Proteolytic agents

Abstract

The application provides an AR protein degradation agent and a preparation method and application thereof. Specifically, the application provides a compound as shown in formula I or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, prodrug thereof. The compound of the application has superior target protein degradation efficiency and stronger anti-tumor cell proliferation effect.

Description

Technical Field

[0001] This invention relates to the pharmaceutical field, and more particularly to a protein degrading agent. Background Technology

[0002] Androgen receptors (ARs), belonging to the nuclear hormone receptor superfamily, are ligand-dependent transcription factors that play an indispensable core role in regulating normal prostate tissue development and the balance of epithelial cell proliferation and differentiation. Blocking the androgen receptor signaling pathway is a classic and highly effective strategy for the clinical treatment of prostate cancer and other androgen-related diseases, and it is also a core direction in the current development of targeted drugs for prostate cancer. Under physiological conditions, ARs maintain the normal structure and function of the prostate. However, under pathological conditions, abnormal amplification, point mutations, or splicing variants of ARs continuously activate downstream oncogenic signals, becoming key molecules driving the occurrence, progression, and even development of castration-resistant prostate cancer.

[0003] Protein degraders are a novel targeted intervention technology that has emerged rapidly in recent years. Unlike traditional small molecule inhibitors, which only inhibit protein function by occupying active sites, protein degraders can specifically recognize and efficiently degrade pathogenic target proteins by leveraging the intracellular ubiquitin-proteasome system. This eliminates key proteins that drive diseases at their source, providing a new treatment paradigm for traditionally difficult-to-drug targets and drug-resistant diseases.

[0004] Although existing AR-targeting small molecule inhibitors and protein degraders have shown some anti-tumor activity in preclinical studies and early clinical trials, bringing new hope for the treatment of prostate cancer, the overall efficacy of these drugs has not met expectations.

[0005] Therefore, there is a need in the field for an AR protein degrader with superior efficacy. Summary of the Invention

[0006] The purpose of this invention is to provide an AR protein degrader with high anti-tumor activity.

[0007] In a first aspect of the invention, a compound is provided, said compound being a compound of Formula I or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof. in, x and m are each independently 0, 1, 2, 3 or 4; X is selected from the following group: chemical bond, -O-, -NH-; The ring W1 is selected from the following group: C3-C8 cycloalkyl sub-groups, 3-8 membered heterocyclic sub-groups containing 1-4 heteroatoms selected from N, O, S, and P; R x R3 Each is independently selected from the following group: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuterylalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterylalkoxy, C1-C6 haloalkylthio, C3-C6 cycloalkyl, oxo, thio, -CN, -OH, -NH2, -NO2, -COOH, acetyl; “ " indicates a single or double bond; X 1 X 2 X 3 Each can be independently selected from C, N, or O, provided that X 1 X 2 When X is N 3 Not C; R 6 This refers to 1-3 substituents, each independently selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterated alkoxy, C1-C6 haloalkylthio, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, substituted or unsubstituted C 6-12 Aryl, -CN, -OH, -NH2, -NO2, -COOH, acetyl, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, oxo, thio, -CN, -OH, -NH2, -NO2, -COOH, acetyl; R 7 Selected from the following group: hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -NH2; R 8 Selected from the following group: C6-C 12 Aryl, C3-C 12Cycloalkyl groups, 4-12 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, and 5-12 membered heteroaryl groups containing 1-4 heteroatoms selected from N, O, S, and P, wherein the C6-C 12 Aryl, C3-C 12 The cycloalkyl, 4-12-membered heterocyclic, and 5-12-membered heteroaryl groups are optionally substituted by 1-4 substituents selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuteralkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuteralkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -(C 1-6 Alkylene, -hydroxy, -NH2, -NO2, -COOH, acetyl, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, wherein "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuterylalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterylalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -NH2, -(C 1-6 (alkylene)-hydroxy; L 1 for ; L 2 L 3 L 4 Each is independently selected from the group consisting of covalently bonded, substituted, or unsubstituted -C1-C6 alkylene groups, wherein any carbon atom on the C1-C6 alkylene group is optionally replaced by a heteroatom selected from O, N, and S; the term "substituted" means that one or more hydrogen atoms (e.g., 2, 3, or 4) on the group are independently replaced by groups selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and oxo groups. Ring V1 and ring V2 are either absent or contain 1-4 3-15 membered subheterocyclic groups selected from N, O, and S heteroatoms.

[0008] In another preferred embodiment, the compound of formula I is as shown in formula II: in, m can be 0, 1, 2, 3 or 4 independently; R 1 R 2R 3 Each is independently selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, oxo, -CN, -OH, -NH2; R 6 This refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, C3-C 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-12 Aryl, -CN, -OH, -NH2, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, oxo groups, thio groups, -CN, -OH, -NH2, -NO2; R 7 Selected from the following group: hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, -CN, -OH, -NH2; R 8 Selected from the following group: C6-C 12 Aryl, containing 1-4 5-12 membered heteroaryl groups selected from N, O, and S heteroatoms, wherein the C6-C 12 The aryl and 5-12 heteroaryl groups are optionally substituted with 1-4 substituents selected from the group consisting of: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, -(C 1-6 Alkylene, -hydroxy, oxo, thio, -CN, -OH, -NH2, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, where "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by groups selected from the following group: halogen, C1-C4 alkyl, C2-C6 alkenyl, C2-C6 ynyl, -(C 1-6 alkylene)-hydroxyl; L 1 Selected from the following group: -NH-(C1-C15 alkylene), -(C0-C5 alkylene)-(5-12 membered heterocyclic)-(C0-C5 alkylene)-, , The heterocyclic alkyl group contains 1-3 heteroatoms selected from N, O, and S; Where m1 is an independent integer from 0 to 5; Any carbon atom on the C0-C5 alkylene group is optionally replaced by N or O, and one or more hydrogen atoms (such as 2, 3 or 4) on the C0-C5 alkylene group are independently replaced by groups selected from the group consisting of: halogen, C1-C6 alkyl, C1-C6 haloalkyl, oxo, -CN, -OH, -NH2; T1, T2, T3, and T4 are each independently selected from C or N.

[0009] In another preferred embodiment, the compound of formula I is as shown in formula III-a or III-b: in, a can be 0, 1, or 2 independently; The ring E is selected from the following group: containing 1-2 5- or 6-membered heterocyclic groups selected from N, O, and S heteroatoms; R 1 R 2 Each is independently selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, oxo, -CN, -OH, -NH2; R 6 It refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, C3-C 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-12 Aryl, -OH, -NH2, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl, 3-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, and S, oxo groups, thio groups, -CN, -OH, -NH2, -NO2; R 7Selected from the following group: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, -CN, -OH, -NH2; R a Selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, -(C 1-6 Alkylene, hydroxyl, oxo, -CN, -NH2, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, wherein "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C 1-6 (alkylene)-hydroxyl, -CN, -OH, -NH2; L 1 Selected from the following group: -NH-(C2-C 13 alkylene), -(C0-C5 alkylene)-(5-12 membered heterocyclic)-(C0-C5 alkylene)-, , The heterocyclic alkyl group contains 1-3 heteroatoms selected from N, O, and S; Where m1 is an independent integer from 0 to 5; Any carbon atom on the C0-C5 alkylene group is optionally replaced by N, and one or more hydrogen atoms (such as 2, 3 or 4) on the C0-C5 alkylene group are independently replaced by groups selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, oxo, -CN, -OH, -NH2; T2 and T3 are each independently selected from C or N.

[0010] In another preferred embodiment, the compound of formula I is as shown in formulas IV-a, IV-b, IV-c, IV-d, or IV-e: in, n1 and n5 are each an independent integer between 0 and 12; n2, n3, and n4 are each independent integers between 0 and 4; T5 and T6 are each independently selected from C and N; W2 is Or a 5-12 membered subheterocyclic group containing 1-4 heteroatoms selected from N, O, and S; T2 and T3 are each independently selected from C or N; b and c are each independently 0, 1, or 2; R 1 R 2 Each is independently selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, oxo, -CN, -OH, -NH2; R 6 It refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C3-C... 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-12 Aryl, -OH, -NH2, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, thiogroups, -CN, -OH, -NH2, -NO2; R 7 Selected from the following group: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, -CN, -OH, -NH2; R b R c Each is independently selected from the following group: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, -(C 1-6 Alkylene)-hydroxyl, -CN, -OH, -NH2.

[0011] In another preferred embodiment, the compound of formula I is as shown in formula Va or Vb: in, n1 is any integer between 4 and 9; n2 and n3 are each independent integers between 0 and 3; R b Selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl; R 6It refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 alkylthio, C3-C... 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-10 Aryl, -OH, -NH2, where "substitution" means that one or more hydrogens (such as 2, 3 or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, -OH, -NH2.

[0012] In another preferred embodiment, X is -O- or -NH-.

[0013] In another preferred embodiment, X is -O-.

[0014] In another preferred embodiment, the ring W1 is selected from the group consisting of C3-C6 cycloalkyl groups and 3-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, and S.

[0015] In another preferred embodiment, the ring W1 is selected from the group consisting of: cyclopropyl, cyclobutyl, cyclopentyl, pyrrolyl, furanyl, pyrazolyl, imidazolyl, imidazolyl, and imidazolyl.

[0016] In another preferred embodiment, the ring W1 is selected from the group consisting of: cyclopropylene, cyclobutylene, and cyclopentylene.

[0017] In another preferred embodiment, m is 0, 1, 2, 3, or 4.

[0018] In another preferred embodiment, m is 2, 3, or 4.

[0019] In another preferred embodiment, the R 3 Selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, C3-C6 cycloalkyl, oxo, thio, -CN, -OH, -NH2, -NO2.

[0020] In another preferred embodiment, the R 3 Selected from the following group: halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 haloalkylthio, C3-C6 cycloalkyl, thiol, -CN, -OH, -NH2.

[0021] In another preferred embodiment, the R 3 Selected from the following groups: F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, methylthio, ethylthio, cyclopropyl, cyclobutyl, cyclopentyl, -CN, -OH, -NH2.

[0022] In another preferred embodiment, the R 3 Selected from the following groups: F, Cl, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, -CN, -OH, -NH2.

[0023] In another preferred embodiment, the R 3 Selected from the following group: methyl, ethyl, propyl, vinyl, propenyl, ethynyl.

[0024] In another preferred embodiment, x is 0, 1, 2 or 3.

[0025] In another preferred embodiment, x is 0, 1, or 2.

[0026] In another preferred embodiment, the R x Selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, C3-C6 cycloalkyl, oxo, thio, -CN, -OH, -NH2, -NO2.

[0027] In another preferred embodiment, the R x Selected from the following group: halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 haloalkylthio, C3-C6 cycloalkyl, thiol, -CN, -OH, -NH2.

[0028] In another preferred embodiment, the R x Selected from the following groups: F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, methylthio, ethylthio, cyclopropyl, cyclobutyl, cyclopentyl, -CN, -OH, -NH2.

[0029] In another preferred embodiment, the R x Selected from the following groups: F, Cl, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, -CN, -OH, -NH2.

[0030] In another preferred embodiment, the R xSelected from the following groups: F, Cl, -CN, -OH, -NH2.

[0031] In another preferred embodiment, the fragment Selected from the following group: pyridine, furanyl, imidazolyl, oxazolyl, thiazolyl, pyrrolinyl, 1,2,4-triazolyl, thiadiazolyl.

[0032] In another preferred embodiment, the fragment Selected from the following group: , .

[0033] In another preferred embodiment, the R 6 This refers to 1-3 substituents, each independently selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 deuterated alkoxy, C1-C4 haloalkylthio, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, and S, substituted or unsubstituted C 6-12 Aryl, -CN, -OH, -NH2, -NO2, -COOH, acetyl, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, oxo, thio, -CN, -OH, -NH2, -NO2, -COOH, acetyl.

[0034] In another preferred embodiment, the R 6 It refers to 1-3 substituents, each independently selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 haloalkylthio, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, and S, substituted or unsubstituted C 6-12Aryl, -OH, -NH2, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C 3-8 Cycloalkyl, -CN, -OH, -NH2, -NO2.

[0035] In another preferred embodiment, the R 6 It refers to two or three substituents, each independently selected from the group consisting of: substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C2-C4 alkenyl, C1-C4 alkoxy, substituted or unsubstituted C1-C4 alkylthio, substituted or unsubstituted C3-C... 10 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, and S, substituted or unsubstituted C 6-12 Aryl, -OH, -NH2, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C 3-8 Cycloalkyl, -OH, -NH2.

[0036] In another preferred embodiment, the R 6 It refers to 2 or 3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, C1-C4 alkylthio, C3-C 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, and S, C 6-10 Aryl, -OH, where "substitution" means that one or more hydrogens (such as 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C 3-8 Cycloalkyl, -OH, -NH2.

[0037] In another preferred embodiment, the R 6 This refers to 2 or 3 substituents, each independently selected from the following group: F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, methoxy, ethoxy, methylthio, ethylthio, cyclopropyl, cyclobutyl, cyclopentyl, 6-8 membered heterocyclic groups containing 1-2 heteroatoms selected from N, O, and S, phenyl, , -OH.

[0038] In another preferred embodiment, the R6 This refers to two or three substituents, each independently selected from the following group: methyl, ethyl, propyl, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, -OH, methylthio, ethylthio, phenyl. , .

[0039] In another preferred embodiment, the R 7 Selected from the following group: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 haloalkylthio, oxo, thio, -CN, -OH, -NH2.

[0040] In another preferred embodiment, the R 7 Selected from the following group: hydrogen, F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, methylthio, ethylthio, -CN, -OH, -NH2.

[0041] In another preferred embodiment, the R 7 Selected from the following group: hydrogen, F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl.

[0042] In another preferred embodiment, the R 8 Selected from the following group: C6-C 10 Aryl, C3-C8 cycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O, and S, 6-12 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, and S, wherein the C6-C 10 The aryl, C3-C8 cycloalkyl, 3-8-membered heterocyclic, and 6-12-membered heteroaryl groups are optionally substituted by 1-4 substituents selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 deuterylalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 deuterylalkoxy, C1-C4 haloalkylthio, oxo, thio, -CN, -OH, -(C 1-4Alkylene, -hydroxy, -NH2, -NO2, -COOH, acetyl, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, wherein "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 deuterylalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 deuterylalkoxy, C1-C4 haloalkylthio, oxo, thio, -CN, -OH, -NH2, -(C 1-6 (alkylene)-hydroxyl.

[0043] In another preferred embodiment, the R 8 Selected from the group consisting of: phenyl, cyclopropyl, cyclobutyl, cyclopentyl, pyridyl, imidazolyl, piperidinyl, thiazolyl, benzimidazole, benzothiazole, wherein the phenyl, cyclopropyl, cyclobutyl, cyclopentyl, pyridyl, imidazolyl, piperidinyl, thiazolyl, benzimidazole, benzothiazole are optionally substituted by 1-4 substituents selected from the group consisting of: deuterium, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 haloalkylthio, oxo, thio, -CN, -OH, -(C 1-4 Alkylene (-hydroxy), -NH2, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, S, P, wherein "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by groups selected from the group consisting of: halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C1-C4 alkylthio, -CN, -OH, -NH2, -(C 1-6 (alkylene)-hydroxyl.

[0044] In another preferred embodiment, the R 8 Selected from the following group: , benzimidazole, benzothiazolyl, wherein the benzimidazole or benzothiazolyl is optionally substituted with 1-4 substituents selected from the group consisting of: deuterium, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, -CN, -OH, -(C 1-4 (alkylene)-hydroxyl, -NH2.

[0045] In another preferred example, a is independently 0 or 1.

[0046] In another preferred embodiment, the R a Selected from the following group: halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -(C1-6 Alkylene, hydroxyl, oxo, -CN, -NH2, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, wherein "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C 1-6 Alkylene)-hydroxyl, -CN, -OH, -NH2.

[0047] In another preferred embodiment, the R a Selected from the group consisting of: halogen, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, -methylene-hydroxy, -ethylene-hydroxy, -CN, -NH2, substituted or unsubstituted pyridyl, imidazolyl, piperidinyl, thiazolyl, where "substituted" means that one or more hydrogens (such as 2, 3 or 4) on the group are independently substituted by a group selected from the group consisting of: F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, methylthio, ethylthio.

[0048] In another preferred embodiment, the ring E is selected from the group consisting of furan, thiophene, imidazole, thiazole, and pyrazole.

[0049] In another preferred embodiment, the ring E is selected from the group consisting of imidazole and pyrazole.

[0050] In another preferred embodiment, ring E is pyrazole.

[0051] In another preferred embodiment, the R 8 Selected from the following group: , Where b and c are each independently 0, 1, or 2; R b R c Each is independently selected from the following group: hydrogen, F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, methylthio, ethylthio, -methylene-hydroxy, -ethylene-hydroxy, -CN, -OH, -NH2.

[0052] In another preferred embodiment, R 8 Selected from the following group: , , , .

[0053] In another preferred embodiment, the L 1 for .

[0054] In another preferred embodiment, the L 2 L 3 L 4 Each is independently selected from the group consisting of covalently bonded or substituted or unsubstituted -C1-C4 alkylene groups, wherein any carbon atom on the C1-C4 alkylene group is optionally replaced by a heteroatom selected from O and N; the term "substituted" means that one or more hydrogen atoms (such as 2, 3 or 4) on the group are independently replaced by a group selected from the group consisting of halogens, C1-C6 alkyl groups, and C1-C6 haloalkyl groups.

[0055] In another preferred embodiment, the L 2 L 3 L 4 Each is independently selected from the group consisting of: covalent bonds or -C1-C4 alkylene groups, wherein any carbon atom on the C1-C4 alkylene group is optionally replaced by a heteroatom selected from O and N.

[0056] In another preferred embodiment, ring V1 and ring V2 are each independently either absent or containing 1-3 3-15 membered subheterocyclic groups selected from N, O, and S heteroatoms.

[0057] In another preferred embodiment, the L 1 Selected from the following group: -NH-(C4-C 11 -alkylene), -(C0-C3 alkylene)-(5-12 membered heterocyclic)-(C0-C3 alkylene)-, -NH-(C1-C3 alkylene)-(5-12 membered heterocyclic)-(C0-C3 alkylene)-, , The heterocyclic alkylene contains 1-3 heteroatoms selected from N, O, and S; wherein m1 is independently an integer from 0 to 5; any carbon atom on the C0-C3 alkylene is optionally replaced by N, and one or more hydrogens (such as 2, 3, or 4) on the C0-C3 alkylene are independently replaced by groups selected from the group consisting of: halogen, C1-C6 alkyl, C1-C6 haloalkyl, oxo, -CN, -OH, -NH2; T1, T2, T3, and T4 are each independently selected from C or N.

[0058] In another preferred embodiment, the L 1 Selected from the following group: -NH-(C4-C 11 alkylene), -NH-(C1-C3 alkylene)-(5-12 membered heterocyclic)-(C0-C3 alkylene)-, , The heterocyclic alkylene contains 1-3 heteroatoms selected from N, O, and S; wherein m1 is independently an integer from 0 to 5; any carbon atom on the C0-C3 alkylene is optionally replaced by N, and one or more hydrogens (such as 2, 3, or 4) on the C0-C3 alkylene are independently replaced by groups selected from the group consisting of: halogen, C1-C6 alkyl, C1-C6 haloalkyl, oxo, -CN, -OH, -NH2; T1, T2, T3, and T4 are each independently selected from C or N.

[0059] In another preferred embodiment, the L 1 Selected from the following group: -NH-(C4-C 11 alkylene), -NH-(C1-C3 alkylene)-(5-12 membered heterocyclic)-(C0-C3 alkylene)-, , The heterocyclic alkyl group contains 1-3 heteroatoms selected from N and O; wherein m1 is an integer from 0 to 5, and T2 and T3 are each independently selected from the group C or N.

[0060] In another preferred embodiment, the L 1 Selected from the following groups: .

[0061] In another preferred embodiment, the L 1 Selected from the following groups: .

[0062] In another preferred embodiment, x, m, X, ring W1, R x R 3 X 1 X 2 X 3 R 6 R 7 R 8 L 1 R a R b R c Each is an independent corresponding group in compounds A-1 to D-5.

[0063] In another preferred embodiment, the compound is selected from the group consisting of:

[0064] In a second aspect, the present invention provides a method for preparing a compound as described in the first aspect of the present invention, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof, comprising the following steps: S1. In the first solvent, under the action of a catalyst, compound A and compound B undergo an azide-alkyne cycloaddition reaction to prepare compound Ia; Where x, m, W1, R x R 3 R 6 R 7 R 8 L 1 The definition is the same as that described in the first aspect of this invention.

[0065] In another preferred embodiment, the first solvent is selected from the group consisting of tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, dichloromethane, tert-butanol, and acetone.

[0066] In another preferred embodiment, the catalyst is selected from the group consisting of copper sulfate, copper acetate, copper chloride, and copper nitrate.

[0067] In another preferred embodiment, the molar ratio of compound A to compound B is 1:(0.8-1.5).

[0068] In a third aspect, the present invention provides a pharmaceutical composition comprising a compound as described in the first aspect of the present invention, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, prodrug, and a pharmaceutically acceptable carrier thereof.

[0069] In another preferred embodiment, the pharmaceutically acceptable carrier is selected from the group consisting of: sustained-release agents, excipients, fillers, diluents, binders, wetting agents, disintegrants, absorption enhancers, adsorbents, surfactants or lubricants, or combinations thereof.

[0070] In another preferred embodiment, the pharmaceutical composition is administered by a method of administration selected from the group consisting of: oral, intravenous, intramuscular, subcutaneous, rectal, and nasal spray.

[0071] In another preferred embodiment, the formulation of the pharmaceutical composition is selected from the group consisting of oral solutions, tablets, capsules, injections, and granules.

[0072] In a fourth aspect, the present invention provides the use of a compound as described in the first aspect of the present invention, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, prodrug, or pharmaceutical composition as described in the third aspect of the present invention, for the preparation of a medicament for treating androgen receptor (AR)-related diseases or conditions, wherein the hormone receptor (AR)-related diseases or conditions are selected from the group consisting of: prostate cancer, breast cancer, bladder cancer, spinal bulbar muscular atrophy, androgen insensitivity syndrome, liver cancer, kidney cancer, melanoma, glioblastoma, head and neck cancer, esophageal cancer, gastric cancer, colorectal cancer, ovarian cancer, endometrial cancer, cervical cancer, polycystic ovary syndrome, and androgenic alopecia.

[0073] In another preferred embodiment, the androgen receptor (AR) related diseases are selected from the group consisting of: prostate cancer, breast cancer, bladder cancer, liver cancer, kidney cancer, melanoma, esophageal cancer, gastric cancer, colorectal cancer, ovarian cancer, endometrial cancer, cervical cancer, polycystic ovary syndrome, and androgenic alopecia.

[0074] In a fifth aspect, the present invention provides an intermediate compound or a pharmaceutically acceptable salt thereof, said compound or a pharmaceutically acceptable salt thereof being of the following formula B: in, R 6 This refers to 1-3 substituents, each independently selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterated alkoxy, C1-C6 haloalkylthio, substituted or unsubstituted C3-C 10 Cycloalkyl, wherein “substitution” means that one or more hydrogens (such as 2, 3 or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylene, C2 ... 3-10 cycloalkyl, C 6-12 Aryl, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, oxo, thio, -CN, -OH, -NH2, -NO2, -COOH, acetyl; R 7 Selected from the following group: hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -NH2; R8 Selected from the group consisting of 5-12-membered heteroaryl groups containing 1-4 heteroatoms selected from N, O, S, and P, wherein the 5-12-membered heteroaryl groups are optionally substituted by 1-4 substituents selected from the group consisting of: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuterylalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterylalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -(C 1-6 Alkylene, -hydroxyl, -NH2, -NO2, -COOH, acetyl.

[0075] In another preferred embodiment, the R 6 R 7 As described in the first aspect of this invention.

[0076] In another preferred embodiment, the R 8 Selected from the group consisting of 1-3 5-12-membered heteroaryl groups selected from N, O, and S heteroatoms, wherein the 5-12-membered heteroaryl groups are optionally substituted by 1-4 substituents selected from the group consisting of: halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 deuterylalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 deuterylalkoxy, C1-C4 haloalkylthio, oxo, thio, -CN, -OH, -(C 1-6 Alkylene, -hydroxyl, -NH2, -NO2, -COOH, acetyl.

[0077] In another preferred embodiment, the R 8 Selected from the group consisting of: benzimidazole, benzothiazolyl, wherein the benzimidazole or benzothiazolyl is optionally substituted by 1-4 substituents selected from the group consisting of: deuterium, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, -CN, -OH, -(C 1-4 (alkylene)-hydroxyl, -NH2.

[0078] In another preferred embodiment, the R 8 for Where b and c are each independently 0, 1, or 2; R b R c Each is independently selected from the following group: hydrogen, F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, methylthio, ethylthio, -methylene-hydroxy, -ethylene-hydroxy, -CN, -OH, -NH2.

[0079] In another preferred embodiment, the R 8 for Where b and c are each independently 0, 1, or 2; R b R c Each is independently selected from the following group: hydrogen, F, Cl, Br, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, trifluoromethyl, trifluoroethyl, -OH, -NH2.

[0080] In another preferred embodiment, the R 8 Selected from the following group: , .

[0081] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0082] Figure 1 The results of the experiment evaluating the degradation efficacy of target proteins at the cellular level are shown. Detailed Implementation

[0083] Through extensive and in-depth research, the inventors have discovered for the first time a novel AR protein degrader with excellent antitumor activity. Based on this discovery, the present invention was completed.

[0084] definition Unless otherwise stated, the definitions of groups and terms recorded in this disclosure and claims, including definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, and definitions of specific compounds in the examples, can be arbitrarily combined and combined with each other. Such combinations and combinations of group definitions and compound structures should be understood as being within the scope of this disclosure and / or claims.

[0085] As used herein, the terms “containing” or “including (comprise)” can be open-ended, semi-closed, or closed. In other words, the terms also include “consistently made of” or “composed of”.

[0086] When a substituent is described using a conventional chemical formula written from left to right, the substituent also includes chemically equivalent substituents obtained when the structural formula is written from right to left. For example, -CH2O- includes -OCH2-.

[0087] In this document, all features or conditions defined in the form of numerical ranges or percentage ranges are for the sake of brevity and convenience only. Accordingly, descriptions of numerical ranges or percentage ranges should be considered as covering and specifically disclosing all possible secondary ranges and individual values ​​within those ranges, particularly integer values. For example, a range description of "1-8" should be considered as specifically disclosing all secondary ranges such as 1 to 7, 2 to 8, 2 to 6, 3 to 6, 4 to 8, 3 to 8, etc., particularly secondary ranges defined by all integer values, and should be considered as specifically disclosing individual values ​​within those ranges such as 1, 2, 3, 4, 5, 6, 7, 8, etc. Unless otherwise specified, the foregoing interpretation applies to all content throughout this invention, regardless of its breadth. Similarly, a range description of "0-4" should be considered as specifically disclosing 0, 1, 2, 3, 4, and ranges such as 0-2 or 1-2, where a value of 0 indicates non-existence.

[0088] If a quantity or other numerical value or parameter is expressed as a range, a preferred range, or a series of upper and lower limits, it should be understood that this document has specifically disclosed all ranges consisting of any upper or preferred value of that range and the lower or preferred value of that range, regardless of whether such ranges are separately disclosed. Furthermore, when a range of numerical values ​​is mentioned herein, unless otherwise stated, the range shall include its endpoints and all integers and fractions within the range.

[0089] In this document, when Markush groups or alternative terms are used to describe features or examples of the invention, those skilled in the art should understand that subgroups of all elements within a Markush group or option list, or any individual element, can also be used to describe the invention. For example, if X is described as "selected from the group consisting of X1, X2, and X3," it also indicates that the claim that X is X1 and the claim that X is X1 and / or X2 have been fully described. Furthermore, when Markush groups or alternative terms are used to describe features or examples of the invention, those skilled in the art should understand that any combination of subgroups of all elements within a Markush group or option list, or any combination of individual elements, can also be used to describe the invention. Accordingly, for example, if X is described as "selected from the group consisting of X1, X2, and X3," and Y is described as "selected from the group consisting of Y1, Y2, and Y3," it indicates that the claim that X is X1 or X2 or X3 and Y is Y1 or Y2 or Y3 has been fully described.

[0090] When listing a series of values, the intention is to cover every value within that range and every subrange. For example, "C 1-6 (or "C") 1- C6 (similar expressions can be used interchangeably) aims to cover C1, C2, C3, C4, C5, C6, and C 1-6 C 1-5 C 1-4 C1-3 C 1-2 C 2-6 C 2-5 C 2-4 C 2-3 C 3-6 C 3-5 C 3-4 C 4-6 C 4-5 and C 5-6 .

[0091] The term "alkyl" refers to a straight-chain or branched saturated hydrocarbon group having 1 to 6 carbon atoms ("C..."). 1-6 Alkyl or "C1-C6" alkyl). In some embodiments, the alkyl group has 1 to 5 carbon atoms ("C1-C6" alkyl). 1-5 Alkyl group). In some embodiments, the alkyl group has 1 to 4 carbon atoms (“C1”). 1-4 Alkyl group). In some embodiments, the alkyl group has 1 to 3 carbon atoms (“C1”). 1-3 Alkyl group (“alkyl”). In some embodiments, the alkyl group has 1 to 2 carbon atoms (“C”). 1-2 Alkyl group (“C1 alkyl”). In some embodiments, the alkyl group has 1 carbon atom (“C1 alkyl”). In some embodiments, the alkyl group has 2 to 6 carbon atoms (“C1 alkyl”). 2-6 Alkyl group). C 1-6 Examples of alkyl groups include methyl (C1), ethyl (C2), propyl (C3) (e.g., n-propyl, isopropyl), butyl (C4) (e.g., n-butyl, tert-butyl, sec-butyl, isobutyl), pentyl (C5) (e.g., n-pentyl, 3-pentyl, neopentyl, 3-methyl-2-butyl, tert-pentyl), and hexyl (C6) (e.g., n-hexyl). Further examples of alkyl groups include n-heptyl (C7), n-octyl (C8), etc. Unless otherwise stated, each example of an alkyl group is independently unsubstituted (“unsubstituted alkyl”) or substituted by one or more substituents (e.g., a halogen, such as F) (“substituted alkyl”). In some embodiments, the alkyl group is an unsubstituted C1 group. 1-6 Alkyl (e.g., unsubstituted C) 1-3 Alkyl group, such as -CH3). In some embodiments, the alkyl group is a substituted C. 1-6 Alkyl (e.g., substituted C) 1-3 Alkyl groups, such as -CF3).

[0092] "Alkenyl" refers to a straight-chain or branched hydrocarbon group having 2 to 6 carbon atoms, one or more carbon-carbon double bonds, and no triple bonds. In some embodiments, the alkenyl group has 2 to 6 carbon atoms ("C..."). 2-6 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 5 carbon atoms (“C”). 2-5Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 4 carbon atoms (“C”). 2-4 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 3 carbon atoms (“C”). 2-3 The alkenyl group (“C2-alkenyl”) has two carbon atoms in some embodiments. The one or more carbon-carbon double bonds can be internal (e.g., in a 2-butenyl group) or terminal (e.g., in a 1-butenyl group). 2-4 Examples of alkenyl groups include vinyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), etc. 2-6 Examples of alkenyl groups include the aforementioned C... 2-4 Alkenyl groups, including pentenyl (C5), pentadienyl (C5), hexenyl (C6), etc. Unless otherwise stated, each instance of an alkenyl group is optionally substituted independently, i.e., unsubstituted (“unsubstituted alkenyl”) or substituted by one or more substituents (“substituted alkenyl”). In some embodiments, the alkenyl group is an unsubstituted C5 group. 2-6 Alkenyl (e.g., unsubstituted C) 2-4 Alkenyl). In some embodiments, the alkenyl group is a substituted C. 2-6 alkenyl (e.g., substituted C) 2-4 Alkenyl). In alkenyl groups, the C=C double bond without specified stereochemistry (e.g., -CH=CHCH3 or) can be ( E )-or( Z )- double bond.

[0093] "Alynyl" refers to a straight-chain or branched hydrocarbon group having 2 to 6 carbon atoms, one or more carbon-carbon triple bonds, and optionally one or more double bonds. In some embodiments, the alkynyl group has 2 to 6 carbon atoms ("C... 2-6 The alkynyl group (“H”) has 2 to 5 carbon atoms in some embodiments. 2-5 The alkynyl group (“C”) is present in some embodiments. In some embodiments, the alkynyl group has 2 to 4 carbon atoms (“C”). 2-4 The alkynyl group (“C”) is present in some embodiments. In some embodiments, the alkynyl group has 2 to 3 carbon atoms (“C”). 2-3 The alkynyl group (“C2-alkynyl”) is present in some embodiments. The one or more carbon-carbon triple bonds can be internal (e.g., in the 2-butynyl group) or terminal (e.g., in the 1-butynyl group). 2-4 Examples of alkynyl groups include, but are not limited to, ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), and 2-butynyl (C4). 2-6 Examples of alkenyl groups include the C group mentioned above. 2-4The alkynyl group includes pentynyl (C5), hexynyl (C6), etc. Unless otherwise stated, each instance of the alkynyl group is optionally substituted independently, i.e., unsubstituted (“unsubstituted alkynyl”) or substituted by one or more substituents (“substituted alkynyl”). In some embodiments, the alkynyl group is an unsubstituted C5 group. 2-6 Alkyne groups (e.g., unsubstituted C) 2-4 (Alynyl group). In some embodiments, the alkynyl group is a substituted C. 2-6 alkynyl groups (e.g., substituted C) 2-4 (Alkyne group).

[0094] The term "alkylene" refers to a divalent group obtained by removing a hydrogen atom from an alkyl group as defined above. Alkylenes can be straight-chain or branched divalent alkyl groups. For example, "C 1-4 "Alkylene" refers to an alkylene group having 1 to 4 carbon atoms. Examples of alkylene groups include, but are not limited to, methylene (i.e., -CH2-), ethylene (i.e., -CH2CH2- or -CH(CH3)-), and propylene (i.e., -CH2-CH2-CH2-, -CH(CH2CH3)-, or -CH2CH(CH3)-). Alkenyl and ynylene groups have similar definitions.

[0095] The term "alkoxy" refers to -O- (alkyl) and -O- (unsubstituted cycloalkyl), where alkyl is defined as described above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, and cyclohexyloxy, and alkoxy groups may be optionally substituted or unsubstituted.

[0096] "Cycloalkyl", "carbocyclic", or "carbocyclic" refers to a non-aromatic ring system having 3 to 12 ring carbon atoms ("C"). 3-12 The cycloalkyl group comprises a non-aromatic cycloalkyl group with 3 to 8 carbon atoms (“C”). 3-10 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 8 cyclic carbon atoms (“C”). 3-8 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 7 cyclic carbon atoms (“C”). 3-7 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 6 cyclic carbon atoms (“C”). 3-6 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 6 cyclic carbon atoms (“C”). 3-4 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 6 cyclic carbon atoms (“C”). 5-6 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 5 to 10 cyclic carbon atoms (“C”). 5-10 Cycloalkyl). Exemplary C 3-6Cycloalkyl groups include, but are not limited to, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), and cyclohexadienyl (C6). An example C... 3-8 Cycloalkyl groups include, but are not limited to, the above-mentioned C 3-6 Cycloalkyl groups, including cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cyclohepttrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptyl (C7), bicyclo[2.2.2]octyl (C8), etc. Exemplary C 3-10 Cycloalkyl groups include, but are not limited to, the above-mentioned C 3-8 Cycloalkyl groups and cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C9) 10 ), cyclodecenyl (C 10 Octahydro-1 H -Indanyl (C9), decahydronaphthyl (C9) 10 ), spiro[4.5]decyl(C 10 As illustrated in the foregoing examples, in some embodiments, the cycloalkyl group is a monocyclic (“monocyclic cycloalkyl”) or contains a fused ring, bridged ring, or spirocyclic system, such as a bicyclic system (“bicyclic cycloalkyl”). The cycloalkyl group may be saturated or partially unsaturated (e.g., containing 1-2 double bonds, preferably 1 double bond). “Cycloalkyl” also includes ring systems in which the carbon ring as defined above is fused with one or more aryl or heteroaryl groups at the connection point on the carbon ring, and in this case, the carbon number continues to refer to the number of carbons in the carbon ring system. Unless otherwise stated, each instance of the cycloalkyl group is optionally independently substituted, i.e., unsubstituted (“unsubstituted cycloalkyl”) or substituted by one or more substituents (“substituted cycloalkyl”). In some embodiments, the cycloalkyl group is an unsubstituted C… 3-10 Cycloalkyl. In some embodiments, the cycloalkyl group is a substituted C-shaped group. 3-10 Cycloalkyl.

[0097] The terms “heterocyclic group,” “heterocyclic alkyl group,” or “heterocyclic” are used interchangeably to refer to a group having a cyclic carbon atom and one to four (e.g., one, two, or three) cyclic heteroatoms, comprising a 3- to 12-membered non-aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, and phosphorus (“3- to 12-membered heterocyclic group”). In heterocyclic groups containing one or more nitrogen atoms, the bonding point can be a carbon atom or a nitrogen atom, provided the valence allows. Heterocyclic groups can be monocyclic (“monocyclic heterocyclic group”) or fused-ring, bridged-ring, or spirocyclic systems, such as bicyclic systems (“bicyclic heterocyclic group”). Heterocyclic groups can be saturated or partially unsaturated (e.g., containing one or two double bonds, preferably one double bond). Heterocyclic bicyclic systems can contain one or more heteroatoms in one or both rings. "Heterocyclic group" also includes ring systems in which a heterocycle as defined above is fused with one or more cycloalkyl groups at the junction point on a cycloalkyl or heterocycle, or a ring system in which a heterocycle as defined above is fused with one or more aryl or heteroaryl groups at the junction point on a heterocycle, and in this case, the number of ring members continues to refer to the number of ring members in the heterocyclic system. Unless otherwise stated, each instance of a heterocyclic group is independently and optionally substituted, i.e., unsubstituted ("unsubstituted heterocyclic group") or substituted with one or more substituents ("substituted heterocyclic group"). In some embodiments, the heterocyclic group is a substituted or unsubstituted 3-10 membered heterocyclic group. In some embodiments, the heterocyclic group is a substituted or substituted 3-6 membered heterocyclic group. In some embodiments, the heterocyclic group is a substituted or substituted 5-6 membered heterocyclic group.

[0098] "Aryl" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic) aromatic ring system (e.g., having 6 or 10 π electrons shared in a cyclic array) having 6-12 ring carbon atoms and zero heteroatoms provided in the aromatic ring system ("C"). 6-10 Aryl group (“C6 aryl”). In some embodiments, the aryl group has 6 ring carbon atoms (“C6 aryl”; for example, phenyl). In some embodiments, the aryl group has 10 ring carbon atoms (“C6 aryl”). 10 "Aryl"; for example, naphthyl, such as 1-naphthyl and 2-naphthyl). "Aryl" also includes ring systems in which the aryl ring as defined above is fused with one or more cycloalkyl or heterocyclic groups, wherein the groups or linkages are on the aromatic ring, and in this case, the number of carbon atoms continues to refer to the number of carbon atoms in the aromatic ring system. Unless otherwise stated, each instance of an aryl group is optionally independently substituted, i.e., unsubstituted ("unsubstituted aryl") or substituted with one or more substituents ("substituted aryl"). In some embodiments, the aryl group is an unsubstituted C 6-10 Aryl. In some embodiments, the aryl group is a substituted C. 6-10 Aryl.

[0099] "Aryl" is a subset of alkyl and aryl and refers to an optionally substituted alkyl group that is optionally substituted with an aryl group. In some embodiments, the aryl group is an optionally substituted benzyl group. In some embodiments, the aryl group is a benzyl group. In some embodiments, the aryl group is an optionally substituted phenethyl group. In some embodiments, the aryl group is a phenethyl group.

[0100] "Heteroaryl" refers to a group having a 5-12 membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 π electrons shared in a cyclic array) containing a cyclic carbon atom and 1-4 cyclic heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, phosphorus, and sulfur ("5-12 membered heteroaryl"). In some embodiments, the heteroaryl has 1, 2, or 3 nitrogen, oxygen, and sulfur heteroatoms. In some embodiments, the heteroaryl has 1 or 2 nitrogen, oxygen, and sulfur heteroatoms. In some embodiments, the heteroaryl has 1 nitrogen, oxygen, and sulfur heteroatom. In some embodiments, the heteroaryl has 1 or 2 nitrogen and oxygen heteroatoms. In some embodiments, the heteroaryl has 1 or 2 nitrogen heteroatoms. In some embodiments, the heteroaryl group is a 5-8 membered aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heteroaryl”). In some embodiments, the heteroaryl group is a 5-8 membered aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heteroaryl”). In some embodiments, the heteroaryl group is a 5-6 membered aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heteroaryl”). In some embodiments, the 5-6 membered heteroaryl group has 1-3 cyclic heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl group has 1-2 cyclic heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl group has one cyclic heteroatom selected from nitrogen, oxygen, and sulfur. In heteroaryl groups containing one or more nitrogen atoms, the linkage can be a carbon or nitrogen atom, provided the valence allows. A heteroaryl bicyclic system may contain one or more heteroatoms in one or both rings. "Hyperaryl" includes a ring system in which a heteroaryl ring as defined above is fused with one or more cycloalkyl or heterocyclic groups, wherein the linkage is on the heteroaryl ring, and in this case, the number of ring members continues to refer to the number of ring members in the heteroaryl ring system. "Hyperaryl" also includes a ring system in which a heteroaryl ring as defined above is fused with one or more aryl groups, wherein the linkage is on the aryl or heteroaryl ring, and in this case, the number of ring members refers to the number of ring members in the fused (aryl / heteraryl) ring system. One of the rings is a bicyclic heteroaryl group (e.g., indole, quinolinyl, carbazolyl, etc.) without heteroatoms. The connection point can be on either ring, i.e., a ring with heteroatoms (e.g., 2-indole) or a ring without heteroatoms (e.g., 5-indole).Examples of heteroaryl groups include imidazole, furanyl, thiophene, thiazolyl, pyrazolyl, oxazolyl, pyrroleyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, thiadiazole, pyrazinyl, etc., preferably pyridyl, oxadiazolyl, triazolyl, thiophene, imidazole, pyrazolyl, oxazolyl, thiazolyl, pyrimidinyl or thiazolyl; more preferably tetrazolyl, pyridyl, oxadiazolyl, pyrazolyl, pyrroleyl, thiazolyl and oxazolyl.

[0101] "Heteroaryl" is a subset of alkyl and heteroaryl, and refers to an alkyl group that is optionally substituted by a heteroaryl group.

[0102] "Unsaturated" or "partially saturated" refers to a group containing at least one double or triple bond. A "partially unsaturated" ring system is also intended to encompass rings having multiple unsaturated sites, but not to include aromatic groups (e.g., aryl or heteroaryl). In some embodiments, a "partially unsaturated" ring system contains one double bond. In some embodiments, a "partially unsaturated" ring system contains two double bonds. Similarly, "saturated" means a group that does not contain double or triple bonds, i.e., contains only single bonds.

[0103] Unless otherwise expressly stated, atoms, portions, or groups described herein may be unsubstituted or substituted, provided that valence permits. The term "optionally substituted" refers to both substituted and unsubstituted atoms.

[0104] Unless otherwise expressly specified, the group may optionally be substituted. The term "optionally substituted" means substituted or unsubstituted. In some embodiments, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups may optionally be substituted (e.g., "substituted" or "unsubstituted" alkyl, "substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" cycloalkyl, "substituted" or "unsubstituted" heterocyclic, "substituted" or "unsubstituted" aryl, or "substituted" or "unsubstituted" heteroaryl). Generally, the term "substituted," regardless of whether it is preceded by the term "optionally," means that at least one hydrogen atom present in the group (e.g., carbon or nitrogen atom) is substituted with a permissible substituent, such that the substituent, upon substitution, forms a stable compound, for example, a compound that does not spontaneously transform (e.g., through rearrangement, cyclization, elimination, or other reactions). Unless otherwise specified, a “substituted” group has substituents at one or more substituted positions of the group, and when more than one position in any given structure is substituted, the substituents are the same or different at each position. The term “substituted” is intended to include all permissible substituents of an organic compound, any substituent described herein that results in the formation of a stable compound. This disclosure contemplates any and all such combinations to obtain stable compounds. For the purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and / or any suitable substituents as described herein that satisfy the valence of the heteroatom and result in the formation of a stable moiety. In some embodiments, the substituent is a carbon atom substituent. In some embodiments, the substituent is a nitrogen atom substituent. In some embodiments, the substituent is an oxygen atom substituent. In some embodiments, the substituent is a sulfur atom substituent. Unless otherwise specified, “substituted” means that one or more (e.g., 2, 3, or 4) hydrogen atoms on a group are independently substituted by a group selected from the group consisting of: deuterium, halogen, halogen-substituted or unsubstituted C1-C6 alkyl, halogen-substituted or unsubstituted C1-C6 alkoxy.

[0105] "Halogen" or "halogen" refers to fluorine (fluorinated, -F), chlorine (chlorinated, -Cl), bromine (brominated, -Br), or iodine (iodinated, -I).

[0106] The term "multiple" refers to two or more, such as 2, 3, 4, 5 or 6.

[0107] As used herein, the term "independently" means when more than one substituent is selected from a large number of possible substituents, which may be the same or different. That is, each substituent is individually selected from the entire group of listed possible substituents. In this invention, when two or more groups have the same label, both are defined independently, that is, each substituent is individually selected from the entire group of listed possible substituents.

[0108] In another preferred embodiment, the compound is any of the compounds in the examples.

[0109] The present invention also aims to include pharmaceutically acceptable salts, stereoisomers, or isotopically labeled compounds of the said compounds, crystal forms (including hydrates, solvates, etc.), prodrugs, or active metabolites.

[0110] The term "pharmaceutically acceptable salt" refers to those salts that, within reasonable medical judgment, are suitable for contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic reactions, etc., and in proportion to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. Pharmaceutically acceptable salts of the compounds described herein include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are amino salts formed with inorganic acids (such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid) or with organic acids (acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid) or by using other methods known in the art (such as ion exchange). Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, hydrogen sulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentylpropionate, diglucuronate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucohepanoate, glyceryl phosphate, glucuronate, hemisulfate, heptahydrate, hexanoate, hydrogen iodide, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, dodecyl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 3-phenylpropionate, phosphate, picrate, neopentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. Salts derived from suitable bases include alkali metals, alkaline earth metals, ammonium, and nitrogen. + (C 1-4 Alkyl)4 - Salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Where appropriate, other pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed using balancing ions such as halide, hydroxide, carboxyl, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate.

[0111] The term "tautomer" or "tautomerizing" refers to a compound in which two or more interconvertions result from at least one formal migration of a hydrogen atom and at least one change in valence (e.g., a single bond becomes a double bond, a triple bond becomes a single bond, or vice versa). The exact proportions of tautomers depend on several factors, including temperature, solvent, and pH. Tautomerization reactions (i.e., reactions that provide tautomer pairs) can be catalyzed by acids or bases. Exemplary tautomerization reactions include keto-enol, amide-imide, lactam-lactamimide, enamine-imide, and enamine-(different enamines) tautomerization reactions.

[0112] It should also be understood that compounds with the same molecular formula but different properties, different atomic bonding sequences, or different spatial arrangements of atoms are called "isomers". Isomers with different atomic spatial arrangements are called "stereoisomers".

[0113] Stereoisomers that are not mirror images of each other are called "diastereomers," while stereoisomers that are not mirror images of each other are called "enantiomers." When a compound has an asymmetry center, for example, if it is bonded to four different groups, a pair of enantiomers may exist. Enantiomers can be characterized by the absolute configuration of their asymmetry center and are described by the R- and S-sequence rules of Cahn and Prelog or by rotating the molecular plane of polarization, and are represented as dextrorotatory or levorotatory (i.e., (+) or (-)- isomers, respectively). Chiral compounds can exist as individual enantiomers or as mixtures thereof. A mixture containing equal proportions of enantiomers is called a "racemic mixture."

[0114] The term "prodrug" or "prodrug" refers to a compound having a cleavable group and being converted into the compound described herein by solvent decomposition or under physiological conditions, and which possesses pharmaceutical activity in vivo. Examples of such compounds include, but are not limited to, choline ester derivatives, N-alkylmorpholine esters, etc. Other derivatives of the compounds described herein, in both their acid and acid derivative forms, are active; however, acid-sensitive forms often offer advantages in mammalian organisms such as solubility, tissue compatibility, or delayed release (see Bundgard, H., "Design of Prodrugs"). Design of Prodrugs(See Elsevier, Amsterdam, 1985, pp. 7-9, 21-24). Prodrugs include acid derivatives known to those skilled in the art, such as esters prepared by reacting a parent acid with a suitable alcohol, or amides prepared by reacting a parent acid compound with a substituted or unsubstituted amine, or acid anhydrides or mixed acid anhydrides. Simple aliphatic or aromatic esters, amides, and acid anhydrides derived from the acidic side groups of the compounds described herein are specific prodrugs. In some cases, it is necessary to prepare diester-type prodrugs, such as (acyloxy)alkyl esters or ((alkoxycarbonyl)oxy)alkyl esters. C1-C8 alkyl esters, C2-C8 alkenyl esters, C2-C8 alkynyl esters, aryl esters, and C7-C8 compounds described herein may be preferred. 12 Substituted aryl esters and C7-C 12 Arylalkyl esters.

[0115] Compositions and Applications The present invention provides a pharmaceutical composition comprising a compound of formula (I) above, or a pharmaceutically acceptable salt, stereoisomer or isotope thereof; and a pharmaceutically acceptable carrier.

[0116] The compounds of the present invention have ubiquitination and / or degradation activities of AR proteins, and therefore can be used to prevent and / or treat AR-mediated diseases, especially those mediated by high AR expression and / or abnormal activation, such as prostate cancer and breast cancer.

[0117] The term "inhibition" or "inhibitor" refers to the ability of a compound to reduce, slow down, stop, or prevent the activity of a particular biological process.

[0118] The terms "abnormal activation" or "abnormal activity" refer to activity that deviates from normal activity. The term "increased activity" refers to activity that is higher than normal activity.

[0119] The terms “composition” and “formulation” are used interchangeably.

[0120] The term "subject" to be administered refers to a person (i.e., a male or female of any age group, such as a pediatric subject (e.g., an infant, child, or adolescent) or an adult subject (e.g., a young adult, middle-aged, or elderly person)). "Patient" refers to a human subject who requires treatment for a disease.

[0121] The term “administration” means the implantation, absorption, ingestion, injection, inhalation or other introduction of the compound or a combination thereof described herein into or onto a subject.

[0122] The term "treatment" refers to reversing, alleviating, delaying the onset of the disease described herein, or inhibiting its development. In some embodiments, treatment may be administered after one or more signs or symptoms of the disease have developed or been observed. In other embodiments, treatment may be administered in the absence of signs or symptoms of the disease. For example, treatment may be administered to susceptible subjects before the onset of symptoms (e.g., based on a history of symptoms and / or based on exposure to a pathogen) to delay or prevent the occurrence of the disease. Treatment may also continue after symptoms have subsided, for example, to delay or prevent recurrence.

[0123] The “effective amount” or “therapeutic effective amount” of a compound described herein is an amount sufficient to provide therapeutic benefit in treating a condition or to delay or minimize one or more symptoms associated with said condition. A therapeutically effective amount of a compound refers to the amount of a therapeutic agent, alone or in combination with other therapies, that provides therapeutic benefit in treating the condition. The term “therapeutic effective amount” can include amounts that improve overall treatment, reduce or avoid symptoms, signs, or causes, and / or enhance the therapeutic efficacy of another therapeutic agent.

[0124] "Pharmaceutically acceptable excipients" and "pharmaceutically acceptable carriers" refer to substances that facilitate the formulation and / or administration and / or absorption of the active agent by an individual and can be included in the compositions disclosed herein without causing significant adverse toxicological effects on that individual. Non-limiting examples of pharmaceutically acceptable carriers and excipients include water, NaCl, physiological saline solutions, lactated Ringer's solution, conventional sucrose, conventional glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, salt solutions (e.g., Ringer's solution), alcohols, oils, gelatin, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethyl cellulose, polyvinylpyrrolidone, and pigments. Such formulations can be sterilized and, if desired, mixed with adjuvants such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts affecting osmotic pressure, buffers, colorants, and / or aromatic substances that will not harmfully react with or interfere with the activity of the compounds provided herein. Those skilled in the art will recognize that other pharmaceutical carriers and excipients are suitable for the disclosed compounds.

[0125] In some embodiments, the pharmaceutical compositions of the present invention may be in solid or liquid form.

[0126] The pharmaceutical product containing the active ingredient of this invention can be a suitable oral dosage form, such as tablets, pills, lozenges, water-soluble or oily suspensions, dispersed latex powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Orally administered pharmaceutical products can be prepared according to known process methods of the pharmaceutical ingredient manufacturer. These compositions may include one or more of the following agents: sweeteners, flavoring agents, coloring agents, and protective agents, to provide an elegant and palatable pharmaceutical formulation. The tablet contains the active ingredient mixed with non-toxic, pharmaceutically acceptable excipients suitable for tablet production. Examples of such excipients include inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, or sodium phosphate; granulating agents, disintegrants such as corn starch or alginic acid; binding agents such as starch, gelatin, or gum arabic; and lubricants such as magnesium stearate, stearic acid, or talc. The tablet may be uncoated or coated to delay degradation and absorption in the gastrointestinal tract, thereby maintaining its activity over a longer period.

[0127] The active compound may be administered to a subject via any suitable route, including orally, parenterally, by inhalation spray, locally, rectally, nasally, sublingually, vaginally, or via an implantable cartridge. As used herein, the term "parenterally" includes subcutaneous, intravenous, intramuscular, intra-articular, intrasynovial, intrasternal, intrasheathic, intrahepatic, intralesional, and intracranial injection or infusion techniques. Preferably, the composition is administered orally, intraperitoneally, or intravenously.

[0128] Pharmaceutical compositions suitable for use in this invention are typically in the form of discrete units in solid form, such as tablets, capsules, pouches, powders, granules, lozenges, patches, suppositories, pills, or in liquid form, such as liquid formulations, injectable or infusionable solutions or suspensions.

[0129] The precise amount of compound provided to an individual for therapeutic efficacy will depend on the route of administration, the type and severity of the disease and / or condition, and individual characteristics such as general health, age, sex, weight, and tolerance to the drug. Those skilled in the art will be able to determine the appropriate dosage based on these and other factors. When administered in combination with other therapeutic agents, the “therapeutic efficacy” of any other therapeutic agent will depend on the type of drug used. Appropriate dosages are known for approved therapeutic agents and can be adjusted by those skilled in the art according to the individual’s condition and the type of condition being treated. Preferably, the compositions should be formulated such that an inhibitory dose of 0.01-100 mg / kg body weight / day can be administered to patients receiving these compositions. In some embodiments, the compositions of the present invention provide doses from 0.01 mg to 50 mg. In other embodiments, doses of 0.1 mg-25 mg or 5 mg-40 mg are provided.

[0130] Examples of subjects to which the pharmaceutical compositions or therapeutic agents of the present invention are administered include mammals (e.g., humans, mice, rats, hamsters, rabbits, cats, dogs, cattle, sheep, monkeys, etc.).

[0131] The present invention also provides a treatment method comprising the steps of: administering to a subject requiring treatment a compound of general formula (I) as described in the present invention, or a pharmaceutically acceptable salt thereof, or administering a pharmaceutical composition as described in the present invention for selectively degrading AR proteins, or for preventing or treating AR and / or AR-mediated diseases (such as AR and / or AR protein-mediated cancers).

[0132] Detailed embodiments of the present invention This invention provides a protein degrading agent or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, or solvate thereof, wherein the protein degrading agent is shown in formula (I): R 1 and R 2 Each is independently selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, C3-C8 cycloalkyl, C1-C6 haloalkyl, and C1-C6 haloalkoxy; X represents none, -O-, or -NH-; W1 is selected from optionally substituted 4-7 membered cycloalkyl groups, with substituents selected from C1-C6 alkyl, halogen, and carbonyl groups; optionally substituted C8-C14 membered spirocyclic rings, with substituents selected from C1-C6 alkyl, halogen, and carbonyl groups; L 1 For -NR 3 R 4 -W2-R 5 -; R 3 and R 4 Each is independently selected from hydrogen, C2-C12 alkyl, C2-C12 alkoxy, C2-C12 alkyl containing heteroatoms, and -(CH2CH2O). n -;R 3 R 4 It forms aliphatic ring groups and spirocyclic ring groups with the attached N atom; W2 is absent, C4-C8 aliphatic ring, or C4-C8 nitrogen-containing heterocycle; R 5 It contains no C1-C6 alkyl or carbonyl groups; X 1 X 2 X 3 Each is independently selected from C, N, or O; R 6Selected from C1-C6 alkyl, C1-C6 alkenyl, or optionally substituted C1-C6 alkyl, wherein the substituent is selected from hydroxyl, methylthio, alkenyl; 3-8 membered aliphatic ring, 4-8 membered nitrogen-containing heterocycle, or 5-8 membered aromatic ring; R 7 Selected from C1-C6 alkyl and hydroxyl groups; R 8 Selected from , , , ; Halogens are selected from F, Cl, and Br; The heteroatoms are selected from N, O, and S.

[0133] n = 1~6 The main advantages of this invention include: (1) This invention provides an AR protein degrader with novel structure, excellent activity and high specificity.

[0134] (2) The compounds of the present invention have superior target protein degradation efficiency and more effective anti-tumor cell proliferation effect.

[0135] (3) The compounds of the present invention have excellent pharmaceutical properties and can be used to prepare drugs for the prevention or treatment of androgen receptor (AR) mediated diseases.

[0136] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and parts by weight.

[0137] Example 1. Synthesis of key intermediates Example 1.1 Synthesis of key intermediate I-1 Step 1: Preparation of Compound 3 Compound 1 (20.00 g, 60.54 mmol) and compound 2 (13.88 g, 63.56 mmol) were dissolved in dichloromethane (100 mL). N,N-diisopropylethylamine (31.30 g, 242.14 mmol) was added, and the mixture was stirred for 5 minutes. 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (24.17 g, 63.56 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was washed once with saturated ammonium chloride solution, once with water, and once with saturated sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to give compound 3 (27.12 g, 84% yield). LCMS (ESI): m / z 531.2 [M+H] + . Step 2: Preparation of Compound 4 Compound 3 (27.12 g, 51.10 mmol) was dissolved in dichloromethane (100 mL), and trifluoroacetic acid (20 mL) was added. The mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, and the residue was washed three times with methyl tert-butyl ether and filtered to give compound 4 (21.40 g, 97% yield). LCMS (ESI): m / z 431.2 [M+H] + . Step 3: Preparation of compound I-1 Compound 4 (5.00 g, 11.61 mmol), anhydrous copper sulfate (370.68 mg, 2.32 mmol), and potassium carbonate (6.42 g, 46.45 mmol) were dissolved in anhydrous methanol (60 mL). The mixture was stirred at room temperature for 15 minutes, and then compound 5 (3.02 g, 17.42 mmol) was added. The mixture was stirred overnight at room temperature under nitrogen protection. The reaction solution was concentrated under reduced pressure, diluted with ethyl acetate, washed once with saturated ammonium chloride, once with water, and once with saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to give intermediate I-1 (2.41 g, 45% yield). 1 H NMR (600 MHz, CDCl ) δ9.00 (s, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.41 (s, 4H), 5.09 – 5.02 (m, 1H), 4.81 (t, J = 7.1 Hz, 1H), 4.68 – 4.63 (m, 1H), 3.67 (dd, J= 10.8, 4.8 Hz, 1H), 3.60 (dd, J = 10.4, 2.9 Hz, 1H), 3.45 (d, J = 8.6 Hz, 1H), 2.62 (s, 3H), 2.59 – 2.54 (m, 1H), 2.31 – 2.25 (m, 1H), 2.08 – 2.03 (m, 1H), 1.48 (d, J =7.0 Hz, 3H), 1.10 (d, J = 6.6 Hz, 3H), 1.01 (d, J = 6.7 Hz, 3H). LCMS (ESI): m / z 457.1 [M+H] + . Example 1.2 Synthesis of key intermediate I-2 Step 1: Preparation of Compound 7. Compound 6 (5.00 g, 31.22 mmol), methyl iodoform (6.65 g, 46.82 mmol), and potassium hydroxide (4.38 g, 78.04 mmol) were dissolved in acetone (20 mL) and stirred at room temperature for 4 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, diluted with ethyl acetate, washed once with saturated ammonium chloride, once with water, and once with saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 7 (3.56 g, yield 65%). LCMS (ESI): m / z 175.1 [M+H] + . Step 2: Preparation of Compound 8. Compound 7 (2.00 g, 11.48 mmol), hydroxylamine hydrochloride (1.20 g, 17.22 mmol), and potassium acetate (4.51 g, 45.92 mmol) were weighed and dissolved in methanol (60 mL). The mixture was refluxed and stirred for 24 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure, diluted with ethyl acetate, washed once with saturated ammonium chloride solution, washed once with water, washed once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 8 (1.41 g, 65% yield). LCMS (ESI): m / z 190.1 [M+H] + . Step 3: Preparation of Compound 9. Compound 8 (1.41 g, 7.45 mmol) was dissolved in methanol (10 mL). 10% palladium on carbon (141 mg) and hydrochloric acid (27.17 mg, 745.17 µmol) were weighed and reacted overnight at 40 °C under hydrogen atmosphere. After the reaction was complete, the mixture was filtered through diatomaceous earth, the filtrate was concentrated under reduced pressure, and the residue was slurried three times with petroleum ether to obtain compound 9 (970 mg, yield 74%). LCMS (ESI): m / z 176.1 [M+H] + . Step 4: Preparation of Compound 10: Compound 9 (200 mg, 1.14 mmol), Compound 1 (396 mg, 1.20 mmol), and DIPEA (1.00 mL, 5.74 mmol) were weighed and dissolved in dichloromethane (10 mL). HATU (455.67 mg, 1.20 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was washed once with saturated ammonium chloride solution, once with water, and once with saturated sodium chloride solution. The solution was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain Compound 10 (273 mg, yield 49%). LCMS (ESI): m / z 488.2 [M+H] + . Step 5: Preparation of Compound 11. Compound 10 (273 mg, 559.88 µmol) was weighed and dissolved in dichloromethane (3 mL), and trifluoroacetic acid (600 µL) was added. The mixture was stirred at room temperature for 3 hours. After the reaction was complete, the reaction solution was concentrated and purified by preparative high-performance liquid chromatography (HPLC) to obtain compound 11 (94 mg, yield 43%). LCMS (ESI): m / z 388.1 [M+H] + . Step 6: Preparation of Intermediate I-2. Compound 11 (94 mg, 242.59 µmol), potassium carbonate (100 mg, 727.77 µmol), and anhydrous copper sulfate (4 mg, 24.26 µmol) were weighed and dissolved in anhydrous methanol (8 mL). The mixture was stirred at room temperature for 15 minutes, and then compound 5 (76.27 mg, 363.89 µmol) was added and stirred overnight at room temperature. After the reaction was complete, the reaction solution was concentrated under reduced pressure, diluted with EA, washed once with saturated ammonium chloride solution, washed once with water, washed once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain intermediate 12 (41 mg, yield 41%). LCMS (ESI): m / z 414.2 [M+H] + . Example 1.3 Synthesis of key intermediate I-3 Step 1: Preparation of Compound 13. Compound 12 (5.00 g, 34.93 mmol), methyl iodoform (7.44 g, 52.39 mmol), and potassium hydroxide (4.90 g, 87.32 mmol) were weighed and dissolved in acetone (60 mL). The mixture was stirred overnight at room temperature. After the reaction was complete, the reaction solution was concentrated under reduced pressure, diluted with EA, washed once with saturated ammonium chloride solution, once with water, once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 13 (4.13 g, 75% yield). LCMS (ESI): m / z 158.0 [M+H] + . Step 2: Preparation of Compound 14. Compound 13 (4.13 g, 26.28 mmol) was weighed and dissolved in tetrahydrofuran (40 mL). Lithium aluminum hydride (2.49 g, 65.69 mmol) was added in portions under ice bath conditions, and the mixture was stirred at room temperature for 6 hours. After the reaction was complete, ethyl acetate was added under ice bath conditions until no more bubbles were produced. Decahydrate and sodium sulfate were added and stirred for 30 minutes. The mixture was allowed to stand and separate into layers. The mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. A solution of 1,4-epoxyhexane hydrochloride was added and stirred for 10 minutes. The solution was then concentrated under reduced pressure to obtain compound 14 (2.41 g, 57% yield). LCMS (ESI): m / z 162.1 [M+H] + . Step 3: Preparation of Compound 15. Compound 14 (200 mg, 1.24 mmol), Compound 1 (430 mg, 1.30 mmol), and DIPEA (1.08 mL, 6.20 mmol) were weighed and dissolved in dichloromethane (10 mL). HATU (495 mg, 1.30 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was washed once with saturated ammonium chloride solution, once with water, and once with saturated sodium chloride solution. The solution was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain Compound 15 (341 mg, yield 58%). LCMS (ESI): m / z 474.2 [M+H] + . Step 4: Preparation of Compound 16. Compound 15 (330 mg, 696.83 µmol) was weighed and dissolved in dichloromethane (3 mL), and trifluoroacetic acid (600 µL) was added. The mixture was stirred at room temperature for 3 hours. After the reaction was complete, the reaction solution was concentrated, and the residue was slurried three times with anhydrous diethyl ether to obtain compound 16 (241 mg, yield 93%). LCMS (ESI): m / z 374.2 [M+H] + . Step 5: Preparation of Intermediate I-3. Compound 16 (220 mg, 612.08 µmol), potassium carbonate (253 mg, 1.84 mmol), and anhydrous copper sulfate (10 mg, 62.66 µmol) were weighed and dissolved in anhydrous methanol (8 mL). The mixture was stirred at room temperature for 15 minutes, and then compound 5 (192 mg, 918.12 µmol) was added and stirred overnight at room temperature. After the reaction was complete, the reaction solution was concentrated under reduced pressure, diluted with EA, washed once with saturated ammonium chloride solution, washed once with water, washed once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain intermediate I-3 (94 mg, 40% yield). 1 H NMR (600 MHz, DMSO- d 6) δ 8.69 (t, J = 6.1 Hz, 1H), 7.97 (s, 1H), 7.69 (s, 1H), 7.66 (d, J =8.3 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 5.18 (d, J = 3.6 Hz, 1H), 4.57 (dd, J = 15.9, 6.9 Hz, 1H), 4.53 (t, J = 8.2 Hz, 1H), 4.37 (d, J = 3.3 Hz, 1H), 4.29(dd, J = 15.9, 5.2 Hz, 1H), 4.04 (s, 3H), 3.78 (d, J = 8.1 Hz, 1H), 3.60 (d, J = 2.8 Hz, 2H), 2.14 – 2.07 (m, 2H), 1.95 – 1.89 (m, 1H), 0.96 (dd, J =19.0, 6.6 Hz, 6H). LCMS (ESI): m / z 400.2 [M+H] + . Example 1.4 Synthesis of key intermediate I-4 The synthetic route for intermediate I-4 follows the route in Example 1.3, starting from step 2, using compound 12 as the starting material, and finally obtaining intermediate I-4 (64 mg, yield 24%). 1H NMR (600 MHz, DMSO- d 6) δ 12.97 (s, 1H), 8.56 (t, J = 6.0 Hz, 1H), 8.00 (s, 1H), 7.67 (d, J = 8.2 Hz, 1H), 7.39(s, 1H), 7.02 (dd, J = 6.1, 2.1 Hz, 1H), 5.15 (d, J = 3.7 Hz, 1H), 4.50 –4.46 (m, 2H), 4.37 – 4.32 (m, 2H), 3.75 (d, J = 8.2 Hz, 1H), 3.57 (s, 1H), 2.12 – 2.07 (m, 2H), 1.90 – 1.86 (m, 1H), 0.98 (d, J = 6.7 Hz, 3H), 0.96 (d, J = 6.8 Hz, 3H). LCMS (ESI): m / z 386.2 [M+H] + . Example 1.5 Synthesis of key intermediate I-5 Step 1: Preparation of Compound 22. Compound 20 (10 g, 41.09 mmol) was dissolved in tetrahydrofuran (150 mL). Sodium hydride (3.44 g, 86.10 mmol) was added in portions with stirring in an ice bath. After stirring at room temperature for 15 minutes, compound 21 (6.09 g, 39.14 mmol) was added under ice bath conditions. The mixture was heated to room temperature and stirred for 6 hours. After the reaction was confirmed to be complete by TLC, saturated ammonium chloride solution was slowly added to the reaction solution under ice bath conditions until no more bubbles were generated. The mixture was extracted with EA, and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 22 (9.47 g, yield 63.8%). LCMS (ESI): m / z 379.1 [M+H] + . Step 2: Preparation of compound 23. Compound 22 (5.00 g, 13.20 mmol) was dissolved in dichloromethane (20 mL), and trifluoroacetic acid (5 mL) was added under ice bath conditions. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure, and the residue was slurried with petroleum ether to obtain the target compound 23 (3.54 g, yield 96.2%). LCMS (ESI): m / z 279.1 [M+H] + . Step 3: Preparation of Compound 25. Compound 23 (3.00 g, 10.76 mmol), compound 24 (2.51 g, 11.30 mmol), and N,N-diisopropylethylamine (6.95 g, 53.81 mmol) were dissolved in dichloromethane (20 mL), and HATU (4.30 g, 11.30 mmol) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 25 (4.75 g, yield 91.4%). LCMS (ESI): m / z 483.2 [M+H] + . Step 4: Preparation of intermediate I-5. Compound 25 (4.75 g, 9.83 mmol) was dissolved in dichloromethane (20 mL), and trifluoroacetic acid (4 mL) was added. The mixture was stirred at room temperature for 2 h. After the reaction was complete, the reaction solution was concentrated under reduced pressure, and the residue was slurried with petroleum ether to obtain the target compound I-5 (4.09 g, yield 97.4%). 1 H NMR (600 MHz, DMSO- d 6) δ 8.07 – 8.02(m, 4H), 7.94 – 7.90 (m, 3H), 7.22 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8,2.4 Hz, 1H), 4.33 (s, 1H), 4.09 (d, J = 9.1 Hz, 1H), 1.24 (s, 6H), 1.14 (s,6H). LCMS (ESI): m / z 427.1 [M+H] + . Example 2. Synthesis of the A-series target products Example 2.1 Synthesis of target products A-1, A-2, A-4, A-6~A-8, A-13 General Step 1: Compound I-5 (1 equivalent), the corresponding monoaminoalkylyne (1.05 equivalent), and DIPEA (4 equivalent) were dissolved in dichloromethane (5 mL), and HATU (1.05 equivalent) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the corresponding intermediate.

[0138] General Step 2: Dissolve the intermediate (1 equivalent), compound I-1 (1.05 equivalent), and copper sulfate pentahydrate (0.2 equivalent) in DMSO (5 mL) and H2O (1 mL), purge with nitrogen three times, add sodium ascorbate (2 equivalent), stir at room temperature under nitrogen for 4 hours, and purify by preparative high performance liquid chromatography to obtain the A series target products (yield 30-60%).

[0139] Preparation of compound A-1. Compound A-1 (12 mg, yield 45%) was obtained from compounds I-5 and 26 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (s, 1H), 8.71 (t, J = 5.6 Hz, 1H), 8.48 (d, J = 7.7 Hz, 1H), 8.00 (s, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.90(d, J = 8.1 Hz, 5H), 7.47 – 7.43 (m, 2H), 7.39 – 7.35 (m, 2H), 7.21 (d, J =2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.5 Hz, 1H), 5.23 (d, J = 10.2 Hz, 1H), 4.97– 4.89 (m, 1H), 4.38 (t, J = 8.1 Hz, 1H), 4.33 (s, 1H), 4.32 (s, 1H), 4.09(d, J = 9.2 Hz, 1H), 3.75 (dd, 1H), 3.63 (d, J = 10.9 Hz, 1H), 3.58 – 3.53(m, 2H), 2.93 (t,J = 7.4 Hz, 2H), 2.45 (s, 3H), 2.39 – 2.33 (m, 1H), 2.04(d, J = 10.3 Hz, 1H), 1.81 – 1.74 (m, 1H), 1.38 (d, J = 7.0 Hz, 3H), 1.24 (s, 6H), 1.14 (s, 6H), 1.03 (d, J = 6.7 Hz, 3H), 0.62 (d, J = 6.6, 3.6 Hz, 3H).LCMS (ESI): m / z 934.4 [M+H] + . Preparation of compound A-2. Compound A-2 (17 mg, yield 54%) was obtained from compounds I-5 and 27 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (s, 1H), 8.60 (t, J = 5.7 Hz, 1H), 8.49 (d, J = 7.6 Hz, 1H), 7.96 – 7.89 (m, 7H), 7.45 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 2.4 Hz, 1H), 7.02 (dd, J = 8.8, 2.4Hz, 1H), 5.22 (d, J = 10.2 Hz, 1H), 4.95 – 4.90 (m, 1H), 4.39 (t, J = 8.1 Hz,1H), 4.34 (s, 1H), 4.32 (s, 1H), 4.09 (d, J = 9.1 Hz, 1H), 3.76 (dd, J =10.8, 4.2 Hz, 1H), 3.64 (d, J = 10.8 Hz, 1H), 3.34 – 3.30 (m, 2H), 2.67 (t, J= 7.5 Hz, 2H), 2.46 (s, 3H), 2.42 – 2.36 (m, 1H), 2.08 – 2.03 (m, 1H), 1.82 –1.76 (m, 1H), 1.69 – 1.63 (m, 2H), 1.61 – 1.57 (m, 2H), 1.38 (d, J = 7.0 Hz,3H), 1.25 (s, 6H), 1.15 (s, 6H), 1.04 (d, J = 6.7 Hz, 3H), 0.64 (d, J = 6.5Hz, 3H). LCMS (ESI): m / z 962.4 [M+H] + . Preparation of compound A-4. Compound A-4 (14 mg, yield 51%) was obtained from compounds I-5 and 28 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.55 (t, J = 5.6 Hz, 1H), 8.48 (d, J = 7.7 Hz, 1H), 7.95 – 7.87 (m, 7H), 7.46 – 7.43 (m, 2H), 7.37– 7.34 (m, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.21 (d, J = 10.2 Hz, 1H), 4.95 – 4.88 (m, 1H), 4.38 (t, J = 8.1 Hz, 1H), 4.33 (s, 1H), 4.31 (s, 1H), 4.09 (d, J = 9.0 Hz, 1H), 3.76 (dd, J = 10.8, 4.2Hz, 1H), 3.63 (d, J = 10.9 Hz, 1H), 3.29 – 3.25 (m, 2H), 2.62 (t, J = 7.7 Hz, 2H), 2.45 (s, 3H), 2.44 – 2.37 (m, 1H), 2.04 (d,J = 10.4 Hz, 1H), 1.82 –1.75 (m, 1H), 1.61 (t, J = 7.3 Hz, 2H), 1.56 – 1.51 (m, 2H), 1.39 – 1.33 (m,7H), 1.24 (s, 6H), 1.14 (s, 6H), 1.03 (d, J = 6.7 Hz, 3H), 0.64 (d, J = 6.6,3.7 Hz, 3H). LCMS (ESI): m / z 990.4 [M+H] + . Preparation of compound A-6. Compound A-6 (12 mg, yield 44%) was obtained from compounds I-5 and 29 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (s, 1H), 8.55 (t, J = 5.7 Hz, 1H), 8.48 (d, J = 7.6 Hz, 1H), 7.96 – 7.88 (m, 7H), 7.44 (d, J = 7.9 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.21 (d, 1H), 7.01 (dd, 1H), 5.20 (d, J = 10.2 Hz,1H), 4.95 – 4.89 (m, 1H), 4.38 (t, J = 8.1 Hz, 1H), 4.33 (s, 1H), 4.31 (s,1H), 4.09 (d, J = 9.1 Hz, 1H), 3.76 (dd, J = 10.9, 4.2 Hz, 1H), 3.63 (d, 1H), 3.29 – 3.24 (m, 2H), 2.61 (t, J = 7.6 Hz, 2H), 2.45 (s, 3H), 2.41 – 2.37 (m,1H), 2.08 – 2.02 (m, 1H), 1.81 – 1.75 (m, 1H), 1.59 (t, J= 7.2 Hz, 2H), 1.56– 1.50 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.30 (s, 8H), 1.24 (s, 6H), 1.14(s, 6H), 1.03 (d, J = 6.7 Hz, 3H), 0.64 (d, J = 6.5 Hz, 3H). LCMS (ESI): m / z1018.4 [M+H] + . Preparation of compound A-7: Using compound I-5 and compound 30 as raw materials, compound A-6 (9 mg, yield 45%) was obtained through a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.55 (t, J = 5.6 Hz, 1H), 8.48 (d, J = 7.6 Hz, 1H), 7.96 – 7.87 (m, 7H), 7.44 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4Hz, 1H), 5.20 (d, J = 10.2 Hz, 1H), 4.95 – 4.88 (m, 1H), 4.38 (t, J = 8.1 Hz,1H), 4.33 (s, 1H), 4.31 (s, 1H), 4.09 (d, J = 9.1 Hz, 1H), 3.75 (dd, J =10.8, 4.2 Hz, 1H), 3.63 (d, 1H), 3.29 – 3.24 (m, 2H), 2.60 (t, J = 7.6 Hz, 2H), 2.45 (d, J= 2.2 Hz, 3H), 2.42 – 2.38 (m, 1H), 2.07 – 2.02 (m, 1H), 1.81 – 1.75 (m, 1H), 1.61 – 1.56 (m, 2H), 1.56 – 1.50 (m, 2H), 1.38 (d, J = 7.0Hz, 3H), 1.31 – 1.25 (m, 12H), 1.24 (s, 6H), 1.14 (s, 6H), 1.03 (d, J = 6.6Hz, 3H), 0.63 (d, J = 6.5 Hz, 3H). LCMS (ESI): m / z 1046.5 [M+H] + . Preparation of compound A-8: Using compounds I-5 and 37 as starting materials, compound A-8 (9 mg, 45% yield) was obtained through a general procedure. 1 HNMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.66 (t, J = 5.6 Hz, 1H), 8.49 (d, J =7.6 Hz, 1H), 8.15 (d, J = 12.2 Hz, 1H), 7.96 – 7.92 (m, 3H), 7.92 – 7.89 (m,3H), 7.44 (d, 2H), 7.38 – 7.34 (m, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.28 (d, J = 10.2 Hz, 1H), 4.94 – 4.87 (m, 1H), 4.54 (s,2H), 4.39 (t, J = 8.1 Hz, 1H), 4.33 (s, 1H), 4.32 (d, J = 4.7 Hz, 1H), 4.09(d, J = 9.1 Hz, 1H), 3.76 (dd, J= 10.8, 4.2 Hz, 1H), 3.66 (d, J = 10.9 Hz,1H), 3.58 (s, 4H), 3.56 (t, J = 6.0 Hz, 2H), 3.45 (t, J = 5.8 Hz, 2H), 2.45(s, 3H), 2.43 – 2.40 (m, 1H), 2.09 – 2.02 (m, 1H), 1.82 – 1.74 (m, 1H), 1.37(d, J = 7.0 Hz, 3H), 1.24 (s, 6H), 1.14 (s, 6H), 1.04 (d, J = 6.6 Hz, 3H), 0.65 (d, J = 6.6, 2.2 Hz, 3H). LCMS (ESI): m / z 1008.4 [M+H] + . Preparation of compound A-13: Starting with compounds I-5 and 1-S, compound A-13 (11 mg, 34% yield) was obtained by following the synthetic steps in Example 1.1 and the general steps described above. LCMS (ESI): m / z 990.4 [M+H] + . Example 3. Synthesis of the B-series target product Example 3.1 Synthesis of target products B-1~B-20 General Step 1: Compound I-5 (1 equivalent), the corresponding heterocycle (1.05 equivalent), and DIPEA (4 equivalent) were dissolved in dichloromethane (5 mL), and HATU (1.05 equivalent) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the corresponding compound 33.

[0140] General Step 2: Dissolve the compound in dichloromethane (5 mL), add trifluoroacetic acid (1 mL), and stir at room temperature for 2 h. After the reaction is complete, concentrate the reaction solution under reduced pressure, and slurry the residue with petroleum ether to obtain the corresponding compound 34.

[0141] General Step 3: Dissolve the corresponding intermediate and DIPEA (4 equivalents) in acetonitrile (5 mL), slowly add chloropropyne (1.5 equivalents), and stir at room temperature for 4 hours. After the reaction is complete, concentrate the reaction solution under reduced pressure, dilute with EA, wash once with saturated sodium bicarbonate solution, wash once with water, wash once with saturated sodium chloride solution, dry the organic phase with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and purify the residue by column chromatography to obtain compound 35.

[0142] General Step 4: Compound 35 (1 equivalent), compound I-1 (1.05 equivalent), and copper sulfate pentahydrate (0.1 equivalent) were dissolved in DMSO (5 mL) and H2O (1 mL), the mixture was purged with nitrogen three times, sodium ascorbate (2 equivalents) was added, and the mixture was reacted at room temperature for 3 hours. Compound B was obtained by preparative high performance liquid chromatography.

[0143] Synthesis of compound B-1. Compound B-1 was obtained from compound 32-a and compound I-5 via a general procedure. LCMS (ESI): m / z 1017.4 [M+H] + . Synthesis of compound B-2.

[0144] Using compounds 38-b and I-5 as starting materials, compound B-2 (14 mg, 49% yield) was obtained via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (s, 1H), 8.67 (t, J = 5.8 Hz, 1H), 8.49(d, J = 7.6 Hz, 1H), 8.41 (s, 1H), 7.97 – 7.89 (m, 6H), 7.45 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 2.4 Hz, 1H), 7.02 (dd, J = 8.7, 2.4 Hz, 1H), 5.42 (d, J = 9.8 Hz, 1H), 4.96 – 4.89 (m, 1H), 4.42 (d, 1H), 4.39 (t, J = 8.2 Hz, 1H), 4.34 (s, 2H), 4.09 (d, J = 9.0 Hz, 1H), 3.76 (dd,J = 11.0, 3.9 Hz, 1H), 3.69 (d, J = 11.0 Hz, 1H), 3.59 (d, J = 12.2 Hz, 2H),3.38 – 3.33 (m, 2H), 3.21 (t, J = 6.3 Hz, 2H), 2.98 (s, 2H), 2.46 (s, 3H), 2.44 – 2.39 (m, 1H), 2.12 – 2.06 (m, 1H), 1.91 (d, J = 13.8 Hz, 2H), 1.85 –1.77 (m, 2H), 1.44 (d, J = 12.9 Hz, 1H), 1.38 (d, J = 7.0 Hz, 3H), 1.25 (s,6H), 1.15 (s, 6H), 1.07 (d, J = 6.5 Hz, 3H), 0.70 (d, J = 6.5 Hz, 3H). LCMS(ESI): m / z 1017.4 [M+H] + . Synthesis of compound B-3.

[0145] Compound B-3 (14 mg, 52% yield) was obtained from compounds 38-c and I-5 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (d, J = 2.7 Hz, 1H), 8.95 (d, J = 8.2Hz, 2H), 8.48 (d, J = 7.6 Hz, 1H), 8.34 (s, 1H), 7.96 – 7.87 (m, 4H), 7.49 –7.43 (m, 4H), 7.36 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.38 (d, J= 10.0 Hz, 1H), 4.95 – 4.89 (m, 1H), 4.48 (s,1H), 4.37 (t, J = 8.2 Hz, 1H), 4.34 – 4.32 (m, 2H), 4.29 (t, J = 5.7 Hz, 2H), 4.08 (d, J = 9.1 Hz, 1H), 3.76 (dd, J = 10.9, 4.0 Hz, 1H), 3.68 (d, J = 11.0Hz, 1H), 3.44 (d, J = 7.0 Hz, 4H), 3.02 (s, 2H), 2.76 (s, 1H), 2.46 (s, 3H), 2.43 – 2.37 (m, 1H), 2.10 – 2.05 (m, 1H), 1.83 – 1.71 (m, 2H), 1.67 – 1.61(m, 1H), 1.58(d, J = 7.7 Hz, 2H), 1.38 (d, J = 7.0 Hz, 3H), 1.24 (s, 6H), 1.14 (s, 6H), 1.06 (d, J = 6.9 Hz, 3H), 0.69 (d, J = 6.6 Hz, 3H). LCMS (ESI): m / z 1031.4 [M+H] + . Synthesis of compound B-4.

[0146] Compound B-4 (13 mg, 57% yield) was obtained from compounds 38-d and I-5 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.58 (t, J = 5.5 Hz, 1H), 8.49(d, J = 7.6 Hz, 1H), 8.41 (s, 1H), 7.97 – 7.88 (m, 6H), 7.45 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.21 (d,J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.41 (d, J = 9.9 Hz, 1H), 4.95 – 4.85 (m, 1H), 4.42 – 4.36 (m,2H), 4.33 (s, 2H), 4.09 (d, J = 9.1 Hz, 1H), 3.77 – 3.67 (m, 2H), 3.33 – 3.29(m, 4H), 3.20 (s, 2H), 2.95 (s, 2H), 2.45 (s, 3H), 2.43 – 2.37 (m, 1H), 2.10– 2.05 (m, 1H), 1.95 (d, J = 13.4 Hz, 2H), 1.82 – 1.76 (m, 1H), 1.57 – 1.46(m, 3H), 1.38 (d, J = 7.0 Hz, 3H), 1.36 – 1.32 (m, 1H), 1.24 (s, 6H), 1.14(s, 6H), 1.07 (d, J = 6.5 Hz, 3H), 0.69 (d, J = 6.5 Hz, 3H). LCMS (ESI): m / z1031.4 [M+H] + . Synthesis of compound B-5.

[0147] Compound B-5 (13 mg, 60% yield) was obtained from compound 38-e and compound I-5 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (d, J = 3.7 Hz, 1H), 8.49 (d, J = 7.7Hz, 1H), 8.40 (s, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.90 (t, J = 8.0 Hz, 3H),7.50 – 7.43 (m, 4H), 7.37 (d, J = 8.1 Hz, 2H), 7.21 (d, J= 2.4 Hz, 1H), 7.01(dd, J = 8.8, 2.5 Hz, 1H), 5.41 (d, J = 9.8 Hz, 1H), 4.96 – 4.88 (m, 1H), 4.47 (s, 2H), 4.38 (t, J = 8.2 Hz, 1H), 4.33 (s, 2H), 4.08 (d, J = 9.1 Hz,1H), 3.76 – 3.66 (m, 4H), 3.33 – 3.24 (m, 4H), 3.13 (d, J = 43.0 Hz, 2H), 2.46 (s, 3H), 2.44 – 2.38 (m, 1H), 2.10 – 2.05 (m, 1H), 1.93 (d, J = 14.3 Hz, 2H), 1.83 – 1.76 (m, 1H), 1.68 (s, 1H), 1.59 – 1.47 (m, 3H), 1.43 (s, 1H), 1.38 (d, J = 7.0 Hz, 3H), 1.31 (s, 1H), 1.24 (s, 6H), 1.14 (s, 6H), 1.07 (d, J = 6.5 Hz, 3H), 0.69 (d, J = 6.5 Hz, 3H). LCMS (ESI): m / z 1057.4 [M+H] + . Synthesis of compound B-6.

[0148] Compound B-6 (17 mg, 51% yield) was obtained from compounds 38-f and I-5 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.52 – 8.39 (m, 2H), 7.94 (d, J = 9.1 Hz, 1H), 7.92 – 7.88 (m, 3H), 7.46 (dd, J = 17.0, 7.9 Hz, 4H), 7.36 (d, J = 8.0 Hz, 2H), 7.21 (d, J= 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.42 (d, J = 9.8 Hz, 1H), 4.96 – 4.88 (m, 1H), 4.42 (s, 1H), 4.38 (d, J = 7.9Hz, 1H), 4.33 (d, J = 8.1 Hz, 2H), 4.08 (d, J = 9.1 Hz, 1H), 3.75 (dd, J =11.1, 3.9 Hz, 1H), 3.68 (d, J = 10.8 Hz, 1H), 3.59 – 3.47 (m, 4H), 3.31 –3.20 (m, 4H), 2.83 (s, 2H), 2.45 (s, 4H), 2.12 – 2.04 (m, 1H), 1.89 (s, 1H),1.85 – 1.67 (m, 4H), 1.60 (s, 1H), 1.56 – 1.49 (m, 1H), 1.45 (s, 1H), 1.38(d, J = 7.0 Hz, 3H), 1.24 (s, 6H), 1.14 (s, 6H), 1.07 (d, J = 6.6 Hz, 3H), 0.69 (d, J = 7.5 Hz, 3H). LCMS (ESI): m / z 1057.4 [M+H] + . Synthesis of compound B-7.

[0149] Using compound 38-g and compound I-5 as starting materials, compound B-7 (15 mg, yield 47%) was obtained through a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.49 (d, J = 7.7 Hz, 1H), 8.42(s, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.89 (t, J = 8.4 Hz, 3H), 7.49 (d, J= 8.0Hz, 1H), 7.44 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.21 (s, 1H), 7.01 (d, J = 8.7 Hz, 1H), 5.41 (d, J = 10.0 Hz, 1H), 4.97 – 4.85 (m, 1H), 4.52 (d, J = 21.8 Hz, 1H), 4.38 (t, J = 8.3 Hz, 1H), 4.33 (s, 2H), 4.08 (d, J = 9.0 Hz, 1H), 3.75 (d, J = 9.5 Hz, 1H), 3.69 (d, J = 10.7 Hz, 1H), 3.65 –3.50 (m, 4H), 3.32 – 3.19 (m, 4H), 3.15 – 2.99 (m, 1H), 2.47 – 2.40 (m, 4H),2.10 – 2.05 (m, 1H), 1.97 – 1.77 (m, 3H), 1.69 (s, 1H), 1.62 – 1.41 (m, 6H), 1.38 (d, J = 6.9 Hz, 3H), 1.23 (s, 6H), 1.14 (d, J = 3.4 Hz, 6H), 1.07 (d, J = 6.4 Hz, 3H), 0.70 (d, J = 6.9 Hz, 3H). LCMS (ESI): m / z 1057.4 [M+H] + . Synthesis of compound B-8.

[0150] Compound B-8 (15 mg, 47% yield) was obtained from compound 38-h and compound I-5 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.49 (d, J = 7.6 Hz, 1H), 8.40(s, 1H), 7.94 (d, J= 9.1 Hz, 1H), 7.90 (dd, J = 8.5, 6.3 Hz, 3H), 7.49 (d, J = 8.1 Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.41 (d, J = 9.9 Hz, 1H), 4.96– 4.91 (m, 1H), 4.42 (s, 1H), 4.38 (t, J = 8.2 Hz, 1H), 4.33 (d, J = 8.5 Hz, 2H), 4.21 (s, 1H), 4.08 (d, J = 9.1 Hz, 1H), 3.86 (s, 2H), 3.75 (dd, J =11.0, 3.9 Hz, 1H), 3.68 (d, J = 11.0 Hz, 1H), 3.62 – 3.54 (m, 4H), 3.36 –3.20 (m, 4H), 3.07 (s, 2H), 2.47 – 2.37 (m, 4H), 2.11 – 2.05 (m, 1H), 1.83 –1.76 (m, 1H), 1.60 (s, 2H), 1.38 (d, J = 7.0 Hz, 3H), 1.24 (s, 6H), 1.14 (s,6H), 1.07 (d, J = 6.7 Hz, 3H), 0.70 (d, J = 6.6 Hz, 3H). LCMS (ESI): m / z1059.4 [M+H] + . Synthesis of compound B-9.

[0151] Using compounds 38-i and I-5 as starting materials, compound B-9 (15 mg, 47% yield) was obtained through a general procedure. 1 H NMR (600 MHz, DMSO- d6) δ 8.99 (s, 1H), 8.49 (d, J = 7.7 Hz, 1H), 8.42(s, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.90 (d, J = 8.5 Hz, 3H), 7.61 – 7.48 (m,2H), 7.45 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.42 (d, J = 9.8 Hz, 1H), 4.95 – 4.88(m, 1H), 4.50 (s, 1H), 4.38 (t, J = 8.3 Hz, 1H), 4.33 (s, 2H), 4.08 (d, J =9.1 Hz, 1H), 3.78 – 3.68 (m, 8H), 3.33 (s, 4H), 3.11 (d, J = 51.7 Hz, 2H),2.47 – 2.38 (m, 4H), 2.22 (s, 2H), 2.11 – 2.05 (m, 1H), 1.83 – 1.76 (m, 1H),1.71 (s, 1H), 1.38 (d, J = 7.0 Hz, 3H), 1.23 (s, 6H), 1.14 (s, 6H), 1.06 (d, J = 6.5 Hz, 3H), 0.69 (d, J = 6.9 Hz, 3H). LCMS (ESI): m / z 1059.4 [M+H] + . Synthesis of compound B-10.

[0152] Compound B-10 (12 mg, 41% yield) was obtained from compounds 38-j and I-5 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (d, J= 2.1 Hz, 1H), 8.49 (d, J = 7.7Hz, 1H), 7.95 (d, J = 9.2 Hz, 1H), 7.92 – 7.87 (m, 3H), 7.48 (d, J = 8.0 Hz,2H), 7.45 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 2.4 Hz,1H), 7.02 (dd, J = 8.8, 2.4 Hz, 1H), 5.19 (s, 1H), 4.95 – 4.88 (m, 1H), 4.54(s, 1H), 4.38 (t, J = 8.2 Hz, 1H), 4.33 (s, 2H), 4.09 (d, J = 9.1 Hz, 1H),3.76 (d, J = 8.2 Hz, 1H), 3.68 (d, J = 10.4 Hz, 1H), 3.60 – 3.44 (m, 6H),3.29 – 3.22 (m, 4H), 3.11 (t, J = 22.3 Hz, 1H), 2.46 (s, 3H), 2.45 – 2.41 (m,1H), 2.07 (d, J = 7.6 Hz, 1H), 2.03 – 1.84 (m, 1H), 1.82 – 1.77 (m, 1H), 1.64(s, 2H), 1.53 (d, J = 7.0 Hz, 2H), 1.38 (d, J = 7.0 Hz, 3H), 1.24 (s, 6H),1.15 (s, 6H), 1.07 (d, J = 6.8 Hz, 3H), 0.69 (d, 3H). LCMS (ESI): m / z 1043.4[M+H] + . Synthesis of Compound B-11

[0153] Compound B-11 (13 mg, 37% yield) was obtained from compounds 38-k and I-5 via a general procedure. LCMS (ESI): m / z 1043.4 [M+H] + . Synthesis of compound B-12.

[0154] Using compounds 38-l and I-5 as starting materials, compound B-12 (13 mg, 37% yield) was obtained through a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (d, J = 3.2 Hz, 1H), 8.48 (d, J = 7.7Hz, 1H), 8.41 (s, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.90 (dd, J = 8.5, 3.6 Hz,3H), 7.47 – 7.43 (m, 4H), 7.36 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.40 (d, J = 10.0 Hz, 1H), 4.94 – 4.89 (m,1H), 4.55 (d, J = 5.1 Hz, 2H), 4.39 – 4.31 (m, 3H), 4.08 (d, J = 9.1 Hz, 1H), 4.03 (d, J = 7.1 Hz, 2H), 3.93 (s, 2H), 3.75 (dd, J = 10.8, 3.9 Hz, 1H), 3.69(s, 1H), 3.63 – 3.55 (m, 4H), 2.45 (s, 3H), 2.41 (d, J = 9.9 Hz, 1H), 2.07(dd, J = 14.1, 6.9 Hz, 1H), 1.90 – 1.73 (m, 5H), 1.38 (d, J= 7.0 Hz, 3H),1.24 (s, 6H), 1.14 (s, 6H), 1.07 (d, 3H), 0.69 (d, J = 6.4 Hz, 3H). LCMS(ESI): m / z 1029.4 [M+H] + . Synthesis of compound B-13.

[0155] Using compound 38-m and compound I-5 as starting materials, compound B-13 (14 mg, yield 41%) was obtained through a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.49 (d, J = 7.6 Hz, 1H), 8.39(d, J = 13.6 Hz, 1H), 7.97 (d, J = 9.0 Hz, 1H), 7.90 (d, J = 9.3 Hz, 3H), 7.72 (d, J = 7.3 Hz, 2H), 7.44 (d, J = 7.9 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 2.6 Hz, 1H), 7.01 (dd, J = 8.8, 2.6 Hz, 1H), 5.40 (d, J = 9.7Hz, 1H), 4.92 (t, J = 7.4 Hz, 1H), 4.47 – 4.31 (m, 5H), 4.08 (dd, J = 23.2,14.1 Hz, 3H), 3.90 (s, 1H), 3.80 (s, 1H), 3.74 (s, 2H), 3.68 (s, 2H), 3.06(s, 1H), 2.96 (s, 1H), 2.46 – 2.38 (m, 4H), 2.18 – 2.04 (m, 3H), 1.88 – 1.75 (m, 3H), 1.38 (d, J = 7.0 Hz, 3H), 1.23 (s, 6H), 1.14 (s, 6H), 1.06 (d,J =6.1 Hz, 3H), 0.69 (d, J = 7.0, 6.6 Hz, 3H). LCMS (ESI): m / z 1029.4 [M+H] + . Synthesis of compound B-14.

[0156] Using compounds 38-n and I-5 as starting materials, compound B-14 (17 mg, yield 57%) was obtained through a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 9.26 (d, J = 10.7 Hz, 2H), 8.99 (s, 1H), 8.47(d, J = 7.7 Hz, 1H), 8.34 (s, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.92 – 7.88 (m,3H), 7.47 – 7.44 (m, 4H), 7.36 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.7, 2.5 Hz, 1H), 5.38 (d, J = 9.9 Hz, 1H), 4.95 – 4.90 (m,1H), 4.38 – 4.32 (m, 3H), 4.17 (t, J = 5.8 Hz, 2H), 4.08 (d, J = 9.1 Hz, 1H), 3.76 (dd, J = 10.9, 4.0 Hz, 1H), 3.67 (d, J = 10.9 Hz, 1H), 3.59 (d, J = 11.1Hz, 2H), 3.34 – 3.31 (m, 1H), 3.20 (d, J = 43.1 Hz, 2H), 2.46 (s, 3H), 2.43 –2.37 (m, 1H), 2.18 (s, 2H), 2.10 – 2.03 (m, 1H), 1.94 (s, 2H), 1.82 – 1.77(m, 1H), 1.63 (d,J = 24.6 Hz, 2H), 1.56 – 1.47 (m, 3H), 1.38 (d, J = 7.0 Hz,3H), 1.24 (s, 6H), 1.14 (s, 6H), 1.06 (d, J = 6.7 Hz, 3H), 0.70 (d, J = 6.7Hz, 3H). LCMS (ESI): m / z 1043.4 [M+H] + . Synthesis of compound B-15.

[0157] Compound B-15 (11 mg, 34% yield) was obtained from compounds 38-o and I-5 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.74 (d, J = 7.1 Hz, 1H), 8.50(d, J = 7.7 Hz, 1H), 8.42 (s, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.93 – 7.89 (m,5H), 7.45 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.41 (d, J = 9.9 Hz, 1H), 4.92 (t, J =7.2 Hz, 1H), 4.43 (s, 2H), 4.38 (t, J = 8.2 Hz, 1H), 4.33 (s, 2H), 4.09 (d, J = 9.1 Hz, 1H), 3.75 (d, J = 8.0 Hz, 1H), 3.69 (d, J = 9.0 Hz, 1H), 3.62 –3.50 (m, 2H), 3.28 – 3.19 (m, 2H), 2.96 (d, J= 63.3 Hz, 2H), 2.45 (s, 4H), 2.35 (s, 1H), 2.14 (s, 1H), 2.11 – 2.05 (m, 1H), 2.03 – 1.95 (m, 2H), 1.88(t, J = 10.0 Hz, 1H), 1.82 – 1.67 (m, 3H), 1.38 (d, J = 7.0 Hz, 3H), 1.24 (s,6H), 1.14 (s, 6H), 1.07 (d, J = 6.6 Hz, 3H), 0.70 (d, J = 6.4 Hz, 3H). LCMS(ESI): m / z 1043.4 [M+H] + . Synthesis of compound B-16.

[0158] Using compounds 38-p and I-5 as starting materials, compound B-16 (14 mg, 37% yield) was obtained through a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.55 – 8.39 (m, 2H), 7.95 (d, J = 9.3 Hz, 1H), 7.91 (t, J = 8.8 Hz, 3H), 7.53 (d, J = 7.6 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 7.7 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.43 (d, J = 9.9 Hz, 1H), 4.97 – 4.87 (m, 1H), 4.56 (s, 2H), 4.43 – 4.32 (m, 3H), 4.08 (d, J = 9.1 Hz, 2H), 3.79 – 3.73 (m, 1H), 3.69(d, J= 10.9 Hz, 1H), 3.63 – 3.54 (m, 4H), 3.35 – 3.18 (m, 4H), 2.45 (d, J =5.6 Hz, 4H), 2.11 – 2.04 (m, 2H), 1.82 – 1.77 (m, 1H), 1.38 (d, J = 7.0 Hz,3H), 1.24 (s, 6H), 1.14 (s, 6H), 1.07 (t, J = 6.1 Hz, 3H), 0.71 (d, J = 6.5Hz, 3H). 1003.3 [M+H] + . Example 3.2 Synthesis of compounds B-17 and B-18. Step 1: Preparation of Compound 52. Compound I-5 (30 mg, 70.27 µmol), compound 37 (16 mg, 73.79 µmol), and DIPEA (50 µL, 281.10 µmol) were dissolved in dichloromethane (8 mL), and HATU (28 mg, 73.79 µmol) was added. The mixture was stirred at room temperature for 3 hours. After the reaction was complete, the reaction solution was washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 52 (17 mg, 39% yield). LCMS (ESI): m / z 623.2 [M+H] + . Step 2: Preparation of Compound 53. Compound 52 (17 mg, 27.28 µmol) was dissolved in dichloromethane (3 mL), and trifluoroacetic acid (600 µL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure, and the residue was slurried with petroleum ether to give compound 53 (14 mg, 98% yield). LCMS (ESI): m / z 523.2 [M+H] + . Step 3: Preparation of Compound 54. Compound 53 (14 mg, 26.76 µmol), propargyl acid (2 mg, 28.10 µmol), and DIPEA (18 µL, 107.06 µmol) were dissolved in dichloromethane (5 mL), and HATU (11 mg, 28.10 µmol) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure, and the residue was slurried with petroleum ether to give compound 54 (13 mg, yield 84%). LCMS (ESI): m / z 575.2 [M+H] + . Step 4: Preparation of compound B-17. Compound 54 (13 mg, 22.60 µmol), compound I-1 (11 mg, 22.60 µmol), and copper sulfate pentahydrate (1 mg, 4 µmol) were dissolved in DMSO (5 mL) and H2O (1 mL). The mixture was purged with nitrogen three times, and sodium ascorbate (9 mg, 45.21 µmol) was added. The reaction was carried out at room temperature for 3 hours. Compound B-17 (11 mg, 33% yield) was obtained by preparative high-performance liquid chromatography. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (s, 1H), 8.67 (t, J = 5.9 Hz, 1H), 8.56 – 8.51 (m, 2H), 7.98 – 7.88 (m, 6H), 7.44 (d, J =8.0 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.39 (d, J = 10.2 Hz, 1H), 4.92 (q, J = 7.2 Hz, 1H), 4.69(s, 1H), 4.48 (d, J = 12.8 Hz, 1H), 4.39 (t, J = 8.2 Hz, 1H), 4.32 (d, J =7.9 Hz, 2H), 4.09 (d, J = 9.1 Hz, 1H), 3.78 – 3.67 (m, 2H), 3.24 – 3.19 (m,2H), 3.16 (d,J = 12.3 Hz, 1H), 2.78 (s, 1H), 2.52 – 2.51 (m, 1H), 2.45 (s,4H), 2.07 (q, J = 8.0, 7.4 Hz, 1H), 1.94 – 1.88 (m, 1H), 1.83 – 1.73 (m, 3H), 1.37 (d, J = 7.0 Hz, 3H), 1.24 (s, 6H), 1.14 (s, 6H), 1.06 (d, J = 6.8 Hz, 3H), 0.69 (d, J = 6.5 Hz, 3H). LCMS (ESI): m / z 1017.4 [M+H] + . Synthesis of compound B-18. Compound B-18 (14 mg, 47% yield) was synthesized from compounds I-5 and 38-f according to the synthesis of compound B-17. LCMS (ESI): m / z 1071.4 [M+H] + . Example 3.3 Synthesis of Compound B-19 Step 1: Preparation of Compound 57. Compound 55 (5.00 g, 20.22 mmol) and Compound 56 (3.77 g, 20.22 mmol) were dissolved in dichloromethane (100 mL), and DIPEA (14.09 mL, 80.88 mmol) was added. The mixture was stirred at room temperature for 2 hours, and then sodium triacetoxyborohydride (8.57 g, 40.44 mmol) was added. The mixture was stirred at room temperature overnight. After the reaction was complete, the reaction solution was washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain Compound 57 (7.41 g, 88% yield). LCMS (ESI): m / z 418.2 [M+H] + . Step 2: Preparation of Compound 58. Compound 57 (3.00 g, 7.18 mmol) was dissolved in methanol (40 mL), and 10% palladium on carbon (300 mg) was added. The mixture was stirred overnight at room temperature under hydrogen atmosphere. After the reaction was complete, the mixture was filtered through diatomaceous earth, and the filter cake was washed three times with a 10% methanol-dichloromethane solution. The filtrate was concentrated under reduced pressure to obtain compound 58 (1.84 g, 90%). LCMS (ESI): m / z 284.2 [M+H] +. Step 3: Preparation of Compound 59. Compound I-5 (100 mg, 234.25 µmol), compound 58 (73.03 mg, 257.67 µmol), and DIPEA (163 µL, 936.99 µmol) were dissolved in dichloromethane (10 mL). HATU (98 mg, 257.67 µmol) was added, and the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 59 (61 mg, 38% yield). LCMS (ESI): m / z 692.3 [M+H] + . Step 4: Preparation of Compound 60. Compound 59 (53 mg, 76.56 µmol) was dissolved in dichloromethane (3 mL), and trifluoroacetic acid (600 µL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure and slurried three times with anhydrous diethyl ether to obtain compound 60 (38 mg, yield 83%). LCMS (ESI): m / z 592.3 [M+H] + . Step 5: Preparation of Compound 61. Compound 60 (38 mg, 64.17 µmol) and DIPEA (45 µL, 256.68 µmol) were dissolved in anhydrous acetonitrile (6 mL), and bromopropyne (11 mg, 96.25 µmol) was added. The mixture was stirred at room temperature for 6 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, diluted with EA, and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 61 (21 mg, 52% yield). LCMS (ESI): m / z 630.3 [M+H] + . Step 6: Preparation of compound B-19. Compound 61 (21 mg, 33.32 µmol), compound I-1 (17 mg, 36.65 µmol), and copper sulfate pentahydrate (1 mg, 4.01 µmol) were dissolved in DMSO (5 mL) and H₂O (1 mL). The mixture was purged with nitrogen three times. Sodium ascorbate (13 mg, 66.64 µmol) was added, and the mixture was stirred at room temperature under nitrogen atmosphere for 3 hours. After the reaction was complete, compound B-19 was obtained by preparative high-performance liquid chromatography (HPLC). LCMS (ESI): m / z 1086.5 [M+H] + . Example 4. Synthesis of C-series target products Example 4.1 Synthesis of compound C-1 Step 1: Preparation of Compound 63. Compound 62 (150 mg, 435.53 µmol), compound 2 (100 mg, 457.31 µmol), and DIPEA (303.46 µL, 1.74 mmol) were dissolved in dichloromethane (10 mL), and HATU (174 mg, 457.31 µmol) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with dichloromethane and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 63 (164 mg, 69% yield). LCMS (ESI): m / z 545.2 [M+H] + . Step 2: Preparation of compound 64. Compound 63 (150 mg, 275.38 µmol) was dissolved in dichloromethane (5 mL), and trifluoroacetic acid (1 mL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was slurried three times with anhydrous diethyl ether to obtain compound 64 (115 mg, yield 94%). LCMS (ESI): m / z 445.2 [M+H] + . Step 3: Preparation of Compound 65. Compound 64 (115 mg, 258.66 µmol), anhydrous copper sulfate (4 mg, 25.87 µmol), and potassium carbonate (143 mg, 1.03 mmol) were dissolved in anhydrous methanol (15 mL). The mixture was stirred at room temperature for 15 minutes, and then compound 5 (67 mg, 388 µmol) was added. The mixture was stirred at room temperature overnight. After the reaction was complete, the reaction solution was concentrated under reduced pressure, diluted with EA, and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 65 (57 mg, 47% yield). LCMS (ESI): m / z 471.2 [M+H] + . Step 4: Preparation of compound C-1. Compound 34 (20 mg, 37.45 µmol), compound 65 (18 mg, 39.32 µmol), and copper sulfate pentahydrate (1 mg, 4.01 µmol) were dissolved in DMSO (5 mL) and H2O (1 mL). The mixture was purged with nitrogen three times. Sodium ascorbate (15 mg, 39.32 µmol) was added, and the mixture was stirred at room temperature under nitrogen for 3 hours. After the reaction was complete, compound C-1 (17 mg, 45% yield) was obtained by preparative high-performance liquid chromatography. 1 H NMR (600 MHz, DMSO- d 6) δ 8.99 (s, 1H), 8.58 (t, J = 5.7 Hz, 1H), 8.52 (d, J = 7.7 Hz, 1H), 8.02(s, 1H), 7.97 (d, J = 9.2 Hz, 1H), 7.94 – 7.88 (m, 5H), 7.44 (d, J = 7.8 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8,2.4 Hz, 1H), 5.43 (s, 1H), 4.95 – 4.88 (m, 1H), 4.42 (t, J = 8.3 Hz, 1H), 4.31 (d, J = 18.6 Hz, 2H), 4.09 (d, J = 9.1 Hz, 1H), 3.68 (dd, J = 11.1, 3.8Hz, 1H), 3.61 (d, J = 11.0 Hz, 1H), 3.28 – 3.24 (m, 2H), 2.63 (t, J= 7.7 Hz,2H), 2.45 (s, 3H), 2.11 – 2.05 (m, 1H), 1.80 – 1.72 (m, 1H), 1.64 – 1.58 (m,2H), 1.55 – 1.51 (m, 2H), 1.41 – 1.32 (m, 7H), 1.24 (s, 6H), 1.14 (s, 6H), 0.96 (s, 9H). LCMS (ESI): m / z 1004.4 [M+H] + . Example 4.2 Synthesis of compound C-3 Step 1: Preparation of Compound 67. Compound 66 (500 mg, 1.50 mmol) was dissolved in dichloromethane (5 mL), and trifluoroacetic acid (1 mL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue was slurried three times with anhydrous diethyl ether to obtain compound 67 (346 mg, 99% yield). LCMS (ESI): m / z 235.0 [M+H] + . Step 2: Preparation of Compound 68. Compound 67 (300 mg, 1.28 mmol), Compound 1 (444 mg, 1.34 mmol), and DIPEA (892.06 µL, 5.12 mmol) were dissolved in dichloromethane (10 mL), and HATU (511 mg, 1.34 mmol) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with dichloromethane and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain Compound 68 (413 mg, 59% yield). LCMS (ESI): m / z 547.2 [M+H] + . Step 3: Preparation of compound 69. Compound 68 (413 mg, 755.47 µmol) was dissolved in dichloromethane (5 mL), and trifluoroacetic acid (1 mL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure and washed three times with anhydrous diethyl ether to obtain compound 69 (321 mg, 95% yield). LCMS (ESI): m / z 447.2 [M+H] + . Step 4: Preparation of Compound 70. Compound 69 (300 mg, 671.79 µmol), anhydrous copper sulfate (11 mg, 67.18 µmol), and potassium carbonate (371 mg, 2.69 mmol) were dissolved in anhydrous methanol (15 mL). The mixture was stirred at room temperature for 15 minutes, and then compound 5 (174 mg, 1.01 mmol) was added. The mixture was stirred at room temperature overnight. After the reaction was complete, the reaction solution was concentrated under reduced pressure, diluted with EA, and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 70 (161 mg, 51% yield). LCMS (ESI): m / z 473.1 [M+H] + . Step 5: Preparation of compound C-3. Compound 34 (20 mg, 37.45 µmol), compound 70 (19 mg, 39.32 µmol), and copper sulfate pentahydrate (1 mg, 4.01 µmol) were dissolved in DMSO (5 mL) and H2O (1 mL). The mixture was purged with nitrogen three times. Sodium ascorbate (15 mg, 74.89 µmol) was added, and the mixture was stirred at room temperature under nitrogen for 3 hours. After the reaction was complete, compound C-3 (13 mg, 35% yield) was purified by preparative high-performance liquid chromatography. 1 H NMR (600 MHz, DMSO- d 6) δ 8.98 (s, 1H), 8.56 (t, J = 5.7 Hz, 1H), 8.45 (d, J = 7.9 Hz, 1H), 7.95– 7.91 (m, 4H), 7.90 – 7.88 (m, 3H), 7.43 (d, J = 8.0 Hz, 2H), 7.37 (d, J =8.1 Hz, 2H), 7.21 (d, J = 2.4 Hz, 1H), 7.01 (dd, J = 8.8, 2.4 Hz, 1H), 5.21(d, J = 10.3 Hz, 1H), 4.84 (q, J = 6.7 Hz, 1H), 4.44 (t, J = 8.0 Hz, 1H), 4.32 (d, J = 12.5 Hz, 2H), 4.08 (d, J= 9.1 Hz, 1H), 3.76 (dd, J = 10.7, 4.0Hz, 1H), 3.63 (d, J = 5.3 Hz, 1H), 3.27 (d, J = 6.7 Hz, 2H), 2.61 (d, J = 6.8Hz, 2H), 2.52 (s, 1H), 2.46 (s, 3H), 2.42 – 2.38 (m, 1H), 2.06 (q, J = 8.6, 7.9 Hz, 1H), 2.01 (t, J = 7.5 Hz, 1H), 1.99 – 1.95 (m, 1H), 1.82 – 1.75 (m,1H), 1.61 (t, J = 7.4 Hz, 2H), 1.54 (t, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 1H), 1.35 (t, J = 4.1 Hz, 4H), 1.24 (s, 6H), 1.14 (s, 6H), 1.03 (d, J = 6.6Hz, 3H), 0.64 (d, J = 6.6 Hz, 3H). LCMS (ESI): m / z 1006.4 [M+H] + . Example 4.3 Synthesis of compounds C-4 to C-6 General Step 1: Compound 34 (1 equivalent), the corresponding azide compound (1.05 equivalent), and copper sulfate pentahydrate (0.1 equivalent) were dissolved in DMSO (5 mL) and H2O (1 mL). The mixture was purged with nitrogen three times. Sodium ascorbate (2 equivalents) was added, and the mixture was stirred at room temperature under nitrogen for 3 hours. After the reaction was completed, the target compound was purified by preparative high-performance liquid chromatography.

[0159] Synthesis of compound C-4. Compound C-4 (17 mg, 45% yield) was obtained from compound 34 and compound I-2 via a general procedure. 1 H NMR (400 MHz, DMSO- d6) δ 8.64 – 8.53 (m, 2H), 8.01 (s, 1H),7.94 (d, J = 7.1 Hz, 2H), 7.92 – 7.88 (m, 5H), 7.68 (d, J = 8.3 Hz, 1H), 7.45(s, 1H), 7.21 (s, 1H), 7.01 (dd, 2H), 5.22 (d, J = 10.2 Hz, 1H), 4.45 (dd, J = 15.3, 6.0 Hz, 1H), 4.40 – 4.32 (m, 4H), 4.10 (s, 1H), 3.83 – 3.81 (m, 1H), 3.65 (d, J = 10.8 Hz, 2H), 3.31 – 3.22 (m, 2H), 2.63 (t, J = 7.7 Hz, 2H), 2.46 – 2.39 (m, 1H), 2.06 (dd, J = 13.5, 7.7 Hz, 1H), 1.95 – 1.87 (m, 1H), 1.65 – 1.57 (m, 2H), 1.56 – 1.49 (m, 2H), 1.36 (s, 4H), 1.24 (s, 6H), 1.14(s, 6H), 1.02 (d, J = 6.8 Hz, 3H), 0.64 (d, J = 6.5 Hz, 3H). LCMS (ESI): m / z919.4 [M+H] + . Synthesis of compound C-5. Compound C-5 (14 mg, 41% yield) was obtained from compounds 34 and I-3 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.65 (t, J = 6.0 Hz, 1H), 8.56 (t, J = 5.6 Hz, 1H), 7.99 (s, 1H), 7.95 – 7.88 (m, 7H), 7.68 (d, J = 8.3 Hz, 1H),7.64 (s, 1H), 7.22 (d, J= 2.4 Hz, 1H), 7.05 – 7.00 (m, 2H), 5.25 (d, J =10.2 Hz, 1H), 4.53 (dd, J = 15.7, 6.5 Hz, 2H), 4.42 (t, J = 8.1 Hz, 1H), 4.41– 4.39 (m, 1H), 4.37 (d, J = 5.5 Hz, 1H), 4.34 (s, 1H), 4.09 (d, J = 9.1 Hz,1H), 4.08 (s, 2H), 3.85 (dd, J = 10.7, 4.2 Hz, 1H), 3.66 (d, J = 10.8 Hz,1H), 3.30 – 3.25 (m, 2H), 2.64 (t, J = 7.7 Hz, 2H), 2.46 – 2.39 (m, 1H), 2.10 – 2.05 (m, 1H), 1.97 – 1.91 (m, 1H), 1.65 – 1.59 (m, 2H), 1.59 – 1.51 (m, 2H), 1.39 – 1.34 (m, 4H), 1.24 (s, 6H), 1.15 (s, 6H), 1.03 (d, J = 6.6 Hz, 3H), 0.66 (d, J = 6.6 Hz, 3H). LCMS (ESI): m / z 933.4 [M+H] + . Synthesis of compound C-6. Compound C-6 (16 mg, 46% yield) was obtained from compounds 34 and I-4 via a general procedure. 1 H NMR (600 MHz, DMSO- d 6) δ 8.59 (t, J = 5.7 Hz, 1H), 8.48 (d, J = 7.9 Hz, 1H), 7.99 (s, 1H), 7.98 (d, J = 9.3 Hz, 1H), 7.94 – 7.92 (m, 3H), 7.92 – 7.89 (m, 3H), 7.61 – 7.56 (m, 2H), 7.33 (dd,J = 8.8, 1.6 Hz, 1H), 7.23 (d, J = 2.4 Hz, 1H), 7.02 (dd, J = 8.8, 2.5 Hz, 1H), 5.21 (d, J = 10.3Hz, 1H), 5.02 – 4.95 (m, 1H), 4.40 – 4.33 (m, 2H), 4.29 (s, 1H), 4.09 (d, J =9.1 Hz, 1H), 4.02 (s, 3H), 3.74 (dd, J = 10.8, 4.2 Hz, 1H), 3.63 (s, 1H), 3.27 (dd, J = 6.6 Hz, 2H), 2.64 (s, 2H), 2.40 – 2.39 (m, 1H), 2.04 – 1.98 (m,1H), 1.75 – 1.68 (m, 1H), 1.65 – 1.59 (m, 2H), 1.56 – 1.53 (m, 2H), 1.40 (d, J = 7.0 Hz, 3H), 1.37 – 1.34 (m, 4H), 1.24 (s, 6H), 1.15 (s, 6H), 1.04 (d, J = 6.7 Hz, 3H), 0.64 (d, J = 6.6 Hz, 3H). LCMS (ESI): m / z 947.4 [M+H] + . Example 4.4 Synthesis of compound C-7 Step 1: Preparation of Compound 72. Compound 71 (250 mg, 2.17 mmol), copper sulfate pentahydrate (35 mg, 217.14 µmol), and potassium carbonate (1.20 g, 8.69 mmol) were dissolved in anhydrous methanol (15 mL) and stirred at room temperature for 15 minutes. Compound 5 (564 mg, 3.26 mmol) was added and stirred at room temperature overnight. After the reaction was complete, the reaction solution was concentrated under reduced pressure, diluted with EA, and the pH was adjusted to 3-4. The mixture was washed twice with acid, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain compound 72 (234 mg, 76% yield). LCMS (ESI): m / z 142.1 [M+H] + . Step 2: Preparation of Compound 73. Compound 72 (234 mg, 1.66 mmol), compound 73 (326 mg, 1.74 mmol), and DIPEA (1.16 mL, 6.63 mmol) were dissolved in dichloromethane (10 mL), and HATU (662 mg, 1.74 mmol) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with dichloromethane and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 73 (417 mg, 81% yield). LCMS (ESI): m / z 311.1 [M+H] + . Step 3: Preparation of compound 74. Compound 73 (400 mg, 1.29 mmol) was dissolved in dichloromethane (5 mL), and trifluoroacetic acid (1 mL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was washed three times with anhydrous diethyl ether and concentrated under reduced pressure to obtain compound 74 (299 mg, yield 91%). LCMS (ESI): m / z 255.2 [M+H] + . Step 4: Preparation of Compound 75. Compound 74 (299 mg, 1.18 mmol), Compound 2 (270 mg, 1.23 mmol), and DIPEA (819.40 µL, 4.70 mmol) were dissolved in dichloromethane (10 mL), and HATU (469 mg, 1.23 mmol) was added and stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with dichloromethane and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain Compound 75 (316 mg, 59% yield). LCMS (ESI): m / z 455.2 [M+H] + . Step 5: Preparation of compound C-7. Compound 34 (20 mg, 37.45 µmol), compound 75 (18 mg, 39.32 µmol), and copper sulfate pentahydrate (1 mg, 4.01 µmol) were dissolved in DMSO (5 mL) and H₂O (1 mL). The mixture was purged with nitrogen three times. Sodium ascorbate (15 mg, 74.89 µmol) was added, and the mixture was stirred at room temperature under nitrogen for 3 hours. After the reaction was complete, compound C-7 (13 mg, 35% yield) was obtained by preparative high-performance liquid chromatography (HPLC). LCMS (ESI): m / z 988.4 [M+H] + . Example 5. Synthesis of D-series target products Example 5.1 Synthesis of D-1 Step 1: Preparation of Compound 78. Compound 21 (1.00 g, 6.98 mmol) was dissolved in tetrahydrofuran (15 mL), and sodium hydride (335 mg, 8.38 mmol, 60% purity) was added in portions under ice bath. The mixture was stirred at room temperature for 15 minutes, and then compound 77 (1.78 g, 8.38 mmol) was added under ice bath, and the mixture was stirred overnight at room temperature. After the reaction was complete, a saturated ammonium chloride solution was slowly added to the reaction mixture under ice bath until no more bubbles were generated. The mixture was extracted with EA, and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 78 (1.54 g, 59% yield). LCMS (ESI): m / z 375.2 [M+H] + . Step 2: Preparation of compound 79. Compound 78 (1.54 g, 4.11 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2 mL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was washed three times with anhydrous diethyl ether and concentrated under reduced pressure to obtain compound 79 (1.10 g, yield 97%). LCMS (ESI): m / z 275.2 [M+H] + . Step 3: Preparation of Compound 80. Compound 79 (1.10 g, 4.01 mmol), compound 24 (936 mg, 4.21 mmol), and DIPEA (2.79 mL, 16.04 mmol) were dissolved in dichloromethane (15 mL), and HATU (1.60 g, 4.21 mmol) was added and stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with dichloromethane and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 80 (1.75 g, 91% yield). LCMS (ESI): m / z 479.2 [M+H] + . Step 4: Preparation of Compound 81. Compound 80 (1.75 g, 3.66 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2 mL) was added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure. The residue was slurried three times with anhydrous diethyl ether and concentrated under reduced pressure to obtain compound 81 (1.43 g, 92% yield). LCMS (ESI): m / z 423.1 [M+H]+ . Step 5: Preparation of Compound 83. Compound 81 (1.43 g, 3.38 mmol), compound 82 (217 mg, 3.55 mmol), and DIPEA (2.36 mL, 13.54 mmol) were dissolved in dichloromethane (10 mL), and HATU (1.35 g, 3.55 mmol) was added and stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with dichloromethane and washed once each with saturated ammonium chloride, saturated sodium bicarbonate, and saturated sodium chloride solutions. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to give compound 83 (1.01 g, 64% yield). LCMS (ESI): m / z 466.2 [M+H] + . Step 6: Preparation of Compound 84. Compound 83 (1.00 g, 2.15 mmol) was dissolved in tetrahydrofuran (10 mL). Sodium hydride (103 mg, 2.58 mmol, 60% purity) was added under ice bath conditions, and the mixture was stirred at room temperature for 15 minutes. Bromopropyne (306 mg, 2.58 mmol) was then added, and the mixture was stirred at room temperature for 6 hours. After the reaction was complete, saturated ammonium chloride solution was slowly added to the reaction mixture under ice bath conditions until no more bubbles were generated. The mixture was extracted with EA, and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound 84 (507 mg, 47% yield). LCMS (ESI): m / z 504.2 [M+H] + . Step 7: Preparation of compound D-1. Compound 84 (20 mg, 39.71 µmol), compound I-1 (19 mg, 41.70 µmol), and copper sulfate pentahydrate (1 mg, 4.01 µmol) were dissolved in DMSO (5 mL) and H2O (1 mL). The mixture was purged with nitrogen three times. Sodium ascorbate (16 mg, 79.43 µmol) was added, and the mixture was stirred at room temperature under nitrogen for 3 hours. After the reaction was complete, compound D-1 (17 mg, 44% yield) was purified by preparative high-performance liquid chromatography. LCMS (ESI): m / z 960.4 [M+H] + . Example 6. In vitro anti-proliferation experiment The following compounds are cited as reference compounds in this invention. Experimental Methods: This cell experiment aimed to evaluate the effect of the test compound on the proliferation of human prostate cancer cell line (LNCaP) using the Cell Counting Kit-8 (CCK8) assay. LNCaP cells were trypsinized, resuspended, and counted. 4000 cells / 90 µL were seeded into 96-well plates, mixed thoroughly, labeled, and incubated at 37°C in a 5% CO2 incubator for 16 h. After 16 h, the corresponding drug was added to each well of the 96-well plate, with a blank control group provided. After 72 h of incubation, 10% CCK-8 solution was added to each well, and the plates were incubated for 1-2 h. After thorough mixing, the OD value was measured using a 450 nm microplate reader, and the IC50 was calculated using GraphPad Prism software. 50 value.

[0160] Representative compound results The inhibitory IC of the compound in the embodiments of the present invention 50 As shown in Table 1.

[0161] Table 1. Activity of the compounds of the present invention in LNCaP cell viability assay A: IC 50 ≤ 250 nM; B: 250 nM < IC 50 ≤ 500 nM; C: 500 nM < IC 50 ≤ 1 µM; D: 1 µM < IC 50 ≤ 10 µM; Example 7. Cell-level target protein degradation efficacy evaluation experiment Protein expression was detected by Western blot. Total protein was extracted from cells, quantified by BCA method, separated by SDS-PAGE electrophoresis, and transferred to PVDF membrane. After blocking with 5% skim milk, the membrane was incubated with primary and secondary antibodies sequentially, developed by ECL chemiluminescence, and the gray values ​​of the bands were semi-quantitatively analyzed using ImageJ software.

[0162] The results showed that compounds A-4 and B-2 were two compounds with AR protein degradation activity, exhibiting concentration-dependent degradation. At 20 nM, the AR band of compound A-4 almost completely disappeared, and at 100 nM, the AR bands of compounds A-4 and B-2 disappeared more completely. Their degradation ability was comparable to or stronger than that of the positive control ARV-766. Figure 1 ).

[0163] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A compound, characterized in that, The compound is a compound of Formula I or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof. in, x and m are each independently 0, 1, 2, 3 or 4; X is selected from the following group: chemical bond, -O-, -NH-; The ring W1 is selected from the following group: C3-C8 cycloalkyl sub-groups, 3-8 membered heterocyclic sub-groups containing 1-4 heteroatoms selected from N, O, S, and P; R x R 3 Each is independently selected from the following group: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuterylalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterylalkoxy, C1-C6 haloalkylthio, C3-C6 cycloalkyl, oxo, thio, -CN, -OH, -NH2, -NO2, -COOH, acetyl; " " indicates a single or double bond; X 1 X 2 X 3 Each can be independently selected from C, N, or O, provided that X 1 X 2 When X is N 3 Not C; R 6 This refers to 1-3 substituents, each independently selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterated alkoxy, C1-C6 haloalkylthio, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, substituted or unsubstituted C 6-12 Aryl, -CN, -OH, -NH2, -NO2, -COOH, acetyl, where "substitution" refers to one or more hydrogens (such as 2, 3, or 4) on the group being independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, oxo, thio, -CN, -OH, -NH2, -NO2, -COOH, acetyl; R 7 Selected from the following group: hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -NH2; R 8 Selected from the following group: C6-C 12 Aryl, C3-C 12 Cycloalkyl groups, 4-12 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, and 5-12 membered heteroaryl groups containing 1-4 heteroatoms selected from N, O, S, and P, wherein the C6-C 12 Aryl, C3-C 12 The cycloalkyl, 4-12-membered heterocyclic, and 5-12-membered heteroaryl groups are optionally substituted by 1-4 substituents selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuteralkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuteralkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -(C 1-6 Alkylene, -hydroxy, -NH2, -NO2, -COOH, acetyl, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, where "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuterylalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterylalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -NH2, -(C 1-6 (alkylene)-hydroxy; L 1 for ; L 2 L 3 L 4 Each is independently selected from the group consisting of covalently bonded, substituted, or unsubstituted -C1-C6 alkylene groups, wherein any carbon atom on the C1-C6 alkylene group is optionally replaced by a heteroatom selected from O, N, and S; the term "substituted" means that one or more hydrogen atoms (e.g., 2, 3, or 4) on the group are independently replaced by groups selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and oxo groups. Ring V1 and ring V2 are either absent or contain 1-4 3-15 membered subheterocyclic groups selected from N, O, and S heteroatoms.

2. The compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof, characterized in that, The compound of formula I is shown in formula II: in, m can be 0, 1, 2, 3 or 4 independently; R 1 R 2 R 3 Each is independently selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, oxo, -CN, -OH, -NH2; R 6 This refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, C3-C 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-12 Aryl, -CN, -OH, -NH2, where "substitution" refers to one or more hydrogens (such as 2, 3, or 4) on the group being independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, oxo groups, thio groups, -CN, -OH, -NH2, -NO2; R 7 Selected from the following group: hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, -CN, -OH, -NH2; R 8 Selected from the following group: C6-C 12 Aryl, containing 1-4 5-12 membered heteroaryl groups selected from N, O, and S heteroatoms, wherein the C6-C 12 The aryl and 5-12 heteroaryl groups are optionally substituted with 1-4 substituents selected from the group consisting of: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, -(C 1-6 Alkylene, -hydroxy, oxo, thio, -CN, -OH, -NH2, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, where "substituted" means that one or more hydrogens (e.g., 2, 3, or 4) on the group are independently substituted by groups selected from the following group: halogen, C1-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -(C 1-6 (alkylene)-hydroxy; L 1 Selected from the following group: -NH-(C1-C 15 alkylene), -(C0-C5 alkylene)-(5-12 membered heterocyclic)-(C0-C5 alkylene)-, , The heterocyclic alkyl group contains 1-3 heteroatoms selected from N, O, and S; Where m1 is an independent integer from 0 to 5; Any carbon atom on the C0-C5 alkylene group is optionally replaced by N or O, and one or more hydrogen atoms (such as 2, 3 or 4) on the C0-C5 alkylene group are independently replaced by groups selected from the group consisting of: halogen, C1-C6 alkyl, C1-C6 haloalkyl, oxo, -CN, -OH, -NH2; T1, T2, T3, and T4 are each independently selected from C or N.

3. The compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof, characterized in that, The compounds of formula I are shown as those of formula III-a or III-b: in, a can be 0, 1, or 2 independently; The ring E is selected from the following group: containing 1-2 5- or 6-membered heterocyclic groups selected from N, O, and S heteroatoms; R 1 R 2 Each is independently selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, oxo, -CN, -OH, -NH2; R 6 It refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, C3-C 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-12 Aryl, -OH, -NH2, where "substitution" refers to one or more hydrogens (such as 2, 3, or 4) on the group being independently substituted by a group selected from the group consisting of: C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl, 3-8 membered heterocyclic groups containing 1-3 heteroatoms selected from N, O, and S, oxo groups, thio groups, -CN, -OH, -NH2, -NO2; R 7 Selected from the following group: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, -CN, -OH, -NH2; R a Selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, -(C 1-6 Alkylene, hydroxyl, oxo, -CN, -NH2, substituted or unsubstituted 4-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, where "substituted" means that one or more hydrogen atoms (e.g., 2, 3, or 4) on the group are independently substituted by a group selected from the group consisting of: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C 1-6 (alkylene)-hydroxyl, -CN, -OH, -NH2; L 1 Selected from the following group: -NH-(C2-C 13 alkylene), -(C0-C5 alkylene)-(5-12 membered heterocyclic)-(C0-C5 alkylene)-, , The heterocyclic alkyl group contains 1-3 heteroatoms selected from N, O, and S; Where m1 is an independent integer from 0 to 5; Any carbon atom on the C0-C5 alkylene group is optionally replaced by N, and one or more hydrogen atoms (such as 2, 3 or 4) on the C0-C5 alkylene group are independently replaced by groups selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, oxo, -CN, -OH, -NH2; T2 and T3 are each independently selected from C or N.

4. The compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof, characterized in that, The compounds of formula I are shown as those of formulas IV-a, IV-b, IV-c, IV-d, or IV-e: in, n1 and n5 are each an independent integer between 0 and 12; n2, n3, and n4 are each independent integers between 0 and 4; T5 and T6 are each independently selected from C and N; W2 is Or a 5-12 membered subheterocyclic group containing 1-4 heteroatoms selected from N, O, and S; T2 and T3 are each independently selected from C or N; b and c are each independently 0, 1, or 2; R 1 R 2 Each is independently selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, oxo, -CN, -OH, -NH2; R 6 It refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C3-C... 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-12 Aryl, -OH, -NH2, where "substitution" refers to one or more hydrogens (such as 2, 3, or 4) on the group being independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C 3-10 Cycloalkyl, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, thiogroups, -CN, -OH, -NH2, -NO2; R 7 Selected from the following group: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, -CN, -OH, -NH2; R b R c Each is independently selected from the following group: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, -(C 1-6 Alkylene)-hydroxyl, -CN, -OH, -NH2.

5. The compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof, characterized in that, The compound of formula I is shown as either formula Va or Vb: in, n1 is any integer between 4 and 9; n2 and n3 are each independent integers between 0 and 3; R b Selected from the following group: halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl; R 6 It refers to 1-3 substituents, each independently selected from the group consisting of: halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 alkylthio, C3-C... 10 Cycloalkyl groups, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, and P, C 6-10 Aryl, -OH, -NH2, where "substitution" means that one or more hydrogens (such as 2, 3 or 4) on the group are independently replaced by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, -OH, -NH2.

6. The compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof, characterized in that, The compounds are selected from the group consisting of: 。 7. A method for preparing a compound as described in any one of claims 1-6, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, or prodrug thereof, characterized in that, Includes the following steps: S1. In the first solvent, under the action of a catalyst, compound A and compound B undergo an azide-alkyne cycloaddition reaction to prepare compound Ia; Where x, m, W1, R x R 3 R 6 R 7 R 8 L 1 The definition is the same as that described in claim 1.

8. A pharmaceutical composition, characterized in that, It includes the compound as described in any one of claims 1-6, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, prodrug, and pharmaceutically acceptable carrier thereof.

9. Use of a compound as described in any one of claims 1-6, or a pharmaceutically acceptable salt, stereoisomer, geometric isomer, hydrate, solvate, prodrug, or pharmaceutical composition as described in claim 8, characterized in that, This is for the preparation of a medicine for treating androgen receptor (AR)-related diseases or conditions, wherein the hormone receptor (AR)-related diseases or conditions are selected from the group consisting of: prostate cancer, breast cancer, bladder cancer, spinal bulbar muscular atrophy, androgen insensitivity syndrome, liver cancer, kidney cancer, melanoma, glioblastoma, head and neck cancer, esophageal cancer, gastric cancer, colorectal cancer, ovarian cancer, endometrial cancer, cervical cancer, polycystic ovary syndrome, and androgenic alopecia.

10. An intermediate compound or a pharmaceutically acceptable salt thereof, characterized in that, The compound or a pharmaceutically acceptable salt thereof is shown in formula B below: in, R 6 This refers to 1-3 substituents, each independently selected from the group consisting of: deuterium, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterated alkoxy, C1-C6 haloalkylthio, substituted or unsubstituted C3-C 10 Cycloalkyl, wherein "substitution" means that one or more hydrogens (such as 2, 3 or 4) on the group are independently substituted by a group selected from the group consisting of: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylene, C2 ... 3-10 cycloalkyl, C 6-12 Aryl, 3-8 membered heterocyclic groups containing 1-4 heteroatoms selected from N, O, S, P, oxo, thio, -CN, -OH, -NH2, -NO2, -COOH, acetyl; R 7 Selected from the following group: hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -NH2; R 8 Selected from the group consisting of 5-12-membered heteroaryl groups containing 1-4 heteroatoms selected from N, O, S, and P, wherein the 5-12-membered heteroaryl groups are optionally substituted by 1-4 substituents selected from the group consisting of: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 deuterylalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 deuterylalkoxy, C1-C6 haloalkylthio, oxo, thio, -CN, -OH, -(C 1-6 Alkylene, -hydroxyl, -NH2, -NO2, -COOH, acetyl.

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