Muscarinic m4 receptor agonist and use thereof

Abstract

A CHRM4 receptor agonist and the use thereof. Disclosed in the present invention are a compound as represented by formula (I), or a stereoisomer, a deuterated substance, a solvate, an eutectic or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition thereof, and the use thereof in the preparation of a drug for treating / preventing CHRM4-mediated diseases, wherein each group in formula (I) is as defined in the description.

Description

Muscarinic M4 receptor agonists and uses thereof Technical Field

[0001] The present invention belongs to the field of medicine, and in particular relates to a small molecule compound having CHRM4 receptor agonist activity, its stereoisomers, deuterated products, solvates, cocrystals or pharmaceutically acceptable salts, and its use in preparing medicines for treating related diseases. Background Art

[0002] mAChRs are widely distributed throughout the human body and, based on their location and receptor subtype, mediate a wide range of physiological functions in the cardiovascular, renal, gastrointestinal, pulmonary, central, and peripheral nervous systems. mAChRs are typically expressed in various parts of the brain, and their functions are associated with regulating a wide range of brain circuits, including neuronal excitability, synaptic plasticity, and acetylcholine release. All five mAChRs are expressed in neurons and glial cells in the brain, but receptor abundance varies by region. The muscarinic acetylcholine receptor M4 (also known as muscarinic 4 or CHRM4) is the protein encoded by the CHRM4 gene in humans. The M4 receptor is primarily expressed in the brain. Key brain regions where M4 receptor expression occurs are the striatum, cortex, and hippocampus, with the highest expression occurring in the striatum (approximately 46%), where M4 is the predominant muscarinic subtype. M4 is occasionally expressed in the periphery (e.g., testis, skin, and colon).

[0003] Summary of the Invention

[0004] The present invention provides a small molecule compound having CHRM4 activity, and its stereoisomers, deuterated forms, solvates, cocrystals or pharmaceutically acceptable salts, wherein the compound has a structure of formula (I), (I-1), (I-1a), (I-2), (I-3), (I-4), (I-5), (I-6), (I-7), (I-8), (I-1b), (II),

[0005] It means that the ring formed by X1-X4 contains one or more double bonds;

[0006] A is selected from 3-20 membered heterocycloalkyl or 5-20 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the heterocycloalkyl or heteroaryl is optionally replaced by 0-5 R A In some embodiments, A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocycloalkyl, 9-10 membered bicyclic heteroaryl, 10-14 membered tricyclic heterocycloalkyl, 10-14 membered tricyclic heteroaryl, wherein the heterocycloalkyl and heteroaryl are optionally substituted by 1-5 R AIn some embodiments, A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heteroaryl, 6-10 membered bicyclic heterocycloalkyl, 10-14 membered tricyclic heteroaryl, 10-14 membered tricyclic heterocycloalkyl, wherein the heterocycloalkyl and heteroaryl groups are optionally substituted with 1-5 R A In some embodiments, A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocycloalkyl, 10-14 membered tricyclic heterocycloalkyl, wherein the heterocycloalkyl and heteroaryl groups are optionally substituted by 1-5 R A In some embodiments, A is selected from 5-membered heteroaryl, 6-membered heteroaryl, 5-6-membered heteroaryl and 5-6-membered heteroaryl, 5-6-membered heteroaryl and 5-7-membered heterocycloalkyl, 5-6-membered heteroaryl and 5-6-membered carbocyclyl, 10-14-membered tricyclic heteroaryl, 10-14-membered tricyclic heterocycloalkyl; the heteroaryl, heterocycloalkyl, carbocyclyl are optionally substituted with 1-5 R A In some embodiments, A is selected from the group consisting of A One of the groups formed by the following structures: In some embodiments, Ring A is selected from the group consisting of: A The following structures are replaced: Or choose Het is a 5-membered heteroaryl group, wherein the heteroaryl group is optionally substituted by 1 or 2 selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 In some embodiments, the A ring is selected from The A ring is optionally further substituted with 1, 2 or 3 R A Substitution; in some embodiments, Ring A is selected from In some embodiments, Ring A is selected from In some embodiments, Ring A is selected from

[0007] A1 is selected from the following groups: In some embodiments, A1 is selected from the following groups: Or A1 is selected from the following groups: Or A1 is selected from the following groups: In some embodiments, A1 is selected from the following groups: Or A1 is selected from the following groups: Or A1 is selected from the following groups: Or A1 is selected from the following groups: Or A1 is selected from the following groups: In some embodiments, A1 is selected from the following groups:

[0008] B is selected from the group consisting of a bond, C 3-10 Cycloalkyl, C 6-12 Aryl, 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, aryl, heterocycloalkyl, and heteroaryl are optionally substituted by 0-5 R B In some embodiments, B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, a C 3-8 Cycloalkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heterocycloalkyl, 5-12 membered spirocyclic heterocycloalkyl, 3-6 membered cycloalkyl and 5-6 membered heterocycloalkyl, benzo 5-6 membered heterocycloalkyl, the heterocycloalkyl, heteroaryl, cycloalkyl, aryl are optionally substituted by 1-5 R B In some embodiments, B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, a 3-8 membered cycloalkyl, a 5-6 membered heteroaryl, a 5-6 membered heteroaryl and a 5-6 membered heterocycloalkyl, a 5-12 membered spirocyclic heterocycloalkyl, a 5-6 membered cycloalkyl and a 5-6 membered heterocycloalkyl, a benzo 5-6 membered heterocycloalkyl, wherein the heterocycloalkyl, heteroaryl, cycloalkyl, aryl are optionally replaced by 1-5 R B replace;

[0009] In some embodiments, B is selected from the group consisting of B Substituted groups: bonds, B1 is selected from the following groups: bond, Or B1 is selected from the following groups: Or B1 is selected from the following groups: In some embodiments, B1 is selected from the group consisting of: a bond,

[0010] in, Terminal L1 or L 1a or L 1b Connected, "*" end to L2 or L 2a connected;

[0011] C is selected from C 3-12 Cycloalkyl, C 6-10 Aryl, 3-14 membered heterocycloalkyl or 5-14 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted by 0-5 R C In some embodiments, C is selected from 5-6 membered monocyclic heteroaryl, phenyl, phenyl and 4-6 membered carbocyclyl, phenyl and 4-6 membered heterocycloalkyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclyl, 8-12 membered tricyclic cycloalkyl, 8-14 membered tricyclic heterocyclyl, said heteroaryl, heterocycloalkyl, heterocyclyl containing 1-4 heteroatoms selected from N, O, S; said phenyl, heterocycloalkyl, carbocyclyl is optionally substituted with 1-5 R C In some embodiments, C is selected from 5-6 membered monocyclic heteroaryl, phenyl, phenyl and 4-6 membered carbocyclyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclyl, 8-12 membered tricyclic cycloalkyl, 8-14 membered tricyclic heterocyclyl, wherein the heteroaryl, heterocycloalkyl and heterocyclyl contain 1-4 heteroatoms selected from N, O and S; wherein the phenyl, heterocycloalkyl and carbocyclyl are optionally substituted with 1-5 R C In some embodiments, C is selected from C 3-12 Cycloalkyl, C 6-10 Aryl, 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted by 0-5 R C In some embodiments, C is selected from 5-6 membered monocyclic heteroaryl, phenyl and 4-6 membered carbocyclyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclyl, 8-12 membered tricyclic cycloalkyl, wherein the heterocycloalkyl contains 1-3 heteroatoms selected from N, O, and S; the phenyl, heterocycloalkyl, and carbocyclyl are optionally substituted with 1-5 R C In some embodiments, C is selected from the group consisting of C Substituted groups: In some embodiments, the C ring is selected from The C ring is optionally further substituted with 1, 2 or 3 R C In some embodiments, C is selected from the group consisting ofC Substituted groups:

[0012] C1 is selected from the following groups:

[0013] C2 is selected from the following groups: Or C2 is selected from the following groups: Or C2 is selected from the following groups: Or C2 is selected from the following groups: Or C2 is selected from the following groups: Or C2 is selected from the following groups: In some embodiments, C2 is selected from the following groups:

[0014] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-4 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 Alkylhydroxyl, -C(=O)C 1-4 Alkyl, halogenated C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 Alkylhydroxyl, -C(=O)C 1-4 Alkyl, halogenated C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-4 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy, -C 1-2 Alkylhydroxyl, -C(=O)C 1-2 Alkyl, halogenated C 1-2 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy, -C 1-2 Alkylhydroxyl, -C(=O)C 1-2 Alkyl, halogenated C 1-2 In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, -CF3, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-2 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 Alkylhydroxyl, halogenated C 1-2 Alkyl, -C(=O)C 1-2 Alkyl, C 1-2 In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 Alkylhydroxyl, halogenated C 1-2 Alkyl, -C(=O)C 1-2 Alkyl, C 1-2 In some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, 5-6 membered heteroaryl, The methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy; the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -C(=O)CH3, -O-CH3, and -O-CH2CH3; In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6Cycloalkyl, 5-6 membered heteroaryl, The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy, -C 1-2 In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, -CF3, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 Alkylhydroxyl, halogenated C 1-2 Alkyl, -C(=O)C 1-2 Alkyl, C 1-2 In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 In some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , -SO2CH3, cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, oxacyclopentyl, -CF3, 7-10 membered bicyclic heterocycloalkyl, the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -C(=O)CH3, -O-CH3, and -O-CH2CH3; in some embodiments, R AEach independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, 5-6 membered heteroaryl, -CF3, 7-10 membered bicyclic heterocycloalkyl, the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -C(=O)CH3, -O-CH3, and -O-CH2CH3; in some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, 5-6 membered heteroaryl, The methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy groups; the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl groups; in some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 In some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C3-6 Cycloalkyl, -NHR aa , the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 In some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -NHR aa , the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, the alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, -O-halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R A Each independently selected from =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from NH2, CN, methyl, and ethyl, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R A Each independently selected from =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, wherein the alkyl group is optionally further substituted by 1-4 groups selected from NH2, CN, C 1-2 The alkyl group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 In some embodiments, R AEach independently selected from =O, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from NH2, CN, methyl, and ethyl, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, the alkyl, alkenyl, alkynyl, heteroaryl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, -O-halogenated C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, 5-6 membered heteroaryl, wherein the alkyl and heteroaryl are optionally further substituted by 1-5 members selected from halogen, OH, NH2, CN, C 1-4 In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, wherein the alkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 In some embodiments, R A Each is independently selected from F, Cl, =O, methyl, ethyl, 5-membered heteroaryl, 6-membered heteroaryl, wherein the methyl, ethyl, 5-membered heteroaryl, 6-membered heteroaryl is optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl; in some embodiments, each R A Each independently selected from halogen, CN, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -OC 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, -SO2-C 1-2 Alkyl, the heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-2 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, C 1-2 Alkoxy, -C(=O)C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0015] Alternatively, two R ATogether with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0016] In some embodiments, both R A Together with the atoms it is connected to form C 3-6 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 In some embodiments, two R A Together with the atoms it is connected to form C 3-6 4-6 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-2 Alkyl radical substitution;

[0017] R A1 Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -SO2-C 1-4 Alkyl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, -SO2CH3, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa , 5-membered heteroaryl, 4-6-membered heterocycloalkyl, wherein the methyl, ethyl, cycloalkyl, 5-membered heteroaryl, 4-6-membered heterocycloalkyl is optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, methoxy; In some embodiments, R A1 Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-4 In some embodiments, R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa , 5-membered heteroaryl, 4-6-membered heterocycloalkyl, wherein the methyl, ethyl, cycloalkyl, 5-membered heteroaryl, 4-6-membered heterocycloalkyl is optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, methoxy; In some embodiments, R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa , the methyl, ethyl, and cycloalkyl groups are optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, and methoxy;

[0018] R B Each independently selected from halogen, CN, =O, OH, -SF5, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, the alkyl, alkoxy, alkenyl, alkynyl may be further selected from halogen, C 1-2 In some embodiments, R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted by halogen; In some embodiments, R B Each is independently selected from F, Cl, =O, methyl, ethyl, wherein the methyl and ethyl groups are optionally further substituted by F and Cl groups;

[0019] R C Each independently selected from D, halogen, CN, ═O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from D, halogen, CN, ═O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n-(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C are independently selected from D, halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 In some embodiments, R C are independently selected from D, halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O) C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl)n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NRa S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl, heterocyclyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0020] In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl group is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 alkyl groups; n is independently selected from 0 or 1; in some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NRa S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from D, halogen, CN, ═O, OH, C1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -OC 5-11 Spiroalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, spiroalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-3 Alkoxy, C 3-4 Cycloalkyl, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 In some embodiments, R C Each is independently selected from D, F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-6 membered monocyclic heterocycloalkyl), The methyl, ethyl, cyclopropyl, cyclobutyl, heteroaryl, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3; in some embodiments, each R C are independently selected from halogen, halogenated C 1-3 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, 5-6 membered heteroaryl, -OC 3-6Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -OC 5-8 Spiroalkyl, The heteroaryl, cycloalkyl, spirocycloalkyl may be further substituted by 1-3 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 In some embodiments, each R C Each independently selected from F, Cl, CF3, CHF2, CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, In some embodiments, R C are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NRa -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 In some embodiments, R C are each independently selected from halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, the alkyl, heteroaryl optionally further 1-4 selected from halogen, C 1-2 In some embodiments, R C Each is independently selected from D, F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-6 membered monocyclic heterocycloalkyl), The methyl, ethyl, heteroaryl, cycloalkyl group is optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3; in some embodiments, R C Each is independently selected from D, F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-membered heteroaryl), -OC 3-6Cycloalkyl, -O-(4-6 membered monocyclic heterocycloalkyl), The methyl, ethyl, heteroaryl, cycloalkyl group is optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl, -CF3; in some embodiments, R C Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, 5-membered heteroaryl, 6-membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, the methyl, ethyl, heteroaryl optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl; In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 3-5 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 In some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, halogenated C 1-2 alkyl, 5-6 membered heteroaryl, 8-10 membered heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 In some embodiments, R C are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl, CN, =O, wherein the alkyl and heteroaryl groups are optionally further substituted by 1-4 groups selected from halogen, C 1-2 In some embodiments, R C Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered heteroaryl, 9-membered heteroaryl, 10-membered heteroaryl, CN, =O, and the methyl, ethyl, heteroaryl is optionally further substituted with 1-4 groups selected from F, Cl, methyl, and ethyl;

[0021] R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, halogenated C 1-3 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(5-6 membered heteroaryl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR aS(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(5-6 membered heteroaryl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(5-6 membered heteroaryl), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4Alkyl, -S(=O)2C 1-4 In some embodiments, R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C1 Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, cyclopentyl, cubane, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered cyclic heteroaryl, 9-membered cyclic heteroaryl, 10-membered cyclic heteroaryl, 7-8-membered spirocyclic heterocycloalkyl, 8-9-membered cyclic heterocycloalkyl, 7-membered bridged heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH-(4-6 membered heterocycloalkyl), -NH-(5-6 membered heteroaryl), -NH-S(=O)2-C 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -C 1-2 Alkyl-phenyl, -C 1-2 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-2 alkyl) n -O-(C 1-2 alkyl) n -(4-6 membered heterocyclic group), -NR aC(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), the cyclopropyl, cyclobutyl, cyclopentyl, alkyl, cycloalkyl, heterocyclyl, heteroaryl, heterocycloalkyl, cubane are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, deuterated methyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-2 In some embodiments, R C1 Each independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, C 4-5 Cycloalkyl, cubane, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered cycloheteroaryl, 9-membered cycloheteroaryl, 10-membered cycloheteroaryl, 7-8-membered spirocyclic heterocycloalkyl, 8-9-membered cycloheterocycloalkyl, 7-membered bridged heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH-(4-6 membered heterocycloalkyl), -NH-(5-6 membered heteroaryl), -NH-S(=O)2-C 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -C 1-2 Alkyl-phenyl, -C1-2 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-2 alkyl) n -O-(C 1-2 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, deuterated methyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-2 In some embodiments, R C1 Each independently selected from halogenated C 1-2 Alkyl, 5-6 membered heteroaryl, -OC 3-6 Cycloalkyl, -O-4-6 membered heterocycloalkyl, -O-5-6 membered heteroaryl, wherein the heteroaryl, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 In some embodiments, R C1 Each is independently selected from 5-membered heteroaryl, 6-membered heteroaryl, -OC 3-6 Cycloalkyl, the heteroaryl, cycloalkyl is optionally further substituted by 1-4 selected from F, Cl, OH, NH2, CN, methyl, ethyl, deuterated methyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-2 In some embodiments, R C1 Each independently selected from halogenated C 1-2alkyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, triazole, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-bicyclo[1.1.1]pentane, -O-spiro[2.3]hexane, -O-oxacyclopentyl, said pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, cyclopropyl, cyclobutyl, cyclopentyl, bicyclo[1.1.1]pentane, spiro[2.3]hexane, oxacyclopentyl are optionally further substituted with 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O; in some embodiments, R C1 Each is independently selected from pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, and the pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, cyclopropyl, cyclobutyl, and cyclopentyl are optionally further substituted with 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, deuterated methyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, and =O;

[0022] R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-4 Alkyl, halogenated 3-6 membered cycloalkyl;

[0023] In some embodiments, R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 alkyl, halogenated 3-6 membered cycloalkyl; in some embodiments, R a is selected from H, F, Cl, methyl, ethyl, cyclopropyl, cyclobutyl, cyclopentyl, difluorocyclobutyl; in some embodiments, R a is selected from H, F, Cl, methyl, ethyl, cyclopropyl, cyclobutyl, and cyclopentyl;

[0024] R aa 、R bb are independently selected from H, halogen, =O, C 1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 In some embodiments, Raa, Rbb are each independently selected from H, halogen, =O, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 Alkoxy; in some embodiments, R aa 、R bbEach is independently selected from H, F, Cl, =O, methyl, ethyl, -CH2-CH2-OH, -CH2-OH, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCH3, -OCH2CH3, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH2CHF2, -OCH2CH2F; in some embodiments, R aa 、R bb Each is independently selected from H, F, Cl, =O, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCH3, -OCH2CH3, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH2CHF2, -OCH2CH2F;

[0025] Alternatively, R aa 、R bb Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0026] In some embodiments, R aa 、R bb Together with the atoms to which it is attached, it forms a 4-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted with 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 3-5 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, wherein the alkyl, cycloalkyl, heteroaryl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 In some embodiments, R C are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl, the alkyl, heteroaryl optionally further 1-5 selected from halogen, C 1-2 In some embodiments, R C are independently selected from halogen, halogenated C 1-2Alkyl, 5-6 membered heteroaryl, the alkyl, heteroaryl optionally further 1-4 selected from halogen, C 1-2 In some embodiments, R C Each is independently selected from F, Cl, -CF3, -CHF2, -CH2CH2F, -CH2CF3, -CH2CHF2, -CH2CH2F, 5-membered heteroaryl, 6-membered heteroaryl, the heteroaryl being optionally further substituted with 1-4 groups selected from F, Cl, methyl, and ethyl;

[0027] Alternatively, two R C Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0028] Alternatively, R B 、R C Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 In some embodiments, alternatively, R B 、R C Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 atoms selected from halogen, C 1-2 Alkyl radical substitution;

[0029] L1 and L2 are each independently selected from W1-R L -W2, the left side of L1 is linked to A, and the left side of L2 is linked to B; L1 and L2 are not keys at the same time;

[0030] R L Selected from bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-6 Cycloalkyl, 5-12 membered heteroaryl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkylene, alkenylene, alkynylene, cycloalkyl, heteroaryl, heterocycloalkyl may be further substituted by 1-4 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 1-4Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, the alkyl, alkoxy, cycloalkyl, heteroaryl may be further substituted by 1-4 groups selected from halogen, CN, OH, C 1-4 Alkoxy and NH2 substituents are substituted; in some embodiments, R L Selected from bond, C 1-4 Alkylene, C 2-4 Alkenylene, the alkylene, alkenylene optionally further 1-4 R L1 Substituted; in some embodiments, R L Selected from bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-6 Cycloalkyl, 5-12 membered heteroaryl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkylene, alkenylene, alkynylene, cycloalkyl, heteroaryl, heterocycloalkyl may be further substituted by 1-4 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 1-4 Alkoxy, 3-6 membered cycloalkyl, wherein the alkyl, alkoxy, cycloalkyl is optionally further substituted by 1-4 substituents selected from halogen, CN, OH and NH2; in some embodiments, R L1 are independently selected from halogen, =O, C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, 3-6 membered cycloalkyl, wherein the alkyl, alkoxy, cycloalkyl is optionally further substituted by 1-4 substituents selected from halogen, CN, OH and NH2; in some embodiments, R L1 Each independently selected from F, Cl, Br, =O, -CH2-, -CH2CH2-, C 2-4 alkenyl, -O-CH2-, -O-CH2CH2-, cyclopropyl, wherein the CH2, alkenyl, and cyclopropyl are optionally further substituted with 1-4 substituents selected from halogen, CN, OH, and NH2; in some embodiments, R L1 Each is independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, vinyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl;

[0031] W1 and W2 are each independently selected from a bond, C 1-4 Alkylene, -O-, -S-, -S(=O)-, -S(=O)2-, -NR W1 -、-CONRW1 -、-NR W1 CO-, -C(=O)O-, -OC(=O)-, -C(=S)-, -C(=O)-, -(C 1-4 Alkylene)-NR W1 CO-, the alkylene group is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-4 In some embodiments, W1 and W2 are each independently selected from a bond, -O-, -S-, -NR W1 -、-CONR W1 -、-NR W1 CO-, -C(=O)O-, -OC(=O)-; In some embodiments, W1 and W2 are each independently selected from -O-, -S-, -NR W1 -、-CONR W1 -、-NR W1 CO-, -C(=O)O-, -OC(=O)-; In some embodiments, W1 and W2 are each independently selected from -O-, -S-, -NH-, -N(CH3)-, -CON(CH3)-, -N(CH3)CO-, -C(=O)O-, -OC(=O)-;

[0032] R W1 Selected from H, C 1-4 Alkyl, halogen;

[0033] In some embodiments, R W1 Selected from H, C 1-2 Alkyl, halogen; in some embodiments, R W1 Selected from H, -CH3, -CH2CH3, F, Cl, Br;

[0034] L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4Alkenylene, -C(=O)-NH-, -C(=O)-N(CH3)-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 Alkoxy; in some embodiments, L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4 Alkenylene, -C(=O)-NH-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 Alkoxy; in some embodiments, L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-NH-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2Alkoxy, 3-6 membered cycloalkyl; in some embodiments, L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-NH-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 Alkoxy; In some embodiments, L1 is selected from a bond, vinylene, -CH2-, -CH2-CH2-, 4-6 membered monocyclic heterocycloalkyl, (4-6 membered monocyclic heterocycloalkyl)-C(=O)-CH2-, -(4-6 membered monocyclic heterocycloalkyl)-CH2-, -CH2-(4-6 membered monocyclic heterocycloalkyl)-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -(5-6 membered heteroaryl)-CH2-, 5-6 membered heteroaryl, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, -CF2-CH2-, -C(=O)-C 2-4 Alkenylene, -C(=O)-O-, the -CH2-, alkenylene, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1 Replacement; R L1 each independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, ethenyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl, methyl-methoxy, 5-membered heteroaryl; in some embodiments, L1 is selected from a bond, ethenylene, -CH2-, -CH2-CH2-, 4-6-membered monocyclic heterocycloalkyl, (4-6-membered monocyclic heterocycloalkyl)-C(=O)-CH2-, -(4-6-membered monocyclic heterocycloalkyl)-CH2-, -CH2-(4-6-membered monocyclic heterocycloalkyl)-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6 Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -(5-6 membered heteroaryl)-CH2-, 5-6 membered heteroaryl, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, -CF2-CH2-, wherein the -CH2-, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1 Replacement; R L1each independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, ethenyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl, methyl-methoxy, 5-membered heteroaryl; in some embodiments, L1 is selected from a bond, ethenylene, -CH2-, 4-6-membered monocyclic heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl-C(=O)-CH2-, -4-6-membered monocyclic heterocycloalkyl-CH2-, -CH2-4-6-membered monocyclic heterocycloalkyl-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6 Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -5-6 membered heteroaryl-CH2-, -5-6 membered heteroaryl-, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, wherein the -CH2-, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1 Replacement; R L1 Each is independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, vinyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl;

[0035] In some embodiments, L1 is selected from The "*" end is connected to the B ring;

[0036] L2 is selected from a bond, C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, the alkylene, alkenylene, alkynylene optionally further 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2Alkoxy, 3-6 membered cycloalkyl; in some embodiments, L2 is selected from a bond, vinylene, ethynylene, -CH2-, -CH2-CH2-, -O-, -NH-, -C(=O)-, -N(CH3)-; in some embodiments, L2 is selected from a bond, vinylene, ethynylene, -O-, -NH-, -C(=O)-, -N(CH3)-; in some embodiments, with the proviso that: when L2 is selected from -O-, -NH-, L1 is not selected from -C(=O)-, or B1 is not selected from a bond;

[0037] R1, R2, R3, and R4 are each independently selected from H and halogen; provided that R1, R2, R3, and R4 cannot all be H at the same time;

[0038] Alternatively, any two substituents among R1, R2, R3, and R4 together form a C 3-6 Cycloalkyl; in some embodiments, R1, R2, R3, R4 are each independently selected from H, F, Cl, Br; in some embodiments, R1, R2 are selected from F, R3, R4 are selected from H; in some embodiments, R3, R4 are selected from F, R1, R2 are selected from H; in some embodiments, alternatively, R3, R4 together form =O;

[0039] L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; in some embodiments, L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4 Alkenylene, -C(=O)-NH-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C1-2 Alkoxy, 3-6 membered cycloalkyl; in some embodiments, L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0040] In some embodiments, L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selected from the bond, R C1 is selected from 5-6 membered heteroaryl, said heteroaryl being optionally further substituted by 1-4 members selected from halogen, C 1-2 Alkyl radical substitution;

[0041] R a 、R bEach independently selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 Alkyl; provided that R a 、R b Not selected from H at the same time;

[0042] L 2a Selected from bond, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, and alkynylene groups are optionally further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; provided that, when L 1a Selected from -C(=O)-, L 2a When selected from -NH-, -O-, B1 is not selected from a bond; in some embodiments, L 2a Selected from bond, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, the alkylene, alkenylene, alkynylene optionally further 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0043] In some embodiments, L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selecting a bond, there is at least one R C1 Selected from =O, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, cubane, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane optionally further substituted by 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0044] In some embodiments, L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selecting a bond, there is at least one R C1 Selected from 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl radical substitution;

[0045] In some embodiments, provided that, when L 1aSelected from -C(=O)-, L 2a When selected from -NH-, -O-, B1 is not selected from a bond;

[0046] In some embodiments, L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, R C1 When selected from -CF3, L 2a Not a key;

[0047] In some embodiments, L 1a Selected from: -C(=O)-CH2-, R C1 Selected from -CHF2, -CF3, L 2a When selecting a bond, there is at least one R A Not selected from C 1-2 Alkyl, and n3 is selected from 1, 2, 3, 4 or 5;

[0048] In some embodiments, L 1b Selected from: bond, 4-6 membered monocyclic heterocycloalkyl, -C(=O)-NH-, wherein the heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-2 Alkyl radical substitution;

[0049] Alternatively, Selected from

[0050] n is each independently selected from 0, 1;

[0051] n1, n2, n3 are each independently selected from 0, 1, 2, 3, 4 or 5;

[0052] In some embodiments, n1 is selected from 0, 1, 2, or 3; in some embodiments, n1 is selected from 1, 2, or 3;

[0053] In some embodiments, n2 is selected from 0 or 1;

[0054] In some embodiments, n3 is selected from 0, 1, 2, 3, or 4; In some embodiments, n3 is selected from 0, 1, or 2;

[0055] X1 selected from CR X1 or N; or X1 is selected from NR X1 ;

[0056] X2 selected from CR X2 or N;

[0057] X3 selected from CR X3 or N;

[0058] X4 selected from CR X4 or N;

[0059] R X1 、R X2 、R X3 、R X4 Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -SO2-C 1-4 Alkyl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R X1 、R X2 、R X3 、R X4 Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R X1 、R X2 、R X3 、R X4 Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-2 Alkyl, C 1-2 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, 5-6 membered heteroaryl, -SO2-C 1-2 Alkyl, -NR a CO-C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkoxy, O-halogenated C 1-2 Alkyl, C 1-2 In some embodiments, R X1 、R X2 、R X3 、R X4Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-2 Alkyl, C 1-2 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, 5-6 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkoxy, -F, O-halogenated C 1-2 Alkyl, C 1-2 In some embodiments, R X1 、R X2 、R X3 、R X4 Each independently selected from H, F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa, the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R X1 、R X2 、R X3 、R X4 Each independently selected from H, F, Cl, =O, CN, -SO2CH3, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , the methyl, ethyl, heteroaryl, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, methoxy; in some embodiments, R X1 、R X2 、R X3 、R X4 Each independently selected from H, F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aaThe methyl, ethyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, methoxy; alternatively, any two R X1 、R X2 、R X3 、R X4 Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0060] In some embodiments, Selected from

[0061] In some embodiments, Selected from

[0062] As a specific technical solution 1 of the present invention, a compound represented by formula (I), a stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt thereof is provided,

[0063] A is selected from 3-20 membered heterocycloalkyl or 5-20 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the heterocycloalkyl or heteroaryl is optionally replaced by 0-5 R A replace;

[0064] B is selected from the group consisting of a bond, C 3-10 Cycloalkyl, C 6-12 Aryl, 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, aryl, heterocyclyl, and heteroaryl are optionally substituted by 0-5 R B replace;

[0065] C is selected from C 3-12 Cycloalkyl, C 6-10 Aryl, 3-14 membered heterocycloalkyl or 5-14 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted by 0-5 R C In some embodiments, C is selected from C 3-12 Cycloalkyl, C 6-10Aryl, 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted by 0-5 R C replace;

[0066] L1 and L2 are each independently selected from W1-R L -W2, the left side of L1 is connected to A, and the left side of L2 is connected to B;

[0067] R L Selected from bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-6 Cycloalkyl, 5-12 membered heteroaryl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkylene, alkenylene, alkynylene, cycloalkyl, heteroaryl, heterocycloalkyl may be further substituted by 1-4 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 1-4 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, the alkyl, alkoxy, cycloalkyl, heteroaryl may be further substituted by 1-4 groups selected from halogen, CN, OH, C 1-4 Alkoxy and NH2 substituents;

[0068] W1 and W2 are each independently selected from a bond, C 1-4 Alkylene, -O-, -S-, -S(=O)-, -S(=O)2-, -NR W1 -、-CONR W1 -、-NR W1 CO-, -C(=O)O-, -OC(=O)-, -C(=S)-, -C(=O)-, -(C 1-4 Alkylene)-NR W1 CO-, the alkylene group is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-4 Alkyl, CN, OH and NH2 group substitution;

[0069] R W1 Selected from H, C 1-4 Alkyl, halogen;

[0070] Alternatively, L1 is selected from The "*" end is connected to the B ring;

[0071] R A Each independently selected from halogen, =O, CN, OH, COOH, C1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-4 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 Alkylhydroxyl, -C(=O)C 1-4 Alkyl, halogenated C 1-4 Alkyl radical substitution;

[0072] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 Alkylhydroxyl, -C(=O)C 1-4 Alkyl, halogenated C 1-4 Alkyl radical substitution;

[0073] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 radical substitution of alkylhydroxy groups;

[0074] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl radical substitution;

[0075] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, the alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl radical substitution;

[0076] Alternatively, two R A Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0077] R B Each independently selected from halogen, CN, =O, OH, -SF5, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, the alkyl, alkoxy, alkenyl, alkynyl may be further selected from halogen, C 1-2 Alkyl radical substitution;

[0078] R C Each independently selected from D, halogen, CN, ═O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -OC 5-11 Spiroalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, spiroalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0079] In some embodiments, R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-3 Alkoxy, C 3-4 Cycloalkyl, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0080] In some embodiments, R C Each independently selected from D, halogen, CN, ═O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0081] In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0082] In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl, heterocyclyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NRa C(=O)-(4-6 membered heterocyclyl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl group is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0083] n is each independently selected from 0 or 1;

[0084] R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-4 alkyl, halogenated 3-6 membered cycloalkyl; in some embodiments, R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-4 alkyl;

[0085] R aa 、R bb are independently selected from H, halogen, =O, C 1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0086] or R aa 、R bb are independently selected from H, halogen, =O, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0087] Alternatively, R aa 、R bb Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0088] Alternatively, two R C Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0089] Alternatively, R B 、R C Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4Alkyl groups are substituted.

[0090] Furthermore, the compound represented by formula (I) of technical solution 1, its stereoisomers, deuterated substances, solvates, cocrystals or pharmaceutically acceptable salts,

[0091] A is selected from 3-20 membered heterocycloalkyl or 5-20 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the heterocycloalkyl or heteroaryl is optionally replaced by 0-5 R A replace;

[0092] B is selected from the group consisting of a bond, C 3-10 Cycloalkyl, C 6-12 Aryl, 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, aryl, heterocyclyl, and heteroaryl are optionally substituted by 0-5 R B replace;

[0093] C is selected from C 3-12 Cycloalkyl, C 6-10 Aryl, 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted by 0-5 R C replace;

[0094] L1 and L2 are each independently selected from W1-R L -W2, the left side of L1 is connected to A, and the left side of L2 is connected to B;

[0095] R L Selected from bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-6 Cycloalkyl, 5-12 membered heteroaryl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkylene, alkenylene, alkynylene, cycloalkyl, heteroaryl, heterocycloalkyl may be further substituted by 1-4 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 1-4 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, the alkyl, alkoxy, cycloalkyl, heteroaryl may be further substituted by 1-4 groups selected from halogen, CN, OH, C 1-4 Alkoxy and NH2 substituents;

[0096] W1 and W2 are each independently selected from a bond, C1-4 Alkylene, -O-, -S-, -S(=O)-, -S(=O)2-, -NR W1 -、-CONR W1 -、-NR W1 CO-, -C(=O)O-, -OC(=O)-, -C(=S)-, -C(=O)-, -(C 1-4 Alkylene)-NR W1 CO-, the alkylene group is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-4 Alkyl, CN, OH and NH2 group substitution;

[0097] R W1 Selected from H, C 1-4 Alkyl, halogen;

[0098] Alternatively, L1 is selected from The "*" end is connected to the B ring;

[0099] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, the alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl radical substitution;

[0100] Alternatively, two R A Together with the atoms it is connected to form C 3-6 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0101] R B Each independently selected from halogen, CN, =O, OH, -SF5, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, the alkyl, alkoxy, alkenyl, alkynyl may be further selected from halogen, C 1-2 Alkyl radical substitution;

[0102] R CEach independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 3-5 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl radical substitution;

[0103] R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-4 Alkyl; Raa, Rbb are each independently selected from H, halogen, =O, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0104] Alternatively, Raa, Rbb and the atoms to which they are attached together form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0105] Alternatively, two R C Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0106] Alternatively, R B 、R C Together with the atoms it is connected to form C 3-64-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl groups are substituted.

[0107] Furthermore, Technical Solution 1 provides a compound represented by formula (I), its stereoisomers, deuterated substances, solvates, cocrystals or pharmaceutically acceptable salts,

[0108] A is selected from a 3-20-membered heterocyclic group or a 5-20-membered heteroaryl group, wherein the heterocyclic group contains 1-5 heteroatoms selected from N, O, and S; the heterocyclic group and heteroaryl group are optionally replaced by 0-5 R A replace;

[0109] B is selected from the group consisting of a bond, C 3-10 Cycloalkyl, C 6-12 Aryl, 3-12 membered heterocyclic group or 5-12 membered heteroaryl, wherein the heterocyclic group or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, aryl, heterocyclic group or heteroaryl is optionally substituted by 0-5 R B replace;

[0110] C is selected from C 3-12 Cycloalkyl, C 6-10 Aryl, 3-12 membered heterocyclic group or 5-12 membered heteroaryl, wherein the heterocyclic group or heteroaryl group contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, heterocyclic group, aryl, and heteroaryl group are optionally substituted by 0-5 R C replace;

[0111] L1 and L2 are each independently selected from W1-R L -W2, the left side of L1 is connected to A, and the left side of L2 is connected to B;

[0112] R L Selected from bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-6 Cycloalkyl, 5-12 membered heteroaryl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkylene, alkenylene, alkynylene, cycloalkyl, heteroaryl, heterocycloalkyl may be further substituted by 1-4 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 1-4 Alkoxy, 3-6 membered cycloalkyl, wherein the alkyl, alkoxy, and cycloalkyl are optionally further substituted with 1-4 substituents selected from halogen, CN, OH, and NH2;

[0113] W1 and W2 are each independently selected from a bond, C 1-4 Alkylene, -O-, -S-, -S(=O)-, -S(=O)2-, -NR W1 -、-CONR W1 -、-NR W1 CO-, -C(=O)O-, -OC(=O)-, -C(=S)-, -C(=O)-, -(C 1-4 Alkylene)-NR W1 CO-, the alkylene group is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-4 Alkyl, CN, OH and NH2 group substitution;

[0114] R W1 Selected from H, C 1-4 Alkyl, halogen;

[0115] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, the alkyl, alkenyl, alkynyl, heteroaryl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, -O-halogenated C 1-4 Alkyl radical substitution;

[0116] Alternatively, two R A Together with the atoms it is connected to form C 3-6 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0117] R B Each independently selected from halogen, CN, =O, OH, -SF5, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, the alkyl, alkoxy, alkenyl, alkynyl may be further selected from halogen, C 1-2 Alkyl radical substitution;

[0118] R C Each independently selected from halogen, CN, =O, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 3-5 Cycloalkyl, C 2-4 Alkenyl, C 2-4Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, wherein the alkyl, cycloalkyl, heteroaryl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0119] Alternatively, two R C Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0120] Alternatively, R B 、R C Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl groups are substituted.

[0121] As a specific technical solution 2 of the present invention, there is provided a compound of formula (I), a stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt thereof, wherein:

[0122] A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocycloalkyl, 9-10 membered bicyclic heteroaryl, 10-14 membered tricyclic heterocycloalkyl, 10-14 membered tricyclic heteroaryl, wherein the heterocycloalkyl and heteroaryl are optionally substituted by 1-5 R A In some embodiments, A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocycloalkyl, 10-14 membered tricyclic heterocycloalkyl, wherein the heterocycloalkyl and heteroaryl groups are optionally substituted by 1-5 R A replace;

[0123] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-4 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy, -C 1-2 Alkylhydroxyl, -C(=O)C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0124] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy, -C 1-2 radical substitution of alkylhydroxy groups;

[0125] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy group substitution;

[0126] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy group substitution;

[0127] In some embodiments, R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6Cycloalkyl, the alkyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0128] Alternatively, two R A Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0129] B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, C 3-8 Cycloalkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heterocycloalkyl, 5-12 membered spirocyclic heterocycloalkyl, 3-6 membered cycloalkyl and 5-6 membered heterocycloalkyl, benzo 5-6 membered heterocycloalkyl, the heterocycloalkyl, heteroaryl, cycloalkyl, aryl are optionally substituted by 1-5 R B In some embodiments, B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, a C 3-8 Cycloalkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heterocycloalkyl, 5-12 membered spirocyclic heterocycloalkyl, 5-6 membered cycloalkyl and 5-6 membered heterocycloalkyl, benzo 5-6 membered heterocycloalkyl, the heterocycloalkyl, heteroaryl, cycloalkyl, aryl are optionally substituted by 1-5 R B replace;

[0130] R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted with halogen;

[0131] C is selected from 5-6 membered monocyclic heteroaryl, phenyl, phenyl and 4-6 membered carbocyclyl, phenyl and 4-6 membered heterocycloalkyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclyl, 8-12 membered tricyclic cycloalkyl, 8-14 membered tricyclic heterocyclyl, said heteroaryl, heterocycloalkyl and heterocyclyl containing 1-4 heteroatoms selected from N, O and S; said phenyl, heterocycloalkyl and carbocyclyl are optionally replaced by 1-5 R C In some embodiments, C is selected from 5-6 membered monocyclic heteroaryl, phenyl, phenyl and 4-6 membered carbocyclyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclyl, 8-12 membered tricyclic cycloalkyl, 8-14 membered tricyclic heterocyclyl, wherein the heteroaryl, heterocycloalkyl and heterocyclyl contain 1-4 heteroatoms selected from N, O and S; wherein the phenyl, heterocycloalkyl and carbocyclyl are optionally substituted with 1-5 R CIn some embodiments, C is selected from 5-6 membered monocyclic heteroaryl, phenyl and 4-6 membered carbocyclyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclyl, 8-12 membered tricyclic cycloalkyl, wherein the heterocycloalkyl contains 1-3 heteroatoms selected from N, O, and S; the phenyl, heterocycloalkyl, and carbocyclyl are optionally substituted with 1-5 R C replace;

[0132] R C are independently selected from D, halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -OC 5-11 Spiroalkyl, -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, spiroalkyl, heterocyclyl are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0133] In some embodiments, R C are independently selected from D, halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0134] In some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR aS(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0135] In some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0136] R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 alkyl, halogenated 3-6 membered cycloalkyl; in some embodiments, R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 alkyl;

[0137] R aa 、R bb are independently selected from H, halogen, =O, C 1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0138] In some embodiments, R aa 、R bb are independently selected from H, halogen, =O, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0139] Alternatively, R aa 、R bb Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0140] Alternatively, R B 、R C Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 atoms selected from halogen, C 1-2 Alkyl radical substitution;

[0141] L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4 Alkenylene, -C(=O)-NH-, -C(=O)-N(CH3)-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 Alkoxy; in some embodiments, L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4Alkenylene, -C(=O)-NH-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 Alkoxy; in some embodiments, L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-NH-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 alkoxy;

[0142] Alternatively, L1 is selected from The "*" end is connected to the B ring;

[0143] L2 is selected from a bond, C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, and alkynylene groups are optionally further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0144] Provided that when L2 is selected from -O-, -NH-, L1 is not selected from -C(=O)-, or B1 is not selected from a bond.

[0145] Further, Technical Solution 2 provides a compound of formula (I), its stereoisomers, deuterated substances, solvates, cocrystals or pharmaceutically acceptable salts, wherein:

[0146] A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocycloalkyl, 10-14 membered tricyclic heterocycloalkyl, wherein the heterocycloalkyl and heteroaryl are optionally replaced by 1-5 R A replace;

[0147] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy, -C 1-2 Alkylhydroxyl, -C(=O)C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution; or

[0148] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, the alkyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0149] B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, a 3-8 membered cycloalkyl, a 5-6 membered heteroaryl, a 5-6 membered heteroaryl and a 5-6 membered heterocycloalkyl, a 5-12 membered spirocyclic heterocycloalkyl, a 5-6 membered cycloalkyl and a 5-6 membered heterocycloalkyl, a benzo 5-6 membered heterocycloalkyl, wherein the heterocycloalkyl, heteroaryl, cycloalkyl, and aryl are optionally replaced by 1-5 R B replace;

[0150] R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted with halogen;

[0151] C is selected from 5-6 membered monocyclic heteroaryl, phenyl and 4-6 membered carbocyclic group, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclic group, 8-12 membered tricyclic cycloalkyl, the heterocycloalkyl contains 1-3 heteroatoms selected from N, O, S; the phenyl, heterocycloalkyl, carbocyclic group is optionally replaced by 1-5 R C replace;

[0152] R C are independently selected from halogen, CN, ═O, C 1-2 Alkyl, halogenated C 1-2 alkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl radical substitution;

[0153] R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 alkyl;

[0154] Raa and Rbb are each independently selected from H, halogen, ═O, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0155] Alternatively, Raa, Rbb and the atoms to which they are attached together form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0156] Alternatively, R B 、R C Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 atoms selected from halogen, C 1-2 Alkyl radical substitution;

[0157] L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-NH-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 alkoxy;

[0158] R W1 Selected from H, C 1-4 Alkyl, halogen;

[0159] Alternatively, L1 is selected from "*" end is connected to the B ring; L2 is selected from the bond, C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, and alkynylene groups are optionally further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0160] Provided that when L2 is selected from -O-, -NH-, L1 is not selected from -C(=O)-, or B1 is not selected from a bond.

[0161] Further, technical solution 2 provides a compound represented by formula (I), its stereoisomers, deuterated substances, solvates, cocrystals or pharmaceutically acceptable salts, wherein

[0162] A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocyclic group, 10-14 membered tricyclic heterocyclic group, wherein the heterocyclic group and heteroaryl are optionally replaced by 1-5 R A replace;

[0163] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, 5-6 membered heteroaryl, wherein the alkyl and heteroaryl are optionally further substituted by 1-5 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0164] B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, a 3-8 membered cycloalkyl, a 5-6 membered heteroaryl, a 5-6 membered heteroaryl and a 5-6 membered heterocyclic group, a 5-12 membered spirocyclic heterocycloalkyl, a 5-6 membered cycloalkyl and a 5-6 membered heterocycloalkyl, a benzo 5-6 membered heterocyclic group, wherein the heterocyclic group, heteroaryl, cycloalkyl, and aryl are optionally replaced by 1-5 R B replace;

[0165] R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted with halogen;

[0166] C is selected from 5-6 membered monocyclic heteroaryl, phenyl and 4-6 membered carbocyclic group, 5-6 membered heterocyclic group and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclic group, 8-12 membered tricyclic cycloalkyl, the heterocyclic group contains 1-3 heteroatoms selected from N, O, S; the phenyl, heterocyclic group, carbocyclic group are optionally replaced by 1-5 R C replace;

[0167] RC are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl, the alkyl, heteroaryl optionally further 1-5 selected from halogen, C 1-2 Alkyl radical substitution;

[0168] Alternatively, R B 、R C Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 atoms selected from halogen, C 1-2 Alkyl radical substitution;

[0169] L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-NH-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0170] L2 is selected from a bond, C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, and alkynylene groups are optionally further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0171] Provided that when L2 is selected from -O-, -NH-, L1 is not selected from -C(=O)-, or B1 is not selected from a bond.

[0172] As a specific technical solution 3 of the present invention, the compound described in Scheme 1 or Scheme 2, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein,

[0173] A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocyclic group, 10-14 membered tricyclic heterocyclic group, wherein the heterocyclic group and heteroaryl are optionally replaced by 1-5 R A replace;

[0174] R A Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, 5-6 membered heteroaryl, wherein the alkyl and heteroaryl are optionally further substituted by 1-5 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl groups are substituted.

[0175] As a specific technical solution 4 of the present invention, the compound described in Scheme 1 or Scheme 2, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein,

[0176] B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, a 3-8 membered cycloalkyl, a 5-6 membered heteroaryl, a 5-6 membered heteroaryl and a 5-6 membered heterocyclic group, a 5-12 membered spirocyclic heterocycloalkyl, a 5-6 membered cycloalkyl and a 5-6 membered heterocycloalkyl, a benzo 5-6 membered heterocyclic group, wherein the heterocyclic group, heteroaryl, cycloalkyl, and aryl are optionally replaced by 1-5 R B replace;

[0177] R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted by halogen.

[0178] As a specific technical solution 5 of the present invention, the compound described in Scheme 1 or Scheme 2, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein

[0179] C is selected from 5-6 membered monocyclic heteroaryl, phenyl and 4-6 membered carbocyclic group, 5-6 membered heterocyclic group and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclic group, 8-12 membered tricyclic cycloalkyl, the heterocyclic group contains 1-3 heteroatoms selected from N, O, S; the phenyl, heterocyclic group, carbocyclic group are optionally replaced by 1-5 R C replace;

[0180] R C are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl, the alkyl, heteroaryl optionally further 1-5 selected from halogen, C 1-2 Alkyl groups are substituted.

[0181] As a specific technical solution 6 of the present invention, the compound described in Scheme 1 or Scheme 2, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein

[0182] Alternatively, R B 、R C Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 atoms selected from halogen, C 1-2 Alkyl groups are substituted.

[0183] As a specific technical solution 7 of the present invention, the compound described in Scheme 1 or Scheme 2, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein

[0184] L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4Alkenylene, -C(=O)-NH-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0185] L2 is selected from a bond, C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, the alkylene, alkenylene, alkynylene optionally further 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0186] Provided that when L2 is selected from -O-, -NH-, L1 is not selected from -C(=O)-, or B1 is not selected from a bond.

[0187] As a specific technical solution 8 of the present invention, the compound of formula (I) described in any one of the technical solutions 1 to 7, its stereoisomer, deuterated product, solvate, cocrystal or pharmaceutically acceptable salt has the structure of formula (I-1a), (I-2), (I-3), (I-4), (I-5) or (I-1b):

[0188] A1 is selected from the following groups:

[0189] Or A1 is selected from the following groups:

[0190] Or A1 is selected from the following groups:

[0191] Or A1 is selected from the following groups:

[0192] Or A1 is selected from the following groups:

[0193] Or A1 is selected from the following groups:

[0194] Or A1 is selected from the following groups:

[0195] B1 is selected from the following groups: bond,

[0196] Or B1 is selected from the following groups:

[0197] Or B1 is selected from the following groups:

[0198] in, Terminal L1 or L 1a or L 1b Connected, "*" end to L2 or L 2a connected;

[0199] C1 is selected from the following groups:

[0200] C2 is selected from the following groups:

[0201] Or C2 is selected from the following groups:

[0202] Or C2 is selected from the following groups: Or C2 is selected from the following groups: Or C2 is selected from the following groups: Or C2 is selected from the following groups:

[0203] The condition is: C2 is selected from When L2 is not selected from a bond; or C2 is selected from When L2 is selected from a bond, n3 is not selected from 0 and R C Not for F;

[0204] R1, R2, R3, and R4 are each independently selected from H and halogen; provided that R1, R2, R3, and R4 cannot all be H at the same time;

[0205] Alternatively, R3 and R4 together form =O;

[0206] Formula (I-3) satisfies one or more of the following conditions:

[0207] (1) L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4 Alkenylene, -C(=O)-NH-, -C(=O)-N(CH3)-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; in some embodiments, L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4 Alkenylene, -C(=O)-NH-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; in some embodiments, L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0208] L 1a The right side is connected to the B1 ring;

[0209] R a 、R b Each independently selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 Alkyl; provided that R a 、R b Not selected from H at the same time;

[0210] L 2a Selected from bond, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, and alkynylene groups are optionally further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; provided that, when L 1a Selected from -C(=O)-, L 2a When selected from -NH-, -O-, B1 is not selected from a bond;

[0211] (2) L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selecting a bond, there is at least one R C1 Selected from =O, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, cubane, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heteroaryl), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selecting a bond, there is at least one R C1 Selected from =O, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, cubane, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4In some embodiments, L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selecting a bond, there is at least one R C1 Selected from =O, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, cubane, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane optionally further substituted by 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl group substitution; preferably, L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selecting a bond, there is at least one R C1 Selected from 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl radical substitution;

[0212] (3) L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a Selected from C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, and alkynylene groups are optionally further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0213] (4) L 1a Selected from: -C(=O)-CH2-, L 2a When selecting a bond, there is at least one R A Not selected from C 1-2 Alkyl, and the compound is not

[0214] L 1b Selected from: bond, 4-6 membered monocyclic heterocycloalkyl, -C(=O)-NH-, wherein the heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-2 Alkyl radical substitution;

[0215] Alternatively, Selected from

[0216] R A are independently selected from halogen, =O, C 1-2 Alkyl, -CF3, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-2 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 Alkylhydroxyl, halogenated C 1-2 Alkyl, -C(=O)C 1-2 Alkyl, C 1-2 Alkoxy group substitution;

[0217] In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, -CF3, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 Alkylhydroxyl, halogenated C 1-2 Alkyl, -C(=O)C 1-2 Alkyl, C 1-2 Alkoxy group substitution;

[0218] In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 Alkylhydroxyl, halogenated C 1-2 Alkyl, -C(=O)C 1-2 Alkyl, C 1-2 Alkoxy group substitution;

[0219] In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, 5-6 membered heteroaryl, The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 radical substitution of alkylhydroxy groups;

[0220] In some embodiments, R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 In some embodiments, R Aare independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl group is optionally further replaced by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 In some embodiments, R A Each independently selected from =O, C 1-2 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, wherein the alkyl group is optionally further substituted by 1-4 groups selected from NH2, CN, C 1-2 The alkyl group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl radical substitution;

[0221] R A1 Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -SO2-C 1-4 Alkyl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 In some embodiments, R A1 Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -NR aa Rbb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-4 In some embodiments, R A1 Each independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, the alkyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0222] Alternatively, two R A Together with the atoms it is connected to form C 3-6 4-6 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-2 Alkyl radical substitution;

[0223] R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted with halogen;

[0224] R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-3 Alkoxy, C 3-4 Cycloalkyl, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0225] In some embodiments, R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0226] In some embodiments, R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0227] In some embodiments, R C are each independently selected from halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, the alkyl, heteroaryl optionally further 1-4 selected from halogen, C 1-2 Alkyl radical substitution;

[0228] Preferred R C are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl, CN, =O, wherein the alkyl and heteroaryl groups are optionally further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl radical substitution;

[0229] R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, halogenated C 1-3 Alkoxy, C 3-5 Cycloalkyl, C 6-10Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(5-6 membered heteroaryl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0230] In some embodiments, R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NRa C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(5-6 membered heteroaryl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0231] In some embodiments, R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(5-6 membered heteroaryl), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a-C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl group is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 In some embodiments, R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a-C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution;

[0232] Preferred R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 alkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further 1-4 selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl radical substitution;

[0233] R aa 、R bb are independently selected from H, halogen, =O, C1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0234] In some embodiments, R aa 、R bb are independently selected from H, halogen, =O, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 alkoxy;

[0235] Alternatively, R aa 、R bb Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0236] n1, n2, n3 are each independently selected from 0, 1, 2, 3, 4 or 5.

[0237] Furthermore, the compound described in Technical Solution 8, its stereoisomer, deuterated form, solvate, cocrystal or pharmaceutically acceptable salt has the structure of Formula (I-1), (I-2), (I-3), (I-4) or (I-5):

[0238] A1 is selected from the following groups:

[0239] B1 is selected from the following groups: bond,

[0240] in, The "*" end is connected to L2;

[0241] C1 is selected from the following groups:

[0242] C2 is selected from the following groups:

[0243] R1, R2, R3, and R4 are each independently selected from H and halogen; provided that R1, R2, R3, and R4 cannot all be H at the same time;

[0244] Alternatively, R3 and R4 together form =O;

[0245] (1) L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -containing 1-3 heteroatoms selected from N, O, S 4-6 membered heterocycloalkyl-C 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl;

[0246] R a 、R b Each independently selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 Alkyl; provided that R a 、R b Not selected from H at the same time;

[0247] L 2a Selected from bond, C 2-4 Alkenylene, C 2-4 Alkynylidene, -C(=O)-NH-, -NH-, -O-, -N(C 1-2Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, and alkynylene groups are optionally further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; provided that, when L 1a Selected from -C(=O)-, L 2a When selected from -NH-, -O-, B1 is not selected from a bond;

[0248] (2) L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selected from the bond, R C1 is selected from 5-6 membered heteroaryl, said heteroaryl being optionally further substituted by 1-4 members selected from halogen, C 1-2 Alkyl radical substitution;

[0249] (3) L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, R C1 When selected from -CF3, L 2a Not a key;

[0250] L 1b Selected from: bond, 4-6 membered monocyclic heterocycloalkyl, -C(=O)-NH-, wherein the heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-2 Alkyl radical substitution;

[0251] Alternatively, Selected from

[0252] R A are independently selected from halogen, =O, C 1-2 Alkyl, 5-6 membered heteroaryl, wherein the alkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl radical substitution;

[0253] R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted with halogen;

[0254] R C are independently selected from halogen, halogenated C 1-2Alkyl, 5-6 membered heteroaryl, the alkyl, heteroaryl optionally further 1-4 selected from halogen, C 1-2 Alkyl radical substitution;

[0255] n1, n2, n3 are each independently selected from 0, 1, 2, 3, 4 or 5.

[0256] As a specific technical solution 9 of the present invention, the compounds of formula (I-1a), (I-2), (I-3), (I-4), (I-5) described in Scheme 7 or Scheme 8, their stereoisomers, deuterated substances, solvates, cocrystals or pharmaceutically acceptable salts, wherein:

[0257] R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, 5-6 membered heteroaryl, The methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy; the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -C(=O)CH3, -O-CH3, and -O-CH2CH3;

[0258] In some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -NHR aa , the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; in some embodiments, R A Each independently selected from =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5-membered heteroaryl, 6-membered heteroaryl, the methyl and ethyl groups are optionally further substituted with 1-4 groups selected from NH2, CN, methyl, and ethyl, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0259] Alternatively, two R A Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0260] R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa, the methyl, ethyl, cycloalkyl group is optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, methoxy; in some embodiments, R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, methyl, ethyl, -OC 3-6 Cycloalkyl, wherein the methyl, ethyl, and cycloalkyl groups are optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0261] R B Each is independently selected from F, Cl, =O, methyl, ethyl, wherein the methyl and ethyl groups are optionally further substituted by F and Cl groups;

[0262] R C Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, wherein the methyl, ethyl, cyclopropyl, cyclobutyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from F, Cl, methyl, and ethyl;

[0263] R C1 Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, cyclopentyl, cubane, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered cyclic heteroaryl, 9-membered cyclic heteroaryl, 10-membered cyclic heteroaryl, 7-8-membered spirocyclic heterocycloalkyl, 8-9-membered cyclic heterocycloalkyl, 7-membered bridged heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH-(4-6 membered heterocycloalkyl), -NH-(5-6 membered heteroaryl), -NH-S(=O)2-C 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -C 1-2 Alkyl-phenyl, -C 1-2 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-2 alkyl) n -O-(C 1-2 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, deuterated methyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-2 In some embodiments, R C1 Each independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, C 4-5 Cycloalkyl, cubane, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered cycloheteroaryl, 9-membered cycloheteroaryl, 10-membered cycloheteroaryl, 7-8-membered spirocyclic heterocycloalkyl, 8-9-membered cycloheterocycloalkyl, 7-membered bridged heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NRa C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH-(4-6 membered heterocycloalkyl), -NH-(5-6 membered heteroaryl), -NH-S(=O)2-C 3-6 Cycloalkyl, the cyclopropyl, cyclobutyl, cyclopentyl, alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-2 Alkyl radical substitution;

[0264] R a is selected from H, F, Cl, methyl, ethyl, cyclopropyl, cyclobutyl, cyclopentyl, difluorocyclobutyl; in some embodiments, R a is selected from H, F, Cl, methyl, ethyl, cyclopropyl, cyclobutyl, and cyclopentyl;

[0265] R aa 、R bb Each is independently selected from H, F, Cl, =O, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCH3, -OCH2CH3, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH2CHF2, -OCH2CH2F;

[0266] Alternatively, R aa 、R bb Together with the atoms to which it is attached, it forms a 4-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0267] n1 is selected from 1, 2, or 3; in some embodiments, n1 is selected from 1, 2, or 3;

[0268] n2 is selected from 0 or 1;

[0269] n3 is selected from 0, 1 or 2;

[0270] L1 is selected from a bond, vinylene, -CH2-, -CH2-CH2-, 4-6 membered monocyclic heterocycloalkyl, (4-6 membered monocyclic heterocycloalkyl)-C(=O)-CH2-, -(4-6 membered monocyclic heterocycloalkyl)-CH2-, -CH2-(4-6 membered monocyclic heterocycloalkyl)-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6 Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -(5-6 membered heteroaryl)-CH2-, 5-6 membered heteroaryl, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, -CF2-CH2-, -C(=O)-C 2-4 Alkenylene, -C(=O)-O-, the -CH2-, alkenylene, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1 Replacement; R L1 each independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, ethenyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl, methyl-methoxy, 5-membered heteroaryl; in some embodiments, L1 is selected from a bond, ethenylene, -CH2-, -CH2-CH2-, 4-6-membered monocyclic heterocycloalkyl, (4-6-membered monocyclic heterocycloalkyl)-C(=O)-CH2-, -(4-6-membered monocyclic heterocycloalkyl)-CH2-, -CH2-(4-6-membered monocyclic heterocycloalkyl)-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6 Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -(5-6 membered heteroaryl)-CH2-, 5-6 membered heteroaryl, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, -CF2-CH2-, wherein the -CH2-, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1Replacement; R L1 Each is independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, vinyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl, methyl-methoxy, 5-membered heteroaryl;

[0271] Alternatively, L1 is selected from The "*" end is connected to the B ring;

[0272] L2 is selected from a bond, vinylene, ethynylene, -CH2-, -CH2-CH2-, -O-, -NH-, -C(=O)-, -N(CH3)-.

[0273] Furthermore, the compound of formula (I) described in technical solution 9, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein,

[0274] R A Each independently selected from =O, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5-membered heteroaryl, 6-membered heteroaryl, the methyl and ethyl groups are optionally further substituted with 1-4 groups selected from NH2, CN, methyl, and ethyl, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0275] R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, methyl, ethyl, -OC 3-6 Cycloalkyl, wherein the methyl, ethyl, and cycloalkyl groups are optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0276] R B Each is independently selected from F, Cl, =O, methyl, ethyl, wherein the methyl and ethyl groups are optionally further substituted by F and Cl groups;

[0277] R C Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, 5-membered heteroaryl, 6-membered heteroaryl, CN, =O, and the methyl, ethyl, heteroaryl is optionally further substituted with 1-4 groups selected from F, Cl, methyl, and ethyl;

[0278] R C1Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered cyclic heteroaryl, 9-membered cyclic heteroaryl, 10-membered cyclic heteroaryl, 7-8-membered spirocyclic heterocycloalkyl, 8-9-membered cyclic heterocycloalkyl, 7-membered bridged heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl radical substitution;

[0279] R a is selected from H, F, Cl, methyl, ethyl, cyclopropyl, cyclobutyl, and cyclopentyl;

[0280] R aa 、R bb Each is independently selected from H, F, Cl, =O, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCH3, -OCH2CH3, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH2CHF2, -OCH2CH2F;

[0281] Alternatively, R aa 、R bb Together with the atoms to which it is attached, it forms a 4-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; n1 is selected from 1, 2, or 3;

[0282] n2 is selected from 0 or 1;

[0283] n3 is selected from 0, 1 or 2;

[0284] L1 is selected from a bond, vinylene, -CH2-, -CH2-CH2-, 4-6 membered monocyclic heterocycloalkyl, (4-6 membered monocyclic heterocycloalkyl)-C(=O)-CH2-, -(4-6 membered monocyclic heterocycloalkyl)-CH2-, -CH2-(4-6 membered monocyclic heterocycloalkyl)-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6 Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -(5-6 membered heteroaryl)-CH2-, 5-6 membered heteroaryl, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, -CF2-CH2-, wherein the -CH2-, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1 Replacement; R L1 Each is independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, vinyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl, methyl-methoxy, 5-membered heteroaryl;

[0285] Alternatively, L1 is selected from The "*" end is connected to the B ring;

[0286] L2 is selected from a bond, vinylene, ethynylene, -CH2-, -CH2-CH2-, -O-, -NH-, -C(=O)-, -N(CH3)-.

[0287] Furthermore, the compound described in Technical Solution 9, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein:

[0288] R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, 5-6 membered heteroaryl, The methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy; the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0289] In some embodiments, R A Each is independently selected from F, Cl, =O, methyl, ethyl, 5-membered heteroaryl, 6-membered heteroaryl, wherein the methyl, ethyl, 5-membered heteroaryl, 6-membered heteroaryl is optionally further substituted with 1-4 groups selected from F, Cl, methyl, and ethyl;

[0290] R B Each is independently selected from F, Cl, =O, methyl, ethyl, wherein the methyl and ethyl groups are optionally further substituted by F and Cl groups;

[0291] R C Each is independently selected from F, Cl, -CF3, -CHF2, -CH2CH2F, -CH2CF3, -CH2CHF2, -CH2CH2F, 5-membered heteroaryl, 6-membered heteroaryl, the heteroaryl being optionally further substituted with 1-4 groups selected from F, Cl, methyl, and ethyl;

[0292] n1 is selected from 1, 2 or 3;

[0293] n2 is selected from 0 or 1;

[0294] n3 is selected from 0, 1 or 2;

[0295] L1 is selected from a bond, vinylene, -CH2-, 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl-C(=O)-CH2-, -4-6 membered monocyclic heterocycloalkyl-CH2-, -CH2-4-6 membered monocyclic heterocycloalkyl-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -5-6 membered heteroaryl-CH2-, -5-6 membered heteroaryl-, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, wherein the -CH2-, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1 Replacement; R L1 Each is independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, vinyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl;

[0296] L2 is selected from a bond, vinylene, ethynylene, -O-, -NH-, -C(=O)-, -N(CH3)-.

[0297] Furthermore, the compound described in Technical Solution 10, its stereoisomer, deuterated form, solvate, cocrystal or pharmaceutically acceptable salt, wherein it has the structure of Formula (I-6), (I-7) or (I-8):

[0298] R C1 Each independently selected from halogenated C 1-2 Alkyl, 5-6 membered heteroaryl, -OC 3-6 Cycloalkyl, -O-4-6 membered heterocycloalkyl, -O-5-6 membered heteroaryl, wherein the heteroaryl, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl group substitution; preferably, R C1 Each is independently selected from 5-membered heteroaryl, 6-membered heteroaryl, -OC 3-6 Cycloalkyl, the heteroaryl, cycloalkyl is optionally further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl group substitution; preferably, R C1 Each independently 5-membered heteroaryl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, the pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, cyclopropyl, cyclobutyl, cyclopentyl optionally further 1-4 selected from halogen, OH, NH2, CN, C1-2 Alkyl, halogenated C 1-2 Alkyl, =O, -C(=O)C 1-2 More preferably, R C1 Each independently selected from halogenated C 1-2 alkyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, triazole, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-bicyclo[1.1.1]pentane, -O-spiro[2.3]hexane, -O-oxacyclopentyl, wherein the pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, cyclopropyl, cyclobutyl, cyclopentyl, bicyclo[1.1.1]pentane, spiro[2.3]hexane, oxacyclopentyl are optionally further substituted with 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O; more preferably, R C1 Each is independently selected from pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, and the pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, cyclopropyl, cyclobutyl, cyclopentyl is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O; more preferably, R C1 Each independently selected from -CF3, More preferably, R C1 Each independently selected from

[0299] X1 selected from CR X1 or N; or X1 is selected from NR X1 ;

[0300] X2 selected from CR X2 or N;

[0301] X3 selected from CR X3 or N;

[0302] X4 selected from CR X4 or N;

[0303] R X1 、R X2 、R X3 、R X4 Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -SO2-C 1-4 Alkyl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl group substitution; preferably, R X1 、R X2 、R X3 、R X4 Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa Rbb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl group substitution; preferably, R X1 、R X2 、R X3 、R X4 Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-2 Alkyl, C 1-2 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, 5-6 membered heteroaryl, -SO2-C 1-2 Alkyl, -NR a CO-C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkoxy, O-halogenated C 1-2 Alkyl, C 1-2 Alkyl group substitution; preferably, R X1 、R X2 、R X3 、R X4 Each independently selected from H, halogen, =O, CN, OH, COOH, C 1-2 Alkyl, C 1-2 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, 5-6 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4Alkyl-(5-6 membered heteroaryl), -O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-7 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkoxy, -F, O-halogenated C 1-2 Alkyl, C 1-2 More preferably, R X1 、R X2 、R X3 、R X4 Each independently selected from H, F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy; the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0304] In some embodiments, R X1 、R X2 、R X3 、R X4Each independently selected from H, F, Cl, =O, CN, -SO2CH3, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , the methyl, ethyl, heteroaryl, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, methoxy;

[0305] In some embodiments, R X1 、R X2 、R X3 、R X4 Each independently selected from H, F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , the methyl, ethyl, heteroaryl, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, methoxy;

[0306] Alternatively, choose any two R X1 、R X2 、R X3 、RX4 Together with the atoms it is connected to form C 3-6 4-10 membered carbocyclic group or heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally further substituted by 1-4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution;

[0307] In some embodiments, Selected from

[0308] In some embodiments, Selected from

[0309] R aa 、R bb are independently selected from H, halogen, =O, C 1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 Alkoxy.

[0310] Furthermore, the compound described in Technical Solution 11, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein

[0311] R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , -SO2CH3, cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, oxacyclopentyl, -CF3, 7-10 membered bicyclic heterocycloalkyl, the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -C(=O)CH3, -O-CH3, and -O-CH2CH3;

[0312] In some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, 5-6 membered heteroaryl, -CF3, 7-10 membered bicyclic heterocycloalkyl, the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy, and the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -C(=O)CH3, -O-CH3, and -O-CH2CH3;

[0313] In some embodiments, R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, 5-6 membered heteroaryl, The methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, methyl, ethyl, and methoxy; the heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0314] Alternatively, two R A Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl;

[0315] R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, -SO2CH3, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa , 5-membered heteroaryl, 4-6-membered heterocycloalkyl, wherein the methyl, ethyl, cycloalkyl, 4-6-membered heterocycloalkyl is optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, methoxy; In some embodiments, R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa , 5-membered heteroaryl, 4-6-membered heterocycloalkyl, wherein the methyl, ethyl, cycloalkyl, 5-membered heteroaryl, 4-6-membered heterocycloalkyl is optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, and methoxy;

[0316] In some embodiments, R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa, the methyl, ethyl, and cycloalkyl groups are optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, and methoxy;

[0317] R B Each is independently selected from F, Cl, =O, methyl, ethyl, wherein the methyl and ethyl groups are optionally further substituted by F and Cl groups;

[0318] R C Each is independently selected from D, F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-6 membered monocyclic heterocycloalkyl), The methyl, ethyl, heteroaryl, cycloalkyl group is optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3; in some embodiments, R C Each is independently selected from D, F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-6 membered monocyclic heterocycloalkyl), The methyl, ethyl, heteroaryl, and cycloalkyl groups are optionally further substituted by 1 to 4 groups selected from F, Cl, methyl, ethyl, and -CF3;

[0319] In some embodiments, R C Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, the methyl, ethyl, heteroaryl group is optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl;

[0320] R C1Each independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, C 4-5 Cycloalkyl, cubane, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered cycloheteroaryl, 9-membered cycloheteroaryl, 10-membered cycloheteroaryl, 7-8-membered spirocyclic heterocycloalkyl, 8-9-membered cycloheterocycloalkyl, 7-membered bridged heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH-(4-6 membered heterocycloalkyl), -NH-(5-6 membered heteroaryl), -NH-S(=O)2-C 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -C 1-2 Alkyl-phenyl, -C 1-2 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-2 alkyl) n -O-(C 1-2 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heterocyclyl, heteroaryl, heterocycloalkyl, cubane is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, deuterated methyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-2 Alkyl radical substitution;

[0321] R a is selected from H, F, Cl, methyl, ethyl, cyclopropyl, cyclobutyl, cyclopentyl, difluorocyclobutyl;

[0322] R aa 、R bb Each is independently selected from H, F, Cl, =O, methyl, ethyl, -CH2-CH2-OH, -CH2-OH, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCH3, -OCH2CH3, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH2CHF2, -OCH2CH2F;

[0323] Alternatively, R aa 、R bb Together with the atoms to which it is attached, it forms a 4-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; n1 is selected from 0, 1, 2, or 3;

[0324] n2 is selected from 0 or 1;

[0325] n3 is selected from 0, 1, 2, 3 or 4;

[0326] In some embodiments, n3 is selected from 0, 1 or 2;

[0327] L1 is selected from a bond, vinylene, -CH2-, -CH2-CH2-, 4-6 membered monocyclic heterocycloalkyl, (4-6 membered monocyclic heterocycloalkyl)-C(=O)-CH2-, -(4-6 membered monocyclic heterocycloalkyl)-CH2-, -CH2-(4-6 membered monocyclic heterocycloalkyl)-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6 Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -(5-6 membered heteroaryl)-CH2-, 5-6 membered heteroaryl, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, -CF2-CH2-, -C(=O)-C 2-4 Alkenylene, -C(=O)-O-, -C(=O)-NH-, -C(=O)-N(CH3)-, wherein the -CH2-, alkenylene, cycloalkyl, heterocycloalkyl, heteroaryl are optionally further substituted by 1-3 R L1 Replacement; R L1 Each is independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, vinyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl, methyl-methoxy, 5-membered heteroaryl;

[0328] Alternatively, L1 is selected from The "*" end is connected to the B ring;

[0329] L2 is selected from a bond, vinylene, ethynylene, -CH2-, -CH2-CH2-, -O-, -NH-, -C(=O)-, -N(CH3)-.

[0330] Furthermore, the compound described in Technical Solution 12, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein it has the structure of Formula (II):

[0331] Ring A is selected from the group consisting of optionally further substituted by 1, 2 or 3 R A The following structures are replaced: Or choose Het is a 5-membered heteroaryl group, wherein the heteroaryl group is optionally substituted by 1 or 2 selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl radical substitution;

[0332] Each R A Each independently selected from halogen, CN, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -OC 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, -SO2-C 1-2Alkyl, the heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-2 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, C 1-2 Alkoxy, -C(=O)C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0333] The C ring is selected from The C ring is optionally further substituted with 1, 2 or 3 R C replace;

[0334] Each R C are independently selected from halogen, halogenated C 1-3 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, 5-6 membered heteroaryl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -OC 5-8 Spiroalkyl, The heteroaryl, cycloalkyl, spirocycloalkyl may be further substituted by 1-3 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl groups are substituted.

[0335] Furthermore, the compound described in Technical Solution 13, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein

[0336] Ring A is selected from

[0337] Each R C Each independently selected from F, Cl, CF3, CHF2, CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl,

[0338] As a specific technical solution of the present invention, the compound of the present invention, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, is selected from one of the structures in Table A below:

[0339] Table A

[0340] The present invention also provides a pharmaceutical composition or pharmaceutical preparation comprising the compound described in any one of the aforementioned schemes, its stereoisomers, deuterated substances, solvates, cocrystals or pharmaceutically acceptable salts, and a pharmaceutically acceptable carrier and / or excipient.

[0341] Furthermore, the composition or pharmaceutical preparation of the present invention contains 1-1500 mg of the compound described in any one of the aforementioned schemes, its stereoisomers, deuterated substances, solvates, cocrystals or pharmaceutically acceptable salts and a carrier and / or excipient.

[0342] The present invention also provides a compound according to any of the foregoing schemes, a stereoisomer, deuterated form, solvate, cocrystal or pharmaceutically acceptable salt thereof, or a composition according to any of the foregoing schemes, for use in the preparation of a medicament for treating / preventing a CHRM4-mediated disease. Further, the CHRM4-mediated disease is selected from Alzheimer's disease, schizophrenia or psychosis, pain, addiction, sleep disorders, cognitive impairment, Parkinson's disease, Parkinson's disease-levodopa-induced dyskinesia, Huntington's disease, movement disorders, dry mouth, pulmonary hypertension, chronic obstructive pulmonary disease, asthma, urinary incontinence, glaucoma, trisomy 21, cerebral amyloid angiopathy, dementia, Dutch hereditary amyloidosis cerebral hemorrhage, prion disorders, amyotrophic lateral sclerosis, progressive supranuclear palsy, head trauma, stroke, pancreatitis, inclusion body myositis, other peripheral amyloidosis, diabetes, autism and atherosclerosis; preferably Alzheimer's disease, schizophrenia, pain, addiction and sleep disorders.

[0343] The present invention also provides a method for treating a disease in a mammal or a human, comprising administering to a subject a therapeutically effective amount of a compound according to any one of the foregoing schemes or a stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt thereof, preferably 1-1500 mg, wherein the disease is selected from Alzheimer's disease, schizophrenia or psychosis, pain, addiction, sleep disorders, cognitive disorders, Parkinson's disease, Parkinson's disease-levodopa-induced dyskinesia, Huntington's disease, dyskinesia, dry mouth, lung disease, Arterial hypertension, chronic obstructive pulmonary disease, asthma, urinary incontinence, glaucoma, trisomy 21, cerebral amyloid angiopathy, dementia, Dutch hereditary amyloidosis cerebral hemorrhage, prion disorders, amyotrophic lateral sclerosis, progressive supranuclear palsy, head trauma, stroke, pancreatitis, inclusion body myositis, other peripheral amyloidosis, diabetes, autism, and atherosclerosis; preferably, the diseases are Alzheimer's disease, schizophrenia, pain, addiction, and sleep disorders. In some embodiments, the mammals described in the present invention do not include humans.

[0344] As used herein, an "effective amount" or "therapeutically effective amount" refers to the administration of a sufficient amount of a compound disclosed herein to alleviate, to some extent, one or more symptoms of the disease or condition being treated. In some embodiments, the result is a reduction and / or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an "effective amount" for therapeutic uses is the amount of a composition comprising a compound disclosed herein required to provide a clinically significant reduction in disease symptoms. Examples of therapeutically effective amounts include, but are not limited to, 1-1500 mg, 1-1400 mg, 1-1300 mg, 1-1200 mg, 1-1000 mg, 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-250 mg, 1-200 mg, 1-150 mg, 1-125 mg, 1-100 mg, 1-80 mg, 1-60 mg, 1-50 mg, 1-40 mg, 1-25 mg, 1- 20mg, 5-1500mg, 5-1000mg, 5-900mg, 5-800mg, 5-700mg, 5-600mg, 5-500mg, 5-400mg, 5-300mg, 5-250mg, 5-200mg, 5 -150mg, 5-125mg, 5-100mg, 5-90mg, 5-70mg, 5-80mg, 5-60mg, 5-50mg, 5-40mg, 5-30mg, 5-25mg, 5-20mg, 10-1500mg, 10-1000mg, 10-900mg, 10-800mg, 10-700mg, 10-600mg, 10-500mg, 10-450mg, 10-400mg, 10-300mg, 10-250mg, 10-20 0mg, 10-150mg, 10-125mg, 10-100mg, 10-90mg, 10-80mg, 10-70mg, 10-60mg, 10-50mg, 10-40mg, 10-30mg, 10-20mg; 2 0-1500mg, 20-1000mg, 20-900mg, 20-800mg, 20-700mg, 20-600mg, 20-500mg, 20-400mg, 20-350mg, 20-300mg, 20-25 0mg, 20-200mg, 20-150mg, 20-125mg, 20-100mg, 20-90mg, 20-80mg, 20-70mg, 20-60mg, 20-50mg, 20-40mg, 20-30mg;50-1500mg, 50-1000mg, 50-900mg, 50-800mg, 50-700mg, 50-600mg, 50-500mg, 50-400mg, 50-300mg, 50-250mg, 50-200mg, 50-150mg, 50-125mg, 5 0-100mg; 100-1500mg, 100-1000mg, 100-900mg, 100-800mg, 100-700mg, 100-600mg, 100-500mg, 100-400mg, 100-300mg, 100-250mg, 100-200mg. ;

[0345] The present invention relates to a kit, which may include a composition in single-dose or multi-dose form, wherein the kit contains a compound of the present invention or a stereoisomer, deuterated substance or pharmaceutically acceptable salt thereof, and the amount of the compound of the present invention or its stereoisomer, deuterated substance or pharmaceutically acceptable salt is the same as that in the above-mentioned pharmaceutical composition.

[0346] The amount of the compound of the invention or its stereoisomer or pharmaceutically acceptable salt in the present invention is in each case calculated as the free base.

[0347] "Preparation specifications" refers to the weight of the main drug contained in each vial, tablet or other unit preparation.

[0348] Synthesis route

[0349] Patent documents such as WO2018002760A1 describe methods for preparing CHRM4 receptor agonists. Those skilled in the art can combine this document with known organic synthesis techniques to prepare the compounds of the present invention, using commercially available chemicals and / or compounds described in chemical literature as starting materials. "Commercially available chemicals" are obtained from legitimate commercial sources, including suppliers such as Titan Technology, Anage Chemical, Shanghai Demo, Chengdu Kelon Chemical, Shaoyuan Chemical Technology, Nanjing Yaoshi, WuXi AppTec, and J&K Technology.

[0350] Specific and similar reactants can be selectively identified by indexing known chemical substances prepared by the American Chemical Society's Chemical Abstracts Service, which is available in most public and university libraries and online. Chemicals that are known but not commercially available in the catalog are optionally prepared by custom chemical synthesis facilities, many of which offer custom synthesis services.

[0351] the term

[0352] Unless otherwise specified in the present invention, the terms of the present invention have the following meanings:

[0353] Unless otherwise specified in the present invention, the terms of the present invention have the following meanings:

[0354] The carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds of the present invention include their isotopes, and the carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds of the present invention are optionally further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 12 C. 13 C and 14 C, hydrogen isotopes include protium (H), deuterium (D, also known as heavy hydrogen), tritium (T, also known as super tritium), oxygen isotopes include 16 O. 17 O and 18 O, sulfur isotopes include 32 S. 33 S. 34 S and 36 S, nitrogen isotopes include 14 N and 15 N, an isotope of fluorine 19 F, chlorine isotopes include 35 Cl and 37 Isotopes of Cl, bromine include 79 Br and 81 Br.

[0355] "Halogen" herein refers to F, Cl, Br, I, or isotopes thereof.

[0356] "Halo" or "halogen substitution" means that a hydrogen atom is replaced by one or more halogens selected from F, Cl, Br, I, or isotopes thereof. The upper limit of the number of halogen substituents is equal to the sum of the number of hydrogen atoms that can be replaced by the substituted group. Unless otherwise specified, the number of halogen substituents is any integer between 1 and the upper limit. When the number of halogen substituents is greater than 1, they may be the same or different halogens.

[0357] "Deuterated" or "deuterated compound" refers to a situation where a hydrogen atom on an alkyl, cycloalkyl, alkylene, aryl, heteroaryl, thiol, heterocycloalkyl, alkenyl, alkynyl or other group is replaced by at least one isotope, deuterium. The upper limit of the number of deuterated groups is equal to the sum of the number of replaceable hydrogen atoms in the substituted group. Unless otherwise specified, the number of deuterated groups is any integer between 1 and the upper limit, preferably 1-20 deuterium atoms, more preferably 1-10 deuterium atoms, more preferably 1-6 deuterium atoms, and even more preferably 1-3 deuterium atoms.

[0358] "Alkyl" refers to a monovalent straight-chain or branched saturated aliphatic hydrocarbon group. Unless otherwise specified, it is an alkyl group having 1 to 20 carbon atoms, preferably an alkyl group having 1 to 8 carbon atoms, more preferably an alkyl group having 1 to 6 carbon atoms, further preferably an alkyl group having 1 to 4 carbon atoms, and further preferably an alkyl group having 1-2 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, neobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, and various branched chain isomers thereof.

[0359] "Alkylene" refers to a divalent straight-chain or branched saturated alkyl group. Examples of alkylene groups include, but are not limited to, methylene, ethylene, propylene, and butylene.

[0360] "Cycloalkyl" refers to a monovalent non-aromatic, partially unsaturated or fully saturated, substituted or unsubstituted carbocyclic hydrocarbon group, which, unless otherwise specified, usually has 3 to 12 carbon atoms, preferably 3 to 10 carbon atoms, more preferably 3 to 6 carbon atoms, and further preferably 3 to 4 carbon atoms. Non-limiting examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Or cycloheptyl, etc.

[0361] "Cycloalkylene" refers to a divalent radical of "cycloalkyl", non-limiting examples of which include cyclopropylene, cyclobutylene, and the like.

[0362] "Heterocycle" or "heterocyclyl" refers to a substituted or unsubstituted, saturated or unsaturated aromatic or non-aromatic ring, and unless otherwise specified, contains 1 to 3 heteroatoms selected from N, O, or S, including monocyclic heterocycles, bicyclic bridged heterocycles, bicyclic heterocycles, bicyclic spiro heterocycles, tricyclic heterocycles, and the like. Unless otherwise specified, it is a 3- to 14-membered heterocycle, more preferably a 4- to 12-membered heterocycle, more preferably a 4- to 10-membered heterocycle, and even more preferably a 4- to 7-membered heterocycle. This definition includes heterocycloalkyl and heteroaryl groups. The N and S in the heterocyclyl ring can be oxidized to various oxidation states. The heterocyclic group can be attached to a heteroatom or a carbon atom, and non-limiting examples include oxirane, aziridine, oxetanyl, azetidinyl, 1,3-dioxolanyl, 1,4-dioxolanyl, 1,3-dioxane, azepanyl, pyridinyl, furanyl, thienyl, pyranyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyridazinyl, imidazolyl, piperidinyl, piperidinyl, morpholinyl, thiomorpholinyl, 1,3-dithianyl, dihydrofuranyl, dihydropyranyl, dithiolanyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydroimidazolyl, oxazolyl, dihydrooxazolyl, tetrahydrooxazolyl, tetrahydrothiazolyl, tetrahydropyranyl, benzimidazolyl, benzopyridinyl, pyrrolopyridinyl, benzodihydrofuranyl, azabicyclo[3.2.1]octyl, azabicyclo[5.2.0]nonyl, oxatricyclo[5.3.1.1]dodecyl, azaadamantyl and oxaspiro[3.3]heptanyl, wait.

[0363] "Heterocyclylene" is a divalent group corresponding to "heterocyclyl", and non-limiting examples include imidazolyl, piperidinyl, aziridinyl, and the like.

[0364] "Carbocycle" or "carbocyclyl" refers to a substituted or unsubstituted, saturated or unsaturated, aromatic or non-aromatic carbocyclic group, including monocyclic carbocycles, bicyclic bridged rings, bicyclic cyclic rings and bicyclic spirocycles, etc., unless otherwise specified, and has 3 to 12 carbon atoms, preferably 3-10 carbon atoms, and more preferably 3-6 carbon atoms. Its definition includes cycloalkyl and aryl. In non-limiting examples, monocyclic carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or phenyl, etc., the bicyclic bridge ring includes etc., double ring and ring include etc., bicyclic spiro ring includes wait.

[0365] "Aryl" refers to a carbon ring having aromatic properties. Non-limiting examples include phenyl, naphthyl, and the like.

[0366] "Alkynyl" refers to a linear or branched monovalent unsaturated hydrocarbon group containing one or more carbon-carbon triple bonds. Unless otherwise specified, the alkynyl group contains 2-6 carbon atoms, preferably 2-4 carbon atoms. Non-limiting examples include ethynyl, propynyl, propargyl, etc.

[0367] "Alkenyl" refers to a linear or branched monovalent unsaturated hydrocarbon group containing one or more carbon-carbon double bonds. Unless otherwise specified, the alkynyl group contains 2-6 carbon atoms, preferably 2-4 carbon atoms. Non-limiting examples include ethenyl, propenyl, allyl, 2-butenyl, 1-butenyl, etc.

[0368] "Alkoxy" or "alkyloxy" refers to -O-alkyl, and unless otherwise specified, -OC 1-8 Alkyl, preferably -OC 1-6 Alkyl, more preferably -OC 1-4 Alkyl, more preferably -OC 1-2 Non-limiting examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexoxy, cyclopropyloxy, cyclobutyloxy, and the like.

[0369] "Haloalkoxy" refers to -O-haloalkyl, unless otherwise specified, -O-haloC 1-8 Alkyl, preferably -O-halogenated C 1-6Alkyl, more preferably -O-halogenated C 1-4 Alkyl, more preferably -O-halogenated C 1-2 Non-limiting examples include monofluoromethoxy, difluoromethoxy, trifluoromethoxy, difluoroethyloxy, and the like.

[0370] “C 1-4 "Alkyl acyl" refers to C 1-4 Alkyl-C(O)-. Non-limiting examples include formyl, acetyl, propionyl.

[0371] “C 1-4 "Alkylsulfonyl" refers to C 1-4 Alkyl-S(O)2-. Non-limiting examples include methylsulfonyl, ethylsulfonyl, and propylsulfonyl.

[0372] "Heteroaromatic ring" or "heteroaryl" refers to a heterocyclic ring having aromatic properties. Non-limiting examples include pyrazolyl, pyrimidinyl, thiazolyl, pyridinyl, furanyl, pyrone, pyridone, and the like.

[0373] "Heterocycloalkyl" refers to a non-aromatic, partially unsaturated or fully saturated heterocycle, generally having 4 to 12 ring members, preferably 4 to 10 ring members, more preferably 4 to 7 ring members, and even more preferably 5 or 6 ring members. In addition to carbon atoms, heterocycloalkyl also contains 1-3 heteroatoms selected from N, S, and O as ring members. Non-limiting examples include azetidinyl, morpholinyl, piperazinyl, piperidinyl, tetrahydropyranyl, oxetanyl, etc.

[0374] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs and instances where it does not. For example, "alkyl optionally substituted with F" means that the alkyl group may but need not be substituted with F, and the description includes instances where the alkyl group is substituted with F and instances where the alkyl group is not substituted with F.

[0375] When the specific structures or fragments listed in the present invention are further substituted, the hydrogen atoms shown in the specific structures can also be optionally substituted. For example, in the general formula (I), (II), etc., the A ring is selected from the group consisting of 1, 2 or 3 R A Replaced Include The hydrogen atoms on nitrogen in the structure can still be R A replace.

[0376] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention that retain the biological effectiveness and properties of the free acids or free bases, and the free acids are reacted with non-toxic inorganic or organic bases, or the free bases are reacted with non-toxic inorganic or organic acids.

[0377] A "pharmaceutical composition" refers to a mixture of one or more compounds described herein, or stereoisomers, solvates, pharmaceutically acceptable salts or cocrystals thereof, with other ingredients, wherein the other ingredients include physiologically / pharmaceutically acceptable carriers and / or excipients.

[0378] "Carrier" refers to a system that does not cause significant irritation to the organism and does not eliminate the biological activity and properties of the administered compound, and can change the way the drug enters the human body and its distribution in the body, control the release rate of the drug and deliver the drug to the target organ. Non-limiting examples include microcapsules and microspheres, nanoparticles, liposomes, etc.

[0379] "Excipient" refers to a substance that is not itself a therapeutic agent and is used as a diluent, adjuvant, binder, and / or vehicle that is added to a pharmaceutical composition to improve its handling or storage properties or to allow or facilitate the formation of a compound or pharmaceutical composition into a unit dosage form for administration. As known to those skilled in the art, pharmaceutical excipients can provide various functions and can be described as wetting agents, buffers, suspending agents, lubricants, emulsifiers, disintegrants, absorbents, preservatives, surfactants, colorants, flavoring agents, and sweeteners. Examples of pharmaceutical excipients include, but are not limited to: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, cellulose acetate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose, and cross-linked carboxymethylcellulose (e.g., sodium cross-linked carboxymethylcellulose); (4) tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) pH buffer solutions; (21) polyesters, polycarbonates, and / or polyanhydrides; and (22) other nontoxic compatible substances used in pharmaceutical preparations.

[0380] "Stereoisomers" refer to isomers resulting from different spatial arrangements of atoms in a molecule, including cis-trans isomers, enantiomers, and conformational isomers.

[0381] The compounds of the present invention may exist in specific geometric or stereoisomeric forms. All such compounds of the present invention, including cis and trans isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereomers, (D)-isomers, (L)-isomers, and racemic mixtures and other mixtures thereof, such as enantiomerically or diastereomerically enriched mixtures, all of which are within the scope of the present invention. Additional asymmetric carbon atoms may be present in the substituents of the compounds of the present invention. All of these isomers and their mixtures are within the scope of the present invention. In certain embodiments, preferred compounds are those isomeric compounds that exhibit superior biological activity. Purified or partially purified isomers and stereoisomers of the compounds of the present invention, or racemic mixtures or diastereomeric mixtures, are also within the scope of the present invention. Purification and separation of such substances can be achieved by standard techniques known in the art.

[0382] "Solvate" refers to a substance formed by a compound of the present invention or a salt thereof and a stoichiometric or non-stoichiometric amount of a solvent bound to the compound or salt thereof by non-covalent forces between the molecules. When the solvent is water, the solvate is a hydrate.

[0383] A "cocrystal" is a crystal formed by the active pharmaceutical ingredient (API) and cocrystal former (CCF) bound together by hydrogen bonds or other non-covalent bonds. Both the API and CCF are solid in their pure form at room temperature, and the components exist in a fixed stoichiometric ratio. A cocrystal is a multi-component crystal, encompassing both binary cocrystals formed between two neutral solids and multi-component cocrystals formed between a neutral solid and a salt or solvate. DETAILED DESCRIPTION

[0384] The present invention will be described in detail below through examples. Where specific conditions are not specified in the examples, the experimental methods are carried out according to conventional conditions. The examples are provided to better illustrate the present invention, but it should not be understood that the present invention is limited to the examples. Any non-essential improvements and adjustments made by those skilled in the art to the embodiments based on the above invention are still within the scope of protection of the present invention.

[0385] Test Method

[0386] The structures of the compounds were confirmed by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shifts (δ) are given in units of 10-6 (ppm). NMR measurements were performed using a Bruker Avance III 400 and Bruker Avance 300 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0387] MS was determined using (Agilent 6120B (ESI) and Agilent 6120B (APCI));

[0388] HPLC determination was performed using an Agilent 1260DAD high-pressure liquid chromatograph (Zorbax SB-C18 100 × 4.6 mm, 3.5 μM);

[0389] Thin layer chromatography silica gel plates used were Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications of the silica gel plates used for thin layer chromatography (TLC) were 0.15 mm to 0.20 mm, and the specifications used for thin layer chromatography separation and purification products were 0.4 mm to 0.5 mm.

[0390] Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[0391] Example 1:

[0392] Step 1: Compound 1A (1.4 g, 9.44 mmol), 3-thiopheneboronic acid (1.81 g, 14.16 mmol), and tetrakistriphenylphosphine palladium (0.55 g, 0.47 mmol) were dissolved in a toluene / ethanol (24 mL / 6 mL) mixture. Nitrogen was bubbled through the mixture for 5 minutes. 2M potassium carbonate solution (10 mL) was added and nitrogen bubbling continued for 5 minutes. The mixture was then heated to 90°C under a nitrogen atmosphere and reacted overnight. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (30 mL x 2). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, which was purified using a Biotage Isolera One (20 g silica gel column, eluent: 0-30% ethyl acetate / petroleum ether) to afford compound 1B (1.50 g, 81.21%).

[0393] LC-MS (ESI): m / z = 196.1 [M+H] + .

[0394] Step 2: Dissolve compound 1C (1.0 g, 4.11 mmol) in dichloromethane (10 mL), then add trifluoroacetic acid (4.0 mL) dropwise. Allow to react overnight at room temperature. Concentrate the reaction mixture to obtain crude compound 1D, which is used directly in the next step.

[0395] LC-MS (ESI): m / z = 144.1 [M+H] + .

[0396] Step 3: Compound 1B (0.5 g, 2.56 mmol) was dissolved in dimethyl sulfoxide (10 mL), followed by the addition of the crude compound 1D obtained in Step 2, DIPEA (0.99 g, 7.66 mmol), and cesium fluoride (0.39 g, 2.56 mmol). The temperature was raised to 100°C and the reaction was allowed to react overnight. After the reaction was complete, the temperature was lowered to room temperature, water (30 mL) was added, and the mixture was extracted with ethyl acetate (30 mL x 2). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, which was purified using a Biotage Isolera One (20 g silica gel column, eluent: 0-50% ethyl acetate / petroleum ether) to afford compound 1E (0.31 g, 40.05%).

[0397] LC-MS (ESI): m / z = 303.1 [M+H] + .

[0398] Step 4: Compound 1E (0.3 g, 0.99 mmol) was dissolved in tetrahydrofuran (3 mL), and then lithium hydroxide monohydrate (0.083 g, 1.98 mmol) and water (3 mL) were added in sequence. The mixture was stirred at room temperature overnight. After the reaction was completed, 5% potassium bisulfate solution was added dropwise to adjust the pH to 5-6. The solvent was removed by concentration, and tetrahydrofuran (5 mL) was added and stirred evenly. The mixture was concentrated to dryness again, and then stirred with methanol (10 mL). The mixture was filtered, and the filter cake was washed with methanol (5 mL × 2). The filtrates were combined and concentrated to dryness to obtain compound 1F (0.19 g, 69.96%).

[0399] LC-MS (ESI): m / z = 275.1 [M+H] + .

[0400] Step 5: Compound 1F (150 mg, 0.55 mmol), 2,4-dimethyl-6,7-dihydro-5H-pyrrolo[3,4-B]pyridine dihydrochloride (Intermediate 1) (0.15 g, 0.83 mmol), and DIPEA (0.36 g, 2.78 mmol) were added sequentially with pyridine (10 mL). The mixture was cooled to 0°C, and then T3P (1.04 g, 50% in EA, 1.63 mmol) was added dropwise. After the addition was complete, the mixture was allowed to warm naturally and reacted overnight. The mixture was concentrated, and ethyl acetate (30 mL) was added to the residue. After stirring and dilution, 10% aqueous potassium carbonate solution (30 mL) was added, and the mixture was stirred for 10 minutes. The layers were allowed to stand and the separated organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product. The crude product was purified using Biotage Isolera One (20 g silica gel column, eluent: 0-50% ethyl acetate / petroleum ether) to obtain compound 1 (85 mg, 38.20%).

[0401] LC-MS (ESI): m / z = 405.4 [M+H] + .

[0402] 1 H NMR(400MHz, CDCl3)δ8.25(d,1H),7.87(s,1H),7.58(d,1H),7.36(dd,1H),6.91(d,1H),6.56(s,1H),6.20-6.18(m,1H ),4.79-4.73(m,4H),4.30-4.25(m,2H),3.77-3.72(m,2H),3.33-3.28(m,1H),2.82(t,2H),2.52(d,3H),2.27(d,3H).

[0403] Example 2:

[0404] Step 1: 2A (0.35 g, 1.62 mmol), intermediate 1 (0.2 g, 1.35 mmol), N-methylimidazole (0.23 g, 2.76 mmol), and TEA (0.0.41 g, 4.05 mmol) were dissolved in DCM (10 mL) in sequence and stirred at room temperature for half an hour. TCFH (0.45 g, 1.61 mmol) was then added and the reaction continued at room temperature for 2 hours. The reaction solution was poured into water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford the crude product, which was purified using a Biotage Isolera One medium-pressure prep system (12 g silica gel column, eluent: 0-5% MeOH / DCM) to afford the target compound 2B (0.25 g, 53.61% yield).

[0405] LC-MS (ESI): m / z = 346.2 [M+H] + .

[0406] Step 2: 2B (0.25 g, 0.69 mmol) was dissolved in DCM (10 mL), followed by the addition of TFA (3 mL) and the reaction mixture was allowed to react at room temperature for 2 h. After completion of the reaction, the mixture was concentrated and the residue was dissolved in ethyl acetate. Saturated aqueous sodium bicarbonate was then added dropwise to adjust the pH to alkaline. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford 2C (0.13 g, 76.80% yield).

[0407] LC-MS (ESI): m / z = 246.2 [M+H] + .

[0408] Step 3: 2C (0.13 g, 0.53 mmol), 2D (0.15 g, 0.8 mmol), and N-methylimidazole (0.13 g, 1.59 mmol) were dissolved in DCM (10 mL) in sequence. After stirring at room temperature for half an hour, TCFH (0.18 g, 0.64 mmol) was added and the reaction continued at room temperature for 2 hours. After completion of the reaction, the reaction solution was poured into water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified using a medium-pressure preparator Biotage Isolera One (12 g silica gel column, eluent: 0-5% MeOH / DCM) to obtain the target compound 2 (0.08 g, yield 36.08%).

[0409] LC-MS (ESI): m / z = 419.1 [M+H] + .

[0410] 1 H NMR(400MHz,Chloroform-d)δ8.85-8.79(m,1H),7.93-7.86m,1H),7.72-7.65(m,1H),6.94-6.88(m,1H),4.78-4.68(m,4H),4.67-4.55(m, 1H),4.51-4.38(m,1H),4.14-4.06(m,1H),4.03-3.94(m,1H),3.33-3 .17(m,1H),2.86-2.67(m,2H),2.55-5.50(m,3H),2.28-2.23(m,3H).

[0411] Example 3:

[0412] Step 1: Dissolve compound 3A (10.0 g, 47.85 mmol) in toluene (100 mL), add p-toluenesulfonic acid (1.6 g, 9.57 mmol) and ethanedithiol (5.4 g, 57.42 mmol), and react at 130°C for 12 hours. After completion of the reaction, concentrate the product, and purify the residue by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 5:1) to afford compound 3B (10.0 g, 73.1%).

[0413] LCMS (ESI): m / z = 287.1 [M+H] + .

[0414] Step 2: Dissolve dibromohydantoin (32.0 g, 111.88 mmol) in dichloromethane (300 mL). Add pyridine hydrofluoride (22.2 g, 223.76 mmol) at -78°C. Add a dichloromethane solution (80 mL) of compound 3B (8.0 g, 27.97 mmol) dropwise. After the addition is complete, warm the mixture to room temperature and react for 2 hours. Add water (300 mL) and extract. The aqueous phase is extracted again with dichloromethane (300 mL). The combined organic phases are washed with saturated brine (300 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 100:0) to obtain compound 3C (4.8 g, 55.4%).

[0415] 1 H NMR (400MHz, CDCl3) δ7.83-7.69(m,1H),7.67-7.56(m,1H),7.20-7.11(m,1H),4.66-4.46(m,1H),3.60-3.41(m,1H),3.30-3.11(m,1H).

[0416] Step 3: Dissolve compound 3C (4.7 g, 15.16 mmol) in dichloromethane (50 mL) and add 1,8-diazabicyclo[5.4.0]undec-7-ene (4.7 g, 15.16 mmol). Allow to react at room temperature for 12 hours. After completion of the reaction, concentrate the product, and purify the residue by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 100:0) to yield compound 3D (2.7 g, 77.4%).

[0417] 1 H NMR (400MHz, CDCl3) δ7.61-7.55(m,1H),7.54-7.40(m,1H),7.03-6.95(m,1H),6.77-6.72(m,1H),6.21-6.09(m,1H).

[0418] Step 4: Compound 3D (1.0 g, 4.35 mmol) and 2-nitrobenzenesulfonyl chloride (1.2 g, 5.22 mmol) were dissolved in acetonitrile (20 mL). Potassium phosphate (184 mg, 0.87 mmol) and hydrazine hydrate (873 mg, 1.74 mmol) were added at 0°C and allowed to react at room temperature for 12 hours. After completion of the reaction, the product was concentrated, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 100:0) to afford compound 3E (0.9 g, 89.9%).

[0419] 1H NMR (400MHz, CDCl3) δ7.72-7.63(m,1H),7.55-7.50(m,1H),7.19-7.12(m,1H),3.02-2.92(m,2H),2.67-2.49(m,2H).

[0420] Step 5: Compound 3E (500 mg, 2.26 mmol) was dissolved in toluene (15 mL), and ethyl 2-(azetidin-3-yl)acetate trifluoroacetate (580 mg, 2.26 mmol), cesium carbonate (2.2 g, 6.78 mmol), tris(dibenzylideneacetone)dipalladium (210 mg, 0.23 mmol), and 4,5-bis(diphenylphosphino-9,9-dimethylxanthene) (260 mg, 0.45 mmol) were added sequentially. The mixture was then heated to 100°C under a nitrogen atmosphere for 12 hours. After completion of the reaction, the mixture was filtered, and the filtrate was concentrated to obtain a residue which was separated by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 5:1) to afford compound 3F (0.3 g, 45.0%).

[0421] LCMS (ESI): m / z = 296.1 [M+H] + .

[0422] Step 6: Dissolve compound 3F (300 mg, 1.02 mmol) in methanol (3 mL), add lithium hydroxide (300 mg) in water (3 mL), and react at room temperature for 1 hour. Add hydrochloric acid (6N) dropwise to adjust the pH to 5-6, extract with dichloromethane (30 mL x 2), and dry the combined organic phases over anhydrous sodium sulfate, filter, and concentrate to yield compound 3G (150 mg, 55.1%).

[0423] LCMS (ESI): m / z = 268.1 [M+H] + .

[0424] Step 7: Compound 3G (150 mg, 0.56 mmol), benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (213 mg, 0.56 mmol), 2,4-dimethyl-6,7-dihydro-5H-pyrrolo[3,4-B]pyridine dihydrochloride (123 mg, 0.56 mmol), and N,N-diisopropylethylamine (361 mg, 2.8 mmol) were dissolved in DMF (5 mL) and reacted at room temperature for 1 hour. Water (10 mL) was added, and the mixture was extracted with ethyl acetate (10 mL of ester 3). The combined organic phases were washed with water (10 mL) and saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 100:6) to obtain the title compound 3 (55 mg, 24.8%).

[0425] LC-MS (ESI): m / z = 398.2 [M+H] + .

[0426] 1 H NMR (400MHz, CDCl3) δ7.15-7.04(m,1H),6.93-6.87(m,1H),6.61-6.48(m,2H),4.83-4.68(m,4H),4.25-4.09(m,2H) ,3.65-3.56(m,2H),3.30-3.13(m,1H),2.99-2.87(m,2H),2.87-2.75(m,2H),2.61-2.44(m,5H),2.33-2.19(m,3H).

[0427] Example 4:

[0428] Step 1: Compound 4B (1.18 g, 8.24 mmol), potassium carbonate (2.85 g, 20.57 mmol), and 2-trifluoromethyl-4-chloropyridine (1.50 g, 8.24 mmol) were dissolved in dimethyl sulfoxide (30 mL) in sequence, stirred evenly, and then heated to 100°C for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, and ethyl acetate (200 mL) and saturated brine (200 mL) were added. Extraction and separation were performed. The organic phase was washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was isolated and purified by silica gel column chromatography (ethyl acetate: petroleum ether (v:v) = 0-100%) to obtain compound 4C (0.8 g, 33.68%).

[0429] LC-MS (ESI): m / z = 289.2 [M+H] + .

[0430] Step 2: Compound 4C (0.8 g, 2.78 mmol) and lithium hydroxide (0.1 g, 4.18 mmol) were dissolved in a mixture of methanol (20 mL) and water (0.5 mL) and heated to 50°C for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to yield crude compound 4D (0.8 g).

[0431] LC-MS (ESI): m / z = 261.1 [M+H] + .

[0432] Step 3: Dissolve 2,4-dichloro-6,7-dihydro-5H-pyrrolo[3,4-D]pyrimidine hydrochloride (5.00 g, 22.08 mmol) and triethylamine (3.35 g, 33.12 mmol) in dichloromethane (100 mL). Add di-tert-butyl dicarbonate (4.82 g, 22.08 mmol) and allow to react overnight at room temperature. After completion of the reaction, the organic phase was washed three times with water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether (v:v) = 0-100%) to obtain compound 4G (6 g, 93.65%).

[0433] LC-MS (ESI): m / z = 290.1 ​​[M+H] + .

[0434] Step 4: Compound 4G (3.00 g, 10.33 mmol) was dissolved in tetrahydrofuran (50 mL). Under a nitrogen atmosphere, 2 mol / L methylzinc chloride in tetrahydrofuran (15 mL) and chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.81 g, 1.03 mmol) were added sequentially. The mixture was then heated to 70°C and reacted overnight. After completion, the reaction was cooled to room temperature and quenched by the addition of water (1 mL). The mixture was filtered and the filtrate was concentrated. The residue was isolated and purified by silica gel column chromatography (ethyl acetate:petroleum ether (v:v) = 0-100%) to obtain compound 4F (0.8 g, 31.06%).

[0435] LC-MS (ESI): m / z = 250.30 [M+H] + .

[0436] Step 5: Dissolve compound 4F (0.80 g, 3.21 mmol) in 4 mol / L 1,4-dioxane hydrochloride (10 mL) and react at room temperature for 1 hour. After completion of the reaction, concentrate to obtain crude compound 4H (1.00 g).

[0437] LC-MS (ESI): m / z = 150.20 [M+H] + .

[0438] Step 6: Compound 4H (0.50 g, 3.35 mmol), compound 4D (0.87 g, 3.35 mmol), N,N-diisopropylethylamine (2.16 g, 16.75 mmol), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.53 g, 4.02 mmol) were dissolved in N,N-dimethylformamide (15 mL) and reacted at room temperature for 5 hours. After completion of the reaction, the mixture was filtered and the filtrate was purified on a reverse-phase preparative column (C18 spherical 20-35 nm 100A 80 g) (acetonitrile:water (v:v) = 10%-80%) to obtain compound 4 (651 mg, 49.65%).

[0439] LC-MS (ESI): m / z = 392.20 [M+H] + .

[0440] 1 H NMR(400MHz,DMSO-d6)δ8.21(d,1H),6.71(d,1H),6.54-6.52(m,1H),4.90-4.77(m,2H),4.59(d,2H), 4.20-4.15(m,2H),3.72-3.68(m,2H),3.19-3.06(m,1H),2.87-2.81(m,2H),2.57(d,3H),2.39(d,3H).

[0441] Example 5:

[0442] Step 1: Dissolve 2C (1.2 g, 1.41 mmol), 2-bromo-4-fluoropyridine (1.03 g, 5.88 mmol), cesium fluoride (894 mg, 5.88 mmol), and triethylamine (1.98 g, 19.61 mmol) in dimethyl sulfoxide (25 mL) in this order and react at 100°C overnight. After the reaction is complete, cool to room temperature, add 50 mL of water, and extract with ethyl acetate (25 mL x 3). The combined organic layers are washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate is concentrated. The residue is purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 30:1) to afford 5A (980 mg, 50%).

[0443] LC-MS (ESI): m / z = 401.6 [M+H] + .

[0444] Step 2: 5A (330 mg, 0.82 mmol), (1-(difluoromethyl)-1H-pyrazol-4-yl)boronic acid pinacol (241 mg, 0.99 mmol), Pd(dppf)Cl2 (60 mg, 0.082 mmol), and potassium carbonate (341 mg, 2.47 mmol) were dissolved in a mixture of 1,4-dioxane (10 mL) and water (1 mL) under a nitrogen atmosphere at 90°C overnight. After the reaction was complete, the mixture was cooled to room temperature, and 30 mL of water was added. The mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 20:1) to afford compound 5 (80 mg, 22%).

[0445] 1 H NMR (400MHz, CD3Cl) δ8.31(s,1H),8.17-8.15(m,1H),8.00(s,1H),7.29-6.97(m,1H),6.85-6.83(m,1H),6.38-6.37(m,1H),6.14-6.11(m, 1H),4.72-4.66(m,4H),4.25-4.19(m,2H),3.73-3.66(m,2H),3.28-3 .21(m,1H),2.78-2.73(m,2H),2.47-2.45(m,3H),2.20-2.18(m,3H).

[0446] LC-MS (ESI): m / z = 439.2 [M+H] + .

[0447] Example 6:

[0448] 5A (150 mg, 0.37 mmol), (1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)boronic acid (115 mg, 0.56 mmol), Pd(dppf)Cl2 (27 mg, 0.037 mmol), and potassium carbonate (153 mg, 1.11 mmol) were dissolved in a mixture of 1,4-dioxane (6 mL) and water (0.5 mL) and reacted at 100°C overnight under a nitrogen atmosphere. After the reaction was complete, the mixture was cooled to room temperature, and 25 mL of water was added. The mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was separated and purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 25:1) to give compound 6 (30 mg, 17%).

[0449] 1 H NMR (400MHz, CDCl3) δ8.30-8.27(m,1H),6.92-6.90(m,1H),6.71(s,1H),6.46(s,1H),6.28-6.25(m,1H),4.79-4.73(m,4H),4 .29-4.24(m,2H),4.19(s,3H),3.79-3.72(m,2H),3.38-3.27(m,1H),2.85-2.80(m,2H),2.54-2.52(m,3H),2.28-2.26(m,3H).

[0450] LC-MS (ESI): m / z = 471.6 [M+H] + .

[0451] Example 7:

[0452] 5A (150 mg, 0.37 mmol), (1-methyl-1H-pyrazol-4-yl)boronic acid pinacol (117 mg, 0.56 mmol), Pd(dppf)Cl2 (27 mg, 0.037 mmol), and potassium carbonate (153 mg, 1.11 mmol) were dissolved in a mixture of 1,4-dioxane (6 mL) and water (0.5 mL) under a nitrogen atmosphere at 100°C overnight. After the reaction was complete, the mixture was cooled to room temperature, 25 mL of water was added, and the mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was separated and purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 20:1) to obtain compound 7 (60 mg, 40%).

[0453] 1 H NMR (400MHz, CDCl3) δ8.18-8.15(m,1H),7.97-7.95(m,1H),7.87(s,1H),6.92-6.89(m,1H),6.41(s,1H),6.14-6.12(m,1H),4.79-4.73 (m,4H),4.28-4.24(m,2H),3.94(s,3H),3.78-3.69(m,2H),3.35-3.24(m,1H),2.84-2.79(m,2H),2.54-2.52(m,3H),2.27-2.25(m,3H).

[0454] LC-MS (ESI): m / z = 403.3 [M+H] + .

[0455] Example 8:

[0456] 5A (150 mg, 0.37 mmol), (2-(trifluoromethyl)thiazol-5-yl)boronic acid pinacol (156 mg, 0.56 mmol), Pd(dppf)Cl2 (27 mg, 0.037 mmol), and potassium carbonate (153 mg, 1.11 mmol) were dissolved in a mixture of 1,4-dioxane (6 mL) and water (0.5 mL) under a nitrogen atmosphere at 100°C overnight. After the reaction was complete, the mixture was cooled to room temperature, 25 mL of water was added, and the mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was separated and purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 25:1) to obtain compound 8 (22 mg, 12%).

[0457] 1 H NMR (400MHz, CDCl3) δ8.24 (s, 1H), 8.22-8.21 (m, 1H), 6.93-6.90 (m, 1H), 6.61 (d, J = 2.1Hz, 1H), 6.26-6.23 (m, 1H), 4.79-4.7 3(m,4H),4.33-4.28(m,2H),3.82-3.75(m,2H),3.37-3.29(m,1H),2.85-2.80(m,2H),2.54-2.52(m,3H),2.28-2.26(m,3H).

[0458] LC-MS (ESI): m / z = 474.0 [M+H] + .

[0459] Example 9:

[0460] Compound 5A (150 mg, 0.47 mmol) was dissolved in DMF (5 mL), followed by the addition of 3-trifluoromethylpyrazole (0.096 g, 0.70 mmol), cuprous iodide (0.031 g, 0.094 mmol), and cesium carbonate (0.18 g, 0.94 mmol). The mixture was replaced with nitrogen and heated to 120°C for 6 hours. After the reaction was complete, the mixture was cooled to room temperature and added to tap water (20 mL). The mixture was extracted with ethyl acetate (10 mL x 3), washed with saturated brine, dried, and concentrated to afford the crude product, which was purified using a Biotage Isolera One (20 g silica gel column, eluent: 0-60% ethyl acetate / petroleum ether) to afford compound 9 (28 mg, 13.1%).

[0461] LC-MS (ESI): m / z = 457.4 [M+H] + .

[0462] 1 H NMR(400MHz, CDCl3)δ8.58(d,1H),8.03(d,1H),6.93(m,2H),6.66(s,1H),6.62(d,1H),4.79-4.74(m, 4H),4.33-4.29(m,2H),3.82-3.77(m,2H),3.35-3.27(m,1H),2.82(t,2H),2.54(s,3H),2.27(d,3H).

[0463] Example 10:

[0464] Compound 5A (150 mg, 0.37 mmol), 4-(trifluoromethyl)-1H-pyrazole (60 mg, 0.44 mmol), potassium carbonate (102 mg, 0.74 mmol), cuprous iodide (7 mg, 0.037 mmol) and L-proline (8 mg, 0.074 mmol) were dissolved in DMSO (15 mL) and reacted at 100°C overnight under nitrogen. The reaction was completed by TLC and quenched with water (20 mL). The mixture was extracted three times with EA (20 mL). The combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give the crude product, which was separated and purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 10:1) to obtain the target compound 10 (8 mg, yield 4.74%).

[0465] LC-MS (ESI): m / z = 457.5 [M+H] + .

[0466] 1 H NMR(400MHz,DMSO-d6)δ9.04(s,1H),8.20(s,1H),8.07-8.00(m,1H),7.03-6.97(m,1H),6.82(s,1H),6.44-6.35(m,1H),4.85-4.7 6(m,2H),4.63-4.52(m,2H),4.23-4.16(m,2H),3.78-3.70(m,2H),3.15(s,1H),2.91-2.82(m,2H),2.42(s,3H),2.26-2.19(m,3H).

[0467] Example 11:

[0468] Compound 1 (0.5 g, 1.24 mmol) was dissolved in dry acetonitrile (20 mL), and 1-chloromethyl-4-fluoro-1,4-diazobicyclo[2.2.2]octane bis(tetrafluoroborate) (1.32 g, 3.72 mmol) was added all at once. The temperature was raised to 70°C and the reaction was allowed to react overnight. After the reaction, the reaction solution was concentrated to dryness, ethyl acetate (30 mL) and tap water (50 mL) were added, and the mixture was stirred and separated. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was purified using a Biotage Isolera One (20 g silica gel column, eluent: 0-70% ethyl acetate / petroleum ether) to obtain compound 11 (55 mg, 10.5%).

[0469] LC-MS (ESI): m / z = 423.4 [M+H] + .

[0470] 1 H NMR(400MHz, CDCl3)δ8.07(d,1H),7.98(s,1H),7.76(dd,1H),7.36(t,1H),6.91(d,1H),6.23(dd,1H),4.7 9-4.73(m,4H),4.43(t,2H),3.92(t,2H),3.30-3.27(m,1H),2.85-2.81(m,2H),2.52(d,3H),2.27(d,3H).

[0471] Example 12:

[0472] Step 1: 12A (30 g, 142.14 mmol) and 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate) (selective fluorine reagent) (58.41 g, 164.88 mmol) were added to methanol (300 mL) and reacted at 60°C for 5 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The filter cake was washed with methanol, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (EA / PE = 1 / 5) to afford 12B (11 g, 33.79%).

[0473] LC-MS(ESI):m / z=229.1,231.1[M+H] + .

[0474] Step 2: Dissolve 12B (6 g, 26.20 mmol) in anhydrous ethanol (60 mL). Add sodium borohydride (1.19 g, 31.44 mmol) portionwise at 0°C. Slowly warm the temperature to room temperature and react for 2 h. Pour the reaction solution into water (300 mL) and extract with ethyl acetate (50 mL x 3). The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate is concentrated under reduced pressure to yield 12C (5.7 g, 94.16%).

[0475] LC-MS(ESI):m / z=212.9,214.9[M+H] + .

[0476] 1 H NMR (400MHz, CDCl3) δ7.45-7.38(m,2H),7.35-7.33(m,1H),5.37-5.20(m,1H),5.09-5.03(m,1H),3.27-3.02(m,2H),2.26(s,1H).

[0477] Step 3: Dissolve 12C (5.5 g, 23.80 mmol) in dichloromethane (70 mL). Add diethylaminosulfur trifluoride (9.59 g, 59.5 mmol) dropwise at -20°C. After the addition is complete, warm the mixture to room temperature and react for 3 h. After completion, pour the reaction solution into ice water, extract, and separate the liquids. The organic phase is concentrated under reduced pressure and purified by silica gel column chromatography (EA / PE = 0-8%) to give 12D-1 (Rf = 0.8 (EA / PE = 1 / 10), 2.1 g) and 12D-2 (Rf = 0.6 (EA / PE = 1 / 10), 2.0 g), respectively.

[0478] Compound 12D-1: 1 H NMR (400MHz, CDCl3) δ7.46-7.42(m,2H),7.35-7.33(m,1H),6.00-5.83(m,1H),5.50-5.30(m,1H),3.50-3.39(m,1H),3.18-3.00(m,1H).

[0479] Compound 12D-2: 1 H NMR (400MHz, CDCl3) δ7.46-7.44(m,2H),7.37-7.34(m,1H),5.80-5.63(m,1H),5.35-5.16(m,1H),3.35-3.13(m,2H).

[0480] Step 4: 12D-1 (0.9 g, 3.86 mmol), 1D (1.49 g, 5.79 mmol), Ruphos-Pd-G3 (0.32 g, 0.38 mmol), and cesium carbonate (5 g, 15.44 mmol) were added to dioxane (20 mL) in sequence. After N2 substitution, the reaction was incubated at 100°C for 16 h. After completion of the reaction, the mixture was cooled to room temperature, filtered through Celite pad, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (EA / PE = 1 / 7) to afford 12E-1 (0.9 g, 78.95%).

[0481] LC-MS (ESI): m / z = 296.2 [M+H] + .

[0482] By referring to the above operation, 12D-2 (0.9 g, 3.86 mmol) was used as the starting material to obtain 12E-2 (0.9 g, 78.9%).

[0483] LC-MS (ESI): m / z = 296.2 [M+H] + .

[0484] Step 5: Add 12E-1 (0.7 g, 2.37 mmol) and lithium hydroxide monohydrate (0.50 g, 11.92 mmol) to a mixture of methanol (5 mL), tetrahydrofuran (5 mL), and water (5 mL) and react at room temperature for 3 h. The reaction mixture was then concentrated under reduced pressure to dryness to yield crude 12F-1.

[0485] LC-MS (ESI): m / z = 268.2 [M+H] + .

[0486] Referring to the above operation, 12E-2 (0.7 g, 2.37 mmol) was used as the starting material to obtain the crude product 12F-2.

[0487] LC-MS (ESI): m / z = 268.2 [M+H] + .

[0488] Step 6: Intermediate 1 (0.52 g, 2.37 mmol), 12F-1 (2.37 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.17 g, 3.08 mmol), and N,N-diisopropylethylamine (1.53 g, 11.85 mmol) were added to N,N-dimethylformamide (15 mL) in sequence and reacted at room temperature for 5 h. Water (60 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate (20 mL × 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and purified on a C18 reverse-phase column with mobile phases A and B: acetonitrile and water (containing 0.1% ammonia) (A / B = 53% / 47%) to afford compound 12, isomer 1 (800 mg, 84.9%).

[0489] By referring to the above operation, 12F-2 (2.37 mmol) was used as the starting material to obtain compound 12 isomer 2 (800 mg, 84.9%).

[0490] Compound 12 Isomer 1: 1 H NMR(400MHz, CDCl3)δ7.08(d,1H),6.91-6.89(m,1H),6.53(s,1H),6.49-6 .43(m,1H),6.03-5.85(m,1H),5.50-5.25(m,1H),4.78-4.73(m,4H),4.18 -4.06(m,2H),3.62-3.58(m,2H),3.40-3.30(m,1H),3.28-3.16(m,1H),3. 02-2.92(m,1H),2.84-2.74(m,2H),2.55-2.50(m,3H),2.28-2.23(m,3H).

[0491] LC-MS (ESI): m / z = 398.3 [M+H] + .

[0492] Compound 12 Isomer 2: 1H NMR(400MHz, CDCl3)δ7.08(d,1H),6.91-6.89(m,1H),6.53(s,1H),6.50-6.46(m,1H),5.78-5.61(m,1H),5.32-5.11(m,1H),4.80 -4.70(m,4H),4.16-4.10(m,2H),3.62-3.56(m,2H),3.28-3.06(m,3H),2.83-2.77(m,2H),2.55-2.50(m,3H),2.29-2.23(m,3H).

[0493] LC-MS (ESI): m / z = 398.3 [M+H] + .

[0494] Step 7: Compound 12 isomer 1 (500 mg, 1.26 mmol) was chirally prepared to obtain compound 12 isomer 1-1 (205 mg, 41%) and compound 12 isomer 1-2 (189 mg, 38%).

[0495] Chiral HPLC analysis method: 1. Instrument: SHIMADZU LC-30ADsf; 2. Column: Chiral Whelk column; 3. Mobile phase: A for CO2; B for 0.05% DEA in ethanol; 4. Gradient: B to 40%; 5. Flow rate: 3 mL / min. Compound 12 isomer 1-1 (retention time: 2.293 min) and compound 12 isomer 1-2 (retention time: 2.138 min).

[0496] Chiral preparative separation conditions: 1. Instrument: Waters 150Prep-SFC; 2. Column: Chiral AD column; 3. Mobile phase: A for CO2; B for 0.1% NH3·H2O in ethanol and acetonitrile; 4. Gradient: B for 55%; 5. Flow rate: 100 mL / min;

[0497] Compound 12 isomer 2 (550 mg, 1.38 mmol) was chirally prepared to give compound 12 isomer 2-1 (238 mg, 43%) and compound 12 isomer 2-2 (227 mg, 41%).

[0498] Chiral HPLC analysis method: 1. Instrument: SHIMADZU LC-30ADsf; 2. Column: Chiral AD column; 3. Mobile phase: A for CO2; B for 0.05% DEA in methanol and acetonitrile; 4. Gradient: B to 40%; 5. Flow rate: 3 mL / min. Compound 12 isomer 2-1 (retention time: 2.356 min) and compound 12 isomer 2-2 (retention time: 2.564 min).

[0499] Chiral preparative separation conditions: 1. Instrument: Waters 150Prep-SFC; 2. Column: Chiral AD column; 3. Mobile phase: A for CO2; B for 0.1% NH3·H2O in methanol and acetonitrile; 4. Gradient: B for 60%; 5. Flow rate: 100 mL / min;

[0500] Compound 12 Isomer 1-1: 1 H NMR(400MHz,DMSO-d6)δ7.12(d,1H),6.99(s,1H),6.52-6.47(m,2H),6.11-5.93(m,1H),5.56-5.32(m,1H),4.79(d,2H),4.56(d ,2H),4.01-3.97(m,2H),3.52-3.48(m,2H),3.38-3.31(m,1H),3.11-2.99(m,1H),2.94-2.80(m,3H),2.42(s,3H),2.22(d,3H).

[0501] LC-MS (ESI): m / z = 398.3 [M+H] + .

[0502] Compound 12 Isomer 1-2: 1 H NMR(400MHz,DMSO-d6)δ7.12(d,1H),6.99(s,1H),6.52-6.47(m,2H),6.11-5.93(m,1H),5.54-5.35(m,1H),4.79(d,2H),4.56(d ,2H),4.01-3.97(m,2H),3.52-3.48(m,2H),3.39-3.31(m,1H),3.10-2.98(m,1H),2.95-2.80(m,3H),2.42(s,3H),2.22(d,3H).

[0503] LC-MS (ESI): m / z = 398.3 [M+H] + .

[0504] Compound 12 Isomer 2-1: 1 H NMR(400MHz,DMSO-d6)δ7.13(d,1H),6.99(s,1H),6.54(s,1H),6.49-6.45(m,1H),5.89-5.73(m,1H),5.42-5.22(m,1H),4.7 9(d,2H),4.56(d,2H),4.01-3.97(m,2H),3.52-3.48(m,2H),3.16-2.93(m,3H),2.83-2.80(m,2H),2.42(s,3H),2.22(d,3H).

[0505] LC-MS (ESI): m / z = 398.3 [M+H] + .

[0506] Compound 12 Isomer 2-2: 1 H NMR(400MHz,DMSO-d6)δ7.13(d,1H),6.99(s,1H),6.54(s,1H),6.49-6.45(m,1H),5.89-5.72(m,1H),5.42-5.22(m,1H),4.7 9(d,2H),4.56(d,2H),4.01-3.97(m,2H),3.52-3.48(m,2H),3.15-2.95(m,3H),2.83-2.79(m,2H),2.42(s,3H),2.22(d,3H).

[0507] LC-MS (ESI): m / z = 398.3 [M+H] + .

[0508] Example 13:

[0509] Step 1: Compound 13A (2.0 g, 8.89 mmol) was dissolved in dichloromethane (20 mL) at room temperature and cooled to 0°C. 1,2-Ethanedithiol (1.67 g, 17.78 mmol) and boron trifluoride etherate (0.63 g, 4.44 mmol) were slowly added and allowed to react at room temperature for 15 h. After completion of the reaction, the pH was adjusted to 7 with 1N sodium hydroxide solution and the mixture was extracted with dichloromethane (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 2:1) to afford compound 13B (1.5 g, 56%).

[0510] 1 H NMR(400MHz, CDCl3)δ8.04(d,1H),7.21(dd,1H),6.85(d,1H),3.62-3.55(m,2H ),3.48-3.41(m,2H),2.75-2.71(m,2H),2.37-2.33(m,2H),2.01-1.96(m,2H).

[0511] Step 2: N-iodosuccinimide (2.24 g, 9.96 mmol) was dissolved in dichloromethane (15 mL) at room temperature and cooled to -70°C. A solution of hydrofluoric acid-pyridine (1.97 g, 19.92 mmol) and compound 13B (1.5 g, 4.98 mmol) in dichloromethane (15 mL) was slowly added dropwise. After the addition was complete, the reaction was continued at -70°C for 30 min. After completion of the reaction, the pH was adjusted to 7 with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane (10 mL x 2). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 9:1) to obtain compound 13C (0.8 g, 65%).

[0512] LC-MS (ESI): m / z = 247.2 [M+H] + .

[0513] Step 3: Compound 13C (0.8 g, 3.24 mmol), 1D (0.55 g, 3.89 mmol), Ruphos-Pd-G3 (0.27 g, 0.32 mmol), and cesium carbonate (3.16 g, 9.72 mmol) were dissolved in 1,4-dioxane (10 mL) at room temperature. The mixture was heated to 100°C under a nitrogen atmosphere and reacted for 16 h. After the reaction, the mixture was cooled to room temperature, filtered after padding with celite, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 7:1) to yield compound 13D (0.7 g, 70%).

[0514] LC-MS (ESI): m / z = 310.1 [M+H] + .

[0515] Step 4: Dissolve compound 13D (0.7 g, 2.26 mmol) and lithium hydroxide monohydrate (0.28 g, 6.78 mmol) in a mixture of methanol (3 mL), tetrahydrofuran (3 mL), and water (3 mL) at room temperature for 2 h. After the reaction, the reaction mixture was concentrated under reduced pressure to afford crude compound 13E (0.72 g), which was carried on to the next step without purification.

[0516] LC-MS (ESI): m / z = 282.2 [M+H] + .

[0517] Step 5: Compound 13E (0.3 g, 1.07 mmol), intermediate 1 (0.23 g, 1.07 mmol), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (0.53 g, 1.39 mmol) were dissolved in N,N-dimethylformamide (10 mL) at room temperature, and then N,N-diisopropylethylamine (0.41 g, 3.21 mmol) was added and the mixture was reacted at room temperature for 5 h. After the reaction, water (20 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate (20 mL×2). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by C18 reverse phase column. The mobile phases A and B were composed as follows: mobile phase A: acetonitrile; mobile phase B: water (containing 0.1% ammonia water), (A / B=60% / 40%) to separate and obtain compound 13 (0.2 g. 46%).

[0518] 1H NMR(400MHz, CDCl3)δ6.99(d,1H),6.91-6.87(m,1H),6.72(d,1H),6.48(dd,1H),4.79-4.75(m,2H),4.74-4.71(m,2H),4.13(t,2H),3.62-3.5 7(m,2H),3.27-3.16(m,1H),2.83-2.75(m,2H),2.74-2.69(m,2H),2.54 -2.50(m,3H),2.27-2.25(m,3H),2.24-2.16(m,2H),1.98-1.91(m,2H).

[0519] LC-MS (ESI): m / z = 412.2 [M+H] + .

[0520] Example 14:

[0521] 5A (80 mg, 0.2 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrazole (72 mg, 0.26 mmol), Pd(dppf)2Cl2 (16 mg, 0.02 mmol), and potassium carbonate (83 mg, 0.60 mmol) were added sequentially to a mixture of 1,4-dioxane (5 mL) and water (1 mL). The mixture was heated to 90°C under a nitrogen atmosphere for 12 h. After completion of the reaction, the mixture was cooled to room temperature and filtered. The filtrate was concentrated, and the residue was isolated by silica gel column chromatography (dichloromethane:methanol = 10:1) to afford compound 14 (35 mg, 37%).

[0522] LC-MS (ESI): m / z = 471.5 [M+H] + .

[0523] 1 H NMR(400MHz,DMSO-d6)δ8.14(d,1H),7.26(s,1H),7.00(s,1H),6.87(d,1H),6.33-6.35(m,1H),4.80(d,2H),4.57(d ,2H),4.15(t,2H),4.02(s,3H),3.66-3.70(m,2H),3.10-3.15(m,1H),2.85-2.86(m,2H),2.42(s,3H),2.23(d,3H).

[0524] Example 15:

[0525] Compound 5A (100 mg, 0.25 mmol) was dissolved in 1,4-dioxane (8 mL), and 15A (88 mg, 0.32 mmol), potassium carbonate (86 mg, 0.62 mmol), and water (2 mL) were added sequentially. Under a nitrogen atmosphere, 1,1-bis(diphenylphosphino)diphenylferric palladium chloride (27 mg, 0.04 mmol) was added, and the mixture was heated to 85°C and stirred for 16 h. After the reaction, the mixture was allowed to cool to room temperature, diluted with water (30 mL), and extracted with ethyl acetate (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, which was purified by column chromatography (dichloromethane:methanol = 95:5) to afford the target compound 15 (45 mg, 38.55%).

[0526] 1 H NMR (400MHz, CDCl3) δ9.39(s,2H),8.36-8.34(m,1H),6.92-6.91(m,1H),6.66(s,1H),6.64-6.32(m,1H),4.79-4. 74(m,4H),4.33-4.29(m,2H),3.83-3.78(m,2H),3.36-3.32(m,1H),2.86-2.82(m,2H),2.54(s,3H),2.74(s,3H).

[0527] LC-MS (ESI): m / z = 469.1 [M+H] + .

[0528] Example 16:

[0529] 5A (80 mg, 0.2 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyridine (71 mg, 0.26 mmol), Pd(dppf)2Cl2 (16 mg, 0.02 mmol), and potassium carbonate (83 mg, 0.60 mmol) were added sequentially to a mixture of 1,4-dioxane (5 mL) and water (1 mL). The mixture was heated to 90°C under a nitrogen atmosphere for 12 h. After completion of the reaction, the mixture was cooled to room temperature, filtered, and concentrated. The residue was isolated and purified by column chromatography (dichloromethane:methanol = 10:1) to afford compound 16 (40 mg, 43%).

[0530] LC-MS (ESI): m / z = 468.5 [M+H] + .

[0531] 1H NMR(400MHz,DMSO-d6)δ8.84(d,1H),8.50(s,1H),8.37(d,1H),8.28(d,1H),7.20(d,1H),7.00(s,1H),6.44-6.46(m,1H ),4.80(d,2H),4.58(d,2H),4.21(t,2H),3.74(t,2H),3.10-3.15(m,1H),2.86-2.88(m,2H),2.42(s,3H),2.23(d,3H).

[0532] Example 17:

[0533] Step 1: Compound 17A (0.5 g, 2.33 mmol), 1D (0.40 g, 2.79 mmol), Ruphos-Pd-G3 (0.19 g, 0.23 mmol), and cesium carbonate (2.27 g, 6.99 mmol) were dissolved in 1,4-dioxane (10 mL) at room temperature. The mixture was heated to 100°C under a nitrogen atmosphere and reacted for 16 h. After the reaction, the mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure to obtain a residue which was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 3:1) to afford compound 17B (0.3 g, 46%).

[0534] LC-MS (ESI): m / z = 278.2 [M+H] + .

[0535] Step 2: Dissolve compound 17B (0.3 g, 1.08 mmol) and lithium hydroxide monohydrate (0.14 g, 3.24 mmol) in a mixture of methanol (2 mL), tetrahydrofuran (2 mL), and water (2 mL) at room temperature for 2 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to afford crude compound 17C (0.35 g), which was used directly in the next step without purification.

[0536] LC-MS (ESI): m / z = 250.1 [M+H] + .

[0537] Step 3: Compound 17C (0.27 g, 1.08 mmol), intermediate 1 (0.24 g, 1.08 mmol), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (0.53 g, 1.40 mmol) were dissolved in DMF (10 mL) at room temperature, and then N,N-diisopropylethylamine (0.41 g, 3.24 mmol) was added and reacted at room temperature for 5 h. After the reaction, water (20 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate (20×2 mL). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by C18 reverse phase column (mobile phase A, B composition: mobile phase A: acetonitrile; mobile phase B: water (containing 0.1% ammonia water), (A / B=65% / 35%)) to separate and obtain compound 17 (0.15 g. 36%).

[0538] LC-MS (ESI): m / z = 380.1 [M+H] + .

[0539] 1 H NMR (400MHz, CDCl3) δ6.92-6.87(m,1H),6.76-6.70(m,1H),6.03-5.96(m,2H),4.79-4.70(m,4H),4.25-4.20(m,2H),4.19 -4.16(m,2H),4.04(t,2H),3.55-3.49(m,2H),3.23-3.11(m,1H),2.83-2.75(m,2H),2.54-2.50(m,3H),2.27-2.23(m,3H).

[0540] Example 18:

[0541] Step 1: Compound 18A (10.0 g, 56.47 mmol) was dissolved in CCl₄ (100 mL). NBS (30 g, 169.41 mmol) and AIBN (0.46 g, 2.82 mmol) were added and refluxed for 16 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA = 10:1 to PE:EA = 3:1) to afford compound 18B (8.5 g, 44.96% yield).

[0542] LC-MS (ESI): m / z = 336.8 [M+H] + .

[0543] Step 2: Triphenylmethylamine (6.58 g, 25.39 mmol) was dissolved in DMF (125 mL), and DIPEA (13.6 mL, 76.17 mmol) was added. The temperature was then raised to 60°C, and a solution of compound 18B (8.5 g, 25.39 mmol) in DMF (125 mL) was added dropwise. After the addition was complete, the reaction was continued at 60°C for 2 hours. After completion of the reaction, as monitored by TLC, the mixture was cooled to room temperature, diluted with water (500 mL), and extracted with ethyl acetate (300 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (PE:EA = 50:1) to afford compound 18C (1.0 g, 9.11% yield).

[0544] 1 H NMR (400MHz, CDCl3) δ7.55-7.53(m,6H),7.32-7.28(m,6H),7.20-7.17(m,3H),4.28-4.19(m,4H).

[0545] Step 3: Compound 18C (0.13 g, 0.30 mmol), trimethylboroxine (113 mg, 0.9 mmol), potassium phosphate (192 mg, 0.9 mmol), Pd2(dba)3 (30 mg, 0.03 mmol), and X-Phos (57 mg, 0.12 mmol) were dissolved in 1.4-dioxane (10 mL) in this order. The temperature was raised to 100°C under a nitrogen atmosphere and the reaction was allowed to proceed for 16 hours. After completion of the reaction, as monitored by TLC, the mixture was cooled to room temperature, diluted with water (60 mL), and extracted with ethyl acetate (50 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford compound 18D (300 mg, crude product), which was directly carried out to the next step.

[0546] LC-MS (ESI): m / z = 392.2 [M+H] + .

[0547] Step 4: 18D (300 mg) was dissolved in DCM (10 mL), trifluoroacetic acid (2.5 mL) was added, and the mixture was reacted at room temperature for 3 hours. After completion of the reaction as monitored by TLC, the mixture was concentrated under reduced pressure to afford compound 18E (190 mg, crude product), which was directly carried out to the next step.

[0548] LC-MS (ESI): m / z = 150.2 [M+H] + .

[0549] Step 5: Compound 18E (190 mg, 0.76 mmol), 4D (99 mg, 0.38 mmol), and N-methylimidazole (1 mL) were dissolved in DMF (10 mL) and N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (210 mg, 0.76 mmol) was added. The mixture was allowed to react at room temperature for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure and the residue was purified by column chromatography (DCM:MeOH = 20:1) to afford compound 18 (41 mg, 13.78% yield).

[0550] 1 H NMR(400MHz, CDCl3)δ8.21(d,1H),6.52-6.50(m,1H),6.27-6.25(m,1H),4.73(s,4H),4.23 -4.19(m,2H),3.68-3.65(m,2H),3.29-3.22(m,1H),2.77(d,2H),2.59(s,3H),2.58(s,3H).

[0551] LC-MS (ESI): m / z = 392.2 [M+H] + .

[0552] Example 19:

[0553] 5A (150 mg, 0.37 mmol), (1,3-dimethyl-1H-pyrazol-5-yl)boronic acid pinacol (108 mg, 0.49 mmol), Pd(dppf)Cl2 (27 mg, 0.037 mmol), and potassium carbonate (153 mg, 1.11 mmol) were dissolved in a mixture of 1,4-dioxane (6 mL) and water (0.5 mL) under a nitrogen atmosphere at 100°C overnight. After the reaction was complete, the mixture was cooled to room temperature, 25 mL of water was added, and the mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was separated and purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 25:1) to obtain compound 19 (70 mg, 45%).

[0554] 1H NMR (400MHz, CDCl3) δ8.27-8.25(m,1H),6.92-6.90(m,1H),6.45-6.44(m,1H),6.26(s,1H),6.25-6.21(m,1H),4.79-4.72(m,4H),4.2 8-4.22(m,2H),4.07(s,3H),3.75-3.69(m,2H),3.35-3.24(m,1H),2.84-2.79(t,J=7.9Hz,2H),2.54-2.52(m,3H),2.30-2.25(m,6H).

[0555] LC-MS (ESI): m / z = 417.5 [M+H] + .

[0556] Example 20:

[0557] 5A (150 mg, 0.37 mmol), (thiazol-5-yl)boronic acid pinacol (103 mg, 0.49 mmol), Pd(dppf)Cl2 (27 mg, 0.037 mmol), and potassium carbonate (153 mg, 1.11 mmol) were dissolved in a mixture of 1,4-dioxane (6 mL) and water (0.5 mL) under a nitrogen atmosphere at 100°C overnight. After the reaction was complete, the mixture was cooled to room temperature, 25 mL of water was added, and the mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was separated and purified by silica gel column chromatography (dichloromethane:methanol (v / v) = 25:1) to obtain compound 20 (64 mg, 42%).

[0558] 1 H NMR (400MHz, CDCl3) δ8.72(s,1H),8.21(s,1H),8.14-8.12(m,1H),6.85-6.82(m,1H),6.54(s,1H),6.14-6.12(m,1H),4.72-4 .66(m,4H),4.25-4.19(m,2H),3.73-3.65(m,2H),3.28-3.21(m,1H),2.78-2.73(m,2H),2.47-2.45(m,3H),2.20-2.18(m,3H).

[0559] LC-MS (ESI): m / z = 406.4 [M+H] + .

[0560] Example 21:

[0561] Compound 5A (0.1 g, 0.20 mmol), compound 21A (58 mg, 0.28 mmol), Pd(dppf)Cl2 (37 mg, 0.050 mmol), and potassium carbonate (0.1 g, 0.76 mmol) were dissolved in dioxane (10 mL) and water (10 mL) in sequence. T...

Claims

1. A compound represented by formula (I), its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, A is selected from 3-20 membered heterocycloalkyl or 5-20 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the heterocycloalkyl or heteroaryl is optionally replaced by 0-5 R A replace; B is selected from the bond, C 3-10 Cycloalkyl, C 6-12 aryl, 3-12 membered heterocycloalkyl or 5-12 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with 0-5 R B replace; C is selected from C 3-12 Cycloalkyl, C 6-10 aryl, 3-14 membered heterocycloalkyl or 5-14 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl contains 1-5 heteroatoms selected from N, O, and S; the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with 0-5 R C replace; L1 and L2 are each independently selected from W1-R L -W2, the left side of L1 is connected to A, and the left side of L2 is connected to B; R L Select from key, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 3-6 Cycloalkyl, 5-12 membered heteroaryl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkylene, alkenylene, alkynylene, cycloalkyl, heteroaryl, heterocycloalkyl may be further substituted by 1-4 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 1-4 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heteroaryl may be further substituted by 1-4 halogen, CN, OH, C 1-4 Alkoxy and NH2 substituents substitution; W1 and W2 are each independently selected from a bond, C 1-4 Alkylene, -O-, -S-, -S(=O)-, -S(=O)2-, -NR W1 -、-CONR W1 -、-NR W1 CO-, -C(=O)O-, -OC(=O)-, -C(=S)-, -C(=O)-, -(C 1-4 Alkylene)-NR W1 CO-, the alkylene group is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-4 Alkyl, CN, OH and NH2 radical substitution; R W1 Selected from H, C 1-4 Alkyl, halogen; Alternatively, L1 is selected from The "*" end is connected to the B ring; R A Each is independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-12 membered heteroaryl, -NR a CO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-4 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl, alkenyl, alkynyl, heteroaryl, cycloalkyl, heterocycloalkyl may be further substituted by 1-5 halogen, OH, NH2, CN, C 1-4 Alkoxy, -O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, -C 1-4 Alkylhydroxyl, -C(=O)C 1-4 Alkyl, halogenated C 1-4 Alkyl radical substitution; Alternatively, two R A Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution; R B Each independently selected from halogen, CN, =O, OH, -SF5, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, wherein the alkyl, alkoxy, alkenyl, alkynyl is optionally further selected from halogen, C 1-2 Alkyl radical substitution; R C Each is independently selected from D, halogen, CN, =O, OH, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -SCF3, -SF5, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -OC 5-11 Spirocycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, spirocycloalkyl, heterocyclyl are optionally further substituted by 1-4 halogens, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution; n is each independently selected from 0 or 1; R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-4 Alkyl, halogenated 3-6 membered cycloalkyl; R aa , R bb are each independently selected from H, halogen, =O, C 1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 Alkoxy; Alternatively, R aa , R bb Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution; Alternatively, two R C Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution; Alternatively, R B , R C Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radicals are substituted.

2. The compound according to claim 1, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein: A is selected from 5-6 membered monocyclic heteroaryl, 6-10 membered bicyclic heterocycloalkyl, 9-10 membered bicyclic heteroaryl, 10-14 membered tricyclic heterocycloalkyl, 10-14 membered tricyclic heteroaryl, wherein the heterocycloalkyl and heteroaryl are optionally substituted by 1-5 R A replace; R A Each is independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC 3-6 Cycloalkyl, -C 1-4 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-4 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-4 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1-5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, C 1-2 Alkoxy, -C 1-2 Alkylhydroxyl, -C(=O)C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution; Alternatively, two R A Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution; B is selected from a bond, a 4-7 membered monocyclic heterocycloalkyl, 3-8 Cycloalkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heterocycloalkyl, 5-12 membered spirocyclic heterocycloalkyl, 3-6 membered cycloalkyl and 5-6 membered heterocycloalkyl, benzo 5-6 membered heterocycloalkyl, wherein the heterocycloalkyl, heteroaryl, cycloalkyl, aryl are optionally substituted by 1-5 R B replace; R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted by halogen; C is selected from 5-6 membered monocyclic heteroaryl, phenyl, phenyl and 4-6 membered carbocyclic group, phenyl and 4-6 membered heterocyclic alkyl, 5-6 membered heterocyclic alkyl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered carbocyclic group, 8-12 membered tricyclic cycloalkyl, 8-14 membered tricyclic heterocyclic group, the heteroaryl, heterocyclic alkyl, heterocyclic group contains 1-4 heteroatoms selected from N, O, S; the phenyl, heterocyclic alkyl, carbocyclic group is optionally replaced by 1-5 R C replace; R C are each independently selected from D, halogen, CN, ═O, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -OC 5-11 Spirocycloalkyl, -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heteroaryl), -C(=O)NR a -(4-6 membered heterocycloalkyl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, spirocycloalkyl, heterocyclyl are optionally further substituted by 1-4 halogens, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution; R a Selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 Alkyl, halogenated 3-6 membered cycloalkyl; R aa , R bb are each independently selected from H, halogen, =O, C 1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 Alkoxy; Alternatively, R aa , R bb Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution; Alternatively, R B , R C Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 atoms selected from halogen, C 1-2 Alkyl radical substitution; L1 is selected from a bond, C 1-2 Alkylene, -C(=O)-C 1-2 Alkylene-, -N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -4-6 membered heterocycloalkyl-C containing 1-3 heteroatoms selected from N, O, S 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4 alkenylene, -C(=O)-NH-, -C(=O)-N(CH3)-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkane -NH-C(=O)-C 1-2 Alkylene-, wherein the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, C 1-2 Alkyl-C 1-2 Alkoxy; Alternatively, L1 is selected from The "*" end is connected to the B ring; L2 is selected from a bond, C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkyne, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, alkynylene may be further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; Provided that: when L2 is selected from -O-, -NH-, L1 is not selected from -C(=O)-, or B1 is not selected from a bond.

3. The compound according to claim 2, wherein the stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt thereof has the structure of formula (I-1a), (I-2), (I-3), (I-4), (I-5) or (I-1b): A1 is selected from the following groups: B1 is selected from the following groups: bond, in, Terminal and L1 or L 1a or L 1b connected, "*" end connected to L2 or L 2a connected; C1 is selected from the following groups: C2 is selected from the following groups: The condition is: C2 is selected from When L2 is not selected from a bond; or C2 is selected from and L2 is selected from a bond, n3 is not selected from 0 and R C Not for F; R1, R2, R3, and R4 are each independently selected from H and halogen; provided that R1, R2, R3, and R4 cannot be selected from H at the same time; Alternatively, R3 and R4 together form =O; Formula (I-3) satisfies one or more of the following conditions: (1) L 1a Selected from: key, C 1-2 Alkylene, -C(=O)-CH(CH3)-, -C(=O)-C(R a R b )-、-N(C 1-2 Alkylene)-C(=O)-C 1-2 Alkylene-, -NH-C(=O)-C 1-2 Alkylene-, -S(=O)2-C 1-2 Alkylene-, -C(=S)-C 1-2 Alkylene-, -4-6 membered heterocycloalkyl-C containing 1-3 heteroatoms selected from N, O, S 1-2 Alkylene-, -C(=O)-C 3-6 Cycloalkyl-, -C 1-2 Alkylene-C(=O)-, -C(=O)-C(=O)-, C 2-4 Alkenylene, -C(=O)-C 2-4 alkenylene, -C(=O)-NH-, -C(=O)-N(CH3)-, -C(=O)-O-, 5-6 membered heteroaryl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl, C 3-6 Cycloalkyl, 5-6 membered heteroaryl, -C(=O)-, 4-6 membered monocyclic heterocycloalkyl-C 1-2 Alkylene-, 4-6 membered monocyclic heterocycloalkyl-C(=O)-C 1-2 Alkylene-, -C 1-2 Alkylene-4-6 membered monocyclic heterocycloalkyl-, -C 1-2 Alkylene-NH-C(=O)-C 1-2 Alkylene-, wherein the alkylene, heterocycloalkyl, cycloalkyl, alkenylene, heteroaryl, heterocycloalkyl may be further substituted by 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; L 1a The right side is connected to the B1 ring; R a , R b Each is independently selected from H, halogen, 3-6 membered cycloalkyl, C 1-2 Alkyl; provided that R a , R b Not selected from H at the same time; L 2a Select from key, C 2-4 Alkenylene, C 2-4 Alkyne, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, alkynylene may be further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; provided that when L 1a Selected from -C(=O)-, L 2a When selected from -NH-, -O-, B1 is not selected from a bond; (2) L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a When selecting a bond, at least one R C1 is selected from =O, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 4-12 membered heterocycloalkyl, -N=S(=O)RaaRbb, -P(=O)RaaRbb, -NRaS(=O)2C 1-4 Alkyl, -NRaP(=O)(C 1-4 alkyl)2, -NRaS(=O)2NRaaRbb, -NRaC(=O)-C 3-6 Cycloalkyl, -C(=O)NRa-C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, cubane, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heteroaryl), The alkyl, cycloalkyl, heteroaryl, heterocycloalkyl, cubane may be further substituted by 1 to 4 alkyl radicals selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution; (3) L 1a Selected from: -C(=O)-CH2-, -C(=O)-CH2CH2-, L 2a Selected from C 1-2 Alkylene, C 2-4 Alkenylene, C 2-4 Alkyne, -C(=O)-NH-, -NH-, -O-, -N(C 1-2 Alkylene)-, -C(=O)-, wherein the alkylene, alkenylene, alkynylene may be further substituted with 1-3 R L1 Replacement; R L1 are independently selected from halogen, =O, C 1-2 Alkyl, halogenated C 1-2 Alkyl, C 2-4 Alkenyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, 3-6 membered cycloalkyl; (4) L 1a Selected from: -C(=O)-CH2-, L 2a When selecting a bond, at least one R A Not selected from C 1-2 Alkyl, and the compound is not L 1b is selected from: a bond, a 4-6 membered monocyclic heterocycloalkyl, -C(=O)-NH-, wherein the heterocycloalkyl is optionally further substituted by 1-4 groups selected from halogen, =O, C 1-2 Alkyl radical substitution; As an alternative, Selected from R A are independently selected from halogen, =O, C 1-2 Alkyl, -CF3, 5-6 membered heteroaryl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-O-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-12 membered heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NR aa -C 3-6 Cycloalkyl, -NR aa R bb 、-SO2-C 1-2 Alkyl, -C 3-6 Cycloalkyl, -NR aa -C 3-6 Cycloalkyl, The alkyl group is optionally further substituted by 1-4 groups selected from OH, NH2, CN, C 1-2 Alkyl, C 1-2 The alkoxy group is substituted, and the heteroaryl, cycloalkyl, and heterocycloalkyl are optionally further substituted with 1-4 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, -C 1-2 Alkylhydroxyl, halogenated C 1-2 Alkyl, -C(=O)C 1-2 Alkyl, C 1-2 Alkoxy group substitution; R A1 Each is independently selected from halogen, =O, CN, OH, COOH, C 1-4 Alkyl, C 1-4 Alkoxy, 5-6 membered heteroaryl, -SO2-C 1-4 Alkyl, -NRaCO-C 3-6 Cycloalkyl, 4-12 membered heterocycloalkyl, -OC 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-6 membered heteroaryl), -NR aa R bb The alkyl, heteroaryl, cycloalkyl, heterocycloalkyl group may be further substituted by 1 to 5 groups selected from halogen, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy group substitution; Alternatively, two R A Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-2 Alkyl radical substitution; R B are independently selected from halogen, =O, C 1-2 Alkyl, said alkyl being optionally further substituted by halogen; R C Each independently selected from D, halogen, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-3 Alkoxy, C 3-4 Cycloalkyl, 5-6 membered heteroaryl, CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-6 membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), The alkyl, heteroaryl, cycloalkyl group may be further substituted by 1-4 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution; R C1 are each independently selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, halogenated C 1-3 Alkoxy, C 3-5 Cycloalkyl, C 6-10 Cycloalkyl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 6-9 membered spirocyclic heterocycloalkyl, 7-10 membered cyclic heterocycloalkyl, 6-8 membered bridged heterocycloalkyl, 4-6 membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NR a -C 3-6 Cycloalkyl, -NR a -(4-12 membered heterocycloalkyl), -NR a -(5-6 membered heteroaryl), -NR a S(=O)2-C 3-6 Cycloalkyl, -C 1-4 Alkyl-(5-6 membered heteroaryl), -C 1-4 Alkyl-(C 6-10 Aryl), -C 1-4 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-4 alkyl) n -O-(C 1-4 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocycloalkyl), -NR a C(=O)-(5-6 membered heteroaryl), -C(=O)NR a -(5-6 membered heteroaryl), -C(=O)-C 3-6 Cycloalkyl, -C(=O)-(4-12 membered heterocycloalkyl), -C(=O)-(5-6 membered heteroaryl), wherein the alkyl, cycloalkyl, heteroaryl, heterocycloalkyl is optionally further substituted by 1-4 halogens, OH, NH2, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-4 Alkyl radical substitution; R aa , R bb are each independently selected from H, halogen, =O, C 1-4 Alkyl, C 1-4 Alkylhydroxyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 Alkoxy; Alternatively, R aa , R bb Together with the atoms it is connected to, it forms C 3-6 The carbocyclic group or heterocyclic group is optionally further substituted by 1 to 4 members selected from halogen, OH, NH2, CN, C 1-4 Alkyl radical substitution; n1, n2, n3 are each independently selected from 0, 1, 2, 3, 4 or 5.

4. The compound according to claim 3, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein: In the compounds of formula (I-1a), (I-2), (I-3), (I-4), (I-5), (I-1b), R A Each independently selected from F, Cl, =O, CN, methyl, ethyl, -NHCO-C 3-6 Cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, 5 membered heteroaryl, 6 membered heteroaryl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -O-(4-6-membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-O-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC 3-6 Cycloalkyl, -C 1-2 Alkyl-OC(=O)-(4-6 membered monocyclic heterocycloalkyl), -C 1-2 Alkyl-OC(=O)-NH-C 3-6 Cycloalkyl, -NHR aa , -SO2CH3, cyclopropyl, cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, oxacyclopentyl, -CF3, 7-10 membered bicyclic heterocycloalkyl, wherein the methyl and ethyl groups are optionally further substituted by 1-4 groups selected from OH, NH2, CN, The heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, -C(=O)CH3, -O-CH3, and -O-CH2CH3; Alternatively, two R A Together with the atoms to which it is attached, it forms a 5-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, and ethyl; R A1 Each independently selected from F, Cl, =O, CN, OH, COOH, -SO2CH3, methyl, ethyl, -OC 3-6 Cycloalkyl, -NHR aa , 5-membered heteroaryl, 4-6-membered heterocycloalkyl, wherein the methyl, ethyl, cycloalkyl, 4-6-membered heterocycloalkyl is optionally further substituted by 1-5 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl, -CHF2, -CH2F, -CF3, methoxy; R B Each is independently selected from F, Cl, =O, methyl, ethyl, wherein the methyl and ethyl are optionally further substituted by F and Cl groups; R C Each is independently selected from D, F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, 5-membered heteroaryl, 6-membered heteroaryl, -CN, =O, -NH-S(=O)2-C 1-2 Alkyl, -O-(5-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(4-6 membered monocyclic heterocycloalkyl), The methyl, ethyl, cyclopropyl, cyclobutyl, heteroaryl, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-4 groups selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3; R C1 Each is independently selected from F, Cl, methyl, ethyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, cyclopentyl, cubane, 5-membered heteroaryl, 6-membered heteroaryl, 8-membered cycloheteroaryl, 9-membered cycloheteroaryl, 10-membered cycloheteroaryl, 7-8-membered spirocyclic heterocycloalkyl, 8-9-membered cycloheterocycloalkyl, 7-membered bridged heterocycloalkyl, 4-6-membered monocyclic heterocycloalkyl, -N=S(=O)R aa R bb 、-P(=O)R aa R bb 、-NR a S(=O)2C 1-4 Alkyl, -NR a P(=O)(C 1-4 Alkyl)2, -NR a S(=O)2NR aa R bb 、-NR a C(=O)-C 3-6 Cycloalkyl, -C(=O)NR a -C 3-6 Cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH-(4-6 membered heterocycloalkyl), -NH-(5-6 membered heteroaryl), -NH-S(=O)2-C 3-6 Cycloalkyl, -C 1-2 Alkyl-(5-membered heteroaryl), -C 1-2 Alkyl-(6-membered heteroaryl), -C 1-2 Alkyl-phenyl, -C 1-2 Alkyl-(4-6 membered heterocycloalkyl), -NR a C(=O)-OR a 、-(C 1-2 alkyl) n -O-(C 1-2 alkyl) n -(4-6 membered heterocyclic group), -NR a C(=O)-(4-6 membered heterocyclyl), -C(=O)NR a -(4-6 membered heterocyclic group), -C(=O)-C 3-6 wherein the cyclopropyl, cyclobutyl, cyclopentyl, alkyl, cycloalkyl, heterocyclyl, heteroaryl, heterocyclylalkyl, cubane is optionally further substituted with 1-4 selected from F, Cl, OH, NH2, CN, methyl, ethyl, deuterated methyl, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, =O, -C(=O)C 1-4 Alkyl, -NH-C(=O)C 1-4 Alkyl, -S(=O)2C 1-2 Alkyl radical substitution; R a is selected from H, F, Cl, methyl, ethyl, cyclopropyl, cyclobutyl, cyclopentyl, difluorocyclobutyl; R aa , R bb Each is independently selected from H, F, Cl, =O, methyl, ethyl, -CH2-CH2-OH, -CH2-OH, -CHF2, -CH2F, -CF3, -CH2CF3, -CH2CHF2, -CH2CH2F, -OCH3, -OCH2CH3, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH2CHF2, -OCH2CH2F; Alternatively, R aa , R bb Together with the atoms to which it is attached, it forms a 4-6 membered heterocyclic group, wherein the heterocyclic group is optionally further substituted by 1-4 groups selected from F, Cl, OH, NH2, CN, methyl, ethyl; n1 is selected from 0, 1, 2 or 3; n2 is selected from 0 or 1; n3 is selected from 0, 1, 2, 3 or 4; L1 is selected from a bond, vinylene, -CH2-, -CH2-CH2-, 4-6-membered monocyclic heterocycloalkyl, (4-6-membered monocyclic heterocycloalkyl)-C(=O)-CH2-, -(4-6-membered monocyclic heterocycloalkyl)-CH2-, -CH2-(4-6-membered monocyclic heterocycloalkyl)-, -CH(CH3)NHC(=O)-CH2-, -CH2NHC(=O)-CH2-, -S(=O)2-CH2-, -C(=S)-CH2-, -C(=O)-C 3-6 Cycloalkyl, -C(=O)-CH(CH3)-, -C(=O)-CH(C 3-6 Cycloalkyl)-, -C(=O)-CF2-, -C(=O)-C(CH3)2-, -CH2-C(=O)-, -C(=O)-C(=O)-, C 3-6 Cycloalkyl, -(5-6 membered heteroaryl)-CH2-, 5-6 membered heteroaryl, -C(=O)-, -C(=O)-CH2-, -N(CH3)-CH2-, -CF2-CH2-, -C(=O)-C 2-4 alkenylene, -C(=O)-O-, -C(=O)-NH-, -C(=O)-N(CH3)-, wherein the -CH2-, alkenylene, cycloalkyl, heterocycloalkyl, heteroaryl may be further substituted with 1-3 R L1 Replacement; R L1 Each is independently selected from F, Cl, Br, =O, methyl, ethyl, -CF3, -CHF2, -CH2F, vinyl, propenyl, methoxy, ethoxy, -OCF3, -OCHF2, -OCH2F, cyclopropyl, cyclobutyl, methyl-methoxy, 5-membered heteroaryl; Alternatively, L1 is selected from The "*" end is connected to the B ring; L2 is selected from a bond, vinylene, ethynylene, -CH2-, -CH2-CH2-, -O-, -NH-, -C(=O)-, -N(CH3)-.

5. The compound according to claim 1, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, which has the structure of formula (II): Ring A is selected from optionally further substituted by 1, 2 or 3 R A The following structures are replaced: Or choose from het is a 5-membered heteroaryl group, which is optionally substituted by 1 or 2 selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl radical substitution; Each R A Each independently selected from halogen, CN, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -OC 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, -SO2-C 1-2 The heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally further substituted with 1 to 2 groups selected from halogen, OH, NH2, CN, C 1-2 Alkyl, C 1-2 Alkoxy, -C(=O)C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution; The C ring is selected from The C ring is optionally further substituted with 1, 2 or 3 R C replace; Each R C Each independently selected from halogen, halogenated C 1-3 Alkyl, halogenated C 1-4 Alkoxy, C 3-5 Cycloalkyl, 5-6 membered heteroaryl, -OC 3-6 Cycloalkyl, -O-(4-12 membered heterocycloalkyl), -O-(5-6 membered heteroaryl), -OC 5-8 Spirocycloalkyl, The heteroaryl, cycloalkyl, spirocycloalkyl may be further substituted by 1-3 groups selected from halogen, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl radicals are substituted.

6. The compound according to claim 5, its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt, wherein Ring A is selected from Each R C Each independently selected from F, Cl, CF3, CHF2, CH2F, -OCHF2, -OCH2F, -OCF3, -OCH2CF3, -OCH(CH3)CF3, cyclopropyl, cyclobutyl, 7. The compound according to claim 1, its stereoisomer, deuterated form, solvate, cocrystal or pharmaceutically acceptable salt, wherein the compound is selected from one of the structures in Table A.

8. A pharmaceutical composition or pharmaceutical preparation comprising the compound according to any one of claims 1 to 7, or a stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier and / or excipient.

9. The pharmaceutical composition or pharmaceutical preparation according to claim 8, comprising 1-1500 mg of the compound according to any one of claims 1-7 or its stereoisomer, deuterated substance, solvate, cocrystal or pharmaceutically acceptable salt and a carrier and / or excipient.

10. Use of the compound according to any one of claims 1 to 7, its stereoisomer, deuterated form, solvate, cocrystal or pharmaceutically acceptable salt, or the composition according to claim 8 or 9 in the preparation of a medicament for treating / preventing a CHRM4-mediated disease.

11. The use of claim 10, wherein the CHRM4-mediated disease is selected from Alzheimer's disease, schizophrenia or psychosis, pain, addiction, sleep disorders, cognitive disorders, Parkinson's disease, Parkinson's disease-levodopa-induced dyskinesia, Huntington's disease, movement disorders, dry mouth, pulmonary hypertension, chronic obstructive pulmonary disease, asthma, urinary incontinence, glaucoma, trisomy 21, cerebral amyloid angiopathy, dementia, Dutch hereditary amyloidosis cerebral hemorrhage, prion disorders, amyotrophic lateral sclerosis, progressive supranuclear palsy, head trauma, stroke, pancreatitis, inclusion body myositis, other peripheral amyloidosis, diabetes, autism and atherosclerosis; preferably Alzheimer's disease, schizophrenia, pain, addiction and sleep disorders.

12. A method for treating a disease in a mammal or a human, the method comprising administering to a subject a therapeutically effective amount of a compound according to any one of claims 1 to 7 or a stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt thereof, the therapeutically effective amount preferably being 1 to 1500 mg, wherein the disease is selected from the group consisting of Alzheimer's disease, schizophrenia or psychosis, pain, addiction, sleep disorders, cognitive disorders, Parkinson's disease, Parkinson's disease-levodopa-induced dyskinesia, Huntington's disease, dyskinesia, dry mouth, pulmonary hypertension, chronic obstructive pulmonary disease Disease, asthma, urinary incontinence, glaucoma, trisomy 21, cerebral amyloid angiopathy, dementia, Dutch hereditary amyloidosis cerebral hemorrhage, prion disorder, amyotrophic lateral sclerosis, progressive supranuclear palsy, head trauma, stroke, pancreatitis, inclusion body myositis, other peripheral amyloidosis, diabetes, autism and atherosclerosis; preferably Alzheimer's disease, schizophrenia, pain, addiction and sleep disorders, preferably Alzheimer's disease, schizophrenia, pain, addiction and sleep disorders. Preferably Alzheimer's disease, schizophrenia, pain, addiction and sleep disorders.

Images