STAT6 protein degrader and pharmaceutical use thereof

Abstract

Disclosed in the present invention are a compound that modulates signal transducer and activator of transcription 6 (STAT6) by means of ubiquitination and / or degradation, and a pharmaceutically acceptable salt thereof, a composition containing the compound, and a method for treating a related disease by means of using the composition.

Description

STAT6 protein degraders and medical uses thereof

[0001] This application claims priority to the Chinese Patent Application No. 2025103065487, filed on March 14, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0002] This application claims priority to the Chinese Patent Application No. 2025103440815, filed on March 23, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0003] This application claims priority to the Chinese Patent Application No. 2025103891059, filed on March 31, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0004] This application claims priority to the Chinese Patent Application No. 2025106129724, filed on May 13, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0005] This application claims priority to the Chinese Patent Application No. 2025108773580, filed on June 27, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0006] This application claims priority to the Chinese Patent Application No. 2025111924938, filed on August 25, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0007] This application claims priority to the Chinese Patent Application No. 2025114239980, filed on September 30, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0008] This application claims priority to the Chinese Patent Application No. 2025117375760, filed on November 25, 2025, and entitled “STAT6 protein degraders and medical uses thereof”, the content of which is incorporated herein by reference in its entirety.

[0009] This application claims priority to Chinese Patent Application No. 2025120429681, filed with the Chinese Patent Office on December 31, 2025, entitled "STAT6 protein degrader and its pharmaceutical use", the entire contents of which are incorporated herein by reference.

[0010] This application claims priority to Chinese Patent Application No. 2026101292160, filed on January 30, 2026, entitled "STAT6 protein degrader and its pharmaceutical use", the entire contents of which are incorporated herein by reference. Technical Field

[0011] This invention relates to the field of pharmaceutical technology, and more specifically to a compound or a pharmaceutically acceptable salt thereof that can regulate signal transduction and transcription activator 6 (STAT6) through ubiquitination and / or degradation, and its use in the prevention or treatment of diseases or conditions mediated by signal transduction and transcription activator 6 (STAT6). Background Technology

[0012] The concept of protein degradation-targeting chimeras (PROTACs) was proposed in 2001 (Proc. Natl. Acad. Sci. USA, 2001, 98, 8584). PROTACs are bifunctional molecules, containing a ligand binding to E3 ubiquitin ligase at one end and a ligand binding to the target protein at the other, linked by a linker unit. This linker unit brings the E3 ligase and target protein very close, leading to polyubiquitination and proteasome degradation of the target protein. PROTACs employ a completely different mechanism of action than small molecule inhibitors. First, the E3 ubiquitin ligase ligand recruits the E3 ubiquitin ligase to the vicinity of the target protein, thereby ubiquitinizing the target protein. The labeled target protein is then degraded by the proteasome system in vivo, thus inhibiting the corresponding protein pathway (Cell Biochem Funct. 2019, 37, 21-30). Compared to traditional small molecule drugs, PROTACs, due to their altered binding mechanism, only require transient binding to the target protein to complete ubiquitin transfer and achieve irreversible degradation of the target protein. Therefore, PROTACs offer the following advantages: 1) stronger degradation and longer-lasting efficacy; 2) higher selectivity for the target protein; and 3) the ability to overcome drug resistance caused by target protein mutations in traditional small molecule inhibitors (Cell Chem. Biol. 2018, 25, 67-77).

[0013] The signal transducers and activators of transcription (STAT) family has six members that can bind to specific phosphorylated tyrosine peptides. STAT6 (Signal Transducer and Activator of Transcription6) is a core member of the STAT protein family, playing a dual role in cell signal transduction and gene transcription regulation. STAT6 consists of approximately 840 amino acids (molecular weight approximately 94 kDa) and contains a highly conserved SH2 domain (Src homology 2 domain), responsible for recognizing phosphorylated tyrosine residues and mediating dimerization and nuclear translocation. Its gene is located on human chromosome 12q13.3 and exists in multiple isoforms (such as STAT6α and STAT6β), with STAT6α being the predominant functional form. It primarily participates in a wide range of physiological and pathological processes, including immune regulation, inflammatory responses, and cell proliferation and differentiation, by mediating downstream signaling pathways of cytokines such as IL-4 and IL-13. In terms of activation mechanism, after IL-4 or IL-13 binds to cell membrane receptors, it induces phosphorylation of STAT6 tyrosine residues (such as the Y641 site) through JAK kinases (such as JAK1 / JAK3). Phosphorylated STAT6 forms a homodimer, translocates to the cell nucleus, and binds to STAT6 response elements (such as GAS sequences) in the promoter regions of target genes, regulating key processes including Th2 cell differentiation, B cell class switching (such as IgE generation), and the release of inflammatory factors.

[0014] In recent years, STAT6 has become a hot topic in drug development due to its core role in various diseases and its potential for targeted therapy. Its abnormal activation or dysregulation is closely related to immune-related diseases. STAT6 is a core regulator of Th2-type immune responses, and its overactivation drives the pathological processes of Th2-type inflammatory diseases such as asthma, atopic dermatitis, and chronic obstructive pulmonary disease (COPD). In rheumatic diseases (such as rheumatoid arthritis), STAT6 promotes autoimmune responses and inflammatory cell infiltration by enhancing the IL-4 / IL-13 signaling pathway. Although the pathological mechanisms of STAT6 are well understood, drug development targeting this target still faces multiple challenges. Summary of the Invention

[0015] Given the central role of STAT6 in diseases and the limitations of existing therapies, this invention focuses on the development of small molecule inhibitors and specific PROTACs. By optimizing SH2 binding affinity and reducing off-target risks, it aims to provide a more efficient and safer STAT6-targeted therapy, filling the gap in current drug development.

[0016] In a first aspect, the present invention provides a compound having the structure shown in formula (I): PTM-L-ULM Formula (I);

[0017] Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein:

[0018] The PTM is a binding site that targets signal transduction and transcription activator 6 (STAT6); preferably, the PTM is as defined in any embodiment of the present invention.

[0019] The ULM is an E3 ubiquitin ligase-binding moiety; preferably, the ULM is the human cerebellar protein (CRBN) E3 ubiquitin ligase-binding moiety; preferably, the ULM is as defined in any embodiment of the present invention; and

[0020] L is the chemical connection portion connecting the ULM and the PTM; preferably, L is as defined in any embodiment of the present invention.

[0021] In some embodiments, the present invention provides a compound of formula (I), wherein the PTM is a binding portion targeting signal transduction and transcriptional activator 6 (STAT6).

[0022] In some embodiments, the present invention provides a compound of formula (I), wherein the structure of the PTM is as shown in formula (1-1):

[0023] Ring A is selected from 8-10 membered bicyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; and 16-20 membered tetracyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; wherein the tricyclic heterocyclic aryl group and the tetracyclic heterocyclic aryl group are fused rings, spirocycles, or spirofused ring structures.

[0024] Ring B is selected from single bonds, 6-10 member monocyclic aryl groups, 8-10 member bicyclic aryl groups, 5-10 member monocyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, 8-10 member bicyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5-10 member monocyclic alkyl groups, saturated or partially unsaturated 5-13 member bicyclic alkyl groups, saturated or partially unsaturated 5-10 member monocyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 5-13 member bicyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the bicyclic alkyl groups and bicyclic heterocyclic groups are bridged rings, spiro rings, or fused ring structures;

[0025] The ring C is absent or selected from 3-10 membered cycloalkyl groups, 3-10 membered monocyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 6-13 membered bicyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 5-10 membered monocyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, and 8-10 membered bicyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, wherein the bicyclic heterocyclic group is a fused ring, spiro ring or bridged ring structure;

[0026] When ring C exists, L c Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X A combination of one or more of C(O), wherein C 3-6 The cycloalkyl group is optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-6 One or more substituents in the alkyl group are substituted;

[0027] When ring C does not exist, L c Selected from C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, -SC 1-6 Alkyl, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -NR X -C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -NR X -C(O)-N(R X )2 and -C(O)-NR X -C 1-6 Alkyl, the C 1-6 Alkyl, C 1-6Heteroalkyl and C 1-6 Alkyl groups are optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-6 One or more substituents in the alkyl group are substituted;

[0028] p1, p2, and p3 are each independently selected from 0, 1, 2, 3, 4, and 5;

[0029] L b Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O);

[0030] R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, -C(O)-C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 heteroaryl groups are optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups;

[0031] R D Selected from R X -OR X -SR X -N(R) X )2、-S(O)R X -S(O)2R X -S(O)N(R) X )2、-S(O)2N(R X )2、-C(O)R X -C(O)OR X -C(O)N(R) X )2、-C(O)N(R X OR X -OC(O)R X -OC(O)N(R) X )2、-NR X C(O)OR X -NR X C(O)R X -NR X C(O)N(R X )2 and -NR X S(O)2R X ;

[0032] R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups are optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 One or more substituents of the haloalkoxy group are substituted;

[0033] When ring B is a saturated or partially unsaturated 5- or 6-membered heterocyclic group, phenylene group, or 5- or 6-membered heteroaryl group containing 1 or 2 independently selected N, O, and S heteroatoms, and ring A is selected from a 9-membered bicyclic heteroaryl group containing 1 to 4 independently selected N, O, and S heteroatoms, the 9-membered bicyclic heteroaryl group is selected from...

[0034] When ring B is L b It is a single bond, and the ring C is At that time, ring A is not

[0035] When ring B is And L b When it is -C(O)-NH-CH2-, ring A is not a bicyclic or tricyclic heterocyclic aryl group or a bicyclic or tricyclic heterocyclic group.

[0036] In some implementation schemes,

[0037] Ring A is selected from 9-10 membered bicyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; and 16-18 membered tetracyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; wherein the tricyclic and tetracyclic heterocyclic aryl groups are fused rings, spirocyclic, or spirofused fused ring structures; preferably, ring A is selected from those containing 1, 2, 3, or... The following are provided: a 9- or 10-membered bicyclic heterocyclic aryl group containing four independently selected N, O, and S heteroatoms; a 13-membered tricyclic heterocyclic aryl group containing one, two, or three independently selected N, O, and S heteroatoms; a 12-, 13-, 14-, or 15-membered tricyclic heterocyclic aryl group containing one, two, or three independently selected N, O, and S heteroatoms; and a 16-, 17-, or 18-membered tetracyclic heterocyclic aryl group containing one, two, three, or four independently selected N, O, and S heteroatoms, wherein the tricyclic and tetracyclic heterocyclic aryl groups are fused rings, spirocyclic, or spirofused ring structures; preferably, ring A is selected from... Each occurrence of Q is independently selected from O, S, and NR. X Each time Q0 appears, it is independently selected from O, S, C(R). X )2 and NR X Preferably, ring A is selected from... and / or

[0038] Ring B is selected from single bonds, 6-8 membered monocyclic aryl groups, 9-10 membered bicyclic aryl groups, 5-8 membered monocyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S, 8-10 membered bicyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5-8 membered monocyclic heterocyclic hydrocarbon groups, saturated or partially unsaturated 6-11 membered bicyclic heterocyclic hydrocarbon groups, saturated or partially unsaturated 5-8 membered monocyclic heterocyclic hydrocarbon groups containing 1-4 heteroatoms independently selected from N, O, and S, and 6-11 membered bicyclic heterocyclic hydrocarbon groups containing 1-4 heteroatoms independently selected from N, O, and S, wherein the bicyclic heterocyclic hydrocarbon groups and bicyclic heterocyclic hydrocarbon groups are bridged rings, spirocyclic rings, or fused ring structures; preferably, ring B... The compounds are selected from single bonds, phenylene, 9- or 10-membered bicyclic aryl groups, 5- or 6-membered monocyclic heteroaryl groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 9- or 10-membered bicyclic heteroaryl groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5- or 6-membered monocyclic heterocyclic hydrocarbon groups, 7-, 8-, 9-, or 10-membered bicyclic heterocyclic hydrocarbon groups, saturated or partially unsaturated 5- or 6-membered monocyclic heterocyclic hydrocarbon groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, and 7-, 8-, 9-, or 10-membered bicyclic heterocyclic hydrocarbon groups, wherein the bicyclic heterocyclic hydrocarbon group and the bicyclic heterocyclic hydrocarbon group are bridged rings, spirocyclic rings, or fused ring structures; preferably, ring B is selected from single bonds, phenylene, phenylene, 9- or 10-membered bicyclic heterocyclic hydrocarbon groups. and / or

[0039] The ring C is absent or selected from 3-8 membered cycloalkyl groups, 3-8 membered monocyclic heterocyclic groups containing 1-4 saturated or partially unsaturated 3-8 membered monocyclic heterocyclic groups containing 1-4 saturated or partially unsaturated 8-11 membered bicyclic heterocyclic groups containing 1-4 saturated or partially unsaturated 8-11 membered bicyclic heterocyclic groups containing 1-4 5-8 membered monocyclic heteroaryl groups containing 1-4 1-4 9-10 membered bicyclic heteroaryl groups containing 1-4 1-4 1-4 fused ring, spiro ring, or bridged ring structures; preferably, the ring C is absent or selected from 3-membered, 4-membered, 5-membered, or... The following are considered as separate categories: 6-membered cycloalkyl groups; 3-, 4-, 5-, or 6-membered monocyclic heterocyclic groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms; 8- or 9-membered bicyclic heterocyclic groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms; 5-membered monocyclic heteroaryl groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms; and 8- or 9-membered bicyclic heteroaryl groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms, wherein the bicyclic heterocyclic group is a fused ring, spiro ring, or bridged ring structure; preferably, the ring C is absent or selected from... and / or

[0040] p1, p2, and p3 are each independently selected from 0, 1, 2, 3, and 4; preferably, p1, p2, and p3 are each independently selected from 0, 1, 2, and 3; and / or

[0041] L b Selected from single bonds, C(R) X 2. C 3-5 Cycloalkylene, O, S, S(O), S(O)2, NR X A combination of one or more of C(O); preferably, L b Selected from single bond, C 1-3 Alkylene, Cyclopropylene, O, S, S(O), S(O)2, NH, N(C) 1-3 A combination of one or more of alkyl groups and C(O); preferably, L b Selected from single bonds; and / or

[0042] When ring C exists, L c Selected from single bond, C 1-3 Alkylene, Cyclopropylene, O, S, S(O), S(O)2, NH, N(C) 1-3 A combination of one or more of alkyl groups and C(O); preferably, when a cyclic C is present, L c Selected from single bonds, NH, C 1-3 Alkylene, Cyclopropylene, N(C) 1-3A combination of one or more of alkyl groups and C(O); preferably, when a cyclic C is present, L c Each occurrence is independently selected from single bonds, -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -C(O)-CH2-, -C(O)-CH2CH2-, -C(O)-cyclopropylidene, -N(CH3)-C(O)-, and -N(CH3)-C(O)-CH2CH2-; preferably, L c It is -C(O)-CH2CH2-;

[0043] When ring C does not exist, L c Selected from C 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, -SC 1-3 Alkyl, -S(O)-C 1-3 Alkyl, -S(O)2-C 1-3 Alkyl, -NR X -C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -NR X -C(O)-N(R X )2、-C(O)-OC 1-3 Alkyl, -C(O)-N(R) X )2- and -C(O)-NR X -C 1-3 Alkyl, the C 1-3 Alkyl, C 1-3 Heteroalkyl and C 1-3 Alkyl groups are optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-3 One or more substituents in the alkyl group are substituted; preferably, when the ring C is absent, L c Selected from C 1-3 Alkyl, C 1-3 Alkoxy, -N(C) 1-3 Alkyl)2、-C(O)-C 1-3 Alkyl, -NH-C(O)-N(C) 1-3 Alkyl)2、-NH-C(O)-NH(C 1-3 Alkyl), -C(O)-OC 1-3 Alkyl, -C(O)-N(C) 1-3 alkyl)2 and -C(O)-N(C 1-3 Alkyl group 2; preferably, when the ring C is absent, L c Selected from -C(O)-C 1-3 Alkyl, -NH-C(O)-N(C) 1-3Alkyl)2、-NH-C(O)-NH(C 1-3 Alkyl), -C(O)-OC 1-3 Alkyl groups and -C(O)-N(C) 1-3 Alkyl)2; and / or

[0044] R A R B and R C Each time it appears, it is independently selected from H, deuterium, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 heteroaryl groups are optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 The aryl group is substituted with one or more substituents of a 5-6 membered heteroaryl group; preferably, R A R B and R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 heteroaryl groups are optionally selected from F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups and C 1-3 The alkoxy group is substituted with one or more substituents of the haloalkoxy group; preferably, R A R B and R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl, C 1-3 Alkoxy group, -C(O)-C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl; preferably, R A R B and R C Each time it appears, it is independently selected from F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl, C 1-3 Alkoxy group, -C(O)-C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl; preferably, R A R B and R C Each occurrence is independently selected from F and -CH3; and / or

[0045] R D Selected from R X -OR X -N(R) X )2、-C(O)R X -C(O)OR X -C(O)N(R)X )2、-C(O)N(R X OR X -OC(O)R X -OC(O)N(R) X )2、-NR X C(O)OR X -NR X C(O)R X -NR X C(O)N(R X )2 and -NR X S(O)2R X Preferably, R D Selected from R X -N(R) X )2、-C(O)R X -C(O)OR X and -C(O)N(R) X )2; and / or

[0046] R X Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 quinone heteroaryl groups are optionally selected from halogens, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups and C 1-3 One or more substituents of the haloalkoxy group are substituted; preferably, R X Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-3 Alkyl, C 2-3 alkenyl, C 2-3alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 The aryl group and the 5-6 heteroaryl group are optionally selected from F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups and C 1-3 One or more substituents of the haloalkoxy group are substituted; preferably, R X Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-3 Alkyl, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are optionally replaced by one or more halogens; preferably, R X Each time it appears, it is independently selected from F, Cl, Br, I, hydroxyl, nitro, cyano, amino, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, cyclopropyl, and halocyclopropyl.

[0047] In some implementation schemes,

[0048] R A Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3, -CH(CH3)2, -OCH3 and -OCH2CH3; and / or

[0049] R B Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3 and -C(O)-CH3; and / or

[0050] R C Each occurrence is independently selected from H, F, Cl, Br, I, -CH3, and -CH2CH3; and / or

[0051] R DEach occurrence is independently selected from H, F, Cl, Br, I, -OCH3, -CH3, -CH2CH3, -CH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -C(O)-NH(CH3), -C(O)-NH(CH2CH3), -C(O)-N(CH3)2, -C(O)-N(CH3)2, -C(O)-N(CH3)(CF3), -C(O)-N(CH3)(CH2CH3), -C(O)-N(CH3)(CH(CH3)2), -C(O)-N(CH2CH3)(CH(CH3)2), Preferably, R D It is -C(O)-N(CH3)2.

[0052] In some implementations, the PTM is selected from the structure shown in the following formula:

[0053] Among them, rings B, C, and L b L c R A R B R C R D p1, p2, and p3 are defined as described above;

[0054] Q2 is selected independently from CR each time it appears. A , N, C(R) A 2. NR A and C;

[0055] This indicates that two double bonds are formed at any position within the ring, together with Q2 on the ring, to form a conjugated system;

[0056] In equations (IC) and (IE), Q1 is independently selected from O, S, and NR each time it appears. X ;

[0057] In (IA), R 4g Does not exist, or R 4g With R 4a Or R 4f Together they form Cy6;

[0058] When R 4g When Q1 does not exist, each occurrence of Q1 is independently selected from O, S, and NR. X When R 4g With R 4a Or R 4f When they jointly form Cy6, Q1 appears independently as N each time;

[0059] R X Same as the definition above;

[0060] In equation (1-A), R 4a R 4b R 4c R 4d R 4e R 4f and R 4g The definition is selected from one of the following groups;

[0061] (iv-1)R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range;

[0062] (iv-2)R 4a and R 4b Together they form Cy3, which is optionally bounded by R D Replace; R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range;

[0063] (iv-3)R 4b and R 4c Together they form Cy4; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range;

[0064] (iv-4)R4c and R 4d Together they form Cy4; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4f Each occurrence is independently selected from R. A Substituents within the specified range;

[0065] (iv-5)R 4d and R 4e Together they form Cy5; R 4c Connected to L, and R 4c It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4f Each occurrence is independently selected from R. A Substituents within the specified range;

[0066] (iv-6)R 4e and R 4f Together they form Cy5; R 4c Connected to L, and R 4c It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4d Each occurrence is independently selected from R. A Substituents within the specified range;

[0067] (iv-7)R 4f and R 4g Together they form Cy6; R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4d Each occurrence is independently selected from R. A Substituents within the range; and

[0068] (iv-8)R 4gand R 4a Together they form Cy6, which is optionally bounded by R D Replace; R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4b R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range;

[0069] Cy3 is selected independently each time it appears.

[0070] Cy4 is selected independently each time it appears.

[0071] Cy5 is selected independently each time it appears.

[0072] Cy6 is selected independently each time it appears.

[0073] F1, F2, F3, F4, and F5 are each selected independently from CR each time they appear. d1 R d2 NR d1 O, C(O) and S; F1 and F2, F2 and F3 or place In equation (1-A) The connection sites of atoms on the ring; preferably, F1, F2, F3, F4 and F5 are each independently selected from CR each time they appear. d1 R d2 NR d1 O and C(O); preferably, F1, F2, F3, F4 and F5 are each independently selected from CH2, O and NH when they appear.

[0074] U6 and U7 are each independently designated as CR each time they appear. d1 Or N; preferably, U6 and U7 are each independently CH or N each time they appear;

[0075] R t and R t1 Each time it appears, it is selected independently from CR. d1 and N; preferably, R t and R t1 Each occurrence is independently either CH or N;

[0076] R t2 Each occurrence is independently designated as C;

[0077] R t and R t2 place Indicates the connection site with L; R t1 place Indicates with L b Connection sites;

[0078] Each occurrence of q0, q1, q2, q3, q4, and q5 is independently selected from 0, 1, 2, 3, 4, and 5; preferably, each occurrence of q0, q1, q2, q3, q4, and q5 is independently selected from 0, 1, 2, and 3; and

[0079] R d1 and R d2 Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-NH-C 1-6 Alkyl, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 The aryl and 5-6 heteroaryl groups are optionally selected from halogens, hydroxyl groups, cyano groups, amino groups, nitro groups, C-groups, etc. 1-3 Alkyl, C 1-3 Alkoxy and C 1-3 The alkyl group is substituted with one or more substituents; preferably, R d1 and R d2 Each time it appears, it is independently selected from H, halogen, cyano, amino, nitro, hydroxyl, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 Hydroxyalkyl.

[0080] In some implementations, the PTM is selected from the structure shown in the following formula:

[0081] Among them, rings B, C, and L b L c R A R B R C R D p1, p2, and p3 are defined as described above;

[0082] Q3 is selected independently from CH and N each time it appears;

[0083] In some implementation schemes,

[0084] Each occurrence of ring B is independently selected from single bonds. and / or

[0085] Ring C either does not exist or is selected independently each time it appears. and / or

[0086] When ring B is a single bond and ring C exists, L b Each occurrence is a single key, L. c Each time it appears, it is independently selected from C(O), cyclopropylene, C 1-3 A combination of one or more of alkylene groups, NH, and N(CH3); when ring B is not a single bond and ring C is absent, L b Each occurrence is independently selected from single bonds, C(O), C 1-3 A combination of one or more of alkylene, NH, and N(CH3), L c Each occurrence is independently selected from -C(O)-C 1-3 Alkyl, N(CH3)-C 1-3 Alkyl groups and -C(O)-N(CH3)-C 1-3 Alkyl; when ring B is not a single bond and ring C is present, L b and L c Each occurrence is independently selected from single bonds, cyclopropyl groups, and C. 1-3 A combination of one or more of alkylene, O, S(O)2, NH, N(CH3), N(CH2CH3), and C(O); and / or

[0087] R A Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C(O)-C. 1-3Alkyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, phenyl and 5-6 membered heteroaryl; and / or

[0088] R B Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)-C. 1-3 Alkyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 aryl and 5-6 heteroaryl groups; and / or

[0089] R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C(O)-C. 1-3 Alkyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 aryl and 5-6 heteroaryl groups; and / or

[0090] R D Each time it appears, it is independently selected from H, F, Cl, Br, I, R. X -N(R) X )2、-C(O)R X and -C(O)N(R) X )2; and / or

[0091] R X Each time it appears, it is independently selected from H, F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic and 3-6 membered halocyclic; and / or

[0092] p1, p2, and p3 are each independently selected from 0, 1, 2, and 3 each time they appear; and / or

[0093] Cy3 is selected independently each time it appears. and / or

[0094] Cy4 is selected independently each time it appears. and / or

[0095] Cy5 is selected independently each time it appears. and / or

[0096] Cy6 is selected independently each time it appears.

[0097] Cy3, Cy4, Cy5 and Cy6 open-loop Indicates and The connection sites of carbon atoms and / or Q1 on the ring.

[0098] In some implementations, the PTM is selected from the structure shown in the following formula:

[0099] Among them, R A R B R C R D and R X Each occurrence is independent of the definition given above;

[0100] Each occurrence of Q0 is independently selected from O, S, CH2, C(O), and NR. X ;

[0101] Q1 is selected independently from O, S, and NH each time it appears;

[0102] Q3 is selected independently from CH and N each time it appears;

[0103] Q4 is selected independently from CR each time it appears. X and N;

[0104] p2 and p3 are each independently selected from 0, 1, and 2;

[0105] Each occurrence of y0 is independently selected from 0 and 1;

[0106] Each occurrence of ring B1 is independently selected from...

[0107] Each occurrence of ring C1 is independently selected from...

[0108] Ring C2 either does not exist or is selected independently each time it appears.

[0109] L b Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -O-, -NH-, -C(O)-, -C(O)-O-, -C(O)-C 1-3 Alkylene-, -N(C) 1-3 alkyl)-、-C(O)-NH-C 1-3 Alkylene- and -N(C) 1-3 Alkyl)-C(O)-; preferably, L b Each occurrence is independently selected from single bonds, -CH2-, -CH2CH2-, -C(O)-NH-C 1-3 Alkylene- and -CH2CH2CH2-; preferably, L b Each occurrence is independently selected from single bonds and -C(O)-NH-C 1-3 alkylene-;

[0110] When ring C2 exists, L c Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -C(O)-, -C(O)-C 1-3 alkylene-, -C(O)-cyclopropylene-, -N(C 1-3 Alkyl)-C(O)-, -C(O)-NH-C 1-3 Alkylene- and -N(C) 1-3 alkyl)-C(O)-C 1-3 Alkylene; preferably, when ring C2 is present, L c Each time it appears, it is independently selected from single bond, -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -C(O)-CH2-, -C(O)-CH2CH2-, -C(O)-cyclopropylidene-, -N(CH3)-C(O)-, -C(O)-NH-CH2- and -N(CH3)-C(O)-CH2CH2-;

[0111] When ring C2 does not exist, L c Each occurrence is independently selected from -C(O)-C 1-3 Alkyl, -NH-C(O)-N(C) 1-3 alkyl)2 and -NH-C(O)-NH(C 1-3 Alkyl); preferably, when the ring C2 is absent, L cEach time it appears, it is independently selected from -C(O)-CH3, -C(O)-CH2CH3, -C(O)-CH(CH3)2, -NH-C(O)-N(CH3)2 and -NH-C(O)-NH(CH3).

[0112] In some implementation schemes,

[0113] R A Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl and C 1-3 Alkoxy; preferably, R A Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3, -CH(CH3)2, -OCH3 and -OCH2CH3; and / or

[0114] R B Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)-C. 1-3 Alkyl and C 1-3 Alkyl; preferably, R B Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3 and -C(O)-CH3; and / or

[0115] R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, and C. 1-3 Alkyl; preferably, R C Each occurrence is independently selected from H, F, Cl, Br, I, -CH3, and -CH2CH3; and / or

[0116] R D Each time it appears, it is independently selected from H, F, Cl, Br, I, R. X 、N(R X 2. C(O)R X and C(O)N(R) X )2; Preferably, R DEach occurrence is independently selected from H, F, Cl, Br, I, -OCH3, -CH3, -CH2CH3, -CH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -C(O)-NH(CH3), -C(O)-NH(CH2CH3), -C(O)-N(CH3)2, -C(O)-N(CH3)2, -C(O)-N(CH3)(CF3), -C(O)-N(CH3)(CH2CH3), -C(O)-N(CH3)(CH(CH3)2), -C(O)-N(CH2CH3)(CH(CH3)2), and / or

[0117] R X Each time it appears, it is independently selected from H, F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-, 5-, 6-, or 7-membered heterocyclic groups containing 1, 2, or 3 heteroatoms each independently selected from N, O, and S, and 6-membered halocyclic groups containing 1, 2, or 3 heteroatoms each independently selected from N, O, and S; preferably, R X Each occurrence is independently selected from H, F, Cl, Br, I, -CF3, -OCH3, -CH3, -CH2CH3, -CH(CH3)2. and / or

[0118] Each occurrence of Q0 is independently selected from O, C(O), S, CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); preferably, each occurrence of Q0 is independently selected from O, C(O), CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); and / or

[0119] Q4 is selected independently from CH, CF, C(CH3), C(OCH3), and N each time it appears.

[0120] In some implementations, the PTM is selected from the structure in implementation 19.

[0121] In some embodiments, the present invention provides a compound of formula (I), wherein ULM is an E3 ubiquitin ligase binding moiety.

[0122] In some embodiments, the present invention provides a compound of formula (I), wherein ULM is the human cerebellar protein (CRBN) E3 ubiquitin ligase binding moiety.

[0123] In some implementations, the structure of the ULM is as shown in the following formula:

[0124] Among them, W1 is independently selected from CR each time it appears. c1 and N;

[0125] R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 1-6 Halogenated alkylene and C 1-6 A combination of one or more heteroalkyl groups;

[0126] R q Each occurrence is independently selected from single bonds and NR. c1 ;R q place Indicates the connection site with L;

[0127] W2, W3, and W4 are each independently selected from C, C(O), O, N, and NR, respectively. c1 CR c1 and CR c1 R c2 The area between W2, W3 and W4 Indicates a single bond or a double bond;

[0128] In Equations 2-2 and 2-8, when there is a double bond between W2 and W3, and a single bond between W3 and W4, W2 is C, and W3 is selected from N and C. c1 W4 is selected from O and CR c1 R c2 and NR c1 When W2 and W3 form a single bond, and W3 and W4 form a double bond, W2, W3, and W4 are each independently selected from N and CR. c1 When all bonds between W2, W3, and W4 are single bonds, W2 is selected from N and CR. c1 W3 and W4 are each independently selected from C(O) and NR. c1 O and CR c1 R c2 ;

[0129] W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is C(O);

[0130] W12 and W 13 Each is independently selected from N and CR c1 ;

[0131] R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups;

[0132] (i-1)R 1a and R 1b Together they form Cy0, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0133] (i-2)R 1b and R 1c Together they form Cy0, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0134] (i-3)R 1c and R 1d Together they form Cy0, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0135] (i-4)R 1d and R 1e Together they form Cy0, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the range; and

[0136] (i-5)R 1a and R W Together they form Cy0, and R 1b R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0137] R 2a R 2b R 2c and R 2dThe definition is selected from one of the following groups;

[0138] (ii-1)R 2a and R 2b Together they form Cy1, and R 2c and R 2d Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0139] (ii-2)R 2b and R 2c Together they form Cy1, and R 2a and R 2d Each occurrence is independently selected from R. S1 Substituents within the range; and

[0140] (ii-3)R 2c and R 2d Together they form Cy1, and R 2a and R 2b Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0141] R 3a R 3b and R 3c The definition is selected from one of the following groups;

[0142] (iii-1)R 3a and R 3b Together they form Cy2, and R 3c Each time it appears, it is selected independently from R. S1 Substituents within the range; and

[0143] (iii-2)R 3b and R 3c Together they form Cy2, and R 3a Each time it appears, it is selected independently from R. S1 Substituents within the specified range;

[0144] Cy0, Cy1, and Cy2 are each selected independently each time they appear. A1, A2, A3, A4, A5, and A6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at A1 and A2 Indicates the connection sites between it and atoms on the connected ring; B1, B2, and R T Each time it appears, it is selected independently from CR. c1 and N;R T place Indicates the connection site with L;

[0145] Each time m1, m3, and m5 appear, they are independently selected from 1, 2, 3, 4, 5, and 6;

[0146] Each time m2, m4, and m6 appear, they are each independently selected from 0, 1, 2, 3, 4, 5, and 6;

[0147] R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl and 5-10 heteroaryl groups are each independently and optionally selected from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, C 1-10 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Heteroalkyl, C 1-10 Alkoxy, C 1-10 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents of a 5-10 member heteroaryl group;

[0148] Each time n appears, it is independently selected from 0, 1, 2, 3, 4, and 5;

[0149] R c1 and R c2 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10Cycloalkyl, 3-10 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl and 5-10 heteroaryl groups are each independently and optionally selected from halogen, cyano, amino, nitro, hydroxyl, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 3-8 cycloalkyl, 3-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 6-8 The aryl group is substituted with one or more substituents of the 5-8 membered heteroaryl group; and

[0150] In the above formulas, The substituent indicates the connection site. Substituents without explicitly marked substitution positions indicate that they can be substituted at any chemically permissible position on the entire ring.

[0151] In some implementation schemes,

[0152] Each occurrence of W1 is independently selected from CH and N; and / or

[0153] R W Each occurrence is independently selected from single bonds, C(O), O, and NR. c1 C(O)NR c1 C 1-3 Alkylene and C 1-3 Halogenated alkylene; preferably, R W Each occurrence is independently selected from single bonds, O, and NR. c1 and C(O)NR c1 Preferably, R WEach occurrence is independently selected from single bonds, NH, N(CH3), C(O)-NH, and C(O)-N(CH3); and / or

[0154] R q Each occurrence is independently selected from single bonds and NH; and / or

[0155] In Equations 2-2 and 2-8, when there is a double bond between W2 and W3, and a single bond between W3 and W4, W2 is C, and W3 is selected from N and C. c1 W4 is selected from O and CR c1 R c2 and NR c1 Preferably, W3 is N; preferably, W4 is selected from N-CH3, NH, O, CH2, CH(CH3) and C(CH3)2;

[0156] When there is a single bond between W2 and W3, and a double bond between W3 and W4, W2, W3, and W4 are each independently selected from N and CR. c1 Preferably, W2, W3, and W4 are each independently selected from N, CH, and C-CH3;

[0157] When all bonds between W2, W3, and W4 are single bonds, W2 is selected from N and CR. c1 W3 and W4 are each independently selected from C(O) and NR. c1 O and CR c1 R c2 Preferably, W2 is selected from N, CH and C-CH3; preferably, W3 and W4 are each independently selected from C(O), O, NH, N(CH3), CH2, CH(CH3) and C(CH3)2; and / or

[0158] W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 And C(O), and at least one of W5 and W6 is C(O); preferably, W5, W6 and W7 are each independently selected from CH2 and C(O) each time they appear, and at least one of W5 and W6 is selected from C(O); preferably, W5 and W6 are each independently selected from CH2 and C(O) each time they appear, and at least one of W5 and W6 is C(O); W7 is C(O); and / or

[0159] W 12 and W 13 Each is independently selected from N, CH and C(C) 1-3 Alkyl); and / or

[0160] A1, A2, A3, A4, A5, and A6 are each independently selected from CH2, C(C) each time they appear. 1-6 Alkyl)2, CH(C)1-6 Alkyl), NH, N(C) 1-6 Alkyl groups), O, and C(O); preferably, A1, A2, A3, A4, A5, and A6 are each independently selected from CH2, C(C) and O when they appear. 1-3 Alkyl)2, CH(C) 1-3 Alkyl), NH, N(C) 1-3 Alkyl groups), O and C(O); and / or

[0161] B1, B2 and R T Each occurrence is independently selected from CH and N; and / or

[0162] R S1 Each time it appears, it is independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 The aryl and 5-8 heteroaryl groups are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-8 The aryl group is substituted with one or more substituents of a 5-8 membered heteroaryl group; preferably, R S1 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl; preferably, R S1Each occurrence is independently selected from H, F, Cl, Br, -CN, -OH, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -OCH2CH3, and -OCH(CH3)2; preferably, R S1 Each occurrence is independently selected from H, F, Cl, Br, -CN, -OH, -CH3, and -OCH3; and / or

[0163] Each occurrence of n is independently selected from 0, 1, 2, and 3; and / or

[0164] R c1 and R c2 Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 cycloalkyl, 3-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-NH-C 1-6 Alkyl, C 6-8 Aryl and 5-8 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 The aryl and 5-8 heteroaryl groups are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-3 Alkyl, -N(C) 1-3 Alkyl)2, C 6-8 The aryl group is substituted with one or more substituents of a 5-8 membered heteroaryl group; preferably, R c1 and R c2Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-3 Alkyl, -N(C) 1-3 Alkyl)2、-C(O)-C 1-3 Alkyl, -C(O)-OC 1-3 Alkyl, -C(O)-NH-C 1-3 Alkyl, C 6-7 Aryl and 5-7 membered heteroaryl, wherein the C 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-7 heteroaryl groups are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-3 Alkyl, -N(C) 1-3 Alkyl)2, C 6-7 The aryl group is substituted with one or more substituents of a 5-7 membered heteroaryl group; preferably, R c1 and R c2 Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 aryl and 5-8 quinone heteroaryl; and / or

[0165] Each time m1, m3, and m5 appear, they are independently selected from 1, 2, 3, 4, and 5; and / or

[0166] Each time m2, m4, and m6 appear, they are independently selected from 0, 1, 2, 3, 4, and 5.

[0167] In some implementations, the ULM is selected from the structure shown in the following formula:

[0168] Among them, R q Each occurrence is independently selected from single bonds and NR. c1 ;

[0169] W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 And C(O), and at least one of W5 and W6 is C(O);

[0170] W8 and W 10 Each occurrence is independently selected from O and NR. c1 and CR c1 R c2 ;

[0171] W9, W 11 W 12 and W 13 Each occurrence is independently selected from N and CR. c1 ;

[0172] Each time W1 appears, it is independently selected from N and CR. c1 ;

[0173] R W Each occurrence is independently selected from single bonds, O, C(O)NR. c1 and NR c1 ;

[0174] A1, A2, A3, A4, A5, and A6 are each independently selected from O, S, C(O), and NR when they appear. c1 and CR c1 R c2 ;

[0175] B1, B2, G, and R T Each occurrence is independently selected from N and CR. c1 ;

[0176] Each time m1 and m2 appear, they are independently selected from 0, 1, 2, 3, 4 and 5, and m1 + m2 ≤ 6;

[0177] Each time m3 and m4 appear, they are independently selected from 0, 1, 2, 3, 4 and 5, and m3 + m4 ≤ 6;

[0178] Each time m5 and m7 appear, they are each independently selected from 0, 1, 2, 3, 4 and 5. Each time m6 and m8 appear, they are each independently selected from 1, 2, 3, 4, 5, 6 and 7. Furthermore, m5+m6≤6 and m7+m8≤6.

[0179] R c1 and R c2 Each time it appears, it is independently selected from H, halogen, hydroxyl, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 cycloalkyl; and

[0180] R1, R2, R3, R4, and R5 are each independently selected from H, halogen, hydroxyl, cyano, amino, nitro, and C groups when they appear. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(O)-C 1-6 Alkyl, -C(O)-C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups.

[0181] In some implementation schemes,

[0182] R q Each occurrence is independently selected from single bonds and NH; and / or

[0183] W5 and W6 are each independently selected from CH2 and C(O) each time they appear, and at least one of W5 and W6 is C(O); and / or

[0184] W7 is C(O); and / or

[0185] W8 and W 10 Each occurrence is independently selected from O, NH, N(C) 1-3 Alkyl), CH(C) 1-3 Alkyl), C(C) 1-3 Alkyl)2 and CH-C 3-6 Cycloalkylene; and / or

[0186] W9, W 11 W 12 and W 13 Each occurrence is independently selected from N, CH, and C(C) 1-3Alkyl); and / or

[0187] R W Each occurrence is independently selected from single bonds, O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 Alkyl); and / or

[0188] A1, A2, A3, A4, A5, and A6 are each independently selected from CH2, C(C) each time they appear. 1-3 Alkyl)2, CH(C) 1-3 Alkyl), NH, N(C) 1-3 Alkyl groups), O and C(O); and / or

[0189] Each time m1 and m2 appear, they are independently selected from 0, 1, 2, 3, and 4, and m1 + m2 ≤ 4; and / or

[0190] Each time m3 and m4 appear, they are independently selected from 0, 1, 2, 3, and 4, and m3 + m4 ≤ 4; preferably, each time m3 and m4 appear, they are independently selected from 0, 1, 2, and 3, and m3 + m4 = 2 or m3 + m4 = 3; and / or

[0191] Each time m5 and m7 appear, they are independently selected from 0, 1, 2, 3, and 4; each time m6 and m8 appear, they are independently selected from 1, 2, 3, 4, and 5; and m5 + m6 ≤ 5, m7 + m8 ≤ 5. Preferably, each time m5 and m7 appear, they are independently selected from 0, 1, 2, and 3; each time m6 and m8 appear, they are independently selected from 1, 2, 3, and 4; and m5 + m6 = 2, m5 + m6 = 3, or m5 + m6 = 4; m7 + m8 = 2, m7 + m8 = 3, or m7 + m8 = 4; and / or

[0192] R c1 and R c2 Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl group, C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy and C 3-6 cycloalkyl; and / or

[0193] R1, R2, R3, R4, and R5 are each independently selected from H, F, Cl, Br, I, -OH, -CN, -NH2, -NO2, and C, respectively. 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups and C 1-3 Hydroxyalkyl.

[0194] In some implementations, the ULM is selected from the structure shown in the following formula:

[0195] in:

[0196] Each time X and Z appear, they are independently selected from N, CH, C(C). 1-6 alkyl) and C(C) 3-6 (cycloalkyl); preferably, X and Z are each independently selected from N and CH each time they appear;

[0197] R w Each occurrence is independently selected from O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 alkyl);

[0198] When W1 and W2 appear, they are each independently selected from CH2 and C(O), and at least one of W1 and W2 is C(O);

[0199] When there is a double bond between W4 and W5, and a single bond between W5 and W6, W4 is C, and W5 is selected from N, CH, and C(C) 1-3 Alkyl), W6 is selected from NH, N(C) 1-3 Alkyl), O, CH2, CH(C) 1-3 alkyl) and C(C) 1-3 Alkyl)2; when there is a single bond between W4 and W5 and a double bond between W5 and W6, W4, W5, and W6 are each independently selected from N, CH, and C (C 1-3 Alkyl); when there are single bonds between W4, W5, and W6, W4 is selected from N, CH, and C (C 1-3 Alkyl groups, W5 and W6 are each independently selected from C(O), NH, N(C) 1-3 Alkyl), O, CH2, CH(C) 1-3 alkyl) and C(C) 1-3 Alkyl)2;

[0200] W8 and W 10 Each occurrence is independently selected from O, NH, N(C) 1-3 Alkyl), CH(C) 1-3 Alkyl), C(C) 1-3 Alkyl)2 and CH-C 3-6 Cycloalkylene;

[0201] W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(C) 1-3 alkyl);

[0202] R 2a Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl and 3-8 membered heterocyclic groups; preferably, R 2a Each occurrence is independently selected from H, F, Cl, Br, C. 1-3 Alkyl and C 1-3 Halogenated alkyl groups;

[0203] R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5g Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl;

[0204] A a A b A c A d A e A f and A h Each occurrence is independently selected from O, S, C(O), NR. d and C(R) d )2, R d Each occurrence is independently selected from H, F, Cl, Br, -OH, -CN, -NH2, -NO2, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl;

[0205] B1a and B 2a Each occurrence is independently selected from N, CH, and C(C) 1-3 alkyl);

[0206] Each time m11, m21 and m31 appear, they are independently 0, 1, 2, 3 or 4, and 1≤m11+m21+m31≤5;

[0207] Each occurrence of m41 and m51 is independently 0, 1, 2, 3, or 4, and 1 ≤ m41 + m51 ≤ 5; and

[0208] Each time m61 and m71 appear, they are independently 0, 1, 2, 3 or 4, and 1≤m61+m71≤5.

[0209] In some implementation schemes,

[0210] Each occurrence of X is independently N; and / or

[0211] W1 is C (=O), and W2 is CH2; W1 is CH2, and W2 is C (=O); or W1 is (=O), and W2 is C (=O); and / or

[0212] When W4 and W5 form a double bond and W5 and W6 form a single bond, W4 is C, W5 is selected from N, CH, and C(CH3), and W6 is selected from NH, N(CH3), O, CH2, CH(CH3), and C(CH3)2; when W4 and W5 form a single bond and W5 and W6 form a double bond, W4, W5, and W6 are each independently selected from N, CH, and C(CH3); when W4, W5, and W6 are all single bonds, W4 is selected from N, CH, and C(CH3), and W5 and W6 are each independently selected from C(O), NH, N(CH3), O, CH2, CH(CH3), and C(CH3)2; and / or

[0213] W8 and W 10 Each time it appears, it is independently selected from O, NH, N(CH3), CH(CH3), C(CH3)2 and CH-C. 3-5 Cycloalkylene; and / or

[0214] W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(CH3); and / or

[0215] A a A b A c A d A e A f and A hEach time it appears, it is independently selected from CH2, C(C) 1-3 Alkyl)2, CH(C) 1-3 Alkyl), NH, N(C) 1-3 Alkyl groups), C(O) and O; preferably, A a A b A c A d A e A f and A h Each occurrence is independently selected from CH2, C(CH3)2, CH(CH3), NH, N(CH3), or C(O); preferably, A a A b A c A d A e A f and A h Each occurrence is independently selected from CH2; and / or

[0216] Each occurrence of m11, m21, and m31 is independently 0, 1, 2, or 3, and 1 ≤ m11 + m21 + m31 ≤ 4; preferably, m11 + m21 + m31 = 1, m11 + m21 + m31 = 2, m11 + m21 + m31 = 3, or m11 + m21 + m31 = 4; and / or

[0217] Each occurrence of m41 and m51 is independently 0, 1, 2, or 3, and 1 ≤ m41 + m51 ≤ 4; preferably, m41 + m51 = 2, m41 + m51 = 3, or m41 + m51 = 4; and / or

[0218] Each occurrence of m61 and m71 is independently 0, 1, 2, or 3, and 1 ≤ m61 + m71 ≤ 4; preferably, m61 + m71 = 2, m61 + m71 = 3, or m61 + m71 = 4; and / or

[0219] R 2a Each time it appears, it is independently selected from H, F, Cl, Br, and C. 1-3 Alkyl; preferably, R 2a Each occurrence is independently -CH3; and / or

[0220] B 1a and B 2a Each occurrence is independently selected from N, CH, and C(CH3); preferably, B 1a and B 2a Each occurrence is independently selected from N and CH; and / or

[0221] R 3aR 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5g Each time it appears, it is independently selected from H, F, Cl, Br, cyano, hydroxyl, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups and C 1-3 Hydroxyalkyl; preferably, R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5g Each occurrence is independently selected from H, F, Cl, Br, -CN, -OH, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -OCH2CH3, and -OCH(CH3)2; preferably, R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5gEach time it appears, it is independently selected from H, F, Cl, Br, -CN, -OH, -CH3 and -OCH3.

[0222] In some implementations, the ULM is selected from the structure in implementation 22.

[0223] In some embodiments, the present invention provides a compound of formula (I), wherein L is a chemical linker connecting the ULM and the PTM.

[0224] In some embodiments, the present invention provides a compound of formula (I), wherein the L is -(B L )q-;

[0225] B L Each occurrence is independently selected from covalent bonds, CR L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 C(O), 3-15 member monocyclic cyclohexane, 3-15 member monocyclic heterocyclic group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15 member bridged cyclohexane, 5-15 member spirocyclic group, 5-15 member spirocyclic group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 6-15 member aryl group and 5-15 member heteroaryl group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, wherein the cycloalkyl group, heterocyclic group, bridged cyclohexane, bridged cyclohexane, spirocyclic group, spirocyclic group, aryl group and heteroaryl group are optionally 1-6 heteroatoms independently selected from R L1 Substitution of groups;

[0226] R L1 and R L2 Each occurrence is independently selected from H, halogens, -OH, -NH2, -SH, -C(O)2H, -CN, -NO2, -S(O)2H, -SF5, -C≡CH, C 1-8 Alkyl, C 1-8 Alkoxy, -SC 1-8 Alkyl, -NH-C 1-8 Alkyl, N(C) 1-8 Alkyl)2, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, -OC 3-8 Cycloalkyl, -O-3-8 membered heterocyclic groups, -OC 6-10 Aryl, -O-5-10 heteroaryl, -SC3-8 cycloalkyl, -NH-C 3-8 cycloalkyl, -N(C) 3-8 cycloalkyl)2, -N(C 3-8 cycloalkyl)(C 1-8 Alkyl), -NH-3-8-membered heterocyclic group, -N(3-8-membered heterocyclic group)2, -N(3-8-membered heterocyclic group) (C 1-8 alkyl), -NH-C 6-10 Aryl, -N(C 6-10 Aryl)(C 1-8 alkyl), -NH-C 5-10 heteroaryl, -N (5-10 quinone heteroaryl) (C 1-8 Alkyl), -S(O)2P(O)(C 1-8 Alkoxy)(C 1-8 Alkyl), -P(O)(C 1-8 Alkoxy)2、-C≡CC 1-8 Alkyl group, -CH=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl)=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl) = C(C 1-8 Alkyl group 2, -Si(OH)3, -Si(C) 1-8 Alkyl)3、-Si(OH)(C 1-8 Alkyl)2、-C(O)-C 1-8 Alkyl group, -S(O)2NH-C 1-8 Alkyl group, -S(O)2N(C) 1-8 Alkyl)2、-S(O)NH-C 1-8 Alkyl, -S(O)N(C) 1-8 Alkyl)2、-C(O)NH-C 1-8 Alkyl, -C(O)N(C) 1-8 Alkyl)2, -N(C 1-8 alkyl)C(O)NH(C 1-8 alkyl), -N(C) 1-8 alkyl)C(O)N(C 1-8 alkyl)2、-NHC(O)NH(C 1-8 Alkyl), -NHC(O)N(C 1-8 Alkyl)2, -NHC(O)NH2, -N(C 1-8 alkyl)S(O)2NH(C 1-8 alkyl), -N(C) 1-8 alkyl)S(O)2N(C 1-8 alkyl)2、-NHS(O)2NH(C 1-8 Alkyl), -NHS(O)2N(C1-8 alkyl)2 and -NHS(O)2NH2, the C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-8 cycloalkyl, C 3-8 Halogenated cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered halocyclic heterocyclic group, C 6-10 Aryl, C 6-10 Substituted by one or more substituents from halogenated aryl, 5-10-membered heteroaryl, and 5-10-membered haloheteroaryl; and

[0227] q is selected from integers greater than or equal to 1 and less than or equal to 15.

[0228] In some implementation schemes,

[0229] B L Each occurrence is independently selected from covalent bonds, CR L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 The following are listed: C(O), 3-12 membered monocyclic cyclohexane, 3-12 membered monocyclic heterocyclic group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 5-12 membered bridged cyclohexane, 5-12 membered bridged cyclohexane containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 5-12 membered spirocyclic group, 5-12 membered spirocyclic group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 6-12 membered aryl group, and 5-12 membered heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, wherein the cycloalkyl group, heterocyclic group, bridged cyclohexane, bridged cyclohexane, spirocyclic group, spirocyclic group, aryl group, and heteroaryl group are optionally composed of 1, 2, 3 or 4 heteroatoms independently selected from R L1 Substitution of groups;

[0230] R L1 and R L2 Each occurrence is independently selected from H, F, Cl, Br, I, -OH, -NH2, -C(O)2H, -CN, -NO2, -S(O)2H, C 1-6 Alkyl, C 1-6Alkoxy group, -C(O)-C 1-6 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Heteroalkyl, C 1-3 Halogenated heteroalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, 3-6 membered heterocyclic group, 3-6 membered halocyclic heterocyclic group, C 6-8 Aryl, C 6-8 Substituted by one or more substituents of haloaryl, 5-8-membered heteroaryl, and 5-8-membered haloaryl; and

[0231] q is selected from integers greater than or equal to 1 and less than or equal to 12; preferably, q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; preferably, q is selected from 1, 2, 3, 4, 5, 6, 7 and 8.

[0232] In some implementation schemes,

[0233] B L Selected from one or more of the following structures: single bond, -O-, -S-, -S(O)-, -S(O)2-, -C≡C-, -CH2-, -C(O)-, -NH-,

[0234] q is 1, 2, 3, 4, 5, 6, 7, or 8; preferably, q is 1, 2, 3, 4, 5, or 6; and

[0235] This is the connection point.

[0236] In some implementations, the L is selected from the structure in implementation 24.

[0237] In some embodiments, the compound has the structure shown in formula (I-AA) or formula (I-BB):

[0238] and

[0239] Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein:

[0240] Q0 is selected independently from O, S, C(O), and C(R) each time it appears. X )2 and NR X ;

[0241] Q1 is selected independently from O, S, and NR each time it appears. X ;

[0242] p2 and p3 are each independently selected from 0, 1, and 2 each time they appear;

[0243] y0 is selected from 0 and 1;

[0244] Each time the ring C appears, it is independently selected from 3-8 membered cycloalkyl groups, 3-8 membered monocyclic heterocyclic groups containing 1-4 saturated or partially unsaturated heteroatoms selected independently from N, O and S, and 5-8 membered monocyclic heteroaryl groups containing 1-4 heteroatoms selected independently from N, O and S.

[0245] L b Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -O-, -NH-, -C(O)-, -C(O)-O-, -C(O)-C 1-3 Alkylene, -N(C) 1-3 alkyl) and -N(C) 1-3 Alkyl)-C(O);

[0246] L c Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -C(O), -C(O)-C 1-3 Alkylene, -C(O)-cyclopropylene, -N(C 1-3 alkyl)-C(O) and -N(C 1-3 alkyl)-C(O)-C 1-3 Alkylene;

[0247] R A Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl and C 1-3 Alkoxy;

[0248] R B Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)-C. 1-3 Alkyl and C 1-3 alkyl;

[0249] R CEach time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, and C. 1-3 alkyl;

[0250] R D Each occurrence is independently selected from H, F, Cl, Br, I, R. X 、N(R X 2. C(O)R X and C(O)N(R) X )2;

[0251] R X Each occurrence is independently selected from H, F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-membered, 5-membered, 6-membered or 7-membered heterocyclic groups containing 1, 2 or 3 heteroatoms each independently selected from N, O and S, and 6-membered halocyclic groups containing 1, 2 or 3 heteroatoms each independently selected from N, O and S.

[0252] L is the chemical bonding part; and

[0253] ULM is the E3 ubiquitin ligase binding site.

[0254] In some implementation schemes,

[0255] The L is as defined above; preferably, the L is -(B L ) q -;

[0256] B L Each occurrence is independently selected from covalent bonds, CR L5 R L6 O, S, S(O), S(O)2, NR L5 C(O)NR L5C(O), 3-12 membered cycloalkylene groups, 3-12 membered heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered bridged heterocyclic groups, 5-12 membered bridged heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered spirocyclic groups, 5-12 membered spirocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 6-1 The 2-membered arylene and 5-12-membered heteroarylene containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein the 3-12-membered cycloalkylene, 3-12-membered heterocyclic, 5-12-membered bridged cycloalkyl, 5-12-membered bridged heterocyclic, 5-12-membered spirocyclic, 5-12-membered spirocyclic, 6-12-membered arylene, and 5-12-membered heteroarylene are optionally represented by 1, 2, 3, or 4 heteroatoms independently selected from R. L5 Substitution of groups;

[0257] R L5 and R L6 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from C. 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 3-6 Halogenated cycloalkyl, 3-6-membered halogenated heteroalkyl, C 6-8 Aryl, 5-8 quinone heteroaryl, C 6-8 The aryl group is substituted by one or more substituents in the 5-8 membered haloaryl group;

[0258] q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and / or

[0259] The ULM is selected from the structure shown in the following formula: Preferably, the ULM is selected from the structure shown in the following formula:

[0260] in:

[0261] Each time X appears, it is independently selected from N, CH, C(C). 1-6 alkyl) and C(C) 3-6 (cycloalkyl); preferably, X is independently selected from N and CH each time it appears;

[0262] R W Each occurrence is independently selected from O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 alkyl);

[0263] When W1 and W2 appear, they are each independently selected from CH2 and C(O), and at least one of W1 and W2 is selected from C(O);

[0264] W8 and W 10 Each occurrence is independently selected from O, NH, N(C) 1-3 Alkyl), CH(C) 1-3 Alkyl), C(C) 1-3 Alkyl)2 and CH-C 3-6 Cycloalkylene;

[0265] W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(C) 1-3 alkyl);

[0266] R q Each occurrence is independently selected from single bonds and NH;

[0267] R 2a Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl and 3-8 membered heterocyclic groups; preferably, R 2a Each occurrence is independently selected from H, F, Cl, Br, C. 1-3 Alkyl and C 1-3 Halogenated alkyl groups;

[0268] R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3f R 4f R5f R 3g R 4g and R 5g Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl;

[0269] A a A b A c A d and A e Each occurrence is independently selected from O, S, C(O), NR. d and C(R) d )2, R d Each occurrence is independently selected from H, F, Cl, Br, -OH, -CN, -NH2, -NO2, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl;

[0270] B 1a and B 2a Each occurrence is independently selected from N, CH, and C(C) 1-3 Alkyl); preferably, B 1a and B 2a Each occurrence is independently selected from N and CH;

[0271] Each occurrence of m11, m21, and m31 is independently 0, 1, 2, 3, or 4, and 1 ≤ m11 + m21 + m31 ≤ 5; and

[0272] Each time m41 and m51 appear, they are independently 0, 1, 2, 3 or 4, and 1≤m41+m51≤5.

[0273] In some implementation schemes,

[0274] Q0 is selected independently from O, S, CH2, C(O) and NR each time it appears. XPreferably, each occurrence of Q0 is independently selected from O, C(O), S, CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); preferably, each occurrence of Q0 is independently selected from O, CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); preferably, each occurrence of Q0 is independently selected from O and CH2; and / or

[0275] Q1 is selected independently from O, S, and NH each time it appears; and / or

[0276] p2 and p3 are each independently selected from 0 and 1 each time they appear; and / or

[0277] y0 is selected from 1; and / or

[0278] Each time ring C appears, it is independently selected from any chosen element R. C Replacement Preferably, each occurrence of ring C is independently selected from any of the arbitrarily chosen R. C Replacement and / or

[0279] L b Each occurrence is independently selected from the single bonds -CH2-, -CH2CH2-, and -CH2CH2CH2-; preferably, L b For single bonds; and / or

[0280] L c Each occurrence is independently selected from single bonds, -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -C(O)-CH2-, -C(O)-CH2CH2-, -C(O)-cyclopropylidene, -N(CH3)-C(O)-, and -N(CH3)-C(O)-CH2CH2-; preferably, L c -C(O)-CH2CH2-; and / or

[0281] R A Each occurrence is independently selected from H, F, Cl, Br, I, -CH3, -CH2CH3, -CH(CH3)2, -OCH3, and -OCH2CH3; and / or

[0282] R B Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3 and -C(O)-CH3; and / or

[0283] R CEach occurrence is independently selected from H, F, Cl, Br, I, -CH3, and -CH2CH3; and / or

[0284] R D Each occurrence is independently selected from H, F, Cl, Br, I, -OCH3, -CH3, -CH2CH3, -CH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -C(O)-NH(CH3), -C(O)-NH(CH2CH3), -C(O)-N(CH3)2, -C(O)-N(CH3)(CF3), -C(O)-N(CH3)(CH2CH3), -C(O)-N(CH3)(CH(CH3)2), -C(O)-N(CH2CH3)(CH(CH3)2), Preferably, R D -C(O)-N(CH3)2; and / or

[0285] R X Each occurrence is independently selected from H, F, Cl, Br, I, -CF3, -OCH3, -CH3, -CH2CH3, -CH(CH3)2. and / or

[0286] B L Each occurrence is independently selected from single bonds, -O-, -S-, -S(O)-, -S(O)2-, -C≡C-, -CH2-, -C(O)-, -NH-, -N(CH3)-, -N(CH2CH3)-, -C(O)-NH-, -C(O)-N(CH3)-, and / or

[0287] R L5 and R L6 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, -C(O)-C 1-3 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 3-6The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from C. 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-8 The aryl group is substituted with one or more substituents from the 5-8 membered heteroaryl group; preferably, R L5 and R L6 Each time it appears, it is independently selected from H, F, Cl, Br, hydroxyl, cyano, nitro, amino, C. 1-3 Alkyl, C 1-3 Alkoxy, -CF3, -CHF2, -CH2F, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups; and / or

[0288] q is selected from 1, 2, 3, 4, 5, 6, 7, and 8; preferably, q is selected from 1, 2, 3, 4, 5, and 6; and / or

[0289] Each occurrence of X is independently N; and / or

[0290] R W Each occurrence is independently selected from O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 Alkyl); and / or

[0291] W1 is C (=O), W2 is CH2; W1 is CH2, W2 is C (=O); or W1 is C (=O), W2 is C (=O); and / or

[0292] W8 and W 10 Each time it appears, it is independently selected from O, NH, N(CH3), CH(CH3), C(CH3)2 and CH-C. 3-5 Cycloalkylene; and / or

[0293] W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(CH3); and / or

[0294] R 2a Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -CH2CH2F; and / or

[0295] R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4dR 5d R 3f R 4f R 5f R 3g R 4g and R 5g Each occurrence is independently selected from H, F, Cl, Br, -CN, -NO2, -CH3, -CH2CH3, -CH(CH3)2, -OCH3, -OCH2CH3, and -OCH(CH3)2; preferably, R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3f R 4f R 5f R 3g R 4g and R 5g Each occurrence is independently selected from H, F, Cl, Br, -CN, -NO2, -CH3, and -OCH3; and / or

[0296] A a A b A c A d and A e Each occurrence is independently selected from O, C(O), and NR. d and C(R) d )2, R d Each occurrence is independently selected from H, F, Cl, Br, -OH, -CN, -NH2, -NO2, C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups and C 1-3 Hydroxyalkyl; preferably, A a A b A c A d and A e Each occurrence is independently CH2; and / or

[0297] B 1a and B 2a Each occurrence is independently selected from N and CH; and / or

[0298] Each occurrence of m11, m21, and m31 is independently 0, 1, 2, or 3, and 1 ≤ m11 + m21 + m31 ≤ 4; preferably, m11 + m21 + m31 = 1, m11 + m21 + m31 = 2, m11 + m21 + m31 = 3, or m11 + m21 + m31 = 4; preferably, each occurrence of m11 is independently 0 or 1, each occurrence of m21 is independently 1, and each occurrence of m31 is independently 0 or 1; preferably, each occurrence of m11 is independently 0, each occurrence of m21 is independently 1, and each occurrence of m31 is independently 0; and / or

[0299] Each time m41 and m51 appear, they are independently 0, 1, 2, or 3, and 1 ≤ m41 + m51 ≤ 4; preferably, m41 + m51 = 2, m41 + m51 = 3, or m41 + m51 = 4; preferably, each time m41 and m51 appear, they are independently 2.

[0300] In some embodiments, the structure is shown in formula (I-AA-1) or formula (I-BB-1):

[0301] and

[0302] Among them, Q0, Q1, p2, p3, y0, ring C, L b L c R A R B R C R D L, X, R 2a R 3a R 4a A a A b A c A d A e m11, m21, m31, m41 and m51 are defined as above;

[0303] Preferably:

[0304] Each occurrence of Q0 is independently selected from O and CH2; and / or

[0305] Q1 is selected independently from O, S, and NH each time it appears; and / or

[0306] p2 and p3 are each independently selected from 0 and 1 each time they appear; and / or

[0307] y0 is 1; and / or

[0308] Each time ring C appears, it is independently selected from any chosen element R. C Replacement and / or

[0309] L b Each occurrence is an independent single key; and / or

[0310] L c Each occurrence is independently -C(O)-CH2CH2-; and / or

[0311] R A Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -OCH3; and / or

[0312] R B Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -OCH3; and / or

[0313] R C Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -OCH3; and / or

[0314] R D Each occurrence is independently -C(O)-N(CH3)2; and / or

[0315] L is the chemical bonding portion; preferably, L is as defined above; preferably, L is -(B L ) q -;

[0316] B L Each occurrence is independently selected from covalent bonds, CR L5 R L6 O, S, S(O), S(O)2, NR L5 C(O)NR L5 C(O), 3-12 membered cycloalkylene groups, 3-12 membered heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered bridged heterocyclic groups, 5-12 membered bridged heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered spirocyclic groups, 5-12 membered spirocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 6-1 The 2-membered arylene and 5-12-membered heteroarylene containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein the 3-12-membered cycloalkylene, 3-12-membered heterocyclic, 5-12-membered bridged cycloalkyl, 5-12-membered bridged heterocyclic, 5-12-membered spirocyclic, 5-12-membered spirocyclic, 6-12-membered arylene, and 5-12-membered heteroarylene are optionally represented by 1, 2, 3, or 4 heteroatoms independently selected from R.L5 Substitution of groups;

[0317] R L5 and R L6 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from C. 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 3-6 Halogenated cycloalkyl, 3-6-membered halogenated heteroalkyl, C 6-8 Aryl, 5-8 quinone heteroaryl, C 6-8 The aryl group is substituted by one or more substituents in the 5-8 membered haloaryl group;

[0318] Preferably, in formula (I-AA) or formula (I-AA-1), L is selected from 3-12-membered heterocyclic groups, 3-12-membered heterocyclic groups-C(O), and 3-12-membered heterocyclic groups-C 1-6 Alkylene, wherein the 3-12 membered heterocyclic group contains 1-4 heteroatoms independently selected from N, O, and S, and the 3-12 membered heterocyclic group and C 1-6 The alkylene group is optionally selected independently by one, two, three, or four R groups. L5 Substitution of groups; and / or

[0319] In formula (I-BB) or formula (I-BB-1), L is selected from phenylene-3-12-membered heterocyclic group-C 1-6 Alkylene, 3-12 membered heterocyclic phenylene-C 1-6 Alkylene, phenylene-3-12-membered heterocyclic-C(O), and 3-12-membered heterocyclic-phenylene-C(O), wherein the 3-12-membered heterocyclic group contains 1-4 heteroatoms independently selected from N, O, and S, wherein the 3-12-membered heterocyclic group, phenylene, and C 1-6 The alkylene group is optionally selected independently by one, two, three, or four R groups. L5 Substitution of groups;

[0320] R L5 Each time it appears, it is independently selected from OH, CN, F, Cl, Br, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups; preferably, R L5 Each time it appears, it is independently selected from the substitution of groups such as OH, CN, F, Cl, Br, CH3, CH2CH3, CH(CH3)2, OCH3, OCH2CH3, OCH2CH2F and cyclopropyl.

[0321] Preferably, the 3-12 membered heterocyclic group is a 5-8 membered heterocyclic group, preferably selected from piperazinyl and piperidinyl, and more preferably selected from... and / or

[0322] q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and / or

[0323] Each occurrence of X is independently N; and / or

[0324] R 2a Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -CH2CH2F; and / or

[0325] A a A b A c A d and A e Each occurrence is independently CH2; and / or

[0326] Each occurrence of m11, m21, and m31 is independently 0, 1, 2, or 3, and 1 ≤ m11 + m21 + m31 ≤ 4; preferably, m11 + m21 + m31 = 1, m11 + m21 + m31 = 2, m11 + m21 + m31 = 3, or m11 + m21 + m31 = 4; and / or

[0327] Each time m41 and m51 appear, they are independently 0, 1, 2, or 3, and 1≤m41+m51≤4; preferably, m41+m51=2, m41+m51=3 or m41+m51=4.

[0328] In some embodiments, the compound is selected from the compounds of claim 21.

[0329] In some embodiments, the compound is selected from the compounds in Examples 7-28.

[0330] A second aspect of the present invention provides a compound having the structure shown in formula (III):

[0331] Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein:

[0332] Ring B, Ring C, p1, p2, p3, L b L c R A R B R C and R D Same as the definition above;

[0333] Ring A1 is selected from 8-10 membered bicyclic heteroaryl groups containing 1-5 independently selected N, O, and S heteroatoms; 11-15 membered tricyclic heteroaryl groups containing 1-5 independently selected N, O, and S heteroatoms; 11-15 membered tricyclic heterocyclic groups containing 1-5 independently selected N, O, and S heteroatoms, either saturated or partially unsaturated; and 16-20 membered tetracyclic heterocyclic groups containing 1-5 independently selected N, O, and S heteroatoms, either saturated or partially unsaturated, wherein the tricyclic and tetracyclic heterocyclic groups are fused rings, spirocyclic rings, or spirofused ring structures; and

[0334] R E Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)H, C 1-8 Alkyl, C 1-8 Alkoxy group, -C(O)-C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl, 5-8 quinone heteroaryl and -C 6-8 arylene-3-8-membered heterocyclic group, wherein C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl, 5-8 quinone heteroaryl and C 6-8 arylene, optionally selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C 1-6 Alkyl and C 1-6 The alkoxy group is substituted by one or more substituents;

[0335] When R E When connected to a N atom, R E Selected from H and C 1-8 alkyl.

[0336] In some implementation schemes,

[0337] Ring A1 is selected from 9-10 membered bicyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic groups containing 1-4 heteroatoms independently selected from N, O, and S; and 16-18 membered tetracyclic heterocyclic groups containing 1-4 heteroatoms independently selected from N, O, and S; wherein the tricyclic and tetracyclic heterocyclic groups are fused rings, spirocyclic rings, or spirofused fused ring structures; preferably, ring A1 is selected from those containing 1, 2, or 3 heteroatoms. Alternatively, it may contain 9- or 10-membered bicyclic heteroaryl groups with four independently selected N, O, and S heteroatoms; 13-membered tricyclic heteroaryl groups with one, two, or three independently selected N, O, and S heteroatoms; partially unsaturated 12-, 13-, 14-, or 15-membered tricyclic heterocyclic groups with one, two, or three independently selected N, O, and S heteroatoms; and partially unsaturated 16-, 17-, or 18-membered tetracyclic heterocyclic groups with one, two, three, or four independently selected N, O, and S heteroatoms, wherein the tricyclic and tetracyclic heterocyclic groups are fused rings, spirocyclic rings, or spirofused fused ring structures; preferably, ring A1 is selected from... Each occurrence of Q is independently selected from O, S, and NR. X Each time Q0 appears, it is independently selected from O, S, C(R). X )2 and NR X R X As defined above; preferably, ring A1 is selected from... and / or

[0338] R E Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)H, C 1-6 Alkyl, C 1-6 Alkoxy group, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl, 5-6 membered heterocyclic, C 6-7 Aryl, 5-6 quinone heteroaryl and -C 6-7 arylene-5-6-membered heterocyclic group, wherein C 3-6 cycloalkyl, 5-6 membered heterocyclic, C 6-7 Aryl, 5-6 membered heteroaryl and C 6-7 arylene, optionally selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C 1-6 Alkyl and C 1-6The alkoxy group is substituted by one or more substituents;

[0339] When R E When connected to a N atom, R E Selected from H and C 1-6 alkyl.

[0340] In some embodiments, the compound is selected from the structure shown in the following formula:

[0341] Among them, rings B, C, and L b L c R A R B R C R D R E p1, p2, and p3 are defined as described above;

[0342] Q2 is selected independently from CR each time it appears. A , N, C(R) A 2. NR A and C;

[0343] This indicates that two double bonds are formed at any position within the ring, together with Q2 on the ring, to form a conjugated system;

[0344] In equations (IC-1) and (IE-1), Q1 is independently selected from O, S, and NR each time it appears. X ;

[0345] In (IA-1), R 5g Does not exist, or R 5g With R 5a Or R 5f Together they form Cy6;

[0346] When R 5g When Q1 does not exist, each occurrence of Q1 is independently selected from O, S, and NR. X When R 5g With R 5a Or R 5f When they jointly form Cy6, Q1 appears independently as N each time;

[0347] R 5a R 5b R 5c R 5d R 5e R 5f and R 5g The definition is selected from one of the following groups;

[0348] (v-1)R 5cEach time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b R 5d and R 5f Each occurrence is independently selected from R. A Substituents within the specified range;

[0349] (v-2)R 5a and R 5b Together they form Cy3, which is optionally bounded by R D Replace, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5d and R 5f Each occurrence is independently selected from R. A Substituents within the specified range;

[0350] (v-3)R 5b and R 5c Together they form Cy7, which is optionally bounded by R E Replace, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5d and R 5f Each occurrence is independently selected from R. A Substituents within the specified range;

[0351] (v-4)R 5c and R 5d Together they form Cy7, which is optionally bounded by R E Replace, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R5f Each occurrence is independently selected from R. A Substituents within the specified range;

[0352] (v-5)R 5d and R 5e Together they form Cy5, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R 5f Each occurrence is independently selected from R. A Substituents within the specified range;

[0353] (v-6)R 5e and R 5f Together they form Cy5, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R 5d Each occurrence is independently selected from R. A Substituents within the specified range;

[0354] (v-7)R 5f and R 5g Together they form Cy6, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, Q1 is selected from N, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R 5d Each occurrence is independently selected from R. A Substituents within the range; and

[0355] (v-8)R 5g and R 5a Together they form Cy6, which is optionally bounded by R D Replace, and R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, R 5b R 5d and R5f Each occurrence is independently selected from R. A Substituents within the specified range;

[0356] Cy3, Cy5, and Cy6 are defined as described above; and

[0357] Cy7 is independently selected and

[0358] F1, F2, F3, F4, F5, q1, q2, q3, q4 and q5 are defined as above.

[0359] In some embodiments, the compound is selected from the following structures:

[0360] In this case, Q3 is selected independently from CH and N each time it appears; ring B, ring C, and ring L b L c R A R B R C R D As defined above;

[0361] Preferably, R E Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)H, C 1-3 Alkyl, C 1-3 Alkoxy, 5-6 membered heterocyclic, phenyl, and phenylene-5-6 membered heterocyclic, wherein the 5-6 membered heterocyclic, phenyl, and phenylene are optionally selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, and C. 1-3 The alkyl group is substituted with one, two, or three substituents; when R E When connected to a N atom, R E Selected from H and C 1-3 alkyl;

[0362] Preferably, Cy7 is selected independently each time it appears.

[0363] In some embodiments, the compound is selected from the following structures:

[0364] Among them, Q0, Q1, Q3, Q4, p2, p3, y0, ring B1, ring C1, ring C2, L b L c R A R B R Cand R D Same as the definition above;

[0365] R E Each time it appears, it is independently selected from H, F, Cl, Br, I, oxo group (=O), -C(O)H, C 1-3 Alkyl groups, 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms each independently selected from N, O, and S, phenyl groups, and phenylene-6-membered heterocyclic groups, wherein the 6-membered heterocyclic group, phenyl group, and phenylene group are optionally selected from H, F, Cl, Br, I, and C. 1-3 The alkyl group is substituted with one or two substituents; preferably, R E Each time it appears, it is independently selected from H, F, Cl, Br, I, oxo group (=O), -C(O)H, -CH3, -CH2CH3, -CH(CH3)2, and

[0366] When R E When connected to a N atom, R E Selected from H, -CH3, -CH2CH3 and -CH(CH3)2.

[0367] In some embodiments, the compound is selected from the compounds of claim 26.

[0368] In some embodiments, the compound is selected from the compounds in Examples 1-6.

[0369] A third aspect of the present invention provides a pharmaceutical composition comprising an effective amount of a compound as described in the first or second aspect of the present invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0370] The fourth aspect of the present invention provides the use of compounds or pharmaceutically acceptable salts thereof as described in the first or second aspect of the present invention, or pharmaceutical compositions as described in the third aspect of the present invention, in the preparation of medicaments for treating or preventing diseases or conditions mediated by STAT6 protein levels; preferably, the diseases or conditions are autoimmune diseases, cancer, inflammatory diseases, genetic diseases, metabolic diseases, cardiovascular diseases, or central nervous system diseases; preferably, the diseases or conditions are hematologic malignancies, lung or cancer; preferably, the diseases or conditions are acute myeloid monocytic leukemia, or non-small cell lung cancer (NSCLC); preferably, the diseases or conditions are asthma, atopic dermatitis, or chronic obstructive pulmonary disease.

[0371] The fifth aspect of the present invention provides compounds or pharmaceutically acceptable salts thereof as described in the first or second aspect of the present invention, or pharmaceutical compositions as described in the third aspect of the present invention, for the treatment or prevention of diseases or conditions mediated by STAT6 protein levels; preferably, the diseases or conditions are autoimmune diseases, cancer, inflammatory diseases, genetic diseases, metabolic diseases, cardiovascular diseases, or central nervous system diseases; preferably, the diseases or conditions are hematologic malignancies, lung or cancer; preferably, the diseases or conditions are acute myeloid monocytic leukemia, or non-small cell lung cancer (NSCLC); preferably, the diseases or conditions are asthma, atopic dermatitis, or chronic obstructive pulmonary disease.

[0372] The sixth aspect of the present invention provides a method for treating or preventing diseases or conditions mediated by STAT6 protein levels, comprising administering to a subject in need an effective amount of a compound as described in the first or second aspect of the present invention or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in the third aspect of the present invention; preferably, the disease or condition is an autoimmune disease, cancer, inflammatory disease, genetic disease, metabolic disease, cardiovascular disease, or central nervous system disease; preferably, the disease or condition is a hematologic malignancy, lung or cancer; preferably, the disease or condition is acute myeloid monocytic leukemia, or non-small cell lung cancer (NSCLC); preferably, the disease or condition is asthma, atopic dermatitis, or chronic obstructive pulmonary disease.

[0373] A seventh aspect of the present invention provides a method for degrading or inhibiting STAT6 in a patient or biological sample, the method comprising administering to the patient a compound of the first aspect of the present invention or a pharmaceutical composition of the third aspect of the present invention, or contacting the biological sample with a compound of the first aspect of the present invention or a pharmaceutical composition of the third aspect of the present invention; or

[0374] STAT6 is brought into contact with the compound described in the second aspect of the invention or a pharmaceutically acceptable salt thereof; preferably, the contact is made in a patient or biological sample. Attached Figure Description

[0375] Figure 1 illustrates the degradation effects of compounds E-2 and G-1 on STAT6 protein in the spleen of a mouse model of MC-903-induced atopic dermatitis (AD).

[0376] Figure 2 shows the inhibitory effects of compounds E-2 and G-1 on serum IgE levels in a mouse model of MC-903-induced atopic dermatitis (AD); Figure 2A shows the inhibitory effect of compound E-2 on serum IgE levels; Figure 2B shows the inhibitory effect of compound G-1 on serum IgE levels.

[0377] Figure 3 illustrates the degradation effects of compounds E-2 and G-1 on STAT6 protein in the spleen and lungs of an OVA-induced asthma mouse model.

[0378] Figure 4 shows the inhibitory effects of compounds E-2 and G-1 on serum IgE levels in an OVA-induced asthma mouse model; Figure 4A shows the inhibitory effect of compound E-2 on serum IgE levels; Figure 2B shows the inhibitory effect of compound G-1 on serum IgE levels.

[0379] Figure 5 shows the inhibitory effect of compound E-2 on inflammatory cells in the lungs of an OVA-induced asthma mouse model; Figure 5A shows the inhibitory effect of compound E-2 on BAL dendritic cells; Figure 5B shows the inhibitory effect of compound E-2 on BAL-activated B cells; Figure 5C shows the inhibitory effect of compound E-2 on BAL eosinophils; Figure 5D shows the inhibitory effect of compound E-2 on BAL CD4. + Inhibitory effect on cells; Figure 5E shows the effect of compound E-2 on BAL CD8. + Inhibitory effect on cells.

[0380] Figure 6 shows the inhibitory effect of compound G-1 on inflammatory cells in the lungs of an OVA-induced asthma mouse model; Figure 6A shows the inhibitory effect of compound G-1 on BAL dendritic cells; Figure 6B shows the inhibitory effect of compound G-1 on BAL-activated B cells; Figure 6C shows the inhibitory effect of compound G-1 on BAL eosinophils; Figure 6D shows the inhibitory effect of compound G-1 on BAL CD4. + Inhibitory effect on cells; Figure 6E shows the effect of compound G-1 on BAL CD8. + Inhibitory effect on cells. Detailed Implementation

[0381] The following detailed description of specific implementation schemes illustrates the contents of this disclosure, but does not imply any adverse limitation thereof. Various specific implementation schemes of this disclosure have been described in detail herein, and it will be apparent to those skilled in the art that various changes and modifications can be made to these specific implementation schemes without departing from the spirit and scope of this disclosure.

[0382] I. Terms and Definitions

[0383] In this invention, unless otherwise stated, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the related terms and laboratory procedures used herein are all widely used terms and routine procedures in the respective fields. To better understand this invention, definitions and explanations of related terms are provided below.

[0384] In the description herein, references to “some embodiments,” “some implementations,” or “some implementation schemes” describe a subset of all possible embodiments. However, it is understood that “some embodiments” may be the same subset or different subsets of all possible embodiments and may be combined with each other without conflict.

[0385] In this specification and claims, the phrase “and / or” is interpreted as meaning “any one or both” of the elements, that is, the elements may exist together in some cases or the elements may exist separately in other cases.

[0386] As used herein and unless otherwise stated, the terms “comprising,” “including,” “having,” and “containing” include their grammatical equivalents and should generally be understood as open-ended and non-restrictive, e.g., not excluding other unlisted elements or steps.

[0387] When listing a range of values, it is assumed that each value and the subranges within that range are included. For example, "C 1-6 Alkyl groups include C1, C2, C3, C4, C5, C6, and C6. 1-6 C 1-5 C 1-4 C 1-3 C 1-2 C 2-6 C 2-5 C 2-4 C 2-3 C 3-6 C 3-4 C 3-5 C 4-6 C 4-5 and C 5-6 Alkyl; for example, "1-5 heteroatoms" includes 1, 2, 3, 4 and 5 heteroatoms.

[0388] The term "heteroatom" is selected from nitrogen, oxygen, and sulfur. Nitrogen atoms may optionally be substituted; sulfur atoms may also optionally be substituted, for example, by oxidizing (=O), thus forming S(O). t3 (where t3 is an integer from 0 to 2).

[0389] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight-chain or branched group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 12 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) carbon atoms, and more preferably an alkyl group containing 1 to 6 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2, 3-Dimethylpentyl, 2,4-Dimethylpentyl, 2,2-Dimethylpentyl, 3,3-Dimethylpentyl, 2-Ethylpentyl, 3-Ethylpentyl, n-Octyl, 2,3-Dimethylhexyl, 2,4-Dimethylhexyl, 2,5-Dimethylhexyl, 2,2-Dimethylhexyl, 3,3-Dimethylhexyl, 4,4-Dimethylhexyl, 2-Ethylhexyl, 3-Ethylhexyl, 4-Ethylhexyl, 2-Methyl-2-Ethylpentyl, 2-Methyl-3-Ethylpentyl, n-Nonyl, 2-Methyl-2-Ethylhexyl, 2-Methyl-3-Ethylhexyl, 2,2-Diethylpentyl, n-Decyl, 3,3-Diethylhexyl, 2,2-Diethylhexyl, and their various branched isomers, etc. More preferably, lower alkyl groups containing 1 to 6 carbon atoms are used. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, etc. The alkyl group may be substituted or unsubstituted. When substituted, the substituent may be substituted at any usable connection point. The substituent is preferably selected independently from one or more substituents chosen from H atom, D atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl and heteroaryl.

[0390] The term "heteroalkyl" refers to an alkyl group in which one or more -CH2- atoms are replaced by heteroatoms selected from NH, O, and S, or where one or more -CH- atoms are replaced by N atoms; wherein the alkyl group is as defined above; the heteroalkyl group may be substituted or unsubstituted, and when substituted, the substituent may be substituted at any usable connection point, wherein the substituent is preferably independently selected independently from one or more substituents selected from H atoms, D atoms, halogens, alkyl groups, alkoxy groups, haloalkyl groups, hydroxy groups, hydroxyalkyl groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups.

[0391] The term "cyclic hydrocarbon group" refers to a group with a cyclic structure consisting of carbon atoms. Cyclic hydrocarbon groups can be monocyclic or polycyclic. In polycyclic compounds, multiple carbon rings can be linked by sharing a carbon atom or a carbon chain. For example, two carbon rings sharing a single carbon atom are called spirocyclic hydrocarbons, and those sharing two or more carbon atoms are called bridged cyclic hydrocarbons. Cyclic hydrocarbon groups can be substituted or unsubstituted. When substituted, the substituent can be replaced at any usable connection point, preferably independently selected independently from one or more substituents chosen from H atoms, D atoms, halogens, alkyl groups, alkoxy groups, haloalkyl groups, hydroxyl groups, hydroxyalkyl groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups. The terms "cyclic hydrocarbon group" and "cyclic hydrocarbon ring" are used interchangeably.

[0392] The term "alkoxy" refers to -O- (alkyl) and -O- (unsubstituted cycloalkyl), wherein alkyl or cycloalkyl is defined as described herein. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, and cyclohexyloxy. Alkoxy groups may be optionally substituted or unsubstituted, and when substituted, the substituent is preferably one or more substituents independently selected from H atom, D atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl.

[0393] The term "alkenyl" refers to an alkyl compound containing a carbon-carbon double bond in its molecule, wherein the definition of alkyl is as described above. Alkenyl groups can be substituted or unsubstituted, and when substituted, the substituent is preferably one or more substituents selected independently from one or more of the following groups: hydrogen atom, alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl.

[0394] The term "alkynyl" refers to an alkyl compound containing a carbon-carbon triple bond in its molecule, wherein the definition of alkyl is as described above. The alkynyl group can be substituted or unsubstituted, and when substituted, the substituent is preferably one or more substituents selected independently from one or more of the following groups: hydrogen atom, alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl.

[0395] The term "cycloalkyl" refers to a cyclic hydrocarbon substituent of a saturated or partially unsaturated monocyclic, bicyclic, or more rings, including, for example, fused, bridged, or spirocyclic groups. The cycloalkyl ring may contain 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 8 (e.g., 3, 4, 5, 6, 7, or 8) carbon atoms, and even more preferably 4 to 7 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, and cyclooctyl. The cycloalkyl group may be substituted or unsubstituted. When substituted, the substituent may be substituted at any usable connection point, and the substituent is preferably independently selected independently from one or more substituents chosen from hydrogen, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl.

[0396] The term "heterocyclic group" refers to a substituent in a saturated or partially unsaturated monocyclic hydrocarbon containing 3 to 20 ring atoms, one or more of which are selected from nitrogen, oxygen, or S(O). m The ring contains 3 to 12 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12) ring atoms, of which 1 to 4 (e.g., 1, 2, 3, and 4) are heteroatoms; more preferably, it contains 3 to 8 ring atoms, of which 1 to 3 are heteroatoms; even more preferably, it contains 3 to 6 ring atoms, of which 1 to 3 are heteroatoms; and most preferably, it contains 5 or 6 ring atoms, of which 1 to 3 are heteroatoms. Non-limiting examples of monocyclic heterocyclic groups include pyrrolidinyl, tetrahydropyranyl, 1,2,3,6-tetrahydropyridyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, and homopiperazinyl, etc. The terms "heterocyclic group" and "heterocyclic ring" are used interchangeably. The heterocyclic group can be substituted or unsubstituted. When substituted, the substituent can be substituted at any usable connection point. The substituent is preferably selected independently and optionally from one or more substituents selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl.

[0397] The term "aryl" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (fused polycyclic) group having a conjugated π-electron system, preferably 6- to 10-membered, such as phenyl and naphthyl. The aryl ring comprises an aryl ring fused to a heteroaryl, heterocyclic, or cycloalkyl ring as described above, wherein the ring attached to the parent structure is an aryl ring. The aryl group can be substituted or unsubstituted; when substituted, the substituent can be substituted at any usable connection point, preferably independently selected independently from one or more substituents chosen from hydrogen, halogen, alkyl, alkoxy, haloalkyl, hydroxyl, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl. The terms "aryl" and "aromatic ring" are used interchangeably. The term "6-10-membered aryl" refers to a C10-100 aryl group. 6-10 Aryl.

[0398] The term "heteroaryl" refers to a heteroaryl system comprising 1 to 4 (e.g., 1, 2, 3, and 4) heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. The heteroaryl group is preferably 5 to 10-membered (e.g., 5, 6, 7, 8, 9, or 10-membered), more preferably 5- or 6-membered, such as indolyl, furanyl, thiophene, pyridyl, pyrroleyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, etc. The heteroaryl ring comprises a heteroaryl group fused to an aryl, heterocyclic, or cycloalkyl ring as described above, wherein the ring connected to the parent structure is a heteroaryl ring. The heteroaryl group can be substituted or unsubstituted. When substituted, the substituent can be replaced at any usable connection point. The substituent is preferably independently selected independently from one or more substituents chosen from hydrogen, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclic, aryl, and heteroaryl. The terms "heteroaryl" and "heteroaryl ring" are used interchangeably.

[0399] The term "bridged ring" refers to a polycyclic hydrocarbon containing 0-5 heteroatoms, either saturated or partially unsaturated, consisting of two or more rings connected by sharing two or more non-adjacent carbon atoms (bridgehead carbon atoms), wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. Unless otherwise specified, it generally refers to a bicyclic structure consisting of 5-15 ring atoms, either saturated or partially unsaturated, connected by sharing two or more non-adjacent carbon atoms (bridgehead carbon atoms).

[0400] The term "spirocyclic" refers to a polycyclic hydrocarbon formed by two or more saturated or partially unsaturated rings containing 0-5 heteroatoms connected by sharing a single carbon atom (spiro atom), wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. Unless otherwise specified, it generally refers to a bicyclic, tricyclic, or tetracyclic structure formed by two, three, or four saturated or partially unsaturated rings containing 5-15 ring atoms connected by sharing a single carbon atom (spiro atom).

[0401] The term "fused ring" or "fused ring" refers to a polycyclic hydrocarbon formed by two or more saturated or partially unsaturated rings containing 0-5 heteroatoms, connected by sharing two or more adjacent carbon atoms (forming a shared edge), wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. Unless otherwise specified, it generally refers to a bicyclic, tricyclic, or tetracyclic structure formed by two, three, or four saturated or partially unsaturated rings containing 0-5 heteroatoms, connected by sharing two or more adjacent carbon atoms (forming a shared edge).

[0402] The term "subunit" refers to a group obtained by removing a hydrogen atom from a carbon atom containing free valence electrons, and has two connection sites for attaching to the rest of the molecule. For example, the term "arylene" refers to a divalent aryl group formed by further substituting one hydrogen atom of an aryl group, as defined above.

[0403] The term "haloalkyl" refers to an alkyl group that has been substituted with one or more halogens, wherein the alkyl group is as defined above. The definitions of other halogenated substituents are the same.

[0404] The term "deuterated alkyl" refers to an alkyl group that has been substituted with one or more deuterium atoms, wherein the alkyl group is as defined above. The definitions of other deuterated substituents are the same.

[0405] The term "hydroxyalkyl" refers to an alkyl group that is substituted with one or more hydroxyl groups, wherein the alkyl group is as defined above.

[0406] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. The term "amino" refers to -NH2. The term "cyano" refers to -CN. The term "nitro" refers to -NO2.

[0407] "Optional" or "optionally" means that the event or situation described below may, but does not have to, occur, and the description includes the circumstances in which the event or situation occurs or does not occur. For example, "optionally substituted cyclopropyl" means that cyclopropyl can be substituted but is not required to be present, and the description includes the cases in which cyclopropyl is substituted and the cases in which cyclopropyl is not substituted.

[0408] "Substituted" refers to one or more hydrogen atoms in a group, preferably up to five, more preferably one to three hydrogen atoms, which are independently substituted by the corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and those skilled in the art can determine possible or impossible substitutions without much effort (through experiment or theory).

[0409] As used in this article, "replaced by one or more substituents" means that, where substitution is possible, one or more hydrogen atoms in the group are independently replaced by the corresponding number of substituents, and "one or more" is preferably 1 to 5 (1, 2, 3, 4 or 5).

[0410] The term "covalent bond" refers to a chemical bond formed by two or more atoms sharing electron pairs. Generally, one pair of electrons between two atoms represents a covalent single bond, two pairs of electrons represent a double bond, and three pairs of electrons represent a triple bond.

[0411] The term "ubiquitin ligase" refers to a family of proteins that facilitate the transfer of ubiquitin to specific substrate proteins, targeting those proteins for degradation. For example, cerebellar proteins are E3 ubiquitin ligase proteins, alone or in combination with E2 ubiquitin-binding enzymes, that cause ubiquitin to attach to a lysine residue on a target protein and subsequently target a specific protein substrate for degradation via the proteasome. Therefore, E3 ubiquitin ligases, alone or in combination with E2 ubiquitin-binding enzymes, are the cause of ubiquitin transfer to the target protein. Generally, ubiquitin ligases participate in polyubiquitination, where a second ubiquitin is attached to a first ubiquitin, a third ubiquitin to a second ubiquitin, and so on. Polyubiquitinated proteins are used for degradation via the proteasome. However, there are some ubiquitination events limited to monoubiquitination, where only a single ubiquitin is added to the substrate molecule via a ubiquitin ligase. Monoubiquitinated proteins are not targeted to the proteasome for degradation but may instead be altered in their cellular location or function, for example, by binding to other proteins with domains capable of binding ubiquitin. Complicating matters further, different lysine residues on ubiquitin can be targeted by E3 to prepare chains. The most common lysine is Lys48 on the ubiquitin chain. This is the lysine used to prepare polyubiquitin, and it is recognized by the proteasome.

[0412] The term "target protein" refers to proteins and peptides that have any biological function or activity (including structural, regulatory, hormonal, enzymatic, genetic, immune, contractile, storage, transport, and signal transduction). In some implementations, target proteins include structural proteins, receptors, enzymes, cell surface proteins, and proteins involved in integrated cellular functions, including proteins involved in: catalytic activity, aromatase activity, motility activity, helicase activity, metabolic processes (anabolism and catabolism), antioxidant activity, proteolysis, biosynthesis, proteins with kinase activity, oxidoreductase activity, transferase activity, hydrolase activity, lyase activity, isomerase activity, ligase activity, enzyme regulator activity, signal transduction factor activity, structural molecule activity, binding activity (proteins, lipids, carbohydrates), receptor activity, cell motility, membrane fusion, cell communication, regulation of biological processes, development, cell differentiation, stimulus response, behavioral proteins, cell adhesion proteins, proteins involved in cell death, proteins involved in transport (including protein transport activity, nuclear transport, ion transport activity, channel transport activity, carrier activity), permease activity, secretory activity, electron transport activity, pathogens, associated protein regulator activity, nucleic acid binding activity, transcription regulator activity, extracellular structure and biological origin activity, and translation regulator activity. The proteins include proteins derived from eukaryotes and prokaryotes, which include microorganisms, viruses, fungi, and parasites, as well as numerous others, including humans, microorganisms, viruses, fungi, and parasites that are targets for drug therapy, other animals including domestic animals, microorganisms and other antimicrobial drugs used to determine the targets of antibiotics, plants, and even viruses, as well as numerous others.

[0413] The term "compound of this invention or disclosure" refers to compounds of formula (I), (I0), (I1), (I2), (I3), (I4), (I5), (I6), (I7), (I-AA), (I-AA0), (I-AA1), (I-AA2), (I-BB), (I-BB2), (II0), or (II) and their sub-formulas, as well as isomers such as stereoisomers (including diastereomers, enantiomers, and racemates), geometric isomers, conformational isomers (including rotational isomers and tautomers), tautomers, isotopically labeled compounds (including deuterium-substituted compounds), and intrinsically formed moieties (e.g., polymorphs, solvates, and / or hydrates). Salts are also included when a salt-forming moiety is present, particularly pharmaceutically acceptable salts.

[0414] The term "isomer" refers to a compound that has the same molecular formula as the compound of this invention but differs in atomic arrangement or spatial configuration. It generally includes structural isomers, stereoisomers, enantiomers, mirror-symmetric chiral molecules, diastereomers, and non-mirror-symmetric stereoisomers. Those skilled in the art will recognize that the compounds disclosed herein may contain chiral centers and therefore may exist in different isomeric forms.

[0415] An enantiomer is a pair of stereoisomers that are non-overlapping mirror images of each other. A 1:1 mixture of a pair of enantiomers is a racemic mixture. This term is used to denote suitable racemic mixtures. When specifying the stereochemistry of the compounds of this disclosure, a single stereoisomer with known relative and absolute configurations of two chiral centers (e.g., (1S,2S)) is specified using the conventional RS system; a single stereoisomer with known relative configurations but unknown absolute configurations is indicated by an asterisk (e.g., (1R*,2R*)); and racemates with two letters (e.g., (1RS,2RS) as a racemic mixture of (1R,2R) and (1S,2S); (1RS,2SR) as a racemic mixture of (1R,2S) and (1S,2R)). A diastereomer is a stereoisomer having at least two asymmetric atoms that are not mirror images of each other. Absolute stereochemistry is specified according to the Cahn-Ingold-Prelog RS system. When the compound is a pure enantiomer, the stereochemistry at each chiral carbon atom can be specified by R or S. Dissociated compounds whose absolute conformation is unknown can be specified (+) or (-) according to the direction (dextrorotatory or levorotatory) in which they rotate plane-polarized light at the wavelength of the sodium D line. Alternatively, the resolved compound can be defined by chiral HPLC using the corresponding retention times of the enantiomers / diastereomers.

[0416] Some of the compounds described herein contain one or more asymmetric centers or axes, and thus can produce enantiomers, diastereomers, and other stereoisomers that can be determined in absolute stereochemistry, such as (R)- or (S)-.

[0417] Geometric isomers occur when a compound contains a double bond or other features that provide a certain degree of structural rigidity to the molecule. If the compound contains a double bond, its substituents can be E or Z configurations. If the compound contains a disubstituted cycloalkyl group, the cycloalkyl substituents can have cis- or trans-configurations.

[0418] Conformational isomers are isomers that differ by rotation of one or more bonds. Rotational isomers are conformational isomers that differ by rotation of only one bond.

[0419] The term "restricted rotation isomer" refers to structural isomers based on axial or planar chirality, which are generated by restricted rotation in the molecule.

[0420] Unless otherwise stated, the compounds disclosed herein are intended to include all such possible isomers, including racemic mixtures, optionally pure forms, and intermediate mixtures. Optically active (R)- and (S)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques (e.g., separation on chiral SFC or HPLC columns, such as those available from Daicel Corp. and other equivalent columns, using suitable solvents or mixed solvents to achieve good separation).

[0421] The compounds of this disclosure can be separated in optically active or racemic form. The optically active form can be prepared by resolving the racemic form or by synthesizing optically active starting materials. All methods used to prepare the compounds of this disclosure and the intermediates prepared therein are considered part of this disclosure. When preparing enantiomers or diastereomers, they can be separated by conventional methods, such as chromatography or fractional crystallization.

[0422] Depending on the process conditions, the final products of this disclosure are obtained in free (neutral) or salt form. Both the free form and the salt of these final products are within the scope of this disclosure. If desired, one form of the compound can be converted to another. Free bases or acids can be converted to salts; salts can be converted to free compounds or another salt; mixtures of isomers of this disclosure can be separated into individual isomers.

[0423] Pharmaceutically acceptable salts are preferred. However, other salts may be useful, for example, in the separation or purification steps that may be used in the preparation process, and are therefore contemplated within the scope of this disclosure.

[0424] The term "pharmaceutically acceptable salt" refers to a salt of the compounds of this invention that possesses the desired biological activity, meets pharmaceutical standards, and is safe and effective when used in mammals. "Pharmaceutically acceptable salt" refers to a derivative of the disclosed compound, wherein the parent compound is modified by preparing its acid or base salt. For example, pharmaceutically acceptable salts include, but are not limited to, acetates, aspartates, benzoates, benzenesulfonates, bicarbonates / carbonates, bisulfates / sulfates, camphorsulfonates, decanoates, chlorides / hydrochlorides, chlorourea acetates, citrates, ethanediosulfates, fumarates, gluconates, glucurons, glucuronides, glutamates, glutarate, glycolates, hippurates, hydroiodates / iodides, hydroxyethylsulfonates, lactates, lactobionates, dodecyl sulfates, and malates. Maleate, malonate / hydroxymalonate, mandelate, methyl sulfate, mucilage, naphthate, naphthalene sulfonate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, dihydroxynaphthalate, phenylacetate, phosphate / hydrogen phosphate / dihydrogen phosphate, polygalacturonate, propionate, salicylate, stearate, succinate, aminosulfonate, sulfosalicylate, tartrate, toluenesulfonate, trifluoroacetate, and xinafoate.

[0425] Pharmaceutically acceptable acid addition salts can be formed from inorganic and organic acids. Inorganic acids from which salts can be obtained include, for example, hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid. Organic acids from which salts can be obtained include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, ethanesulfonic acid, toluenesulfonic acid, and sulfosalicylic acid.

[0426] Pharmaceutically acceptable base addition salts can be formed from inorganic and organic bases. Inorganic bases from which salts can be obtained include, for example, ammonium salts and metals from columns I through XII of the periodic table. In some embodiments, salts are obtained from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper; particularly suitable salts include ammonium, potassium, sodium, calcium, and magnesium salts. Organic bases from which salts can be obtained include, for example, primary, secondary, and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, basic ion exchange resins, etc. Certain organic amines include isopropylamine, benzylamine, choline, diethanolamine, diethylamine, lysine, meglumine, piperazine, and tromethamine.

[0427] The pharmaceutically acceptable salts disclosed herein can be synthesized by conventional chemical methods from parent compounds containing a basic or acidic moiety. Typically, such salts are prepared by reacting the free acidic or basic form of these compounds with a stoichiometric amount of a suitable base or acid in water, in an organic solvent, or in a mixture of both; typically, non-aqueous media such as diethyl ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred.

[0428] The term "polymorph" refers to the different crystal structures formed by the compounds of this invention due to different molecular packing arrangements.

[0429] Compounds of this disclosure containing groups capable of acting as hydrogen bond donors and / or acceptors can form cocrystals with suitable cocrystal formers. These cocrystals can be prepared from the compounds of this disclosure using known cocrystal formation methods. Such methods include grinding, heating, co-sublimation, co-melting the compounds of this disclosure with a cocrystal former under crystallization conditions, or contacting the compounds of formula (I) with a cocrystal former in solution and separating the resulting cocrystal. Therefore, this disclosure also provides cocrystals comprising the compounds of this disclosure.

[0430] The term "isotope derivative" refers to a derivative of a compound of the present invention in which one or more atoms are substituted with their isotopes. Any formula given herein is also intended to represent both the unlabeled and isotopically labeled forms of the compound. Isotopically labeled compounds have a structure represented by the formulas given herein, except that one or more atoms are substituted with atoms having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the compounds of this disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, respectively, for example... 2 H, 3 H, 11 C 13 C 14 C 15 N、 18 F, 31 P, 32 P, 35 S, 36 Cl、 125 I. This disclosure includes various isotopically labeled compounds as described herein, for example, those such as 3 H and 14 Those radioactive isotopes of C, or those containing, etc. 2 H and 13 Those are non-radioactive isotopes of carbon. Compounds labeled with these isotopes can be used in metabolic studies (using...). 14 C) Reaction kinetic studies (using, for example) 2 H or 3 H), including in the tissue distribution testing of drugs or substrates using detection or imaging techniques (such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT)), or in the treatment of patients with radiation. Specifically, this may be particularly necessary. 18 F-labeled compounds are used in PET or SPECT studies.

[0431] In addition, heavier isotopes, especially deuterium (i.e., 2H or D substitution can provide certain therapeutic advantages due to increased metabolic stability, such as prolonged in vivo half-life, reduced dose requirements, or improved therapeutic parameters. It should be understood that deuterium as described herein is considered a substituent for the compounds disclosed herein. The concentration of such heavier isotopes (specifically deuterium) can be defined by an isotope enrichment factor. As used herein, the term "isotope enrichment factor" refers to the ratio between the isotopic abundance and the native abundance of a particular isotope. If the substituent in the compounds disclosed herein is deuterium, then such compounds have an isotopic enrichment factor for each specified deuterium atom of at least 3500 (52.5% deuterium doping for each specified deuterium atom), at least 4000 (60% deuterium doping), at least 4500 (67.5% deuterium doping), at least 5000 (75% deuterium doping), at least 5500 (82.5% deuterium doping), at least 6000 (90% deuterium doping), at least 6333.3 (95% deuterium doping), at least 6466.7 (97% deuterium doping), at least 6600 (99% deuterium doping), or at least 6633.3 (99.5% deuterium doping).

[0432] The isotopically labeled compounds disclosed herein can generally be prepared using conventional techniques known to those skilled in the art or by the methods disclosed in the schemes or examples and the preparation methods described below (or processes similar to those described herein): by replacing any other non-isotopically labeled reagents with a suitable or readily available isotopically labeled reagent. Such compounds have a variety of potential uses, for example, as standards and reagents for determining the ability of potential pharmaceutical compounds to bind to target proteins or receptors, or for imaging substances binding to the disclosed biological receptors in vivo or in vitro.

[0433] The term "solvent" refers to the physical combination of the disclosed compound with one or more solvent molecules, whether organic or inorganic. This physical combination includes hydrogen bonds. In some cases, the solvate will be separable, such as when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. Solvent molecules in a solvate may be present in a regular and / or disordered arrangement. A solvate may contain stoichiometric or non-stoichiometric amounts of solvent molecules. "Solvent" includes both a solution phase and a separable solvate. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Methods of solvation are generally known in the art.

[0434] The compounds of the present invention may also be in prodrug form. The term "prodrug" refers to a compound that produces an active compound when metabolized (e.g., in vivo or in vitro). In some embodiments, a prodrug may be inactive or have lower activity than the free drug, but may provide advantageous processing, administration, or metabolic properties.

[0435] The term "pharmaceuticalally acceptable carrier" refers to an inactive ingredient or medium used in pharmaceuticals that is formulated with the active ingredient without significantly reducing its therapeutic effect and without causing toxic side effects to the human body.

[0436] Example II

[0437] The following examples pertain to the intermediate compounds and final products identified in the specification and synthetic regimens. The preparation of the compounds of the present invention is described in detail using the following examples, but the described chemical reactions are disclosed in accordance with their general applicability to the preparation of the compounds of the present invention. Sometimes, the reactions may not be applicable to every compound as described in the present invention. Compounds in which this may occur are readily identifiable to those skilled in the art. In these cases, the reactions can be successfully carried out with conventional modifications known to those skilled in the art. In all preparation methods, all starting materials are known or can be readily prepared using known starting materials.

[0438] The starting materials, chemical reagents, and solvents used in this disclosure are all commercially available and were purchased from companies such as Anaiji Chemical, Shanghai Bid Pharmaceutical, Beijing Innocare, Jiangsu Aikon, Sinopharm Group, Beijing Bailingwei, and Yunnan Xinlanjing.

[0439] The structures of all compounds synthesized in this application were determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS).

[0440] Nuclear magnetic resonance (NMR) measurements were performed using a Bruke AVANCE-400 / 600 NMR spectrometer. The deuterated solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3 or Chloroform-d), and deuterated methanol (CD3OD or Methanol-d4). The internal standard was tetramethylsilane (TMS).

[0441] Mass spectrometry (MS) measurements were performed using Waters Acquity Plus device implementation.

[0442] High-performance liquid chromatography (HPLC) preparation was carried out using a Waters 2489 system.

[0443] The medium-pressure rapid preparative chromatograph is a COMBIFLASH NEXTGEN300+.

[0444] The thin-layer chromatography silica gel plates used are Silica gel60 thin-layer chromatography silica gel plates (aluminum plates, containing fluorescence).

[0445] The silica gel (100-200 mesh, 200-300 mesh) used in silica gel thin-layer chromatography was purchased from Inokai.

[0446] The reaction process in the examples was monitored using thin-layer chromatography (TLC). The systems used to monitor the developing solvent and the eluent used to purify the compounds by TLC included: petroleum ether / ethyl acetate system and dichloromethane / methanol system.

[0447] The ULM portion in this disclosure can be prepared by referring to the preparation methods described in patent applications WO2025049820A1, WO2025049821A1, CN118632848A and WO2024240268A1.

[0448] Example 1: Synthesis of compound a-1

[0449] 6-(3-(3-(1H-1,2,3-triazol-1-yl)propionyl)-3-azabicyclo[4.1.0]hept-1-yl)-7-fluoro-N,N-dimethyl-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indole-2-carboxamide (compound a-1)

[0450] Synthesis scheme

[0451] Step 1: 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-3-azabicyclo[4.1.0]heptane (compound a-1b)

[0452] Add 50 mL of ultra-dry dichloromethane to a 500 mL round-bottom flask and place it under an inert atmosphere (N2). Add diethylzinc (60 mL, 1 M / n-hexane, 8.00 eq) through a delivery tube. Cool the flask to -40 °C (dry ice / MeCN). Dissolve 8.6 mL of diiodomethane (16.0 eq) in 20 mL of dichloromethane and slowly add it to the flask through a dropping funnel. Stir the reaction mixture at -40 °C for 1 hour. Dissolve 4 mL of trifluoroacetic acid (8.00 eq) in 20 mL of dichloromethane and slowly add it dropwise to the flask through a funnel at -40 °C. Heat the reaction mixture to -15 °C and stir at this temperature for 1 hour. Dissolve 2.0 g of commercially available compound a-1a (1.00 eq) in 20 mL of dichloromethane and slowly add it to the reaction mixture. Heat the reaction mixture to room temperature and stir overnight. The reaction solution was concentrated to obtain 5.23 g of crude product (compound a-1b). The crude product was used directly in the next reaction step.

[0453] Step 2: 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-3-azabicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (compound a-1c)

[0454] Add 50 mL of tetrahydrofuran to a 250 mL round-bottom flask, followed by di-tert-butyl dicarbonate (9.8 g, 5.00 eq), triethylamine (9.07 g, 10.0 eq), and 4-dimethylaminopyridine (274 mg, 0.25 eq). Continue stirring at room temperature for 3 hours, then dilute with 100 mL of ethyl acetate and wash three times with 100 mL of 20% sodium hydroxide aqueous solution, 100 mL of water, and 100 mL of saturated ammonium chloride aqueous solution. Back-extract the aqueous phase once with 100 mL of ethyl acetate. Dry the organic phase over anhydrous sodium sulfate, filter, and concentrate to give 2 g of a reddish-brown oily crude product. Dissolve the crude product in 40 mL of tetrahydrofuran and 20 mL of water. Bromosuccinimide (890 mg, 2 eq) was added to the solution, and the reaction was carried out at room temperature for 30 minutes. The reaction solution was diluted with ethyl acetate (100 mL) and washed with sodium bicarbonate (100 mL) and water (100 mL). The aqueous phase was back-extracted once with ethyl acetate (100 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by column chromatography (0-35% EA / PE) to give 238 mg of a pale yellow solid (compound a-1c).

[0455] 1 H NMR (600MHz, DMSO-d6) δ3.85–3.34(m,3H),3.15(dt,J=12.7,6.1Hz,1H),2.94(s,1H),1.88(dq,J=12. 6, 6.2Hz, 1H), 1.66 (s, 1H), 1.38 (s, 9H), 1.17 (s, 12H), 0.75 (dq, J = 8.3, 4.1Hz, 1H), 0.43–0.33 (m, 1H).

[0456] Step 3: 1-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-3-azabicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (compound a-1e)

[0457] Compound a-1d (160 mg, 1 eq) was dissolved in dioxane:water = 10:1 (3 mL), and compound a-1c (160 mg, 1 eq), 1,1-bis(diphenylphosphine)dimerferropalladium dichloride (74 mg, 0.2 eq), and potassium phosphate (307 mg, 3 eq) were added. The reaction was carried out overnight at 100 °C under nitrogen protection. After the reaction was complete, saturated ammonium chloride solution (5 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (10 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under vacuum. The crude product was purified by column chromatography to obtain compound a-1e (38 mg, 17.41%).

[0458] 1H NMR (400MHz, Methanol-d4) δ7.06(d,J=5.2Hz,1H),6.89(d,J=3.0Hz,1H),3.37(s,2H),3.14(d,J=24.6Hz,3H),2.2 5–2.16(m,1H),1.91–1.80(m,1H),1.55–1.39(m,9H),1.38–1.29(m,1H),1.22(s,6H),1.10(dd,J=9.3,5.2Hz,1H).

[0459] LC-MS(ESI):[M-Boc+H] + =380.39.

[0460] Step 4: 1-(2-(dimethylcarbamoyl)-7-fluoro-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indol-6-yl)-3-azabicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (compound a-1g)

[0461] Compound a-1e (30 mg, 1 eq) was dissolved in dioxane:water = 10:1 (2 mL), and compound a-1f (31 mg, 1.5 eq), Xphos Pd G3 (12 mg, 0.2 eq), and potassium phosphate (43 mg, 3 eq) were added. The reaction was carried out at 100 °C for 2 hours under nitrogen protection. After the reaction was complete, saturated ammonium chloride solution (5 mL) was added to the reaction system, followed by extraction three times with ethyl acetate (10 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under vacuum. The crude product was purified by thin-layer chromatography to obtain compound a-1g (5 mg, 12.62%).

[0462] LC-MS(ESI):[M+H] + =576.58

[0463] Step 5: 6-(3-azabicyclo[4.1.0]heptane-1-yl)-7-fluoro-N,N-dimethyl-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indole-2-carboxamide (compound D-1h)

[0464] Compound a-1g (5 mg, 1 eq) was dissolved in 4 M HCl in dioxane (2 mL) and reacted at room temperature for 0.5 hours. After the reaction was completed, the solution was concentrated under vacuum to obtain crude compound a-1h (5 mg).

[0465] LC-MS(ESI):[M+H] + =476.59

[0466] Step 6: 6-(3-(3-(1H-1,2,3-triazol-1-yl)propionyl)-3-azabicyclo[4.1.0]heptane-1-yl)-7-fluoro-N,N-dimethyl-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indole-2-carboxamide (compound a-1)

[0467] Compound a-1h (5 mg, 1 eq) was dissolved in N,N-dimethylformamide (1 mL), and compound a-1i (2.23 mg, 1.5 eq), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (3.8 mg, 2 eq), 1-hydroxybenzotriazole (2.7 mg, 2 eq), and N,N-diisopropylethylamine (3.9 mg, 3 eq) were added. The reaction was carried out at room temperature for 2 hours. After the reaction was completed, compound a-1 (0.6 mg, 9.53%) was obtained by HPLC purification.

[0468] 1 H NMR (400MHz, Methanol-d4) δ7.99(dd,J=12.6,1.0Hz,1H),7.70(dd,J=6.9,1.0Hz,1H),7.58(dd,J=8.5,3.0Hz,2H),7.17(d,J=8.2Hz,2H),7.02(dd,J =11.9,6.0Hz,1H),6.92(dd,J=3.3,2.1Hz,1H),4.79-4.68(m,3H),4.43(d ,J=13.2Hz,1H),4.00(d,J=13.6Hz,1H),3.91–3.84(m,1H),3.73(d,J=13.6 Hz,1H),3.65(dt,J=13.6,5.2Hz,1H),3.47(d,J=13.2Hz,1H),3.42–3.35( m,2H),3.23–3.08(m,6H),3.01(d,J=4.7Hz,3H),2.26(qd,J=18.0,16.3,7. 4Hz,2H),1.91(d,J=39.2Hz,2H),1.53–1.43(m,1H),1.31(s,2H),1.12(ddd ,J=14.2,9.1,5.2Hz,1H),0.96–0.85(m,1H),0.69(dt,J=25.2,5.4Hz,1H).

[0469] LC-MS(ESI):[M+H] + =599.58

[0470] Example 2 Synthesis of compound b-1

[0471] 5'-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4'-fluoro-N,N-dimethyl-4-oxo-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (compound b-1)

[0472] Synthesis scheme

[0473] Step 1: 2,6-Difluoro-4-iodo-3-methylaniline (compound b-1b)

[0474] 2,6-Difluoro-3-methylaniline (5 g, 34.93 mmol) was dissolved in N,N-dimethylformamide (50 mL), cooled to 0 °C, and N-iodosuccinimide (10.22 g, 45.41 mmol) was slowly added to the reaction system. The reaction system was then reacted at room temperature for 8 hours. After the reaction was completed, water (100 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (50 mL). The organic phases were combined, washed three times with saturated sodium chloride (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to give compound b-1b (9.28 g, 98.80%).

[0475] 1 H NMR (400MHz, DMSO-d6) δ7.35 (dd, J=10.2, 2.1Hz, 1H), 5.33 (s, 2H), 2.19 (dd, J=3.0, 1.1Hz, 3H).

[0476] LC-MS(ESI):[M+H] + =270.07

[0477] Step 2: 2-Chloro-1,3-difluoro-5-iodo-4-methylbenzene (compound b-1c)

[0478] Cuprous chloride (5.89 g, 59.47 mmol) and tert-butyl nitrite (5.75 g, 55.76 mmol) were dissolved in acetonitrile (50 mL). The mixture was heated to 65 °C, and compound b-1b (10 g, 37.17 mmol) was slowly added to the reaction system. The reaction was allowed to proceed at room temperature for 20 minutes. The reaction system was filtered through diatomaceous earth, and the filtrate was concentrated under vacuum. The crude product was purified by column chromatography to give compound b-1c (7.20 g, 67.15%).

[0479] 1H NMR (400MHz, DMSO-d6) δ7.66 (dd, J=7.2, 1.9Hz, 1H), 2.31 (dd, J=2.9, 1.2Hz, 3H).

[0480] Step 3: 2-(bromomethyl)-4-chloro-3,5-difluoro-1-iodobenzene (compound b-1d)

[0481] Compound b-1c (6 g, 20.80 mmol) and azobisisobutyronitrile (0.68 g, 4.16 mmol) were dissolved in 1,2-dichloroethane (300 mL). The reaction was heated to 80 °C under a nitrogen atmosphere, and N-bromosuccinimide (7.40 g, 41.60 mmol) was added. The reaction was continued at 80 °C for 8 hours. The reaction mixture was concentrated, and the crude product was purified by column chromatography to give compound b-1d (5.30 g, 69.30%).

[0482] 1 H NMR (400MHz, DMSO-d6) δ7.77 (dd, J=7.1, 1.8Hz, 1H), 4.71–4.67 (m, 3H).

[0483] Step 4: 8-(3-chloro-2,4-difluoro-6-iodobenzyl)-1,4-dioxospiro[4.5]decane-8-carboxaldehyde (compound b-1e)

[0484] 1,4-Dioxospiro[4.5]decane-8-carboxaldehyde (2.78 g, 16.33 mmol) was dissolved in ultra-dry tetrahydrofuran (40 mL). The reaction mixture was cooled to -30 °C under a nitrogen atmosphere. Potassium tert-butoxide (1.68 g, 14.97 mmol) was slowly added to the reaction mixture, and the mixture was stirred at -30 °C for 1 hour. A tetrahydrofuran solution of compound b-1d (5.00 g, 13.61 mmol) was slowly added at -30 °C. After stirring at -30 °C for 2 hours, the mixture was allowed to cool to room temperature and the reaction was continued for 8 hours. The reaction mixture was concentrated, and the crude product was purified by column chromatography to give compound b-1e (2.85 g, 45.85%).

[0485] Step 5: (8-(3-chloro-2,4-difluoro-6-iodobenzoyl)-1,4-dioxospiro[4.5]nonane-8-yl)methanol (compound b-1f)

[0486] Compound b-1e (4.00 g, 8.76 mmol) was dissolved in methanol (20 mL). The reaction mixture was cooled to 0 °C, and sodium borohydride (0.33 g, 8.76 mmol) was slowly added to the reaction system. The mixture was stirred at 0 °C for 10 minutes. Then, a tetrahydrofuran solution of compound b-1d (5.00 g, 13.61 mmol) was slowly added to the reaction system at -30 °C. After stirring at -30 °C for 2 hours, the mixture was allowed to cool to room temperature and the reaction continued for 8 hours. After the reaction was complete, water (20 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (20 mL). The organic phases were combined, washed once with saturated sodium chloride (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound b-1f (3.58 g, 89.11%).

[0487] LC-MS(ESI):[M+H] + =459.19

[0488] Step 6: 8-Chloro-7-fluoro-5-iodopispiro[chromane-3,1'-cyclohexane-4',2”-[1,3]dioxolane] (compound b-1g)

[0489] Compound b-1f (1.00 g, 2.18 mmol) was dissolved in N,N-dimethylformamide (20 mL). Sodium hydride (95.92 mg, 2.40 mmol) was added to the reaction system, and the reaction was heated to 80 °C for 8 hours. After the reaction was completed, water (40 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (40 mL). The organic phases were combined and washed three times with saturated sodium chloride (40 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound b-1g (0.78 g, 81.56%).

[0490] 1 H NMR (600MHz, DMSO-d6) δ7.55 (d, J = 8.4Hz, 1H), 4.02 (s, 2H), 3.87 (s, 4H), 2.49 (s, 2H), 1.67–1.39 (m, 8H).

[0491] Step 7: 8-Chloro-7-fluorodispiro[chromane-3,1'-cyclohexane-4',2”-[1,3]dioxolane]-5-carboxaldehyde (compound b-1h)

[0492] Compound b-1 g (1.80 g, 4.10 mmol) was dissolved in toluene (10 mL), and the reaction was cooled to -30 °C. Isopropyl magnesium chloride (0.63 mg, 6.16 mmol) was slowly added, and the reaction was stirred at -30 °C for 1 hour. Then, N,N-dimethylformamide (1.20 g, 16.41 mmol) was slowly added, and the temperature was gradually raised to 0 °C with stirring for 1 hour. After the reaction was complete, water (10 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (20 mL). The organic phases were combined, washed once with saturated sodium chloride (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound b-1h (0.56 g, 40.05%).

[0493] LC-MS(ESI):[M+H] + =341.39

[0494] 1 H NMR (400MHz, DMSO-d6) δ10.18–10.16(m,1H),7.43(d,J=9.2Hz,1H),4.09(s,2H),3.87(s,4H),3.09(s,2H),1.66–1.57(m,4H),1.55–1.39(m,4H).

[0495] Step 8: (Z)-2-azido-3-(8-chloro-7-fluorodispiro[chromane-3,1'-cyclohexane-4',2”-[1,3]dioxyglycan]-5-yl)methyl acrylate (compound b-1i)

[0496] Compound b-1h (300 mg, 1.0 eq) was dissolved in methanol (10 mL) in a 50 mL two-necked flask under nitrogen protection. Methyl azide (510 mg, 5.0 eq) was added, and the mixture was cooled to -20 °C. Then, sodium methoxide solution (0.9 mL, 5.4 M / methanol, 5.00 eq) was slowly added dropwise. The reaction mixture was slowly heated to room temperature and stirred overnight. The reaction solution was quenched with ice water, extracted with dichloromethane, and the organic phase was evaporated to dryness and purified by column chromatography to obtain compound b-1i (150 mg, 38.9%).

[0497] 1 H NMR(400MHz,DMSO-d6)δ7.49(d,J=10.7Hz,1H),6.92(s,1H),4.03(s,2H),3 .88(s,3H),3.86(s,4H),2.58(s,2H),1.64–1.56(m,4H),1.50–1.41(m,4H).

[0498] Step 9: Methyl 5-chloro-4-fluoro-3,9-dihydro-7H-dispiro[pyrano[3,2-e]indole-8,1'-cyclohexane-4',2”-[1,3]dioxolane]-2-carboxylic acid (compound b-1j)

[0499] In a 50 mL round-bottom flask, compound b-1i (150 mg, 1.0 eq) was dissolved in xylene (5 mL) and stirred in an oil bath at 150 °C for 2 hours. After the reaction was complete, the reaction solution was cooled to 0 °C, and the precipitated white solid was the product. After filtration, compound b-1i (70 mg, 49.8%) was obtained.

[0500] 1 H NMR (400MHz, DMSO-d6) δ12.46(s,1H),7.30–7.26(m,1H),3.98(s,2H),3.90–3.84(m,7H),2.81(s,2H),1.75–1.57(m,4H),1.56–1.43(m,4H).

[0501] LC-MS(ESI):[M+H] + =410.29.

[0502] Step 10: 5-Chloro-4-fluoro-3,9-dihydro-7H-dispiro[pyrano[3,2-e]indole-8,1'-cyclohexane-4',2”-[1,3]dioxolane]-2-carboxylic acid (compound b-1k)

[0503] Compound b-1i (60 mg, 1 eq) was dissolved in methanol:dimethyl sulfoxide:water = 4:1:1 (5 mL), and lithium hydroxide monohydrate (95 mg, 10 eq) was added. The mixture was stirred overnight at room temperature. After the reaction was complete, dilute hydrochloric acid was added to adjust the pH to acidic, and the mixture was extracted twice with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected and concentrated under vacuum to give compound b-1k (45 mg, 77.6%). This crude product was used directly in the next step.

[0504] LC-MS(ESI):[M+H] + =396.39.

[0505] Step 11: 5-Chloro-4-fluoro-N,N-dimethyl-3,9-dihydro-7H-dispiro[pyrano[3,2-e]indole-8,1'-cyclohexane-4',2”-[1,3]dioxolane]-2-carboxamide (compound b-1l)

[0506] Compound b-1k (45 mg, 1.0 eq), dimethylamine hydrochloride (28 mg, 3.0 eq), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (33 mg, 1.5 eq), and 1-hydroxybenzotriazole (46 mg, 3.0 eq) were dissolved in N,N-dimethylformamide (5 mL), and N,N-diisopropylethylamine (75 mg, 5.0 eq) was added. The mixture was stirred overnight at room temperature. After the reaction was complete, compound b-1l (40 mg, 93.7%) was purified by high pressure.

[0507] 1 H NMR (400MHz, DMSO-d6) δ12.02–11.94(m,1H),6.93–6.90(m,1H),3.97(s,2H),3.87( s,4H),3.27(s,3H),3.05(s,3H),2.80(s,2H),1.71–1.58(m,4H),1.56–1.42(m,4H).

[0508] LC-MS(ESI):[M+H] + =423.30.

[0509] Step 12: 5-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-fluoro-N,N-dimethyl-3,9-dihydro-7H-dispiro[pyrano[3,2-e]indole-8,1'-cyclohexane-4',2”-[1,3]dioxybenzene]-2-carboxamide (compound b-1m)

[0510] Compound b-1l (40 mg, 1.0 eq), A-2f (38 mg, 1.2 eq), potassium phosphate (60 mg, 3.0 eq), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (9 mg, 0.1 eq) were dissolved in 1,4-dioxane (5 mL) and water (1 mL). The reaction system was carried out at 100 °C for 2 hours under a nitrogen atmosphere. The reaction system was concentrated, and the crude product was purified by high pressure to obtain compound b-1m (25 mg, 44.5%).

[0511] LC-MS(ESI):[M+H] + =593.45

[0512] Step 13: 5'-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4'-fluoro-N,N-dimethyl-4-oxo-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (compound b-1)

[0513] Compound b-1m (25 mg, 1 eq) was dissolved in formic acid (2 mL) and reacted at room temperature for 1 hour. After evaporation to dryness, it was dissolved in dichloromethane, ice water was added, and the pH was adjusted to alkaline with saturated sodium bicarbonate aqueous solution. The mixture was extracted twice with dichloromethane, and the combined organic phases were evaporated to dryness to give intermediate b-1 (20 mg, 86.4%).

[0514] 1 H NMR (400MHz, DMSO-d6) δ11.88–11.79(m,1H),8.15–8.10(m,1H),7.73–7.66(m,1H),6.85–6.79(m,1H),5.84–5.78(m,1H),4.67–4.58(m,2 H),4.15–4.05(m,2H),4.03–3.94(m,2H),3.72–3.53(m,2H),3.24–3.00(m,8H),2.95–2.83(m,2H),2.46–2.21(m,6H),1.79–1.66(m,4H).

[0515] LC-MS(ESI):[M+H] + =549.58

[0516] Example 3 Synthesis of compound b-2

[0517] 5'-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4'-fluoro-4-carboxyl-N,N-dimethyl-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (compound b-2)

[0518] Synthesis scheme

[0519] Step 1: 5'-Chloro-4'-Fluoro-N,N-Dimethyl-4-oxo-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (compound b-2a)

[0520] Compound b-1l (188 mg, 1.0 eq) was dissolved in formic acid (5 mL) and stirred at room temperature for 2 hours. Ice water was added to the reaction solution, and the pH was adjusted to weakly alkaline with saturated sodium bicarbonate aqueous solution. The mixture was extracted twice with dichloromethane, and the combined organic phases were evaporated to dryness to obtain compound b-2a (150 mg, 89.0%).

[0521] LC-MS(ESI):[M+H] + =379.30.

[0522] Step 2: 5'-Chloro-4'-Fluoro-4-(methoxymethylene)-N,N-dimethyl-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (compound b-2b)

[0523] In a 50 mL two-necked flask, methoxymethyltriphenylphosphine chloride (180 mg, 2.0 eq) was dissolved in ultra-dry tetrahydrofuran (10 mL). Under nitrogen protection, the solution was cooled to -78 °C, and bis(trimethylsilylaminolithium) (1.1 mL, 1.0 M in THF, 4.0 eq) was slowly added dropwise. After stirring at this temperature for 1 hour, compound b-2a (100 mg, 1.0 eq) was added, and the solution was slowly heated to room temperature and stirred overnight. The mixture was then quenched with ice water, extracted twice with dichloromethane, and the organic phase was evaporated to dryness and purified by silica gel ablation to obtain compound b-2b (55 mg, 51.2%).

[0524] 1 H NMR (400MHz, DMSO-d6) δ12.03–11.93(m,1H),6.89–6.85(m,1H),5.90(s,1H),3.97(s,2H),3.48( s,3H),3.30–2.98(m,6H),2.79(s,2H),2.35–2.22(m,1H),2.19–1.92(m,3H),1.45–1.33(m,4H).

[0525] LC-MS(ESI):[M+H] + =407.39.

[0526] Step 3: 5'-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4'-fluoro-4-(methoxymethylene)-N,N-dimethyl-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (compound b-2c)

[0527] Intermediates b-2b (40 mg, 1.0 eq), b-2d (40 mg, 1.2 eq), potassium phosphate (65 mg, 3.0 eq), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (9 mg, 0.1 eq) were dissolved in 1,4-dioxane (5 mL) and water (1 mL). The reaction system was carried out at 100 °C for 2 hours under a nitrogen atmosphere. The reaction system was concentrated, and the crude product was purified by silica gel ablation to obtain compound b-2c (55 mg, 97.1%).

[0528] LC-MS(ESI):[M+H] + =576.45.

[0529] Step 4: 5'-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4'-fluoro-4-carboxyl-N,N-dimethyl-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyran[3,2-e]indole]-2'-carboxamide (compound b-2)

[0530] Compound b-2c (55 mg, 1 eq) was dissolved in acetonitrile (2 mL), and hydrochloric acid (2 mL, 4.0 M in dioxane) was added. The mixture was reacted at room temperature for 1 hour. The solution was poured into ice water, and the pH was adjusted to weakly alkaline with saturated sodium bicarbonate solution. The mixture was extracted twice with dichloromethane, and the combined organic phases were evaporated to dryness to obtain compound b-2 (45 mg, 83.8%).

[0531] LC-MS(ESI):[M+H] + =562.58

[0532] Example 4 Synthesis of compound a-2

[0533] 7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-(4-bromophenyl)-6-fluoro-2-methyl-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one (compound a-2)

[0534] Synthesis scheme

[0535] Step 1: 7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-9-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)-3,4-dihydropyrazolo[1,2-a]indol-1(2H)-one (compound a-2a)

[0536] Compound A-2 g (75 mg, 0.16 mmol), pinacol diboronate (83 mg, 0.32 mmol), potassium acetate (48 mg, 0.49 mmol), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (12 mg, 0.01 mmol) were dissolved in 1,4-dioxane (1 mL). The reaction system was reacted at 80 °C for 2 hours under a nitrogen atmosphere. The reaction system was concentrated, and the crude product was purified by column chromatography to give a yellow solid compound a-2a (70 mg, 77%).

[0537] LC-MS(ESI):[M+H] + =549.55

[0538] Step 2: 7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-(4-bromophenyl)-6-fluoro-2-methyl-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one (compound a-2)

[0539] Compound a-2a (70 mg, 0.12 mmol) and p-bromoiodobenzene (39 mg, 0.14 mmol) were dissolved in a mixed solvent of dioxane (2 mL) and water (0.4 mL). Potassium carbonate (53 mg, 0.38 mmol) and dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium (18 mg, 0.02 mmol) were then added sequentially. The reaction mixture was then heated to 80 °C and stirred for 2 hours. After the reaction was complete, the mixture was concentrated under reduced pressure, and the crude product was purified by high-performance liquid chromatography (HPLC) to give a white solid compound a-2 (5 mg, 7%).

[0540] 1H NMR(400MHz,DMSO-d6)δ8.11(d,J=11.4Hz,1H),7.74–7.69(m,2H),7.68–7.58(m,2H),7 .14(d,J=6.2Hz,1H),7.09–7.04(m,1H),6.18(d,J=9.8Hz,1H),4.67–4.54(m,3H),4.35( d,J=19.3Hz,2H),3.88–3.79(m,2H),3.72–3.64(m,1H),3.63–3.58(m,1H),3.15–3.09(m ,1H),3.06(s,2H),2.32(d,J=31.0Hz,2H),2.05–1.96(m,1H),1.46(s,1H),1.24(s,2H).

[0541] LC-MS(ESI):[M+H] + =577.28

[0542] Example 5 Synthesis of compound e-1

[0543] 6-(7-(3-(1H-1,2,3-triazol-1-yl)propionyl)-7-azabicyclo[2.2.1]hept-2-en-2-yl)-7-fluoro-N,N-dimethyl-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indole-2-carboxamide (compound e-1)

[0544] Synthesis scheme

[0545] Step 1: tert-butyl 2-(((trifluoromethyl)sulfonyl)oxy)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate (compound e-1b)

[0546] In a 50 mL round-bottom flask, add 5 mL of ultra-dry tetrahydrofuran and compound e-1a (500 mg, 1.0 eq). Place the flask under an inert atmosphere (N2) and cool it to -78 °C (dry ice / EtOH). Add lithium bis(trimethylsilylamino)amine (3.5 mL, 1 M / n-hexane, 1.5 eq) through a delivery tube. Then, stir the reaction mixture at -78 °C for 3 hours. At -78 °C, slowly add 2-[N, n-bis(trifluoromethanesulfonyl)amino]-5-chloropyridine (1.86 g, 2.0 eq) dropwise to the flask through a funnel. Raise the temperature to 0 °C and stir at this temperature for 1 hour. Finally, raise the temperature to room temperature and stir overnight. After the reaction was completed, saturated ammonium chloride solution (5 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (10 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound e-1b (400 mg, 49.23%).

[0547] Step 2: 4-Chloro-7-fluoro-N,N-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)-1H-indole-2-carboxamide (compound e-1c)

[0548] 1,4-Dioxane (5 mL) was added to a 50 mL round-bottom flask, followed by compound a-1d (500 mg, 1.0 eq), pinacol diborate (476 mg, 1.2 eq), 1,1-bis(diphenylphosphine)diberberine palladium dichloride (114 mg, 0.1 eq), and potassium acetate (460 mg, 3.0 eq). The reaction was carried out at 80 °C for 2 hours under nitrogen protection. After the reaction was complete, water (5 mL) and ethyl acetate (10 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under vacuum. The crude product was purified by column chromatography to obtain compound e-1c (400 mg, 69.73%).

[0549] LC-MS(ESI):[M+H] + =367.39

[0550] Step 3: Tert-butyl 2-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-7-azabicyclo[2.2.1]hept-2-en-7-carboxylic acid ester (compound e-1d)

[0551] Compound e-1c (200 mg, 1.0 eq) was dissolved in dioxane:water = 10:1 (3 mL), and compound e-1b (187 mg, 1.0 eq), 1,1-bis(diphenylphosphine)dimerferropalladium dichloride (40 mg, 0.1 eq), and potassium carbonate (226 mg, 3.0 eq) were added. The reaction was carried out at 80 °C for 2 hours under nitrogen protection. After the reaction was complete, water (5 mL) and ethyl acetate (10 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under vacuum. The crude product was purified by column chromatography to obtain compound e-1d (80 mg, 48.8%).

[0552] LC-MS(ESI):[M+H] + =434.39

[0553] Step 4: Tert-butyl 2-(2-(dimethylcarbamoyl)-7-fluoro-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indol-6-yl)-7-azabicyclo[2.2.1]hept-2-en-7-carboxylic acid ester (compound e-1e)

[0554] Compound e-1d (50 mg, 1.0 eq) was dissolved in dioxane:water = 10:1 (5 mL), and compound a-1f (38 mg, 1.1 eq) and Xphos Pd G were added. 3( 9 mg (0.1 eq) and potassium phosphate (73 mg (3.0 eq) were added. The reaction was carried out at 100 °C for 2 hours under nitrogen protection. After the reaction was completed, water (5 mL) and ethyl acetate (10 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by thin-layer chromatography to obtain compound e-1e (65 mg, 48.8%).

[0555] LC-MS(ESI):[M+H] + =574.58

[0556] Step 5: 6-(7-azabicyclo[2.2.1]hept-2-en-2-yl)-7-fluoro-N,N-dimethyl-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indole-2-carboxamide (compound e-1f)

[0557] Compound e-1e (65 mg, 1.0 eq) was dissolved in 4 M HCl-Dioxane (2 mL) and reacted at room temperature for 1 hour. After the reaction was completed, the solution was concentrated under vacuum to obtain crude compound e-1f (50 mg).

[0558] LC-MS(ESI):[M+H] + =474.59

[0559] Step 6: 6-(7-(3-(1H-1,2,3-triazol-1-yl)propionyl)-7-azabicyclo[2.2.1]hept-2-en-2-yl)-7-fluoro-N,N-dimethyl-4-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indole-2-carboxamide (compound e-1)

[0560] Compound e-1f (40 mg, 1.0 eq) was dissolved in N,N-dimethylformamide (2 mL), and compound e-1g (13 mg, 1.1 eq), HATU (48 mg, 1.5 eq), and DIEA (32 mg, 3.0 eq) were added. The reaction was carried out at room temperature for 2 hours. After the reaction was completed, compound e-1 (2 mg, 3.97%) was obtained by HPLC purification.

[0561] 1 H NMR (400MHz, DMSO-d6) δ12.24(d,J=4.8Hz,1H),9.67(s,1H),8.07(d,J=8.7Hz,1H),7.68(d,J=20.4H z,1H),7.61(dd,J=8.4,5.6Hz,2H),7.16–7.13(m,2H),6.83(d,J=2.7Hz,1H),6.71(s,1H),5.54–5.4 2(m,1H),5.04(d,J=4.1Hz,1H),4.57(q,J=6.9Hz,2H),3.95(d,J=13.2Hz,2H),3.56(d,J=12.1Hz,2H ),3.24–3.15(m,6H),3.10–2.98(m,6H),2.89(d,J=4.2Hz,4H),1.88–1.78(m,2H),1.33–1.29(m,1H).

[0562] LC-MS(ESI):[M+H] + =597.58

[0563] Example 6 Synthesis of compound a-3

[0564] 6-[2-[2-(1H-1,2,3-triazol-1-yl)ethyl]-3-oxoisoindoline-5-yl]-7-fluoro-N,N-dimethyl-4-[4-(4-methylpiperazin-1-yl)phenyl]-1H-indole-2-carboxamide (compound a-3)

[0565] Synthesis scheme

[0566] Step 1: 2-[2-(1H-1,2,3-triazol-1-yl)ethyl]-6-bromoisoindolin-1-one (compound a-3c)

[0567] Compound a-3a (300 mg, 1.00 eq), compound a-3b (324 mg, 5 eq), potassium carbonate (389 mg, 3.00 eq), and DMF (10 mL) were added to a 25 mL round-bottom flask and placed under nitrogen atmosphere. The flask was stirred at 100 °C for 2 hours. After the reaction was complete, 2 M hydrochloric acid was added dropwise to adjust the pH to approximately 5. The mixture was extracted three times with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected and concentrated under vacuum to give a white solid compound. The crude product was purified by column chromatography (0-50% PE / EA) to give a brown solid compound a-3c (70 mg, 24%).

[0568] 1 H NMR (400MHz, DMSO-d6) δ7.84–7.70(m,4H),7.60–7.51(m,1H),4.73(dd,J=6.6,5.2Hz,2H),4.25(s,2H),3.98(dd,J=6.6,5.2Hz,2H).

[0569] LC-MS(ESI):[M+H] + =307.15.

[0570] Step 2: 2-[2-(1H-1,2,3-triazol-1-yl)ethyl]-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborone-2-yl)isoindoline-1-one (compound a-3d)

[0571] Compound a-3c (50 mg, 1.00 eq) was dissolved in dioxane (5 mL), and pinacol diborate (82 mg, 2 eq), 1,1-bis(diphenylphosphine)diberberine palladium dichloride (12 mg, 0.10 eq), and potassium acetate (48 mg, 3.00 eq) were added. The reaction was carried out overnight at 100 °C under nitrogen protection. After the reaction was completed, water (5 mL) and ethyl acetate (10 mL) were added to the reaction system, and the mixture was extracted three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography (0-50% EA / PE) to give a yellow solid compound a-3d (40 mg).

[0572] 1H NMR(400MHz,DMSO-d6)δ7.93–7.81(m,2H),7.74(s,2H),7.61–7.55(m,1H), 4.73(dd,J=6.6,5.1Hz,2H),4.30(s,2H),4.02–3.94(m,2H),1.31(s,12H).

[0573] LC-MS(ESI):[M+H] + =355.39.

[0574] Step 3: 6-[2-[2-(1H-1,2,3-triazol-1-yl)ethyl]-3-oxoisoindoline-5-yl]-7-fluoro-N,N-dimethyl-4-[4-(4-methylpiperazin-1-yl)phenyl]-1H-indole-2-carboxamide (compound a-3)

[0575] Compound b-1a (40 mg, 1.00 eq), compound a-3d (34 mg, 1 eq), methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (8 mg, 0.10 eq), potassium phosphate (61 mg, 3.00 eq), and 1,4-dioxane:water = 5:1 (1 mL) were added to a 25 mL round-bottom flask and placed under an inert atmosphere (N2). The flask was stirred at 80 °C for 2 hours. The reaction solution was purified by high pressure to obtain compound a-3 (10 mg, 17%) as a white solid.

[0576] 1 H NMR (400MHz, DMSO-d6) δ12.31(d,J=2.1Hz,1H),7.97–7.84(m,2H),7.78(s,2H),7.68(dd,J=11.7,8.2Hz,3H),7.30–7.06(m,3H),6.90(dd, J=3.2,2.1Hz,2H),4.76(dd,J=6.6,5.0Hz,3H),4.32(s,2H),4.08–3.88(m,4H),3.04(d,J=13.3Hz,9H),2.89(s,3H),1.99(p,J=7.1Hz,1H).

[0577] LC-MS(ESI):[M+H] + =607.58.

[0578] Example 7 Synthesis of Compound A-2

[0579] 1-(1'-((1-(4-(7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indol-9-yl)phenyl)piperidin-4-yl)methyl)spiro[3,4'-piperidin]-7-yl)dihydropyrimidine-2,4(1H,3H)-dione (Compound A-2)

[0580] Synthesis scheme

[0581] Step 1: Methyl acrylate (Z)-2-azido-3-(4-bromo-2-chloro-5-fluorophenyl) methyl acrylate (intermediate A-2a)

[0582] 4-Bromo-2-chloro-5-fluorobenzaldehyde (6.0 g, 25.3 mmol) and methyl azide acetate (13.1 g, 113.7 mmol) were dissolved in methanol (60 mL). The reaction mixture was cooled to -10 °C under a nitrogen atmosphere, and sodium methoxide (5.5 g, 101.1 mmol) was slowly added to the reaction system. The reaction was carried out at room temperature for 8 hours. The reaction mixture was quenched at 0 °C with a supersaturated aqueous solution of ammonium chloride. After filtration, a filter cake was obtained. The crude product was purified by column chromatography to give a white solid intermediate A-2a (5.0 g, 59%).

[0583] 1 H NMR (600MHz, Chloroform-d) δ8.12(d,J=10.1Hz,1H),7.63(dd,J=6.5,1.1Hz,1H),7.16(s,1H),3.97(d,J=1.2Hz,3H).

[0584] Step 2: Methyl 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid (intermediate A-2b)

[0585] Intermediate A-2a (3.8 g, 11.4 mmol) was dissolved in xylene (38 mL). The reaction system was reacted at 150 °C for 3 hours. The reaction system was filtered to give a white solid intermediate A-2b (2.2 g, 63%).

[0586] 1 H NMR (600MHz, DMSO-d6) δ13.12(s,1H),7.46(d,J=4.9Hz,1H),7.17(d,J=2.7Hz,1H),3.91(s,3H).

[0587] Step 3: 6-Bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid (intermediate A-2c)

[0588] Intermediate A2-b (700 mg, 2.3 mmol) and lithium hydroxide monohydrate (290 mg, 6.9 mmol) were dissolved in methanol (14 mL), tetrahydrofuran (3.5 mL), and water (3.5 mL). This reaction system was reacted at 45 °C for 12 hours. The reaction system was then added to water, filtered, and the filter cake was washed three times with water. After drying the filter cake, a white solid intermediate A-2c (500 mg, 74%) was obtained.

[0589] 1 H NMR (400MHz, DMSO-d6) δ13.62(s,1H),12.87(s,1H),7.40(d,J=4.9Hz,1H),7.08(d,J=2.9Hz,1H).

[0590] Step 4: 6-Bromo-4-chloro-7-fluoro-N-methyl-1H-indole-2-carboxamide (Intermediate A-2d)

[0591] Intermediate A-2c (500 mg, 1.7 mmol), methylamine hydrochloride (210 mg, 2.6 mmol), N,N-diisopropylethylamine (1.1 g, 6.5 mmol), and HATU (780 mg, 2.1 mmol) were dissolved in N,N-dimethylformamide (10 mL). This reaction system was reacted at room temperature for 2 hours. The reaction system was then added to water, filtered, and the filter cake was washed three times with water. After drying, a brown solid intermediate A-2d (350 mg, 64%) was obtained.

[0592] 1 H NMR (400MHz, DMSO-d6) δ12.72(s,1H),8.69(q,J=4.5Hz,1H),7.40(d,J=4.9Hz,1H),7.24(d,J=2.9Hz,1H),2.82(d,J=4.6Hz,3H).

[0593] LC-MS(ESI):[M+H] + =305.18

[0594] Step 5: 7-Bromo-9-chloro-6-fluoro-2-methyl-3,4-dihydropyrazinyl[1,2-a]indole-1(2H)-one (intermediate A-2e)

[0595] Intermediate A-2d (350 mg, 1.2 mmol) and potassium hydroxide (160 mg, 2.9 mmol) were dissolved in dichloromethane (2 mL). The reaction mixture was cooled to 0 °C under a nitrogen atmosphere. A solution of diphenyl(vinyl)sulfonium trifluoromethanesulfonate (450 mg, 1.2 mmol) in dichloromethane (2 mL) was slowly added to the reaction system. The reaction was carried out at room temperature for 8 hours. The reaction system was concentrated, and the crude product was purified by column chromatography to give a white solid intermediate A-2e (210 mg, 55%).

[0596] 1 H NMR (400MHz, Chloroform-d) δ7.34 (d, J = 2.0 Hz, 1H), 7.26 (d, J = 5.0 Hz, 1H), 4.57 (dd, J = 6.9, 4.9 Hz, 2H), 3.84 (dd, J = 6.8, 5.1 Hz, 2H), 3.22 (s, 3H).

[0597] LC-MS(ESI):[M+H] + =331.19

[0598] Step 6: 7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-chloro-6-fluoro-2-methyl-3,4-dihydropyrazinyl[1,2-a]indol-1(2H)-one (Intermediate A-2g)

[0599] Intermediates A-2e (210 mg, 0.65 mmol), A-2f (220 mg, 0.6 mmol, WO2025 / 049820A1), potassium carbonate (270 mg, 1.9 mmol), and Pd(dppf)Cl2 (70 mg, 0.01 mmol) were dissolved in 1,4-dioxane (5 mL) and water (51 mL). The reaction system was carried out at 100 °C for 2 hours under a nitrogen atmosphere. The reaction system was concentrated, and the crude product was purified by column chromatography to obtain a yellow oily intermediate A-2g (290 mg, 99%).

[0600] 1H NMR(400MHz,Chloroform-d)δ7.77(t,J=1.2Hz,1H),7.72–7.66(m,1H),7.35–7.31( m,1H),7.01–6.94(m,1H),6.14–6.03(m,1H),4.81(q,J=6.1Hz,2H),4.62–4.53(m,2H ),4.42(d,J=2.5Hz,1H),4.23(d,J=2.4Hz,1H),3.86–3.80(m,2H),3.81–3.70(m,1H) ,3.59(t,J=5.8Hz,1H),3.22(d,J=2.6Hz,3H),3.12–3.02(m,2H),2.42–2.33(m,2H).

[0601] LC-MS(ESI):[M+H] + =457.40

[0602] Step 7: 7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-(4-(4-(4-(dimethoxymethyl)piperidin-1-yl)phenyl)-6-fluoro-2-methyl-3,4-dihydropyrazinyl[1,2-a]indol-1(2H)-one (intermediate A-2h)

[0603] Intermediate A-2g (310mg, 0.70mmol), A-1g (540mg, 1.4mmol, WO2025 / 049820A1), potassium phosphate (440mg, 2.1mmol), and XPons Pd G3 (60mg, 0.01mmol) were dissolved in 1,4-dioxane (5mL) and water (1mL). The reaction system was reacted at 100°C for 2 hours under a nitrogen atmosphere. The reaction system was concentrated, and the crude product was purified by column chromatography to obtain a yellow solid intermediate A-2h (240mg, 53%).

[0604] 1H NMR(600MHz,Chloroform-d)δ7.78(d,J=3.4Hz,1H),7.68(dd,J=2.3,1.1Hz,1H),7.58(d,J=8.3Hz,2H),7.39(dd,J=6.5,2.0Hz, 1H),7.23(s,2H),6.97(dd,J=13.5,5.9Hz,1H),6.22–6.01(m,1H),4.85–4.77(m,2H),4.61(q,J=5.5Hz,2H),4.48(d,J=2.6Hz,1H ),4.29(d,J=2.6Hz,1H),4.14(dd,J=7.3,1.6Hz,1H),3.86–3.76(m,5H),3.60(t,J=5.8Hz,1H),3.45–3.40(m,6H),3.21(d,J=4. 1Hz,3H),3.10–3.05(m,2H),2.95–2.86(m,2H),2.41–2.36(m,2H),1.97(d,J=13.5Hz,2H),1.90–1.82(m,1H),1.73–1.62(m,2H).

[0605] LC-MS(ESI):[M+H] + =656.60

[0606] Step 8: 1-(4-(7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indol-9-yl)phenyl)piperidine-4-aminocarboxaldehyde (intermediate A-2i)

[0607] Intermediate A2-h (120 mg, 0.18 mmol) was dissolved in formic acid (1 mL), and the reaction system was reacted at room temperature for 3 hours. The reaction system was concentrated to give a yellow solid crude product intermediate A-2i (100 mg, 90%).

[0608] LC-MS(ESI):[M+H] + =610.33

[0609] Step 9: 1-(1'-((1-(4-(7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indol-9-yl)phenyl)piperidin-4-yl)methyl)spiro[3,4'-piperidin]-7-yl)dihydropyrimidine-2,4(1H,3H)-dione (A-2)

[0610] Intermediates A-2i (40 mg, 0.07 mmol), A-1j (40 mg, 0.07 mmol), sodium triacetoxyborohydride (20 mg, 0.1 mmol), and acetic acid (0.1 mL) were dissolved in dimethyl sulfoxide (1 mL), and the reaction mixture was allowed to react at room temperature for 0.5 hours. The reaction mixture was purified by high pressure to obtain a white solid product A-2 (26 mg, 40%).

[0611] 1 H NMR (400MHz, DMSO-d6) δ10.35(s,1H),8.11(d,J=10.4Hz,1H),7.69(d,J=12.4Hz,1H),7. 52(dd,J=8.8,2.9Hz,2H),7.13–7.03(m,4H),7.00(dd,J=27.5,6.1Hz,1H),6.85(ddd,J=8 .6,6.7,2.2Hz,1H),6.79(d,J=2.1Hz,1H),6.21–6.10(m,1H),4.63(q,J=7.0Hz,2H),4.56 (dt,J=7.6,4.0Hz,2H),4.34(dd,J=19.4,2.6Hz,2H),4.15(s,1H),3.86–3.82(m,5H),3.7 3(t,J=6.7Hz,3H),3.67(d,J=5.8Hz,1H),3.61(t,J=5.8Hz,1H),3.46(t,J=12.3Hz,2H), 3.08(d,J=22.4Hz,6H),2.88(s,1H),2.82(t,J=12.2Hz,2H),2.68(t,J=6.6Hz,2H),2.59( s,1H),2.41–2.25(m,2H),2.01(dd,J=8.6,6.5Hz,2H),1.86(d,J=12.6Hz,2H),1.75(q,J= 9.8,8.6Hz,2H),1.63(d,J=14.0Hz,1H),1.38(q,J=12.5,10.5Hz,2H),1.28–1.21(m,2H).

[0612] LC-MS(ESI):[M+H] + =909.56

[0613] Example 8 Synthesis of Compound A-3

[0614] (S)-1'-((1-(4-(7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-1-oxo-1,2,3,4-tetrahydropyrazinyl[1,2-a]indol-9-yl)phenyl)piperidin-4-yl)methyl)-N-(2,6-dioxopiperidin-3-yl)-5-methoxy-2H-spiro[benzofuran-3,4'-piperidin]-6-carboxamide (Compound A-3)

[0615] Synthesis scheme

[0616] Step 1: (S)-1'-((1-(4-(7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-1-oxo-1,2,3,4-tetrahydropyrazinyl[1,2-a]indol-9-yl)phenyl)piperidin-4-yl)methyl)-N-(2,6-dioxopiperidin-3-yl)-5-methoxy-2H-spiro[benzofuran-3,4'-piperidin]-6-carboxamide (Compound A-3)

[0617] Intermediates A-2i (40 mg, 0.07 mmol), A-3a (0.04 g, 0.07 mmol), sodium triacetoxyborohydride (20 mg, 0.1 mmol), and acetic acid (0.1 mL) were dissolved in dimethyl sulfoxide (1 mL), and the reaction mixture was allowed to react at room temperature for 0.5 hours. The reaction mixture was purified by high pressure to give a white solid product A-3 (32 mg, 50%).

[0618] 1H NMR (400MHz, DMSO-d6) δ10.90(s,1H),8.68(t,J=7.2Hz,1H),8.11(d,J=10.2Hz,1H),7.69(d,J=12.3Hz,1H),7.52(dd,J=8.7,2.9Hz,2H),7.24(d,J=8. 6Hz,1H),7.13(d,J=8.4Hz,2H),7.07(s,1H),7.01(dd,J=27.4,6.0Hz,1H), 6.88(s,1H),6.20–6.11(m,1H),4.73(dt,J=10.2,7.4Hz,1H),4.63(q,J=6. 9Hz,2H),4.60–4.51(m,3H),4.34(d,J=19.2Hz,2H),3.92(s,3H),3.85(d,J =9.6Hz,8H),3.66–3.59(m,4H),3.38(s,1H),3.11(t,J=7.0Hz,3H),3.06(s ,3H),2.79(dt,J=27.2,10.8Hz,3H),2.36(s,1H),2.32–2.22(m,2H),2.14– 2.05(m,2H),2.02–1.82(m,4H),1.39(q,J=11.0Hz,2H),1.29–1.20(m,2H).

[0619] LC-MS(ESI):[M+H] + =967.80

[0620] Example 9 Synthesis of Compound A-4

[0621] 3-(1'-((1-(4-(7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-1-oxo-1,2,3,4-tetrahydropyrazinyl[1,2-a]indol-9-yl)phenyl)piperidin-4-yl)methyl)-1-methyl-2-oxo-1,2-dihydro-3H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-3-yl)piperidin-2,6-dione (compound A-4)

[0622] Synthesis scheme

[0623] Step 1: 3-(1'-((1-(4-(7-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-fluoro-2-methyl-1-oxo-1,2,3,4-tetrahydropyrazinyl[1,2-a]indol-9-yl)phenyl)piperidin-4-yl)methyl)-1-methyl-2-oxo-1,2-dihydro-3H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-3-yl)piperidin-2,6-dione (A-4)

[0624] Intermediate A2-i (40 mg, 0.07 mmol), A-4a (35 mg, 0.07 mmol), sodium borohydride acetate (21 mg, 0.1 mmol), and acetic acid (0.1 mL) were dissolved in dimethyl sulfoxide (1 mL), and the reaction mixture was allowed to react at room temperature for 0.5 hours. The reaction mixture was purified by high pressure to give a white solid product A-4 (10 mg, 16%).

[0625] 1 H NMR (400MHz, DMSO-d6) δ11.12(s,1H),8.11(d,J=10.2Hz,1H),7.69(d,J=12.3Hz,1H),7.52(dd,J=8.7,3.0Hz,2H),7.18–7.06(m ,2H),7.01(dd,J=27.4,6.1Hz,1H),6.78(d,J=8.0Hz,1H),6.70(d,J=8.0Hz,1H),6.22–6.12(m,1H),5.35(dd,J=12.7,5.3Hz,1H ),4.71–4.53(m,5H),4.39–4.29(m,2H),3.84(q,J=5.3Hz,3H),3.46(d,J=3.0Hz,3H),3.11(q,J=8.2,7.7Hz,3H),3.06(s,3H),2 .98–2.76(m,3H),2.74–2.57(m,2H),2.32(d,J=30.6Hz,2H),2.20(t,J=13.6Hz,2H),2.03–1.84(m,5H),1.39(d,J=11.4Hz,2H).

[0626] LC-MS(ESI):[M+H] + =964.70.

[0627] Example 10 Synthesis of Compound B-1

[0628] 5'-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)-4'-fluoro-N,N-dimethyl-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (Compound B-1)

[0629] Synthesis scheme

[0630] Compound A-4a (16 mg, 1.2 eq), compound b-1 (20 mg, 1.0 eq), and tetraisopropyl titanate (55 mg, 5.0 eq) were dissolved in dimethyl sulfoxide (3 mL). After stirring in an oil bath at 50 °C for 3 hours, sodium cyanoborohydride (7 mg, 3.0 eq) was added. The reaction was carried out overnight at 50 °C. The reaction system was purified by high pressure to obtain a white solid compound B-1 (2.54 mg, 8.9%).

[0631] 1 H NMR(400MHz, Methanol-d4)δ8.09–8.02(m,1H),7.80–7.72(m,1H),6.95(d,J=7.6Hz,1H),6.89-6 .78(m,1H),6.73–6.67(m,1H),5.90-5.83(m,1H),5.31(dd,J=12.2,5.3Hz,1H),4.84–4.75(m,2H) ,4.67-4.59(m,6H),4.27-4.20(m,1H),4.17(s,1H),4.08(s,1H),3.85-3.77(m,2H),3.71–3.65( m,1H),3.58(s,3H),3.26-3.12(m,5H),3.00–2.70(m,7H),2.43-2.33(m,2H),2.25-1.70(m,13H).

[0632] Example 11 Synthesis of Compound B-2

[0633] 5'-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-((3-(2,6-dioxopiridine-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4'-fluoro-N,N-dimethyl-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (compound B-2)

[0634] Synthesis scheme

[0635] Step 1: 5'-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)-4'-fluoro-N,N-dimethyl-3',9'-dihydro-7'H-spiro[cyclohexane-1,8'-pyrano[3,2-e]indole]-2'-carboxamide (Compound B-2)

[0636] Intermediate A-4a (40 mg, 1.2 eq), compound b-2 (45 mg, 1.0 eq), and acetic acid (15 mg, 3.0 eq) were dissolved in dimethyl sulfoxide (3 mL). After stirring at room temperature for half an hour, sodium triacetoxyborohydride (50 mg, 3.0 eq) was added. The reaction was allowed to proceed overnight at room temperature. The reaction system was purified by high pressure to obtain a white solid product B-1 (10 mg).

[0637] 1H NMR(400MHz,DMSO-d6)δ11.91–11.78(m,1H),11.11(s,1H),7.76-7.71(m,1H),7.47-7.42(m,1H),6.80-6.73(m,2H), 6.69(d,J=7.9Hz,1H),6.25-6.19(m,1H),5.83–5.76(m,1H),5.34(dd,J=12.6,5.0Hz,1H),4.69–4.60(m,2H),4.42-4. 33(m,2H),4.15–3.93(m,3H),3.82–3.63(m,2H),3.69-3.63(m,1H),3.60-3.51(m,3H),3.45(s,3H),3.17–2.75(m,13 H),2.72-2.57(m,4H),2.35-2.12(m,5H),2.04–1.87(m,5H),1.74-1.61(m,3H),1.59–1.43(m,1H),1.59–1.43(m,2H).

[0638] LC-MS(ESI):[M+H] + =916.75

[0639] Example 12 Synthesis of Compound B-3

[0640] 6-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)cyclohexyl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound B-3)

[0641] Synthesis scheme

[0642] Step 1: Ethyl 2,3,4,5-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid ethyl ester (compound B-3b)

[0643] The starting materials 1-bromo-4-iodo-2-methoxybenzene (1 g, 3.20 mmol), 1-ethoxycarbonylcyclohexyl-3-ene-4-boronic acid pinacol ester (0.98 g, 3.52 mmol), potassium carbonate (1.32 g, 9.59 mmol), and 1,1-bis(diphenylphosphine)dimerferropalladium dichloride (467 mg, 639.12 μmol) were dissolved in a mixed solvent of 1,4-dioxane and water (16 / 4 mL). Under nitrogen protection, the mixture was stirred in an oil bath at 80°C for 2 hours. The mixture was extracted twice with ethyl acetate, and the organic phase was evaporated to dryness and purified by column chromatography to give a white solid product B-3b (842 mg, 77%).

[0644] 1 H NMR(400MHz,Chloroform-d)δ7.47(d,J=8.2Hz,1H),6.91(d,J=2.0Hz,1H),6.86(dd,J=8.2,2.0Hz,1H),6.15–6.09(m,1H),4.2 0(q,J=7.1Hz,2H),3.93(s,3H),2.68–2.59(m,1H),2.55–2.44(m,4H),2.25–2.16(m,1H),1.93–1.82(m,1H),1.33–1.28(m,3H).

[0645] Step 2: Ethyl 4-phenylcyclohexane-1-carboxylate (compound B-3c)

[0646] Compound B-3b (700 mg, 2.06 mmol) was dissolved in tetrahydrofuran (15 mL) under N2 protection. Diisobutylaluminum hydride (1.47 g, 1 M) was added dropwise at 0 °C, and the reaction was carried out at room temperature for 1 hour. After the reaction was completed, the mixture was quenched with water, the pH was adjusted to 6 with 2 M HCl, and the mixture was extracted twice with ethyl acetate. The organic phase was evaporated to dryness and purified by column chromatography to give the yellow solid product compound B-3c (500 mg, 81%).

[0647] 1 H NMR (400MHz, DMSO-d6) δ7.47(d,J=8.2Hz,1H),7.07(d,J=2.0Hz,1H),6.91(dd,J=8.3,2.1Hz,1H),6.25–6.21(m,1H),4.53(t ,J=5.3Hz,1H),3.87(s,3H),3.35–3.23(m,2H),2.48–2.21(m,3H),1.96–1.79(m,2H),1.75–1.60(m,1H),1.37–1.22(m,1H).

[0648] Step 3: Ethyl 4-(4-iodophenyl)cyclohexane-1-carboxylate (compound B-3d)

[0649] Compound B-3c (1 g, 3.36 mmol) was dissolved in dichloromethane (10 mL) under N2 protection. Boron tribromide (2.11 g, 2 M) was slowly added at 0 °C, and the reaction was carried out at room temperature for 1 hour. After the reaction was completed, the mixture was quenched with methanol, evaporated to dryness, and purified by column chromatography to give a yellow oily product, compound B-3d (800 mg, 84%).

[0650] 1 H NMR (400MHz, DMSO-d6) δ10.13(s,1H),7.37(d,J=8.3Hz,1H),6.95(d,J=2.1Hz,1H),6.79(dd,J=8.4,2.2H z,1H),6.12–6.07(m,1H),2.37–2.18(m,3H),1.93–1.76(m,3H),1.72–1.60(m,1H),1.18(t,J=7.2Hz,3H).

[0651] Step 4: 6-Chloro-7-fluoro-4-(3-hydroxy-4'-(hydroxymethyl)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-yl)-N,N-dimethyl-1H-indole-2-carboxamide (compound B-3e)

[0652] Compound B-3d (450 mg, 1.58 mmol), compound E-1d (580 mg, 1.58 mmol), potassium carbonate (550 mg, 3.97 mmol), and 1,1-bis(diphenylphosphine)dimerferropalladium dichloride (120 mg, 164.16 μmol) were dissolved in a mixed solvent of 1,4-dioxane and water (30 / 4 mL). The mixture was stirred in an oil bath at 80°C for 2 hours under nitrogen protection. The mixture was extracted twice with ethyl acetate, and the organic phase was evaporated to dryness and purified by column chromatography to give the yellow solid product compound B-3e (500 mg, 71%).

[0653] 1 H NMR(400MHz,DMSO-d6)δ12.26(s,1H),9.52(s,1H),7.25(d,J=7.9Hz,1H),7 .10(d,J=6.2Hz,1H),7.02(s,1H),6.98(d,J=8.0Hz,1H),6.63–6.37(M,1H) ,6.20–6.13(m,1H),4.55(t,J=5.1Hz,1H),3.37-3.33(m,2H),3.25-2.95(m ,6H),2.44-2.20(m,3H),1.98-1.82(m,2H),1.69(s,1H),1.40–1.27(m,1H).

[0654] LC-MS(ESI):[M+H] + =443.39

[0655] Step 5: 6-Chloro-7-fluoro-4-(2-hydroxy-4-(4-(hydroxymethyl)cyclohexyl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound B-3f)

[0656] Compound B-3e (440 mg, 993.41 μmol) was dissolved in a mixed solvent of ethyl acetate and tetrahydrofuran (20 / 10 mL), and palladium hydroxide on carbon (200 mg, 10%) was added. The mixture was then purged with hydrogen and reacted overnight in an oil bath at 60°C. After the reaction was complete, the mixture was filtered, and the filtrate was evaporated to dryness. The crude product obtained was used directly in the next step (430 mg, 97%).

[0657] 1 H NMR(400MHz,DMSO-d6)δ12.24(s,1H),9.45(s,1H),7.21(dd,J=7.8,1.9Hz,1H),7 .11-7.07(m,1H),6.85(d,J=8.3Hz,1H),6.81–6.76(m,1H),6.60(d,J=2.9Hz,1H), 4.47(dd,J=11.8,5.3Hz,1H),3.51–3.45(m,2H),3.29–3.24(m,1H),3.20–2.99(m ,6H),1.91–1.82(m,2H),1.78–1.68(m,2H),1.65–1.51(m,4H),1.47-1.37(m,1H).

[0658] LC-MS(ESI):[M+H] + =445.20

[0659] Step 6: 10-Chloro-11-fluoro-6-(4-(hydroxymethyl)cyclohexyl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (Compound B-3g)

[0660] Compound B-3f (430 mg, 966.44 μmol) was dissolved in N,N-dimethylformamide, and hexamethylenetetramine (270 mg, 1.92 mmol) was added. The mixture was stirred overnight in an oil bath at 120°C under nitrogen protection. After the reaction was complete, the mixture was purified by reverse mixing to give the green solid product compound B-3g (210 mg, 45%).

[0661] 1H NMR (400MHz, DMSO-d6) δ12.28(s,1H),7.85(d,J=8.3Hz,1H),7.52(d,J=5.8Hz,1H),7.18-7.10(m,1H),7.04-7.01(m,1H),5.1 1(s,2H),3.49-3.47(m,2H),3.26(d,J=6.2Hz,1H),3.02(s,6H),1.85(d,J=10.7Hz,2H),1.76–1.53(m,5H),1.51-1.38(m,2H).

[0662] LC-MS(ESI):[M+H] + =457.29

[0663] Step 7: tert-butyl 5-(2-(dimethylcarbamoyl)-11-fluoro-6-(4-(hydroxymethyl)cyclohexyl)-1,3-dihydrobenzo[6,7]oxophenyl[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylate (compound B-3h)

[0664] Compound B-3g (180 mg, 393.32 μmol), compound a-1a (160 mg, 517.45 μmol), potassium phosphate (210 mg, 989.32 μmol), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (35 mg, 41.3 μmol) were dissolved in 1,4-dioxane (12 mL) and water (2 mL). The reaction system was carried out at 85 °C for 1 hour under a nitrogen atmosphere. The reaction solution was extracted twice with dichloromethane, the organic phase was concentrated, and the crude product was purified by column chromatography to give a yellow solid compound B-3h (220 mg, 92%).

[0665] 1H NMR (400MHz, DMSO-d6) δ12.04(s,1H),7.85(d,J=8.3Hz,1H),7.30(d,J=5.7Hz,1H),7.1 6-7.09(m,1H),7.03–6.99(m,1H),6.18–6.10(m,1H),5.11(s,2H),4.46(t,J=5.3Hz,1H ),4.25(s,2H),3.53(t,J=5.4Hz,2H),3.49–3.45(m,2H),3.26(t,J=5.8Hz,1H),3.02(s ,6H),2.35-2.26(m,2H),1.85(d,J=11.3Hz,2H),1.79–1.50(m,5H),1.49–1.37(m,11H).

[0666] LC-MS(ESI):[M+H] + =548.38

[0667] Step 8: Tert-butyl 5-(2-(dimethylcarbamoyl)-11-fluoro-6-(4-formylcyclohexyl)-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylate (compound B-3i)

[0668] Compound B-3h (240 mg, 397.53 μmol) was dissolved in dichloromethane (10 mL), and Desmartin oxidant (340 mg, 801.62 μmol) was added under ice-water bath conditions. The reaction system was reacted at room temperature for 1 hour. The reaction solution was extracted with dichloromethane, and the organic phase was evaporated to dryness to give the crude green solid product compound B-3i (270 mg, 112%).

[0669] LC-MS(ESI):[M+H] + =546.28

[0670] Step 9: Tert-butyl 5-(2-(dimethylcarbamoyl)-6-(4-((3-(2,6-dioxoperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)cyclohexyl)-11-fluoro-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylate (compound B-3j)

[0671] Compound A-4a (150 mg, 404.96 μmol) was dissolved in dimethyl sulfoxide (5 mL), and N,N-diisopropylethylamine (55 mg, 425.54 μmol) was added. The mixture was stirred for 5 minutes, followed by the sequential addition of acetic acid (100 mg, 666.67 μmol) and compound B-3i (270 mg, 448.71 μmol). The reaction mixture was stirred at room temperature for 1 hour, and then sodium triacetoxyborohydride (260 mg, 1.23 mmol) was added. The reaction solution was purified by high-performance liquid chromatography to obtain the yellow solid product compound B-3j-1 (180 mg, 46%).

[0672] LC-MS(ESI):[M+H] + =956.75

[0673] Step 10: 6-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spirooxy[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)cyclohexyl)-11-fluoro-N,N-dimethyl-10-(1,2,5,6-tetrahydropyridin-3-yl)-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound B-3k)

[0674] Compound B-3j (180 mg, 188.26 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2 mL) was added. The mixture was reacted at room temperature for 1 hour. After rotary evaporation and lyophilization, a white solid product, compound B-3k (150 mg, 93%), was obtained.

[0675] 1H NMR (400MHz, DMSO-d6) δ12.12(s,1H),11.11(s,1H),7.88(d,J=8.3Hz,1H),7.35(d,J=5.7Hz,1H),7.15(d,J=8.2 Hz,1H),7.04(s,1H),6.79(d,J=8.0Hz,1H),6.70(d,J=8.0Hz,1H),6.34-6.29(m,1H),5.33(dd,J=12.7,5.0Hz,1H ),5.11(s,2H),4.64(s,2H),4.06(s,2H),3.64–3.53(m,5H),3.33–3.29(m,2H),3.15–2.83(m,9H),2.74–2.53(m ,4H),2.27–2.10(m,2H),2.05–1.84(m,7H),1.54(dd,J=23.6,12.2Hz,2H),1.31–1.25(m,1H),1.21-1.12(m,2H).

[0676] LC-MS(ESI):[M+H] + =856.76

[0677] Step 11: 6-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)cyclohexyl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound B-3)

[0678] Compound B-3k (50 mg, 58.41 μmol), compound B-3l (23 mg, 177.95 μmol), and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)hexafluorophosphate urea (45 mg, 118.34 μmol) were dissolved in N,N-dimethylformamide (3 mL), and N,N-diisopropylethylamine (47 mg, 297.22 μmol) was added. The reaction mixture was reacted at room temperature for 1 hour. The reaction mixture was purified by preparative HPLC to give white solid products B-3-1 and B-3-2 (20 mg, 34%).

[0679] Compound B-3-1: 11H NMR (600 MHz, DMSO-d6) δ 12.10-12.03 (m, 1H), 11.11 (s, 1H), 7.93–7.84 (m, 1H), 7.68-7.63 (m, 1H), 7.37–7.28 (m, 1H), 7.15 (d, J=8.1 Hz, 1H), 7.03 (s, 1H), 6.79 (d, J=8.0 Hz, 1H), 6.71 (d, J=7.8 Hz, 1H), 6.19-6.15 (m, 1H), 5.91-5.85 (m, 1H), 5.37-5.30 (m, 1H), 5.12 (s, 2H), 4.64 (s, 2H), 4.40-4.32 (m, 2H), 4.28–4.20 (m, 2H), 3.70-3.54 (m, 4H), 3.46 (s, 3H), 3.15-2.85 (m, 12H), 2.72–2.61 (m, 2H), 2.59-2.54 (m, 1H), 2.54–2.52 (m, 1H), 2.40–2.25 (m, 2H), 2.24-2.15 (m, 2H), 2.04–1.86 (m, 8H), 1.60-1.50 (m, 2H), 1.21–1.14 (m, 2H).

[0680] LC-MS (ESI): [M+H] + = 996.65

[0681] Compound B-3-2: 1H NMR (600MHz, DMSO-d6) δ12.10-12.03(m,1H),11.11(s,1H),7.93-7.85(m,1H),7.67–7.62(m,1H),7.38–7.30(m,1H),7.19(d,J=8.1Hz,1H ),7.16-7.11(m,1H),6.80(d,J=8.0Hz,1H),6.71(d,J=7.9Hz,1H),6.19-6.15(m,1H),5.91-5.85(m,1H),5.36–5.31(m,1H),5.12(s,2H), 4.65(s,2H),4.38(s,1H),4.33(s,1H),4.27-4.21(m,2H),3.67-3.60(m,4H),3.46(s,3H),3.33-3.29(m,2H),3.13-3.03(s,8H),2.99–2. 87(m,3H),2.69-2.60(m,3H),2.53–2.52(m,1H),2.41–2.35(m,1H),2 .29(s,1H),2.23-2.14(m,2H),2.03–1.91(m,4H),1.73-1.69(m,8H).

[0682] LC-MS(ESI):[M+H] + =996.65

[0683] Example 13 Synthesis of Compound E-1

[0684] 10-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound E-1)

[0685] Synthesis scheme

[0686] Step 1: 2-Bromo-5-(4-(dimethoxymethyl)piperidin-1-yl)phenol (compound E-1b)

[0687] 2-Bromo-5-iodophenol (5 g, 1.0 eq), 4-(dimethoxymethyl)piperidine (4 g, 1.5 eq), cuprous iodide (637 mg, 0.2 eq), L-proline (770 mg, 0.2 eq), and potassium carbonate (4.6 g, 2.0 eq) were dissolved in dimethyl sulfoxide. The reaction was carried out at 80 °C for 4 hours under nitrogen protection. After the reaction was complete, water (50 mL) and ethyl acetate (100 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to give compound E-1b (1.9 g, 34.39%).

[0688] LC-MS(ESI):[M+H] + =332.29

[0689] Step 2: 6-Chloro-7-fluoro-N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxonaphtho-2-yl)-1H-indole-2-carboxamide (compound E-1d)

[0690] Compound E-1c (1.8 g, 1.0 eq) was dissolved in dioxane, and pinacol diboronate (2.1 g, 1.5 eq), 1,1-bis(diphenylphosphine)diberberine palladium dichloride (412 mg, 0.1 eq), and potassium acetate (1.65 g, 3.0 eq) were added. The reaction was carried out overnight at 85 °C under nitrogen protection. After the reaction was completed, saturated ammonium chloride solution (50 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (100 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound E-1d (2.0 g, 96.8%).

[0691] LC-MS(ESI):[M+H] + =367.39

[0692] Step 3: 6-Chloro-4-(4-(dimethoxymethyl)piperidin-1-yl)-2-hydroxyphenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (compound E-1e)

[0693] Compound E-1d (1 g, 1.0 eq) was dissolved in dioxane:water = 10:1 (12 mL), and compound E-1b (900 mg, 1.0 eq), 1,1-bis(diphenylphosphine)dimerferropalladium dichloride (200 mg, 0.1 eq), and potassium carbonate (1.1 g, 3.0 eq) were added. The reaction was carried out at 100 °C for 3 hours under nitrogen protection. After the reaction was complete, water (50 mL) and ethyl acetate (10 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under vacuum. The crude product was purified by column chromatography to obtain compound E-1e (1.1 g, 82.7%).

[0694] LC-MS(ESI):[M+H] + =490.39

[0695] Step 4: 10-Chloro-6-(4-(dimethoxymethyl)piperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound E-1f)

[0696] Compound E-1e (700 mg, 1.0 eq) was dissolved in N,N-dimethylformamide, and iodine (72 mg, 0.2 eq) and hexamethylenetetramine (400 mg, 2.0 eq) were added. The reaction was carried out at 120 °C for 2 hours under nitrogen protection. After the reaction was complete, water (50 mL) and ethyl acetate (100 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound E-1f (250 mg, 33.78%).

[0697] LC-MS(ESI):[M+H] + =502.39

[0698] Step 5: 10-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-(4-(dimethoxymethyl)piperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound E-1g)

[0699] Compound E-1f (50 mg, 1.0 eq) was dissolved in dioxane, and compound A-2f (40 mg, 1.2 eq), cesium fluoride (60 mg, 4.0 eq), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (8 mg, 0.1 eq) were added. The reaction was carried out at 100 °C for 3 hours under nitrogen protection. After the reaction was complete, water (50 mL) and ethyl acetate (100 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound E-1g (50 mg, 74.6%).

[0700] LC-MS(ESI):[M+H] + =672.67

[0701] Step 6: 10-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-11-fluoro-6-(4-formylpiperidin-1-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound a-1i)

[0702] Compound E-1g (50mg, 1.0rq) was dissolved in formic acid (1mL), and the reaction system was reacted at room temperature for 2 hours. The reaction system was concentrated to give compound E-1h (50mg, 107.36%).

[0703] LC-MS(ESI):[M+H] + =626.58

[0704] Step 7: 10-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-(4-((3-(2,6-dioxoperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxo[3,4,5-cd]indole-2-carboxamide (compound E-1)

[0705] Compound E-1h (50 mg, 1.0 eq), compound E-1i (37 mg, 1.0 eq), and sodium triacetoxyborohydride (51 mg, 3.0 eq) were dissolved in dimethyl sulfoxide, and the reaction system was reacted at room temperature for 2 hours. The reaction system was purified by high pressure to obtain a white solid compound E-1 (13 mg, 16.6%).

[0706] 1 H NMR (400MHz, DMSO-d6) δ11.97(d,J=9.3Hz,1H),11.12(s,1H),8.12(d,J=16.4Hz,1H),7.82–7.67(m,2H),7.21(dd,J=24.2,7.7Hz,1H),6.88(d,J=8 .8Hz,1H),6.79(d,J=7.9Hz,1H),6.71(s,2H),6.16(s,1H),5.34(dt,J=10 .2,5.1Hz,2H),5.10(s,2H),4.69–4.55(m,4H),4.36(d,J=29.8Hz,2H),3. 86(d,J=11.9Hz,2H),3.64–3.57(m,3H),3.15–3.05(m,6H),3.03(d,J=2.9 Hz, 6H), 2.90 (d, J = 16.3Hz, 1H), 2.80 (q, J = 9.0, 5.8Hz, 2H), 2.68 (d, J = 35. 7Hz,2H),2.38(s,2H),2.30(s,1H),2.19(t,J=14.3Hz,2H),2.07(d,J=9.8 Hz,1H),2.04–1.91(m,6H),1.85(d,J=12.5Hz,2H),1.46(t,J=7.3Hz,1H).

[0707] LC-MS(ESI):[M+H] + =980.65

[0708] Example 14 Synthesis of Compound D-1

[0709] 10-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-(4-(3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7Hspiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indole-2-carboxamide (compound D-1)

[0710] Synthesis scheme

[0711] Step 1: 5-(6-(4-(dimethoxymethyl)piperidin-1-yl)-2-(dimethylcarbamoyl)-11-fluoro-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (compound D-1a)

[0712] Compound E-1f (400 mg, 1.0 eq) was dissolved in dioxane, and tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid ester (369.59 mg, 1.5 eq), potassium phosphate (507.43 mg, 3.0 eq), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (67.53 mg, 0.1 eq) were added. The reaction was carried out at 80 °C for 3 hours under nitrogen protection. After the reaction was completed, water (50 mL) and ethyl acetate (100 mL) were added to the reaction system and extracted three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered and collected. The filtrate was concentrated under vacuum and purified by column chromatography to obtain compound D-1a (420 mg, 81.24%).

[0713] LC-MS(ESI):[M+H] + =649.67

[0714] Step 2: 11-Fluoro-6-(4-formylpiperidin-1-yl)-N,N-dimethyl-10-(1,2,5,6-tetrahydropyridin-3-yl)-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indole-2-carboxamide (compound D-1b)

[0715] Compound D-1a (400 mg, 1.0 eq) was dissolved in formic acid (5 mL) and reacted at room temperature for 2 hours. After the reaction was completed, the solution was concentrated under vacuum to obtain crude compound D-1b (400 mg).

[0716] LC-MS(ESI):[M+H] + =503.49

[0717] Step 3: 5-(2-(dimethylcarbamoyl)-11-fluoro-6-(4-formylpiperidin-1-yl)-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (compound D-1c)

[0718] Compound D-1b (400 mg, 1.0 eq) was dissolved in dichloromethane (10 mL), and compound di-tert-butyl dicarbonate (347.40 mg, 2.0 eq) and triethylamine (241.60 mg, 3.0 eq) were added. The reaction was carried out at room temperature for 2 hours. After the reaction was completed, the solution was concentrated under vacuum to obtain crude compound D-1c (550 mg).

[0719] LC-MS(ESI):[M+H] + =603.58

[0720] Step 4: 5-(2-(dimethylcarbamoyl)-6-(4-(3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7Hspiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-1,3-dihydrobenzo[6,7]oxetane-heptano[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (compound D-1d)

[0721] Compound D-1c (550 mg, 1.0 eq), compound A-4a (405.62 mg, 1.2 eq), and sodium triacetoxyborohydride (384.99 mg, 2.0 eq) were dissolved in dimethyl sulfoxide, and the reaction system was reacted at room temperature for 2 hours. The reaction system was purified by reverse-phase preparation to give a white solid compound D-1d (500 mg, 57.24%).

[0722] LC-MS(ESI):[M+H] + =957.85

[0723] Step 5: 6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7Hspiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-N,N-dimethyl-10-(1,2,5,6-tetrahydropyridin-3-yl)-1,3-dihydrobenzo[6,7]oxepyno[3,4,5-cd]indole-2-carboxamide (compound D-1f)

[0724] Compound D-1d (500 mg, 1.0 eq) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (5 mL) was added. The reaction was carried out at room temperature for 2 hours. After the reaction was completed, the compound D-1e (440 mg, 98.28%) was purified by reverse-phase reaction to obtain a white solid.

[0725] LC-MS(ESI):[M+H] + =857.66

[0726] Step 6: 10-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-6-(4-(3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7Hspiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indole-2-carboxamide (compound D-1)

[0727] Compounds D-1e (20 mg, 1.0 eq) and D-1f (4.91 mg, 1.5 eq) were dissolved in N,N-dimethylformamide (1 mL), and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (17.75 mg, 2.0 eq) and N,N-diisopropylethylamine (9.05 mg, 3.0 eq) were added. The reaction mixture was reacted at room temperature for 2 hours. The reaction mixture was purified by high pressure to give a white solid compound D-1 (15 mg, 65.64%).

[0728] 1H NMR (400MHz, DMSO-d6) δ11.96 (d, J=6.9Hz, 1H), 11.11 (s, 1H), 7.83–7.69 (m, 2H), 7.71–7.63(m,1H),7.42(td,J=11.6,1.8Hz,2H),7.21(dd,J=16.3,5.6Hz,1H),6. 92–6.84(m,1H),6.79(d,J=8.0Hz,1H),6.70(d,J=8.2Hz,2H),6.20(dt,J=12.7,1 .9Hz,2H),6.14(s,1H),5.32(t,J=4.5Hz,1H),5.09(s,2H),4.64(s,2H),4.48(p, J=6.9Hz,1H),4.42–4.27(m,6H),4.00(p,J=6.7Hz,1H),3.85(d,J=12.2Hz,2H),3 .67(t,J=5.8Hz,1H),3.61(d,J=5.5Hz,3H),3.21–3.10(m,3H),3.11–3.06(m,3H) ,3.03(d,J=1.8Hz,6H),2.85(dd,J=9.1,5.1Hz,2H),2.80(t,J=5.4Hz,2H),2.65( s,2H),2.35(s,2H),2.29(s,1H),2.19(t,J=13.8Hz,2H),1.85(d,J=12.2Hz,2H).

[0729] LC-MS(ESI):[M+H] + =979.75

[0730] Example 15 Synthesis of Compound D-2

[0731] 6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7Hspiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxetane-heptano[3,4,5-cd]indole-2-carboxamide (compound D-2)

[0732] Synthesis scheme

[0733] Step 1: 6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7Hspiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxetane-heptano[3,4,5-cd]indole-2-carboxamide (compound D-2)

[0734] Compound D-1e (15 mg, 17.50 μmol), compound B-3l (4.15 mg, 26.25 μmol), N,N-diisopropylethylamine (6.79 mg, 52.51 μmol), and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (13.31 mg, 35.00 μmol) were dissolved in N,N-dimethylformamide (0.5 mL). The reaction mixture was reacted at room temperature for 2 hours. The reaction mixture was purified by high pressure to give a white solid compound D-2 (12 mg, 68.76%).

[0735] 1H NMR(400MHz,DMSO-d6)δ11.97(d,J=5.2Hz,1H),11.11(s,1H),7.78(m,J=12.9,9.0Hz, 1H),7.66(m,J=10.1,2.5Hz,1H),7.21(m,J=20.4,5.7Hz,1H),6.88(m,J=9.0,2.6Hz,1H ),6.78(d,J=8.0Hz,1H),6.71(d,J=2.8Hz,2H),6.14(m,J=5.0,2.8Hz,1H),5.88(m,J=1 3.7, 6.0, 2.4Hz, 1H), 5.34 (m, J=12.8, 5.4Hz, 1H), 5.10 (s, 2H), 4.64 (s, 2H), 4.35 (d, J= 19.3Hz,2H),4.24(q,J=6.6Hz,2H),3.85(d,J=12.1Hz,2H),3.62(s,5H),3.28(s,1H), 3.15–3.05(m,3H),3.03(s,6H),2.95(m,J=11.4,6.8Hz,3H),2.81(t,J=12.0Hz,2H),2. 74–2.59(m,2H),2.53(d,J=1.8Hz,1H),2.41–2.34(m,1H),2.22(m,J=31.0,17.3Hz,3H) ,2.10–1.97(m,2H),1.89(m,J=31.4,13.1Hz,4H),1.34(d,J=11.8Hz,2H),1.24(s,1H).

[0736] LC-MS(ESI):[M+H] + =997.65

[0737] Example 18 Synthesis of Compound E-3

[0738] 10-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropiperidin-3-yl)-6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzo[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxidin[3,4,5-cd]indole-2-carboxamide (compound E-3)

[0739] Synthesis scheme

[0740] Step 1: 10-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropiperidin-3-yl)-6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzo[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxidin[3,4,5-cd]indole-2-carboxamide (compound E-3)

[0741] Compound E-2l (40 mg, 1.0 eq) was dissolved in N,N-dimethylformamide (2 mL), and compound E-3a (7 mg, 1.1 eq), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (26 mg, 1.5 eq), and N,N-diisopropylethylamine (29 mg, 5.0 eq) were added. The reaction was carried out at room temperature for 2 hours. After the reaction was completed, compound E-3 (4.9 mg, 10.7%) was obtained by pre-purification under high pressure.

[0742] 1 H NMR (600MHz, DMSO-d6) δ11.96(d,J=5.8Hz,1H),11.11(s,1H),8.47(s,1H),8.12(d,J=11.1Hz,1H),7.80–7.67(m,2H),7.19(d,J=5.8Hz,1H),6. 89(dd,J=8.9,2.6Hz,1H),6.78(d,J=8.0Hz,1H),6.72(s,1H),6.19–6.1 2(m,1H),5.37–5.31(m,1H),5.09(s,2H),4.64(d,J=6.2Hz,3H),4.36(d, J=20.7Hz,2H),3.55(d,J=10.7Hz,4H),3.45(s,2H),3.31(dd,J=32.0,14.1Hz,4H),3.22–3.09(m,5H),3.03(d,J=1.9Hz,4H),2.90(d,J=15.9Hz, 2H),2.70–2.59(m,2H),2.33(d,J=29.8Hz,4H),2.04–1.95(m,2H),1.88 (d, J=13.7Hz, 2H), 1.66 (dd, J=31.3, 11.2Hz, 5H), 1.23 (d, J=3.5Hz, 5H).

[0743] LC-MS(ESI):[M+H] + =994.45

[0744] Example 16 Synthesis of Compound D-3

[0745] 6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-10-(1-(3-(4-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxacyclopenta[3,4,5-cd]indole-2-carboxamide (compound D-3)

[0746] Synthesis scheme

[0747] Step 1: 6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)piperidin-1-yl)-11-fluoro-10-(1-(3-(4-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxacyclopenta[3,4,5-cd]indole-2-carboxamide (compound D-3)

[0748] Preparation was carried out with reference to compound D-2.

[0749] 1H NMR(400MHz, DMSO-d6)δ11.96(d,J=5.4Hz,1H),11.11(s,1H),7.86(dd,J=10.3, 4.6Hz,1H),7.77(dd,J=11.3,9.0Hz,1H),7.43(dd,J=25.2,4.3Hz,1H),7.21(dd ,J=18.1,5.8Hz,1H),6.91–6.83(m,1H),6.78(d,J=8.0Hz,1H),6.74–6.67(m,2H ),6.15(s,1H),5.39–5.29(m,2H),5.09(s,2H),4.64(s,2H),4.35(d,J=24.9Hz, 2H),4.29(d,J=6.7Hz,2H),3.85(d,J=12.1Hz,2H),3.67(t,J=5.8Hz,1H),3.60( q,J=10.1,8.0Hz,4H),3.09(d,J=7.1Hz,3H),3.03(d,J=1.2Hz,6H),2.99(s,3H) ,2.79(d,J=11.5Hz,2H),2.63(d,J=16.9Hz,2H),2.40–2.31(m,1H),2.22(dd,J= 32.3,18.5Hz,3H),2.05–1.81(m,6H),1.39–1.27(m,2H),1.24(d,J=3.0Hz,2H).

[0750] LC-MS(ESI):[M+H] + =997.12

[0751] Example 17 Synthesis of Compound E-2

[0752] 6-(4-((3-(2,6-piperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazole-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxopyridine[3,4,5-cd]indole-2-carboxamide (compound E-2)

[0753] Synthesis scheme

[0754] Step 1: Benzyl 4-formyl-4-methylpiperidine-1-carboxylic acid ester (compound E-2b)

[0755] 4-Formyl-N-CBZ piperidine (40 g, 1.0 eq) was dissolved in dichloromethane, and potassium tert-butoxide (27 g, 1.5 eq) and iodomethane (68.8 g, 3 eq) were added sequentially. The reaction was carried out at 25 °C for 2 hours under nitrogen protection. After the reaction was completed, water (500 mL) was added to the reaction system, and the mixture was extracted three times with dichloromethane (500 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under vacuum. The crude product was purified by column chromatography to give compound E-2b (14 g, 30.75%).

[0756] Step 2: 4-Methylpiperidine-4-carboxaldehyde (compound E-2c)

[0757] Compound E-2b was dissolved in methanol, palladium on carbon was added, and the reaction was carried out at 25°C for 2 hours under a hydrogen atmosphere. After the reaction was completed, the reaction system was filtered, the filtrate was collected, and the solution was concentrated under vacuum to obtain compound E-2c (6 g, 94.82%).

[0758] Step 3: 1-(4-bromo-3-hydroxyphenyl)-4-methylpiperidine-4-carboxaldehyde (compound E-2d)

[0759] Compound E-1a (8.6 g, 1.0 eq), compound E-2c (4 g, 1.0 eq), cuprous iodide (1.1 g, 0.2 eq), L-proline (1.3 g, 0.2 eq), and potassium carbonate (12 g, 3.0 eq) were dissolved in dimethyl sulfoxide. The reaction mixture was reacted at 80 °C for 2 hours under nitrogen protection. After the reaction was complete, water (50 mL) and ethyl acetate (100 mL) were added to the reaction mixture for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under vacuum. The crude product was purified by column chromatography to give compound E-2d (1.9 g, 34.39%).

[0760] Step 4: 6-Chloro-7-fluoro-4-(4-(4-formaldehyde-4-methylpiperidin-1-yl)-2-hydroxyphenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound E-2e)

[0761] Compound E-1d (1 g, 1.0 eq) was dissolved in dioxane:water = 10:1 (12 mL), and compound E-2d (900 mg, 1.0 eq), 1,1-bis(diphenylphosphine)dimerferropalladium dichloride (200 mg, 0.1 eq), and potassium carbonate (1.1 g, 3.0 eq) were added. The reaction was carried out at 100 °C for 3 hours under nitrogen protection. After the reaction was completed, water (50 mL) and ethyl acetate (10 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound E-2e (1.1 g, 82.7%).

[0762] LC-MS(ESI):[M+H] + =458.39

[0763] Step 5: 10-Chloro-11-Fluoro-6-(4-formyl-4-methylpiperidin-1-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxoindole-2-carboxylic acid (compound E-2f)

[0764] Compound E-2e (1 g, 1.0 eq) was dissolved in N,N-dimethylformamide, and hexamethylenetetramine (1.2 g, 4.0 eq) was added. The reaction was carried out at 120 °C for 2 hours under nitrogen protection. After the reaction was complete, water (50 mL) and ethyl acetate (100 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to give compound E-2f (500 mg, 48.72%).

[0765] LC-MS(ESI):[M+H] + =470.29

[0766] Step 6: Tert-butyl 5-(2-(dimethylamino)-11-fluoro-6-(4-formyl-4-methylpiperidin-1-yl)-1,3-dihydrobenzo[6,7]oxoquinoline[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylate (compound E-2g)

[0767] Compound E-2f (480 mg, 1.0 eq) was dissolved in dioxane:water = 10:1 (11 mL), and compound a-1a (315 mg, 1.0 eq), potassium phosphate (650 mg, 3.0 eq), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (8 mg, 0.1 eq) were added. The reaction was carried out at 80 °C for 3 hours under nitrogen protection. After the reaction was completed, water (50 mL) and ethyl acetate (100 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound E-2g (420 mg, 66.67%).

[0768] LC-MS(ESI):[M+H] + =617.59

[0769] Step 7: Tert-butyl 5-(2-(dimethylamino)-6-(4-((3-(2,6-dioxopiridin-3-yl)-1-methyl-2-oxo-2,3-tetrahydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-1,3-tetrahydrobenzo[6,7]oxoperidin[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylate (compound E-2h)

[0770] Compound E-2g (50 mg, 1.0 eq), compound A-4a (60 mg, 2.0 eq), and tetraisopropyl titanate (230 mg, 10.0 eq) were dissolved in tetrahydrofuran:dimethyl sulfoxide = 2:1 (3 mL), and the reaction system was reacted at 60 °C for 3 hours. Then, sodium triacetoxyborohydride (85 mg, 5.0 eq) was added to the reaction system, and the reaction was carried out at 60 °C for 1 hour. After the reaction was completed, the mixture was purified by high pressure to obtain a white solid compound E-2h (25 mg, 31.75%).

[0771] LC-MS(ESI):[M+H] + =971.29

[0772] Step 8: 6-(4-((3-(2,6-dioxypiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-N,N-dimethyl-10-(1,2,5,6-tetrahydropyridin-3-yl)-1,3-dihydrobenzo[6,7]oxoquinoline-2-carboxamide (compound E-2i)

[0773] Compound E-2h (25 mg, 1.0 rq) was dissolved in dichloromethane (1 mL), and trifluoroacetic acid (0.5 mL) was added. The reaction system was reacted at room temperature for 1 hour. The reaction system was concentrated to give compound E-2i (20 mg, 89.20%).

[0774] LC-MS(ESI):[M+H] + =871.66

[0775] Step 9: 6-(4-((3-(2,6-piperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazole-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxopyridine[3,4,5-cd]indole-2-carboxamide (compound E-2)

[0776] Compound E-2i (15 mg, 1.0 eq), compound B-3l (5 mg, 2.0 eq), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (13 mg, 2.0 eq), and N,N-diisopropylethylamine (7 mg, 3.0 eq) were dissolved in N,N-dimethylformamide, and the reaction system was reacted at 25 °C for 1 hour. After the reaction was completed, the mixture was purified by high pressure to obtain a white solid compound E-2 (2 mg, 11.49%).

[0777] 1H NMR (600MHz, DMSO-d6) δ11.97(d,J=7.8Hz,1H),11.12(s,1H),7.79(dd,J=19.7,9.0Hz ,1H),7.66(dt,J=15.1,2.5Hz,1H),7.22(dd,J=30.6,5.7Hz,1H),6.89(dd,J=8.9,2.6H z,1H),6.79(d,J=8.1Hz,1H),6.72(t,J=5.2Hz,2H),6.15(dd,J=4.5,2.4Hz,1H),5.88 (ddd,J=20.5,5.9,2.4Hz,1H),5.34(dd,J=13.3,5.3Hz,1H),5.10(s,2H),4.64(s,2H), 4.40–4.30(m,2H),4.24(q,J=7.5Hz,2H),3.64(dt,J=29.2,5.8Hz,3H),3.60–3.55(m, 3H),3.46(s,7H),3.35(d,J=19.5Hz,2H),3.27(d,J=11.8Hz,2H),3.20–3.08(m,4H),2. 96(dt,J=17.5,6.7Hz,3H),2.71–2.59(m,2H),2.41–2.26(m,4H),1.99(dd,J=9.3,4.9H z,1H),1.88(d,J=14.4Hz,2H),1.76–1.68(m,2H),1.63(d,J=13.4Hz,2H),1.23(s,3H).

[0778] LC-MS(ESI):[M+H] + =1011.65

[0779] Example 19 Synthesis of Compound G-1

[0780] 6-(4-((3-(2,6-piperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazole-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxopyridine[3,4,5-cd]indole-2-carboxamide (compound G-1)

[0781] Synthesis scheme

[0782] Step 1: tert-butyl 5-(2-(dimethylamino)-11-fluoro-6-(4-formyl-4-methylpiperidin-1-yl)-1,3-dihydrobenzo[6,7]oxoquinoline[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylate (compound G-1b)

[0783] Compound E-2f (480 mg, 1.0 eq) was dissolved in dioxane:water = 10:1 (11 mL), and compound G-1a (315 mg, 1.0 eq), potassium phosphate (650 mg, 3.0 eq), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (8 mg, 0.1 eq) were added. The reaction was carried out at 90 °C for 1 hour under nitrogen protection. After the reaction was completed, water (50 mL) and ethyl acetate (100 mL) were added to the reaction system for extraction three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was collected. The filtrate was concentrated under vacuum, and the crude product was purified by column chromatography to obtain compound G-1b (420 mg, 66.67%).

[0784] LCMS(ESI):[M+H] + =631.58.

[0785] Step 2: Tert-butyl 5-(2-(dimethylamino)-6-(4-((3-(2,6-dioxoperidin-3-yl)-1-methyl-2-oxo-2,3-tetrahydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-1,3-tetrahydrobenzo[6,7]oxoperidin[3,4,5-cd]indol-10-yl)-3,6-dihydropyridine-1(2H)-carboxylate (compound G-1c)

[0786] Compound G-1b (50 mg, 1.0 eq), compound A-4a (60 mg, 2.0 eq), and tetraisopropyl titanate (230 mg, 10.0 eq) were dissolved in dimethyl sulfoxide (2 mL), and the reaction system was reacted at 80 °C for 3 hours. Then, sodium triacetoxyborohydride (85 mg, 5.0 eq) was added to the reaction system, and the reaction was carried out at 80 °C for 1 hour. After the reaction was completed, the mixture was purified by high pressure to obtain a white solid compound G-1c (38.00 mg, 49%).

[0787] LC-MS(ESI):[M+H] + =985.75.

[0788] Step 3: 6-(4-((3-(2,6-dioxypiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-N,N-dimethyl-10-(1,2,5,6-tetrahydropyridin-3-yl)-1,3-dihydrobenzo[6,7]oxoquinoline-2-carboxamide (compound G-1d)

[0789] Compound G-1c (0.13 g, 0.13 mmol) was dissolved in dichloromethane (1 mL), and trifluoroacetic acid (0.5 mL) was added. The reaction system was reacted at room temperature for 1 hour. The reaction system was concentrated to give compound G-1d (116 mg, 99%).

[0790] LCMS(ESI):[M+H] + =885.76.

[0791] Step 4: 6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-((R)-1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-6-methyl-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxacyclopenta[3,4,5-cd]indole-2-carboxamide (compound G-1)

[0792] Compound G-1d (116.00 mg, 0.13 mmol) and compound B-3l (62.18 mg, 0.39 mmol) were dissolved in 2 mL of DMF. Then, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (99.67 mg, 0.26 mmol) and N,N-diisopropylethylamine (101.63 mg, 0.79 mmol) were added. The reaction mixture was reacted at 25 °C for 1 hour. After the reaction was complete, the mixture was purified by high pressure to obtain a white solid compound G-1 (41.62 mg, 31%).

[0793] 1H NMR(600MHz,DMSO-d6)δ11.99–11.92(m,1H),11.13–11.07(m,1H),7.83–7.76(m,1H),7.69–7.63(m,1H),7.26–7.16(m,1H) ,6.91–6.84(m,1H),6.80–6.65(m,3H),6.07–6.00(m,1H),5.91–5.85(m,1H),5.37–5.29(m,1H),5.09(s,2H),4.96–4.85(m, 1H),4.63(s,2H),4.39–4.32(m,1H),4.27–4.19(m,2H),4.14–4.06(m,1H),3.66–3.52(m,5H),3.37–2.79(m,17H),2.69–2.6 0(m,2H),2.38–2.09(m,4H),2.03–1.96(m,1H),1.91–1.85(m,2H),1.74–1.68(m,2H),1.65–1.58(m,2H),1.24–1.22(m,6H).

[0794] LC-MS(ESI):[M+H] + =1025.65

[0795] Example 20 Synthesis of Compound B-4

[0796] 4-(4-(4-((3-(2,6-dioxoperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-6-(2-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-2-azabicyclo[4.1.0]hept-4-en-4-yl)-N,N-dimethyl-1H-indole-2-carboxamide (compound B-4)

[0797] Synthesis scheme

[0798] Step 1: Ethyl 4-methylpiperidine-4-carboxylate (compound B-4b)

[0799] A 4.0 M hydrochloric acid solution of dioxane (50 mL) was added to a dichloromethane solution of compound B-4a (10 g, 38.86 mmol), and the mixture was stirred at 20 °C for 1 hour. After the reaction was complete, the mixture was concentrated under reduced pressure to obtain a yellow solid crude compound B-4b (7.2 g).

[0800] LC-MS(ESI):[M+H] + =158.20

[0801] Step 2: Methyl 1-(4-bromophenyl)-4-methylpiperidine-4-carboxylate (compound B-4c)

[0802] Compound B-4-b (7 g, 44.53 mmol), p-bromoiodobenzene (12.6 g, 44.53 mmol), tris(dibenzylacetone)dipalladium (2.04 g, 2.23 mmol), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (2.58 g, 4.45 mmol), and sodium tert-butoxide were added to a toluene (140 mL) solution and stirred at 80 °C for 2 hours. After the reaction was complete, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography to finally give a yellow solid compound B-4c (6.9 g, 49.64%).

[0803] 1 H NMR(400MHz,DMSO-d6)δ7.35–7.29(m,2H),6.91–6.85(m,2H),3.64(s,3H),3.43–3 .37(m,2H),2.88–2.81(m,2H),2.08–2.01(m,2H),1.57–1.45(m,2H),1.18(s,3H).

[0804] LC-MS(ESI):[M+H] + =312.15

[0805] Step 3: (1-(4-bromophenyl)-4-methylpiperidin-4-yl)methanol (compound B-4d)

[0806] Compound B-4c (2.4 g, 7.69 mmol) was added to tetrahydrofuran (30 mL), and lithium aluminum hydride solution (2.5 M, 15.4 mL, 38.44 mmol) was added at 0 °C. The mixture was stirred at 25 °C for 1 hour. After the reaction was complete, methanol was added at 0 °C to quench the reaction, followed by the addition of saturated brine and extraction three times with ethyl acetate. The organic phase was concentrated to obtain crude yellow colloidal compound B-4d (1.5 g).

[0807] LC-MS(ESI):[M+H] + =284.15

[0808] Step 4: 6-Chloro-7-fluoro-4-(4-(4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound B-4e)

[0809] Compounds B-4d (3 g, 10.56 mmol) and E-1d (4.64 g, 12.67 mmol) were dissolved in a mixed solvent of dioxane (60 mL) and water (12 mL). Potassium carbonate (4.38 g, 31.67 mmol) and dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium (1.54 g, 2.11 mmol) were added sequentially, and the mixture was stirred at 25 °C. The reaction mixture was then heated to 90 °C and stirred for 3 hours. After the reaction was complete, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography to give a yellow solid compound B-4e (1.96 g, 41.8%).

[0810] 1 H NMR (400MHz, DMSO-d6) δ12.36(s,1H),7.50(d,J=8.7Hz,2H),7.09(d,J=6.1Hz,1H),7.07–7.01(m,2H),6.91–6.87(m,1H),4.56(t,J=5. 4Hz,1H),3.47–3.35(m,2H),3.27–2.97(m,10H),3.07(ddd,J=12.7,9.7,3.3Hz,5H),1.67–1.54(m,2H),1.38–1.28(m,2H),0.93(s,3H).

[0811] LC-MS(ESI):[M+H] + =444.30

[0812] Step 5: Phenethyl 3-hydroxy-3,4-dihydropyridine-1(2H)-carboxylic acid ester (compound B-4g)

[0813] Compound B-4f (10 g, 0.1 mol), sodium bicarbonate (6.62 g, 0.07 mol), and methanol (100 ml) were added to a three-necked flask. The reaction system was then cooled to -78°C, and sodium borohydride (10.54 g, 0.27 mol) was added in portions at this temperature, maintaining the temperature below -60°C throughout the process. After the addition was complete, benzyl chloroformate (36.77 g, 0.21 mol) was slowly added dropwise at -78°C. After the addition was complete, the reaction was allowed to proceed at this temperature for one hour. Upon completion of the reaction, 1 M sodium hydroxide solution was added to quench the reaction, and the mixture was extracted with ethyl acetate, washed with saturated sodium chloride solution, concentrated, and subjected to column chromatography to obtain a yellow oily compound B-4f (11 g).

[0814] 1H NMR(600MHz,Chloroform-d)δ7.45–7.35(m,5H),6.98–6.85(m,1H),5.27–5.17(m,2H),4.9 4–4.76(m,1H),4.22–4.08(m,1H),3.74–3.59(m,2H),2.47–2.33(m,1H),2.14–2.08(m,1H).

[0815] LC-MS(ESI):[M+H] + =234.26

[0816] Step 6: Benzyl 4-hydroxy-2-azacyclohexane-2-carboxylic acid ester (compound B-4h)

[0817] Compound B-4 g (5 g, 41.33 mmol) and 1,2-dichloroethane (50 ml) were added to a three-necked flask. After the addition was complete, the mixture was kept under nitrogen protection and cooled to 0°C. Diethylzinc (62 mmol) and diiodomethane (16.6 g, 62 mmol) were added dropwise to the reaction system. After the addition was complete, the mixture was allowed to rise naturally to room temperature for 3 hours. After the reaction was complete, saturated sodium bicarbonate solution was added to quench the reaction. The system was filtered under reduced pressure using diatomaceous earth. The filter cake was washed with dichloromethane, and the filtrate was extracted with dichloromethane. The organic phase was washed with saturated sodium chloride solution, concentrated, and subjected to column chromatography to obtain a yellow oily compound B-4 h (3.5 g).

[0818] LC-MS(ESI):[M+H] + =248.37

[0819] Step 7: Phenethyl-4-one-2-azacyclohexane-2-carboxylic acid ester (compound B-4i)

[0820] Compound B-4h (5 g, 20.21 mmol), methanol (50 mL), pyridinium chlorochromate (21.79 g, 101.09 mmol), and silica gel (21.79 g) were added to the reaction flask. After the additions were complete, the mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was filtered under reduced pressure, the filter cake was washed with ethyl acetate, the filtrate was concentrated, and the solution was subjected to column chromatography to obtain a yellow oily compound B-4i (3 g).

[0821] LC-MS(ESI):[M+H] + =246.47

[0822] Step 8: tert-butyl-4-one-2-azacyclohexane-2-carboxylic acid ester (compound B-4j)

[0823] Compound B-4i (5 g, 20.38 mmol), methanol (50 ml), palladium on carbon (1 g), and di-tert-butyl dicarbonate (6.67 g, 30.57 mmol) were added to the reaction flask. After the addition was complete, the mixture was reacted overnight under hydrogen atmosphere. After the reaction was complete, the mixture was filtered under reduced pressure using diatomaceous earth. The filter cake was washed with methanol, and the filtrate was concentrated. The filtrate was then subjected to column chromatography to obtain a yellow oily compound, compound B-4j (2 g).

[0824] 1 H NMR (400MHz, DMSO-d6) δ4.14–3.90(m,1H),3.77–3.45(m,1H),2.78–2.64(m,2H),2.20(dd, J=16.7,6.1Hz,1H),1.43(s,9H),1.32–1.22(m,1H),1.15–1.03(m,1H),0.67–0.52(m,1H).

[0825] LC-MS(ESI):[M+H] + =212.35

[0826] Step 9: tert-butyl-4-one-2-azacyclohexane-2-carboxylic acid ester (compound B-4k)

[0827] Intermediate B-4j (2 g, 10.14 mmol) and ultra-dry tetrahydrofuran (20 ml) were added to a 500 ml reaction flask. After the addition was complete, the mixture was cooled to -100 °C under nitrogen protection. At this temperature, bis(trimethylsilylaminolithium) (10.24 mmol) was added dropwise to the reaction system. After the addition was complete, the mixture was reacted at -100 °C for 30 minutes. Then, N-phenylbis(trifluoromethanesulfonyl)imide (3.62 g, 10.14 mmol, dissolved in 10 ml of tetrahydrofuran) was added dropwise to the system. The mixture was allowed to rise naturally to room temperature and reacted for 2 hours. After the reaction was complete, the reaction was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and the organic phase was washed with saturated sodium chloride solution. The organic phase was concentrated and subjected to column chromatography to obtain the crude product, compound B-4k (3 g), which was used directly in the next step.

[0828] Step 10: tert-butyl-4-one-2-azacyclohexane-2-carboxylic acid ester (compound B-4l)

[0829] Crude compound B-4k (3 g), pinacol diborate (4.43 g, 17.47 mmol), potassium acetate (2.57 g, 26.21 mmol), dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium (0.63 g, 0.87 mmol), and 1,4-dioxane (30 ml) were added to the reaction flask. Under nitrogen protection, the mixture was heated to 80 °C and reacted overnight. After the reaction was completed, the mixture was cooled to room temperature, concentrated, and purified by normal-phase column chromatography and reverse-phase column chromatography to obtain a yellow oily compound B-4l (0.3 g).

[0830] LC-MS(ESI):[M-tBu+H] + =266.27

[0831] Step 11: Tert-butyl 4-(2-(dimethylcarbamoyl)-7-fluoro-4-(4-(4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)phenyl)-1H-indol-6-yl)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid ester (compound B-4m)

[0832] Compound B-4e (160 mg, 360.4 μmol), compound B-4l (130 mg, 404.71 μmol), potassium phosphate (195 mg, 918.66 μmol), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (30 mg, 35.4 μmol) were dissolved in a mixed solvent of 1,4-dioxane and water (10 / 1 mL). Under nitrogen protection, the mixture was stirred in an oil bath at 80 °C for 2 hours. The mixture was extracted twice with dichloromethane, and the organic phase was evaporated to dryness and purified by column chromatography to give a yellow solid compound B-4m (150 mg, 69%).

[0833] 1 H NMR (400MHz, DMSO-d6) δ12.13(s,1H),7.50(d,J=8.6Hz,2H),7.04(d,J=8.7Hz,2H),6. 90(d,J=6.1Hz,1H),6.87–6.83(m,1H),6.45–6.37(m,1H),4.56(t,J=5.4Hz,1H),3.95( s,2H),3.44-3.36(m,2H),3.26–2.97(m,11H),1.76–1.65(m,1H),1.64–1.55(m,2H),1. 47-1.41(m,9H),1.37-1.30(m,2H),1.27-1.12(m,1H),0.93(s,3H),0.57-0.48(m,1H).

[0834] LC-MS(ESI):[M+H] + =603.58

[0835] Step 12: Tert-butyl 4-(2-(dimethylcarbamoyl)-7-fluoro-4-(4-(4-formyl-4-methylpiperidin-1-yl)phenyl)-1H-indol-6-yl)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid ester (compound B-4n)

[0836] Compound B-4m (110 mg, 182.5 μmol) was dissolved in dimethyl sulfoxide (5 mL). 2-Iodobenzoic acid (80 mg, 285.7 μmol) was added, and the reaction was carried out at room temperature for 4 hours. The mixture was extracted with dichloromethane, and the organic phase was washed successively with saturated sodium thiosulfate and brine to give a yellow oily compound B-4n (120 mg, >99%).

[0837] LC-MS(ESI):[M+H] + =601.68

[0838] Step 13: Tert-butyl 4-(2-(dimethylcarbamoyl)-4-(4-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-1H-indo-6-yl)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid ester (compound B-4o)

[0839] Compound B4-n (100 mg, 166.46 μmol) and compound A-4a (90 mg, 242.97 μmol) were dissolved in dimethyl sulfoxide (30 mL), and tetraisopropyl titanate (285 mg, 1.00 mmol) was added. The mixture was stirred in an oil bath at 60 °C for 2 hours, and then sodium cyanoborohydride (30 mg, 501.5 μmol) was added. The mixture was stirred at 60 °C for another hour. The reaction solution was diluted with a mixed solvent of dichloromethane and methanol (10:1), and water was added before filtration. The organic phase obtained from the filtrate was washed with saturated brine, and after rotary evaporation, the organic phase was purified by preparative agar (MeOH:DCM = 1:15) to obtain a yellow solid compound B-4o (90 g, 56%).

[0840] LC-MS(ESI):[M+H] + =955.75

[0841] Step 14: 6-(2-azabicyclo[4.1.0]hept-4-en-4-yl)-4-(4-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (compound B-4p)

[0842] Compound B-4o (90 g, 94.22 μmol) was dissolved in dichloromethane (6 mL), and trifluoroacetic acid (1.5 mL) was added. The mixture was stirred at room temperature for 1 hour. After evaporation to dryness, a yellow oily compound B-4p was obtained.

[0843] LC-MS(ESI):[M+H] + =855.66.

[0844] Step 15: 4-(4-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-6-(2-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-2-azabicyclo[4.1.0]hept-4-en-4-yl)-N,N-dimethyl-1H-indole-2-carboxamide (compound B-4)

[0845] Compound B-4p (60 mg, 70.17 μmol), 3-(3-fluoro-1H-pyrazol-1-yl)propionic acid (23 mg, 145.44 μmol), and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)hexafluorophosphate urea (60 mg, 157.79 μmol) were dissolved in N,N-dimethylformamide (4 mL), and N,N-diisopropylethylamine (90 mg, 696.34 μmol) was added. The reaction mixture was reacted at room temperature for 1 hour. The reaction system was purified by high pressure to obtain a white solid compound B-4 (20 mg, 28%).

[0846] 1H NMR (400MHz, DMSO-d6) δ12.18(s,1H),11.12(s,1H),7.67-7.63(m,1H),7.54(d,J=8.5Hz,2H),7.11(d,J=8.3Hz,2H),6.91(d,J=6.1Hz,1 H),6.86-6.82(m,1H),6.78(d,J=8.0Hz,1H),6.71(d,J=7.9Hz,1H),6.46-6.39(m,1H),5.91–5.86(m,1H),5.35(dd,J=13.6,5.0Hz,1H),4 .71–4.60(m,3H),4.29–4.18(m,2H),3.85–3.76(m,1H),3.59(s,3H),3.48–3.00(m,18H),2.96–2.86(m,1H),2.73–2.57(m,2H),2.38-2.2 8(m,2H),2.03-1.95(m,2H),1.92–1.83(m,3H),1.80-1.71(m,2H),1.69-1.61(m,2H),1.37–1.30(m,1H),1.23(s,3H),0.57-0.52(m,1H).

[0847] LC-MS(ESI):[M+H] + =995.75

[0848] Example 21 Synthesis of Compound A-5

[0849] (S)-6-(4-((7'-(2,6-dioxopiperidin-3-yl)-8'-oxo-4',6',7',8'-tetrahydro-3'H-spiro[azacyclobutane-3,2'-pyran[2,3-f]isoindole]-1-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxanthracene[3,4,5-cd]indole-2-carboxamide (Compound A-5)

[0850] The synthesis scheme is the same as that for compound E2, a white solid with a yield of 8%.

[0851] 1H NMR (400MHz, DMSO-d6) δ11.96(d,J=5.3Hz,1H),10.99(s,1H),7.76(dd,J=13.4,9.0Hz,1H),7.68–7.64(m,1H),7.38(s,1H),7.16(d,J=12. 9Hz,1H),7.09(d,J=7.8Hz,1H),6.86(d,J=8.8Hz,1H),6.67(d,J=7.0Hz,1H),6.14(d,J=3.7Hz,1H),5.91–5.85(m,1H),5.08–5.05(m,2H), 4.60–4.46(m,2H),4.40–4.31(m,4H),4.26–4.19(m,3H),3.67–3.60(m,4H),3.44–3.43(m,6H),3.33(d,J=5.1Hz,1H),3.16(s,1H),3.02(s ,4H),2.99–2.85(m,5H),2.63–2.56(m,1H),2.41–2.21(m,5H),2.01– 1.96(m,1H),1.63–1.61(m,2H),1.52–1.44(m,2H),1.09–1.03(m,3H).

[0852] LCMS(ESI):[M+H] + =982.45.

[0853] Example 22 Synthesis of Compound A-6

[0854] (S)-6-(4-((6-((2,6-dioxopiperidin-3-yl)carbamoyl)-5-methoxy-2H-spiro[benzofuran-3,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indole-2-carboxamide (Compound A-6)

[0855] The synthesis scheme is the same as that for compound E2, a white solid with a yield of 18%.

[0856] 1H NMR (400MHz, DMSO-d6) δ11.97(d,J=5.1Hz,1H),10.90(s,1H),8.67(dd,J=7.4,3.7Hz,1H),7.78(dd,J=13.4,8.9Hz,1H),7.68–7.64(m,1H),7.26–7.16 (m,2H),6.93–6.83(m,2H),6.71(d,J=2.5Hz,1H),6.14(s,1H),5.91–5.85( m,1H),5.09(s,2H),4.76–4.69(m,1H),4.53(s,2H),4.37–4.32(m,1H),4.2 6–4.21(m,1H),3.92–3.91(m,2H),3.69–3.59(m,8H),3.46–3.41(m,4H),3. 35–3.34(m,1H),3.27–3.24(mz,1H),3.16–3.08(m,4H),3.02(s,4H),2.98– 2.92(m,2H),2.80–2.72(m,1H),2.41–2.28(m,4H),2.11–2.06(m,2H),1.91 –1.87(m,2H),1.76–1.58(m,4H),1.22–1.21(m,2H),1.05(t,J=7.0Hz,1H).

[0857] LCMS(ESI):[M+H] + =1014.45.

[0858] Example 23 Synthesis of Compound A-7

[0859] 6-(4-((1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3,7,8-tetrahydro-1H-spiro[enzo[6,7-d]imidazo-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indole-2-carboxamide (Compound A-7)

[0860] The synthesis scheme is the same as that for compound E2, a white solid with a yield of 21%.

[0861] 1H NMR (400MHz, DMSO-d6) δ11.97(d,J=5.3Hz,1H),11.07(s,1H),7.80–7.74(m,1H),7.68–7.64(m,1H),7.20(dd,J=21.2,5.8Hz,1H),6.88–6.8 4(m,2H),6.70–6.65(m,2H),6.15–6.14(m,1H),5.91–5.85(m,1H),5.30(dd,J=12.8,5.6Hz,1H),5.08(s,2H),4.43–4.17(m,4H),3.67–3.60 (m,3H),3.45–3.40(m,6H),3.35–3.32(m,1H),3.28–3.27(m,2H),3.2 2(s,1H),3.16(s,1H),3.13–3.08(m,2H),3.02(s,4H),2.99–2.84(m,3 H),2.81–2.54(m,5H),2.42–2.23(m,3H),2.09–1.86(m,5H),1.82–1.7 9(m,1H),1.74–1.53(m,4H),1.23–1.17(m,2H),1.05(t,J=7.0Hz,1H).

[0862] LCMS(ESI):[M+H] + =1025.50.

[0863] Example 24 Synthesis of Compound A-8

[0864] 6-(4-((7'-(2,6-dioxopiperidin-3-yl)-6'-oxo-4',6',7',8'-tetrahydro-3'H-spiro[azacyclobutane-3,2'-pyrano[2,3-f]isoindole]-1-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxetane[3,4,5-cd]indole-2-carboxamide (compound A-8)

[0865] The synthesis scheme is the same as that for compound E2, a white solid with a yield of 43%.

[0866] 1H NMR (400MHz, DMSO-d6) δ11.97(d,J=5.3Hz,1H),10.98(d,J=2.5Hz,1H),7.80–7.73(m,1H),7.69–7.64(m,1H),7.53(s,1H),7.24–7.17(m,1H), 7.07(d,J=16.8Hz,1H),6.88–6.85(m,1H),6.69–6.68(m,1H),6.15–6. 13(m,1H),5.91–5.85(m,1H),5.08(s,2H),4.63–4.58(m,1H),4.52–4.4 8(m,1H),4.42–4.32(m,5H),4.26–4.20(m,3H),3.63–3.60(m,2H),3.5 1–3.33(m,5H),3.15–3.06(m,2H),3.02(s,6H),2.98–2.92(m,3H),2.89 –2.86(m,1H),2.64–2.55(m,2H),2.38–2.33(m,2H),2.28–2.20(m,3H) ,2.02–1.95(m,1H),1.67–1.58(m,2H),1.53–1.42(m,2H),1.09(s,3H).

[0867] LC-MS(ESI):[M+H] + =982.45

[0868] Example 25 Synthesis of Compound A-9

[0869] 6-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,6Hspiro[benzofurano[5,6-d]imidazol-7,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazole-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxepepto[3,4,5-cd]indole-2-carboxamide (Compound A-9)

[0870] The synthesis scheme is the same as that for compound E2, a white solid with a yield of 33%.

[0871] 1H NMR (400MHz, DMSO-d6) δ11.98(s,1H),11.09(s,1H),7.81–7.75(m,1H),7.69–7.65(m,1H),7.25–7.18(m,1H),6.89(dd,J=8.9,2.6Hz,1H),6. 81(s,1H),6.76–6.71(m,2H),6.15–6.13(m,1H),5.92–5.86(m,1H),5. 34–5.30(m,1H),5.09(s,2H),4.48(s,2H),4.37–4.32(m,2H),4.26–4.2 1(m,2H),3.53–3.51(m,2H),3.35–3.33(m,4H),3.27–3.20(m,2H),3.1 7–3.09(m,4H),3.03(s,6H),2.98–2.92(m,3H),2.87–2.83(m,1H),2.77 –2.66(m,2H),2.65–2.59(m,1H),2.43–2.25(m,4H),2.02–1.93(m,2H) ,1.91–1.84(m,2H),1.75–1.69(m,2H),1.64–1.59(m,2H),1.23(s,3H).

[0872] LC-MS(ESI):[M+H] + =1011.45

[0873] Example 26 Synthesis of Compound A-10

[0874] 6-(4-(((S)-9-(((S)-2,6-dioxopiperidin-3-yl)carbamoyl)-10-methoxy-1,2,4,4a,5,6-hexahydro-3H-benzo[b]pyrazino[1,2-d][1,4]oxazapheno-3-yl)methyl)-4-methylpiperidin-1-yl)-11-fluoro-10-(1-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N,N-dimethyl-1,3-dihydrobenzo[6,7]oxecycloheptano[3,4,5-cd]indole-2-carboxamide (Compound A-10)

[0875] The synthesis scheme is the same as that for compound E2, a white solid with a yield of 42%.

[0876] 1H NMR (400MHz, DMSO-d6) δ11.97(s,1H),10.90(s,1H),8.52(d,J=7.2Hz,1H),7.81–7.75(m,1H),7.68–7.65(m,1H),7.39(s,1H),7.24–7.17(m,1H) ),6.88(dd,J=9.0,2.6Hz,1H),6.71(d,J=3.1Hz,2H),6.15–6.13(m,1H) ,5.91–5.85(m,1H),5.09(s,2H),4.74–4.68(m,1H),4.39–4.32(m,2H), 4.26–4.16(m,3H),4.11–4.05(m,1H),3.91(s,3H),3.57–3.46(m,5H),3 .41–3.31(m,2H),3.29–3.06(m,6H),3.03(s,6H),2.99–2.93(m,2H),2. 81–2.73(m,1H),2.56–2.52(m,1H),2.43–2.23(m,3H),2.12–2.06(m,2H ),2.05–1.95(m,2H),1.91–1.80(m,1H),1.74–1.59(m,4H),1.23(s,3H).

[0877] LC-MS(ESI):[M+H] + =1029.45

[0878] Example 27 Synthesis of compound B-5-A

[0879] 4-(4-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-6-(2-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-2-azabicyclo[4.1.0]hept-4-en-4-yl)-N,N-dimethyl-1H-indole-2-carboxamide (Compound B-5-A)

[0880] Synthesis scheme

[0881] Step 1: 4-(((trifluoromethyl)sulfonyl)oxy)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid benzyl ester (compound B-5a)

[0882] Compound B-4i (10 g, 40.77 mmol) and ultra-dry tetrahydrofuran (100 ml) were added to a 500 ml reaction flask. After the addition was complete, the mixture was cooled to -80 °C under nitrogen protection. At this temperature, bis(trimethylsilylaminolithium) (44.84 mmol) was added dropwise to the reaction system. After the addition was complete, the mixture was reacted at -80 °C for 30 minutes. Then, N-phenylbis(trifluoromethanesulfonyl)imide (16.02 g, 44.84 mmol, dissolved in 50 ml of tetrahydrofuran) was added dropwise to the system. The mixture was allowed to rise naturally to room temperature and reacted for 2 hours. After the reaction was complete, the reaction was quenched with water, extracted with ethyl acetate, and the organic phase was washed with saturated sodium chloride solution. The organic phase was concentrated and subjected to column chromatography to obtain product B-5a (4 g).

[0883] LC-MS(ESI):[M+H-44] + =334.29

[0884] Step 2: 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborocyclo-2-yl)-2-azabicyclo[4.1.0]hept-4-ene-2-carboxylic acid benzyl ester (compound B-5b)

[0885] B-5a (6 g, 15.90 mmol), pinacol diborate (6.05 g, 23.85 mmol), potassium acetate (4.68 g, 47.70 mmol), 1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (1.16 g, 1.59 mmol), and 1,4-dioxane (60 ml) were added to the reaction flask. Under nitrogen protection, the mixture was heated to 80 °C and reacted overnight. After the reaction was complete, the mixture was cooled to room temperature, concentrated, and purified by normal-phase column chromatography to obtain compound B-5b (1.5 g, 26.55%).

[0886] 1 H NMR(600MHz,Chloroform-d)δ7.48–7.31(m,5H),6.98–6.78(m,1H),5.29–5.14(m,2H),4.24–3.99(m,1H),3 .94–3.66(m,1H),3.39–3.15(m,1H),1.59–1.51(m,1H),1.27(s,12H),1.23–1.15(m,1H),0.61–0.48(m,1H).

[0887] LC-MS(ESI):[M+H] + =356.49

[0888] Step 3: (2-((benzyloxy)carbonyl)-2-azabicyclo[4.1.0]hept-4-en-4-yl)boronic acid (compound B-5c-A)

[0889] Add B-5b (7 g, 19.70 mmol), acetone (42 ml), water (24 ml), sodium periodate (12.64 g, 59.11 mmol), and ammonium acetate (4.55 g, 59.11 mmol) to the reaction flask, and stir overnight at room temperature. After the reaction is complete, add water, extract with ethyl acetate, wash the organic phase with saturated sodium chloride solution, concentrate, and purify the crude product by reversed-phase column chromatography to obtain a yellow oily substance B-5c (1.82 g). The oily substance is resolved by SFC to obtain compounds B-5c-A (0.8 g) and B-5c-B (0.7 g).

[0890] B-5c-A / B: 1 H NMR(400MHz,DMSO-d6)δ7.71(s,2H),7.43–7.27(m,5H),6.86-6.75(m,1H),5.198–5.16(m,2H),4.02–3.7 3(m,1H),3.63–3.43(m,1H),3.26–3.15(m,1H),1.60-1.50(m,1H),1.18–1.08(m,1H),0.42–0.33(m,1H).

[0891] LC-MS(ESI):[M-44+H] + =230.36

[0892] Step 4: 4-(2-(dimethylcarbamoyl)-7-fluoro-4-(4-(4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)phenyl)-1H-indol-6-yl)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid benzyl ester (compound B-5d-A)

[0893] The compound (1.4 g, 3.15 mmol), B-5c-A (1.0 g, 3.66 mmol), potassium phosphate (1.68 g, 7.91 mmol), and methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (270 mg, 318.58 μmol) were dissolved in a mixed solvent of 1,4-dioxane and water (30 / 5 mL). Under nitrogen protection, the mixture was stirred in an oil bath at 90 °C for 2 hours. The mixture was extracted twice with dichloromethane, and the organic phase was evaporated to dryness and purified by reversed-phase column chromatography to give the yellow solid product compound B-5d-A (1.20 g, 60%).

[0894] 1H NMR(400MHz,DMSO-d6)δ12.14(s,1H),7.59–7.26(m,7H),7.03(d,J=8.3Hz,2H),6 .95–6.82(m,2H),6.46–6.40(m,1H),5.26–5.08(m,2H),4.57(t,J=5.5Hz,1H),4. 38–4.02(m,2H),3.50–3.38(m,4H),3.31–2.94(m,9H),1.84–1.72(m,1H),1.66–1 .50(m,2H),1.40–1.29(m,2H),1.28–1.17(m,1H),0.92(s,3H),0.62–0.54(m,1H).

[0895] LC-MS(ESI):[M+H] + =637.58

[0896] Step 5: 6-(2-azabicyclo[4.1.0]hept-4-en-4-yl)-7-fluoro-4-(4-(4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound B-5e-A)

[0897] Compound B-5d-A (1.0 g, 1.57 mmol) was dissolved in methanol (5 mL), and hydrochloric acid (0.8 mL, 4.0 M in EA) and palladium / carbon (400 mg, 10%) were added. The mixture was then purged with hydrogen and reacted at room temperature for 1 hour. After filtration and evaporation, the product was a yellow solid, compound B-5e-A (800 mg, 101%).

[0898] LC-MS(ESI):[M+H] + =503.59

[0899] Step 6: 4-(2-(dimethylcarbamoyl)-7-fluoro-4-(4-(4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)phenyl)-1H-indol-6-yl)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid tert-butyl ester (compound B-5f-A)

[0900] Compound B-5e-A (950 mg, 1.89 mmol) was dissolved in dichloromethane (30 mL), and triethylamine (770 mg, 7.60 mmol) and di-tert-butyl dicarbonate (830 mg, 3.80 mmol) were added. The mixture was stirred at room temperature for 1 hour and then evaporated to dryness. After purification by reversed-phase column chromatography, a yellow solid product, compound B-5f-A (820 mg, 72%), was obtained.

[0901] 1H NMR (400MHz, DMSO-d6) δ12.13(s,1H),7.50(d,J=8.5Hz,2H),7.04(d,J=8.8Hz,2H),6.9 0(d,J=6.0Hz,1H),6.88–6.83(m,1H),6.45–6.36(m,1H),4.56(t,J=5.5Hz,1H),4.31–3. 93(m,1H),3.50–3.37(m,4H),3.28–2.97(m,10H),1.72(s,1H),1.65–1.53(m,2H),1.43( d,J=11.9Hz,9H),1.38–1.29(m,2H),1.23–1.09(m,1H),0.93(s,3H),0.58–0.46(m,1H).

[0902] LC-MS(ESI):[M+H] + =603.58

[0903] Step 7: 4-(2-(dimethylcarbamoyl)-7-fluoro-4-(4-(4-formyl-4-methylpiperidin-1-yl)phenyl)-1H-indol-6-yl)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid tert-butyl ester (compound B-5g-A)

[0904] Compound B-5f-A (820 mg, 1.36 mmol) was dissolved in dimethyl sulfoxide (10 mL). 2-Iodobenzoic acid (580 mg, 2.07 mmol) was added, and the mixture was reacted at room temperature for 1 hour, followed by the addition of 380 mg, 1.36 mmol of 2-iodobenzoic acid. The mixture was extracted with ethyl acetate, and the organic phase was washed successively with saturated sodium thiosulfate and brine to give the yellow solid product, compound B-5g-A (750 mg, 91%).

[0905] LC-MS(ESI):[M+H] + =601.68

[0906] Step 8: 4-(2-(dimethylcarbamoyl)-4-(4-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-1H-indol-6-yl)-2-azabicyclo[4.1.0]hept-4-en-2-carboxylic acid tert-butyl ester (compound B-5h-A)

[0907] B-5g-A (750 mg, 1.24 mmol) and A-4a (700 mg, 1.88 mmol) were dissolved in dimethyl sulfoxide (20 mL), and tetraisopropyl titanate (2.13 g, 7.49 mmol) was added. The mixture was stirred in an oil bath at 60 °C for 2 hours, and then sodium cyanoborohydride (225 mg, 3.76 mmol) was added. The mixture was stirred at 60 °C for another hour. The reaction solution was diluted with a mixture of dichloromethane and methanol (10:1), and water was added before filtration. The organic phase obtained from the filtrate was washed with saturated brine, and after rotary evaporation to dryness, it was purified by column chromatography to obtain a yellow solid product B-5h-A (950 mg, 80%).

[0908] LC-MS(ESI):[M+H] + =955.75

[0909] Step 9: 6-(2-azabicyclo[4.1.0]hept-4-en-4-yl)-4-(4-(4-((3-(2,6-dioxopiperidin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (compound B-5i-A)

[0910] Compound B-5h-A (950 mg, 994.61 μmol) was dissolved in dichloromethane (10 mL). Trifluoroacetic acid (3 mL) was added, and the mixture was stirred at room temperature for 30 minutes. After evaporation to dryness, a yellow oily product, compound B-5i-A, was obtained.

[0911] LC-MS(ESI):[M+H] + =855.76.

[0912] Step 10: 4-(4-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofurano[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-6-(2-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-2-azabicyclo[4.1.0]hept-4-en-4-yl)-N,N-dimethyl-1H-indole-2-carboxamide (Compound B-5-A)

[0913] B-5i-A (70 mg, 81.86 μmol), 3-(3-fluoro-1H-pyrazol-1-yl)propionic acid (26 mg, 164.41 μmol), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (70 mg, 184.09 μmol) were dissolved in N,N-dimethylformamide (2 mL), and N,N-diisopropylethylamine (110 mg, 851.08 μmol) was added. The reaction mixture was reacted at room temperature for 30 min. The reaction system was purified by high pressure to obtain a white solid product B-5A (15 mg, 18%).

[0914] 1 H NMR (400MHz, DMSO-d6) δ12.17(s,1H),11.12(s,1H),7.69–7.64(m,1H),7.58–7.51(m,2H),7.11(d,J=8.4Hz,2H),6.91(d,J=6.1Hz,1H) ,6.87–6.82(m,1H),6.78(d,J=8.0Hz,1H),6.71(d,J=8.0Hz,1H),6.44–6.39(m,1H),5.92–5.87(m,1H),5.39–5.30(m,1H),4.72–4.61( m,3H),4.30–4.23(m,2H),3.84–3.75(m,1H),3.63–3.48(m,4H),3.43–3.01(m,16H),2.98–2.86(m,2H),2.74–2.58(m,2H),2.43–2.28( m,2H),2.06–1.95(m,2H),1.94–1.84(m,3H),1.82–1.71(m,2H),1.71–1.56(m,2H),1.39–1.30(m,1H),1.24(s,3H),0.60–0.52(m,1H).

[0915] LC-MS(ESI):[M+H] + =995.55.

[0916] Example 28 Synthesis of compound B-5-B

[0917] 4-(4-(4-((3-(2,6-dioxadiazin-3-yl)-1-methyl-2-oxo-2,3-dihydro-1H,7H-spiro[benzofuran[6,7-d]imidazol-6,4'-piperidin]-1'-yl)methyl)-4-methylpiperidin-1-yl)phenyl)-7-fluoro-6-(2-(3-(3-fluoro-1H-pyrazol-1-yl)propionyl)-2-azabicyclo[4.1.0]hept-4-en-4-yl)-N,N-dimethyl-1H-indole-2-carboxamide (compound B-5-B)

[0918] Synthesis scheme

[0919] The synthesis method is the same as that for B-5-A.

[0920] 1 H NMR (400MHz, DMSO-d6) δ12.18(s,1H),11.12(s,1H),7.69–7.64(m,1H),7.55(d,J=8.2Hz,2H),7.11(d,J=8.2Hz,2H),6.92(d,J=6.0Hz, 1H),6.88–6.83(m,1H),6.79(d,J=8.0Hz,1H),6.72(d,J=8.0Hz,1H),6.45–6.41(m,1H),5.93-5.88(m,1H),5.40–5.31(m,1H),4.72–4.6 3(m,3H),4.31–4.25(m,2H),3.84–3.78(m,1H),3.62–3.56(m,4H),3.35–3.01(m,16H),2.98–2.83(m,1H),2.69–2.59(m,2H),2.40–2.31 (m,2H),2.04–1.96(m,2H),1.94–1.85(m,3H),1.80–1.72(m,2H),1.71–1.60(m,2H),1.37–1.32(m,1H),1.24(s,3H),0.58–0.53(m,1H).

[0921] LC-MS(ESI):[M+H] + =995.55.

[0922] Test Example 1: Test of the degradation of STAT6 protein in MV4-11 cells by the disclosed compounds.

[0923] MV4-11 cells (ATCC, CRL-9591) were cultured in IMDM (Hyclone, SH30228.01) complete medium containing 10% fetal bovine serum (Hyclone, SH30406.05) and sporulated at 4.0 × 10⁻⁶. 5 Cells were seeded in 12-well plates (LabServ, 310109024) with a volume of 1 mL per well. Different concentrations of the prepared test compound solutions were added at 1 μL / well to achieve final concentrations of 0.1 nM and 0.01 nM, with corresponding solvent controls included. Cells were cultured for 18 h. After 18 h of culture, the culture medium was removed by centrifugation, and cells were washed with PBS. RIPA lysis buffer containing 1% Protease Inhibitor Cocktail was added, followed by lysis and centrifugation to obtain the total protein extract. The protein concentration in the extract was determined by the BCA method. Protein electrophoresis was performed using SDS-PAGE, followed by electroporation at 100 V for 60 min to transfer the protein onto a PVDF (Millipore Sigma, PSRP010R5) membrane. The PVDF membrane was then blocked in 5% milk powder 1×TBST solution at room temperature for 1 h. Primary antibody solutions (Anti-STAT6, Cell Signaling Technology, 5397S; Anti-Actin, Cell Signaling Technology, 4970S; 1:1000 dilution) were prepared and incubated overnight at 4°C. The primary antibody solution was recovered, and the PVDF membrane was washed with 1×TBST for 5 min / wash three times. Secondary antibody solutions (Thermo, A32735; 1:20000 dilution) were prepared and incubated at room temperature for 1 h. The secondary antibody solution was discarded, and the PVDF membrane was washed with 1×TBST for 5 min / wash three times. Western spectral imaging of the membrane was performed using a dual-color infrared laser imaging system (Licor, Odyssey CLX). Grayscale analysis of the bands was performed using Image Studio software. Actin protein bands were simultaneously detected for each sample as internal controls. The STAT6 protein degradation rate of the compounds was calculated based on the grayscale values ​​of the protein bands.

[0924] Table 1. Degradation of STAT6 protein in MV4-11 cells by the compounds disclosed herein. Note: In this table, letter A indicates >90%, B indicates 70%-90%, C indicates 50%-69%, D indicates <50%, and "-" indicates not tested.

[0925] The results showed that the exemplary compound of this disclosure has a significant degradation effect on STAT6 protein in MV4-11 cells.

[0926] Experimental Example 2: Test of the degradation of STAT6 protein in A549 cells by the disclosed compounds.

[0927] A549 cells (ATCC, CRL-185) were cultured in F12K (ATCC, 30-2004) complete medium containing 10% fetal bovine serum (Hyclone, SH30406.05) and sporulated at 2.0 × 10⁻⁶. 5 Cells were seeded in 6-well plates (LabServ, 310109023) with a volume of 2 mL per well. After overnight culture in a CO2 incubator, different concentrations of the test compound were added at 1 μL / well to achieve final concentrations of 0.1 nM and 0.01 nM, with corresponding solvent controls included. Cells were cultured for 24 h. After 24 h, the culture medium was removed, cells were washed with PBS, and RIPA lysis buffer containing 1% Protease Inhibitor Cocktail was added. After lysis and centrifugation, total protein extract was obtained, and the protein concentration was determined by the BCA method. Protein electrophoresis was performed using SDS-PAGE, followed by electroporation at 100 V for 60 min to transfer the protein onto a PVDF (Millipore Sigma, PSRP010R5) membrane. The PVDF membrane was then blocked in 5% milk powder 1×TBST solution at room temperature for 1 h. Primary antibody solutions (Anti-STAT6, Cell Signaling Technology, 5397S; Anti-Actin, Cell Signaling Technology, 4970S; 1:1000 dilution) were prepared and incubated overnight at 4°C. The primary antibody solution was recovered, and the PVDF membrane was washed with 1×TBST for 5 min / wash three times. Secondary antibody solutions (Thermo, A32735; 1:20000 dilution) were prepared and incubated at room temperature for 1 h. The secondary antibody solution was discarded, and the PVDF membrane was washed with 1×TBST for 5 min / wash three times. Western spectral imaging of the membrane was performed using a dual-color infrared laser imaging system (Licor, Odyssey CLX). Grayscale analysis of the bands was performed using Image Studio software. Actin protein bands were simultaneously detected for each sample as internal controls. The STAT6 protein degradation rate of the compounds was calculated based on the grayscale values ​​of the protein bands.

[0928] Table 2. Degradation of STAT6 protein in A549 cells by the disclosed compounds. Note: In this table, letter A indicates >90%, B indicates 70%-90%, C indicates 50%-69%, D indicates <50%, and "-" indicates not tested.

[0929] The results showed that the example compound of this disclosure has a significant degradation effect on STAT6 protein in A549 cells.

[0930] Test Example 3: Test of the degradation of STAT6 protein in A549-Hibit-STAT6 cells by the disclosed compounds

[0931] A549 cells stably expressing Stat6-HiBiT were cultured in F12K (ATCC, 30-2004) complete medium containing 10% fetal bovine serum (Hyclone, SH30406.05). Cells were seeded at a density of 2500 cells per well in 384-well plates (Perkin Elmer, 6007680). After overnight culture in a CO2 incubator, cells were treated with DMSO or serially diluted PROTAC compounds for 24 hours. After 24 hours of compound treatment, the medium was aspirated from the wells, and a lysis assay kit containing LgBiT protein and furimazine substrate was added. The cells were incubated at room temperature for 10 minutes, and the luminescence signal was detected using a microplate reader. The intensity of the luminescence signal was proportional to the amount of HiBiT-tagged protein in the cell lysate. Degradation histograms and degradation curve fitting were performed using GraphPad Prism 8.0, and DC was calculated. 50 value.

[0932] Table 3. Degradation of STAT6 protein in A549-Hibit-STAT6 cells by the disclosed compounds. Note: DC in this table 50 Results: A indicates <1 nM, B indicates 1-10 nM, C indicates >10-100 nM (greater than 10 nM, less than or equal to 100 nM), D indicates >100-1000 nM, and "-" indicates not tested. max Results: A indicates >90%, B indicates 70%-90%, C indicates 50%-69%, D indicates <50%, and "-" indicates not tested.

[0933] The results show that the example compound of this disclosure has a significant degradation effect on STAT6 protein in A549-Hibit-STAT6 cells.

[0934] Experiment 4: Test of STAT6 protein degradation in Jurkat-Hibit-STAT6 cells

[0935] Jurakat cells stably expressing Stat6-HiBiT were cultured in RPMI-1640 (ATCC, 30-2001) complete medium containing 10% fetal bovine serum (Hyclone, SH30406.05). Cells were seeded at a density of 10,000 cells per well in 384-well plates (Perkin Elmer, 6007680). Cells were treated with DMSO or serially diluted PROTAC compounds for 18 hours. After 18 hours of compound treatment, the medium was aspirated from the wells, and a lysis assay kit containing LgBiT protein and furimazine substrate was added. The cells were incubated at room temperature for 10 minutes, and the luminescence signal was detected using a microplate reader. The intensity of the luminescence signal was proportional to the amount of HiBiT-tagged protein in the cell lysate. Degradation histograms and degradation curve fitting were performed using GraphPad Prism 8.0, and DC was calculated. 50 value.

[0936] Table 4. Degradation of STAT6 protein in Jurkat-Hibit-STAT6 cells by the disclosed compounds. Note: DC 50 Results: A indicates <1 nM, B indicates 1-10 nM, C indicates >10-100 nM, D indicates >100-1000 nM, and "-" indicates not tested; D max Results: A indicates >90%, B indicates 70%-90%, C indicates 50%-69%, D indicates <50%, and "-" indicates not tested.

[0937] The results show that the example compounds of this disclosure have a significant degradation effect on STAT6 protein in Jurkat-Hibit-STAT6 cells.

[0938] Experimental Example 5: Binding affinity of the disclosed compound to the STAT6 protein

[0939] The experiment was conducted in black 384-well low-volume plates. The reaction system consisted of 20 μL of a 10 nM fluorescent tracer, 20 nM STAT6, and different concentrations of the analyte (maximum final concentration 1 μL, serially diluted 3-fold, for a total of 11 concentration points). The reaction buffer consisted of 25 mM HEPES pH 7.5, 150 mM NaCl, and 0.05% Triton X-100. After incubation at room temperature for 2 hours, the parallel and vertical fluorescence values ​​at 485 / 530 nm were read using a Tecan Spark microplate reader, and the polarization values ​​(mP) were calculated. The inhibition rate at each compound concentration was calculated based on the polarization values. The dose-response curve fitted to the inhibition rate was analyzed using Graphpad Prism software, and the IC50 was obtained through nonlinear regression analysis. 50 value.

[0940] The results show that the compound disclosed herein has a high affinity for the STAT6 protein.

[0941] Experimental Example 6: Testing the efficacy model of MC-903-induced atopic dermatitis (AD)

[0942] Experimental animals: SPF-grade 8-week-old female hIL4 / IL4RA humanized mice (Biocytok Pharmaceutical Technology Co., Ltd.).

[0943] Preparation of modeling reagent: Prepare a 20mM stock solution of MC903 powder with anhydrous ethanol, aliquot as needed, and store at -20℃ for later use. When using, dilute with anhydrous ethanol to a final concentration of 100μM for modeling solution, and prepare fresh before use.

[0944] Preparation of test sample: Weigh an appropriate amount of test sample powder according to the animal's body weight, dissolve and mix with DMSO until clear, dispense into individual containers, and store at -20℃. Before daily administration, add PEG200 and 30% SBE-β-CD solution in the specified ratio (administration solvent: 5% DMSO + 20% PEG200 + 75% (30% SBE-β-CD solution)). The Vehicle group was administered pure solvent (-MC903 was the control group without modeling, and +MC903 was the control group with MC903-induced model).

[0945] Inflammation induction: After one week of acclimatization, mice with similar body weight and ear thickness were divided into groups of six. Inflammation model was induced by applying 20 μL of MC903 solution (2 nmol / mouse) to the left ear of each mouse on Day 1-Day 5 and Day 8-Day 14. Mouse body weight and left ear thickness were measured three times weekly.

[0946] Dosage: Mice were administered the test compound daily by gavage starting the day before modeling, at doses of 10 mg / kg, 30 mg / kg, and 60 mg / kg, with a volume of 10 mL / kg, for 15 consecutive days, once daily. Dupilumab was used as a positive control, administered subcutaneously in the neck at a dose of 25 mg / kg, with a volume of 5 mL / kg, twice weekly.

[0947] Sample collection: 100 μL of blood was collected from the orbital sinus at 1, 2, 4, 6, and 24 hours after the last administration and placed in EDTA-K2 anticoagulant tubes. The plasma was collected after centrifugation at 4000 rpm for 10 min to test the last PK (pharmacokinetic) result. Serum was collected at the experimental endpoint to test IgE levels. Mice were euthanized after blood collection, and the spleen was harvested, flash-frozen in liquid nitrogen, and stored at -80°C to test STAT6 protein content.

[0948] Data analysis: The change in left ear thickness in mice 14 days after drug administration relative to ear thickness on day 1 after administration was calculated. The final pharmacokinetic (PK) assay was performed using LC / MS / MS. Serum IgE concentration was measured using enzyme-linked immunosorbent assay (ELISA). STAT6 protein levels in mouse spleens were detected using Western blotting.

[0949] Serum IgE ELISA assay: The Icosai EM024-96 kit was used for detection. Serum samples were added to pre-coated antibody-impregnated ELISA plates and incubated for 2 hours. After washing the plates 5 times, biotinylated antibody and enzyme conjugate working solution were added and incubated for 1 hour. After washing the plates 5 times, TMB substrate was added and incubated in the dark for 15 minutes. Then, stop solution was added, and the OD450 value was measured using a Spark M1000pro microplate reader. A standard curve was fitted using GraphPad Prism 8.0, and the sample concentration was quantified.

[0950] STAT6 degradation detection in spleen tissue: 50 mg of spleen was weighed and placed in a grinding tube containing magnetic beads. 500 μL of lysis buffer was added to each tube, and the grinder was set to -20℃, 70 Hz, and ground for 120 s. Then, the mixture was centrifuged at 4℃, 20,000 rpm for 20 min, the precipitate was discarded, and the supernatant was collected. This process was repeated twice. Quantification and sample preparation were then performed using the BCA method, followed by heat denaturation at 95℃ for 5 min in a metal bath. Protein samples were electrophoresed on a 12% precast gel. After the protein bands separated, the proteins were transferred to a 0.45 μm PVDF membrane using a transfer device. The membrane was blocked with 5% skim milk powder for 1 h, and primary antibodies were added: anti-STAT61:1000 (CST cat#:5397s) and anti-ACTIN1:1000 (CST cat#:4970s, Beyotime cat#:AF5003). The membrane was incubated overnight at 4℃. On the second day, the gel was washed three times with TBST, then incubated with the fluorescent secondary antibody Goat anti-Rabbit 1:30000 (Thermo cat#: A32735) at room temperature for 1 hour, and washed three more times with TBST. Finally, the gel was exposed using a gel imaging system (LI-COR, Odyssey CLx System). The bands were analyzed using ImageStudio, and the data were processed using GraphPad Prism 8.0.

[0951] Conclusion: As shown in Figure 1, the exemplary compounds E-2 of this disclosure reduced STAT6 in mouse spleen by 52% and 74% at doses of 10 and 30 mg / kg, respectively, while G-1 reduced STAT6 in mouse spleen by 59% and 89% at doses of 10 and 30 mg / kg, respectively. As shown in Figure 2, the inhibition of IgE by the exemplary compounds of this disclosure is dose-dependent. This indicates that the exemplary compounds of this disclosure can efficiently degrade STAT6 in vivo.

[0952] Experiment Example 7: Testing of an OVA-induced asthma efficacy model

[0953] 7-8 week old hIL4 / hIL4RA mice (Biocytok Pharmaceutical Technology Co., Ltd., 120551) were randomly grouped according to body weight after the quarantine period. After grouping, mice in the model group were sensitized by intraperitoneal injection (ip) of 100 μL of a 1:1 mixture of ovalbumin (OVA, MCE, HY-W250978) and aluminum hydroxide adjuvant on Day 0, Day 7, and Day 14. The ovalbumin injection dose was 40 μg / mouse. From Day 21 to 25, mice were challenged daily by nebulization with 2% OVA saline solution for 30 min. During the experiment, mouse body weight was measured once a week. Drug administration began on Day 15, with STAT6 degradation agent administered by gavage. The drug solution was 5% DMSO + 20% PEG200 + 75% (30% SEB-β-CD in saline), at a volume of 10 mL / kg, once daily for a total of 12 times. Dupilumab (in-house, Batch No. P3BJ24002) was diluted with physiological saline and administered subcutaneously in the neck at a volume of 10 mL / kg, twice a week for a total of three times. The vehicle group received pure solvent (+OVA served as the OVA-induced model control group). At the experimental endpoint (Day 26), whole blood was collected from the orbital sinus at 1, 2, 4, 6, 8, and 24 hours after administration. 50 μL of blood was collected from each mouse and placed in an EDTA anticoagulant tube. The tubes were centrifuged at 4000 rpm for 10 min, and the plasma was used to determine the concentration. The plasma was stored at -20°C. Six hours after the last administration, 200 μL of blood was collected from the orbital sinus of each mouse and placed in a non-anticoagulant EP tube. After standing at room temperature for 30 min, the tubes were centrifuged at 4000 rpm for 15 min, and the serum was stored at -80°C. Serum IgE was measured using an ELISA kit (ExCell, EM024-96). After blood collection, the spleen and lung tissue of mice were flash-frozen in liquid nitrogen for Western blotting to determine STAT6 protein content. Twenty-four hours after the last administration, mice were euthanized by dislocation after blood collection. The thoracic cavity was opened to expose the trachea and lungs. The left lung was ligated with sutures, and a gavage needle was inserted into the tracheal opening and ligated with sutures. The lavage fluid was lavaged with HBSS buffer, approximately 0.3 mL each time, 2-3 times per lavage. 1 mL of lavage fluid was collected from each mouse. The collected lavage fluid was centrifuged, and the precipitate was analyzed for immune cells by flow cytometry on the same day. The supernatant was stored at -80°C to test the concentrations of TARC, periosteal protein, and IL-13 in the bronchoalveolar lavage fluid. After collecting BALF from the mice, the ligated, un-lavaged left lung was fixed in 10% formalin and sectioned in paraffin. HE & PAS staining was used to observe inflammatory cell infiltration and changes in lung structural remodeling (goblet cell metaplasia) in the mouse lungs.

[0954] Serum IgE ELISA assay: The Icosai EM024-96 kit was used for detection. Serum samples were added to pre-coated antibody-impregnated ELISA plates and incubated for 2 hours. After washing the plates 5 times, biotinylated antibody and enzyme conjugate working solution were added and incubated for 1 hour. After washing the plates 5 times, TMB substrate was added and incubated in the dark for 15 minutes. Then, stop solution was added, and the OD450 value was measured using a Spark M1000pro microplate reader. A standard curve was fitted using GraphPad Prism 8.0, and the sample concentration was quantified.

[0955] STAT6 degradation detection in tissues: Tissues were placed in grinding tubes containing magnetic beads, and 500 μL of lysis buffer was added to each tube. The grinder was set to -20℃, 70 Hz, and ground for 120 s. Then, the tissues were centrifuged at 4℃, 20,000 rpm for 20 min, the precipitate was discarded, and the supernatant was collected. This process was repeated twice. Quantification and sample preparation were then performed using the BCA method, followed by heat denaturation at 95℃ for 5 min in a metal bath. Protein samples were electrophoresed on a 12% precast gel. After the protein bands separated, the proteins were transferred to a 0.45 μm PVDF membrane using a transfer apparatus. The membrane was blocked with 5% skim milk powder for 1 h, and primary antibodies were added: anti-STAT6 1:1000 (CST, Cat.#5397s) and anti-ACTIN 1:1000 (CST, Cat.#4970s, Beyotime, Cat.#AF5003). The membrane was incubated overnight at 4℃. On the second day, the gel was washed three times with TBST, then incubated with the fluorescent secondary antibody Goat anti-Rabbit 1:30000 (Thermo, Cat.#A32735) at room temperature for 1 hour, and washed three more times with TBST. Finally, the gel was exposed using a gel imaging system (LI-COR, Odyssey CLx System). The bands were analyzed using ImageStudio, and the data were processed using GraphPad Prism 8.0.

[0956] Conclusions: As shown in Figure 3, compound E-2, at doses of 10 mg / kg and 30 mg / kg, reduced STAT6 in mouse spleen by 50% and 74%, respectively, and in lung by 93% and 95%, respectively. Compound G-1, at doses of 10 mg / kg and 30 mg / kg, reduced STAT6 in mouse spleen by 82% and 93%, respectively, and in lung by -16% and 57%, respectively. As shown in Figure 4, the compounds of this disclosure dose-dependently inhibited IgE. As shown in Figures 5 and 6, compounds E-2 and G-1 significantly inhibited inflammatory cell infiltration in BALF, showing superior effects compared to dupilumab. These results indicate that the exemplary compounds of this disclosure can efficiently degrade STAT6 in vivo and effectively alleviate lung inflammation, with effects superior to dupilumab.

[0957] Experimental Example 8: Testing of a PPE-induced COPD model

[0958] Male hIL4-hIL4RA mice aged 7–9 weeks (purchased from Shanghai Jihui Experimental Animal Breeding Co., Ltd.) were randomly divided into groups of 10 mice each according to their body weight. On Day 1 (after grouping), Day 7, Day 14, and Day 21, mice in the model group were anesthetized with 1–4% isoflurane and injected intratracheally with 50 μL of physiological saline solution containing 50 U / kg PPE, according to their body weight. Mice in the blank control group were injected with the same volume of sterile physiological saline. From Day 1 to Day 27, mice were administered the drug by gavage once daily. The drug solution was 5% DMSO / 20% PEG200 / 75% physiological saline (containing 30% SBE-β-CD), and the administration volume was 10 mL / kg. Dupilumab was administered subcutaneously twice a week for a total of 8 times. At the experimental endpoint (Day 27), blood was collected from the orbital venous plexus of mice at 1, 2, 4, 6, 8, and 24 hours after drug administration, and plasma was centrifuged to test drug concentration. Twenty-four hours after the last administration, endotracheal intubation was performed under anesthesia with salbutamol (25-50 mg / kg) and methaqualone (5-10 mg / kg) to measure pulmonary function parameters, including total lung capacity (TLC), forced vital capacity (FVC), functional residual capacity (FRC), and the ratios of forced expiratory volume to forced vital capacity at 20, 50, and 100 ms (FEV20 / FVC, FEV50 / FVC, and FEV100 / FVC). Following pulmonary function testing, serum samples were collected, and IgE concentrations were measured using an ELISA kit. Subsequently, bronchoalveolar lavage fluid was collected and analyzed by flow cytometry for inflammatory cells (CD45+). + Cells, CD4 + T cells, CD8 + The number of T cells, B cells, eosinophils, neutrophils, and macrophages was measured. The left lung was collected and fixed after bronchoalveolar lavage for H&E staining and PAS staining.

[0959] The results showed that the compound disclosed herein had better or comparable effects than dupilumab in inhibiting biomarkers and improving lung function in mice in a COPD pharmacodynamic model.

[0960] Exemplary implementation schemes

[0961] 1. A compound having the structure shown in formula (I0), PTM-L-ULM formula (I0);

[0962] Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein:

[0963] The PTM is a binding site targeting signal transduction and transcription activator 6 (STAT6), and its structure is shown in equation (1-10):

[0964] Ring A is selected from 7-10-membered subbicyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, 11-15-membered subtricyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 16-20-membered subtetracyclic groups containing 1-5 heteroatoms independently selected from N, O, and S. The 7-10-membered subbicyclic groups, 11-15-membered subtricyclic groups, and 16-20-membered subtetracyclic groups are saturated or unsaturated fused-ring or spirocyclic structures, optionally divided by p1 R... A Replaced;

[0965] Ring B is absent or selected from 5-10 bridging cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S; 5-10 mono-heterocyclic alkyl groups containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S; 5-10 mono-heteroaryl groups containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S; C 5-10 arylene, 7-11 fused-ring cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S, 5-10 spirocyclic cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S, and 5-11 fused-ring cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S, wherein the 5-10 bridging cycloalkanes, 5-10 monoheterocyclic cycloalkanes, 5-10 arylene, 5-10 monoheteroarylene, 7-11 fused-ring cycloalkanes, 5-10 spirocyclic cycloalkanes, and 5-11 fused-ring cycloalkanes are optionally surrounded by p2 R B Replaced;

[0966] Ring C does not exist or is selected from C. 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups containing 1-5 heteroatoms independently selected from N, O, and S, 5-10 membered heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, and unsaturated 7-11 membered difused cycloalkyl groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the C 3-10 Cycloalkyl, 3-10-membered heterocycloalkyl, 5-10-membered heteroaryl and 7-11-membered bifused cycloalkyl, optionally surrounded by p3 R C Replaced;

[0967] L a Selected from single bond, C 1-6 Alkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O);

[0968] When ring C exists, L b Selected from single bond, C 1-6 Alkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); when ring C does not exist, L b Independently selected from single bonds, C 1-6 Alkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X and one or more of C(O) with C 1-6 Combinations of alkyl groups;

[0969] R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, deuterated C 1-8 Alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, deuterated C 1-8 Alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 aryl and 5-8 heteroaryl groups, optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6cycloalkyl, 3-6 membered heterocyclic, C 5-6 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups;

[0970] R D It does not exist or is selected independently each time it appears from halogen, cyano, nitro, -R X -OR X -SR X -N(R) X )2、-Si(R X 3、-S(O)R X -S(O)2R X -S(O)(NR) X )R X -S(O)2N(R) X )2、-C(O)R X -C(O)OR X -C(O)N(R) X )2、-C(O)N(R X OR X -OC(O)R X -OC(O)N(R) X )2、-P(O)(R X )2、-P(O)(OR X )2、-OP(O)(R X )2、-OP(O)(OR X )2、-NR X C(O)OR X -NR X C(O)R X -NR X C(O)N(R X )2、-NR X S(O)2R X C 1-8 Alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy group, -C(O)C1-6 Alkyl, Halogenated C 1-6 Alkyl and Halogenated C 1-6 One or more substituents of the alkoxy group are used for substitution;

[0971] R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl and Halogenated C 1-6 One or more substituents of the alkoxy group are used for substitution;

[0972] p1, p2, and p3 are each independently selected from 1, 2, 3, 4, and 5;

[0973] The L is the bond or chemical linker connecting the ULM and PTM, and its structure is a covalent bond or -(B) bond. L ) q -;

[0974] B L Each time it appears, it is selected independently from CR. L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1C(O), -C≡C-, 3-15-membered cycloalkylene, 3-15-membered heterocyclic group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15-membered bridged cycloalkyl group containing 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15-membered spirocyclic group containing 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 6-15-membered aryl group and 5-15-membered heteroaryl group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, wherein the 3-15-membered cycloalkylene, 3-15-membered heterocyclic group, 5-15-membered bridged cycloalkyl group, 5-15-membered spirocyclic group, 6-15-membered aryl group and 5-15-membered heteroaryl group are optionally surrounded by 1-6 R L1 and / or R L2 Group substitution;

[0975] R L1 and R L2 Each occurrence is independently selected from H, halogens, -OH, -NH2, -SH, -C(O)2H, -CN, -CF3, -CHF2, -CH2F, -NO2, -S(O)2, -SF5, -C≡CH, C 1-8 Alkyl, -OC 1-8 Alkyl, -SC 1-8 Alkyl, -NH-C 1-8 Alkyl, N(C) 1-8 Alkyl)2, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, -OC 3-8 Cycloalkyl, -O-3-8 membered heterocyclic groups, -OC 6-10 Aryl, -O-5-10 heteroaryl, -SC 3-8 cycloalkyl, -NH-C 3-8 cycloalkyl, -N(C) 3-8 cycloalkyl)2, -N(C 3-8 cycloalkyl)(C 1-8 Alkyl), -NH-3-8-membered heterocyclic group, -N(3-8-membered heterocyclic group)2, -N(3-8-membered heterocyclic group) (C 1-8 alkyl), -NH-C 6-10 Aryl, -N(C 6-10 Aryl)(C 1-8 alkyl), -NH-C 5-10 heteroaryl, -N (5-10 quinone heteroaryl) (C 1-8 Alkyl), S(O)2P(O)(OC 1-8 Alkyl)(C 1-8 Alkyl), -P(O)(OC 1-8 Alkyl)2、-C≡CC1-8 Alkyl group, -CH=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl)=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl) = C(C 1-8 Alkyl group 2, -Si(OH)3, -Si(C) 1-8 Alkyl)3、-Si(OH)(C 1-8 Alkyl)2、-C(O)-C 1-8 Alkyl group, -S(O)2NH-C 1-8 Alkyl group, -S(O)2N(C) 1-8 Alkyl)2、-S(O)NH-C 1-8 Alkyl, -S(O)N(C) 1-8 Alkyl)2、-C(O)NH-C 1-8 Alkyl, -C(O)N(C) 1-8 Alkyl)2, -N(C 1-8 alkyl)C(O)NH(C 1-8 alkyl), -N(C) 1-8 alkyl)C(O)N(C 1-8 alkyl)2、-NHC(O)NH(C 1-8 Alkyl), -NHC(O)N(C 1-8 Alkyl)2, -NHC(O)NH2, -N(C 1-8 alkyl)S(O)2NH(C 1-8 alkyl), -N(C) 1-8 alkyl)S(O)2N(C 1-8 alkyl)2、-NHS(O)2NH(C 1-8 Alkyl), -NHS(O)2N(C 1-8 alkyl)2 and -NHS(O)2NH2, the C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, halogenated C 3-8 Cycloalkyl, halogenated 3-8 heteroalkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, halogenated C 6-10The aryl group is substituted by one or more substituents in the aryl and halogenated 5-10 heteroaryl groups;

[0976] q is selected from integers greater than or equal to 1 and less than or equal to 15;

[0977] The ULM is the human cerebellar protein (CRBN) E3 ubiquitin ligase binding site, and its structure is shown in formulas (2-1), (2-2), (2-3), (2-4), (2-5), (2-6), and (2-7):

[0978] Among them, W1 is independently selected from CR each time it appears. c1 and N;

[0979] R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 NR c1 C(O), C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, halogenated C 1-6 Alkylene and C 1-6 A combination of one or more heteroalkyl groups;

[0980] W2 and W3 are each independently selected from O, C(O), N, NR each time they appear. c1 CR c1 and CR c1 R c2 , Indicates a single or double bond; when When W2 and W3 are single bonds, they are each independently selected from O, C(O), and CR each time they appear. c1 R c2 and NR c1 ,when When it is a double bond, W2 and W3 are each independently selected from N and CR each time they appear. c1 ;

[0981] W4, W5, and W6 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is selected from C(O);

[0982] R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups;

[0983] (i-1)R 1a and R 1b The carbon atoms bonded to it together form a ring Cy1, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0984] (i-2)R 1b and R 1c The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0985] (i-3)R 1c and R 1d The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the range; and

[0986] (i-4)R 1d and R 1e The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0987] R 2a R 2b R 2c R 2d and R 2e The definition is selected from one of the following groups;

[0988] (ii-1)R 2a and R 2b The carbon atoms bonded to it together form a ring Cy2, and R 2c R 2d and R 2e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0989] (ii-2)R 2b and R 2c The carbon atoms bonded to it together form a ring Cy2, and R 2a R 2d and R 2eEach occurrence is independently selected from R. S1 Substituents within the range; and

[0990] (ii-3)R 2c and R 2d The carbon atoms bonded to it together form a ring Cy2, and R 2a R 2b and R 2e Each occurrence is independently selected from R. S1 Substituents within the specified range;

[0991] Cy1 and Cy2 are each independently selected from

[0992] D1, D2, D3, D4, D5, and D6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at D1 and D2 This represents the connection site with a carbon atom on the benzene ring;

[0993] U4 and U5 are each selected independently from CR each time they appear. c1 and N;

[0994] R T Each time it appears, it is selected independently from CR. c1 and N;

[0995] R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 5-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 4-12 membered heterocyclic groups, C 5-12The aryl group and the 5-12 heteroaryl group are each independently and optionally selected from one or more groups chosen from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, Halogenated C 1-10 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Heteroalkyl, C 1-10 Alkoxy, halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 5-12 Substituents of aryl and 5-12 heteroaryl groups;

[0996] R c1 and R c2 Each time it appears, it is independently selected from H, deuterium, halogen, oxo group (=O), hydroxyl group, nitro group, cyano group, amino group, and C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 4-12 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 5-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 5-12 The aryl group and the 5-12 heteroaryl group are each independently selected from halogen, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, hydroxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 4-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 5-12The aryl group is substituted with one or more substituents of a 5-12 heteroaryl group; and

[0997] Each time n1, n2, n3, n4, n5, and n6 appear, they are each independently selected from 0, 1, 2, 3, 4, and 5;

[0998] In the above formulas, Indicates the connection site.

[0999] 2. The compound as described in embodiment 1, wherein,

[1000] Ring A is selected from 9-10-membered subbicyclic groups containing 1-4 independently selected N, O, and S heteroatoms, 12-15-membered subtricyclic groups containing 1-4 independently selected N, O, and S heteroatoms, and 16-18-membered subtetracyclic groups containing 1-4 independently selected N, O, and S heteroatoms. The 9-10-membered subbicyclic, 12-15-membered subtricyclic, and 16-18-membered subtetracyclic groups are saturated, partially saturated, or unsaturated fused-ring or spirocyclic structures, optionally divided by p1 R... A Replaced; and / or

[1001] Ring B is absent or selected from 5-8 fused subbridged rings containing 1-4 saturated or unsaturated heteroatoms selected independently of N, O, and S; 5-8 fused submonocyclic rings containing 1-4 saturated or unsaturated heteroatoms selected independently of N, O, and S; and 7-10 fused subcyclic rings containing 1-4 saturated or unsaturated heteroatoms selected independently of N, O, and S. The 5-8 fused subbridged rings, 5-8 fused submonocyclic rings, and 7-10 fused subcyclic rings are optionally separated by p2 R groups. B Replaced; and / or

[1002] Ring C does not exist or is selected from C. 3-8 Cycloalkyl groups, 3-8 membered heterocycloalkyl groups containing 1-4 heteroatoms independently selected from N, O, and S, 5-8 membered heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S, and unsaturated 8-10 membered difused cycloalkyl groups containing 1-4 heteroatoms independently selected from N, O, and S, wherein the C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-8 membered heteroaryl and 8-10 membered difused cycloalkyl, optionally surrounded by p3 R C Replaced; and / or

[1003] p1, p2, and p3 are each independently selected from 1, 2, 3, and 4; and / or

[1004] L a Independently selected from single bonds, C 1-3 Alkylene, C 1-3 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); and / or

[1005] When ring C exists, L b Independently selected from single bonds, C 1-3 Alkylene, C 1-3 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); when ring C does not exist, L b Independently selected from single bonds, C 1-3 Alkylene, C 1-3 Heteroalkyl, O, S, S(O), S(O)2, NR X and one or more of C(O) with C 1-3 Combinations of alkyl groups; and / or

[1006] R A R B and R C Each time it appears, it is independently selected from H, deuterium, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 a...

Claims

1. A compound having the structure shown in formula (I): PTM-L-ULM formula (I); Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: The structure of the PTM is shown in equation (1-1): Ring A is selected from 8-10 membered bicyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; and 16-20 membered tetracyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; wherein the tricyclic heterocyclic aryl group and the tetracyclic heterocyclic aryl group are fused rings, spirocycles, or spirofused ring structures. Ring B is selected from single bonds, 6-10 member monocyclic aryl groups, 8-10 member bicyclic aryl groups, 5-10 member monocyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, 8-10 member bicyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5-10 member monocyclic alkyl groups, saturated or partially unsaturated 5-13 member bicyclic alkyl groups, saturated or partially unsaturated 5-10 member monocyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 5-13 member bicyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the bicyclic alkyl groups and bicyclic heterocyclic groups are bridged rings, spiro rings, or fused ring structures; The ring C is absent or selected from 3-10 membered cycloalkyl groups, 3-10 membered monocyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 6-13 membered bicyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 5-10 membered monocyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, and 8-10 membered bicyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, wherein the bicyclic heterocyclic group is a fused ring, spiro ring or bridged ring structure; When ring C exists, L c Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X A combination of one or more of C(O), wherein C 3-6 The cycloalkyl group is optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-6 One or more substituents in the alkyl group are substituted; When ring C does not exist, L c Selected from C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, -SC 1-6 Alkyl, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -NR X -C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -NR X -C(O)-N(R X )2 and -C(O)-NR X -C 1-6 Alkyl, the C 1-6 Alkyl, C 1-6 Heteroalkyl and C 1-6 Alkyl groups are optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-6 One or more substituents in the alkyl group are substituted; p1, p2, and p3 are each independently selected from 0, 1, 2, 3, 4, and 5; L b Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, -C(O)-C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 heteroaryl groups are optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups; R D selected from R X , -OR X , -SR X , -N(R X )₂, -S(O)R X , -S(O)₂R X , -S(O)N(R X )₂, -S(O)₂N(R X )₂, -C(O)R X , -C(O)OR X , -C(O)N(R X )₂, -C(O)N(R X )OR X , -OC(O)R X , -OC(O)N(R X )₂, -NR X C(O)OR X , -NR X C(O)R X , -NR X C(O)N(R X )₂ and -NR X S(O)₂R X ; R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups are optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 One or more substituents of the haloalkoxy group are substituted; When ring B is a saturated or partially unsaturated 5- or 6-membered heterocyclic group, phenylene group, or 5- or 6-membered heteroaryl group containing 1 or 2 independently selected N, O, and S heteroatoms, and ring A is selected from a 9-membered bicyclic heteroaryl group containing 1 to 4 independently selected N, O, and S heteroatoms, the 9-membered bicyclic heteroaryl group is selected from... When ring B is L b It is a single bond, and the ring C is At that time, ring A is not When ring B is And L b When it is -C(O)-NH-CH2-, ring A is not a bicyclic or tricyclic heteroaryl group or a bicyclic or tricyclic heterocyclic group; The L is the chemical connection portion that connects the PTM and the ULM; The structure of the ULM is shown in the following formula: Among them, W1 is independently selected from CR each time it appears. c1 and N; R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 1-6 Halogenated alkylene and C 1-6 A combination of one or more heteroalkyl groups; R q Each occurrence is independently selected from single bonds and NR. c1 ;R q place Indicates the connection site with L; W2, W3, and W4 are each independently selected from C, C(O), O, N, and NR, respectively. c1 CR c1 and CR c1 R c2 The area between W2, W3 and W4 Indicates a single bond or a double bond; In Equations 2-2 and 2-8, when there is a double bond between W2 and W3, and a single bond between W3 and W4, W2 is C, and W3 is selected from N and C. c1 W4 is selected from O and CR c1 R c2 and NR c1 When W2 and W3 form a single bond, and W3 and W4 form a double bond, W2, W3, and W4 are each independently selected from N and CR. c1 When all bonds between W2, W3, and W4 are single bonds, W2 is selected from N and CR. c1 W3 and W4 are each independently selected from C(O) and NR. c1 O and CR c1 R c2 ; W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is C(O); W 12 and W 13 Each is independently selected from N and CR c1 ; R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups; (i-1)R 1a and R 1b Together they form Cy0, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-2)R 1b and R 1c Together they form Cy0, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-3)R 1c and R 1d Together they form Cy0, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-4)R 1d and R 1e Together they form Cy0, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the range; and (i-5)R 1a and R W Together they form Cy0, and R 1b R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; R 2a R 2b R 2c and R 2d The definition is selected from one of the following groups; (ii-1)R 2a and R 2b Together they form Cy1, and R 2c and R 2d Each occurrence is independently selected from R. S1 Substituents within the specified range; (ii-2)R 2b and R 2c Together they form Cy1, and R 2a and R 2d Each occurrence is independently selected from R. S1 Substituents within the range; and (ii-3)R 2c and R 2d Together they form Cy1, and R 2a and R 2b Each occurrence is independently selected from R. S1 Substituents within the specified range; R 3a R 3b and R 3c The definition is selected from one of the following groups; (iii-1)R 3a and R 3b Together they form Cy2, and R 3c Each time it appears, it is selected independently from R. S1 Substituents within the range; and (iii-2)R 3b and R 3c Together they form Cy2, and R 3a Each time it appears, it is selected independently from R. S1 Substituents within the specified range; Cy0, Cy1, and Cy2 are each selected independently each time they appear. A1, A2, A3, A4, A5, and A6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at A1 and A2 Indicates the connection sites between it and atoms on the connected ring; B1, B2, and R T Each time it appears, it is selected independently from CR. c1 and N;R T place Indicates the connection site with L; Each time m1, m3, and m5 appear, they are independently selected from 1, 2, 3, 4, 5, and 6; Each time m2, m4, and m6 appear, they are each independently selected from 0, 1, 2, 3, 4, 5, and 6; R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl and 5-10 heteroaryl groups are each independently and optionally selected from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, C 1-10 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Heteroalkyl, C 1-10 Alkoxy, C 1-10 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents of a 5-10 member heteroaryl group; Each time n appears, it is independently selected from 0, 1, 2, 3, 4, and 5; R c1 and R c2 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl and 5-10 heteroaryl groups are each independently and optionally selected from halogen, cyano, amino, nitro, hydroxyl, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 3-8 cycloalkyl, 3-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 6-8 The aryl group is substituted with one or more substituents of the 5-8 membered heteroaryl group; and In the above formulas, The substituent indicates the connection site. Substituents without explicitly marked substitution positions indicate that they can be substituted at any chemically permissible position on the entire ring.

2. A compound having the structure shown in formula (I0): PTM-L-ULM formula (I0); Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: The PTM is a binding site targeting signal transduction and transcription activator 6 (STAT6), and its structure is shown in equation (1-10): Ring A is selected from 7-10-membered subbicyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, 11-15-membered subtricyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 16-20-membered subtetracyclic groups containing 1-5 heteroatoms independently selected from N, O, and S. The 7-10-membered subbicyclic groups, 11-15-membered subtricyclic groups, and 16-20-membered subtetracyclic groups are saturated or unsaturated fused-ring or spirocyclic structures, optionally divided by p1 R... A Replaced; Ring B is absent or selected from 5-10 bridging cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S; 5-10 mono-heterocyclic alkyl groups containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S; 5-10 mono-heteroaryl groups containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S; C 5-10 arylene, 7-11 fused-ring cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S, 5-10 spirocyclic cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S, and 5-11 fused-ring cycloalkanes containing 1-5 saturated or unsaturated heteroatoms independently selected from N, O, and S, wherein the 5-10 bridging cycloalkanes, 5-10 monoheterocyclic cycloalkanes, 5-10 arylene, 5-10 monoheteroarylene, 7-11 fused-ring cycloalkanes, 5-10 spirocyclic cycloalkanes, and 5-11 fused-ring cycloalkanes are optionally surrounded by p2 R B Replaced; Ring C does not exist or is selected from C. 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups containing 1-5 heteroatoms independently selected from N, O, and S, 5-10 membered heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, and unsaturated 7-11 membered difused cycloalkyl groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the C 3-10 Cycloalkyl, 3-10-membered heterocycloalkyl, 5-10-membered heteroaryl and 7-11-membered bifused cycloalkyl, optionally surrounded by p3 R C Replaced; L a Selected from single bond, C 1-6 Alkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); When ring C exists, L b Selected from single bond, C 1-6 Alkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); when ring C does not exist, L b Independently selected from single bonds, C 1-6 Alkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X and one or more of C(O) with C 1-6 Combinations of alkyl groups; R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, deuterated C 1-8 Alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, deuterated C 1-8 Alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 aryl and 5-8 heteroaryl groups, optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups; R D It does not exist or is selected independently each time it appears from halogen, cyano, nitro, -R X -OR X -SR X -N(R) X )2、-Si(R X 3、-S(O)R X -S(O)2R X -S(O)(NR) X )R X -S(O)2N(R) X )2、-C(O)R X -C(O)OR X -C(O)N(R) X )2、-C(O)N(R X OR X -OC(O)R X -OC(O)N(R) X )2、-P(O)(R X )2、-P(O)(OR X )2、-OP(O)(R X )2、-OP(O)(OR X )2、-NR X C(O)OR X -NR X C(O)R X -NR X C(O)N(R X )2、-NR X S(O)2R X C 1- 8-alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy group, -C(O)C 1-6 Alkyl, Halogenated C 1-6 Alkyl and Halogenated C 1-6 One or more substituents of the alkoxy group are used for substitution; R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl and Halogenated C 1-6 One or more substituents of the alkoxy group are used for substitution; p1, p2, and p3 are each independently selected from 1, 2, 3, 4, and 5; The L is the bond or chemical linker connecting the ULM and PTM, and its structure is a covalent bond or -(B) bond. L ) q -; B L Each time it appears, it is selected independently from CR. L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 C(O), -C≡C-, 3-15-membered cycloalkylene, 3-15-membered heterocyclic group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15-membered bridged cycloalkyl group containing 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15-membered spirocyclic group containing 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 6-15-membered aryl group and 5-15-membered heteroaryl group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, wherein the 3-15-membered cycloalkylene, 3-15-membered heterocyclic group, 5-15-membered bridged cycloalkyl group, 5-15-membered spirocyclic group, 6-15-membered aryl group and 5-15-membered heteroaryl group are optionally surrounded by 1-6 R L1 and / or R L2 Group substitution; R L1 and R L2 Each occurrence is independently selected from H, halogens, -OH, -NH2, -SH, -C(O)2H, -CN, -CF3, -CHF2, -CH2F, -NO2, -S(O)2, -SF5, -C≡CH, C 1-8 Alkyl, -OC 1-8 Alkyl, -SC 1-8 Alkyl, -NH-C 1-8 Alkyl, N(C) 1-8 Alkyl)2, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, -OC 3-8 Cycloalkyl, -O-3-8 membered heterocyclic groups, -OC 6-10 Aryl, -O-5-10 heteroaryl, -SC 3-8 cycloalkyl, -NH-C 3-8 cycloalkyl, -N(C) 3-8 cycloalkyl)2, -N(C 3-8 cycloalkyl)(C 1-8 Alkyl), -NH-3-8-membered heterocyclic group, -N(3-8-membered heterocyclic group)2, -N(3-8-membered heterocyclic group) (C 1- 8-alkyl), -NH-C 6-10 Aryl, -N(C 6-10 Aryl)(C 1-8 alkyl), -NH-C 5-10 heteroaryl, -N (5-10 quinone heteroaryl) (C 1-8 Alkyl), S(O)2P(O)(OC 1-8 Alkyl)(C 1-8 Alkyl), -P(O)(OC 1-8 Alkyl)2、-C≡CC 1-8 Alkyl group, -CH=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl)=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl) = C(C 1-8 Alkyl group 2, -Si(OH)3, -Si(C) 1-8 Alkyl)3、-Si(OH)(C 1-8 Alkyl)2、-C(O)-C 1-8 Alkyl group, -S(O)2NH-C 1-8 Alkyl group, -S(O)2N(C) 1-8 Alkyl)2、-S(O)NH-C 1-8 Alkyl, -S(O)N(C) 1-8 Alkyl)2、-C(O)NH-C 1-8 Alkyl, -C(O)N(C) 1-8 Alkyl)2, -N(C 1-8 alkyl)C(O)NH(C 1-8 alkyl), -N(C) 1- 8alkyl)C(O)N(C 1-8 alkyl)2、-NHC(O)NH(C 1-8 Alkyl), -NHC(O)N(C 1-8 Alkyl)2, -NHC(O)NH2, -N(C 1-8 alkyl)S(O)2NH(C 1-8 alkyl), -N(C) 1-8 alkyl)S(O)2N(C 1-8 alkyl)2、-NHS(O)2NH(C 1-8 Alkyl), -NHS(O)2N(C 1-8 alkyl)2 and -NHS(O)2NH2, the C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, halogenated C 3-8 Cycloalkyl, halogenated 3-8 heteroalkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, halogenated C 6-10 The aryl group is substituted by one or more substituents in the aryl and halogenated 5-10 heteroaryl groups; q is selected from integers greater than or equal to 1 and less than or equal to 15; The ULM is the human cerebellar protein (CRBN) E3 ubiquitin ligase binding site, and its structure is shown in formulas (2-1), (2-2), (2-3), (2-4), (2-5), (2-6), and (2-7): Among them, W1 is independently selected from CR each time it appears. c1 and N; R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 NR c1 C(O), C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, halogenated C 1-6 Alkylene and C 1-6 A combination of one or more heteroalkyl groups; W2 and W3 are each independently selected from O, C(O), N, NR each time they appear. c1 CR c1 and CR c1 R c2 , Indicates a single or double bond; when When W2 and W3 are single bonds, they are each independently selected from O, C(O), and CR each time they appear. c1 R c2 and NR c1 ,when When it is a double bond, W2 and W3 are each independently selected from N and CR each time they appear. c1 ; W4, W5, and W6 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is selected from C(O); R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups; (i-1)R 1a and R 1b The carbon atoms bonded to it together form a ring Cy1, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-2)R 1b and R 1c The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-3)R 1c and R 1d The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the range; and (i-4)R 1d and R 1e The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the specified range; R 2a R 2b R 2c R 2d and R 2e The definition is selected from one of the following groups; (ii-1)R 2a and R 2b The carbon atoms bonded to it together form a ring Cy2, and R 2c R 2d and R 2e Each occurrence is independently selected from R. S1 Substituents within the specified range; (ii-2)R 2b and R 2c The carbon atoms bonded to it together form a ring Cy2, and R 2a R 2d and R 2e Each occurrence is independently selected from R. S1 Substituents within the range; and (ii-3)R 2c and R 2d The carbon atoms bonded to it together form a ring Cy2, and R 2a R 2b and R 2e Each occurrence is independently selected from R. S1 Substituents within the specified range; Cy1 and Cy2 are each independently selected from D1, D2, D3, D4, D5, and D6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at D1 and D2 This represents the connection site with a carbon atom on the benzene ring; U4 and U5 are each selected independently from CR each time they appear. c1 and N; R T Each time it appears, it is selected independently from CR. c1 and N; R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 5-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 4-12 membered heterocyclic groups, C 5-12 The aryl group and the 5-12 heteroaryl group are each independently and optionally selected from one or more groups chosen from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, Halogenated C 1-10 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Heteroalkyl, C 1-10 Alkoxy, halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 5-12 Substituents of aryl and 5-12 heteroaryl groups; R c1 and R c2 Each time it appears, it is independently selected from H, deuterium, halogen, oxo group (=O), hydroxyl group, nitro group, cyano group, amino group, and C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 4-12 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 5-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 5-12 The aryl group and the 5-12 heteroaryl group are each independently selected from halogen, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, hydroxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 4-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 5-12 The aryl group is substituted with one or more substituents of a 5-12 membered heteroaryl group; n1, n2, n3, n4, n5, and n6 are each independently selected from 0, 1, 2, 3, 4, and 5 each time they appear; and In the above formulas, Indicates the connection site; Preferably: Ring A is selected from 7-10-membered subbicyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, 11-15-membered subtricyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 16-20-membered subtetracyclic groups containing 1-5 heteroatoms independently selected from N, O, and S. The 7-10-membered subbicyclic groups, 11-15-membered subtricyclic groups, and 16-20-membered subtetracyclic groups are saturated or unsaturated fused-ring or spirocyclic structures, optionally divided by p1 R... A Replaced; Ring B is absent or selected from 5-10 fused sub-bridged rings containing 0-5 independently selected N, O, and S heteroatoms (saturated or unsaturated), 6-12 fused sub-spirocyclic rings containing 1-5 independently selected N, O, and S heteroatoms (saturated or unsaturated), 5-10 fused sub-monocyclic rings containing 0-5 independently selected N, O, and S heteroatoms (saturated, partially saturated, or unsaturated), and 7-11 fused sub-bicyclic rings containing 1-5 independently selected N, O, and S heteroatoms (saturated or unsaturated). The 5-10 fused sub-bridged rings, 5-10 fused sub-monocyclic rings, and 7-11 fused sub-bicyclic rings are optionally separated by p2 R atoms. B Replaced; and Ring C does not exist or is selected from C. 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups containing 1-3 heteroatoms independently selected from N, O, and S, 5-10 membered heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, and unsaturated 7-11 membered difused cycloalkyl groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the C 3-10 Cycloalkyl, 3-10-membered heterocycloalkyl, 5-10-membered heteroaryl and 7-11-membered bifused cycloalkyl, optionally surrounded by p3 R C Replaced; Preferably: Ring A is selected from 8-10 membered bicyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; and 16-20 membered tetracyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S. The tricyclic and tetracyclic heterocyclic aryl groups are fused rings, spirocyclic rings, or fused ring structures. The 8-10 membered bicyclic heterocyclic aryl groups, 11-15 membered tricyclic heterocyclic aryl groups, 11-15 membered tricyclic heterocyclic aryl groups, and 16-20 membered tetracyclic heterocyclic aryl groups are optionally divided by p1 R. A Replaced; Ring B is absent or selected from 5-10 member monocyclic or bicyclic aryl groups, 5-10 member monocyclic or bicyclic heterocyclic aryl groups containing 1-5 independently selected N, O, and S heteroatoms, saturated or partially unsaturated 5-13 member monocyclic or bicyclic heterocyclic hydrocarbon groups, and 5-13 member monocyclic or bicyclic heterocyclic groups containing 1-5 independently selected N, O, and S heteroatoms, wherein the bicyclic hydrocarbon groups and bicyclic heterocyclic groups are bridged rings, spirocyclic rings, or fused ring structures, and the 5-10 member aryl group, 5-10 member heterocyclic aryl group, 5-13 member monocyclic or bicyclic heterocyclic hydrocarbon group, and 5-13 member monocyclic or bicyclic heterocyclic group are optionally separated by p2 R groups. B Replaced; The ring C is absent or selected from 3-10 membered cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, 5-10 membered monocyclic or bicyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, and 6-13 membered bicyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated, wherein the bicyclic heterocyclic group has a fused ring structure, and the 3-10 membered cycloalkyl group, 3-10 membered heterocyclic group, 5-10 membered monocyclic or bicyclic heteroaryl group, and 6-13 membered bicyclic heterocyclic group are optionally surrounded by p3 R groups. C Replaced; L a Selected from single bond, C 1-6 Alkylene, C 3-6 Cycloalkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); When ring C exists, L b Selected from single bond, C 1-6 Alkylene, C 3-6 Cycloalkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); when ring C does not exist, L b Selected from single bond, C 1-6 Alkylene, C 3-6 Cycloalkylene, C 1-6 Heteroalkyl, O, S, S(O), S(O)2, NR X and one or more of C(O) with C 1-6 Combinations of alkyl groups; When ring A is In this case, ring B is selected from 9-10-membered bicyclic aryl groups, 9-10-membered bicyclic heterocyclic aryl groups containing 1-5 independently selected N, O, and S heteroatoms (saturated or partially unsaturated), 9-10-membered saturated or unsaturated monocyclic heterocyclic hydrocarbon groups, 9-10-membered monocyclic heterocyclic aryl groups containing 1-5 independently selected N, O, and S heteroatoms, 5-13-membered monocyclic or bicyclic heterocyclic hydrocarbon groups (saturated or partially unsaturated), and 5-13-membered monocyclic or bicyclic heterocyclic aryl groups containing 1-5 independently selected N, O, and S heteroatoms. The 9-10-membered bicyclic aryl groups, 9-10-membered bicyclic heterocyclic aryl groups, 9-10-membered monocyclic heterocyclic aryl groups, 5-13-membered monocyclic or bicyclic heterocyclic hydrocarbon groups, and 5-13-membered monocyclic or bicyclic heterocyclic aryl groups are optionally surrounded by p2 R groups. B Replaced; When ring A is selected from an unsaturated 9-membered bicyclic heteroaryl group containing 1-4 independently selected N, O, and S heteroatoms, and ring B is selected from a 5-8-membered monocyclic aryl group, a 5-8-membered monocyclic heteroaryl group containing 1-4 independently selected N, O, and S heteroatoms, and a 5-8-membered monocyclic heterocyclic hydrocarbon group containing 1-3 independently selected N, O, and S heteroatoms, and is saturated or partially unsaturated, isolating from N, O, and S heteroatoms, ring A is... When ring B is L a It is a single bond, and the ring C is At that time, ring A is not and In the above formulas, Indicates the connection site; R is not explicitly marked as the substitution site. A R B R C and R D This means that it can be replaced at any position on the entire ring.

3. A compound having the structure shown in formula (Ι3): PTM-L-ULM formula (Ι3); Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: The PTM is a binding site targeting signal transduction and transcription activator 6 (STAT6), and its structure is shown in equation (1-13): Ring A is selected from 8-10 membered bicyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; and 16-20 membered tetracyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S. The tricyclic and tetracyclic heterocyclic aryl groups are fused rings, spirocyclic rings, fused-coiled spirocyclic rings, or spirofused-fused ring structures. The 8-10 membered bicyclic heterocyclic aryl groups, 11-15 membered tricyclic heterocyclic aryl groups, 11-15 membered tricyclic heterocyclic aryl groups, and 16-20 membered tetracyclic heterocyclic aryl groups are optionally divided by a p1 R group. A Replaced; Ring B is absent or selected from 6-10 member monocyclic or 8-10 member bicyclic aryl groups, 5-10 member monocyclic or 8-10 member bicyclic heterocyclic aryl groups containing 1-5 independently selected N, O, and S heteroatoms, saturated or partially unsaturated 5-10 member monocyclic or 5-13 member bicyclic heterocyclic hydrocarbon groups, and 5-10 member monocyclic or 5-13 member bicyclic heterocyclic groups containing 1-5 independently selected N, O, and S heteroatoms, wherein the bicyclic hydrocarbon groups and bicyclic heterocyclic groups are bridged rings, spirocyclic rings, or fused ring structures, and the 6-10 member monocyclic or 8-10 member bicyclic aryl groups, 5-10 member monocyclic or 8-10 member bicyclic heterocyclic aryl groups, 5-10 member monocyclic or 5-13 member bicyclic hydrocarbon groups, and 5-10 member monocyclic or 5-13 member bicyclic heterocyclic groups are optionally separated by p2 R groups. B Replaced; The ring C is absent or selected from 3-10 membered cycloalkyl groups, 3-10 membered monocyclic or 6-13 membered bicyclic heterocyclic groups containing 1-5 independently selected N, O, and S heteroatoms (saturated or partially unsaturated), and 5-10 membered monocyclic or 8-10 membered bicyclic heteroaryl groups containing 1-5 independently selected N, O, and S heteroatoms, wherein the bicyclic heterocyclic group is a fused ring structure, and the 3-10 membered cycloalkyl group, 3-10 membered monocyclic or 6-13 membered bicyclic heterocyclic group, and 5-10 membered monocyclic or 8-10 membered bicyclic heteroaryl group are optionally surrounded by p3 R groups. C Replaced; p1, p2, and p3 are each independently selected from 0, 1, 2, 3, 4, and 5; L b Selected from single bond, C 1-6 Alkylene, C 3-6 Cycloalkylene, C 2-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); When ring C exists, L c Selected from single bond, C 1-6 Alkylene, C 3-6 Cycloalkylene, C 2-6 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); when ring C does not exist, L c Selected from C 1-6 Alkyl, C 3-6 cycloalkyl, C 2-6 Heteroalkyl, C 1-6 Alkoxy, SC 1-6 Alkyl, S(O)-C 1-6 Alkyl, S(O)2-C 1-6 Alkyl, NR X -C 1-6 Alkyl, C(O)-C 1-6 Alkyl and C(O)-NR X C 1-6 Alkyl, the C 1-6 Alkyl, C 3-6 cycloalkyl, C 2-6 Heteroalkyl, C 1- 6-alkoxy, SC 1-6 Alkyl, S(O)-C 1-6 Alkyl, S(O)2-C 1-6 Alkyl, NR X -C 1-6 Alkyl, C(O)-C 1-6 Alkyl and C(O)-NR X C 1-6 Alkyl groups, optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C2 groups. 1-6 One or more substituents in the alkyl group are substituted; R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, deuterated C 1-8 Alkyl, C 2-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, deuterated C 1-8 Alkyl, C 2-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 aryl and 5-8 heteroaryl groups, optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups; R D It is absent or selected from halogen, cyano, nitro, -R X -OR X -SR X -N(R) X )2、-Si(R X 3、-S(O)R X -S(O)2R X -S(O)(NR) X )R X -S(O)2N(R) X )2、-C(O)R X -C(O)OR X -C(O)N(R) X )2、-C(O)N(R X OR X -OC(O)R X -OC(O)N(R) X )2、-P(O)(R X )2、-P(O)(OR X )2、-OP(O)(R X )2、-OP(O)(OR X )2、-NR X C(O)OR X -NR X C(O)R X -NR X C(O)N(R X )2、-NR X S(O)2R X C 1-8 Alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy group, -C(O)C 1-6 Alkyl, Halogenated C 1-6 Alkyl and Halogenated C 1-6 One or more substituents of the alkoxy group are used for substitution; R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, halogenated C 1-8 Alkyl, Halogenated C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl and Halogenated C 1-6 One or more substituents of the alkoxy group are used for substitution; When ring B is selected from a 5- or 6-membered saturated or partially unsaturated heterocyclic hydrocarbon group containing one or two independently selected N, O, and S heteroatoms, a benzene ring, and a 5- or 6-membered heteroaryl group containing one or two independently selected N, O, and S heteroatoms, and ring A is selected from a 9-membered bicyclic heteroaryl group containing one to four independently selected N, O, and S heteroatoms, the 9-membered bicyclic heteroaryl group is selected from... When ring B is L a It is a single bond, and the ring C is At that time, ring A is not The structure of L is the same as that defined in claim 2; The ULM is the human cerebellar protein (CRBN) E3 ubiquitin ligase binding site, and its structure is shown in formulas (2-1), (2-2), (2-3), (2-4), (2-5), (2-6), (2-7), (2-8), (2-9), and (2-10): Among them, W1 is independently selected from CR each time it appears. c1 and N; R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 NR c1 C(O), C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, halogenated C 1-6 Alkylene and C 2-6 A combination of one or more heteroalkyl groups; W2 and W3 are each independently selected from O, C(O), N, NR each time they appear. c1 CR c1 and CR c1 R c2 , Indicates a single or double bond; when When W2 and W3 are single bonds, they are each independently selected from O, C(O), and CR each time they appear. c1 R c2 and NR c1 ,when When it is a double bond, W2 and W3 are each independently selected from N and CR each time they appear. c1 ; W4, W5, and W6 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is selected from C(O); R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups; (i-1)R 1a and R 1b The carbon atoms bonded to it together form a ring Cy1, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-2)R 1b and R 1c The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-3)R 1c and R 1d The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-4)R 1d and R 1e The carbon atoms bonded to it together form a ring Cy1, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the range; and (i-5)R 1a and R W The carbon atoms bonded to it together form a ring Cy1, and R 1b R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; R 2a R 2b R 2c R 2d and R 2e The definition is selected from one of the following groups; (ii-1)R 2a and R 2b The carbon atoms bonded to it together form a ring Cy2, and R 2c R 2d and R 2e Each occurrence is independently selected from R. S1 Substituents within the specified range; (ii-2)R 2b and R 2c The carbon atoms bonded to it together form a ring Cy2, and R 2a R 2d and R 2e Each occurrence is independently selected from R. S1 Substituents within the range; and (ii-3)R 2c and R 2d The carbon atoms bonded to it together form a ring Cy2, and R 2a R 2b and R 2e Each occurrence is independently selected from R. S1 Substituents within the specified range; Cy1 and Cy2 are each independently selected from D1, D2, D3, D4, D5, and D6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at D1 and D2 The carbon atom bonding site on the benzene ring, thiophene ring, or pyrazole ring to which it is attached; U4 and U5 are each selected independently from CR each time they appear. c1 and N; R T Each time it appears, it is selected independently from CR. c1 and N; R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 2-10 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 2-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group and the 5-12 heteroaryl group are each independently and optionally selected from one or more groups chosen from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, Halogenated C 1-10 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 2-10 Heteroalkyl, C 1-10 Alkoxy, halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Substituents of aryl and 5-12 heteroaryl groups; R c1 and R c2 Each time it appears, it is independently selected from H, deuterium, halogen, oxo group (=O), hydroxyl group, nitro group, cyano group, amino group, and C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 2-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 6-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 2-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group and the 5-12 heteroaryl group are each independently selected from halogen, cyano, amino, nitro, C 1-6 Alkyl, C 2-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, hydroxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 4-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 6-12 The aryl group is substituted with one or more substituents of a 5-12 membered heteroaryl group; n1, n2, n3, n4, n5, and n6 are each independently selected from 0, 1, 2, 3, 4, and 5 each time they appear; and In the above formulas, Indicates the connection site; R is not explicitly marked as the substitution site. A R B R C and R D This means that it can be replaced at any position on the entire ring.

4. A compound having the structure shown in formula (Ι4): PTM-L-ULM formula (Ι4); Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: The structure of the PTM is the same as that defined in claim 3; The L is the chemical linker connecting the ULM and PTM, and the chemical linker is a covalent bond or -(B) bond. L ) q -; B L Each time it appears, it is selected independently from CR. L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 C(O), -C≡C-, 3-15-membered monocyclic cyclohexane, 3-15-membered monocyclic heterocyclic group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15-membered bridged cyclohexane group containing 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15-membered spirocyclic group containing 0, 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 6-15-membered aryl group and 5-15-membered heteroaryl group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, wherein the 3-15-membered monocyclic cyclohexane, 3-15-membered monocyclic heterocyclic group, 5-15-membered bridged cyclohexane group, 5-15-membered spirocyclic group, 6-15-membered aryl group and 5-15-membered heteroaryl group are optionally surrounded by 1-6 R L1 and / or R L2 Group substitution; R L1 and R L2 Each occurrence is independently selected from H, halogens, -OH, -NH2, -SH, -C(O)2H, -CN, -CF3, -CHF2, -CH2F, -NO2, -S(O)2H, -SF5, -C≡CH, C 1-8 Alkyl, -OC 1-8 Alkyl, -SC 1-8 Alkyl, -NH-C 1-8 Alkyl, N(C) 1-8 Alkyl)2, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, -OC 3-8 Cycloalkyl, -O-3-8 membered heterocyclic groups, -OC 6-10 Aryl, -O-5-10 heteroaryl, -SC 3-8 cycloalkyl, -NH-C 3-8 cycloalkyl, -N(C) 3-8 cycloalkyl)2, -N(C 3-8 cycloalkyl)(C 1-8 Alkyl), -NH-3-8-membered heterocyclic group, -N(3-8-membered heterocyclic group)2, -N(3-8-membered heterocyclic group) (C 1- 8-alkyl), -NH-C 6-10 Aryl, -N(C 6-10 Aryl)(C 1-8 alkyl), -NH-C 5-10 heteroaryl, -N (5-10 quinone heteroaryl) (C 1-8 Alkyl), S(O)2P(O)(OC 1-8 Alkyl)(C 1-8 Alkyl), -P(O)(OC 1-8 Alkyl)2、-C≡CC 1-8 Alkyl group, -CH=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl)=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl) = C(C 1-8 Alkyl group 2, -Si(OH)3, -Si(C) 1-8 Alkyl)3、-Si(OH)(C 1-8 Alkyl)2、-C(O)-C 1-8 Alkyl group, -S(O)2NH-C 1-8 Alkyl group, -S(O)2N(C) 1-8 Alkyl)2、-S(O)NH-C 1-8 Alkyl, -S(O)N(C) 1-8 Alkyl)2、-C(O)NH-C 1-8 Alkyl, -C(O)N(C) 1-8 Alkyl)2, -N(C 1-8 alkyl)C(O)NH(C 1-8 alkyl), -N(C) 1- 8alkyl)C(O)N(C 1-8 alkyl)2、-NHC(O)NH(C 1-8 Alkyl), -NHC(O)N(C 1-8 Alkyl)2, -NHC(O)NH2, -N(C 1-8 alkyl)S(O)2NH(C 1-8 alkyl), -N(C) 1-8 alkyl)S(O)2N(C 1-8 alkyl)2、-NHS(O)2NH(C 1-8 Alkyl), -NHS(O)2N(C 1-8 alkyl)2 and -NHS(O)2NH2, the C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 2-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, halogenated C 3-8 Cycloalkyl, halogenated 3-8 heteroalkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, halogenated C 6-10 The aryl group is substituted by one or more substituents in the aryl and halogenated 5-10 heteroaryl groups; q is selected from integers greater than or equal to 1 and less than or equal to 15; The ULM is the human cerebellar protein (CRBN) E3 ubiquitin ligase binding site; preferably, its structure is shown in the following formula: Among them, W1 is independently selected from CR each time it appears. c1 and N; R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 NR c1 C(O), C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, halogenated C 1-6 Alkylene and C 2-6 A combination of one or more heteroalkyl groups; Rq is selected independently from single bonds and NR each time it appears. c1 ; W2, W3, and W4 are each independently selected from C, C(O), O, N, and NR, respectively. c1 CR c1 and CR c1 R c2 The area between W2, W3 and W4 Indicates a single bond or a double bond; In Equation 2-2, when there is a double bond between W2 and W3 and a single bond between W3 and W4, W2 is selected from C, and W3 is selected from N and C. c1 W4 is selected from O and CR c1 R c2 and NR c1 When W2 and W3 form a single bond, and W3 and W4 form a double bond, W2, W3, and W4 are each independently selected from N and CR. c1 When all bonds between W2, W3, and W4 are single bonds, W2 is selected from N and CR. c1 W3 and W4 are each independently selected from C(O) and NR. c1 O and CR c1 R c2 ; W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is selected from C(O); R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups; (i-1)R 1a and R 1b The carbon atoms bonded to it together form a ring Cy0, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-2)R 1b and R 1c The carbon atoms bonded to it together form a ring Cy0, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-3)R 1c and R 1d The carbon atoms bonded to it together form a ring Cy0, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the range; and (i-4)R 1d and R 1e The carbon atoms bonded to it together form a ring Cy0, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-5)R 1a and R W The carbon or nitrogen atom bonded to it forms a ring Cy0, and R 1b R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; R 2a R 2b R 2c and R 2d The definition is selected from one of the following groups; (ii-1)R 2a and R 2b The carbon atoms bonded to it together form a ring Cy1, and R 2c and R 2d Each occurrence is independently selected from R. S1 Substituents within the specified range; (ii-2)R 2b and R 2c The carbon atoms bonded to it together form a ring Cy1, and R 2a and R 2d Each occurrence is independently selected from R. S1 Substituents within the range; and (ii-3)R 2c and R 2d The carbon atoms bonded to it together form a ring Cy1, and R 2a and R 2b Each occurrence is independently selected from R. S1 Substituents within the specified range; R 3a R 3b and R 3c The definition is selected from one of the following groups; (iii-1)R 3a and R 3b The carbon atoms bonded to it together form a ring Cy2, and R 3c Each time it appears, it is selected independently from R. S1 Substituents within the range; and (iii-2)R 3b and R 3c The carbon atoms bonded to it together form a ring Cy2, and R 3a Each time it appears, it is selected independently from R. S1 Substituents within the specified range; Cy0, Cy1, and Cy2 are each independently selected from... A1, A2, A3, A4, A5, and A6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at A1 and A2 The carbon atom bonding site on the benzene ring, thiophene ring, or pyrazole ring to which it is attached; B1, B2 and R T Each time it appears, it is selected independently from CR. c1 and N; R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 2-10 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 2-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, halogenated C 1-10 Alkyl, Halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group and the 5-12 heteroaryl group are each independently and optionally selected from one or more groups chosen from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, Halogenated C 1-10 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 2-10 Heteroalkyl, C 1-10 Alkoxy, halogenated C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Substituents of aryl and 5-12 heteroaryl groups; Each time n appears, it is independently selected from 0, 1, 2, 3, 4, and 5; R c1 and R c2 Each time it appears, it is independently selected from H, deuterium, halogen, oxo group (=O), hydroxyl group, nitro group, cyano group, amino group, and C. 1-10 Alkyl, deuterated C 1-10 Alkyl, C 2-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 6-12 Aryl and 5-12 heteroaryl, the C 1-10 Alkyl, deuterated C 1-10 Alkyl, C 2-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-11 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 The aryl group and the 5-12 heteroaryl group are each independently selected from halogen, cyano, amino, nitro, C 1-6 Alkyl, C 2-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, hydroxyl, halogenated C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 4-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 6-12 The aryl group is substituted with one or more substituents of a 5-12 membered heteroaryl group; Each time m1, m3, and m5 appear, they are independently selected from 1, 2, 3, 4, 5, and 6; Each time m2, m4, and m6 appear, they are independently selected from 0, 1, 2, 3, 4, 5, and 6; and In the above formulas, Substituents that do not explicitly indicate the location of substitution can be substituted at any position on the ring.

5. A compound having the structure shown in formula (Ι5): PTM-L-ULM formula (Ι5); Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: The structure of the PTM is shown in equation (1-15): Ring A is selected from 8-10 membered bicyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; and 16-20 membered tetracyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; wherein the tricyclic heterocyclic aryl group and the tetracyclic heterocyclic aryl group are fused rings, spirocycles, or spirofused ring structures. Ring B is selected from single bonds, 6-10 member monocyclic aryl groups, 8-10 member bicyclic aryl groups, 5-10 member monocyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, 8-10 member bicyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5-10 member monocyclic alkyl groups, saturated or partially unsaturated 5-13 member bicyclic alkyl groups, saturated or partially unsaturated 5-10 member monocyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 5-13 member bicyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the bicyclic alkyl groups and bicyclic heterocyclic groups are bridged rings, spiro rings, or fused ring structures; The ring C is absent or selected from 3-10 membered cycloalkyl groups, 3-10 membered monocyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 6-13 membered bicyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 5-10 membered monocyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, and 8-10 membered bicyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, wherein the bicyclic heterocyclic group is a fused ring, spiro ring or bridged ring structure; When ring C exists, L c Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X A combination of one or more of C(O), wherein C 3-6 The cycloalkyl group is optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-6 One or more substituents in the alkyl group are substituted; When ring C does not exist, L c Selected from C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, -SC 1-6 Alkyl, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -NR X -C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -NR X -C(O)-N(R X )2 and -C(O)-NR X -C 1-6 Alkyl, the C 1-6 Alkyl, C 1-6 Heteroalkyl and C 1-6 Alkyl groups, optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C atoms. 1-6 One or more substituents in the alkyl group are substituted; p1, p2, and p3 are each independently selected from 0, 1, 2, 3, 4, and 5; L b Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, -C(O)-C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 aryl and 5-8 heteroaryl groups, optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups; R D Absent or selected from R X , -OR X , -SR X , -N(R X )₂, -S(O)R X , -S(O)₂R X , -S(O)N(R X )₂, -S(O)₂N(R X )₂, -C(O)R X , -C(O)OR X , -C(O)N(R X )₂, -C(O)N(R X )OR X , -OC(O)R X , -OC(O)N(R X )₂, -NR X C(O)OR X , -NR X C(O)R X , -NR X C(O)N(R X )₂ and -NR X S(O)₂R X ; R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 One or more substituents of the haloalkoxy group are substituted; When ring B is a saturated or partially unsaturated 5- or 6-membered heterocyclic group, phenylene group, or 5- or 6-membered heteroaryl group containing 1 or 2 independently selected N, O, and S heteroatoms, and ring A is selected from a 9-membered bicyclic heteroaryl group containing 1 to 4 independently selected N, O, and S heteroatoms, the 9-membered bicyclic heteroaryl group is selected from... When ring B is L b It is a single bond, and the ring C is At that time, ring A is not When ring B is And L b When the form is -C(O)-NH-CH2-, ring A is not a bicyclic or tricyclic heteroaryl or heterocyclic group; and The structures of L and ULM are the same as those defined in claim 4.

6. A compound having the structure shown in formula (I6): PTM-L-ULM formula (Ι6); Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: The structure of the PTM is shown in equation (1-16): Ring A is selected from 8-10 membered bicyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; and 16-20 membered tetracyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; wherein the tricyclic heterocyclic aryl group and the tetracyclic heterocyclic aryl group are fused rings, spirocycles, or spirofused ring structures. Ring B is selected from single bonds, 6-10 member monocyclic aryl groups, 8-10 member bicyclic aryl groups, 5-10 member monocyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, 8-10 member bicyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5-10 member monocyclic alkyl groups, saturated or partially unsaturated 5-13 member bicyclic alkyl groups, saturated or partially unsaturated 5-10 member monocyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 5-13 member bicyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the bicyclic alkyl groups and bicyclic heterocyclic groups are bridged rings, spiro rings, or fused ring structures; The ring C is absent or selected from 3-10 membered cycloalkyl groups, 3-10 membered monocyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 6-13 membered bicyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 5-10 membered monocyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, and 8-10 membered bicyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, wherein the bicyclic heterocyclic group is a fused ring, spiro ring or bridged ring structure; When ring C exists, L c Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X A combination of one or more of C(O), wherein C 3-6 The cycloalkyl group is optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-6 One or more substituents in the alkyl group are substituted; When ring C does not exist, L c Selected from C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, -SC 1-6 Alkyl, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -NR X -C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -NR X -C(O)-N(R X )2 and -C(O)-NR X -C 1-6 Alkyl, the C 1-6 Alkyl, C 1-6 Heteroalkyl and C 1-6 Alkyl groups, optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C atoms. 1-6 One or more substituents in the alkyl group are substituted; p1, p2, and p3 are each independently selected from 0, 1, 2, 3, 4, and 5; L b Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, -C(O)-C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 aryl and 5-8 heteroaryl groups, optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups; R D is absent or selected from R X , -OR X , -SR X , -N(R X )₂, -S(O)R X , -S(O)₂R X , -S(O)N(R X )₂, -S(O)₂N(R X )₂, -C(O)R X , -C(O)OR X , -C(O)N(R X )₂, -C(O)N(R X )OR X , -OC(O)R X , -OC(O)N(R X )₂, -NR X C(O)OR X , -NR X C(O)R X , -NR X C(O)N(R X )₂ and -NR X S(O)₂R X ; R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 One or more substituents of the haloalkoxy group are substituted; When ring B is a saturated or partially unsaturated 5- or 6-membered heterocyclic group, phenylene group, or 5- or 6-membered heteroaryl group containing 1 or 2 independently selected N, O, and S heteroatoms, and ring A is selected from a 9-membered bicyclic heteroaryl group containing 1 to 4 independently selected N, O, and S heteroatoms, the 9-membered bicyclic heteroaryl group is selected from... When ring B is L b It is a single bond, and the ring C is At that time, ring A is not When ring B is And L b When it is -C(O)-NH-CH2-, ring A is not a bicyclic or tricyclic heteroaryl or heterocyclic group; The L is the chemical linker connecting the PTM and the ULM; preferably, the L is -(B L ) q -; B L Each occurrence is independently selected from covalent bonds, CR L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 C(O), 3-15 member monocyclic cycloalkylene groups, 3-15 member monocyclic heterocyclic groups containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15 member bridged cycloalkylene groups, 5-15 member spirocyclic groups, 5-15 member spirocyclic groups containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 6-15 member aryl groups and 5-15 member heteroaryl groups containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, wherein the cycloalkylene group, heterocyclic group, bridged cycloalkyl group, bridged cycloalkyl group, spirocyclic group, spirocyclic group, aryl group and heteroaryl group are optionally surrounded by 1-6 R L1 and / or R L2 Group substitution; R L1 and R L2 Each occurrence is independently selected from H, halogens, -OH, -NH2, -SH, -C(O)2H, -CN, -NO2, -S(O)2H, -SF5, -C≡CH, C 1-8 Alkyl, C 1-8 Alkoxy, -SC 1-8 Alkyl, -NH-C 1-8 Alkyl, N(C) 1-8 Alkyl)2, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, -OC 3-8 Cycloalkyl, -O-3-8 membered heterocyclic groups, -OC 6-10 Aryl, -O-5-10 heteroaryl, -SC 3-8 cycloalkyl, -NH-C 3-8 cycloalkyl, -N(C) 3-8 cycloalkyl)2, -N(C 3-8 cycloalkyl)(C 1-8 Alkyl), -NH-3-8-membered heterocyclic group, -N(3-8-membered heterocyclic group)2, -N(3-8-membered heterocyclic group) (C 1-8 alkyl), -NH-C 6-10 Aryl, -N(C 6-10 Aryl)(C 1-8 alkyl), -NH-C 5-10 heteroaryl, -N (5-10 quinone heteroaryl) (C 1-8 Alkyl), -S(O)2P(O)(C 1-8 Alkoxy)(C 1-8 Alkyl), -P(O)(C 1- 8-alkoxy)2、-C≡CC 1-8 Alkyl group, -CH=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl)=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl) = C(C 1-8 Alkyl group 2, -Si(OH)3, -Si(C) 1-8 Alkyl)3、-Si(OH)(C 1-8 Alkyl)2、-C(O)-C 1-8 Alkyl group, -S(O)2NH-C 1-8 Alkyl group, -S(O)2N(C) 1-8 Alkyl)2、-S(O)NH-C 1-8 Alkyl, -S(O)N(C) 1- 8-alkyl)2、-C(O)NH-C 1-8 Alkyl, -C(O)N(C) 1-8 Alkyl)2, -N(C 1-8 alkyl)C(O)NH(C 1-8 alkyl), -N(C) 1-8 alkyl)C(O)N(C 1-8 alkyl)2、-NHC(O)NH(C 1-8 Alkyl), -NHC(O)N(C 1-8 Alkyl)2, -NHC(O)NH2, -N(C 1-8 alkyl)S(O)2NH(C 1-8 alkyl), -N(C) 1-8 alkyl)S(O)2N(C 1- 8-alkyl)2、-NHS(O)2NH(C 1-8 Alkyl), -NHS(O)2N(C 1-8 alkyl)2 and -NHS(O)2NH2, the C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-8 cycloalkyl, C 3-8 Halogenated cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered halocyclic heterocyclic group, C 6-10 Aryl, C 6-10 The substituent is one or more of the following: haloaryl, 5-10 heteroaryl, and 5-10 haloheteraryl. q is selected from integers greater than or equal to 1 and less than or equal to 15; The structure of the ULM is shown in the following formula: Among them, W1 is independently selected from CR each time it appears. c1 and N; R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 1-6 Halogenated alkylene and C 1-6 A combination of one or more heteroalkyl groups; R q Each occurrence is independently selected from single bonds and NR. c1 ;R q place Indicates the connection site with L; W2, W3, and W4 are each independently selected from C, C(O), O, N, and NR, respectively. c1 CR c1 and CR c1 R c2 The area between W2, W3 and W4 Indicates a single bond or a double bond; In Equations 2-2 and 2-8, when W2 and W3 form a double bond and W3 and W4 form a single bond, W2 is selected from C, and W3 is selected from N and C. c1 W4 is selected from O and CR c1 R c2 and NR c1 When W2 and W3 form a single bond, and W3 and W4 form a double bond, W2, W3, and W4 are each independently selected from N and CR. c1 When all bonds between W2, W3, and W4 are single bonds, W2 is selected from N and CR. c1 W3 and W4 are each independently selected from C(O) and NR. c1 O and CR c1 R c2 ; W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is selected from C(O); R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups; (i-1)R 1a and R 1b The carbon atoms bonded to it together form a ring Cy0, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-2)R 1b and R 1c The carbon atoms bonded to it together form a ring Cy0, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-3)R 1c and R 1d The carbon atoms bonded to it together form a ring Cy0, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-4)R 1d and R 1e The carbon atoms bonded to it together form a ring Cy0, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the range; and (i-5)R 1a and R W The carbon or nitrogen atom bonded to it forms a ring Cy0, and R 1b R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; R 2a R 2b R 2c and R 2d The definition is selected from one of the following groups; (ii-1)R 2a and R 2b The carbon atoms bonded to it together form a ring Cy1, and R 2c and R 2d Each occurrence is independently selected from R. S1 Substituents within the specified range; (ii-2)R 2b and R 2c The carbon atoms bonded to it together form a ring Cy1, and R 2a and R 2d Each occurrence is independently selected from R. S1 Substituents within the range; and (ii-3)R 2c and R 2d The carbon atoms bonded to it together form a ring Cy1, and R 2a and R 2b Each occurrence is independently selected from R. S1 Substituents within the specified range; R 3a R 3b and R 3c The definition is selected from one of the following groups; (iii-1)R 3a and R 3b The carbon atoms bonded to it together form a ring Cy2, and R 3c Each time it appears, it is selected independently from R. S1 Substituents within the range; and (iii-2)R 3b and R 3c The carbon atoms bonded to it together form a ring Cy2, and R 3a Each time it appears, it is selected independently from R. S1 Substituents within the specified range; Cy0, Cy1, and Cy2 are each independently selected from... A1, A2, A3, A4, A5, and A6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at A1 and A2 Indicates the connection site of an atom in the ring to which it is connected; B1, B2 and R T Each time it appears, it is selected independently from CR. c1 and N;R T place Indicates the connection site with L; R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, C 1-10 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Heteroalkyl, C 1-10 Alkoxy, C 1-10 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents of a 5-10 member heteroaryl group; Each time n appears, it is independently selected from 0, 1, 2, 3, 4, and 5; R c1 and R c2 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, cyano, amino, nitro, hydroxyl, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 3-8 cycloalkyl, 3-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 6-8 It is substituted by one or more substituents of aryl and 5-8 heteroaryl groups; Each time m1, m3, and m5 appear, they are independently selected from 1, 2, 3, 4, 5, and 6; Each time m2, m4, and m6 appear, they are independently selected from 0, 1, 2, 3, 4, 5, and 6; and In the above formulas, Substituents that do not explicitly indicate the location of substitution can be substituted at any position on the ring.

7. A compound having the structure shown in formula (I7): PTM-L-ULM formula (Ι7); Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: The structure of the PTM is shown in equation (1-17): Ring A is selected from 8-10 membered bicyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; 11-15 membered tricyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; and 16-20 membered tetracyclic heterocyclic aryl groups containing 1-5 heteroatoms independently selected from N, O, and S; wherein the tricyclic heterocyclic aryl group and the tetracyclic heterocyclic aryl group are fused rings, spirocycles, or spirofused ring structures. Ring B is selected from single bonds, 6-10 member monocyclic aryl groups, 8-10 member bicyclic aryl groups, 5-10 member monocyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, 8-10 member bicyclic heteroaryl groups containing 1-5 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5-10 member monocyclic alkyl groups, saturated or partially unsaturated 5-13 member bicyclic alkyl groups, saturated or partially unsaturated 5-10 member monocyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, and 5-13 member bicyclic heterocyclic groups containing 1-5 heteroatoms independently selected from N, O, and S, wherein the bicyclic alkyl groups and bicyclic heterocyclic groups are bridged rings, spiro rings, or fused ring structures; The ring C is absent or selected from 3-10 membered cycloalkyl groups, 3-10 membered monocyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 6-13 membered bicyclic heterocyclic groups containing 1-5 saturated or partially unsaturated heteroatoms selected independently of N, O and S, 5-10 membered monocyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, and 8-10 membered bicyclic heteroaryl groups containing 1-5 heteroatoms selected independently of N, O and S, wherein the bicyclic heterocyclic group is a fused ring, spiro ring or bridged ring structure; When ring C exists, L c Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X A combination of one or more of C(O), wherein C 3-6 The cycloalkyl group is optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-6 One or more substituents in the alkyl group are substituted; When ring C does not exist, L c Selected from C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, -SC 1-6 Alkyl, -S(O)-C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -NR X -C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -NR X -C(O)-N(R X )2 and -C(O)-NR X -C 1-6 Alkyl, the C 1-6 Alkyl, C 1-6 Heteroalkyl and C 1-6 Alkyl groups, optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C atoms. 1-6 One or more substituents in the alkyl group are substituted; p1, p2, and p3 are each independently selected from 0, 1, 2, 3, 4, and 5; L b Selected from single bonds, C(R) X 2. C 3-6 Cycloalkylene, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); R A R B and R C Each time it appears, it is independently selected from H, deuterium, halogen, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-8 Alkyl, -C(O)-C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 1-8 Deuterated alkyl, C 1-8 Heteroalkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 1-8 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 aryl and 5-8 heteroaryl groups, optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 It is substituted by one or more substituents of aryl and 5-6 heteroaryl groups; R D selected from R X , -OR X , -SR X , -N(R X )2, -S(O)R X , -S(O)2R X , -S(O)N(R X )2, -S(O)2N(R X )2, -C(O)R X , -C(O)OR X , -C(O)N(R X )2, -C(O)N(R X )OR X , -OC(O)R X , -OC(O)N(R X )2, -NR X C(O)OR X , -NR X C(O)R X , -NR X C(O)N(R X )2 and -NR X S(O)2R X ; R X Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 1-8 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups, optionally selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 One or more substituents of the haloalkoxy group are substituted; When ring B is a saturated or partially unsaturated 5- or 6-membered heterocyclic group, phenylene group, or 5- or 6-membered heteroaryl group containing 1 or 2 independently selected N, O, and S heteroatoms, and ring A is selected from a 9-membered bicyclic heteroaryl group containing 1 to 4 independently selected N, O, and S heteroatoms, the 9-membered bicyclic heteroaryl group is selected from... When ring B is L b It is a single bond, and the ring C is At that time, ring A is not When ring B is And L b When it is -C(O)-NH-CH2-, ring A is not a bicyclic or tricyclic heteroaryl or heterocyclic group; The L is the chemical linker connecting the PTM and the ULM; preferably, the L is -(B L ) q -; B L Each occurrence is independently selected from covalent bonds, CR L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 C(O), 3-15 member monocyclic cycloalkylene groups, 3-15 member monocyclic heterocyclic groups containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15 member bridged cycloalkylene groups, 5-15 member spirocyclic groups, 5-15 member spirocyclic groups containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 6-15 member aryl groups and 5-15 member heteroaryl groups containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, wherein the cycloalkylene group, heterocyclic group, bridged cycloalkyl group, bridged cycloalkyl group, spirocyclic group, spirocyclic group, aryl group and heteroaryl group are optionally surrounded by 1-6 R L1 and / or R L2 Group substitution; R L1 and R L2 Each occurrence is independently selected from H, halogens, -OH, -NH2, -SH, -C(O)2H, -CN, -NO2, -S(O)2H, -SF5, -C≡CH, C 1-8 Alkyl, C 1-8 Alkoxy, -SC 1-8 Alkyl, -NH-C 1-8 Alkyl, N(C) 1-8 Alkyl)2, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, -OC 3-8 Cycloalkyl, -O-3-8 membered heterocyclic groups, -OC 6-10 Aryl, -O-5-10 heteroaryl, -SC 3-8 cycloalkyl, -NH-C 3-8 cycloalkyl, -N(C) 3-8 cycloalkyl)2, -N(C 3-8 cycloalkyl)(C 1-8 Alkyl), -NH-3-8-membered heterocyclic group, -N(3-8-membered heterocyclic group)2, -N(3-8-membered heterocyclic group) (C 1-8 alkyl), -NH-C 6-10 Aryl, -N(C 6-10 Aryl)(C 1-8 alkyl), -NH-C 5-10 heteroaryl, -N (5-10 quinone heteroaryl) (C 1-8 Alkyl), -S(O)2P(O)(C 1-8 Alkoxy)(C 1-8 Alkyl), -P(O)(C 1- 8-alkoxy)2、-C≡CC 1-8 Alkyl group, -CH=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl)=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl) = C(C 1-8 Alkyl group 2, -Si(OH)3, -Si(C) 1-8 Alkyl)3、-Si(OH)(C 1-8 Alkyl)2、-C(O)-C 1-8 Alkyl group, -S(O)2NH-C 1-8 Alkyl group, -S(O)2N(C) 1-8 Alkyl)2、-S(O)NH-C 1-8 Alkyl, -S(O)N(C) 1- 8-alkyl)2、-C(O)NH-C 1-8 Alkyl, -C(O)N(C) 1-8 Alkyl)2, -N(C 1-8 alkyl)C(O)NH(C 1-8 alkyl), -N(C) 1-8 alkyl)C(O)N(C 1-8 alkyl)2、-NHC(O)NH(C 1-8 Alkyl), -NHC(O)N(C 1-8 Alkyl)2, -NHC(O)NH2, -N(C 1-8 alkyl)S(O)2NH(C 1-8 alkyl), -N(C) 1-8 alkyl)S(O)2N(C 1- 8-alkyl)2、-NHS(O)2NH(C 1-8 Alkyl), -NHS(O)2N(C 1-8 alkyl)2 and -NHS(O)2NH2, the C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-8 cycloalkyl, C 3-8 Halogenated cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered halocyclic heterocyclic group, C 6-10 Aryl, C 6-10 The substituent is one or more of the following: haloaryl, 5-10 heteroaryl, and 5-10 haloheteraryl. q is selected from integers greater than or equal to 1 and less than or equal to 15; The structure of the ULM is shown in the following formula: Among them, W1 is independently selected from CR each time it appears. c1 and N; R W Each occurrence is independently selected from single bonds, O, S, S(O)2, C(O), NR. c1 C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 1-6 Halogenated alkylene and C 1-6 A combination of one or more heteroalkyl groups; R q Each occurrence is independently selected from single bonds and NR. c1 ;R q place Indicates the connection site with L; W2, W3, and W4 are each independently selected from C, C(O), O, N, and NR, respectively. c1 CR c1 and CR c1 R c2 The area between W2, W3 and W4 Indicates a single bond or a double bond; In Equations 2-2 and 2-8, when W2 and W3 form a double bond and W3 and W4 form a single bond, W2 is selected from C, and W3 is selected from N and C. c1 W4 is selected from O and CR c1 R c2 and NR c1 When W2 and W3 form a single bond, and W3 and W4 form a double bond, W2, W3, and W4 are each independently selected from N and CR. c1 When all bonds between W2, W3, and W4 are single bonds, W2 is selected from N and CR. c1 W3 and W4 are each independently selected from C(O) and NR. c1 O and CR c1 R c2 ; W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 C(O), S(O)2 and NR c1 And at least one of W5 and W6 is selected from C(O); R 1a R 1b R 1c R 1d and R 1e The definition is selected from one of the following groups; (i-1)R 1a and R 1b The atoms connected to it together form a ring Cy0, and R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-2)R 1b and R 1c The atoms connected to it together form a ring Cy0, and R 1a R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-3)R 1c and R 1d The atoms connected to it together form a ring Cy0, and R 1a R 1b and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; (i-4)R 1d and R 1e The atoms connected to it together form a ring Cy0, and R 1a R 1b and R 1c Each occurrence is independently selected from R. S1 Substituents within the range; and (i-5)R 1a and R W The atoms connected to it together form a ring Cy0, and R 1b R 1c R 1d and R 1e Each occurrence is independently selected from R. S1 Substituents within the specified range; R 2a R 2b R 2c and R 2d The definition is selected from one of the following groups; (ii-1)R 2a and R 2b The atoms connected to it together form a ring Cy1, and R 2c and R 2d Each occurrence is independently selected from R. S1 Substituents within the specified range; (ii-2)R 2b and R 2c The atoms connected to it together form a ring Cy1, and R 2a and R 2d Each occurrence is independently selected from R. S1 Substituents within the range; and (ii-3)R 2c and R 2d The atoms connected to it together form a ring Cy1, and R 2a and R 2b Each occurrence is independently selected from R. S1 Substituents within the specified range; R 3a R 3b and R 3c The definition is selected from one of the following groups; (iii-1)R 3a and R 3b The atoms connected to it together form a ring Cy2, and R 3c Each time it appears, it is selected independently from R. S1 Substituents within the range; and (iii-2)R 3b and R 3c The atoms connected to it together form a ring Cy2, and R 3a Each time it appears, it is selected independently from R. S1 Substituents within the specified range; Cy0, Cy1, and Cy2 are each independently selected from... A1, A2, A3, A4, A5, and A6 are each independently selected from CR each time they appear. c1 R c2 NR c1 O, C(O) and S; at A1 and A2 Indicates the connection sites of atoms on the ring to which it is connected; B1, B2, and R T Each time it appears, it is selected independently from CR. c1 and N;R T place Indicates the connection site with L; R S1 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-10 Alkyl, C 1-10 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Heteroalkyl, C 1-10 Alkoxy, C 1-10 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group is substituted with one or more substituents of a 5-10 member heteroaryl group; Each time n appears, it is independently selected from 0, 1, 2, 3, 4, and 5; R c1 and R c2 Each time it appears, it is independently selected from hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C. 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, -NH-C 1-10 Alkyl, -N(C) 1-10 Alkyl)2、-C(O)-C 1-10 Alkyl, -C(O)-OC 1-10 Alkyl, -C(O)-NH-C 1-10 Alkyl, C 6-10 Aryl and 5-10 heteroaryl, the C 1-10 Alkyl, C 1-10 Deuterated alkyl, C 1-10 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-10 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, cyano, amino, nitro, hydroxyl, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 3-8 cycloalkyl, 3-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 6-8 It is substituted by one or more substituents of aryl and 5-8 heteroaryl groups; Each time m1, m3, and m5 appear, they are independently selected from 1, 2, 3, 4, 5, and 6; Each time m2, m4, and m6 appear, they are independently selected from 0, 1, 2, 3, 4, 5, and 6; and In the above formulas, Substituents that do not explicitly indicate the location of substitution can be substituted at any position on the ring.

8. The compound of claim 2, wherein, Ring A is selected from 9-10 membered bicyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; and 16-18 membered tetracyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; wherein the tricyclic and tetracyclic heterocyclic aryl groups are fused rings, spirocyclic, or fused-spirocyclic structures; and the 9-10 membered bicyclic heterocyclic aryl group, 12-15 membered tricyclic heterocyclic aryl group, 12-15 membered tricyclic heterocyclic aryl group, and 16-18 membered tetracyclic heterocyclic aryl group are optionally divided by p1 R A Replaced; and / or Ring B is absent or selected from 5-8 membered monocyclic or 9-10 membered bicyclic aryl groups, containing 1-4 5-8 membered monocyclic or 9-10 membered bicyclic heterocyclic aryl groups independently selected from N, O, and S heteroatoms, saturated or partially unsaturated 5-8 membered monocyclic or 6-11 membered bicyclic heterocyclic hydrocarbon groups, and containing 1-4 saturated or partially unsaturated 5-8 membered monocyclic or 6-11 membered bicyclic heterocyclic groups independently selected from N, O, and S heteroatoms, wherein the bicyclic hydrocarbon groups and bicyclic heterocyclic groups are bridged rings, spirocyclic rings, or fused ring structures, and the 5-8 membered monocyclic or 9-10 membered bicyclic aryl groups, 5-8 membered monocyclic or 9-10 membered bicyclic heterocyclic aryl groups, 5-8 membered monocyclic or 6-11 membered bicyclic hydrocarbon groups, and 5-8 membered monocyclic or 6-11 membered bicyclic heterocyclic groups are optionally surrounded by p2 R groups. B Replaced; and / or The ring C is absent or selected from 3-8 membered cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms independently selected from N, O, and S, 5-8 membered monocyclic or 9-10 membered bicyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S, and 8-11 membered bicyclic heterocyclic groups containing 1-4 heteroatoms independently selected from N, O, and S, either saturated or partially unsaturated, wherein the bicyclic heterocyclic group has a fused ring structure, and the 3-8 membered cycloalkyl group, 3-8 membered heterocyclic group, 5-8 membered monocyclic or 9-10 membered bicyclic heteroaryl group, and 8-11 membered bicyclic heterocyclic group are optionally surrounded by p3 R groups. C Replaced; and / or p1, p2, and p3 are each independently selected from 1, 2, 3, and 4; and / or L a Selected from single bond, C 1-3 Alkylene, C 3-5 Cycloalkylene, C 1-3 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); and / or When ring C exists, L b Selected from single bond, C 1-3 Alkylene, C 3-5 Cycloalkylene, C 1-3 Heteroalkyl, O, S, S(O), S(O)2, NR X Combinations of one or more of C(O); when ring C does not exist, L b Selected from single bond, C 1-3 Alkylene, C 3-5 Cycloalkylene, C 1-3 Heteroalkyl, O, S, S(O), S(O)2, NR X and one or more of C(O) with C 1-3 Combinations of alkyl groups; and / or R A R B and R C Each time it appears, it is independently selected from H, deuterium, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1- 6-alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 aryl and 5-6 heteroaryl groups, optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, halogenated C 1-3 Alkyl, Halogenated C 1-3 Alkoxy, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 The aryl group is substituted with one or more substituents of a 5-6 membered heteroaryl group; and / or R D It does not exist or is selected independently from F, Cl, Br, I, cyano, nitro, and -R each time it appears. X -OR X -SR X -N(R) X )2、-Si(R X 3、-S(O)R X -S(O)2R X -S(O)(NR) X )R X -S(O)2N(R) X )2、-C(O)R X -C(O)OR X -C(O)N(R) X )2、-C(O)N(R X OR X -OC(O)R X -OC(O)N(R) X )2、-P(O)(R X )2、-P(O)(OR X )2、-OP(O)(R X )2、-OP(O)(OR X )2、-NR X C(O)OR X -NR X C(O)R X -NR X C(O)N(R X )2、-NR X S(O)2R X C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 Aryl and 5-6 membered heteroaryl, said C 1- 6-alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 Aryl and 5-6 heteroaryl groups, optionally selected from halogens, C 1-3 Alkyl, C 1-3 Alkoxy group, -C(O)C 1-3 Alkyl, Halogenated C 1-3 Alkyl and Halogenated C 1-3 One or more substituents of the alkoxy group are substituted; and / or R X Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 5-6 Aryl and 5-6 heteroaryl groups, optionally selected from halogens, C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkyl and Halogenated C 1-3 One or more substituents of the alkoxy group are substituted; and / or B L Each time it appears, it is selected independently from CR. L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 C(O), -C≡C-, 3-12-membered cycloalkylene, 3-12-membered heterocyclic group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 5-12-membered bridged cycloalkyl group containing 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 5-12-membered spirocyclic group containing 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 6-12-membered aryl group and 5-12-membered heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, wherein the 3-12-membered cycloalkylene, 3-12-membered heterocyclic group, 5-12-membered bridged cycloalkyl group, 5-12-membered spirocyclic group, 6-12-membered aryl group and 5-12-membered heteroaryl group are optionally separated by 1, 2, 3 or 4 R L1 and / or R L2 Group substitution; R L1 and R L2 Each occurrence is independently selected from H, F, Cl, Br, I, -OH, -NH2, -SH, -C(O)2H, -CN, -CF3, -CHF2, -CH2F, -NO2, -S(O)2, C 1-6 Alkyl, -OC 1-6 Alkyl, -C(O)-C 1-6 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-3 Alkyl, 1-3 heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, halogenated C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic groups, halogenated C 3-6 Cycloalkyl, halogenated 3-6 heteroalkyl, C 6-8 Aryl, 5-8 quinone heteroaryl, halogenated C 6-8 The aryl group is substituted with one or more substituents in the 5-8 membered heteroaryl group of halogenated group; and / or q is selected from integers greater than or equal to 1 and less than or equal to 10; preferably, q is selected from 1, 2, 3, 4, 5, 6, 7, and 8; and / or W1 is selected independently from CH and N each time it appears; and / or R W Each occurrence is independently selected from single bonds, C(O), O, and NR. c1 NR c1 C(O), C 1-3 Alkylene and Halogenated C 1-3 Alkylene; preferably, R W Each occurrence is independently selected from single bonds and NR. c1 and NR c1 C(O); and / or W5 and W6 are each selected independently from CR each time they appear. c1 R c2 and C(O), and at least one of W5 and W6 is selected from C(O); and / or D1, D2, D3, D4, D5, and D6 are each independently selected from CH2 and C(C) each time they appear. 1-6 Alkyl)2, NH, N(C) 1-6 Alkyl groups), O, and C(O); preferably, D1, D2, D3, D4, D5, and D6 are each independently selected from CH2, C(C) and O when they appear. 1-3 Alkyl)2, NH, N(C) 1-3 Alkyl groups), O and C(O); and / or R T Each occurrence is independently selected from CH and N; and / or The substituents in group S1 are selected from: hydrogen, deuterium, halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 3-6 cycloalkyl, 4-8 membered heterocyclic, C 6-10 Aryl and 5-10 heteroaryl, the C 1- 6-alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, C 3-6 cycloalkyl, 4-8 membered heterocyclic, C 6-10 Aryl and 5-10 heteroaryl groups are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, 4-8 membered heterocyclic, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 The aryl group is substituted with one or more substituents of a 5-10 heteroaryl group; and / or R c1 and R c2 Each time it appears, it is independently selected from H, deuterium, F, Cl, Br, I, oxo group (=O), hydroxyl group, nitro group, cyano group, amino group, C. 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-NH-C 1-6 Alkyl, C 5-10 aryl and 5-10 heteroaryl, wherein the C 1-6 Alkyl, deuterated C 1- 6-alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 cycloalkyl, 4-8 membered heterocyclic, C 5-10 The aryl group and the 5-12 heteroaryl group are each independently and optionally bonded by one or more groups selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1- 3-alkoxy, halogenated C 1-3 Alkyl, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 4-6 membered heterocyclic groups, -NH-C 1-3 Alkyl, -N(C) 1-3 Alkyl)2, C 5-8 Substituents of aryl and 5-8 heteroaryl groups; and / or Each of n1, n2, n3, n4, n5, and n6 is independently selected from 0, 1, 2, and 3 when it appears.

9. The compound according to any one of claims 1 and 3-7, wherein, Ring A is selected from 9-10 membered bicyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; and 16-18 membered tetracyclic heterocyclic aryl groups containing 1-4 heteroatoms independently selected from N, O, and S; wherein the tricyclic and tetracyclic heterocyclic aryl groups are fused rings, spirocyclic, or spirofused fused ring structures; preferably, ring A is selected from those containing 1, 2, 3, or... The following are provided: a 9- or 10-membered bicyclic heterocyclic aryl group containing four independently selected N, O, and S heteroatoms; a 13-membered tricyclic heterocyclic aryl group containing one, two, or three independently selected N, O, and S heteroatoms; a 12-, 13-, 14-, or 15-membered tricyclic heterocyclic aryl group containing one, two, or three independently selected N, O, and S heteroatoms; and a 16-, 17-, or 18-membered tetracyclic heterocyclic aryl group containing one, two, three, or four independently selected N, O, and S heteroatoms, wherein the tricyclic and tetracyclic heterocyclic aryl groups are fused rings, spirocyclic, or spirofused ring structures; preferably, ring A is selected from... Each occurrence of Q is independently selected from O, S, and NR. X Each time Q0 appears, it is independently selected from O, S, C(R). X )2 and NR X Preferably, ring A is selected from... and / or Ring B is selected from single bonds, 6-8 membered monocyclic aryl groups, 9-10 membered bicyclic aryl groups, 5-8 membered monocyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S, 8-10 membered bicyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5-8 membered monocyclic heterocyclic hydrocarbon groups, saturated or partially unsaturated 6-11 membered bicyclic heterocyclic hydrocarbon groups, saturated or partially unsaturated 5-8 membered monocyclic heterocyclic hydrocarbon groups containing 1-4 heteroatoms independently selected from N, O, and S, and 6-11 membered bicyclic heterocyclic hydrocarbon groups containing 1-4 heteroatoms independently selected from N, O, and S, wherein the bicyclic heterocyclic hydrocarbon groups and bicyclic heterocyclic hydrocarbon groups are bridged rings, spirocyclic rings, or fused ring structures; preferably, ring B... The compounds are selected from single bonds, phenylene, 9- or 10-membered bicyclic aryl groups, 5- or 6-membered monocyclic heteroaryl groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 9- or 10-membered bicyclic heteroaryl groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, saturated or partially unsaturated 5- or 6-membered monocyclic heterocyclic hydrocarbon groups, 7-, 8-, 9-, or 10-membered bicyclic heterocyclic hydrocarbon groups, saturated or partially unsaturated 5- or 6-membered monocyclic heterocyclic hydrocarbon groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, and 7-, 8-, 9-, or 10-membered bicyclic heterocyclic hydrocarbon groups, wherein the bicyclic heterocyclic hydrocarbon group and the bicyclic heterocyclic hydrocarbon group are bridged rings, spirocyclic rings, or fused ring structures; preferably, ring B is selected from single bonds, phenylene, phenylene, 9- or 10-membered bicyclic heterocyclic hydrocarbon groups. and / or The ring C is absent or selected from 3-8 membered cycloalkyl groups, 3-8 membered monocyclic heterocyclic groups containing 1-4 saturated or partially unsaturated 3-8 membered monocyclic heterocyclic groups containing 1-4 saturated or partially unsaturated 8-11 membered bicyclic heterocyclic groups containing 1-4 saturated or partially unsaturated 8-11 membered bicyclic heterocyclic groups containing 1-4 5-8 membered monocyclic heteroaryl groups containing 1-4 1-4 9-10 membered bicyclic heteroaryl groups containing 1-4 1-4 1-4 fused ring, spiro ring, or bridged ring structures; preferably, the ring C is absent or selected from 3-membered, 4-membered, 5-membered, or... The following are considered as separate categories: 6-membered cycloalkyl groups; 3-, 4-, 5-, or 6-membered monocyclic heterocyclic groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms; 8- or 9-membered bicyclic heterocyclic groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms; 5-membered monocyclic heteroaryl groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms; and 8- or 9-membered bicyclic heteroaryl groups containing 1, 2, or 3 saturated or partially unsaturated N, O, and S heteroatoms, wherein the bicyclic heterocyclic group is a fused ring, spiro ring, or bridged ring structure; preferably, the ring C is absent or selected from... and / or p1, p2, and p3 are each independently selected from 0, 1, 2, 3, and 4; preferably, p1, p2, and p3 are each independently selected from 0, 1, 2, and 3; and / or L b Selected from single bonds, C(R) X 2. C 3-5 Cycloalkylene, O, S, S(O), S(O)2, NR X A combination of one or more of C(O); preferably, L b Selected from single bond, C 1-3 Alkylene, Cyclopropylene, O, S, S(O), S(O)2, NH, N(C) 1-3 A combination of one or more of alkyl groups and C(O); preferably, L b Selected from single bonds; and / or When ring C exists, L c Selected from single bond, C 1-3 Alkylene, Cyclopropylene, O, S, S(O), S(O)2, NH, N(C) 1-3 A combination of one or more of alkyl groups and C(O); preferably, when a cyclic C is present, L c Selected from single bonds, NH, C 1-3 Alkylene, Cyclopropylene, N(C) 1-3 A combination of one or more of alkyl groups and C(O); preferably, when a cyclic C is present, L c Each occurrence is independently selected from single bonds, -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -C(O)-CH2-, -C(O)-CH2CH2-, -C(O)-cyclopropylidene, -N(CH3)-C(O)-, and -N(CH3)-C(O)-CH2CH2-; preferably, L c It is -C(O)-CH2CH2-; When ring C does not exist, L c Selected from C 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, -SC 1-3 Alkyl, -S(O)-C 1-3 Alkyl, -S(O)2-C 1-3 Alkyl, -NR X -C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -NR X -C(O)-N(R X )2、-C(O)-OC 1-3 Alkyl, -C(O)-N(R) X )2- and -C(O)-NR X -C 1-3 Alkyl, the C 1-3 Alkyl, C 1-3 Heteroalkyl and C 1-3 Alkyl groups are optionally selected from deuterium, halogen, hydroxyl, nitro, cyano, amino, and C. 1-3 One or more substituents in the alkyl group are substituted; preferably, when the ring C is absent, L c Selected from C 1-3 Alkyl, C 1-3 Alkoxy, -N(C) 1-3 Alkyl)2、-C(O)-C 1-3 Alkyl, -NH-C(O)-N(C) 1-3 Alkyl)2、-NH-C(O)-NH(C 1-3 Alkyl), -C(O)-OC 1-3 Alkyl, -C(O)-N(C) 1-3 alkyl)2 and -C(O)-N(C 1-3 Alkyl group 2; preferably, when the ring C is absent, L c Selected from -C(O)-C 1-3 Alkyl, -NH-C(O)-N(C) 1-3 Alkyl)2、-NH-C(O)-NH(C 1-3 Alkyl), -C(O)-OC 1-3 Alkyl groups and -C(O)-N(C) 1-3 Alkyl)2; and / or R A R B and R C Each time it appears, it is independently selected from H, deuterium, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1- 6-alkyl, -C(O)-C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 heteroaryl groups are optionally selected from halogen, hydroxyl, nitro, cyano, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 The aryl group is substituted with one or more substituents of a 5-6 membered heteroaryl group; preferably, R A R B and R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl, -C(O)-C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 heteroaryl groups are optionally selected from F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C 1-3 Alkyl, C 1- 3-alkoxy group, C 1-3 Halogenated alkyl groups and C 1-3 The alkoxy group is substituted with one or more substituents of the haloalkoxy group; preferably, R A R B and R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl, C 1-3 Alkoxy group, -C(O)-C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl; preferably, R A R B and R C Each time it appears, it is independently selected from F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl, C 1-3 Alkoxy group, -C(O)-C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl; preferably, R A R B and R C Each occurrence is independently selected from F and -CH3; and / or R D selected from R X , -OR X , -N(R X )2, -C(O)R X , -C(O)OR X , -C(O)N(R X )2, -C(O)N(R X )OR X , -OC(O)R X , -OC(O)N(R X )2, -NR X C(O)OR X , -NR X C(O)R X , -NR X C(O)N(R X )2 and -NR X S(O)2R X ; preferably, R D is selected from R X , -N(R X )2, -C(O)R X , -C(O)OR X and -C(O)N(R X )2; and / or R X Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 quinone heteroaryl groups are optionally selected from halogens, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups and C 1-3 One or more substituents of the haloalkoxy group are substituted; preferably, R X Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-3 Alkyl, C 2- 3-Alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 The aryl group and the 5-6 heteroaryl group are optionally selected from F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups and C 1-3 One or more substituents of the haloalkoxy group are substituted; preferably, R X Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-3 Alkyl, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are optionally replaced by one or more halogens; preferably, R X Each time it appears, it is independently selected from F, Cl, Br, I, hydroxyl, nitro, cyano, amino, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, cyclopropyl, and halocyclopropyl; and / or Each occurrence of W1 is independently selected from CH and N; and / or R W Each occurrence is independently selected from single bonds, C(O), O, and NR. c1 C(O)NR c1 C 1-3 Alkylene and C 1-3 Halogenated alkylene; preferably, R W Each occurrence is independently selected from single bonds, O, and NR. c1 and C(O)NR c1 Preferably, R W Each occurrence is independently selected from single bonds, NH, N(CH3), C(O)-NH, and C(O)-N(CH3); and / or R q Each occurrence is independently selected from single bonds and NH; and / or In Equations 2-2 and 2-8, when there is a double bond between W2 and W3, and a single bond between W3 and W4, W2 is C, and W3 is selected from N and C. c1 W4 is selected from O and CR c1 R c2 and NR c1 Preferably, W3 is N; preferably, W4 is selected from N-CH3, NH, O, CH2, CH(CH3) and C(CH3)2; When there is a single bond between W2 and W3, and a double bond between W3 and W4, W2, W3, and W4 are each independently selected from N and CR. c1 Preferably, W2, W3, and W4 are each independently selected from N, CH, and C-CH3; When all bonds between W2, W3, and W4 are single bonds, W2 is selected from N and CR. c1 W3 and W4 are each independently selected from C(O) and NR. c1 O and CR c1 R c2 Preferably, W2 is selected from N, CH and C-CH3; preferably, W3 and W4 are each independently selected from C(O), O, NH, N(CH3), CH2, CH(CH3) and C(CH3)2; and / or W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 And C(O), and at least one of W5 and W6 is C(O); preferably, W5, W6 and W7 are each independently selected from CH2 and C(O) each time they appear, and at least one of W5 and W6 is selected from C(O); preferably, W5 and W6 are each independently selected from CH2 and C(O) each time they appear, and at least one of W5 and W6 is C(O); W7 is C(O); and / or W 12 and W 13 Each is independently selected from N, CH and C(C) 1-3 Alkyl); and / or A1, A2, A3, A4, A5, and A6 are each independently selected from CH2, C(C) each time they appear. 1-6 Alkyl)2, CH(C) 1-6 Alkyl), NH, N(C) 1-6 Alkyl groups), O, and C(O); preferably, A1, A2, A3, A4, A5, and A6 are each independently selected from CH2, C(C) and O when they appear. 1-3 Alkyl)2, CH(C) 1-3 Alkyl), NH, N(C) 1- 3 alkyl), O and C(O); and / or B1, B2 and R T Each occurrence is independently selected from CH and N; and / or R S1 Each time it appears, it is independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 The aryl and 5-8 heteroaryl groups are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 2-6 alkenyl, C 2-6 alkynyl group, C 6- The 8-aryl group is substituted with one or more substituents of 5-8 heteroaryl groups; preferably, R S1 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl; preferably, R S1 Each occurrence is independently selected from H, F, Cl, Br, -CN, -OH, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -OCH2CH3, and -OCH(CH3)2; preferably, R S1 Each occurrence is independently selected from H, F, Cl, Br, -CN, -OH, -CH3, and -OCH3; and / or Each occurrence of n is independently selected from 0, 1, 2, and 3; and / or R c1 and R c2 Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 cycloalkyl, 3-8 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-NH-C 1-6 Alkyl, C 6-8 Aryl and 5-8 membered heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 The aryl and 5-8 heteroaryl groups are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-3 Alkyl, -N(C) 1-3 Alkyl)2, C 6-8 The aryl group is substituted with one or more substituents of a 5-8 membered heteroaryl group; preferably, R c1 and R c2 Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-3 Alkyl, -N(C) 1-3 Alkyl)2、-C(O)-C 1-3 Alkyl, -C(O)-OC 1-3 Alkyl, -C(O)-NH-C 1-3 Alkyl, C 6-7 Aryl and 5-7 membered heteroaryl, wherein the C 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 Aryl and 5-7 heteroaryl groups are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-3 Alkyl, C 1-3 Heteroalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-3 Alkyl, -N(C) 1-3 Alkyl)2, C 6- The 7-aryl group and one or more substituents of the 5-7 heteroaryl group are substituted; preferably, R c1 and R c2 Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 aryl and 5-8 quinone heteroaryl; and / or Each time m1, m3, and m5 appear, they are independently selected from 1, 2, 3, 4, and 5; and / or Each time m2, m4, and m6 appear, they are independently selected from 0, 1, 2, 3, 4, and 5; Preferably: R A Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3, -CH(CH3)2, -OCH3 and -OCH2CH3; and / or R B Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3 and -C(O)-CH3; and / or R C Each occurrence is independently selected from H, F, Cl, Br, I, -CH3, and -CH2CH3; and / or R D Each occurrence is independently selected from H, F, Cl, Br, I, -OCH3, -CH3, -CH2CH3, -CH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -C(O)-NH(CH3), -C(O)-NH(CH2CH3), -C(O)-N(CH3)2, -C(O)-N(CH3)2, -C(O)-N(CH3)(CF3), -C(O)-N(CH3)(CH2CH3), -C(O)-N(CH3)(CH(CH3)2), -C(O)-N(CH2CH3)(CH(CH3)2), Preferably, R D It is -C(O)-N(CH3)2.

10. The compound according to any one of claims 1, 3-7 and 9, wherein, The PTM is selected from the structure shown in the following formula: Among them, rings B, C, and L b L c R A R B R C R D p1, p2, and p3 are defined as in any one of claims 1, 3-7, and 9; Q2 is selected independently from CR each time it appears. A , N, C(R) A 2. NR A and C; This indicates that two double bonds are formed at any position within the ring, together with Q2 on the ring, to form a conjugated system; In equations (IC) and (IE), Q1 is independently selected from O, S, and NR each time it appears. X ; In (IA), R 4g Does not exist, or R 4g With R 4a Or R 4f Together they form Cy6; When R 4g When Q1 does not exist, each occurrence of Q1 is independently selected from O, S, and NR. X When R 4g With R 4a Or R 4f When they jointly form Cy6, Q1 appears independently as N each time; R X Same as the definition of any one of claims 1-9; In equation (1-A), R 4a R 4b R 4c R 4d R 4e R 4f and R 4g The definition is selected from one of the following groups; (iv-1)R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range; (iv-2)R 4a and R 4b Together they form Cy3, which is optionally bounded by R D Replace; R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range; (iv-3)R 4b and R 4c Together they form Cy4; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range; (iv-4)R 4c and R 4d Together they form Cy4; R 4e With L b Connected, and R 4e It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4f Each occurrence is independently selected from R. A Substituents within the specified range; (iv-5)R 4d and R 4e Together they form Cy5; R 4c Connected to L, and R 4c It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4f Each occurrence is independently selected from R. A Substituents within the specified range; (iv-6)R 4e and R 4f Together they form Cy5; R 4c Connected to L, and R 4c It is a single bond; R 4g Does not exist; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4d Each occurrence is independently selected from R. A Substituents within the specified range; (iv-7)R 4f and R 4g Together they form Cy6; R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4a Each occurrence is independently selected from R. D Substituents within the range; R 4b and R 4d Each occurrence is independently selected from R. A Substituents within the range; and (iv-8)R 4g and R 4a Together they form Cy6, which is optionally bounded by R D Replace; R 4c Connected to L, and R 4c It is a single bond; R 4e With L b Connected, and R 4e It is a single bond; R 4b R 4d and R 4f Each occurrence is independently selected from R. A Substituents within the specified range; Cy3 is selected independently each time it appears. Cy4 is selected independently each time it appears. Cy5 is selected independently each time it appears. Cy6 is selected independently each time it appears. F1, F2, F3, F4, and F5 are each selected independently from CR each time they appear. d1 R d2 NR d1 O, C(O) and S; F1 and F2, F2 and F3 or place In equation (1-A) The connection sites of atoms on the ring; preferably, F1, F2, F3, F4 and F5 are each independently selected from CR each time they appear. d1 R d2 NR d1 O and C(O); preferably, F1, F2, F3, F4 and F5 are each independently selected from CH2, O and NH when they appear. U6 and U7 are each independently designated as CR each time they appear. d1 Or N; preferably, U6 and U7 are each independently CH or N each time they appear; R t and R t1 Each time it appears, it is selected independently from CR. d1 and N; preferably, R t and R t1 Each occurrence is independently either CH or N; R t2 Each occurrence is independently designated as C; R t and R t2 place Indicates the connection site with L; R t1 place Indicates with L b Connection sites; Each occurrence of q0, q1, q2, q3, q4, and q5 is independently selected from 0, 1, 2, 3, 4, and 5; preferably, each occurrence of q0, q1, q2, q3, q4, and q5 is independently selected from 0, 1, 2, and 3; and R d1 and R d2 Each time it appears, it is independently selected from H, halogen, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 3-6 cycloalkyl, 3-6 membered heterocyclic groups, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-NH-C 1-6 Alkyl, C 6-7 Aryl and 5-6 membered heteroaryl, said C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 The aryl and 5-6 heteroaryl groups are optionally selected from halogens, hydroxyl groups, cyano groups, amino groups, nitro groups, C-groups, etc. 1-3 Alkyl, C 1-3 Alkoxy and C 1-3 The alkyl group is substituted with one or more substituents; preferably, R d1 and R d2 Each time it appears, it is independently selected from H, halogen, cyano, amino, nitro, hydroxyl, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 Hydroxyalkyl; Preferably, the PTM is selected from the structure shown in the following formula: Among them, rings B, C, and L b L c R A R B R C R D p1, p2, and p3 are as defined in any one of claims 1, 3-7, and 9; and Q3 is selected independently from CH and N each time it appears; Preferably: Each occurrence of ring B is independently selected from single bonds. and / or Ring C either does not exist or is selected independently each time it appears. and / or When ring B is a single bond and ring C exists, L b Each occurrence is a single key, L. c Each time it appears, it is independently selected from C(O), cyclopropylene, C 1-3 A combination of one or more of alkylene groups, NH, and N(CH3); when ring B is not a single bond and ring C is absent, L b Each occurrence is independently selected from single bonds, C(O), C 1-3 A combination of one or more of alkylene, NH, and N(CH3), L c Each occurrence is independently selected from -C(O)-C 1-3 Alkyl, N(CH3)-C 1-3 Alkyl groups and -C(O)-N(CH3)-C 1-3 Alkyl; when ring B is not a single bond and ring C is present, L b and L c Each occurrence is independently selected from single bonds, cyclopropyl groups, and C. 1-3 A combination of one or more of alkylene, O, S(O)2, NH, N(CH3), N(CH2CH3), and C(O); and / or R A Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C(O)-C. 1-3 Alkyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, phenyl and 5-6 membered heteroaryl; and / or R B Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)-C. 1-3 Alkyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 aryl and 5-6 heteroaryl groups; and / or R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C(O)-C. 1-3 Alkyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-7 aryl and 5-6 heteroaryl groups; and / or R D Each time it appears, it is independently selected from H, F, Cl, Br, I, R. X -N(R) X )2、-C(O)R X and -C(O)N(R) X )2; and / or R X Each time it appears, it is independently selected from H, F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic and 3-6 membered halocyclic; and / or p1, p2, and p3 are each independently selected from 0, 1, 2, and 3 each time they appear; and / or Cy3 is selected independently each time it appears. and / or Cy4 is selected independently each time it appears. and / or Cy5 is selected independently each time it appears. and / or Cy6 is selected independently each time it appears. Cy3, Cy4, Cy5 and Cy6 open-loop Indicates and The connection sites of carbon atoms and / or Q1 on the ring.

11. The compound according to any one of claims 1, 3-7, and 9-10, wherein, The PTM is selected from the structure shown in the following formula: Among them, R A R B R C R D and R X Each occurrence is independently defined as in any one of claims 1, 3-7, and 9-10; Each occurrence of Q0 is independently selected from O, S, CH2, C(O), and NR. X ; Q1 is selected independently from O, S, and NH each time it appears; Q3 is selected independently from CH and N each time it appears; Q4 is selected independently from CR each time it appears. X and N; p2 and p3 are each independently selected from 0, 1, and 2; Each occurrence of y0 is independently selected from 0 and 1; Each occurrence of ring B1 is independently selected from... Each occurrence of ring C1 is independently selected from... Ring C2 either does not exist or is selected independently each time it appears. L b Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -O-, -NH-, -C(O)-, -C(O)-O-, -C(O)-C 1-3 Alkylene-, -N(C) 1-3 alkyl)-、-C(O)-NH-C 1-3 Alkylene- and -N(C) 1-3 Alkyl)-C(O)-; preferably, L b Each occurrence is independently selected from single bonds, -CH2-, -CH2CH2-, -C(O)-NH-C 1- 3 alkylene- and -CH2CH2CH2-; preferably, L b Each occurrence is independently selected from single bonds and -C(O)-NH-C 1-3 alkylene-; When ring C2 exists, L c Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -C(O)-, -C(O)-C 1-3 alkylene-, -C(O)-cyclopropylene-, -N(C 1- 3alkyl)-C(O)-, -C(O)-NH-C 1-3 Alkylene- and -N(C) 1-3 alkyl)-C(O)-C 1-3 Alkylene; preferably, when ring C2 is present, L c Each time it appears, it is independently selected from single bond, -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -C(O)-CH2-, -C(O)-CH2CH2-, -C(O)-cyclopropylidene-, -N(CH3)-C(O)-, -C(O)-NH-CH2- and -N(CH3)-C(O)-CH2CH2-; When ring C2 does not exist, L c Each occurrence is independently selected from -C(O)-C 1-3 Alkyl, -NH-C(O)-N(C) 1-3 alkyl)2 and -NH-C(O)-NH(C 1-3 Alkyl); preferably, when the ring C2 is absent, L c Each time it appears, it is independently selected from -C(O)-CH3, -C(O)-CH2CH3, -C(O)-CH(CH3)2, -NH-C(O)-N(CH3)2 and -NH-C(O)-NH(CH3); Preferably: R A Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C. 1-3 Alkyl and C 1-3 Alkoxy; preferably, R A Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3, -CH(CH3)2, -OCH3 and -OCH2CH3; and / or R B Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)-C. 1-3 Alkyl and C 1-3 Alkyl; preferably, R B Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3 and -C(O)-CH3; and / or R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, and C. 1-3 Alkyl; preferably, R C Each occurrence is independently selected from H, F, Cl, Br, I, -CH3, and -CH2CH3; and / or R D Each time it appears, it is independently selected from H, F, Cl, Br, I, R. X 、N(R X 2. C(O)R X and C(O)N(R) X )2; Preferably, R D Each occurrence is independently selected from H, F, Cl, Br, I, -OCH3, -CH3, -CH2CH3, -CH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -C(O)-NH(CH3), -C(O)-NH(CH2CH3), -C(O)-N(CH3)2, -C(O)-N(CH3)2, -C(O)-N(CH3)(CF3), -C(O)-N(CH3)(CH2CH3), -C(O)-N(CH3)(CH(CH3)2), -C(O)-N(CH2CH3)(CH(CH3)2), and / or R X Each time it appears, it is independently selected from H, F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-, 5-, 6-, or 7-membered heterocyclic groups containing 1, 2, or 3 heteroatoms each independently selected from N, O, and S, and 6-membered halocyclic groups containing 1, 2, or 3 heteroatoms each independently selected from N, O, and S; preferably, R X Each occurrence is independently selected from H, F, Cl, Br, I, -CF3, -OCH3, -CH3, -CH2CH3, -CH(CH3)2. and / or Each occurrence of Q0 is independently selected from O, C(O), S, CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); preferably, each occurrence of Q0 is independently selected from O, C(O), CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); and / or Q4 is selected independently from CH, CF, C(CH3), C(OCH3), and N each time it appears.

12. The compound according to any one of claims 1-11, wherein, The PTM is selected from the following structures:

13. The compound according to any one of claims 1-12, wherein, The ULM is selected from the structure shown in the following formula: Among them, R q Each occurrence is independently selected from single bonds and NR. c1 ; W5, W6, and W7 are each selected independently from CR each time they appear. c1 R c2 And C(O), and at least one of W5 and W6 is C(O); W8 and W 10 Each occurrence is independently selected from O and NR. c1 and CR c1 R c2 ; W9, W 11 W 12 and W 13 Each occurrence is independently selected from N and CR. c1 ; Each time W1 appears, it is independently selected from N and CR. c1 ; R W Each occurrence is independently selected from single bonds, O, C(O)NR. c1 and NR c1 ; A1, A2, A3, A4, A5, and A6 are each independently selected from O, S, C(O), and NR when they appear. c1 and CR c1 R c2 ; B1, B2, G, and R T Each occurrence is independently selected from N and CR. c1 ; Each time m1 and m2 appear, they are independently selected from 0, 1, 2, 3, 4 and 5, and m1 + m2 ≤ 6; Each time m3 and m4 appear, they are independently selected from 0, 1, 2, 3, 4 and 5, and m3 + m4 ≤ 6; Each time m5 and m7 appear, they are each independently selected from 0, 1, 2, 3, 4 and 5. Each time m6 and m8 appear, they are each independently selected from 1, 2, 3, 4, 5, 6 and 7. Furthermore, m5+m6≤6 and m7+m8≤6. R c1 and R c2 Each time it appears, it is independently selected from H, halogen, hydroxyl, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 cycloalkyl; and R1, R2, R3, R4, and R5 are each independently selected from H, halogen, hydroxyl, cyano, amino, nitro, and C groups when they appear. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2- 6-olefin, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(O)-C 1-6 Alkyl, -C(O)-C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl and 5-8 quinone heteroaryl groups; Preferably: R q Each occurrence is independently selected from single bonds and NH; and / or W5 and W6 are each independently selected from CH2 and C(O) each time they appear, and at least one of W5 and W6 is C(O); and / or W7 is C(O); and / or W8 and W 10 Each occurrence is independently selected from O, NH, N(C) 1-3 Alkyl), CH(C) 1-3 Alkyl), C(C) 1-3 Alkyl)2 and CH-C 3-6 Cycloalkylene; and / or W9, W 11 W 12 and W 13 Each occurrence is independently selected from N, CH, and C(C) 1-3 Alkyl); and / or R W Each occurrence is independently selected from single bonds, O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 Alkyl); and / or A1, A2, A3, A4, A5, and A6 are each independently selected from CH2, C(C) each time they appear. 1-3 Alkyl)2, CH(C) 1-3 Alkyl), NH, N(C) 1-3 Alkyl groups), O and C(O); and / or Each time m1 and m2 appear, they are independently selected from 0, 1, 2, 3, and 4, and m1 + m2 ≤ 4; and / or Each time m3 and m4 appear, they are independently selected from 0, 1, 2, 3, and 4, and m3 + m4 ≤ 4; preferably, each time m3 and m4 appear, they are independently selected from 0, 1, 2, and 3, and m3 + m4 = 2 or m3 + m4 = 3; and / or Each time m5 and m7 appear, they are independently selected from 0, 1, 2, 3, and 4; each time m6 and m8 appear, they are independently selected from 1, 2, 3, 4, and 5; and m5 + m6 ≤ 5, m7 + m8 ≤ 5. Preferably, each time m5 and m7 appear, they are independently selected from 0, 1, 2, and 3; each time m6 and m8 appear, they are independently selected from 1, 2, 3, and 4; and m5 + m6 = 2, m5 + m6 = 3, or m5 + m6 = 4; m7 + m8 = 2, m7 + m8 = 3, or m7 + m8 = 4; and / or R c1 and R c2 Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl group, C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy and C 3-6 cycloalkyl; and / or R1, R2, R3, R4, and R5 are each independently selected from H, F, Cl, Br, I, -OH, -CN, -NH2, -NO2, and C, respectively. 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups and C 1-3 Hydroxyalkyl.

14. The compound according to any one of claims 1-13, wherein, The ULM is selected from the structure shown in the following formula: in: Each time X and Z appear, they are independently selected from N, CH, C(C). 1-6 alkyl) and C(C) 3-6 (cycloalkyl); preferably, X and Z are each independently selected from N and CH each time they appear; R w Each occurrence is independently selected from O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 alkyl); When W1 and W2 appear, they are each independently selected from CH2 and C(O), and at least one of W1 and W2 is C(O); When there is a double bond between W4 and W5, and a single bond between W5 and W6, W4 is C, and W5 is selected from N, CH, and C(C) 1-3 Alkyl), W6 is selected from NH, N(C) 1-3 Alkyl), O, CH2, CH(C) 1-3 alkyl) and C(C) 1-3 Alkyl)2; when there is a single bond between W4 and W5 and a double bond between W5 and W6, W4, W5, and W6 are each independently selected from N, CH, and C (C 1-3 Alkyl); when there are single bonds between W4, W5, and W6, W4 is selected from N, CH, and C (C 1-3 Alkyl groups, W5 and W6 are each independently selected from C(O), NH, N(C) 1-3 Alkyl), O, CH2, CH(C) 1-3 alkyl) and C(C) 1-3 Alkyl)2; W8 and W 10 Each occurrence is independently selected from O, NH, N(C) 1-3 Alkyl), CH(C) 1-3 Alkyl), C(C) 1-3 Alkyl)2 and CH-C 3-6 Cycloalkylene; W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(C) 1-3 alkyl); R 2a Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl and 3-8 membered heterocyclic groups; preferably, R 2a Each occurrence is independently selected from H, F, Cl, Br, C. 1-3 Alkyl and C 1-3 Halogenated alkyl groups; R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5g Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl; A a A b A c A d A e A f and A h Each occurrence is independently selected from O, S, C(O), NR. d and C(R) d )2, R d Each occurrence is independently selected from H, F, Cl, Br, -OH, -CN, -NH2, -NO2, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl; B 1a and B 2a Each occurrence is independently selected from N, CH, and C(C) 1-3 alkyl); Each time m11, m21 and m31 appear, they are independently 0, 1, 2, 3 or 4, and 1≤m11+m21+m31≤5; Each occurrence of m41 and m51 is independently 0, 1, 2, 3, or 4, and 1 ≤ m41 + m51 ≤ 5; and Each time m61 and m71 appear, they are independently 0, 1, 2, 3 or 4, and 1≤m61+m71≤5; Preferably: Each occurrence of X is independently N; and / or W1 is C (=O), and W2 is CH2; W1 is CH2, and W2 is C (=O); or W1 is (=O), and W2 is C (=O); and / or When W4 and W5 form a double bond and W5 and W6 form a single bond, W4 is C, W5 is selected from N, CH, and C(CH3), and W6 is selected from NH, N(CH3), O, CH2, CH(CH3), and C(CH3)2; when W4 and W5 form a single bond and W5 and W6 form a double bond, W4, W5, and W6 are each independently selected from N, CH, and C(CH3); when W4, W5, and W6 are all single bonds, W4 is selected from N, CH, and C(CH3), and W5 and W6 are each independently selected from C(O), NH, N(CH3), O, CH2, CH(CH3), and C(CH3)2; and / or W8 and W 10 Each time it appears, it is independently selected from O, NH, N(CH3), CH(CH3), C(CH3)2 and CH-C. 3-5 Cycloalkylene; and / or W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(CH3); and / or A a A b A c A d A e A f and A h Each time it appears, it is independently selected from CH2, C(C) 1-3 Alkyl)2, CH(C) 1-3 Alkyl), NH, N(C) 1-3 Alkyl groups), C(O) and O; preferably, A a A b A c A d A e A f and A h Each occurrence is independently selected from CH2, C(CH3)2, CH(CH3), NH, N(CH3), or C(O); preferably, A a A b A c A d A e A f and A h Each occurrence is independently selected from CH2; and / or Each occurrence of m11, m21, and m31 is independently 0, 1, 2, or 3, and 1 ≤ m11 + m21 + m31 ≤ 4; preferably, m11 + m21 + m31 = 1, m11 + m21 + m31 = 2, m11 + m21 + m31 = 3, or m11 + m21 + m31 = 4; and / or Each occurrence of m41 and m51 is independently 0, 1, 2, or 3, and 1 ≤ m41 + m51 ≤ 4; preferably, m41 + m51 = 2, m41 + m51 = 3, or m41 + m51 = 4; and / or Each occurrence of m61 and m71 is independently 0, 1, 2, or 3, and 1 ≤ m61 + m71 ≤ 4; preferably, m61 + m71 = 2, m61 + m71 = 3, or m61 + m71 = 4; and / or R 2a Each time it appears, it is independently selected from H, F, Cl, Br, and C. 1-3 Alkyl; preferably, R 2a Each occurrence is independently -CH3; and / or B 1a and B 2a Each occurrence is independently selected from N, CH, and C(CH3); preferably, B 1a and B 2a Each occurrence is independently selected from N and CH; and / or R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5g Each time it appears, it is independently selected from H, F, Cl, Br, cyano, hydroxyl, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups and C 1-3 Hydroxyalkyl; preferably, R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5g Each occurrence is independently selected from H, F, Cl, Br, -CN, -OH, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -OCH2CH3, and -OCH(CH3)2; preferably, R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3e R 4e R 3f R 4f R 3g R 4g and R 5g Each time it appears, it is independently selected from H, F, Cl, Br, -CN, -OH, -CH3 and -OCH3.

15. The compound according to any one of claims 1-14, wherein, The ULM is selected from the following structures: Preferably, the ULM is selected from the following structures:

16. The compound according to any one of claims 1-15, wherein, The L is -(B) L ) q -; B L Each occurrence is independently selected from covalent bonds, CR L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 C(O), 3-15 member monocyclic cyclohexane, 3-15 member monocyclic heterocyclic group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 5-15 member bridged cyclohexane, 5-15 member spirocyclic group, 5-15 member spirocyclic group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, 6-15 member aryl group and 5-15 member heteroaryl group containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O and S, wherein the cycloalkyl group, heterocyclic group, bridged cyclohexane, bridged cyclohexane, spirocyclic group, spirocyclic group, aryl group and heteroaryl group are optionally 1-6 heteroatoms independently selected from R L1 Substitution of groups; R L1 and R L2 Each occurrence is independently selected from H, halogens, -OH, -NH2, -SH, -C(O)2H, -CN, -NO2, -S(O)2H, -SF5, -C≡CH, C 1-8 Alkyl, C 1-8 Alkoxy, -SC 1-8 Alkyl, -NH-C 1-8 Alkyl, N(C) 1-8 Alkyl)2, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, -OC 3-8 Cycloalkyl, -O-3-8 membered heterocyclic groups, -OC 6-10 Aryl, -O-5-10 heteroaryl, -SC 3-8 cycloalkyl, -NH-C 3-8 cycloalkyl, -N(C) 3-8 cycloalkyl)2, -N(C 3-8 cycloalkyl)(C 1-8 Alkyl), -NH-3-8-membered heterocyclic group, -N(3-8-membered heterocyclic group)2, -N(3-8-membered heterocyclic group) (C 1-8 alkyl), -NH-C 6-10 Aryl, -N(C 6-10 Aryl)(C 1-8 alkyl), -NH-C 5-10 heteroaryl, -N (5-10 quinone heteroaryl) (C 1-8 Alkyl), -S(O)2P(O)(C 1-8 Alkoxy)(C 1-8 Alkyl), -P(O)(C 1- 8-alkoxy)2、-C≡CC 1-8 Alkyl group, -CH=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl)=CH-(C 1-8 alkyl), -C(C 1-8 Alkyl) = C(C 1-8 Alkyl group 2, -Si(OH)3, -Si(C) 1-8 Alkyl)3、-Si(OH)(C 1-8 Alkyl)2、-C(O)-C 1-8 Alkyl group, -S(O)2NH-C 1-8 Alkyl group, -S(O)2N(C) 1-8 Alkyl)2、-S(O)NH-C 1-8 Alkyl, -S(O)N(C) 1- 8-alkyl)2、-C(O)NH-C 1-8 Alkyl, -C(O)N(C) 1-8 Alkyl)2, -N(C 1-8 alkyl)C(O)NH(C 1-8 alkyl), -N(C) 1-8 alkyl)C(O)N(C 1-8 alkyl)2、-NHC(O)NH(C 1-8 Alkyl), -NHC(O)N(C 1-8 Alkyl)2, -NHC(O)NH2, -N(C 1-8 alkyl)S(O)2NH(C 1-8 alkyl), -N(C) 1-8 alkyl)S(O)2N(C 1- 8-alkyl)2、-NHS(O)2NH(C 1-8 Alkyl), -NHS(O)2N(C 1-8 alkyl)2 and -NHS(O)2NH2, the C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently selected from halogen, hydroxyl, cyano, amino, nitro, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-8 cycloalkyl, C 3-8 Halogenated cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered halocyclic heterocyclic group, C 6-10 Aryl, C 6-10 The substituent is one or more of the following: haloaryl, 5-10 heteroaryl, and 5-10 haloheteraryl. and q is selected from integers greater than or equal to 1 and less than or equal to 15; Preferably: B L Each occurrence is independently selected from covalent bonds, CR L1 R L2 O, S, S(O), S(O)2, NR L1 C(O)NR L1 The following are listed: C(O), 3-12 membered monocyclic cyclohexane, 3-12 membered monocyclic heterocyclic group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 5-12 membered bridged cyclohexane, 5-12 membered bridged cyclohexane containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 5-12 membered spirocyclic group, 5-12 membered spirocyclic group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, 6-12 membered aryl group, and 5-12 membered heteroaryl group containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, wherein the cycloalkyl group, heterocyclic group, bridged cyclohexane, bridged cyclohexane, spirocyclic group, spirocyclic group, aryl group, and heteroaryl group are optionally composed of 1, 2, 3 or 4 heteroatoms independently selected from R L1 Substitution of groups; R L1 and R L2 Each occurrence is independently selected from H, F, Cl, Br, I, -OH, -NH2, -C(O)2H, -CN, -NO2, -S(O)2H, C 1-6 Alkyl, C 1-6 Alkoxy group, -C(O)-C 1-6 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from F, Cl, Br, I, hydroxyl, cyano, amino, nitro, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Heteroalkyl, C 1-3 Halogenated heteroalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, 3-6 membered heterocyclic group, 3-6 membered halocyclic heterocyclic group, C 6-8 Aryl, C 6-8 Substituted by one or more substituents of haloaryl, 5-8-membered heteroaryl, and 5-8-membered haloaryl; and q is selected from integers greater than or equal to 1 and less than or equal to 12; preferably, q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10; preferably, q is selected from 1, 2, 3, 4, 5, 6, 7 and 8. Preferably: B L Selected from one or more of the following structures: single bond, -O-, -S-, -S(O)-, -S(O)2-, -C≡C-, -CH2-, -C(O)-, -NH-, q is 1, 2, 3, 4, 5, 6, 7, or 8; preferably, q is 1, 2, 3, 4, 5, or 6; and This is the connection point.

17. The compound according to any one of claims 1-16, wherein, The L is selected from the following structures: Single bond, -(CH2) j -、-C(O)-、-(CH2) j -C(O)-, -NH-(CH2) j -、-(CH2) j -NH-, -NH-(CH2) j -NH-、 Where j appears independently as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 each time; and Each time p and y appear, they are independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; Preferably, the L is selected from the following structures: covalent bond, -CH2-, -C(O)-, -CH2-C(O)-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -NH-CH2-, -NH-(CH2)2-, -NH-(CH2)3-, -NH-(CH2)4-, -NH-(CH2)5-, -NH-(CH2)6-, -NH-(CH2)7-, -NH-(CH2)8-, -C(O)-NH-CH2-, -C(O)-NH-(CH2)2-, -C(O)-NH-(CH2)3-, -C(O)-NH-(CH2)4-, -C(O)-NH-(CH2)5-, -C(O)-NH-(CH2)6-, -C(O)-NH-(CH2)7-, -C(O)-NH-(CH2)8-, -CH2-NH-, -(CH2)2-NH-, -(CH2)3-NH-, -(CH2 )4-NH-, -(CH2)5-NH-, -(CH2)6-NH-, -(CH2)7-NH-, -(CH2)8-NH-, -NH-CH2-NH-, -NH-(CH2)2-NH-, -NH-(CH2)3-NH-, -NH-(CH2)4-NH-, -NH-(CH2)5-N H-, -NH-(CH2)6-NH-, -NH-(CH2)7-NH-, -NH-(CH2)8-NH-, -C(O)-NH-CH2-NH-, -C(O)-NH-(CH2)2-NH-, -C(O)-NH-(CH2)3-NH-, -C(O)-NH-(CH2)4-NH -, -C(O)-NH-(CH2)5-NH-, -C(O)-NH-(CH2)6-NH-, -C(O)-NH-(CH2)7-NH-, -C(O)-NH-(CH2)8-NH-, -(CH2-CH2-O)-CH2-CH2-, -(CH2-CH2-O)2-CH2-C H2-, -(CH2-CH2-O)3-CH2-CH2-, -NH-(CH2-CH2-O)-CH2-CH2-, -NH-(CH2-CH2-O)2-CH2-CH2-, -NH-(CH2-CH2-O)3-CH2-CH2-, -C(O)-NH-(CH2-CH2-O )-CH2-CH2-, -C(O)-NH-(CH2-CH2-O)2-CH2-CH2-, -C(O)-NH-(CH2-CH2-O)3-CH2-CH2-, -(CH2-CH2-O)-CH2-CH2-NH-, -(CH2-CH2-O)2-CH2-CH2-NH-,-(CH2-CH2-O)3-CH2-CH2-NH-、-NH-(CH2-CH2-O)-CH2-CH2-NH-、-NH-(CH2-CH2-O)2-CH2-CH2-NH-、-NH-(CH2-CH2-O)3-CH2-CH2-NH-、-C(O)-NH-(CH2-CH2-O)-CH2-CH2-NH-、-C(O)-NH-(CH2-CH2-O)2-CH2-CH2-NH- -C(O)-NH-(CH2-CH2-O)3-CH2-CH2-NH-,-CH2-CH2-(O-CH2-CH2)-,-CH2-CH2-(O-CH2-CH2)2-,-CH2-CH2-(O-CH2-CH2)3-,-NH-CH2-CH2-(O-CH2-CH2)-,-NH-CH2-CH2-(O-CH2-CH2)2-,-NH-CH2-CH2-(O-CH2-CH2)3- 、-C(O)-NH-CH2-CH2-(O-CH2-CH2)-、-C(O)-NH-CH2-CH2-(O-CH2-CH2)2-、-C(O)-NH-CH2-CH2-(O-CH2-CH2)3-、-CH2-CH2-(O-CH2-CH2)-NH-、-CH2-CH2-(O-CH2-CH2)2-NH-、-CH2-CH2-(O-CH2-CH2)3-NH-、-NH-CH2- CH2-(O-CH2-CH2)-NH-,-NH-CH2-CH2-(O-CH2-CH2)2-NH-,-NH-CH2-CH2-(O-CH2-CH2)3-NH-,-C(O)-NH-CH2-CH2-(O-CH2-CH2)-NH-,-C(O)-NH-CH2-CH2-(O-CH2-CH2)2-NH-,-C(O)-NH-CH2-CH2-(O-CH2-CH2)3-NH-, Preferably, the L is selected from the following structures: single bond, -CH2-, 18. A compound having the structure shown in formula (I-AA) or formula (I-BB): Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: Q0 is selected independently from O, S, C(O), and C(R) each time it appears. X )2 and NR X ; Q1 is selected independently from O, S, and NR each time it appears. X ; p2 and p3 are each independently selected from 0, 1, and 2 each time they appear; y0 is selected from 0 and 1; Each time the ring C appears, it is independently selected from 3-8 membered cycloalkyl groups, 3-8 membered monocyclic heterocyclic groups containing 1-4 saturated or partially unsaturated heteroatoms selected independently from N, O and S, and 5-8 membered monocyclic heteroaryl groups containing 1-4 heteroatoms selected independently from N, O and S. L b Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -O-, -NH-, -C(O)-, -C(O)-O-, -C(O)-C 1-3 Alkylene, -N(C) 1-3 alkyl) and -N(C) 1- 3alkyl)-C(O); L c Each time it appears, it is independently selected from single-key, C 1-3 Alkylene, -C(O), -C(O)-C 1-3 Alkylene, -C(O)-cyclopropylene, -N(C 1-3 alkyl)-C(O) and -N(C 1- 3alkyl)-C(O)-C 1-3 Alkylene; R A Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-3 Alkyl and C 1-3 Alkoxy; R B Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)-C. 1-3 Alkyl and C 1-3 Alkyl; R C Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, and C. 1-3 alkyl; R D Each occurrence is independently selected from H, F, Cl, Br, I, R. X 、N(R X 2. C(O)R X and C(O)N(R) X )2; R X Each occurrence is independently selected from H, F, Cl, Br, I, C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-membered, 5-membered, 6-membered or 7-membered heterocyclic groups containing 1, 2 or 3 heteroatoms each independently selected from N, O and S, and 6-membered halocyclic groups containing 1, 2 or 3 heteroatoms each independently selected from N, O and S. L is the chemical bonding part; and ULM is the E3 ubiquitin ligase binding site.

19. The compound of claim 18, wherein, The L is defined as in any one of claims 1-17; preferably, the L is -(B L ) q -; B L Each occurrence is independently selected from covalent bonds, CR L5 R L6 O, S, S(O), S(O)2, NR L5 C(O)NR L5 C(O), 3-12 membered cycloalkylene groups, 3-12 membered heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered bridged heterocyclic groups, 5-12 membered bridged heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered spirocyclic groups, 5-12 membered spirocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 6-1 The 2-membered arylene and 5-12-membered heteroarylene containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein the 3-12-membered cycloalkylene, 3-12-membered heterocyclic, 5-12-membered bridged cycloalkyl, 5-12-membered bridged heterocyclic, 5-12-membered spirocyclic, 5-12-membered spirocyclic, 6-12-membered arylene, and 5-12-membered heteroarylene are optionally represented by 1, 2, 3, or 4 heteroatoms independently selected from R. L5 Substitution of groups; R L5 and R L6 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from C. 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 3-6 Halogenated cycloalkyl, 3-6-membered halogenated heteroalkyl, C 6-8 Aryl, 5-8 quinone heteroaryl, C 6-8 The aryl group is substituted by one or more substituents in the 5-8 membered haloaryl group; q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and / or The ULM is selected from the structure shown in the following formula: Preferably, the ULM is selected from the structure shown in the following formula: in: Each time X appears, it is independently selected from N, CH, C(C). 1-6 alkyl) and C(C) 3-6 (cycloalkyl); preferably, X is independently selected from N and CH each time it appears; R W Each occurrence is independently selected from O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 alkyl); When W1 and W2 appear, they are each independently selected from CH2 and C(O), and at least one of W1 and W2 is selected from C(O); W8 and W 10 Each occurrence is independently selected from O, NH, N(C) 1-3 Alkyl), CH(C) 1-3 Alkyl), C(C) 1-3 Alkyl)2 and CH-C 3-6 Cycloalkylene; W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(C) 1-3 alkyl); R q Each occurrence is independently selected from single bonds and NH; R 2a Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl and 3-8 membered heterocyclic groups; preferably, R 2a Each occurrence is independently selected from H, F, Cl, Br, C. 1-3 Alkyl and C 1-3 Halogenated alkyl groups; R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3f R 4f R 5f R 3g R 4g and R 5g Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl; A a A b A c A d and A e Each occurrence is independently selected from O, S, C(O), NR. d and C(R) d )2, R d Each occurrence is independently selected from H, F, Cl, Br, -OH, -CN, -NH2, -NO2, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6 Hydroxyalkyl; B 1a and B 2a Each occurrence is independently selected from N, CH, and C(C) 1-3 Alkyl); preferably, B 1a and B 2a Each occurrence is independently selected from N and CH; Each occurrence of m11, m21, and m31 is independently 0, 1, 2, 3, or 4, and 1 ≤ m11 + m21 + m31 ≤ 5; and Each time m41 and m51 appear, they are independently 0, 1, 2, 3 or 4, and 1≤m41+m51≤5; Preferably: Q0 is selected independently from O, S, CH2, C(O) and NR each time it appears. X Preferably, each occurrence of Q0 is independently selected from O, C(O), S, CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); preferably, each occurrence of Q0 is independently selected from O, CH2, NH, N(CH(CH3)2), N(CH3), and N(CH2CH3); preferably, each occurrence of Q0 is independently selected from O and CH2; and / or Q1 is selected independently from O, S, and NH each time it appears; and / or p2 and p3 are each independently selected from 0 and 1 each time they appear; and / or y0 is 1; and / or Each time ring C appears, it is independently selected from any chosen element R. C Replacement Preferably, each occurrence of ring C is independently selected from any of the arbitrarily chosen R. C Replacement and / or L b Each occurrence is independently selected from single bonds, -CH2-, -CH2CH2-, and -CH2CH2CH2-; preferably, L b For single bonds; and / or L c Each occurrence is independently selected from single bonds, -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -C(O)-CH2-, -C(O)-CH2CH2-, -C(O)-cyclopropylidene, -N(CH3)-C(O)-, and -N(CH3)-C(O)-CH2CH2-; preferably, L c -C(O)-CH2CH2-; and / or R A Each occurrence is independently selected from H, F, Cl, Br, I, -CH3, -CH2CH3, -CH(CH3)2, -OCH3, and -OCH2CH3; and / or R B Each occurrence is independently selected from H, F, Cl, Br, I, oxo group (=O), -CH3, -CH2CH3 and -C(O)-CH3; and / or R C Each occurrence is independently selected from H, F, Cl, Br, I, -CH3, and -CH2CH3; and / or R D Each occurrence is independently selected from H, F, Cl, Br, I, -OCH3, -CH3, -CH2CH3, -CH(CH3)2, -N(CH3)2, -N(CH3)(CH2CH3), -C(O)-NH(CH3), -C(O)-NH(CH2CH3), -C(O)-N(CH3)2, -C(O)-N(CH3)(CF3), -C(O)-N(CH3)(CH2CH3), -C(O)-N(CH3)(CH(CH3)2), -C(O)-N(CH2CH3)(CH(CH3)2), Preferably, R D -C(O)-N(CH3)2; and / or R X Each occurrence is independently selected from H, F, Cl, Br, I, -CF3, -OCH3, -CH3, -CH2CH3, -CH(CH3)2. and / or B L Each occurrence is independently selected from single bonds, -O-, -S-, -S(O)-, -S(O)2-, -C≡C-, -CH2-, -C(O)-, -NH-, -N(CH3)-, -N(CH2CH3)-, -C(O)-NH-, -C(O)-N(CH3)-, and / or R L5 and R L6 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, -C(O)-C 1-3 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from C. 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-8 The aryl group is substituted with one or more substituents from the 5-8 membered heteroaryl group; preferably, R L5 and R L6 Each time it appears, it is independently selected from H, F, Cl, Br, hydroxyl, cyano, nitro, amino, C. 1-3 Alkyl, C 1-3 Alkoxy, -CF3, -CHF2, -CH2F, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups; and / or q is selected from 1, 2, 3, 4, 5, 6, 7, and 8; preferably, q is selected from 1, 2, 3, 4, 5, and 6; and / or Each occurrence of X is independently N; and / or R W Each occurrence is independently selected from O, C(O)NH, C(O)N(C) 1-3 Alkyl), NH and N(C) 1-3 Alkyl); and / or W1 is C (=O), W2 is CH2; W1 is CH2, W2 is C (=O); or W1 is C (=O), W2 is C (=O); and / or W8 and W 10 Each time it appears, it is independently selected from O, NH, N(CH3), CH(CH3), C(CH3)2 and CH-C. 3-5 Cycloalkylene; and / or W9, W 12 and W 13 Each occurrence is independently selected from N, CH, and C(CH3); and / or R 2a Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -CH2CH2F; and / or R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3f R 4f R 5f R 3g R 4g and R 5g Each occurrence is independently selected from H, F, Cl, Br, -CN, -NO2, -CH3, -CH2CH3, -CH(CH3)2, -OCH3, -OCH2CH3, and -OCH(CH3)2; preferably, R 3a R 4a R 3b R 4b R 3c R 4c R 5c R 3d R 4d R 5d R 3f R 4f R 5f R 3g R 4g and R 5g Each occurrence is independently selected from H, F, Cl, Br, -CN, -NO2, -CH3, and -OCH3; and / or A a A b A c A d and A e Each occurrence is independently selected from O, C(O), and NR. d and C(R) d )2, R d Each occurrence is independently selected from H, F, Cl, Br, -OH, -CN, -NH2, -NO2, C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy groups and C 1-3 Hydroxyalkyl; preferably, A a A b A c A d and A e Each occurrence is independently CH2; and / or B 1a and B 2a Each occurrence is independently selected from N and CH; and / or Each occurrence of m11, m21, and m31 is independently 0, 1, 2, or 3, and 1 ≤ m11 + m21 + m31 ≤ 4; preferably, m11 + m21 + m31 = 1, m11 + m21 + m31 = 2, m11 + m21 + m31 = 3, or m11 + m21 + m31 = 4; preferably, each occurrence of m11 is independently 0 or 1, each occurrence of m21 is independently 1, and each occurrence of m31 is independently 0 or 1; preferably, each occurrence of m11 is independently 0, each occurrence of m21 is independently 1, and each occurrence of m31 is independently 0; and / or Each time m41 and m51 appear, they are independently 0, 1, 2, or 3, and 1 ≤ m41 + m51 ≤ 4; preferably, m41 + m51 = 2, m41 + m51 = 3, or m41 + m51 = 4; preferably, each time m41 and m51 appear, they are independently 2.

20. The compound of claim 18 or 19, having the structure shown in formula (I-AA-1) or formula (I-BB-1): in, Q0, Q1, p2, p3, y0, ring C, L b L c R A R B R C R D L, X, R 2a R 3a R 4a A a A b A c A d A e m11, m21, m31, m41 and m51 are as defined in claim 18 or 19; Preferably: Each occurrence of Q0 is independently selected from O and CH2; and / or Q1 is selected independently from O, S, and NH each time it appears; and / or p2 and p3 are each independently selected from 0 and 1 each time they appear; and / or y0 is 1; and / or Each time ring C appears, it is independently selected from any chosen element R. C Replacement and / or L b Each occurrence is an independent single key; and / or L c Each occurrence is independently -C(O)-CH2CH2-; and / or R A Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -OCH3; and / or R B Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -OCH3; and / or R C Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -OCH3; and / or R D Each occurrence is independently -C(O)-N(CH3)2; and / or L is a chemically bonded portion; preferably, L is as defined in any one of claims 1-19; preferably, L is -(B L ) q -; B L Each occurrence is independently selected from covalent bonds, CR L5 R L6 O, S, S(O), S(O)2, NR L5 C(O)NR L5 C(O), 3-12 membered cycloalkylene groups, 3-12 membered heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered bridged heterocyclic groups, 5-12 membered bridged heterocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 5-12 membered spirocyclic groups, 5-12 membered spirocyclic groups containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, 6-1 The 2-membered arylene and 5-12-membered heteroarylene containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein the 3-12-membered cycloalkylene, 3-12-membered heterocyclic, 5-12-membered bridged cycloalkyl, 5-12-membered bridged heterocyclic, 5-12-membered spirocyclic, 5-12-membered spirocyclic, 6-12-membered arylene, and 5-12-membered heteroarylene are optionally represented by 1, 2, 3, or 4 heteroatoms independently selected from R. L5 Substitution of groups; R L5 and R L6 Each time it appears, it is independently selected from H, halogen, hydroxyl, cyano, amino, nitro, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally selected from C. 1-3 Alkyl, C 1-3 Heteroalkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 3-6 Halogenated cycloalkyl, 3-6-membered halogenated heteroalkyl, C 6-8 Aryl, 5-8 quinone heteroaryl, C 6-8 The aryl group is substituted by one or more substituents in the 5-8 membered haloaryl group; Preferably, in formula (I-AA) or formula (I-AA-1), L is selected from 3-12-membered heterocyclic groups, 3-12-membered heterocyclic groups-C(O), and 3-12-membered heterocyclic groups-C 1-6 Alkylene, wherein the 3-12 membered heterocyclic group contains 1-4 heteroatoms independently selected from N, O, and S, and the 3-12 membered heterocyclic group and C 1-6 The alkylene group is optionally selected independently by one, two, three, or four R groups. L5 Substitution of groups; and / or In formula (I-BB) or formula (I-BB-1), L is selected from phenylene-3-12-membered heterocyclic group-C 1-6 Alkylene, 3-12 membered heterocyclic phenylene-C 1-6 Alkylene, phenylene-3-12-membered heterocyclic-C(O), and 3-12-membered heterocyclic-phenylene-C(O), wherein the 3-12-membered heterocyclic group contains 1-4 heteroatoms independently selected from N, O, and S, wherein the 3-12-membered heterocyclic group, phenylene, and C 1-6 The alkylene group is optionally selected independently by one, two, three, or four R groups. L5 Substitution of groups; R L5 Each time it appears, it is independently selected from OH, CN, F, Cl, Br, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic groups; preferably, R L5 Each time it appears, it is independently selected from the substitution of groups such as OH, CN, F, Cl, Br, CH3, CH2CH3, CH(CH3)2, OCH3, OCH2CH3, OCH2CH2F and cyclopropyl. Preferably, the 3-12 membered heterocyclic group is a 5-8 membered heterocyclic group, preferably selected from piperazinyl and piperidinyl, and more preferably selected from... and / or q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and / or Each occurrence of X is independently N; and / or R 2a Each occurrence is independently selected from H, F, Cl, Br, -CH3, and -CH2CH2F; and / or A a A b A c A d and A e Each occurrence is independently CH2; and / or Each occurrence of m11, m21, and m31 is independently 0, 1, 2, or 3, and 1 ≤ m11 + m21 + m31 ≤ 4; preferably, m11 + m21 + m31 = 1, m11 + m21 + m31 = 2, m11 + m21 + m31 = 3, or m11 + m21 + m31 = 4; and / or Each time m41 and m51 appear, they are independently 0, 1, 2, or 3, and 1≤m41+m51≤4; preferably, m41+m51=2, m41+m51=3 or m41+m51=4.

21. The compound according to any one of claims 1-20, wherein the compound is selected from the group consisting of: Preferably, the compound is selected from the compounds in Examples 7-28.

22. A compound having the structure shown in formula (III): Or its isomers, isotopic derivatives, polymorphs, prodrugs, or pharmaceutically acceptable salts or solvates thereof, wherein: Ring B, Ring C, p1, p2, p3, L b L c R A R B R C and R D Same as the definition of any one of claims 1-21; Ring A1 is selected from 8-10 membered bicyclic heteroaryl groups containing 1-5 independently selected N, O, and S heteroatoms; 11-15 membered tricyclic heteroaryl groups containing 1-5 independently selected N, O, and S heteroatoms; 11-15 membered tricyclic heterocyclic groups containing 1-5 independently selected N, O, and S heteroatoms, either saturated or partially unsaturated; and 16-20 membered tetracyclic heterocyclic groups containing 1-5 independently selected N, O, and S heteroatoms, either saturated or partially unsaturated, wherein the tricyclic and tetracyclic heterocyclic groups are fused rings, spirocyclic rings, or spirofused ring structures; and R E Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)H, C 1-8 Alkyl, C 1- 8-alkoxy group, -C(O)-C 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl, 5-8 quinone heteroaryl and -C 6-8 arylene-3-8-membered heterocyclic group, wherein C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-8 Aryl, 5-8 quinone heteroaryl and C 6-8 arylene, optionally selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C 1-6 Alkyl and C 1-6 The alkoxy group is substituted by one or more substituents; When R E When connected to a N atom, R E Selected from H and C 1-8 alkyl.

23. The compound of claim 22, wherein, Ring A1 is selected from 9-10 membered bicyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heteroaryl groups containing 1-4 heteroatoms independently selected from N, O, and S; 12-15 membered tricyclic heterocyclic groups containing 1-4 heteroatoms independently selected from N, O, and S; and 16-18 membered tetracyclic heterocyclic groups containing 1-4 heteroatoms independently selected from N, O, and S; wherein the tricyclic and tetracyclic heterocyclic groups are fused rings, spirocyclic rings, or spirofused fused ring structures; preferably, ring A1 is selected from those containing 1, 2, or 3 heteroatoms. Alternatively, it may contain 9- or 10-membered bicyclic heteroaryl groups with four independently selected N, O, and S heteroatoms; 13-membered tricyclic heteroaryl groups with one, two, or three independently selected N, O, and S heteroatoms; partially unsaturated 12-, 13-, 14-, or 15-membered tricyclic heterocyclic groups with one, two, or three independently selected N, O, and S heteroatoms; and partially unsaturated 16-, 17-, or 18-membered tetracyclic heterocyclic groups with one, two, three, or four independently selected N, O, and S heteroatoms, wherein the tricyclic and tetracyclic heterocyclic groups are fused rings, spirocyclic rings, or spirofused fused ring structures; preferably, ring A1 is selected from... Each occurrence of Q is independently selected from O, S, and NR. X Each time Q0 appears, it is independently selected from O, S, C(R). X )2 and NR X R X As defined in any one of claims 1-21; preferably, ring A1 is selected from... and / or R E Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)H, C 1-6 Alkyl, C 1- 6-alkoxy group, -C(O)-C 1-6 Alkyl, C 3-6 cycloalkyl, 5-6 membered heterocyclic, C 6-7 Aryl, 5-6 quinone heteroaryl and -C 6-7 arylene-5-6-membered heterocyclic group, wherein C 3-6 cycloalkyl, 5-6 membered heterocyclic, C 6-7 Aryl, 5-6 membered heteroaryl and C 6-7 arylene, optionally selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), C 1-6 Alkyl and C 1-6 The alkoxy group is substituted by one or more substituents; When R E When connected to a N atom, R E Selected from H and C 1-6 alkyl.

24. The compound of claim 22 or 23, wherein the compound is selected from the structure shown in the following formula: in, Ring B, Ring C, L b L c R A R B R C R D R E p1, p2 and p3 are as defined in claim 22 or 23; Q2 is selected independently from CR each time it appears. A , N, C(R) A 2. NR A and C; This indicates that two double bonds are formed at any position within the ring, together with Q2 on the ring, to form a conjugated system; In equations (IC-1) and (IE-1), Q1 is independently selected from O, S, and NR each time it appears. X ; In (IA-1), R 5g Does not exist, or R 5g With R 5a Or R 5f Together they form Cy6; When R 5g When Q1 does not exist, each occurrence of Q1 is independently selected from O, S, and NR. X When R 5g With R 5a Or R 5f When they jointly form Cy6, Q1 appears independently as N each time; R 5a R 5b R 5c R 5d R 5e R 5f and R 5g The definition is selected from one of the following groups; (v-1)R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b R 5d and R 5f Each occurrence is independently selected from R. A Substituents within the specified range; (v-2)R 5a and R 5b Together they form Cy3, which is optionally bounded by R D Replace, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5d and R 5f Each occurrence is independently selected from R. A Substituents within the specified range; (v-3)R 5b and R 5c Together they form Cy7, which is optionally bounded by R E Replace, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5d and R 5f Each occurrence is independently selected from R. A Substituents within the specified range; (v-4)R 5c and R 5d Together they form Cy7, which is optionally bounded by R E Replace, R 5e With L b Connected, and R 5e For a single bond, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R 5f Each occurrence is independently selected from R. A Substituents within the specified range; (v-5)R 5d and R 5e Together they form Cy5, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R 5f Each occurrence is independently selected from R. A Substituents within the specified range; (v-6)R 5e and R 5f Together they form Cy5, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5g It does not exist, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R 5d Each occurrence is independently selected from R. A Substituents within the specified range; (v-7)R 5f and R 5g Together they form Cy6, R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, Q1 is selected from N, R 5a Each time it appears, it is selected independently from R. D Substituents within the range, R 5b and R 5d Each occurrence is independently selected from R. A Substituents within the range; and (v-8)R 5g and R 5a Together they form Cy6, which is optionally bounded by R D Replace, and R 5c Each time it appears, it is selected independently from R. E Substituents within the range, R 5e With L b Connected, R 5b R 5d and R 5f Each occurrence is independently selected from R. A Substituents within the specified range; Cy3, Cy5, and Cy6 are as defined in claim 10; and Cy7 is independently selected and F1, F2, F3, F4, F5, q1, q2, q3, q4 and q5 are as defined in claim 10; Preferably: The compound is selected from the following structures: In this case, Q3 is selected independently from CH and N each time it appears; ring B, ring C, and ring L b L c R A R B R C R D As defined in claim 10; Preferably, R E Each time it appears, it is independently selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, oxo (=O), -C(O)H, C 1-3 Alkyl, C 1-3 Alkoxy, 5-6 membered heterocyclic, phenyl, and phenylene-5-6 membered heterocyclic, wherein the 5-6 membered heterocyclic, phenyl, and phenylene are optionally selected from H, F, Cl, Br, I, hydroxyl, nitro, cyano, amino, and C. 1-3 The alkyl group is substituted with one, two, or three substituents; when R E When connected to a N atom, R E Selected from H and C 1- 3-alkyl groups; Preferably, Cy7 is selected independently each time it appears. Preferably: The compound is selected from the following structures: Among them, Q0, Q1, Q3, Q4, p2, p3, y0, ring B1, ring C1, ring C2, L b L c R A R B R C and R D As defined in claim 22 or 23; R E Each time it appears, it is independently selected from H, F, Cl, Br, I, oxo group (=O), -C(O)H, C 1-3 Alkyl groups, 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms each independently selected from N, O, and S, phenyl groups, and phenylene-6-membered heterocyclic groups, wherein the 6-membered heterocyclic group, phenyl group, and phenylene group are optionally selected from H, F, Cl, Br, I, and C. 1-3 The alkyl group is substituted with one or two substituents; preferably, R E Each time it appears, it is independently selected from H, F, Cl, Br, I, oxo group (=O), -C(O)H, -CH3, -CH2CH3, -CH(CH3)2, and When R E When connected to a N atom, R E Selected from H, -CH3, -CH2CH3 and -CH(CH3)2.

25. The compound according to any one of claims 22-24, wherein the compound is selected from the following structures: Preferably, the compound is selected from the compounds in Examples 1-6.

26. A pharmaceutical composition comprising an effective amount of the compound as described in any one of claims 1-25 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

27. The use of any compound of claims 1-25 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 26, in the preparation of a medicament for treating or preventing diseases or conditions mediated by signal transduction and transcription activator 6 (STAT6) protein levels; preferably, the disease or condition is an autoimmune disease, cancer, inflammatory disease, genetic disease, metabolic disease, cardiovascular disease, or central nervous system disease; preferably, the disease or condition is a hematologic malignancy or lung cancer; preferably, the disease or condition is acute myeloid monocytic leukemia or non-small cell lung cancer (NSCLC); preferably, the disease or condition is asthma, atopic dermatitis, or chronic obstructive pulmonary disease.

28. The compound of any one of claims 1-25 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 26, for the treatment or prevention of a disease or condition mediated by the level of signal transduction and activating factor 6 (STAT6) protein; preferably, the disease or condition is an autoimmune disease, cancer, inflammatory disease, genetic disease, metabolic disease, cardiovascular disease, or central nervous system disease; preferably, the disease or condition is a hematologic malignancy or lung cancer; preferably, the disease or condition is acute myeloid monocytic leukemia or non-small cell lung cancer (NSCLC); preferably, the disease or condition is asthma, atopic dermatitis, or chronic obstructive pulmonary disease.

29. A method for treating or preventing a disease or condition mediated by signal transduction and activating factor 6 (STAT6) levels, comprising administering to a subject in need an effective amount of a compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1-25, or a pharmaceutical composition as described in claim 26; preferably, the disease or condition is an autoimmune disease, cancer, inflammatory disease, genetic disease, metabolic disease, cardiovascular disease, or central nervous system disease; preferably, the disease or condition is a hematologic malignancy or lung cancer; preferably, the disease or condition is acute myeloid monocytic leukemia or non-small cell lung cancer (NSCLC); preferably, the disease or condition is asthma, atopic dermatitis, or chronic obstructive pulmonary disease.

30. A method for degrading or inhibiting STAT6 in a patient or biological sample, the method comprising administering to the patient a compound of any one of claims 1-21 or a pharmaceutical composition of claim 26, or contacting the biological sample with a compound of any one of claims 1-21 or a pharmaceutical composition of claim 26; or STAT6 is brought into contact with the compound of any one of claims 22-25 or a pharmaceutically acceptable salt thereof; preferably, the contact is made in a patient or biological sample.

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