bonds in formula (PBM-18-1A), formula (PBM-18-1B), formula (PBM-18-1C) or formula (PBM-18-1D) TIFF2024539269000082.tif1013 indicates that the bonds may be in either a cis or trans configuration.

[0143] In some embodiments, PBM represents a small molecule ligand that targets the ER and has the structure of formula (PBM-18-1), (PBM-18-2), (PBM-18-3), (PBM-18-4), (PBM-18-5) or (PBM-18-6): [ka] This includes, but is not limited to, representing

[0144] In some embodiments, PBM represents a small molecule ligand that targets the ER and has the structure of formula (PBM-19-1A) or formula (PBM-19-1B): [ka] Including, but not limited to, representing where: (R 49 ) p18 The 1,2,3,4-tetrahydronaphthalene ring of formula (PBM-19-1A) or formula (PBM-19-1B) has p18 R 49 Each R represents a substitution 49 are the same or different and each independently represent hydrogen, hydroxy, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); p18 represents an integer of 0, 1, 2, 3 or 4; and R 50 and R 51 are each independently hydrogen, halogen (e.g., fluorine, chlorine, bromine, or iodine), C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, for example, CD3, CD3CD2-, CD3CD2CD2-, etc.) or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-).

[0145] In some embodiments, PBM represents a small molecule ligand that targets the ER and has the structure of the following formula (PBM-19-1): [ka] This includes, but is not limited to, representing

[0146] In some embodiments, the R 1 is a structure of the formula: Bonds, -O-, halogens and C 1-3 C optionally substituted with a substituent selected from the group consisting of alkyl 1-6alkylene (e.g., methylene, ethylene, propylene, isopropylidene, butylene, tert-butylene, pentylene, and hexylene), —N(R 1a )-R 2a -*** (e.g., -N(CH3)-CH2CH2-***, -NH-CH2CH2-***), -OR 2a -***(e.g. -O-(CH2)3-***, -O-CH2-***sum-O-(CH2)2-***), -C(O)NH-R 2a -*** (e.g., -C(O)NH-(CH2)2-***, -C(O)NH-(CH2)3-***, -C(O)NH-CH=CH-CH2-***, and -C(O)NH-CH2-CH=CH-CH2-***), or -NHC(O)-R 2a -*** (e.g., -NHC(O)-CH=CH-CH2-***, -NHC(O)-CH2-CH=CH-CH2-***, -NHC(O)-(CH2)2-***, and -NHC(O)-(CH2)3-***), where the symbol *** represents the point of attachment to W1, and R 1a is hydrogen or C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), and R 2a is halogen and C 1-3 C optionally substituted with a substituent selected from the group consisting of alkyl 1-6 Alkylene (e.g., methylene, ethylene, propylene, isopropylidene, butylene, tert-butylene, pentylene, and hexylene) or halogen and C 1-3 C optionally substituted with a substituent selected from the group consisting of alkyl 2-6 alkenylene (e.g., vinylene, propenylene, isopropenylene, butenylene, pentenylene, and hexenylene); or phenylene or naphthylene, wherein the phenylene or naphthylene each independently represents one or more R 3a and each R 3aare the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), a hydroxy, cyano, amino, or nitro group, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, for example F3C—O—, FCH2—O—, F2CH—O—, ClCH2—O—, Cl2CH—O—, CF3CF2—O—, CF3CHF—O—, CHF2CF2—O—, CHF2CHF—O—, CF3CH2—O— or CH2ClCH2—O—); or furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]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, wherein each group independently represents one or more R 3a and each R 3a are the same or different and each independently represent a halogen (e.g., fluorine, chlorine, bromine, or iodine), a hydroxy, cyano, amino, or nitro group, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 1-6 Alkoxy (e.g., C 1-4Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-); Represents.

[0147] In some embodiments, the W 1 is a ring W having t rings represented by the following structural formula: 2 are concatenated, [ka] Here, each ring W 2 are the same or different and each independently represent one of the following groups: A monocyclic ring C containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur. 3-10 heterocyclylene (representing, for example, the following groups: piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene or diazacyclooctylene); or C containing one nitrogen atom and optionally containing heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur 5-20 Bridged heterocyclylene (representing, for example, the following groups: azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene or diazabicyclo[2.2.2]octanylene, for example: [ka] Or, C 3-15 Cycloalkylene (representing, for example, the following groups: cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, C 5-15 spirocycloalkylene, adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, or biscyclo[2.2.1]heptenylene); and wherein the monocyclic ring C 3-10 Heterocyclylene, 5-20 Bridged heterocyclylene and the C 3-15 Cycloalkylene may each independently be selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, and optionally deuterated C 1-6 Alkyl, halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof; and t represents an integer of 1 or 2.

[0148] In some embodiments, the W 1 is the following group: [ka] represents wherein the group may further comprise deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, amino, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Optionally substituted with one or more substituents selected from the group consisting of alkoxy or any combination thereof.

[0149] In some embodiments, the R 1 -W 1 is the following group: [ka] represents wherein the group may further comprise deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, amino, C 1-6 Alkyl (e.g., C 1-6 Alkyl, C 1-5 Alkyl or C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl or hexyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-6 Alkyl, fully deuterated C 1-5 Alkyl or fully deuterated C 1-4 Alkyl, e.g., CD3, CD3CD2-, CD3CD2CD2-), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Optionally substituted with one or more substituents selected from the group consisting of alkoxy or any combination thereof.

[0150] In some embodiments, the ULM has a structure of formula (ULM-1), (ULM-2), (ULM-3), (ULM-4), (ULM-5), (ULM-6), (ULM-7), (ULM-8), (ULM-9), or (ULM-10): [ka] represents; where: A represents CO, CH2 or CD2; R1, R2, R3 and R4 are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine or iodine), optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), or halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-); (R b ) n The benzene ring is optionally connected to n R b Each R represents a substitution b are the same or different and each independently represent hydrogen, deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), C 2-6 Alkenyl, or C 2-6 represents alkynyl; n represents an integer of 0, 1, 2, or 3; U1 and U2 are the same or different and each independently represent a bond, N(R d ) or O, where R d is H or optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl; R c is an optionally substituted monocyclic C ring containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur. 3-10 represents heterocyclylene, such as the following groups: piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene or diazacyclooctylene; or R c is an optionally substituted C containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur. 5-20represents a bridged heterocyclylene, such as the following groups: azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene or diazabicyclo[2.2.2]octanylene, such as the following groups: [ka] represents wherein the monocyclic ring C 3-10 Heterocyclylene and the C 5-20 The bridged heterocyclylenes may each independently further comprise deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6It is optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof.

[0151] In some embodiments, the R c is the following group: [ka] [ka] represents; Here, the symbol * represents the connection point with the base U1.

[0152] In some embodiments, the ULM has a structure of formula (ULM-11), (ULM-12), (ULM-13), (ULM-14), (ULM-15), (ULM-16), (ULM-17), (ULM-18), (ULM-19), (ULM-20), (ULM-21), or (ULM-22): [ka] represents; Here, the A, (R b ) n , R b , R c , U1, and U2 are as defined above.

[0153] In some embodiments, the ULM has the structure of the following formula: [ka] [ka] [ka] [ka] [ka] [ka] Represents.

[0154] In some embodiments, the LIN has the structure of the following formula: #-C 1-30 Alkylene-; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -(R e (C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -; #-(C(Ra1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -(R f (C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(R e -R f -(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R f -R e -(C(R a3 )(Ra4 )) n2 ) m1 -or #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 - represents; where each group R e is O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O)2, S(O)2NH, NHS(O)2, C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g are independently H or C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl); each group R f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), hydroxy, amino, mercapto groups, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy, optionally deuterated C1-6 Alkyl-NH-, halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof; Said C 1-30 The hydrogen(s) of the CH2 of the alkylene may further be replaced by deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH- or any combination thereof; R a1 , R a2 , R a3 , Ra4 , R a5 , R a6 , R a7 and R a8 are each independently H, deuterium, hydroxy, amino, mercapto group, nitro, halogen, cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 alkyl-C(O)NH- or any combination thereof; The symbol # represents the point of attachment to the group U2; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15.

[0155] In some embodiments, the LIN has the structure of the following formula: #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 ))n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -(O(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -(O(C(R a5 )(R a6 )) n3 ) m2 -(O(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -(N(R g )(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -(N(R g )(C(R a5 )(R a6 )) n3 ) m2-(N(R g )(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(C(O)N(R g )-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(C(O)N(R g )-(C(R a5 )(R a6 )) n3 ) m2 -(C(O)N(R g )-(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 )m2 -; #-(C(R a1 )(R a2 )) n1 -C(O)N(R g )-(C(R a3 )(R a4 )) n2 -(O(C(R a5 )(R a6 )) n3 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -(O-(C(R g )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -N(R g )C(O)-(C(R a3 )(R a4 )) n2-(O(C(R a5 )(R a6 )) n3 ) m1 -; #-(C(R a1 )(R a2 )) n1 -N(R g )C(O)N(R g )-(C(R a3 )(R a4 )) n2 -; #-(C(R a1 )(R a2 )) n1 -C(O)-(C(R a3 )(R a4 )) n2 -; #-(C(R a1 )(R a2 )) n1 -(arylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(arylene-(C(R a3 )(R a4 )) n2 ) m1 -Arylene-(C(R a5 )(R a6 )) n3 -; #-(C(R a1 )(R a2 )) n1 -(heterocyclylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(heterocyclylene-(C(R a3 )(R a4 )) n2 ) m1 -(heterocyclylene-(C(R a5 )(R a6 )) n3 )m2 -; #-(C(R a1 )(R a2 )) n1 -(heteroarylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(heteroarylene-(C(R a3 )(R a4 )) n2 ) m1 -(heteroarylene-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(cycloalkylene-(C(R a3 )(R a4 )) n2 ) m1 -or #-(C(R a1 )(R a2 )) n1 -(cycloalkylene-(C(R a3 )(R a4 )) n2 ) m1 -(cycloalkylene-(C(R a5 )(R a6 )) n3 ) m2 - represents; Here, each R g are independently H or C 1-6 represents alkyl; The cycloalkylene, the arylene, the heterocyclylene and the heteroarylene may each independently further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), hydroxy, amino, mercapto groups, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 and R a8 are each independently H, deuterium, hydroxy, amino, mercapto, nitro, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), optionally deuterated C 3-6 Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally deuterated C 1-6Alkoxy, optionally deuterated C 1-6 Alkyl-NH-, NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 alkyl-C(O)NH- or any combination thereof; The symbol # represents the point of attachment to the group U2; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15.

[0156] In some embodiments, the LIn is a group that is: #-CH2-, #-(CH2)2-, #-(CH2)3-, #-(CH2)4-, #-(CH2)5-, #-(CH2)6-, #-(CH2)7-, #-(CH2)8-, #-(CH2)9-, #-(CH2) 10 -, #-(CH2) 11 -, #-(CH2) 12 -, #-(CH2) 13 -, #-(CH2) 14 -, #-(CH2) 15 -, #-(CH2) 16 -, #-(CH2) 17 -, #-(CH2) 18 -, #-(CH2) 19 -, #-(CH2) 20 -, #-(CH2) 21 -, #-(CH2) 22 -, #-(CH2) 25 - or #-(CH2) 30 -;#-CH2-O-CH2-, #-CH2-O-(CH2)2-, #-(CH2)1-O-(CH2)3-, #-(CH2)1-O-(CH2)4-, #-(CH2)1-O-(CH2)5-, #- (CH2)1-O-(CH2)6-, #-(CH2)1-O-(CH2)7-, #-(CH2)1-O-(CH2)8-, #-(CH2)1-O-(CH2)9-, #-(CH2)1-O-(CH2) 10-、#-(CH2)2-O-(CH2)1-、#-(CH2)2-O-(CH2)2-、#-(CH2)2-O-(CH2)3-、#-(CH2)2-O-(CH2)4-、#-(CH2)2-O-(CH2)5-、#-(CH2)2-O-(CH2)6-、#-(CH2)2-O-(CH2)7-、#-(CH2)2-O-(CH2)8-、#-(CH2)2-O-(CH2)9-、#-(CH2)2-O-(CH2) 10 -、#-(CH2)2-O-(CH2) 11 -、#-(CH2)2-O-(CH2) 12 -、#-(CH2)3-O-(CH2)1-、#-(CH2)3-O-(CH2)2-、#-(CH2)3-O-(CH2)3-、#-(CH2)3-O-(CH2)4-、#-(CH2)3-O-(CH2)5-、#-(CH2)3-O-(CH2)6-、#-(CH2)3-O-(CH2)7-、#-(CH2)4-O-(CH2)1-、#-(CH2)4-O-(CH2)2-、#-(CH 2)4-O-(CH2)3-、#-(CH2)4-O-(CH2)4-、#-(CH2)4-O-(CH2)5-、#-(CH2)4-O-(CH2)6-、#-(CH2)5-O-(CH2)1-、#-(CH2)5-O-(CH2)2-、#-(CH2)5-O-(CH2)3-、#-(CH2)5-O-(CH2)4-、#-(CH2)5-O-(CH2)5-、#-(CH2)6-O-( CH2)1-、#-(CH2)6-O-(CH2)2-、#-(CH2)6-O-(CH2)3-、#-(CH2)6-O-(CH2)4-、#-(CH2)7-O-(CH2)1-、#-(CH2)7-O-(CH2)2-、#-(CH2)7-O-(CH2)3-、#-(CH2)8-O-(CH2)1-、#-(CH2)8-O-(CH2)2-、#-CH(CH3)-O-(CH2)1- 、#-CH(CH3)-O-(CH2)2-、#-CH(CH3)-O-(CH2)3-、#-CH(CH3)-O-(CH2)4-、#-CH(CH3)-O-(CH2)5-、#-CH(CH3)-O-(CH2)6-、#-CH(CH3)-O-(CH2)7-、#-CH(CH3)-O-(CH2)8-、#-CH(CH3)-O-(CH2)9-、#-CH(CH3)-O-(CH2) 10-、#-CH2-(O(CH2)2)2-、#-CH2-(O(CH2)2)3-、#-CH2-(O(CH2)2)4-、#-CH2-(O(CH2)2)5-、#-CH2-(O(CH2)2)6-、#-CH2-(O(CH2)2)7-、#-CH2-(O(CH2)2)8-、#-CH2-(O(CH2)2)9-、#-CH2-(O(CH2)2) 10 -、#-CH2-(O(CH2)2)1-OCH2-、#-CH2-(O(CH2)2)2-OCH2-、#-CH2-(O(CH2)2)3-OCH2-、#-CH2-(O(CH2)2)4-OCH2-、#-CH2-(O(CH2)2)5-OCH2-、#-CH2-(O(CH2)2)6-OCH2-、#-CH2-(O(CH2)2)7-OCH2-、#-CH2-(O(CH2)2)8-OCH2-、#-CH2-(O(CH2)2)9-OCH2-、#-CH2-(O(CH2)2) 10 -OCH2-、#-(CH2)2-(O(CH2)2)2-、#-(CH2)2-(O(CH2)2)3-、#-(CH2)2-(O(CH2)2)4-、#-(CH2)2-(O(CH2)2)5-、#-(CH2)2-(O(CH2)2)6-、#-(CH2)2-(O(CH2)2)7-、#-(CH2)2-(O(CH2)2)8-、#-(CH2)2-(O(CH2)2)9-、#-(CH2)2-(O(CH2)2) 10 -、#-(CH2)3-(O(CH2)2)2-、#-(CH2)3-(O(CH2)2)3-、#-(CH2)3-(O(CH2)2)4-、#-(CH2)3-(O(CH2)2)5-、#-(CH2)3-(O(CH2)2)6-、#-(CH2)3-(O(CH2)2)7-、#-(CH2)3-(O(CH2)2)8-、#-(CH2)3-(O(CH2)2)9-、#-(CH2)3-(O(CH2)2) 10-、#-(CH2)4-(O(CH2)2)2-、#-(CH2)4-(O(CH2)2)3-、#-(CH2)4-(O(CH2)2)4-、#-(CH2)4-(O(CH2)2)5-、#-(CH2)4-(O(CH2)2)6-、#-(CH2)4-(O(CH2)2)7-、#-(CH2)4-(O(CH2)2)8-、#-(CH2)4-(O(CH2)2)9-、#-(CH2)4-(O(CH2)2) 10 -、#-CH2-(O(CH2)3)2-、#-CH2-(O(CH2)3) 3-、#-CH2-(O(CH2)3)4-、#-CH2-(O(CH2)3)5-、#-CH2-(O(CH2)3)6-、#-CH2-(O(CH2)3)7-、#-CH2-(O(CH2)3)8-、#-CH2-(O(CH2)3)9-、#-CH2-(O(CH2)3) 10 -、#-(CH2)2-(O(CH2)3)2-、#-(CH2)2-(O(CH2)3)3-、#-(CH2)2-(O(CH2)3)4-、#-(CH2)2-(O(CH2)3)5-、#-(CH2)2-(O(CH2)3)6-、#-(CH2)2-(O(CH2)3)7-、#-(CH2)2-(O(CH2)3)8-、#-(CH2)2-(O(CH2)3)9-、#-(CH2)2-(O(CH2)3) 10 -、#-(CH2)3-(O(CH2)3)2-、#-(CH2)3-(O(CH2)3)3-、#-(CH2)3-(O(CH2)3)4-、#-(CH2)3-(O(CH2)3)5-、#-(CH2)3-(O(CH2)3)6-、#-(CH2)3-(O(CH2)3)7-、#-(CH2)3-(O(CH2)3)8-、#-(CH2)3-(O(CH2)3)9-、#-(CH2)3-(O(CH2)3) 10-、#-CH2-O-(CH2)2-O-(CH2)3-、#-CH2-(O(CH2)2)2-(O(CH2)3)2-、#-CH2-(O(CH2)2)3-(O(CH2)3)3-、#-CH2-(O(CH2)2)4-(O(CH2)3)4-、#-CH2-(O(CH2)2)5-(O(CH2)3)5-、#-CH2-(O(CH2)2)6-(O(CH2)3)6-、#-(CH2)2-O-(CH2)2-O-(CH2)3-、#-(CH2)2-(O(CH2)2)2-(O(CH2)3)2-、#-(CH2)2-(O(CH2)2 )3-(O(CH2)3)3-、#-(CH2)2-(O(CH2)2)4-(O(CH2)3)4-、#-(CH2)2-(O(CH2)2)5-(O(CH2)3)5-、#-(CH2)2-(O(CH2)2)6-(O(CH2)3)6-、#-(CH2)3-O-(CH2)2-O-(CH2)3-、#-(CH2)3-(O(CH2)2)2-(O(CH2)3)2-、#-(CH2)3-(O(CH2)2)3-(O(CH2)3)3-、#-(CH2)3-(O(CH2)2)4-(O(CH2)3)4-、#-(CH2)3-(O(CH2 )2)5-(O(CH2)3)5-、#-(CH2)3-(O(CH2)2)6-(O(CH2)3)6-、#-CH2-O-(CH2)3-O-(CH2)2-、#-CH2-(O(CH2)3)2-(O(CH2)2)2-、#-CH2-(O(CH2)3)3-(O(CH2)2)3-、#-CH2-(O(CH2)3)4-(O(CH2)2)4-、#-CH2-(O(CH2)3)5-(O(CH2)2)5-、#-CH2-(O(CH2)3)6-(O(CH2)2)6-、#-(CH2)2-O-(CH2)3-O-(CH2)2-、#- (CH2)2-(O(CH2)3)2-(O(CH2)2)2-、#-(CH2)2-(O(CH2)3)3-(O(CH2)2)3-、#-(CH2)2-(O(CH2)3)4-(O(CH2)2)4-、#-(CH2)2-(O(CH2)3)5-(O(CH2)2)5-、#-(CH2)2-(O(CH2)3)6-(O(CH2)2)6-、#-(CH2)3-O-(CH2)3-O-(CH2)2-、#-(CH2)3-(O(CH2)3)2-(O(CH2)2)2-、#-(CH2)3-(O(CH2)3)3-(O(CH2)2)3-、#-(CH2)3-(O(CH2)3)4-(O(CH2)2)4-、#-(CH2)3-(O(CH2)3)5-(O(CH2)2)5-、#-(CH2)3-(O(CH2)3)6-(O(CH2)2)6-、#-CH2-O-(CH2)2-O-CH2-、#-(CH2)2-O-(CH2)2-O-CH2-、#-(CH2)2-(O(CH2)2)2-O-(CH2)3-、#-(CH2)2-(O(CH2)2)3-O-(CH2)3-、#-(CH2)2-(O(CH2)2)4-O-(CH2)3-、#-(CH2)5-(O(CH2)2)2-O-(CH2)5-、#-(CH2)5-(O(CH2)2)2-O-(CH2)6-、#-(CH2)1-N(R、 g )-(CH2)1-、#-(CH2)1-N(R g )-(CH2)2-、#-(CH2)1-N(R g )-(CH2)3-、#-(CH2)1-N(R g )-(CH2)4-、#-(CH2)1-N(R g )-(CH2)5-、#-(CH2)1-N(R g )-(CH2)6-、#-(CH2)1-N(R g )-(CH2)7-、#-(CH2)1-N(R g )-(CH2)8-、#-(CH2)1-N(R g )-(CH2)9-、#-(CH2)1-N(R g )-(CH2) 10 -、#-(CH2)2-N(R g )-(CH2)1-、#-(CH2)2-N(R g )-(CH2)2-、#-(CH2)2-N(R g )-(CH2)3-、#-(CH2)2-N(R g )-(CH2)4-、#-(CH2)2-N(R g )-(CH2)5-、#-(CH2)2-N(R g )-(CH2)6-、#-(CH2)2-N(R g )-(CH2)7-、#-(CH2)2-N(R g )-(CH2)8-、#-(CH2)2-N(R g )-(CH2)9-、#-(CH2) 2-N(Rg )-(CH2) 10 -、#-(CH2)2-N(R g )-(CH2) 11 -、#-(CH2)2-N(R g )-(CH2) 12 -、#-(CH2)3-N(R g )-(CH2)1-、#-(CH2)3-N(R g )-(CH2)2-、#-(CH2)3-N(R g )-(CH2)3-、#-(CH2)4-N(R g )-(CH2)1-、#-(CH2)4-N(R g )-(CH2)2-、#-(CH2)4-N(R g )-(CH2)3-、#-(CH2)4-N(R g )-(CH2)4-、#-(CH2)5-N(R g )-(CH2)1-、#-(CH2)5-N(R g )-(CH2)2-、#-(CH2)5-N(R g )-(CH2)3-、#-(CH2)5-N(R g )-(CH2)4-、#-(CH2)5-N(R g )-(CH2)5-、#-(CH2)6-N(R g )-(CH2)1-、#-(CH2)6-N(R g )-(CH2)2-、#-(CH2)6-N(R g )-(CH2)3-、#-(CH2)7-N(R g )-(CH2)1-、#-(CH2)7-N(R g )-(CH2)2-、#-(CH2)7-N(R g )-(CH2)3-、#-(CH2)8-N(R g )-(CH2)1-、#-(CH2)8-N(R g )-(CH2)2-、#-(CH2)8-N(R g )-(CH2)3-、#-CH(CH3)-N(R g )-(CH2)1-、#-CH(CH3)-N(R g )-(CH2)2-、#-CH(CH3)-N(R g )-(CH2)3-、#-CH(CH3)-N(R g)-(CH2)4-、#-CH(CH3)-N(R g )-(CH2)5-、#-CH(CH3)-N(R g )-(CH2)6-、#-CH(CH3)-N(R g )-(CH2)7-、#-CH(CH3)-N(R g )-(CH2)8-、#-CH(CH3)-N(R g )-(CH2)9-、#-CH(CH3)-N(R g )-(CH2) 10 -、#-CH2C(O)NHCH2-、#-(CH2)2C(O)NH(CH2)2-、#-(CH2)2C(O)NH(CH2)3-、#-(CH2)2C(O)NH(CH2)4-、#-(CH2)2C(O)NH(CH2)5-、#-(CH2)3C(O)NH(CH2)3-、#-(CH2)3C(O)NH(CH2)4-、#-(CH 2)4C(O)NH(CH2)4-、#-(CH2)5C(O)NH(CH2)5-、#-(CH2)6C(O)NH(CH2)7-、#-(CH2)6C(O)NH(CH2)6-、#-(CH2)7C(O)NH(CH2)7-、#-(CH2)8C(O)NH(CH2)8、U-(CH2)9C(O)NH(CH2)9-、#-(CH2) 10 C(O)NH(CH2) 10 -、#-(CH2)2C(O)NH(CH2)2-O-(CH2)2-、#-CH2NHC(O)CH2-、#-(CH2)2NHC(O)(CH2)2-、#-(CH2)2NHC(O) (CH2)3-、#-(CH2)2NHC(O)(CH2)4-、#-(CH2)2NHC(O)(CH2)5-、#-(CH2)3NHC(O)(CH2)3-、#-(CH2)3NHC (O)(CH2)4-、#-(CH2)4NHC(O)(CH2)4-、#-(CH2)5NHC(O)(CH2)5-、#-(CH2)6NHC(O)(CH2)7-、#-(CH2)6 NHC(O)(CH2)6-、#-(CH2)7NHC(O)(CH2)7-、#-(CH2)8NHC(O)(CH2)8、#-(CH2)9NHC(O)(CH2)9-、#-(CH2) 10 NHC(O)(CH2) 10-, #-(CH2)4NHC(O)(CH2)8-, #-(CH2)2NHC(O)(CH2)2-O-(CH2)2-, #-(CH2)4NHC(O)CH2-, #-CH2-piperidinylene-CH2-, #-CH2-piperidinylene-(CH2)2-, #-CH2-piperidinylene-(CH2)3-, #-CH2-piperidinylene-(CH2)4-, #-CH2-piperidinylene-(CH2)5-, #-CH2-piperidinylene-(CH2)6-, #-CH2-piperidinylene-(CH2)7-, #-CH2-piperidinylene-(CH2)8-, #-(CH2)2-piperidinylene-(CH2)1-, #-(CH2)2-piperidinylene-(CH2)2-, #-(CH2)2-piperidinylene-(CH2)3-, #-(CH2)2-piperidinylene-(CH2)4-, #-(CH2)2-piperidinylene-(CH2)5-, #-(CH2)2-piperidinylene-(CH2)6-, #-(CH2)2-piperidinylene-(CH2)7-, #-(CH2)2-piperidinylene-(CH2)8-, #-(CH2)3-piperidinylene-CH2-, #-(CH2)3-piperidinylene-(CH2)2-, # -(CH2)3-piperidinylene-(CH2)3-, #-(CH2)3-piperidinylene-(CH2)4-, #-(CH2)3-piperidinylene-(CH2)5-, #-(CH2)3-piperidinylene-(CH2)6-, #-(CH2)3-piperidinylene-(CH2)7-, #-(CH2)3-piperidinylene-(CH2)8-, #-(CH2)4-piperidinylene-CH2-, #-(CH2)4-piperidinylene-(CH2)2-, #-(CH2)4-piperidinylene-(CH2)3-, #-(CH2)4-piperidinylene-(CH2)4-, #- (CH2)4-piperidinylene-(CH2)5-, #-(CH2)4-piperidinylene-(CH2)6-, #-(CH2)4-piperidinylene-(CH2)7-, #-(CH2)4-piperidinylene-(CH2)8-, #-(CH2)5-piperidinylene-(CH2)1-, #-(CH2)5-piperidinylene-(CH2)2-, #-(CH2)5-piperidinylene-(CH2)3-, #-(CH2)5-piperidinylene-(CH2)4-, #-(CH2)5-piperidinylene-(CH2)5-, #-(CH2)5-piperidinylene-(CH2)6-,#-(CH2)5-piperidinylene-(CH2)7-, #-(CH2)5-piperidinylene-(CH2)8-, #-(CH2)6-piperidinylene-(CH2)1-, #-(CH2)6-piperidinylene-(CH2)2-, #-(CH2)6-piperidinylene-(CH2)3-, #-(CH2)6-piperidinylene-(CH2, )4-, #-(CH2)6-piperidinylene-(CH2)5-, #-(CH2)6-piperidinylene-(CH2)6-, #-(CH2)6-piperidinylene-(CH2)7-, #-(CH2)6-piperidinylene-(CH2)8-, #-(CH2)7-piperidinylene-(CH2)1-, #-(CH2)7-piperidinylene-(CH2)2-, #-(CH2)7-piperidinylene-(CH2)3-, #-(CH2)7-piperidinylene-(CH2)4-, #-(CH2)7-piperidinylene Nylene-(CH2)8-, #-(CH2)8-piperidinylene-CH2-, #-(CH2)8-piperidinylene-(CH2)2-, #-(CH2)8-piperidinylene-(CH2)3-, #-(CH2)8-piperidinylene-(CH2)4-, #-(CH2)8-piperidinylene-(CH2)5-, #-(CH2)8-piperidinylene-(CH2)6-, #-(CH2)8-piperidinylene-(CH2)7-, #-(CH2)8-piperidinylene-(CH2)8-, #-CH2-N(R g )-CH2-piperidinylene-CH2-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)2-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)3-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)4-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)5-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)6-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)7-, #-CH2-N(R g )-CH2-piperidinylene-(CH2)8-, #-CH2-N(R g )-(CH2)2-piperidinylene-CH2-, #-CH2-N(R g)-(CH2)2-piperidinylene-(CH2)2-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)3-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)4-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)5-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)6-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)7-, #-CH2-N(R g )-(CH2)2-piperidinylene-(CH2)8-, #-(CH2)2-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)4-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)5-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)6-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)7-, #-(CH2)2-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)3-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)3-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)3-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)3-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)4-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)4-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)4-N(R g)-CH2-piperidinylene-(CH2)3-, #-(CH2)4-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)5-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)5-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)6-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)6-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)7-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)7-N(R g )-CH2-piperidinylene-(CH2)8-, #-(CH2)8-N(R g )-CH2-piperidinylene-CH2-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)2-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)3-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)4-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)5-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)6-, #-(CH2)8-N(R g )-CH2-piperidinylene-(CH2)7-, #-(CH2)8-N(R g)-CH2-piperidinylene-(CH2)8-, #-CH2-piperazinylene-CH2-, #-CH2-piperazinylene-(CH2)2-, #-CH2-piperazinylene-(CH2)3-, #-CH2-piperazinylene-(CH2)4-, #-CH2-piperazinylene-(CH2)5-, #-CH2-piperazinylene-(CH2)6-, #-CH2-piperazinylene-(CH2)7-, #-CH2-piperazinylene ylene-(CH2)8-, #-(CH2)2-piperazinylene-(CH2)1-, #-(CH2)2-piperazinylene-(CH2)2-, #-(CH2)2-piperazinylene-(CH2)3-, #-(CH2)2-piperazinylene-(CH2)4-, #-(CH2)2-piperazinylene-(CH2)5-, #-(CH2)2-piperazinylene-(CH2)6-, #-(CH2)2-piperazinylene-(CH2)7 -, #-(CH2)2-piperazinylene-(CH2)8-, #-(CH2)3-piperazinylene-CH2-, #-(CH2)3-piperazinylene-(CH2)2-, #-(CH2)3-piperazinylene-(CH2)3-, #-(CH2)3-piperazinylene-(CH2)4-, #-(CH2)3-piperazinylene-(CH2)5-, #-(CH2)3-piperazinylene-(CH2)6-, #-(CH2)3-piperazinylene Perazinylene-(CH2)7-, #-(CH2)3-piperazinylene-(CH2)8-, #-(CH2)4-piperazinylene-CH2-, #-(CH2)4-piperazinylene-(CH2)2-, #-(CH2)4-piperazinylene-(CH2)3-, #-(CH2)4-piperazinylene-(CH2)4-, #-(CH2)4-piperazinylene-(CH2)5-, #-(CH2)4-piperazinylene-(CH2)6 -, #-(CH2)4-piperazinylene-(CH2)7-, #-(CH2)4-piperazinylene-(CH2)8-, #-(CH2)5-piperazinylene-(CH2)1-, #-(CH2)5-piperazinylene-(CH2)2-, #-(CH2)5-piperazinylene-(CH2)3-, #-(CH2)5-piperazinylene-(CH2)4-, #-(CH2)5-piperazinylene-(CH2)5-, #-(CH2)5-piperazinylene- (CH2)6-, #-(CH2)5-piperazinylene-(CH2)7-, #-(CH2)5-piperazinylene-(CH2)8-, #-(CH2)6-piperazinylene-(CH2)1-, #-(CH2)6-piperazinylene-(CH2)2-, #-(CH2)6-piperazinylene-(CH2)3-, #-(CH2)6-piperazinylene-(CH2)4-, #-(CH2)6-piperazinylene-(CH2)5-, #-(CH2)6-pipera Dinylene-(CH2)6-, #-(CH2)6-piperazinylene-(CH2)7-, #-(CH2)6-piperazinylene-(CH2)8-, #-(CH2)7-piperazinylene-(CH2)1-, #-(CH2)7-piperazinylene-(CH2)2-, #-(CH2)7-piperazinylene-(CH2)3-, #-(CH2)7-piperazinylene-(CH2)4-, #-(CH2)7-piperazinylene-(CH2)8-, #-(CH2) 8-piperazinylene-CH2-, #-(CH2)8-piperazinylene-(CH2)2-, #-(CH2)8-piperazinylene-(CH2)3-, #-(CH2)8-piperazinylene-(CH2)4-, #-(CH2)8-piperazinylene-(CH2)5-, #-(CH2)8-piperazinylene-(CH2)6-, #-(CH2)8-piperazinylene-(CH2)7-, or #-(CH2)8-piperazinylene-(CH2)8-; wherein the piperidinylene and the piperazinylene may each independently further comprise deuterium, optionally deuterated C 1-6 Alkyl (e.g., optionally deuterated C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), optionally deuterated C 3-6Cycloalkyl (e.g., optionally deuterated cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), hydroxy, amino, mercapto groups, halogen (e.g., fluorine, chlorine, bromine, or iodine), optionally deuterated C 1-6 Alkoxy (e.g., optionally deuterated C 1-4 Alkoxy, for example methoxy, CD3-O-, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), optionally deuterated C 1-6 Alkyl-NH-, halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), NH2-C 1-6 Alkylene, optionally deuterated C 1-6 Alkyl-NHC(O)-, optionally deuterated C 1-6 optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH-, cyano, or any combination thereof; Each R g are independently H or C 1-6 represents alkyl; The symbol # represents the point of attachment to the group U2; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15.

[0157] In some embodiments, the -W 1 -LIN-U2-R c -U1- is a group: [ka] [ka] [ka] represents; wherein the group may further comprise deuterium, halogen (e.g., fluorine, chlorine, bromine, or iodine), cyano, amino, C 1-6 Alkyl (e.g., C 1-4 alkyl, for example methyl, CD3, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), halogenated C 1-6 Alkyl (e.g., halogenated C 1-4 Alkyl, for example F3C-, FCH2-, F2CH-, ClCH2-, Cl2CH-, CF3CF2-, CF3CHF-, CHF2CF2-, CHF2CHF-, CF3CH2- or CH2ClCH2-), deuterated C 1-6 Alkyl (e.g., fully deuterated C 1-4 Alkyl, such as fully deuterated methyl (CD3), fully deuterated ethyl, fully deuterated propyl, fully deuterated isopropyl, fully deuterated butyl, fully deuterated sec-butyl or fully deuterated tert-butyl), C 1-6 Alkoxy (e.g., C 1-4 Alkoxy, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy or tert-butoxy), halogenated C 1-6 Alkoxy (e.g., halogenated C 1-4 Alkoxy, for example F3C-O-, FCH2-O-, F2CH-O-, ClCH2-O-, Cl2CH-O-, CF3CF2-O-, CF3CHF-O-, CHF2CF2-O-, CHF2CHF-O-, CF3CH2-O- or CH2ClCH2-O-), deuterated C 1-6 Alkoxy (e.g., fully deuterated C 1-4 alkoxy, e.g., D3C-O-, CD3CD2-O-, or CD3CD2CD2-O-), or any combination thereof.

[0158] In some embodiments, the compound of Formula (III) is also represented by the structure of Formula (III-1), Formula (III-2), Formula (III-3), Formula (III-4), Formula (III-5), Formula (III-6), Formula (III-7), Formula (III-8), Formula (III-9), Formula (III-10), Formula (III-11), Formula (III-12), Formula (III-13), Formula (III-14), Formula (III-15), Formula (III-16), Formula (III-17), Formula (III-18), Formula (III-19), Formula (III-20), Formula (III-21), Formula (III-22), Formula (III-23), or Formula (III-24). [ka] [ka] Here, A, R1, R2, R3, R4, (R b ) n , U1, U2, R c ,LIN,W. 1 , R 1 , (R 2 ) p1 , (R 3 ) p2 , (R 5 ) p3 , (R 6 ) p4 , (R 7 ) p5 , R 8 , R 9 , R 10 , (R 11 ) p7 , Ring A, Ring B, Ring C, X1, X2, R 14 , R 15 , R 16 , X3, X4, X5, X6, R 18 , R 19 , R 20 , R 25 , R 26 , R 27 , (R 28 ) p8 , R 29 , X7, X8, X9, (R 32 ) p9 , R 33 , R 34 , (R36 ) p10 , (R 37 ) p11 , (R 38 ) p12 , (R 39 ) p13 , (R 40 ) p14 , R 41 , (R 42 ) p15 , (R 43 ) p16 , (R 44 ) p17 , R 45 , R 46 , R 47 , R 48 , (R 49 ) p18 , R 50 , R 51 is as defined above for compounds of formula (III) and each subembodiment thereof.

[0159] In some embodiments, when PBM in a compound of formula (III) of the present disclosure has a structure of formula (PBM-6-1A-1) or a structure of formula (PBM-6-1), and ULM has a structure of formula (ULM): [ka] W 1 represents an optionally substituted piperidinylene, and R c represents an optionally substituted piperidinylene, U represents a bond, and A, R, R, R, R, (R b ) n ,U2,LIN,R 1 , (R 6a ) t1 , ring B, (R 7a ) t2 , (R 8a ) t3 , Q1 is as defined above for compounds of formula (III) and each subembodiment thereof, where W 1 and R c The substituents of the piperidinylene represented by the formula: are each independently as defined herein.

[0160] In some embodiments, specific compounds of Formula (III) in Table 4 below and salts (including pharmaceutically acceptable salts, e.g., hydrochloride salts thereof), pharmaceutical precursors, solvates, isotopically enriched analogs, polycrystalline forms, stereoisomers (including enantiomers and non-enantiomers), or mixtures of stereoisomers thereof are provided. Table 4. Compounds of the present disclosure II. Other Aspects of the Compounds (Including Salts, Enantiomers, Stereoisomers, Solvates, Isotopically Enriched Analogues, Pharmaceutical Precursors, or Polymorphs of the Compounds)

[0161] The compounds of the present disclosure have a structure represented by any one of formulas (I), (II), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), (III-8), (III-9), (III-10), (III-11), (III-12), (III-13), (III-14), (III-15), (III-16), (III-17), (III-18), (III-19), (III-20), (III-21), (III-22), (III-23), or (III-24). Unless otherwise stated, reference to compounds of the present disclosure includes compounds of any of Formula (I), Formula (II), Formula (III), Formula (III-1), Formula (III-2), Formula (III-3), Formula (III-4), Formula (III-5), Formula (III-6), Formula (III-7), Formula (III-8), Formula (III-9), Formula (III-10), Formula (III-11), Formula (III-12), Formula (III-13), Formula (III-14), Formula (III-15), Formula (III-16), Formula (III-17), Formula (III-18), Formula (III-19), Formula (III-20), Formula (III-21), Formula (III-22), Formula (III-23), or Formula (III-24), and includes specific compounds falling within these general formulas.

[0162] It should be recognized that the compounds of the present disclosure (compounds of formula (I), formula (II), formula (III), formula (III-1), formula (III-2), formula (III-3), formula (III-4), formula (III-5), formula (III-6), formula (III-7), formula (III-8), formula (III-9), formula (III-10), formula (III-11), formula (III-12), formula (III-13), formula (III-14), formula (III-15), formula (III-16), formula (III-17), formula (III-18), formula (III-19), formula (III-20), formula (III-21), formula (III-22), formula (III-23), and formula (III-24)) can have different spatial configurations and therefore can exist in one or more stereoisomeric forms. The present disclosure also relates to compounds having an optically enriched spatial configuration (e.g., greater than about 90% ee, e.g., greater than about 95% ee, or 97% ee, or greater than 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 as 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.

[0163] In some embodiments, polymorphic forms of the compounds of the present disclosure or salts of the compounds of the present disclosure are also provided. The salts of the compounds of the present disclosure may be pharmaceutically acceptable salts, such as hydrohalides (including hydrochlorides and hydrobromides), sulfates, citrates, maleates, sulfonates, citrates, lactates, L-tartrates, fumarates, L-malates, hippurates, D-glucuronates, glycolates, mucates, orotates, glycinates, alanines, arginines, cinnamates, pamoates, benzenesulfonates, methanesulfonates, acetates, propionates, pentanoates, triphenylacetates, L-prolines, ferulates, 2-hydroxyethanesulfonates, nitrates, gentisates, salicylates, glutarates, stearates, camphorsulfonates, phosphates, etc. The compounds of the present disclosure may be present in a non-solvated or solvated form in a pharmaceutically acceptable solvent, such as water, ethanol, or the like. In some embodiments, the compounds of the present disclosure may be prepared into a precursor drug or a pharmaceutical precursor. The precursor drug is converted to the parent drug in the body and functions. In some embodiments, isotope-labeled compounds of the present disclosure are also provided, with examples of isotopes including deuterium (D or 2 H) is included. III. Drug Compositions / Formulations

[0164] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a compound of the present disclosure or a pharmaceutically acceptable salt, solvate, isotopically enriched analogue, polycrystalline form, pharmaceutical precursor, stereoisomer (including enantiomer), or mixture of stereoisomers thereof as an active ingredient, and at least one pharmaceutically acceptable carrier.

[0165] 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; surfactants, phosphate buffers; and other non-toxic compatible substances used in drug formulations.

[0166] 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), Formula (II), or Formula (III) described herein to treat the diseases or conditions described herein. Second therapeutic agents include, but are not limited to, chemotherapeutic agents, immunotherapeutic agents, and gene therapy agents.

[0167] The pharmaceutical compositions described in the present disclosure, which contain the compounds of Formula (I), Formula (II) or Formula (III) according to the present disclosure or pharmaceutically acceptable salts thereof as an active ingredient, can be administered in appropriate dosage forms, such as spoolies, patches, tablets (e.g., regular tablets, dispersible tablets, orally disintegrating tablets), by appropriate routes of administration (including, but not limited to, nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural cavity administration, peritoneal administration, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration, and intravenous administration). The compounds of formula (I), formula (II) or formula (III) may be prepared into the following forms: broken tablets), capsules (e.g., soft capsules, hard capsules, enteric-coated capsules), dragees, troches, powders, granules, powder injections, suppositories, or liquid preparations (e.g., suspensions (e.g., aqueous or oily suspensions), solutions, emulsions, or syrups), or into conventional injection forms, such as injectable solutions (e.g., sterile injection solutions prepared using water, Ringer's solution, isotonic sodium chloride solution, or the like as a carrier or solvent by methods known in the art) or freeze-dried compositions. Furthermore, those skilled in the art can also prepare the compounds of formula (I), formula (II) or formula (III) into conventional, dispersible, chewable, or oral fast-disintegrating or fast-dissolving preparations, or sustained-release or controlled-release capsules, as needed. IV. Kits / Packaged Products

[0168] The compounds of Formula (I), Formula (II), or Formula (III) 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. V. Methods and Uses

[0169] The compounds of formula (I) or formula (II) of the present disclosure, or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polycrystalline forms, pharmaceutical precursors, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, can further be used as pharmaceuticals. In particular, the compounds of formula (I) or formula (II) of the present disclosure, or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, polycrystalline forms, pharmaceutical precursors, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, can be used in the manufacture of a medicament for preventing and / or treating a disease or condition mediated by cereblon protein.

[0170] A method for preventing and / or treating a disease or condition mediated by cereblon protein in a subject comprises administering to the subject a therapeutically effective amount of a compound of Formula (I) or Formula (II) according to the present disclosure, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I) or Formula (II) according to the present disclosure, or a pharmaceutically acceptable salt thereof, as an active ingredient. In some embodiments, the disease or condition mediated by cereblon protein comprises tumor, infectious disease, autoinflammatory disease, inflammatory disease, autoimmune disease, neurological disease, respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, adult respiratory distress syndrome, congestive heart failure, myocardial infarction, Onwell-Richter syndrome, Richter syndrome (RS), acute liver failure, or diabetes. In some embodiments, the disease or condition mediated by Cereblon protein is 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); diffuse large B-cell lymphoma, non-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 Lymphomas, including 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, and refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer; inflammatory myofibroblastic tumor; colorectal cancer; glioma; astrocytoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and Cowden's disease; pancreatic cancer; neuroblastoma;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; 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; Williams syndrome; Richter 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, Sjogren's syndrome, and atopic dermatitis; keratoconjunctivitis sicca; autoinflammatory diseases including gout; inflammatory diseases including Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, and bronchitis; cerebral malaria; viral Infectious diseases, including but not limited to HIV pneumonia, AIDS, COVID-19, gram-negative bacterial infections, gram-positive bacterial infections, and tuberculosis; septic shock; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, and lung) or tissue transplant rejection; diabetes; sarcoidosis; acute respiratory distress syndrome; congestive heart failure; myocardial infarction; multiple organ failure due to cachexia and septic shock; or acute liver failure;

[0171] In a method for preventing and / or treating a disease or condition mediated by cereblon protein in a subject, a therapeutically effective amount of a compound of formula (I) or formula (II) according to the present disclosure, or a pharmaceutical composition comprising a compound of formula (I) or formula (II) 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.

[0172] The compounds of formula (III) according to the present disclosure, or pharmaceutically acceptable salts, solvates, isotopically enriched analogues, polycrystalline forms, pharmaceutical precursors, stereoisomers (including enantiomers), or mixtures of stereoisomers thereof, can be used as medicaments. In particular, the compound of formula (III) according to the present disclosure, or a pharmaceutically acceptable salt, solvate, isotopically enriched analogue, polycrystalline form, pharmaceutical precursor, stereoisomer (including enantiomer), or mixture of stereoisomers thereof, can be used to manufacture a medicament for treating and / or preventing a disease or condition selected from the group consisting of tumors, infectious diseases, autoinflammatory diseases, inflammatory diseases, autoimmune diseases, neurological diseases, respiratory diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, acute respiratory distress syndrome, congestive heart failure, myocardial infarction, Williams syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin diseases, cardiovascular diseases, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, and thyroid diseases. In some embodiments, the disease or condition is 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); diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, Lymphomas, including 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 squamous cell carcinoma; inflammatory myofibroblastic tumor; colorectal cancer; glioma; astrocytoma; ovarian cancer;Bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and Cowden's disease; pancreatic cancer; neuroblastoma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumors; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; brain cancer; oral cancer; sarcomas, including rhabdomyosarcoma, various lipogenic tumors, Ewing's 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; Williams syndrome; Richter's 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; autoinflammatory diseases including gout; 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, COVID-19, and gram-negative The compound may be used to manufacture a medicament for preventing and / or treating a disease or condition selected from the group consisting of infectious diseases including bacterial infections, gram-positive bacterial infections, tuberculosis, etc.; septic shock; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, and lung) or tissue transplant rejection; diabetes; sarcoidosis; acute respiratory distress syndrome; multiple organ failure due to cachexia and septic shock; acute liver failure; functional uterine bleeding; anemia; childhood aplastic anemia; endometriosis; polycystic ovary syndrome; thyroid disease; cardiovascular disease (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); skin disease (e.g., acne); Kennedy disease; seborrheic alopecia; and hirsutism.

[0173] A method for preventing and / or treating a disease or condition in a subject comprises administering to the subject a therapeutically effective amount of a compound of formula (III) according to the present disclosure, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (III) or a pharmaceutically acceptable salt thereof as an active ingredient, as described herein, wherein the disease or condition includes, but is not limited to, tumor, infectious disease, autoinflammatory disease, inflammatory disease, autoimmune disease, neurological disease, respiratory disease, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, acute respiratory distress syndrome, congestive heart failure, myocardial infarction, Williams syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin disease, cardiovascular disease, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, and thyroid disease. In some embodiments, the disease or condition is 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); diffuse large B-cell lymphoma, non-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, and relapsed diffuse large B-cell lymphoma. Lymphomas, including follicular 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 squamous cell carcinoma; inflammatory myofibroblastic tumor; colorectal cancer; glioma; astrocytoma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer, including triple-negative breast cancer, incidental breast cancer, and Cowden's disease; pancreatic cancer; neuroblastoma; 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; 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; Williams syndrome; 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; autoinflammatory diseases including gout; 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, COVID-19, and gram-negative Infectious diseases, including bacterial infections, gram-positive bacterial infections, tuberculosis, etc.; septic shock; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ (including kidney, heart, lung) or tissue transplant rejection; diabetes; sarcoidosis; acute respiratory distress syndrome; cachexia and multiple organ failure due to septic shock; acute liver failure; functional uterine bleeding; anemia; childhood aplastic anemia; endometriosis; polycystic ovary syndrome; thyroid disease; cardiovascular disease (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); skin diseases (e.g., acne); Kennedy disease; seborrheic alopecia; and hirsutism.

[0174] The term "treatment" or "treatment" refers to slowing (alleviating) the progression of an unwanted disease or condition, such as cancer or tumor, by administering to a subject a compound of Formula (I), Formula (II), or Formula (III) or a pharmaceutically acceptable salt thereof according to the present disclosure, or a pharmaceutical composition comprising a compound of Formula (I), Formula (II), or Formula (III) 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 palliation of the condition, and remission of the disease.

[0175] 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 based on these and other factors.

[0176] It should be understood that the use of one or more active compounds and / or compositions and the selection of the dosage thereof will vary depending on the individual's basic condition (generally should be optimized for the individual's condition).Dosage and administration method 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)).

[0177] 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.

[0178] A compound of Formula (I) or Formula (II) according to the present disclosure, or a pharmaceutically acceptable salt, solvate, isotopically enriched analogue, polycrystalline form, pharmaceutical precursor, stereoisomer (including enantiomer), or mixture of stereoisomers thereof, can be used in the preparation of a compound of Formula (III) according to the present disclosure. The compounds of formula (III) according to the present disclosure can be used to treat and / or prevent a disease or condition selected from the group consisting of tumors, infectious diseases, autoinflammatory diseases, inflammatory diseases, autoimmune diseases, neurological diseases, respiratory diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome (MODS), sarcoidosis, acute respiratory distress syndrome, congestive heart failure, myocardial infarction, Williams syndrome, Richter syndrome (RS), acute liver failure, diabetes, Kennedy disease, seborrheic alopecia, hirsutism, skin diseases, cardiovascular diseases, dysfunctional uterine bleeding, anemia, childhood aplastic anemia, endometriosis, transplant rejection, polycystic ovary syndrome, and / or thyroid disease. VI.Definition

[0179] Unless otherwise specified, the following terms, phrases and symbols used in this specification generally have the following meanings:

[0180] 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, all scientific and technical terms used herein in conjunction with the present disclosure described herein have the same meaning as commonly understood by one of ordinary skill in the art. Also, 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.

[0181] 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.

[0182] The term "about" is used herein to mean approximately, roughly, roughly, or to the extent 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, e.g., by 10%, 5%, 2%, 1%, etc.

[0183] As used herein, the term "represents a bond" refers to a bond connector (i.e., represents an absence). For example, the term "U represents a bond" refers to U being a bond connector. In other words, when U 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). For example, the term "R 12 represents a bond" means that R 12 is a bond connective. In other words, R 12 is a bond, the ring atom C in the structure of formula (PBM-7) is R in the compound of formula (III) 1 is connected directly to

[0184] As used herein, "straight or branched chain C" used alone or in combination 2-30 The alkylene carbon backbone may contain one or more groups R e and / or one or more groups R f or one or more groups R e and R f "Intercalated" in "intercalated with any combination of" has the definition known in the art, i.e., a group R e , R f or group R e and R fIn this specification, examples of the term "inserted in one or more..." include one or more (1-30, 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2, or 1) groups R as defined in the present text inserted in the carbon backbone. e and / or one or more (1-30, 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) groups R f , and / or one or more (1-30, 1-20, or 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3 or 1-2, or 1) groups R e and R f The main chain groups formed thereby are consistent with covalent bonding theory. For example, "linear or branched C 2-30 The alkylene carbon backbone may contain one or more groups R e and / or one or more groups R f、 or one or more groups R e and R f The phrase "any combination of -CH-R is inserted" refers to one or more (e.g., 1-30, 1-20, 1-15, 1-10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2 or 1) "-CH-R e -CH2-" fragment and / or one or more (e.g., 1-30, 1-20, 1-15, 1-10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2 or 1) "-CH2-R f -CH2-" fragment and / or one or more (e.g., 1-30, 1-20, 1-15, 1-10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2 or 1) "-CH2-R e -R f -CH2- fragments, 2-30In the carbon main chain of the alkylene chain, there are one or more (for example, 1-30, 1-20, 1-15, 1-10, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1) R between any pair or pairs of adjacent carbon atoms. e and / or R f and / or one or more groups R e and R f where each R e are the same or different, and each R f are the same or different and are as defined herein.

[0185] In the context of the present disclosure, "the linear or branched C 2-30 The alkylene carbon backbone may contain one or more groups R e and / or one or more groups R f or one or more groups R e and R f The expression "any combination of the above linear or branched C 2-30 One or more groups R e and / or one or more groups R f or one or more groups R e and R f and "the linear or branched C 2-30 One or more groups R e and / or one or more groups R f or one or more groups R e and R f It should be understood that the implementation scheme includes "any combination of the above is not inserted."

[0186] 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 represented by the formula (ULM) shown below: [ka] represents the connection between said group U2 and group LIN of the compound of formula (III).

[0187] In the present text, the term "the above C" used alone or in combination x-y "One or more CH2 hydrogen atoms of alkylene are replaced..." refers to a straight or branched C x-y This means that one or more hydrogen atoms in CH2 in alkylene are substituted with a substituent as defined herein. In the present specification, the term "groups #-CH2-, #-(CH2)2-, #-(CH2)3-, #-(CH2)4-, #-(CH2)5-, #-(CH2)6-, #-(CH2)7-, #-(CH2)8-, #-(CH2)9-, #-(CH2) 10 -, #-(CH2) 11 -, #-(CH2) 12 -, #-(CH2) 13 -, #-(CH2) 14 -, #-(CH2) 15 -, #-(CH2) 16 -, #-(CH2) 17 -, #-(CH2) 18 -, #-(CH2) 19 -, #-(CH2) 20 -, #-(CH2) 21 -, #-(CH2) 22 -, #-(CH2) 25 - or #-(CH2) 30 The term "one or more" in "one or more CH hydrogens" may refer to some or all of the hydrogens in each alkylene group referred to, including, but not limited to, 1-60 hydrogens. In some embodiments, the term "one or more CH hydrogens" may refer to some or all of the hydrogens in the alkylene group referred to, including, but not limited to, 1-30 (e.g., 1-25, 1-20, 1-15, 1-10, 1-5, 1-4, 1-3, 1-2, or 1) hydrogens. In some embodiments, the term "one or more CH hydrogens" may refer to 1-3 of the hydrogens in the alkylene group referred to. The number is not limited in principle or is automatically limited by the size of the constituent unit.

[0188] As used herein, the terms "optionally substituted" and "unsubstituted or substituted" may be used interchangeably. The term "substituted" generally refers to the replacement of one or more hydrogens in the referenced structure with the same or different specified substituents.

[0189] As used herein, the term "oxo" or "oxo group" refers to =O.

[0190] As used herein, the term "nicotinoyl" [ka] Refers to...

[0191] The terms "halogen atom" or "halogen", as used herein, alone or in combination, refer to fluorine, chlorine, bromine or iodine.

[0192] 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" (where x and y are each integers) refers to a straight or branched chain alkyl containing x to y carbon atoms. 1-10 "Alkyl" refers to a straight or branched chain alkyl containing 1 to 10 carbon atoms. 1-10 Examples of alkyl are C 1-9 Alkyl, C 1-8 Alkyl, C 2-8 Alkyl, C 1-7 Alkyl, C 1-6 Alkyl, C 1-5 Alkyl, and C 1-4 Representative examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, and decyl. 1-3"Alkyl" or "C1-C3 alkyl" refers to an alkyl containing 1 to 3 carbon atoms. Representative examples include methyl, ethyl, n-propyl, and isopropyl. In this disclosure, the "alkyl" is optionally substituted, and the substituents include halogen, hydroxy, cyano, C 1-3 Alkyl, C 1-3 one or more substituents optionally selected from the group consisting of alkoxy, trifluoromethyl, heterocyclyl, or combinations thereof.

[0193] 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 1-10 "Alkyl" refers to a straight or branched chain alkyl containing 1 to 10 carbon atoms substituted with one or more halogens. 1-10 Examples of alkyls include halogenated C 1-9 Alkyl, e.g., halogenated C 1-8 Alkyl, halogenated C 2-8 Alkyl, halogenated C 1-7 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-5 Alkyl or halogenated C 1-4Representative examples 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, hexyl halides, heptyl halides, octyl halides, nonyl halides, and decyl halides. The term "halogenated C 1-3 Alkyl" or "halogenated C 1― "C3 alkyl" refers to an alkyl containing 1 to 3 carbon atoms substituted with one or more halogens, representative examples of which include methyl halide, ethyl halide, n-propyl halide, and isopropyl halide.

[0194] As used herein, the term "deuterated alkyl," alone or in combination, refers to a straight or branched chain alkyl substituted with one or more deuterium atoms, where one or more hydrogen atoms in the alkyl are replaced with deuterium atoms. 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 1-10 "Alkyl" refers to a straight or branched chain alkyl containing 1 to 10 carbon atoms substituted with one or more deuterium atoms. 1-10 Examples of alkyls include deuterated C 1-9 Alkyl, e.g., deuterated C 1-8 Alkyl, deuterated C 2-8 Alkyl, deuterated C 1-7 Alkyl, deuterated C 1-6 Alkyl, deuterated C 1-5 Alkyl or deuterated C 1-4Representative examples include fully deuterated methyl (CD3), fully deuterated ethyl (CD3CD2), fully deuterated n-propyl, fully deuterated isopropyl, fully deuterated n-butyl, fully deuterated isobutyl, fully deuterated sec-butyl, fully deuterated tert-butyl, fully deuterated pentyl, fully deuterated isopentyl, fully deuterated neopentyl, fully deuterated tert-pentyl, fully deuterated hexyl, fully deuterated heptyl, fully deuterated octyl, fully deuterated nonyl, and fully deuterated decyl. 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).

[0195] 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" (where x and y are each integers) refers to a straight or branched chain alkylene containing x to y carbon atoms. 30 Examples of alkylene are C1-C 30 Alkylene, C1-C 29 Alkylene, C1-C 28 Alkylene, C1-C 27 Alkylene, C1-C 26 Alkylene, C1-C 25 Alkylene, C1-C 24 Alkylene, C1-C 23 Alkylene, C1-C 22 Alkylene, C1-C 21 Alkylene, C1-C 20 Alkylene, C1-C 19 Alkylene, C1-C 18 Alkylene, C1-C 17 Alkylene, C1-C 16 Alkylene, C1-C15 Alkylene, C1-C 14 Alkylene, C1-C 13 Alkylene, C1-C 12 Alkylene, C1-C 11 Alkylene, C1-C 10 alkylene, C1-C9 alkylene, C1-C8 alkylene, C1-C7 alkylene, C1-C6 alkylene, C1-C5 alkylene, C1-C4 alkylene, C1-C3 alkylene, or C1-C2 alkylene. Representative examples include, but are not limited to, methylene, ethylene, propylene, isopropylidene, butylene, isobutylene, sec-butylene, tert-butylene, n-pentylene, isopentylene, neopentylidene, tert-pentylene, hexylene, heptylene, octylene, nonylene, decylene, undecylene, dodecylene, tridecylene, tetradecylene, pentadecylene, hexadecylene, heptadecylene, octadecylene, nonadecylene, eicosylene, heneicosylene, docosylene, tricosylene, tetracosylene, pentacosylene, hexacosylene, heptacosylene, octacosylene, nonacosylene, and triacontylene. In the present disclosure, the "alkylene" is optionally substituted, and the substituents are optionally C 1-3 Alkyl, C 3-6 Cycloalkyl, hydroxy, amino, mercapto group, halogen, C 1-3 Alkoxy, C 1-3 Alkylamino, halogenated C 1-3 Alkyl, Amino C 1-3 Alkylene, C 1-3 Alkyl-NHC(O)-, C 1-3 One or more substituents selected from the group consisting of alkyl-C(O)NH-, cyano group, or any combination thereof.

[0196] As used herein, the term "alkoxy," alone or in combination, refers to a straight or branched chain alkoxy and has the formula -O-alkyl. 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, isopentyloxy, neopentyloxy, hexyloxy, 2-hexyloxy, 3-hexyloxy, 3-methylpentyloxy, and the like. The terms "C1-C3 alkoxy" or "C 1-3 "Alkoxy" refers to a straight or branched chain alkoxy containing 1-3 carbon atoms. 1-3 Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, and isopropoxy.

[0197] As used herein, the term "alkylamino," alone or in combination, refers to a straight or branched chain alkylamino, the structural formula of which is alkyl-NH-. The alkyl portion of the alkylamino may optionally contain 1-10 carbon atoms. Representative examples of "alkylamino" 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-C3 alkyl-NH-" or "C 1-3 "Alkyl-NH-" refers to a straight or branched chain alkyl-NH- containing 1 to 3 carbon atoms. 1-3 Representative examples of alkyl-NH- include, but are not limited to, methyl-NH-, ethyl-NH-, n-propyl-NH-, and isopropyl-NH-.

[0198] As used herein, the term "amino-substituted alkylene," alone or in combination, refers to a straight or branched chain alkylene substituted with an amino group and has the structural formula NH-alkylene-. Optionally, the alkylene portion of the "amino-substituted alkylene" may contain 1-10 carbon atoms. 1-3alkylene" or "amino-C 1-3 "Alkylene-" refers to a straight or branched chain alkylene containing 1 to 3 carbon atoms substituted with an amino group. 1-3 Representative examples of alkylene include, but are not limited to, NH2-CH2-, NH2-CH2CH2-, and NH2-CH2CH2CH2-.

[0199] As used herein, the term "alkyl-NHC(O)-," alone or in combination, refers to a straight or branched chain alkyl-NHC(O)-, which has the structural formula alkyl-NHC(O)-. The alkyl portion of alkyl-NHC(O)- may optionally contain 1-10 carbon atoms. The terms "C1-C3 alkyl-NHC(O)-" or "C 1-3 "Alkyl-NHC(O)-" refers to a straight or branched chain alkyl-NHC(O)- containing 1 to 3 carbon atoms. 1-3 Representative examples of alkyl-NHC(O)- include, but are not limited to, CH3-NHC(O)-, CH3CH2-NHC(O)-, and CH3CH2CH2-NHC(O)-.

[0200] As used herein, the term "alkyl-C(O)NH-," alone or in combination, refers to a straight or branched chain alkyl-C(O)NH-, which has the structural formula alkyl-C(O)NH-. Optionally, the alkyl portion of alkyl-C(O)NH- may contain 1-10 carbon atoms. The terms "C1-C3 alkyl-C(O)NH-" or "C 1-3 "Alkyl-C(O)NH-" refers to a straight or branched chain alkyl-C(O)NH- containing 1 to 3 carbon atoms. 1-3 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-.

[0201] As used herein, the term "heteroaryl," used alone or in combination, refers to a 5- to 20-membered (optionally 5- to 15-, 5- to 12-, 5- to 11-, 5- to 10-, 5- to 9-, 5- to 8-, 5- to 7-, 5- to 6-, 6- to 15-, or 6- to 9-membered) monocyclic, bicyclic, or polycyclic monovalent aromatic ring radical containing one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. 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, pyrimidyl, 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, quinolyl, isoquinolyl, naphthyridinyl, and the like. Examples of tricyclic heteroaryls include, but are not limited to, phenyl, 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 heteroaryls include, but are not limited to, acridinyl, benzoindolyl, 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 group, 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.

[0202] 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, where 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 ring 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, pyrimi...

Claims

1. A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, comprising: 【Chemical 1】 Formula (I) where: A is CO, CH ２ or CD ２ represents; R １ , R ２ , R ３ and R ４ are the same or different and each independently represent hydrogen, deuterium, halogen, or optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy or halogenated C １－６ represents alkyl; R ５ , R ６ , R ７ and R ８ are the same or different and each independently represent R ９ , hydrogen, deuterium, halogen, hydroxy, mercapto group, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl, where R ５ , R ６ , R ７ and R ８ 1 to 3 of the inside are R ９ represents; R ９ represents the group R-U-, where: U represents a bond, or U represents N(R １０ ) or O, where R １０ is H or optionally deuterated C １－６ represents alkyl; R represents an optionally substituted nitrogen-containing heterocyclyl, which is an optionally substituted nitrogen-containing monocyclic heterocyclyl or an optionally substituted nitrogen-containing bridged heterocyclyl; where: R ５ , R ６ , R ７ and R ８ 2 to 4 of them are independently R ９ wherein the compound of formula (I) is optionally partially or fully deuterated, or R ５ , R ６ , R ７ and R ８ Only one of them is R ９ wherein the compound of formula (I) is optionally partially or fully deuterated, Here, R ５ , R ６ , R ７ and R ８ Only one of them is R ９ and the compound of formula (I) is not deuterated, When R represents said optionally substituted nitrogen-containing bridged heterocyclyl, the compound of formula (I) is the following compound: 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(8-azabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 3-(5-(9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonan-7-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione does not contain; or A represents CO, and R ６ and R ７ One of them is R ９ where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl and R ６ and R ７ Another one in the middle, R ５ and R ８ are each independently hydrogen, halogen, hydroxy, mercapto group, nitro, amino, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ When alkynyl is represented by the above R ６ and R ７ Another one in the middle, R ５ and R ８ One to three of the three represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from hydroxy, amino, mercapto, nitro, halogen, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, C １－６ Alkyl-NH-, C １－６ Alkyl-NHC(O)-, C １－６ substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; A represents CO, and R ６ and R ７ One of them is R ９ where when the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, R ６ and R ７ The other one is hydrogen, halogen, hydroxy, mercapto group, nitro, amino, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl, and R ５ and R ８ each independently represents a halogen; A represents CO, and R ５ and R ８ One of them is R ９ where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl and R ５ and R ８ Another one in the middle, R ６ and R ７ are each independently hydrogen, halogen, hydroxy, mercapto group, nitro, amino, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ When alkynyl is represented by the above R ５ and R ８ Another one in the middle, R ６ and R ７ One to three of the three represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from hydroxy, amino, mercapto, nitro, halogen, cyano, CHO, C １－６ Alkyl, halogenated C １－６ Alkyl, C ３－６ Cycloalkyl, C １－６ Alkoxy, C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, C １－６ Alkyl-NHC(O)-, C １－６ substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; A represents CO, and R ５ and R ８ One of them is R ９ where when the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, R ５ and R ８ Another one in and / or R ７ each independently represents a halogen, and R ６ is hydrogen, halogen, hydroxy, mercapto group, nitro, amino, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; A is CH ２ and R ６ and R ７ One of them is R ９ where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl and R ６ and R ７ Another one in the middle, R ５ and R ８ are each independently hydrogen, halogen, hydroxy, mercapto group, nitro, amino, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ When alkynyl is represented by the above R ６ and R ７ Another one in the middle, R ５ and R ８ One to three of the three represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from the group consisting of hydroxy, amino, mercapto, nitro, halogen, cyano, C １－６ Alkyl, halogenated C １－６ Alkyl, C ３－６ Cycloalkyl, C １－６ Alkoxy, C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, C １－６ Alkyl-NHC(O)-, C １－６ substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; A is CH ２ and R ６ and R ７ One of them is R ９ where when the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl, R ５ represents a halogen, and R ６ and R ７ Another one in and / or R ８ are each independently a halogen, a hydroxyl, a mercapto group, a nitro, an amino, a cyano, or C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; A is CH ２ and R ５ and R ８ One of them is R ９ where the group R represents a substituted nitrogen-containing monocyclic heterocyclyl and R ５ and R ８ Another one in the middle, R ６ and R ７ are each independently hydrogen, halogen, hydroxy, mercapto group, nitro, amino, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ When alkynyl is represented by the above R ５ and R ８ Another one in the middle, R ６ and R ７ In the above, 1 to 3 represent halogen, and the nitrogen-containing monocyclic heterocyclyl is selected from hydroxy, amino, mercapto, nitro, halogen, cyano, C １－６ Alkyl, halogenated C １－６ Alkyl, C ３－６ Cycloalkyl, C １－６ Alkoxy, C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, C １－６ Alkyl-NHC(O)-, C １－６ substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; or A is CH ２ and R ５ and R ８ One of them is R ９ where the group R represents an unsubstituted nitrogen-containing monocyclic heterocyclyl and R ５ and R ８ Another one in the middle, R ６ and R ７ are each independently hydrogen, halogen, hydroxy, mercapto group, nitro, amino, cyano, C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ When alkynyl is represented by the above R ５ and R ８ Another one in the middle, R ６ and R ７ cannot be hydrogen at the same time, and R ６ is halogen, ５ and R ８ Another one in and R ７ A compound of formula (I) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein:

2. It is also a compound of formula (I-1) or formula (I-2), 【Chemistry 2】 Here, A and R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ 2. A compound of formula (I) according to claim 1, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein:

3. (i) R ５ , R ６ , R ７ and R ８ 2 to 4 of them are independently R ９ wherein the compound of formula (I) is optionally partially deuterated, for example having 1 to 20 deuterium atoms, or the compound of formula (I) is optionally fully deuterated, or (ii) the nitrogen-containing monocyclic heterocyclyl and the nitrogen-containing bridged heterocyclyl are optionally substituted with one or more substituents selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, CHO, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH—, or any combination thereof; 3. A compound of formula (I) according to claim 1 or 2 or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

4. R ５ , R ６ , R ７ and R ８ Only one of them is R ９ wherein, when R represents an integer from 1 to 15, said compound of formula (I) is partially deuterated, for example having 1 to 15 deuterium atoms, or said compound of formula (I) is fully deuterated.

5. The nitrogen-containing monocyclic heterocyclyl is a 4- to 10-membered monocyclic heterocyclyl containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, such as the following groups: piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl or diazacyclooctyl; or The nitrogen-containing bridged heterocyclyl is a C 1 -C 2 -C 3 -C 4 -C 5 -C 6 -C 7 -C 8 -C 9 -C 10 -C 11 -C 12 -C 13 -C 14 -C 15 -C 16 -C 17 -C 18 -C 19 -C 20 -C 21 -C 22 -C 23 -C 24 -C 25 - ５－２０ is a bridged heterocyclyl, for example the following groups: azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl or diazabicyclo[2.2.2]octanyl, for example the following groups: 【Chemistry 3】 represents; wherein the nitrogen-containing monocyclic heterocyclyl and the nitrogen-containing bridged heterocyclyl are selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, CHO, and optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ３ - C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ 3. A compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof.

6. R ９ is the following group: 【Chemistry 4】 3. A compound of formula (I) according to claim 1 or 2, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, which represents:

7. The following: 5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 5-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-azabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(2-azabicyclo[2.2.1]heptan-5-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(2-azabicyclo[2.2.2]octan-5-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-6-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5-difluoro-6-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5,7-trifluoro-6-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 6-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 6-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5,7-trifluoro-6-(piperazin-1-yl)isoindoline-1,3-dione; 6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 6-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 6-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 6-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-azabicyclo[3.1.1]heptan-6-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(6-azabicyclo[3.1.1]heptan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3-azabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,6-dimethylpiperazin-1-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,5-dimethylpiperazin-1-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-fluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,6-dimethylpiperazin-1-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,5-dimethylpiperazin-1-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,6-dimethylpiperazin-1-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,5-dimethylpiperazin-1-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6,7-difluoro-1-oxo-5-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4,7-difluoro-1-oxo-5-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4,6,7-trifluoro-1-oxo-5-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-8-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,5-diazabicyclo[2.2.2]octan-2-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(6,7-difluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(4,7-difluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(4,6-difluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(4,6,7-trifluoro-1-oxo-5-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,6-dimethylpiperazin-1-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,6-dimethylpiperazin-1-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,6-dimethylpiperazin-1-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(2,6-dimethylpiperazin-1-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,5-dimethylpiperazin-1-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,5-dimethylpiperazin-1-yl)-4,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,5-dimethylpiperazin-1-yl)-4,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(3,5-dimethylpiperazin-1-yl)-4,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-4-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-7-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5-difluoro-7-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5,6-difluoro-4-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5,7-difluoro-4-(piperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5,6-trifluoro-7-(piperazin-1-yl)isoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-6-fluoro-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-7-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5-difluoro-7-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5,7-difluoro-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5,6-difluoro-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5,6-trifluoro-7-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-4-(piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-7-(piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5-difluoro-7-(piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5,6-difluoro-4-(piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5,7-difluoro-4-(piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5,6-trifluoro-7-(piperidin-4-yl)isoindoline-1,3-dione; 4-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(3-azabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(6-azabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 4-(3,5-dimethylpiperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione; 4-(3,5-dimethylpiperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 4-(3,5-dimethylpiperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-7-fluoroisoindoline-1,3-dione; 7-(3,5-dimethylpiperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 4-(3,5-dimethylpiperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione; 4-(3,5-dimethylpiperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-5,7-difluoroisoindoline-1,3-dione; 4-(3,5-dimethylpiperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-5,6,7-trifluoroisoindoline-1,3-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5-fluoro-1-oxo-4-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-4-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6,7-difluoro-1-oxo-4-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5,6-difluoro-1-oxo-4-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5,7-difluoro-1-oxo-4-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5,6,7-trifluoro-1-oxo-4-(piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-6-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-8-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,6-dimethylpiperazin-1-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,6-dimethylpiperazin-1-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,6-dimethylpiperazin-1-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,6-dimethylpiperazin-1-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,6-dimethylpiperazin-1-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,6-dimethylpiperazin-1-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(2,6-dimethylpiperazin-1-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-fluoro-1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(6-fluoro-1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(6,7-difluoro-1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5,7-difluoro-1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5,6-difluoro-1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5,6,7-trifluoro-1-oxo-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindolin-2-yl)piperidine-2,6-dione; 3-(5-fluoro-1-oxo-4-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(7-fluoro-1-oxo-4-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(6,7-difluoro-1-oxo-4-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5,6-difluoro-1-oxo-4-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5,7-difluoro-1-oxo-4-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(5,6,7-trifluoro-1-oxo-4-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3-azabicyclo[3.1.1]heptan-6-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3-azabicyclo[3.1.1]heptan-6-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3-azabicyclo[3.1.1]heptan-6-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3-azabicyclo[3.1.1]heptan-6-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3-azabicyclo[3.1.1]heptan-6-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3-azabicyclo[3.1.1]heptan-6-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3-azabicyclo[3.1.1]heptan-6-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(6-azabicyclo[3.1.1]heptan-3-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(6-azabicyclo[3.1.1]heptan-3-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(6-azabicyclo[3.1.1]heptan-3-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(6-azabicyclo[3.1.1]heptan-3-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(6-azabicyclo[3.1.1]heptan-3-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; ； 3-(4-(6-azabicyclo[3.1.1]heptan-3-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(6-azabicyclo[3.1.1]heptan-3-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((1R,5S,8r)-3-azabicyclo[3.2.1]octan-8-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,5-dimethylpiperidin-4-yl)-5-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,5-dimethylpiperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,5-dimethylpiperidin-4-yl)-7-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,5-dimethylpiperidin-4-yl)-6,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,5-dimethylpiperidin-4-yl)-5,6-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(3,5-dimethylpiperidin-4-yl)-5,7-difluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 3-(4-(3,5-dimethylpiperidin-4-yl)-5,6,7-trifluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione 2. A compound of formula (I) according to claim 1, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, selected from the group consisting of:

8. 1. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, 【Chemistry 5】 where: A is CO, CH ２ or CD ２ represents; R １ , R ２ , R ３ and R ４ are the same or different and each independently represent hydrogen, deuterium, halogen, or optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy or halogenated C １－６ represents alkyl; (R ｂ ) ｎ is a group in which the benzene ring of the formula (II) is n R ｂ and each R ｂ are the same or different and each independently represent hydrogen, deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; (R ａ ) ｍ is a group in which the benzene ring is m in number ａ and each R ａ are the same or different and each independently represent a structure of the formula: W-LIN-U ２ -R ｃ -U １ - where: U １ and U ２ are the same or different and each independently represent a bond, N(R ｄ ) or O, where R ｄ is H or optionally deuterated C １－６ represents alkyl; R ｃ represents an optionally substituted nitrogen-containing monocyclic heterocyclylene or an optionally substituted nitrogen-containing bridged heterocyclylene; W is hydrogen, optionally substituted nitrogen-containing monocyclic heterocyclyl, optionally substituted nitrogen-containing bridged heterocyclyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted aryl, C ２－６ Alkenyl, C ２－６ Alkynyl, leaving group, CHO, COOH, NH ２ , represents a hydroxy or mercapto group; and where: When the compound of formula (II) is partially or fully deuterated, When W represents an optionally substituted nitrogen-containing monocyclic heterocyclyl, an optionally substituted nitrogen-containing bridged heterocyclyl, an optionally substituted cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted aryl, LIN represents a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C ２－３０ alkylene, wherein the straight or branched chain C ２－３０ The alkylene carbon backbone may optionally contain one or more groups R ｅ and / or one or more groups R ｆ or one or more groups R ｅ and R ｆ Any combination of the groups R ｅ , R ｆ or group R ｅ and R ｆ The combination of these groups cleaves the carbon-carbon bond between one or more pairs of adjacent carbon atoms in the carbon backbone; ｅ is O, N (R ｇ ), C(O), C(O)O, OC(O), S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , C(O)N(R ｇ ), N(R ｇ ) C(O), or N(R ｇ )C(O)N(R ｇ ) wherein each R ｇ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ The alkylene carbon backbone may have two or more groups R ｅ When inserted, each group R ｅ are not directly connected to each other; ｆ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; or W is hydrogen, C ２－６ Alkenyl, C ２－６ Alkynyl, leaving group, CHO, COOH, NH ２ , hydroxy or mercapto group, LIN is an optionally substituted methylene or an optionally substituted straight or branched C ２－３０ alkylene, wherein the straight or branched chain C ２－３０ The alkylene carbon backbone may optionally contain one or more groups R ｅ and / or one or more groups R ｆ or one or more groups R ｅ and R ｆ Any combination of the groups R ｅ , R ｆ or group R ｅ and R ｆ The combination of R ｅ is O, N (R ｇ ), C(O), C(O)O, OC(O), S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , C(O)N(R ｇ ), N(R ｇ ) C(O), or N(R ｇ )C(O)N(R ｇ ) wherein each R ｇ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ The alkylene carbon backbone may have two or more groups R ｅ When inserted, each group R ｅ are not directly connected to each other; ｆ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; or When the compound of formula (II) is non-deuterated, LIN represents optionally substituted methylene and W represents optionally substituted nitrogen-containing monocyclic heterocyclyl or optionally substituted nitrogen-containing bridged heterocyclyl; and m represents an integer of 1, 2, 3, or 4, n represents an integer of 0, 1, 2, or 3, and the sum of m and n represents an integer of 1, 2, 3, or 4; The proviso is that when the compound of formula (II) is not deuterated, the compound of formula (II) is the following compound: 3-(4,6-difluoro-1-oxo-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl)isoindoline-1,3-dione; 3-(4-chloro-1-oxo-5-(4-(piperidin-4-ylmethyl)piperidin-1-yl)isoindolin-2-yl)piperidine-2,6-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and 2-(2,6-dioxopiperidin-3-yl)-5-(3-(piperazin-1-ylmethyl)azetidin-1-yl)isoindoline-1,3-dione is not a compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

9. Also compounds of formula (II-1) or formula (II-2): 【Chemistry 6】 Here, A and R １ , R ２ , R ３ , R ４ , R a、 R ｂ 9. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to claim 8, wherein m and n are as defined in claim 8.

10. When the compound of formula (II) is partially deuterated (e.g., having 1 to 20 deuterium atoms) or fully deuterated, and W represents an optionally substituted nitrogen-containing monocyclic heterocyclyl, an optionally substituted nitrogen-containing bridged heterocyclyl, an optionally substituted cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted aryl, LIN represents a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C ２－３０ alkylene, wherein the straight or branched chain C ２－３０ The alkylene carbon backbone may optionally contain one or more groups R ｅ and / or one or more groups R ｆ or one or more groups R ｅ and R ｆ Any combination of the groups R ｅ , R ｆ or group R ｅ and R ｆ The combination of R ｅ is O, N (R ｇ ), C(O), C(O)O, S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , OC(O), C(O)N(R ｇ ), N(R ｇ ) C(O), or N(R ｇ )C(O)N(R ｇ ) wherein each R ｇ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ The alkylene carbon backbone may have two or more groups R ｅ When inserted, each group R ｅ are not directly connected to each other; ｆ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; or The compound of formula (II) may be partially deuterated (e.g., having 1 to 20 deuterium atoms) or fully deuterated, and W is hydrogen, C ２－６ Alkenyl, C ２－６ Alkynyl, leaving group, CHO, COOH, NH ２ , hydroxy or mercapto group, LIN is an optionally substituted methylene or an optionally substituted straight or branched chain C ２－３０ alkylene, wherein the straight or branched chain C ２－３０ The alkylene carbon backbone may optionally contain one or more groups R ｅ and / or one or more groups R ｆ or one or more groups R ｅ and R ｆ Any combination of the groups R ｅ , R ｆ or group R ｅ and R ｆ The combination of R ｅ is O, N (R ｇ ), C(O), C(O)O, S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , OC(O), C(O)N(R ｇ ), N(R ｇ ) C(O), or N(R ｇ )C(O)N(R ｇ ) wherein each R ｇ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ The alkylene carbon backbone may have two or more groups R ｅ When inserted, each group R ｅ are not directly connected to each other; ｆ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein the cycloalkylene, the arylene, the heterocyclylene, and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; or When the compound of formula (II) is non-deuterated, LIN represents optionally substituted methylene, and W represents optionally substituted nitrogen-containing monocyclic heterocyclyl or optionally substituted nitrogen-containing bridged heterocyclyl; wherein the methylene and the linear or branched C ２－３０ Alkylene is a group selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, and optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ 10. The compound of formula (II) according to claim 8 or 9, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH- or any combination thereof.

11. (i) R ｃ is the following group: A monocyclic ring C containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur. ３－１０ heterocyclylene, such as piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene or diazacyclooctylene; or C containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur ５－２０ Bridged heterocyclylenes, such as azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene or diazabicyclo[2.2.2]octanylene, for example the group 【Chemistry 7】 represents where the symbol * represents the base U １ represents the connection point with wherein the monocyclic ring C ３－１０ Heterocyclylene and the C ５－２０ The bridged heterocyclylenes each independently represent deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, CHO, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ and / or optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; (ii) W is the following group: monocyclic C3-10 heterocyclyl containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, such as piperidinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, thiomorpholinyl, azepanyl, diazacycloheptanyl, azacyclooctyl or diazacyclooctyl; or C5-20 bridged heterocyclyl containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, such as azabicyclo[3.1.1]heptanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl or diazabicyclo[2.2.2]octanyl, such as the following groups: 【Chemistry 9】 or a saturated or partially unsaturated, mono-, bi- or polycyclic C 3-20 cyclic hydrocarbon group, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, C 7-11 spirocycloalkyl, adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl or biscyclo[2.2.1]heptenyl; or Heteroaryl, for example, one or more 5- to 20-membered monocyclic or bicyclic C 5-20 aromatic ring groups independently selected from the group consisting of oxygen, nitrogen, and sulfur, such as furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]ox ... thiadiazolyl, benzo[2,1,3]thiadiazolyl, benzo[1,2,3]thiadiazolyl, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolyl, pyrrolo[2,1-b]thiazolyl, or imidazo[2,1-b]thiazolyl; or C 5-14 aryl, optionally containing one or more fused rings, such as phenyl, or naphthyl or fluorenyl; represents wherein the monocyclic C 3-10 heterocyclyl, the C 5-20 bridged heterocyclyl, the C 3-20 cyclic hydrocarbon group, the heteroaryl and the C 5-14 aryl are each independently selected from deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, CHO, COOH, N 3 , methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-6 alkyl, deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl (e.g., deuterium, halogen, amino, hydroxy, mercapto, cyano, CHO, COOH, N 3 , methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy), optionally substituted 4- to 9-membered heterocyclyl (e.g., substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, mercapto group, cyano, CHO, COOH, N 3 , methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy), C 1-6 alkoxy, deuterated C 1-6 alkyl-O—, C 1-6 alkyl-NH—, deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, C 1-6 alkyl-NHC(O)—, deuterated C 1-6 alkyl-NHC(O)—, C 1-6 alkyl-C(O)NH—, deuterated C 1-6 and / or optionally substituted with one or more substituents selected from the group consisting of alkyl-C(O)NH— or any combination thereof; (iii) LIN has the structure of the following formula: #-C 1-30 alkylene-; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(Ra1)(Ra2))n1-(Re(C(Ra3)(Ra4))n2)m1-(Re(C(Ra5)(Ra6))n3)m2-(Re(C(Ra7)(Ra8))n4)m3-; #-(C(Ra1)(Ra2))n1-(Rf(C(Ra3)(Ra4))n2)m1-; #-(C(Ra1)(Ra2))n1-(Rf(C(Ra3)(Ra4))n2)m1-(Rf(C(Ra5)(Ra6))n3)m2-; #-(C(Ra1)(Ra2))n1-(Rf(C(Ra3)(Ra4))n2)m1-(Rf(C(Ra5)(Ra6))n3)m2-(Rf(C(Ra7)(Ra8))n4)m3-; #-(C(Ra1)(Ra2))n1-(Re-Rf-(C(Ra3)(Ra4))n2)m1-; #-(C(Ra1)(Ra2))n1-(Re(C(Ra3)(Ra4))n2)m1-(Rf(C(Ra5)(Ra6))n3)m2-; #-(C(Ra1)(Ra2))n1-(Rf-Re-(C(Ra3)(Ra4))n2)m1-; or #-(C(Ra1)(Ra2))n1-(Rf(C(Ra3)(Ra4))n2)m1-(Re(C(Ra5)(Ra6))n3)m2- represents; wherein each group R e is selected from the group consisting of O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O) 2 , S(O) 2 NH, NHS(O) 2 , C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g independently represents H or C 1-6 alkyl; and each group R f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein said cycloalkylene, said arylene, said heterocyclylene, and said heteroarylene, independently of one another, may further comprise deuterium, optionally deuterated C 1-6 alkyl, optionally deuterated C 3-6 alkyl, or optionally deuterated C 3-6 alkyl. optionally substituted with a substituent selected from the group consisting of cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, halogenated C 1-6 alkyl, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH—, cyano, or any combination thereof; one or more hydrogens of CH 2 of said C 1-30 alkylene are optionally substituted with a substituent selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH— or any combination thereof; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 and R a8 each independently represent H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH— or any combination thereof; The symbol # represents the point of attachment to the group U 2 ; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of integers of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15; 10. A compound of formula (II) according to claim 8 or 9, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

12. R ｃ is the following group: 【Chemistry 8】 【change】 represents where the symbol * represents the base U １ 10. A compound of formula (II) according to claim 8 or 9, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, which represents a junction point with

13. LIN has the structure of the following formula: #-(C(R ａ１ )(R ａ２ )) ｎ１ -(O(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(O(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(O(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(O(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(O(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -(O(C(R ａ７ )(R ａ８ )) ｎ４ ) ｍ３ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(N(R ｇ )(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(N(R ｇ )(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(N(R ｇ )(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(N(R ｇ )(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(N(R ｇ )(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -(N(R ｇ )(C(R ａ７ )(R ａ８ )) ｎ４ ) ｍ３ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(C(O)N(R ｇ )-(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(C(O)N(R ｇ )-(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(C(O)N(R ｇ )-(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(C(O)N(R ｇ )-(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(C(O)N(R ｇ )-(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -(C(O)N(R ｇ )-(C(R ａ７ )(R ａ８ )) ｎ４ ) ｍ３ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(C(O)N(R ｇ )-(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(O-(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -C(O)N(R ｇ )-(C(R ａ３ )(R ａ４ )) ｎ２ -(O(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ１ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(N(R ｇ )C(O)-(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(N(R ｇ )C(O)-(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(O-(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -(N(R ｇ )C(O)-(C(R ａ３ )(R ａ４ )) ｎ２ ) ｍ１ -(O-(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ２ -(O-(C(R ｇ )(R ａ８ )) ｎ４ ) ｍ３ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -N(R ｇ )C(O)-(C(R ａ３ )(R ａ４ )) ｎ２ -(O(C(R ａ５ )(R ａ６ )) ｎ３ ) ｍ１ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -N(R ｇ )C(O)N(R ｇ )-(C(R ａ３ )(R ａ４ )) ｎ２ -; #-(C(R ａ１ )(R ａ２ )) ｎ１ -C(O)-(C(R ａ３ )(R ａ４ )) ｎ２ -; #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(arylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ -; #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(arylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ -arylene-(C(R ａ５ ) (R ａ６ )) ｎ３ -; #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(heterocyclylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ -; #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(heterocyclylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ -(heterocyclylene-(C(R ａ５ ) (R ａ６ )) ｎ３ ) ｍ２ -; #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(heteroarylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ -; #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(heteroarylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ -(heteroarylene-(C(R ａ５ ) (R ａ６ )) ｎ３ ) ｍ２ -; #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(cycloalkylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ - or #-(C(R ａ１ ) (R ａ２ )) ｎ１ -(cycloalkylene-(C(R ａ３ ) (R ａ４ )) ｎ２ ) ｍ１ -(cycloalkylene-(C(R ａ５ ) (R ａ６ )) ｎ３ ) ｍ２ represents -; Here, each R ｇ are independently H or C １－６ represents alkyl; The cycloalkylene, the arylene, the heterocyclylene and the heteroarylene may each independently further comprise deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; R ａ１ , R ａ２ , R ａ３ , R ａ４ , R ａ５ , R ａ６ , R ａ７ and R ａ８ are each independently H, deuterium, hydroxy, amino, mercapto group, nitro, halogen, cyano, optionally deuterated C １－６ Alkyl, halogenated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ alkyl-C(O)NH— or any combination thereof; The symbol # is the base U ２ represents the connection point with; and 10. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to claim 8 or 9, wherein n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

14. LIN is the following group: #-CH ２ -, #-(CH ２ ) ２ -, #-(CH ２ ) ３ -, #-(CH ２ ) ４ -, #-(CH ２ ) ５ -, #-(CH ２ ) ６ -, #-(CH ２ ) ７ -, #-(CH ２ ) ８ -, #-(CH ２ ) ９ -, #-(CH ２ ) １０ -, #-(CH ２ ) １１ -, #-(CH ２ ) １２ -, #-(CH ２ ) １３ -, #-(CH ２ ) １４ -, #-(CH ２ ) １５ -, #-(CH ２ ) １６ -, #-(CH ２ ) １７ -, #-(CH ２ ) １８ -, #-(CH ２ ) １９ -, #-(CH ２ ) ２０ -, #-(CH ２ ) ２１ -, #-(CH ２ ) ２２ -, #-(CH ２ ) ２５ -, or #-(CH ２ ) ３０ -; #-CH ２ -O-CH ２ -, #-CH ２ -O-(CH ２ ) ２ -, #-(CH ２ ) １ [[ID=10​​​​​​​​ ２ ) ４ -、#-(CH ２ ) １ -O-(CH ２ ) ５ -、#-(CH ２ ) １ -O-(CH ２ ) ６ -、#-(CH ２ ) １ -O-(CH ２ ) ７ -、#-(CH ２ ) １ -O-(CH ２ ) ８ -、#-(CH ２ ) １ -O-(CH ２ ) ９ -、#-(CH ２ ) １ -O-(CH ２ ) １０ -、#-(CH ２ ) ２ -O-(CH ２ ) １ -、#-(CH ２ ) ２ -O-(CH ２ ) ２ -、#-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -O-(CH ２ ) ４ -、#-(CH ２ ) ２ -O-(CH ２ ) ５ -、#-(CH ２ ) ２ -O-(CH ２ ) ６ -、#-(CH ２ ) ２ -O-(CH ２ ) ７ -、#-(CH ２ ) ２ -O-(CH ２ ) ８ -、#-(CH ２ ) ２ -O-(CH ２ ) ９ -、#-(CH ２ ) ２ -O-(CH ２ ) １０ -、#-(CH ２ ) ２ -O-(CH ２ ) １１ -、#-(CH ２ ) ２ -O-(CH ２ ) １２ -、#-(CH ２ ) ３ -O-(CH ２ ) １ -、#-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-(CH ２ ) ３ -O-(CH ２ ) ３ -、#-(CH ２ ) ３ -O-(CH ２ ) ４ -、#-(CH ２ ) ３ -O-(CH ２ ) ５ -、#-(CH ２ ) ３ -O-(CH ２ ) ６ -、#-(CH ２ ) ３ -O-(CH ２ ) ７ -、#-(CH ２ ) ４ -O-(CH ２ ) １ -、#-(CH ２ ) ４ -O-(CH ２ ) ２ -、#-(CH ２ ) ４ -O-(CH ２ ) ３ -、#-(CH ２ ) ４ -O-(CH ２ ) ４ -、#-(CH ２ ) ４ -O-(CH ２ ) ５ -、#-(CH ２ ) ４ -O-(CH ２ ) ６ -、#-(CH ２ ) ５ -O-(CH ２ ) １ -、#-(CH ２ ) ５ -O-(CH ２ ) ２ -、#-(CH ２ ) ５ -O-(CH ２ ) ３ -、#-(CH ２ ) ５ -O-(CH ２ ) ４ -、#-(CH ２ ) ５ -O-(CH ２ ) ５ -、#-(CH ２ ) ６ -O-(CH ２ ) １ -、#-(CH ２ ) ６ -O-(CH ２ ) ２ -、#-(CH ２ ) ６ -O-(CH ２ ) ３ -、#-(CH ２ ) ６ -O-(CH ２ ) ４ -、#-(CH ２ ) ７ -O-(CH ２ ) １ -、#-(CH ２ ) ７ -O-(CH ２ ) ２ -、#-(CH ２ ) ７ -O-(CH ２ ) ３ -、#-(CH ２ ) ８ -O-(CH ２ ) １ -、#-(CH ２ ) ８ -O-(CH ２ ) ２ -、#-CH(CH ３ )-O-(CH ２ ) １ -、#-CH(CH ３ )-O-(CH ２ ) ２ -、#-CH(CH ３ )-O-(CH ２ ) ３ -、#-CH(CH ３ )-O-(CH ２ ) ４ -、#-CH(CH ３ )-O-(CH ２ ) ５ -、#-CH(CH ３ )-O-(CH ２ ) ６ -、#-CH(CH ３ )-O-(CH ２ ) ７ -、#-CH(CH ３ )-O-(CH ２ ) ８ -、#-CH(CH ３ )-O-(CH ２ ) ９ -、#-CH(CH ３ )-O-(CH ２ ) １０ -、#-CH ２ -(O(CH ２ ) ２ ) ２ -、#-CH ２ -(O(CH ２ ) ２ ) ３ -、#-CH ２ -(O(CH ２ ) ２ ) ４ -、#-CH ２ -(O(CH ２ ) ２ ) ５ -、#-CH ２ -(O(CH ２ ) ２ ) ６ -、#-CH ２ -(O(CH ２ ) ２ ) ７ -、#-H ２ -(O(CH ２ ) ２ ) ８ -、#-H ２ -(O(CH ２ ) ２ ) ９ -、#-H ２ -(O(CH ２ ) ２ ) １０ -、#-H ２ -(O(CH ２ ) ２ ) １ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ２ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ３ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ４ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ５ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ６ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ７ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ８ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ９ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) １０ -OCH ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ７ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ８ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ９ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) １０ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ７ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ８ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ９ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) １０ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ７ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ８ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ９ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) １０ -、#-CH ２ -(O(CH ２ ) ３ ) ２ -、#-CH ２ -(O(CH ２ ) ３ ) ３ -、#-CH ２ -(O(CH ２ ) ３ ) ４ -、#-CH ２ -(O(CH ２ ) ３ ) ５ -、#-CH ２ -(O(CH ２ ) ３ ) ６ -、#-CH ２ -(O(CH ２ ) ３ ) ７ -、#-CH ２ -(O(CH ２ ) ３ ) ８ -、#-CH ２ -(O(CH ２ ) ３ ) ９ -、#-CH ２ -(O(CH ２ ) ３ ) １０ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ７ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ８ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ９ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) １０ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ７ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ８ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ９ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) １０ -、#-CH ２ -O-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-CH ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-CH ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-CH ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ４ -、#-CH ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ５ -、#-CH ２ -(O(CH ２ ) ２ ) ６ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ２ -O-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ６ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ３ -O-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ６ -(O(CH ２ ) ３ ) ６ -、#-CH ２ -O-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-CH ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) ２ -、#-CH ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ３ -、#-CH ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ４ -、#-CH ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ５ -、#-CH ２ -(O(CH ２ ) ３ ) ６ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ２ -O-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ６ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ３ -O-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ６ -(O(CH ２ ) ２ ) ６ -、#-CH ２ -O-(CH ２ ) ２ -O-CH ２ -、#-(CH ２ ) ２ -O-(CH ２ ) ２ -O-CH ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -O-(CH ２ ) ３ -、#-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ５ -、#-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ６ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ５ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ６ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ７ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ８ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ９ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) １０ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ５ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ６ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ７ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ８ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ９ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １０ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １１ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １２ -、#-(CH ２ ) ３ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ３ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ３ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ５ -、#-(CH ２ ) ６ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ６ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ６ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ７ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ７ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ７ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ８ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ８ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ８ -N(R ｇ )-(CH ２ ) ３ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) １ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ２ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ３ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ４ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ５ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ６ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ７ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ８ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ９ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) １０ -、#-CH ２ C(O)NHCH ２ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ３ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ４ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ５ -、#-(CH ２ ) ３ C(O)NH(CH ２ ) ３ -、#-(CH ２ ) ３ C(O)NH(CH ２ ) ４ -、#-(CH ２ ) ４ C(O)NH(CH ２ ) ４ -、#-(CH ２ ) ５ C(O)NH(CH ２ ) ５ -、#-(CH ２ ) ６ C(O)NH(CH ２ ) ７ -、#-(CH ２ ) ６ C(O)NH(CH ２ ) ６ -、#-(CH ２ ) ７ C(O)NH(CH ２ ) ７ -、#-(CH ２ ) ８ C(O)NH(CH ２ ) ８ 、U-(CH ２ ) ９ C(O)NH(CH ２ ) ９ -、#-(CH ２ ) １０ C(O)NH(CH ２ ) １０ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -O-(CH ２ ) ２ -、#-CH ２ NHC(O)CH ２ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ２ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ３ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ４ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ５ -、#-(CH ２ ) ３ NHC(O)(CH ２ ) ３ -、#-(CH ２ ) ３ NHC(O)(CH ２ ) ４ -、#-(CH ２ ) ４ NHC(O)(CH ２ ) ４ -、#-(CH ２ ) ５ NHC(O)(CH ２ ) ５ -、#-(CH ２ ) ６ NHC(O)(CH ２ ) ７ -、#-(CH ２ ) ６ NHC(O)(CH ２ ) ６ -、#-(CH ２ ) ７ NHC(O)(CH ２ ) ７ -、#-(CH ２ ) ８ NHC(O)(CH ２ ) ８ 、#-(CH ２ ) ９ NHC(O)(CH ２ ) ９ -、#-(CH ２ ) １０ NHC(O)(CH ２ ) １０ -、#-(CH ２ ) ４ NHC(O)(CH ２ ) ８ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ２ -O-(CH ２ ) ２ -, #- (CH ２ ) ４ NHC(O)CH ２ -, #-CH ２ -piperidinylene-CH ２ -, #-CH ２ -piperidinylene-(CH ２ ) ２ -, #-CH ２ -piperidinylene-(CH ２ ) ３ -, #-CH ２ -piperidinylene-(CH ２ ) ４ -, #-CH ２ -piperidinylene-(CH ２ ) ５ -, #-CH ２ -piperidinylene-(CH ２ ) ６ -, #-CH ２ -piperidinylene-(CH ２ ) ７ -, #-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ３ -piperidinylene-CH ２ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ４ -piperidinylene-CH ２ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ８ -piperidinylene-CH ２ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ８ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ４ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ５ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ６ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ７ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-CH ２ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ５ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ５ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ６ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ６ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ７ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ７ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #-CH ２ -piperazinylene-CH ２ -, #-CH ２ -piperazinylene-(CH ２ ) ２ -, #-CH ２ -piperazinylene-(CH ２ ) ３ -, #-CH ２ -piperazinylene-(CH ２ ) ４ -, #-CH ２ -piperazinylene-(CH ２ ) ５ -, #-CH ２ -piperazinylene-(CH ２ ) ６ -, #-CH ２ -piperazinylene-(CH ２ ) ７ -, #-CH ２ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ３ -piperazinylene-CH ２ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ４ -piperazinylene-CH ２ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ８ -piperazinylene-CH ２ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ７ - or #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ８ represents -; wherein the piperidinylene and the piperazinylene may each independently further contain deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; Each R ｇ are independently H or C １－６ represents alkyl; The symbol # is the base U ２ represents the connection point with; and 10. The compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to claim 8 or 9, wherein n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

15. R ａ is the following group: 【Chemistry 10】 represents; 10. A compound of formula (II) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof according to claim 8 or 9, wherein said group is optionally partially or fully deuterated.

16. The following: 2-(2,6-dioxopiperidin-3-yl)-5-(3-(piperidin-4-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(3-(piperidin-4-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(6-(piperidin-4-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(6-(piperidin-4-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(3-(piperidin-4-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(3-(piperidin-4-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(8-(piperidin-4-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(8-(piperidin-4-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((1R,4R)-5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-((1R,4R)-5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((1S,4S)-5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-((1S,4S)-5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(5-(piperidin-4-ylmethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-6-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-5-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5-difluoro-6-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5,7-trifluoro-6-(4-(piperidin-4-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 5-(2,6-dimethyl-4-(piperidin-4-ylmethyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(2,6-dimethyl-4-(piperidin-4-ylmethyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3,5-dimethyl-4-(piperidin-4-ylmethyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3,5-dimethyl-4-(piperidin-4-ylmethyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(1-(piperidin-4-ylmethyl)piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(1-(piperidin-4-ylmethyl)piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((R)-3-((piperidin-4-ylmethyl)amino)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((S)-3-((piperidin-4-ylmethyl)amino)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(((S)-1-(piperidin-4-ylmethyl)piperidin-3-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(((R)-1-(piperidin-4-ylmethyl)piperidin-3-yl)amino)isoindoline-1,3-dione; 5-(3-(azetidin-3-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-(azetidin-3-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-(azetidin-3-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-(azetidin-3-ylmethyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-(azetidin-3-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-(azetidin-3-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-(azetidin-3-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(8-(piperidin-4-ylmethyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)isoindoline-1,3-dione; 5-(5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((1R,4R)-5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1R,4R)-5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((1S,4S)-5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1S,4S)-5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-(azetidin-3-ylmethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 6-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-(azetidin-3-ylmethyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-(azetidin-3-ylmethyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-(azetidin-3-ylmethyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((R)-3-((azetidin-3-ylmethyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((S)-3-((azetidin-3-ylmethyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-1-(azetidin-3-ylmethyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and 10. The compound of formula (II) of claim 9, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, selected from the group consisting of 5-(((R)-1-(azetidin-3-ylmethyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

17. 1. A compound of formula (III) or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, PBM-R １ -W １ -LIN-ULM Formula (III) Here, PBM-R １ -W １ - represents a targeting moiety capable of binding to a protein, ULM represents a ligand moiety capable of binding to an E3 ubiquitin ligase, LIN is a connecting moiety, and PBM-R １ -W １ - is covalently attached to ULM via the group LIN; ULM represents a structure of the following formula (ULM): 【Chemistry 11】 Formula (ULM) where: A is CO, CH ２ or CD ２ represents; R １ , R ２ , R ３ and R ４ are the same or different and each independently represent hydrogen, deuterium, halogen, or optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy or halogenated C １－６ represents alkyl; (R ｂ ) ｎ The benzene ring of the formula (ULM) is optionally selected from n R ｂ and each R ｂ are the same or different and each independently represent hydrogen, deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C １－６ Alkyl, optionally deuterated C １－６ Alkoxy, halogenated C １－６ Alkyl, C ２－６ Alkenyl, or C ２－６ represents alkynyl; n represents an integer of 0, 1, 2, or 3; U １ and U ２ are the same or different and each independently represent a bond, N(R ｄ ) or O, where R ｄ is H or optionally deuterated C １－６ represents alkyl; R ｃ represents an optionally substituted nitrogen-containing monocyclic heterocyclylene or an optionally substituted nitrogen-containing bridged heterocyclylene; LIN is a bond, an optionally substituted methylene, or an optionally substituted straight or branched chain C ２－３０ alkylene, wherein the straight or branched chain C ２－３０ The alkylene carbon backbone may optionally contain one or more groups R ｅ and / or one or more groups R ｆ or one or more groups R ｅ and R ｆ Any combination of the groups R ｅ , R ｆ or group R ｅ and R ｆ The combination of R ｅ is O, N (R ｇ ), C(O), C(O)O, OC(O), S(O), S(O) ２ , S(O) ２ NH, NHS (O) ２ , C(O)N(R ｇ ), N(R ｇ ) C(O), or N(R ｇ )C(O)N(R ｇ ) wherein each R ｇ are independently H or C １－６ represents alkyl, and the straight or branched C ２－３０ The alkylene carbon backbone may have two or more groups R ｅ When inserted, each group R ｅ are not directly connected to each other; ｆ is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein said cycloalkylene, said arylene, said heterocyclylene, and said heteroarylene are each independently selected from deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ - C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; W １ is represented by the following structural formula: ２ are concatenated, 【Chemistry 12】 Each ring W ２ are the same or different and each independently an optionally substituted nitrogen-containing monocyclic heterocyclylene, an optionally substituted nitrogen-containing bridged heterocyclylene, or an optionally substituted cycloalkylene; and t represents an integer of 1 or 2; and R １ teeth: a bond, —O—, an optionally substituted C １－６ alkylene (e.g., methylene), 【Chemistry 13】 where the symbol *** represents the connection point with W1, and R １ａ is hydrogen or C １－６ alkyl, and R ２ａ is an optionally substituted C １－６ Alkylene or optionally substituted C １－６ alkenylene; or C ６－１０ aryl or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein ６－１０ The aryl and the heteroaryl each optionally have one or more R ３ａ and each R ３ａ are the same or different and each independently represent a halogen, a hydroxy, a cyano, an amino, a nitro group, C １－６ Alkyl, halogenated C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ is alkoxy; wherein one or more hydrogen atoms of the compound of formula (III) are optionally replaced with deuterium atoms; wherein when the compound of formula (III) is not substituted with deuterium, the compound of formula (III) is the following compound: 【Chemistry 14】 Formula (IV-1) In formula (IV-1), R １ represents a bond, W １ represents piperidinylene, LIN represents methylene, R ｃ represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents fluorine, n represents an integer of 1, 2 or 3, and U １ and U ２ are the same or different and each independently represent a bond, NH, or O; or In formula (IV-1), R １ represents a bond, W １ represents piperazinylene, LIN represents methylene, R ｃ represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents fluorine, n represents an integer of 1, 2 or 3, and U １ and U ２ are the same or different and each independently represent a bond, NH, or O; 【Chemistry 15】 Formula (IV-2) In formula (IV-2), R １ represents a bond, W １ represents piperidinylene, LIN represents methylene, R ｃ represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents fluorine, n represents an integer of 1, 2 or 3, and U １ and U ２ are the same or different and each independently represent a bond, NH, or O; or In formula (IV-2), R １ represents a bond, W １ represents piperazinylene, LIN represents methylene, R ｃ represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents fluorine, n represents an integer of 1, 2 or 3, and U １ and U ２ are the same or different and each independently represent a bond, NH, or O; 【Chemistry 16】 Formula (IV-3) In formula (IV-3), R １ is a bond or —O—CH ２ -CH ２ - represents W １ represents piperidinylene, LIN represents methylene, R ｃ represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents hydrogen, and U １ and U ２ are the same or different and each independently represent a bond, NH, or O; or In formula (IV-3), R １ is a bond or —O—CH ２ -CH ２ - represents W １ represents piperazinylene, LIN represents methylene, R ｃ represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents hydrogen, and U １ and U ２ are the same or different and each independently represent a bond, NH, or O; and 【Chemistry 17】 Formula (IV-4) Not including, In formula (IV-4), R １ is a bond or —O—CH ２ -CH ２ - represents W １ represents piperidinylene, LIN represents methylene, R ｃ represents piperazinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents hydrogen, and U １ and U ２ are the same or different and each independently represent a bond, NH, or O; or In formula (IV-4), R １ is a bond or —O—CH ２ -CH ２ - represents W １ represents piperazinylene, LIN represents methylene, R ｃ represents piperidinylene, 2,5-diazabicyclo[2.2.1]heptanylene, 8-azabicyclo[3.2.1]octanylene, or 9-ethyl-3-methyl-3,9-diazabicyclo[3.3.1]nonanylene; R ｂ represents hydrogen, and U １ and U ２ are the same or different and each independently represent a bond, NH or O, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

18. 18. The compound of formula (III) according to claim 17, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein the PBM is a small molecule ligand targeting EGFR, a small molecule ligand targeting CDK4 / 6, a small molecule ligand targeting ALK, a small molecule ligand targeting RET, a small molecule ligand targeting FAK, a small molecule ligand targeting BCR-ABL, a small molecule ligand targeting BTK, a small molecule ligand targeting AR, a small molecule ligand targeting ER or a small molecule ligand targeting BET. (i) The PBM has the following formula: 【Chemistry 18】 and where: (R ２ ) ｐ１ The benzene ring of formula (PBM-1) is p1 R ２ and each R ２ are the same or different and each independently represent a halogen or halogenated C １－６ represents alkyl; (R ３ ) ｐ２ The quinazoline ring of the formula (PBM-1) is p2 R ３ represents a group substituted with a substituent, and each R ３ are the same or different and each independently represent C １－１０ Alkyl, deuterated C １－１０ Alkyl, C １－１０ Alkoxy, heterocyclyloxy, or —NHC(O)R ４ where R ４ is C １－１０ Alkyl or C ２－１０ alkenyl, for example, R ３ is methyl, methoxy, 【Chemistry 19】 represents; p1 represents an integer of 1, 2, 3, 4, or 5; p2 represents an integer of 1, 2 or 3; (R ５ ) ｐ３ The benzene ring of formula (PBM-2) is p3 R ５ and each R ５ are the same or different and each independently represent C １－１０ Alkyl, deuterated C １－１０ Alkyl, C １－１０ Alkoxy or -NHC(O)R ４ where R ４ is C １－１０ Alkyl, deuterated C １－１０ Alkyl or C ２－１０ alkenyl, for example, R ５ is methyl, methoxy or 【Chemistry 20】 represents; p3 represents an integer of 1, 2, 3, or 4; (R ６ ) ｐ４ The 1H-indole ring of the formula (PBM-2) is p4 R ６ , each R ６ are the same or different and each independently represent C １－１０ Alkyl or deuterated C １－１０ represents alkyl; p4 represents an integer of 0, 1, 2 or 3; (R ７ ) ｐ５ The benzene ring of formula (PBM-3) has p5 R ７ and each R ７ are the same or different and each independently represent halogen, hydroxy, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, NO ２ , N.H. ２ or cyano, p5 represents an integer of 2, 3, 4, or 5; R ８ is C ６－１０ aryl or heteroaryl containing one or two 5- to 7-membered rings and 1 to 4 heteroatoms selected from the group consisting of N, O and S, wherein ６－１０ The aryl and the heteroaryl each optionally have one or more R ４ａ and each R ４ａ are the same or different and each independently represent a halogen, a hydroxy, a cyano, an amino, a nitro group, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ is alkoxy; R ９ is C １－１０ Alkyl (e.g. 【change】 ) or deuterated C １－１０ represents alkyl; R １０ teeth 【Chemical 21】 where (R ５ａ ) ｐ６ The piperidine ring of R 10 has p6 R ５ａ and each R ５ａ are the same or different and each independently represent deuterium, halogen, hydroxy, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy, deuterated C １－６ Alkoxy, NO ２ , N.H. ２ or cyano, and p6 represents an integer of 1, 2, 3, 4, or 5; (R １１ ) ｐ７ The benzene ring and the pyridine ring of formula (PBM-5) each optionally have p7 R １１ and each R １１ are the same or different and each independently represent a halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ alkyl, and p7 represents an integer of 0, 1, 2, or 3; Ring A of formula (PBM-6) is C ６－１０ aryl, or a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, wherein the ring A is one or more R ６ａ and each R ６ａ are the same or different and each independently represent a deuterium, a halogen, a hydroxyl, a cyano, an amino, a nitro group, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkoxy, C ２－６ Alkenyl, or C ２－６ is alkynyl; Ring B of formula (PBM-6) is C ３－１５ cycloalkyl, or a 3- to 20-membered heterocyclyl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein said ring B optionally contains one or more R ７ａ and each R ７ａ are the same or different and each independently represent deuterium, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ is alkoxy; Ring C in formula (PBM-6) represents a 5- to 20-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and said ring C optionally contains one or more R ８ａ and each R ８ａ are the same or different and each independently represent deuterium, halogen, hydroxy, cyano, amino, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ is alkoxy; X in formula (PBM-7) １ is N or CR １２ where R １２ represents hydrogen or a bond, and X ２ represents CH or N; R １３ represents hydrogen or a bond, where R １３ When represents a bond, X １ represents N or CH, and R １３ The ring constituent atom N connected to R １ or R １３ is hydrogen, X １ is CR １２ where R １２ represents a bond, and R １２ The ring constituent atom C connected to R １ connected to; R １４ is —O-aryl, —O-heteroaryl, —C １－３ alkylene-NHC(O)-heteroaryl, or -C １－３ alkylene-C(O)NH-heteroaryl, wherein the aryl and heteroaryl are each independently optionally selected from one or more R ９ａ and each R ９ａ are the same or different and each independently represent deuterium, halogen, hydroxy, cyano, amino, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy or halogenated C １－６ is alkoxy; R １５ are deuterium, hydrogen, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl or -NHC(O)R １７ where R １７ is C １－１０ Alkyl or C ２－１０ alkenyl, for example, R １５ is hydrogen, methyl, or 【Chemical 22】 represents; R １６ represents hydrogen, cyano, or amino group; X in formula (PBM-8) ３ is CR ２１ or fragment 【Chemical 23】 where the symbol ## represents X ３ and the adjacent N, and the symbol ### represents the connection point of X ４ represents the connection point with, and R ２１ are deuterium, hydrogen, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, —C(O)—C １－６ Alkyl, —C(O)-deuterated C １－６ Alkyl or —C(O)NR ２２ R ２３ where R ２２ , R ２３ are the same or different and each independently represent hydrogen, C １－６ Alkyl or deuterated C １－６ represents alkyl, and R ２２ , R ２３ is not simultaneously hydrogen; X in formula (PBM-8) ４ is N or CR ２４ where R ２４ are hydrogen, deuterium, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; X ５ and X ６ each independently represents CH or N; R １８ represents a bond or an optionally substituted heteroarylene (e.g., halogen-substituted heteroarylene); R １９ is hydrogen, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ alkyl, or optionally substituted C ３－７ represents cycloalkyl; R ２０ and R ２５ are the same or different and each independently represent hydrogen, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R ２６ is hydrogen, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; R ２７ is hydrogen, cyano, halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; (R ２８ ) ｐ８ The benzene ring of formula (PBM-10) is p8 R ２８ and each R ２８ are the same or different and each independently represent halogen, C １－６ Alkyl, halogenated C １－６ Alkyl or deuterated C １－６ represents alkyl; p8 represents an integer of 1, 2, 3, or 4; R ２９ is NR ３０ R ３１ where R ３０ , R ３１ are the same or different and each independently represent hydrogen, C １－６ Alkyl or deuterated C １－６ represents alkyl; X in formula (PBM-11) ７ , X ８ and X ９ are the same or different and each independently represent N or CH; (R ３２ ) ｐ９ is the X in formula (PBM-11). ８ and X ９ A six-membered ring containing p9 R ３２ and each R ３２ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p9 represents an integer of 0, 1, 2, 3, or 4; R ３３ is halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; R ３４ -C(O)NHR ３５ , -NHC(O)-R ３５ , -S(O) ２ NHR ３５ , -S(O) ２ R ３５ or -P(O)(R ３５ ) ２ where each R ３５ are the same or different and each independently represent C １－６ Alkyl or deuterated C １－６ represents alkyl; (R ３６ ) ｐ１０ The benzene ring of formula (PBM-12) may optionally be p10 R ３６ and each R ３６ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p10 represents an integer of 0, 1, 2, 3 or 4; (R ３７ ) ｐ１１ The benzene ring of formula (PBM-13) is p11 R ３７ and each R ３７ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p11 represents an integer of 0, 1, 2, 3, or 4; (R ３８ ) ｐ１２ The benzene ring of formula (PBM-14) is p12 R ３８ and each R ３８ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p12 represents an integer of 0, 1, 2, 3, or 4; (R ３９ ) ｐ１３ The 4-oxo-3,4-dihydroquinazoline ring of formula (PBM-14) is ３９ and each R ３９ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p13 represents an integer of 1, 2, 3, or 4; (R ４０ ) ｐ１４ The benzene ring of formula (PBM-15) is p14 R ４０ and each R ４０ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p14 represents an integer of 1, 2, 3, or 4; R ４１ is halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; (R ４２ ) ｐ１５ The quinoline ring of the formula (PBM-16) is p15 R ４２ and each R ４２ are the same or different and each independently represent a halogen, a cyano, or C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p15 represents an integer of 2, 3, or 4; (R ４３ ) ｐ１６ The benzene ring of formula (PBM-16) is p16 R ４３ and each R ４３ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p16 represents an integer of 3 or 4; (R ４４ ) ｐ１７ The benzene ring, pyrimidine ring, and pyridine ring of formula (PBM-17) each have p17 R ４４ and each R ４４ are the same or different and each independently represent halogen, C １－６ Alkoxy, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p17 represents an integer of 0, 1, 2, 3, or 4; R ４５ , R ４６ , R ４７ and R ４８ One of them represents a bond, and the remaining three are the same or different and each independently represent hydrogen, halogen, or hydroxy, where R ４５ , R ４６ , R ４７ and R ４８ When one of them represents a bond, the benzene ring or methylene in formula (PBM-18) connected by the bond is R １ directly connected to; In formula (PBM-18), the symbol " " connecting the double bond may be a bond of any spatial configuration (cis or trans); (R ４９ ) ｐ１８ The 1,2,3,4-tetrahydronaphthalene ring of formula (PBM-19) has p18 R ４９ and each R ４９ are the same or different and each independently represent hydrogen, hydroxy, halogen, C １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl; p18 represents an integer of 0, 1, 2, 3, or 4; and R ５０ and R ５１ One of them represents a bond, and the other represents hydrogen, halogen, or C. １－６ Alkyl, deuterated C １－６ Alkyl or halogenated C １－６ represents alkyl, where R ５０ and R ５１ When one of them represents a bond, the benzene ring in formula (PBM-19) connected by the bond is R １ and / or (ii) said R 1 is a structure of the following formula: a bond, —O—, optionally substituted C 1-6 alkylene (for example, methylene, ethylene, propylene, isopropylidene, butylene, tert-butylene, pentylene, and hexylene), —N(R 1a )—R 2a -*** (for example, —N(CH 3 )—CH 2 CH 2 -***, —NH—CH 2 CH 2 -***), —O—R 2a -*** (for example, —O—(CH 2 ) 3 -***, —O—CH 2 -***, and —O—(CH 2 ) 2 -***), —C(O)NH—R 2a -*** (for example, —C(O)NH—(CH 2 ) 2 -***, —C(O)NH—(CH 2 ) 3 -***, -C(O)NH-CH=CH-CH 2 -***, and -C(O)NH-CH 2 -CH=CH-CH 2 -***, or -NHC(O)-R 2a -*** (for example, -NHC(O)-CH=CH-CH 2 -***, -NHC(O)-CH 2 -CH=CH-CH 2 -***, -NHC(O)-(CH 2 ) 2 -***, and -NHC(O)-(CH 2 ) 3 -***), where the symbol *** represents the connection point to W1, R 1a is hydrogen or C 1-6 alkyl, and R 2a is optionally substituted C 1-6 alkylene or optionally substituted C 2-6 alkenylene; or phenylene or naphthylene, wherein said phenylene or naphthylene is independently optionally substituted with one or more R 3a , and each R 3a is the same or different and each independently halogen, hydroxy, cyano, amino, nitro group, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, or halogenated C 1-6 alkoxy; or furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]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, each group independently being one or more R 3a , and each R 3a is the same or different and is each independently halogen, hydroxy, cyano, amino, nitro, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, or halogenated C 1-6 alkoxy; and / or (iii) W 1 is represented by the following structural formula, in which t rings W 2 are linked together: 【Chemical 26】 Here, each ring W 2 is the same or different and independently represents one of the following groups: monocyclic C 3-10 heterocyclylenes containing one nitrogen atom and optionally containing heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, such as the following groups: piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene or diazacyclooctylene; or C 5-20 bridged heterocyclylenes containing one nitrogen atom and optionally containing heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, such as the following groups: azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene or diazabicyclo[2.2.2]octanylene, such as the following groups: 【Chemical 27】 or C 3-15 cycloalkylene (for example the following groups: cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, C 5-15 spirocycloalkylene, adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, or biscyclo[2.2.1]heptenylene); and wherein the monocyclic C 3-10 heterocyclylene, the C 5-20 bridged heterocyclylene and the C 3-15 cycloalkylene are each independently optionally substituted with one or more substituents selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH—, or any combination thereof; and t represents an integer of 1 or 2, and / or (iv) The ULM has a structure of the following formula (ULM-1), (ULM-2), (ULM-3), (ULM-4), (ULM-5), (ULM-6), (ULM-7), (ULM-8), (ULM-9), or (ULM-10): 【Chemistry 30】 represents; where: A represents CO, CH 2 or CD 2 ; R 1 , R 2 , R 3 and R 4 are the same or different and each independently represent hydrogen, deuterium, halogen, optionally deuterated C 1-6 alkyl, optionally deuterated C 1-6 alkoxy, or halogenated C 1-6 alkyl; (R b ) n represents that the benzene ring is optionally substituted with n R b s, and each R b is the same or different and independently represents hydrogen, deuterium, halogen, hydroxy, mercapto, nitro, amino, cyano, optionally deuterated C 1-6 alkyl, optionally deuterated C 1-6 alkoxy, halogenated C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl; n represents an integer of 0, 1, 2, or 3; U 1 and U 2 are the same or different and each independently represent a bond, N(R d ) or O, where R d represents H or optionally deuterated C 1-6 alkyl; R c represents an optionally substituted monocyclic C 3-10 heterocyclylene containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, such as the following groups: piperidinylene, piperazinylene, morpholinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, oxazolidinylene, thiazolidinylene, thiomorpholinylene, azepanylene, diazacycloheptanylene, azacyclooctylene or diazacyclooctylene; or R c represents an optionally substituted C 5-20 bridged heterocyclylene containing one nitrogen atom and optionally containing a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, such as the following groups: azabicyclo[3.1.1]heptanylene, azabicyclo[2.2.1]heptanylene, azabicyclo[3.2.1]octanylene, azabicyclo[2.2.2]octanylene, diazabicyclo[3.1.1]heptanylene, diazabicyclo[2.2.1]heptanylene, diazabicyclo[3.2.1]octanylene or diazabicyclo[2.2.2]octanylene, such as the following groups: 【Chemical Formula 31】 represents wherein the monocyclic C 3-10 heterocyclylene and the C 5-20 bridged heterocyclylene are each independently further optionally substituted with one or more substituents selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH— or any combination thereof; and / or (v) said LIN has the following formula: #-C 1-30 alkylene-; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -(R e (C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -(R f (C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(R e -R f -(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(R e (C(R a3 )(R a4 )) n2 ) m1 -(R f (C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(R f -R e -(C(R a3 )(R a4 )) n2 ) m1 -; or #-(C(R a1 )(R a2 )) n1 -(R f (C(R a3 )(R a4 )) n2 ) m1 -(R e (C(R a5 )(R a6 )) n3 ) m2 -; wherein each group R e is selected from the group consisting of O, N(R g ), C(O), C(O)O, OC(O), S(O), S(O) 2 , S(O) 2 NH, NHS(O) 2 , C(O)N(R g ), N(R g )C(O), or N(R g )C(O)N(R g ), wherein each R g independently represents H or C 1-6 alkyl; each group R f is selected from the group consisting of cycloalkylene, arylene, heterocyclylene, heteroarylene, alkynylene, alkenylene, or any combination thereof, wherein said cycloalkylene, said arylene, said heterocyclylene, and said heteroarylene may, independently of one another, further comprise deuterium, optionally deuterated C 1-6 alkyl, optionally deuterated C 3-6 alkyl, or optionally deuterated C 6 alkyl. optionally substituted with a substituent selected from the group consisting of cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, halogenated C 1-6 alkyl, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH—, cyano, or any combination thereof; one or more hydrogen atoms of CH 2 of said C 1-30 alkylene are optionally further substituted with a substituent selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH—, or any combination thereof; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 and R a8 are each independently optionally substituted with a substituent selected from the group consisting of H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH—, or any combination thereof; The symbol # represents the point of attachment to the group U 2 ; and 18. The compound of formula (III) of claim 17, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of the integers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. (i) the PBM has the structure of the following formula: 【Chemistry 24】 【Chemistry 25】 and / or (ii) W 1 is the following group: 【Chemical 28】 represents wherein said group is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, cyano, amino, C 1-6 alkyl, halogenated C 1-6 alkyl, deuterated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, deuterated C 1-6 alkoxy, or any combination thereof; and / or (iii) R 1 -W 1 is one of the following groups: 【Chemical 29】 represents wherein said group is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, cyano, amino, C 1-6 alkyl, halogenated C 1-6 alkyl, deuterated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, deuterated C 1-6 alkoxy, or any combination thereof; and / or (iv) The R c is one of the following groups: 【Chemical Formula 32】 【Chemical 33】 represents; where the symbol * denotes the point of attachment to the group U 1 and / or (v) said LIN has the structure of the following formula: #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -(O(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(O(C(R a3 )(R a4 )) n2 ) m1 -(O(C(R a5 )(R a6 )) n3 ) m2 -(O(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -(N(R g )(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )(C(R a3 )(R a4 )) n2 ) m1 -(N(R g )(C(R a5 )(R a6 )) n3 ) m2 -(N(R g )(C(R a7 )(R a8 )) n4) m3 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(C(O)N(R g )-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(C(O)N(R g )-(C(R a5 )(R a6 )) n3 ) m2 -(C(O)N(R g )-(C(R a7 )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -(C(O)N(R g )-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -C(O)N(R g )-(C(R a3 )(R a4 )) n2 -(O(C(R a5 )(R a6 )) n3 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(N(R g )C(O)-(C(R a3 )(R a4 )) n2 ) m1 -(O-(C(R a5 )(R a6 )) n3 ) m2 -(O-(C(R g )(R a8 )) n4 ) m3 -; #-(C(R a1 )(R a2 )) n1 -N(R g )C(O)-(C(R a3 )(R a4 )) n2 -(O(C(R a5 )(R a6 )) n3 ) m1 -; #-(C(R a1 )(R a2 )) n1 -N(R g )C(O)N(R g )-(C(R a3 )(R a4 )) n2 -; #-(C(R a1 )(R a2 )) n1 -C(O)-(C(R a3 )(R a4 )) n2 -; #-(C(R a1 )(R a2 )) n1 -(アリーレン-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(アリーレン-(C(R a3 )(R a4 )) n2 ) m1 -アリーレン-(C(R a5 )(R a6 )) n3 -; #-(C(R a1 )(R a2 )) n1 -(heterocyclylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(heterocyclylene-(C(R a3 )(R a4 )) n2 ) m1 -(heterocyclylene-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(heteroarylene-(C(R a3 )(R a4 )) n2 ) m1 -; #-(C(R a1 )(R a2 )) n1 -(heteroarylene-(C(R a3 )(R a4 )) n2 ) m1 -(heteroarylene-(C(R a5 )(R a6 )) n3 ) m2 -; #-(C(R a1 )(R a2 )) n1 -(cycloalkylene-(C(R a3 )(R a4 )) n2 ) m1 -; or #-(C(R a1 )(R a2 )) n1 -(cycloalkylene-(C(R a3 )(R a4 )) n2 ) m1 -(cycloalkylene-(C(R a5 )(R a6 )) n3 ) m2 -; wherein each R g independently represents H or C 1-6 alkyl; The cycloalkylene, the arylene, the heterocyclylene and the heteroarylene are each independently optionally substituted with a substituent selected from the group consisting of deuterium, optionally deuterated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, hydroxy, amino, mercapto, halogen, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, halogenated C 1-6 alkyl, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH—, cyano or any combination thereof; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 and R a8 each independently represent H, deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, optionally deuterated C 1-6 alkyl, halogenated C 1-6 alkyl, optionally deuterated C 3-6 cycloalkyl, optionally deuterated C 1-6 alkoxy, optionally deuterated C 1-6 alkyl-NH—, NH 2 —C 1-6 alkylene, optionally deuterated C 1-6 alkyl-NHC(O)—, optionally deuterated C 1-6 alkyl-C(O)NH— or any combination thereof; The symbol # represents the point of attachment to the group U 2 ; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of integers of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15; 18. A compound of formula (III) according to claim 17 or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof. (i) The ULM has a structure of the following formula (ULM-11), (ULM-12), (ULM-13), (ULM-14), (ULM-15), (ULM-16), (ULM-17), (ULM-18), (ULM-19), (ULM-20), (ULM-21), or (ULM-22): 【Chemical Formula 34】 represents; Here, the A, (R ｂ ) ｎ , R ｂ , R ｃ , U １ , U ２ is as defined in claim 17, or (ii) said LIN is the following group: #-CH ２ -, #-(CH ２ ) ２ -, #-(CH ２ ) ３ -, #-(CH ２ ) ４ -, #-(CH ２ ) ５ -, #-(CH ２ ) ６ -, #-(CH ２ ) ７ -, #-(CH ２ ) ８ -, #-(CH ２ ) ９ -, #-(CH ２ ) １０ -, #-(CH ２ ) １１ -, #-(CH ２ ) １２ -, #-(CH ２ ) １３ -, #-(CH ２ ) １４ -, #-(CH ２ ) １５ -, #-(CH ２ ) １６ -, #-(CH ２ ) １７ -, #-(CH ２ ) １８ -, #-(CH ２ ) １９ -, #-(CH ２ ) ２０ -, #-(CH ２ ) ２１ -, #-(CH ２ ) ２２ -, #-(CH ２ ) ２５ -, or #-(CH ２ ) ３０ -; #-CH ２ -O-CH ２ -, #-CH ２ -O-(CH ２ ) ２ -, #-(CH ２ ) １ -O-(CH ２ ) ３ -, #-(CH ２ ) １ -O-(CH ２ ) ４ -、#-(CH ２ ) １ -O-(CH ２ ) ５ -、#-(CH ２ ) １ -O-(CH ２ ) ６ -、#-(CH ２ ) １ -O-(CH ２ ) ７ -、#-(CH ２ ) １ -O-(CH ２ ) ８ -、#-(CH ２ ) １ -O-(CH ２ ) ９ -、#-(CH ２ ) １ -O-(CH ２ ) １０ -、#-(CH ２ ) ２ -O-(CH ２ ) １ -、#-(CH ２ ) ２ -O-(CH ２ ) ２ -、#-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -O-(CH ２ ) ４ -、#-(CH ２ ) ２ -O-(CH ２ ) ５ -、#-(CH ２ ) ２ -O-(CH ２ ) ６ -、#-(CH ２ ) ２ -O-(CH ２ ) ７ -、#-(CH ２ ) ２ -O-(CH ２ ) ８ -、#-(CH ２ ) ２ -O-(CH ２ ) ９ -、#-(CH ２ ) ２ -O-(CH ２ ) １０ -、#-(CH ２ ) ２ -O-(CH ２ ) １１ -、#-(CH ２ ) ２ -O-(CH ２ ) １２ -、#-(CH ２ ) ３ -O-(CH ２ ) １ -、#-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-(CH ２ ) ３ -O-(CH ２ ) ３ -、#-(CH ２ ) ３ -O-(CH ２ ) ４ -、#-(CH ２ ) ３ -O-(CH ２ ) ５ -、#-(CH ２ ) ３ -O-(CH ２ ) ６ -、#-(CH ２ ) ３ -O-(CH ２ ) ７ -、#-(CH ２ ) ４ -O-(CH ２ ) １ -、#-(CH ２ ) ４ -O-(CH ２ ) ２ -、#-(CH ２ ) ４ -O-(CH ２ ) ３ -、#-(CH ２ ) ４ -O-(CH ２ ) ４ -、#-(CH ２ ) ４ -O-(CH ２ ) ５ -、#-(CH ２ ) ４ -O-(CH ２ ) ６ -、#-(CH ２ ) ５ -O-(CH ２ ) １ -、#-(CH ２ ) ５ -O-(CH ２ ) ２ -、#-(CH ２ ) ５ -O-(CH ２ ) ３ -、#-(CH ２ ) ５ -O-(CH ２ ) ４ -、#-(CH ２ ) ５ -O-(CH ２ ) ５ -、#-(CH ２ ) ６ -O-(CH ２ ) １ -、#-(CH ２ ) ６ -O-(CH ２ ) ２ -、#-(CH ２ ) ６ -O-(CH ２ ) ３ -、#-(CH ２ ) ６ -O-(CH ２ ) ４ -、#-(CH ２ ) ７ -O-(CH ２ ) １ -、#-(CH ２ ) ７ -O-(CH ２ ) ２ -、#-(CH ２ ) ７ -O-(CH ２ ) ３ -、#-(CH ２ ) ８ -O-(CH ２ ) １ -、#-(CH ２ ) ８ -O-(CH ２ ) ２ -、#-CH(CH ３ )-O-(CH ２ ) １ -、#-CH(CH ３ )-O-(CH ２ ) ２ -、#-CH(CH ３ )-O-(CH ２ ) ３ -、#-CH(CH ３ )-O-(CH ２ ) ４ -、#-CH(CH ３ )-O-(CH ２ ) ５ -、#-CH(CH ３ )-O-(CH ２ ) ６ -、#-CH(CH ３ )-O-(CH ２ ) ７ -、#-CH(CH ３ )-O-(CH ２ ) ８ -、#-CH(CH ３ )-O-(CH ２ ) ９ -、#-CH(CH ３ )-O-(CH ２ ) １０ -、#-CH ２ -(O(CH ２ ) ２ ) ２ -、#-CH ２ -(O(CH ２ ) ２ ) ３ -、#-CH ２ -(O(CH ２ ) ２ ) ４ -、#-CH ２ -(O(CH ２ ) ２ ) ５ -、#-CH ２ -(O(CH ２ ) ２ ) ６ -、#-CH ２ -(O(CH ２ ) ２ ) ７ -、#-H ２ -(O(CH ２ ) ２ ) ８ -、#-H ２ -(O(CH ２ ) ２ ) ９ -、#-H ２ -(O(CH ２ ) ２ ) １０ -、#-H ２ -(O(CH ２ ) ２ ) １ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ２ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ３ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ４ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ５ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ６ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ７ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ８ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) ９ -OCH ２ -、#-H ２ -(O(CH ２ ) ２ ) １０ -OCH ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ７ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ８ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ９ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) １０ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ７ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ８ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ９ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) １０ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ７ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ８ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) ９ -、#-(CH ２ ) ４ -(O(CH ２ ) ２ ) １０ -、#-CH ２ -(O(CH ２ ) ３ ) ２ -、#-CH ２ -(O(CH ２ ) ３ ) ３ -、#-CH ２ -(O(CH ２ ) ３ ) ４ -、#-CH ２ -(O(CH ２ ) ３ ) ５ -、#-CH ２ -(O(CH ２ ) ３ ) ６ -、#-CH ２ -(O(CH ２ ) ３ ) ７ -、#-CH ２ -(O(CH ２ ) ３ ) ８ -、#-CH ２ -(O(CH ２ ) ３ ) ９ -、#-CH ２ -(O(CH ２ ) ３ ) １０ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ７ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ８ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ９ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) １０ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ７ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ８ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ９ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) １０ -、#-CH ２ -O-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-CH ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-CH ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-CH ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ４ -、#-CH ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ５ -、#-CH ２ -(O(CH ２ ) ２ ) ６ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ２ -O-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ６ -(O(CH ２ ) ３ ) ６ -、#-(CH ２ ) ３ -O-(CH ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ２ -(O(CH ２ ) ３ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ３ -(O(CH ２ ) ３ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ４ -(O(CH ２ ) ３ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ５ -(O(CH ２ ) ３ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ２ ) ６ -(O(CH ２ ) ３ ) ６ -、#-CH ２ -O-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-CH ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) ２ -、#-CH ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ３ -、#-CH ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ４ -、#-CH ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ５ -、#-CH ２ -(O(CH ２ ) ３ ) ６ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ２ -O-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ２ -(O(CH ２ ) ３ ) ６ -(O(CH ２ ) ２ ) ６ -、#-(CH ２ ) ３ -O-(CH ２ ) ３ -O-(CH ２ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ２ -(O(CH ２ ) ２ ) ２ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ３ -(O(CH ２ ) ２ ) ３ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ４ -(O(CH ２ ) ２ ) ４ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ５ -(O(CH ２ ) ２ ) ５ -、#-(CH ２ ) ３ -(O(CH ２ ) ３ ) ６ -(O(CH ２ ) ２ ) ６ -、#-CH ２ -O-(CH ２ ) ２ -O-CH ２ -、#-(CH ２ ) ２ -O-(CH ２ ) ２ -O-CH ２ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ３ -O-(CH ２ ) ３ -、#-(CH ２ ) ２ -(O(CH ２ ) ２ ) ４ -O-(CH ２ ) ３ -、#-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ５ -、#-(CH ２ ) ５ -(O(CH ２ ) ２ ) ２ -O-(CH ２ ) ６ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ５ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ６ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ７ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ８ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) ９ -、#-(CH ２ ) １ -N(R ｇ )-(CH ２ ) １０ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ５ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ６ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ７ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ８ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) ９ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １０ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １１ -、#-(CH ２ ) ２ -N(R ｇ )-(CH ２ ) １２ -、#-(CH ２ ) ３ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ３ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ３ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ４ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ４ -、#-(CH ２ ) ５ -N(R ｇ )-(CH ２ ) ５ -、#-(CH ２ ) ６ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ６ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ６ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ７ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ７ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ７ -N(R ｇ )-(CH ２ ) ３ -、#-(CH ２ ) ８ -N(R ｇ )-(CH ２ ) １ -、#-(CH ２ ) ８ -N(R ｇ )-(CH ２ ) ２ -、#-(CH ２ ) ８ -N(R ｇ )-(CH ２ ) ３ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) １ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ２ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ３ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ４ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ５ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ６ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ７ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ８ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) ９ -、#-CH(CH ３ )-N(R ｇ )-(CH ２ ) １０ -、#-CH ２ C(O)NHCH ２ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ３ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ４ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ５ -、#-(CH ２ ) ３ C(O)NH(CH ２ ) ３ -、#-(CH ２ ) ３ C(O)NH(CH ２ ) ４ -、#-(CH ２ ) ４ C(O)NH(CH ２ ) ４ -、#-(CH ２ ) ５ C(O)NH(CH ２ ) ５ -、#-(CH ２ ) ６ C(O)NH(CH ２ ) ７ -、#-(CH ２ ) ６ C(O)NH(CH ２ ) ６ -、#-(CH ２ ) ７ C(O)NH(CH ２ ) ７ -、#-(CH ２ ) ８ C(O)NH(CH ２ ) ８ 、U-(CH ２ ) ９ C(O)NH(CH ２ ) ９ -、#-(CH ２ ) １０ C(O)NH(CH ２ ) １０ -、#-(CH ２ ) ２ C(O)NH(CH ２ ) ２ -O-(CH ２ ) ２ -、#-CH ２ NHC(O)CH ２ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ２ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ３ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ４ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ５ -、#-(CH ２ ) ３ NHC(O)(CH ２ ) ３ -、#-(CH ２ ) ３ NHC(O)(CH ２ ) ４ -、#-(CH ２ ) ４ NHC(O)(CH ２ ) ４ -、#-(CH ２ ) ５ NHC(O)(CH ２ ) ５ -、#-(CH ２ ) ６ NHC(O)(CH ２ ) ７ -、#-(CH ２ ) ６ NHC(O)(CH ２ ) ６ -、#-(CH ２ ) ７ NHC(O)(CH ２ ) ７ -、#-(CH ２ ) ８ NHC(O)(CH ２ ) ８ 、#-(CH ２ ) ９ NHC(O)(CH ２ ) ９ -、#-(CH ２ ) １０ NHC(O)(CH ２ ) １０ -、#-(CH ２ ) ４ NHC(O)(CH ２ ) ８ -、#-(CH ２ ) ２ NHC(O)(CH ２ ) ２ -O-(CH ２ ) ２ -, #- (CH ２ ) ４ NHC(O)CH ２ -, #-CH ２ -piperidinylene-CH ２ -, #-CH ２ -piperidinylene-(CH ２ ) ２ -, #-CH ２ -piperidinylene-(CH ２ ) ３ -, #-CH ２ -piperidinylene-(CH ２ ) ４ -, #-CH ２ -piperidinylene-(CH ２ ) ５ -, #-CH ２ -piperidinylene-(CH ２ ) ６ -, #-CH ２ -piperidinylene-(CH ２ ) ７ -, #-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ３ -piperidinylene-CH ２ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ３ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ４ -piperidinylene-CH ２ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ４ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ５ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ６ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) １ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ７ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ８ -piperidinylene-CH ２ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ８ -piperidinylene-(CH ２ ) ８ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ４ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ５ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ６ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ７ -, #-CH ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-CH ２ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ２ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ３ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ４ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ５ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ６ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ７ -, #-CH ２ -N(R ｇ )-(CH ２ ) ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ２ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ３ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ４ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ５ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ５ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ６ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ６ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ７ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ７ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-CH ２ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ２ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ３ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ４ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ５ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ６ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ７ -, #- (CH ２ ) ８ -N(R ｇ )-CH ２ -piperidinylene-(CH ２ ) ８ -, #-CH ２ -piperazinylene-CH ２ -, #-CH ２ -piperazinylene-(CH ２ ) ２ -, #-CH ２ -piperazinylene-(CH ２ ) ３ -, #-CH ２ -piperazinylene-(CH ２ ) ４ -, #-CH ２ -piperazinylene-(CH ２ ) ５ -, #-CH ２ -piperazinylene-(CH ２ ) ６ -, #-CH ２ -piperazinylene-(CH ２ ) ７ -, #-CH ２ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ２ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ３ -piperazinylene-CH ２ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ３ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ４ -piperazinylene-CH ２ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ４ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ５ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ７ -, #- (CH ２ ) ６ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) １ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ７ -piperazinylene-(CH ２ ) ８ -, #- (CH ２ ) ８ -piperazinylene-CH ２ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ２ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ３ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ４ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ５ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ６ -, #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ７ - or #- (CH ２ ) ８ -piperazinylene-(CH ２ ) ８ represents -; wherein the piperidinylene and the piperazinylene may each independently further contain deuterium, optionally deuterated C １－６ Alkyl, optionally deuterated C ３－６ Cycloalkyl, hydroxy, amino, mercapto group, halogen, optionally deuterated C １－６ Alkoxy, optionally deuterated C １－６ Alkyl-NH-, halogenated C １－６ Alkyl, NH ２ -C １－６ Alkylene, optionally deuterated C １－６ Alkyl-NHC(O)-, optionally deuterated C １－６ optionally substituted with a substituent selected from the group consisting of alkyl-C(O)NH—, cyano, or any combination thereof; Each R ｇ are independently H or C １－６ represents alkyl; The symbol # is the base U ２ represents the connection point with; and n1, n2, n3, n4, m1, m2, and m3 are each independently selected from the group consisting of integers of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15; 18. A compound of formula (III) according to claim 17 or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof.

22. The ULM has the structure of the following formula: 【Chemical 35】 【Chemical 36】 【Chemical 37】 【Chemical Formula 38】 【Chemical 39】 【Chemistry 40】 【Chemistry 41】 18. The compound of formula (III) of claim 17, wherein:

23. Said -W １ -LIN-U ２ -R ｃ -U １ - is the following group: 【Chemistry 42】 【Chemistry 43】 【Chemical 44】 【Chemistry 45】 represents; wherein the group may further include deuterium, halogen, cyano, amino, C １－６ Alkyl, halogenated C １－６ Alkyl, deuterated C １－６ Alkyl, C １－６ Alkoxy, halogenated C １－６ Alkoxy, deuterated C １－６ 18. The compound of formula (III) of claim 17, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, optionally substituted with one or more substituents selected from the group consisting of alkoxy or any combination thereof.

24. Also, the following formula (III-1), formula (III-2), formula (III-3), formula (III-4), formula (III-5), formula (III-6), formula (III-7), formula (III-8), formula (III-9), formula (III-10), formula (III-11), formula (III-12), formula (III-13), formula (III-14), formula (III-15), formula (III-16), formula (III-17), formula (III-18), formula (III-19), formula (III-20), formula (III-21), formula (III-22), formula (III-23) or formula (III-24) structure: 【Chemistry 46】 【Chemistry 47】 【Chemistry 48】 Also represented by Here, A and R １ , R ２ , R ３ , R ４ , (R ｂ ) ｎ , U １、 U ２ , R ｃ , LIN,W. １ , R １ , (R ２ ) ｐ１ , (R ３ ) ｐ２ , (R ５ ) ｐ３ , (R ６ ) ｐ４ , (R ７ ) ｐ５ , R ８ , R ９ , R １０ , (R １１ ) ｐ７ , ring A, ring B, ring C, X １ , X ２ , R １４ , R １５ , R １６ , X ３ , X ４ , X ５ , X ６ , R １８ , R １９ , R ２０ , R ２５ , R ２６ , R ２７ , (R ２８ ) ｐ８ , R ２９ , X ７ , X ８ , X ９ , (R ３２ ) ｐ９ , R ３３ , R ３４ , (R ３６ ) ｐ１０ , (R ３７ ) ｐ１１ , (R ３８ ) ｐ１２ , (R ３９ ) ｐ１３ , (R ４０ ) ｐ１４ , R ４１ , (R ４２ ) ｐ１５ , (R ４３ ) ｐ１６ , (R ４４ ) ｐ１７ , R ４５ , R ４６ , R ４７ , R ４８ , (R ４９ ) ｐ１８ , R ５０ , R ５１ 20. The compound of formula (III) according to claim 19, or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analogue, pharmaceutical precursor or polymorph thereof, wherein:

25. The following: N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(((1S,4S)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(((1R,4R)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(8-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(3-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyridazine-3-carboxamide; N-((1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(6-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3S)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-(((1S,4S)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3R)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-(((1R,4R)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)nicotinamide; N-((1r,3R)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)nicotinamide; N-((1r,3S)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)nicotinamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-6-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1S,4S)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1S,4S)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1R,4R)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((1R,4R)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((1S,4S)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((1S,4S)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((1R,4R)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((1R,4R)-5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 6-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 6-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-(4-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-((R)-3-(((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3R)-3-(((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((S)-3-(((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((3S)-3-(((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((3S)-1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((R)-1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((3R)-1-((4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-fluorocyclohexyl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((1S,4S)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((1R,4R)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((1S,4S)-5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((1R,4R)-5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 3-(tert-butyl)-N-(4-(5-(4-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)-1H-indazol-3-yl)-2-methylbenzyl)-1,2,4-oxadiazole-5-carboxamide; 2-(2,6-dioxopiperidin-3-yl)-5-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(3-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(3-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(6-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(6-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(3-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(3-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-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-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(8-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((1S,4S)-5-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-((1S,4S)-5-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((1R,4R)-5-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-((1R,4R)-5-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(5-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(5-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-5-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-fluoro-6-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5-difluoro-6-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-5-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-5-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4,5,7-trifluoro-6-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ ) isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(4-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(1-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(1-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperidin-4-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((R)-3-(((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-((S)-3-(((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(((R)-1-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-5-(((S)-1-((1-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)isoindoline-1,3-dione; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((1R,4R)-5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((1S,4S)-5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((1S,4S)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((1R,4R)-5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-Cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-((5-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 6-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((R)-3-(((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((S)-3-(((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-1-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((R)-1-((1-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 6-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((R)-3-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((S)-3-(((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-1-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((R)-1-((1-(4-((5-chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 6-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((R)-3-(((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((S)-3-(((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-1-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((R)-1-((1-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 6-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((R)-3-(((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((S)-3-(((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-1-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((R)-1-((4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)cyclohexyl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)propoxy)quinazolin-6-yl)acrylamide; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 6-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)cyclohexyl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(6-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(6-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(3-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(3-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(8-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(8-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(5-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(5-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 6-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6-difluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,7-difluoroisoindoline-1,3-dione; 6-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,5-difluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )-2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-2,6-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(4-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)-3,5-dimethylpiperazin-1-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-(1-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(1-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperidin-4-yl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindoline-1,3-dione; 5-((R)-3-(((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-((S)-3-(((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)amino)piperidin-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((S)-1-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 5-(((R)-1-((1-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)piperidin-4-yl)methyl)piperidin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-(2-((2-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((((3R)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-((((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-3-yl)amino)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-(((3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(4-(((3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)piperidin-1-yl)methyl)piperidin-1-yl)but-2-enamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((6-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((8-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((3-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-7-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6,7-difluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-4,6,7-trifluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl-2,2,3,3,5,5,6,6-d ８ )methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-3,5-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxoisoindolin-2-yl)-2-(5-fluoro-2-hydroxyphenyl)-N-(thiazol-2-yl)acetamide; 2-(6-(6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2,6-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)pyridazin-3-yl)-1-oxois...

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