Benzazepine derivatives and their use in medicine

Abstract

The present application relates to a kind of compound described in general formula (I) or its stereoisomer, deuteride, solvate, prodrug, metabolite, pharmaceutically acceptable salt or co-crystal, and intermediate and preparation method, and application in preparation of the drug for treating the disease related to the activity or expression amount of complement factor B.

Description

Technical Field

[0001] This invention relates to a compound of general formula (I) or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals, intermediates and preparation methods thereof, and its use in the preparation of medicaments for treating diseases related to the activity or expression level of complement factor B. Background Technology

[0002] Complement factor B is a component of the alternative complement pathway, participating in both specific and nonspecific immune mechanisms. It contains a serine protease (SP) domain, which, when activated, provides catalytic activity for the C3 and C5 convertases in the alternative pathway. Complement factor B circulates as an inactive proenzyme (zymogen) and is only activated upon cleavage by protein factor D. However, protein factor D can only cleave complement factor B when bound to the activated forms C3:C3(H2O) and C3b. Complement factor B is produced as a single-chain protein and cleaved by factor D to produce two peptide fragments (Ba and Bb). The Bb region (containing the SP domain) remains bound to C3(H2O) and C3b, forming the alternative pathway convertases [C3(H2O)Bb and C3bBb]. The SP domain of Bb, as part of the C3 convertase, possesses specific catalytic activity for the cleavage of the C3 molecule. Adding another C3b molecule to the alternative pathway C3 convertase produces the C5 convertase (C3bBbC3b). As part of the alternative pathway C5 convertase, the SP domain of Bb cleaves the C5 molecule, enabling C5-C9 to assemble and ultimately form the membrane attack complex (MAC). MAC participates in mediating various kidney diseases through multiple pathways, including cell lysis, promoting the release of cytokines and inflammatory mediators, synergistic cytokine action, and promoting collagen IV synthesis. Therefore, complement factor B is a key enzyme in the activation of the alternative complement pathway and can serve as a suitable target for inhibiting complement activation. Summary of the Invention

[0003] The purpose of this invention is to provide a compound or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals capable of inhibiting complement factor B, as well as intermediates and preparation methods thereof, and its use in the preparation of medicaments for treating diseases related to complement factor B activity or expression levels.

[0004] The compounds of this invention exhibit good complement factor B inhibitory activity, good in vivo C3a level inhibition rate, bioavailability, and safety.

[0005] This invention provides a compound of formula (I) or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein...

[0006] In some embodiments, the compound of general formula (I) is selected from compounds represented by general formulas (Ia), (Ib), (Ic), (Id), (Ie), or (If). ; In some embodiments, the compound of general formula (I) is selected from compounds represented by general formula (Id-1) or general formula (Id-2). ; In some embodiments, the compound of general formula (I) is selected from the compounds represented by general formula (Id-3) and general formula (Id-4). (Id-3) (Id-4); In some embodiments, the compound of general formula (I) is selected from compounds represented by general formulas (Id-5), (Id-6), (Id-7), and (Id-8). (Id-5) (Id-6) (Id-7) (Id-8); In some implementation schemes, R 1 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy group, -C(=O)C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy group, -C(=O)C 1-4 Alkyl group, -S (=O) p C 1-4 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthio, -WR 1d C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1 Selected from R 1A ; In some implementation schemes, R 1 Each group is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, eththio, cyclopropyl, cyclobutyl, or -WR. 1d The methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, ethio, cyclopropyl, and cyclobutyl groups are optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1 Each of the following groups is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, eththio, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl The ethyl, propynyl, propynyl, methylthio, ethylthio, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl are optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrrolidinyl. In some implementation schemes, R 1 Each is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, -OCD3, CD3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, ethynyl, -CH2-cyclopropyl, or -O-cyclopropyl; In some implementation schemes, R1 Each is independently selected from -OCH2F, -OCHF2, -OCF3, , ; In some implementation schemes, R 1 Selected from H, F, Cl, Br, I, -OCD3, CD3, methyl, ethyl, propyl, methoxy, ethoxy, isopropoxy, cyclopropyl, -CH2-cyclopropyl, or -O-cyclopropyl; In some implementation schemes, R 1 Selected from -OCH3 or -OCD3; In some implementation schemes, R 1A The group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further composed of 0 to 2 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1A The group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further substituted by 0 to 2 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, azacyclobutyl or pyrrolidinyl; In some implementations, W is selected from O or S; In some implementations, n is selected from 0, 1, or 2; In some implementations, p is selected from 0, 1, or 2; In some implementations, X1 and X2 are each independently selected from N or CR. 3; In some implementations, X1 is selected from CR 3 X2 is selected from CR 3 ; In some implementations, X1 is selected from N, and X2 is selected from CR. 3 ; In some implementations, X1 is selected from CR 3 X2 is selected from N; In some embodiments, X1 is selected from N or CH, and X2 is selected from N or CH, wherein the CH is optionally substituted with one methyl or ethyl molecule; In some implementations, X1 and X2 are each independently selected from N; In some implementations, Y is selected from NR 7 or C(R) 7 )2; In some implementation schemes, Y is selected from CR 7 R 7’ ; In some implementations, Y is selected from NR 7A ; In some implementations, Y is selected from C(R) 7a )2; In some implementations, Y is selected from C(R) 7B )2; In some implementation schemes, Y is selected from n is selected from 1, 2, or 3; In some implementation schemes, Selected from , or ; In some implementation schemes, Selected from , or ; In some implementation schemes, Selected from or ; In some implementation schemes, Selected from , Selected from , , ; In some implementation schemes, R 3 Each is independently selected from H, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 3 Each is independently selected from H, halogen, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-4 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted, wherein the heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 3Each of the following is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some implementation schemes, R 3 Each of the following groups is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, cyano. In some implementation schemes, R 3 Each is independently selected from H, methyl, or ethyl; In some implementation schemes, R 2 Selected from halogens, C 1-6 Alkyl or C 1-6 Alkyl group, wherein the alkyl group or alkoxy group is optionally further substituted with 0 to 4 substituents selected from H, D, halogen, OH, cyano or NH2; In some implementation schemes, R 2 Selected from halogens, C 1-4 Alkyl or C 1-4 Alkyl group, wherein the alkyl group or alkoxy group is optionally further substituted with 0 to 4 substituents selected from H, D, halogen, OH, cyano or NH2; In some implementation schemes, R 2 The group is selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, cyano or NH2. In some implementation schemes, R 2 Selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy; In some implementation schemes, R 2 Each is independently selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; In some implementation schemes, R 2Selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; In some implementation schemes, R 2 Each is independently selected from CD3, CHD2, and CH2D; In some implementation schemes, R 2 Each is independently selected from -CH3 and -CD3; In some implementation schemes, R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6 Alkyl or C 1-6 alkoxy groups, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl or C 1-4 alkoxy groups, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 6 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some implementation schemes, R 6 Each of the following groups is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, or -CH2OH; In some implementation schemes, R 6 Each is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy; In some implementation schemes, R 6 Each is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, and isopropyl. In some implementation schemes, R is selected from H, C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 Substituents of alkyl groups; In some implementation schemes, R is selected from H, C 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some embodiments, R is selected from H, methyl, ethyl, propyl or isopropyl, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl or CF3; In some implementations, R is selected from H; In some implementation schemes, R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further composed of 0 to 4 elements selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 1-6 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-6 A carbocyclic or 3- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 7 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, Ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxazine, oxazine-butyl, oxazine-pentyl, oxazine-hexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 7 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, -C(=O)R 1d -S(=O)2R 1dCyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl The pyridyl, morpholinyl, piperazine, oxetyl, oxetyl, oxetylpentyl, oxetylhexyl, pyrazolyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, propynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrrolidinyl; In some implementation schemes, R 7Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH 2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxygen Heterocyclohexyl, pyrazolyl, pyrroloyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein cyclopropyl, cyclobutyl, cyclopentyl, azirrobutyl, pyrroloalkyl, piperidinyl, morpholinyl, piperazinyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroloyl, imidazolyl, furanyl, thiophenyl, ... The thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, propynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrrolidinyl; In some implementation schemes, R 7 The molecule is selected from methoxymethyl, methoxyethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, and methoxy. In some implementation schemes, R 7 The group is selected from ethynyl, propynyl or propynyl, wherein the ethynyl, propynyl or propynyl is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, methoxy; In some implementations, 2 R 7B Together with the carbon atoms connected to it, they form the following ring: , , , , , , ; In some implementation schemes, R 7’ Selected from R 7 ; In some implementation schemes, R 7 'Selected from H, F, OH, NH2, methyl, ethyl, methoxy, ethoxy, wherein the methyl, ethyl, methoxy, ethoxy may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, methyl, ethyl, methoxy, or ethoxy; In some implementation schemes, Selected from , , , Selected from a single bond or a double bond; when selected from a double bond, R 7’ It does not exist, and middle At most one can be selected from a double bond; In some embodiments, ring B is selected from 3-6 membered heterocyclic groups, wherein the heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, -C(=O)R. 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some embodiments, ring B is selected from 3-6 membered heterocyclic alkyl groups, wherein the heterocyclic alkyl group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group or heteroalkyl group contains 1 to 4 heteroatoms selected from O, S or N; In some embodiments, ring B is selected from oxetyl, oxetyl, oxetylhexyl, thiophene, azirone, pyrrolyl, piperidinyl, morpholinyl, or piperazine, wherein the oxetyl, oxetyl, oxetyl, thiophene, azirone, pyrrolyl, piperidinyl, morpholinyl, or piperazine is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some embodiments, ring B is selected from oxetyl, oxetyl, oxetylhexyl, thiophene, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine, wherein the oxetyl, oxetyl, oxetyl, thiophene, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, CF3, OH, =O, cyano, NH2, -C(=O)CH3, methyl, ethyl, methoxy, or ethoxy. In some implementation schemes, R in 6 Each element is independently selected from H, halogens, OH, NH2, and C. 1-4 Alkyl or C 1-4 Alkyl groups, wherein the alkyl or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some implementation schemes, R in 6 Each is independently selected from H, F, Cl, Br, CF3, methyl, or ethyl; In some implementation schemes, R in 7 Selected from C 2-4 alkynyl group, C 3-6 Carbocyclic groups, 3- to 8-membered heterocyclic groups, R 7 Selected from H, halogens, OH, -NR 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d The alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R in 7 Selected from C 2-4 alkynyl, phenyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycloalkyl or 5- to 6-membered heteroaryl, R 7 Selected from H, halogens, OH, -NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)C 1-4 Alkyl group, -S(=O)2C 1-4 Alkyl groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, phenyl, cycloalkyl, heteroaryl, or heterocycloalkyl group is optionally further selected from 0 to 4 elements chosen from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6The alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic alkyl, heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R in 7 Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R 7 R 7 When substituted, it may be further replaced by 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R in 7 Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R7 R 7 When substituted, it may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl or piperazine; In some implementation schemes, R in 7 Selected from ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, and cyclopentyl, wherein the propynyl, propynyl, cyclopropyl, cyclobutyl, and cyclopentyl groups are optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, methyl, ethyl, methoxy, ethoxy, and cyclopropyl, R 7 'Selected from H, F, OH, NH2, methyl, ethyl, methoxy, ethoxy, wherein the methyl, ethyl, methoxy, ethoxy may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, methyl, ethyl, methoxy, or ethoxy; In some implementation schemes, Choose from one of the following structures:

[0007] In some implementation schemes, R 7 Selected from R 7B 2 R 7B Together with the carbon atoms connected to it, they form the following ring: , , , , , , ; In some implementation schemes, R 7 Selected from R 7A Or R 7a ; In some implementation schemes, R 7A Selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, -C(=O)R 1d -S(=O)2R 1dCyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridyl, pyrazinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 7A Selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl, pyrazolyl, pyrroleyl, or imidazoleyl The group consisting of methyl, furanyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl may be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl or cyclobutyl. In some implementation schemes, R 7ASelected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -CH2CH2OCH3, -CH2CF3, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, or imidazolyl; In some implementation schemes, R 7a Each is independently selected from R d F, Cl, Br, I, vinyl, ethynyl, propynyl, propyrynyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the vinyl, ethynyl, propynyl, propargyl, or cyclopropyl groups are... Cyclobutyl, cyclopentyl, azacyclobutyl, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl may optionally be further composed of 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 7a Each is independently selected from R d F, Cl, Br, I, vinyl, ethynyl, propynyl, propyrynyl, -C(=O)R 1d -S(=O)2R 1dCyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the vinyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, pyrroleyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, pyrroleyl, piperidinyl, py ... Cyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroloyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrroloalkyl; In some implementation schemes, R 7a Selected from F, Cl, Br, I, CF3, -CH2F, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O) -phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazinyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl; In some implementation schemes, R d Each of the following is independently selected from methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy groups are further selected by one to three groups selected from halogen, ethynyl, and C. 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 Substituted with cycloalkyl or 3 to 8-membered heterocyclic groups; In some implementation schemes, R d Each of the following groups is independently selected from methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy groups are further substituted by 1 to 3 substituents selected from F, Cl, Br, I, ethynyl, methoxy, ethoxy, CF3, -CH2F, cyclopropyl, cyclobutyl, aziridine, or pyrrolidinyl. In some implementations, two R 7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R. 1d -S(=O)2R 1d NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementations, two R 7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementations, two R 7Together with the carbon atom attached thereto, it forms an oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group, wherein the oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group is optionally further composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some implementations, the R at adjacent locations 6 With R 7 Double bonds can be formed; In some implementations, two R 6 Together with the atoms attached to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementations, two R 6 Together with the atoms attached to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementations, two R 6 Together with the atoms attached thereto, they form cyclobutyl, cyclopentyl, cyclohexyl, oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazineyl. In some implementation schemes, Selected from , or , It indicates a single bond or a double bond, and contains only one double bond; In some implementation schemes, Selected from , , , or Above it is R 4 Connected; In some implementation schemes, Selected from the excerpt in the table below, above which is R 4 Connected, In some implementation schemes, R 4 Selected from C 5-12 Carbocyclic groups, 5- to 12-membered heterocyclic groups, C 6-12 aryl or 5 to 12-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The substitution, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4 Selected from C 5-7 Monocyclic carbocyclic group, C 5-12 fused carbonyl group, C 5-12 Spirocyclic carbocyclic group, C 5-12 5- to 7-membered bridged carbide ring groups, 5- to 12-membered monocyclic heterocyclic groups, 5- to 12-membered fused ring heterocyclic groups, 5- to 12-membered spirocyclic heterocyclic groups, or 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4 Selected from C 5-6 Monocyclic carbocyclic group, C 5-10 fused carbonyl group, C 5-11 Spirocyclic carbocyclic group, C 5-12 5- to 6-membered bridged carbide ring groups, 5- to 10-membered fused ring heterocyclic groups, 5- to 11-membered spirocyclic heterocyclic groups, 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4 Each of the following groups is independently selected from cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrazolyl, pyrimidinyl, or naphthidinyl, wherein the cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrimidinyl, or naphthidinyl is optionally further divided by 0 to 4 R groups. 5 replace; In some implementation schemes, R 4 Each independently selected , , , , or ; In some implementation schemes, R 4 Selected from , , ; In some implementation schemes, R 4 Selected from , , wherein R 4 It may be optionally substituted with one, two or three substituents selected from F, Cl, Br, I, OH, cyano, methyl, ethyl, methoxy or ethoxy; In some implementation schemes, R 4 Selected from , wherein R 4 Optionally further substituted with 0, 1, 2 or 3 substituents selected from F, Cl, Br, I, OH, cyano, methyl, ethyl, methoxy or ethoxy; In some implementation schemes, R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, C3-10 Cycloalkyl or 4- to 12-membered heterocyclic groups, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; In some implementation schemes, R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; In some implementation schemes, R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 3-6 Cycloalkyl or 4- to 6-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; In some implementation schemes, R 5 Each is independently selected from H, F, Cl, Br, I, OH, cyano, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -COOH, -CH2OH, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2OH, , , -C(=O)NH2, -C(=O)NHOH, -S(=O)2NHC(=O)CH3, -C(=O)NHS(=O)2CH3, pyrazolyl, tetrazolyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, pyrazolyl, tetrazolyl are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl or cyclobutyl; In some implementation schemes, R 1c Selected from OH, NH2, C 1-6 Alkoxy, NHC 1-4 Alkyl or N(C) 1-4 Alkyl)2; In some implementation schemes, R 1c Selected from OH, NH2, C 1-4 Alkoxy, NHC 1-4Alkyl or N(C) 1-4 Alkyl)2; In some implementation schemes, R 1c Selected from OH, NH2, methoxy, ethoxy, NHCH3, N(CH3)2; In some implementation schemes, R 4a R 4b Each group is independently selected from H, OH, cyano, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4a R 4b Each group is independently selected from H, OH, cyano, NH2, and C. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10 aryl or 5- to 6-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4c R 4d Each is independently selected from H, OH, and C. 1-6 Alkyl, C 1-6 Alkoxy, -NR 1a R 1b -OR 1d -C3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4c R 4d Each is independently selected from H, OH, and C. 1-4 Alkyl, C 1-4 Alkoxy, -NR 1a R 1b -OR 1d C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 12-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy or C 3-6Cycloalkyl groups, 5- to 10-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4a R 4b R 4c R 4d Each of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl is optionally further selected from 0 to 4 of the following: H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 4a R 4b R 4c R 4d Each of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, or CF3; In some implementation schemes, R 4e R 4f Each is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl; In some implementation schemes, R 1d Each is independently selected from H and C 1-6 Alkyl, C 3-8 A carbocyclic or 4- to 10-membered heterocyclic group, wherein the alkyl, carbocyclic, or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R1d Each is independently selected from H and C 1-4 Alkyl, C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, carbocyclic or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1d Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl is optionally selected from 0 to 4 of the following: H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1d Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetyl, aziridine, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetyl, aziridine, pyrrolidinyl, or phenyl is optionally substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine, or pyrrolidinyl; In some implementation schemes, R 1d Each is independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, phenyl, -CH2-cyclopropyl or -CH2-cyclobutyl; In some implementation schemes, R 8 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 8 R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthioyl, wherein the alkyl, alkenyl, alkoxy, or alkylthioyl group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some implementation schemes, R 8 R 9 Or R 10 Each is independently selected from H, F, Cl, Br, I, OH, cyano, CF3, NH2, methyl, or ethyl; In some implementation schemes, R 1a R 1b Each is independently selected from H and C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; In some implementation schemes, R 1a R 1b Each is independently selected from H and C 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some implementation schemes, R 1a R 1b Each is independently selected from H, methyl, ethyl, propyl, or isopropyl, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; In some implementation schemes, R 1a R 1bEach of the groups is independently selected from H, methyl, ethyl, propyl or isopropyl, wherein the methyl, ethyl, propyl or isopropyl groups are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH; In some implementations, when Y is selected from C(R) 7 )2, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, cyano C 1-6 Alkyl or unsubstituted C 1-6 alkoxy group, and two R groups 7 For the carbon atom attached to it to not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1)R 1 Selected from C 2-6 alkynyl group, C 3-6 Cycloalkyl-substituted C 1-6 Alkyl, 3- to 8-membered heterocyclic substituted C 1-6 Alkyl, -WC 3-8 A carbocyclic or -W-4 to 10-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N; In some implementations, when Y is selected from C(R) 7 )2, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-4 Alkyl, hydroxyl C 1-4 Alkyl, cyano C 1-4 Alkyl or unsubstituted C 1-4 alkoxy group, and two R groups 7 For the carbon atom attached to it to not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1)R 1 Selected from C 2-4 alkynyl group, C 3-6 Cycloalkyl-substituted C 1-4 Alkyl, 3- to 8-membered heterocyclic substituted C 1-4 Alkyl, -WC 3-6 A carbocyclic or -W-4 to 8-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N; In some embodiments, the compound of general formula (I) is not a racemate of the following compounds: Furthermore, compounds of general formula (I) are not stereoisomers of the following compounds: .

[0009] As a first embodiment of the present invention, the compound represented by the aforementioned general formula (I) or its stereoisomers, deuterated products, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, (I) R 1 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy group, -C(=O)C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further composed of 0 to 4 elements selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; p is selected from 0, 1, or 2; n is selected from 0, 1, or 2; W is selected from O or S; R 2 Selected from halogens, C1-6 Alkyl or C 1-6 Alkoxy group, wherein the alkyl group or alkoxy group is optionally further substituted by 0 to 4 substituents selected from H, halogen, OH, cyano or NH2; X1 and X2 are each independently selected from N or CR. 3 ; Y is selected from NR 7 or C(R) 7 )2; R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6 Alkyl or C 1-6 alkoxy groups, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further composed of 0 to 4 elements selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 1-6 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; As an option, two R 7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R. 1d -S(=O)2R 1d NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; As an option, R at adjacent positions 6 With R 7 Double bonds can be formed; As an option, two R 6 Together with the atoms attached to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 3 Each is independently selected from H, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 1c Selected from OH, NH2, C 1-6 Alkoxy, NHC 1-4 Alkyl or N(C) 1-4 Alkyl)2; R is selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 Substituents of alkyl groups; R 4 Selected from C 5-12 Carbocyclic groups, 5- to 12-membered heterocyclic groups, C 6-12 aryl or 5 to 12-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The substitution, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10Cycloalkyl or 4- to 12-membered heterocyclic groups, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; R 4a R 4b Each group is independently selected from H, OH, cyano, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; R 4c R 4d Each is independently selected from H, OH, and C. 1-6 Alkyl, C 1-6 Alkoxy, -NR 1a R 1b -OR 1d -C 3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 12-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 1a R 1b Each is independently selected from H and C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 1d Each is independently selected from H and C 1-6 Alkyl, C 3-8 A carbocyclic or 4- to 10-membered heterocyclic group, wherein the alkyl, carbocyclic, or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 8 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-8A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; When Y is selected from C(R) 7 At 2 o'clock, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, cyano C 1-6 Alkyl or unsubstituted C 1-6 alkoxy group, and two R groups 7 For the carbon atom attached to it to not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1)R 1 Selected from C 2-6 alkynyl group, C 3-6 Cycloalkyl-substituted C 1-6 Alkyl, 3- to 8-membered heterocyclic substituted C 1-6 Alkyl, -WC 3-8A carbocyclic or -W-4 to 10-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N.

[0010] As a second embodiment of the present invention, the compound represented by the aforementioned general formula (I) or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy group, -C(=O)C 1-4 Alkyl group, -S (=O) p C 1-4 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 2 Selected from halogens, C 1-4 Alkyl or C 1-4 Alkyl group, wherein the alkyl group or alkoxy group is optionally further substituted with 0 to 4 substituents selected from H, D, halogen, OH, cyano or NH2; X1 and X2 are each independently selected from N or CR. 3 ; R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl or C 1-4 alkoxy groups, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-6 A carbocyclic or 3- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; As an option, two R 7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; As an option, R at adjacent positions 6 With R 7 Double bonds can be formed; As an option, two R 6 Together with the atoms attached to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 3 Each is independently selected from H, halogen, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-4 Alkyl group, -CH2NHC(O)C 1-4Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted, wherein the heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 1c Selected from OH, NH2, C 1-4 Alkoxy, NHC 1-4 Alkyl or N(C) 1-4 Alkyl)2; R is selected from H and C. 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 4 Selected from C 5-7 Monocyclic carbocyclic group, C 5-12 fused carbonyl group, C 5-12 Spirocyclic carbocyclic group, C 5-12 5- to 7-membered bridged carbide ring groups, 5- to 12-membered monocyclic heterocyclic groups, 5- to 12-membered fused ring heterocyclic groups, 5- to 12-membered spirocyclic heterocyclic groups, or 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N; R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; R 4a R 4b Each group is independently selected from H, OH, cyano, NH2, and C. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10 aryl or 5- to 6-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; R 4c R 4d Each is independently selected from H, OH, and C. 1-4 Alkyl, C 1-4 Alkoxy, -NR 1a R 1b -OR 1d C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl substituent contains 1 to 4 heteroatoms selected from O, S or N; R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy or C 3-6 Cycloalkyl groups, 5- to 10-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 1a R 1b Each is independently selected from H and C 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 1d Each is independently selected from H and C 1-4 Alkyl, C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, carbocyclic or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 8 R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkenyl, C2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthioyl, wherein the alkyl, alkenyl, alkoxy, or alkylthioyl group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; When Y is selected from C(R) 7 )2, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-4 Alkyl, hydroxyl C 1-4 Alkyl, cyano C 1-4 Alkyl or unsubstituted C 1-4 alkoxy group, and two R groups 7 When the carbon atom attached to it does not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1)R 1 Selected from C 2-4 alkynyl group, C 3-6 Cycloalkyl-substituted C 1-4 Alkyl, 3- to 8-membered heterocyclic substituted C 1-4 Alkyl, -WC 3-6 A carbocyclic or -W-4 to 8-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N.

[0011] The definitions of the remaining substituents are consistent with those of Scheme 1 of this invention; As a third embodiment of the present invention, the compound represented by the aforementioned general formula (I) or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthio, -WR 1d C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 2 The group is selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, cyano or NH2. R 3 Each of the following is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 6 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R is selected from H, methyl, ethyl, propyl or isopropyl, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl or CF3; R 4 Selected from C 5-6 Monocyclic carbocyclic group, C 5-10 fused carbonyl group, C 5-11 Spirocyclic carbocyclic group, C 5-12 5- to 6-membered bridged carbide ring groups, 5- to 10-membered fused ring heterocyclic groups, 5- to 11-membered spirocyclic heterocyclic groups, 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N; R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C2-4 alkenyl, C 2-4 alkynyl group, C 3-6 Cycloalkyl or 4- to 6-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; R 4a R 4b R 4c R 4d Each of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl is optionally further selected from 0 to 4 of the following: H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 1a R 1b Each is independently selected from H, methyl, ethyl, propyl, or isopropyl, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 4e R 4f Each is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl; R 1dEach of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl is optionally selected from 0 to 4 of the following: H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 8 R 9 or R 10 Each is independently selected from H, F, Cl, Br, I, OH, cyano, CF3, NH2, methyl, or ethyl; The definitions of the remaining substituents are consistent with those of Scheme 2 of this invention.

[0012] As a fourth embodiment of the present invention, the compounds or their stereoisomers, deuterated products, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals represented by the following general formulas (Ia), (Ib), (Ic), (Id), (Ie) or (If) are used.

[0013] n is independently selected from 0, 1, or 2; R 3 Each of the following groups is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, cyano. R 6 Each of the following groups is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, or -CH2OH; R 7Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, Ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxazine, oxazine-butyl, oxazine-pentyl, oxazine-hexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 7A Selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, -C(=O)R 1d -S(=O)2R 1dCyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridyl, pyrazinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 7a Each is independently selected from R d F, Cl, Br, I, vinyl, ethynyl, propynyl, propyrynyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the vinyl, ethynyl, propynyl, propargyl, or cyclopropyl groups are... Cyclobutyl, cyclopentyl, azacyclobutyl, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl may optionally be further composed of 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; Rd Each of the following is independently selected from methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy groups are further selected by one to three groups selected from halogen, ethynyl, and C. 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 Substituted with cycloalkyl or 3 to 8-membered heterocyclic groups; (Ib) It indicates a single bond or a double bond, and contains only one double bond; In (Id), as a choice, the two Rs 7 Together with the carbon atom attached thereto, it forms an oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group, wherein the oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group is optionally further composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; Or in (Id), two Rs 6 Together with the atoms attached thereto, they form cyclobutyl, cyclopentyl, cyclohexyl, oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazineyl. R 1AThe group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further composed of 0 to 2 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 1 Each group is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, eththio, cyclopropyl, cyclobutyl, or -WR. 1d The methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, ethio, cyclopropyl, and cyclobutyl groups are optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 4 Each of the following groups is independently selected from cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrazolyl, pyrimidinyl, or naphthidinyl, wherein the cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrimidinyl, or naphthidinyl is optionally further divided by 0 to 4 R groups. 5 replace; R 4a R 4b R 4c R 4dEach of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, or CF3; R 1d Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetyl, aziridine, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetyl, aziridine, pyrrolidinyl, or phenyl is optionally substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine, or pyrrolidinyl; The definitions of the remaining substituents are consistent with those of Scheme 3 of this invention.

[0014] As a fifth embodiment of the present invention, the compound represented by the aforementioned general formula (Id) or its stereoisomers, deuterated products, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, R 4 Each independently selected , , , , or ; Or R 4 Each independently selected , , ; R 5 Each is independently selected from H, F, Cl, Br, I, OH, cyano, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -COOH, -CH2OH, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2OH, , , -C(=O)NH2, -C(=O)NHOH, -S(=O)2NHC(=O)CH3, -C(=O)NHS(=O)2CH3, pyrazolyl, tetrazolyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, pyrazolyl, tetrazolyl are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl or cyclobutyl; Selected from , or ; R 1 Each is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, -OCD3, CD3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, ethynyl, -CH2-cyclopropyl, or -O-cyclopropyl; Or R 1 Each is independently selected from -OCH2F, -OCHF2, -OCF3, , ; R 2 Each is independently selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; R 2 Each is independently selected from CD3, CHD2, and CH2D; R 3 Each is independently selected from H, methyl, or ethyl; Selected from the excerpt in the table below, above which is R 4 Connected, The definitions of the remaining substituents are consistent with those of Scheme 4 of this invention.

[0016] As a sixth embodiment of the present invention, the compound or its stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal represented by the aforementioned general formulas (Ia), (Ib), (Ic), (Ie) or (If) Selected from , or ; Selected from or ; R 1AThe group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further substituted by 0 to 2 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, azacyclobutyl or pyrrolidinyl; R 1 Each is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, -OCD3, CD3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, ethynyl, -CH2-cyclopropyl, or -O-cyclopropyl; Or R 1 Each is independently selected from -OCH2F, -OCHF2, -OCF3, , ; R 2 Each is independently selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; Or R 2 Each is independently selected from CD3, CHD2, and CH2D; R 3 Each is independently selected from H, methyl, or ethyl; R 4 Each independently selected , , , , or ; R 5 Each is independently selected from H, F, Cl, Br, I, OH, cyano, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -COOH, -CH2OH, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2OH, , , -C(=O)NH2, -C(=O)NHOH, -S(=O)2NHC(=O)CH3, -C(=O)NHS(=O)2CH3, pyrazolyl, tetrazolyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, pyrazolyl, tetrazolyl are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl or cyclobutyl; (Ia) Selected from Above it is R 4 Connected; In (Ib), Selected from or Above it is R 4 Connected; In (Ic) or (If), Selected from Above it is R 4 Connected; (Ie), Selected from Above it is R 4 Connected; R 6 Each is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, and isopropyl. R 7 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, imidazolyl, furanyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl; R 7ASelected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -CH2CH2OCH3, -CH2CF3, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, or imidazolyl; R 7a Selected from F, Cl, Br, I, CF3, -CH2F, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O) -phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazinyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl; The definitions of the remaining substituents are consistent with those of Scheme 4 of this invention.

[0017] As a seventh embodiment of the present invention, the compound represented by the aforementioned general formula (Id) or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound of general formula (Id) is selected from the compounds represented by general formula (Id-1) or general formula (Id-2).

[0018] R 4 Selected from , wherein R 4 The radical can be further selected from 0, 1, 2 or 3 of the following groups: F, Cl, Br, I, OH, cyano, C. 1-4 Alkyl, C 1-4 Substituents of alkoxy groups; R 1 Selected from H, F, Cl, Br, I, -OCD3, CD3, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, -CH2-C 3-6 cycloalkyl or -OC 3-6Cycloalkyl, wherein the alkyl, alkoxy, or cycloalkyl group is optionally further substituted with 0 to 4 F, ethynyl, or propynyl groups; R 2 Selected from F, Cl, Br, I, C 1-4 alkyl; R 7 Selected from methoxymethyl, methoxyethyl, C 2-4 alkynyl group, C 3-6 Cycloalkyl or 4- to 7-membered heterocycles, wherein the alkynyl, cycloalkyl, or heterocyclic group is optionally further substituted with 0 to 4 H, D, halogen, CF3, OH, =O, cyano, NH2, methyl, or methoxy substituents; 2 Rs 7B Together with the carbon atoms connected thereto, a 4- to 7-membered heterocycle is formed, preferably a 4- to 6-membered heterocycle, wherein the heterocycle is optionally further replaced by 0 to 2 =O atoms.

[0019] As an eighth embodiment of the present invention, the compound represented by the aforementioned general formula (Id) or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound of general formula (Id) is selected from the compounds represented by general formula (Id-1) or general formula (Id-2).

[0020] R 4 Selected from , , wherein R 4 Optionally further substituted with 0, 1, 2 or 3 substituents selected from F, Cl, Br, I, OH, cyano, methyl, ethyl, methoxy or ethoxy; R 1 Selected from H, F, Cl, Br, I, -OCD3, CD3, methyl, ethyl, propyl, methoxy, ethoxy, isopropoxy, cyclopropyl, -CH2-cyclopropyl, or -O-cyclopropyl; Or R 1 Each is independently selected from -OCH2F, -OCHF2, -OCF3, , ; R 2 Selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; Or R 2 Each is independently selected from CD3, CHD2, and CH2D; R 7The molecule is selected from methoxymethyl, methoxyethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, and methoxy. 2 Rs 7B Together with the carbon atoms connected to it, they form the following ring: , , , , , , .

[0021] As a ninth embodiment of the present invention, the compound represented by the aforementioned general formula (I) or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound of general formula (I) is selected from the compounds represented by general formulas (Id-3) and (Id-4). (Id-3) (Id-4) Selected from a single bond or a double bond; when selected from a double bond, R 7’ It does not exist, and in general formula (Id-4) At most one can be selected from a double bond; Ring B is selected from 3-6 membered heterocyclic groups, wherein the heterocyclic group is optionally further surrounded by 0 to 4 groups selected from H, halogen, OH, =O, cyano, -C(=O)R. 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 6 Each element is independently selected from H, halogens, OH, NH2, and C. 1-4 Alkyl or C 1-4 alkoxy groups, wherein the alkyl or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 7 Selected from C 2-4 alkynyl group, C 3-6 Carbocyclic groups, 3- to 8-membered heterocyclic groups, R 7 Selected from H, halogens, OH, -NR 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d The alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; The definitions of the remaining groups are the same as in the second embodiment of the present invention.

[0022] As a tenth embodiment of the present invention, the compounds or their stereoisomers, deuterated products, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals represented by the aforementioned general formulas (Id-3) and (Id-4) are used. X1 is selected from N or CH, X2 is selected from N or CH, wherein the CH is optionally substituted with one methyl or ethyl molecule; Ring B is selected from 3-6 membered heterocyclic alkyl groups, wherein the heterocyclic alkyl group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group or heteroalkyl group contains 1 to 4 heteroatoms selected from O, S or N; R 7 Selected from C 2-4 alkynyl, phenyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycloalkyl or 5- to 6-membered heteroaryl, R 7 Selected from H, halogens, OH, -NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)C 1-4 Alkyl group, -S(=O)2C 1-4 Alkyl groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, phenyl, cycloalkyl, heteroaryl, or heterocycloalkyl group is optionally further selected from 0 to 4 elements chosen from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic alkyl, heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; Preferably, Ring B is selected from oxetyl, oxetyl, oxetylhexyl, thiophene, azirone, pyrrolyl, piperidinyl, morpholinyl, or piperazine, wherein the oxetyl, oxetyl, oxetyl, thiophene, azirone, pyrrolyl, piperidinyl, morpholinyl, or piperazine may optionally be further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 7 Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R 7 R 7 When substituted, it may be further replaced by 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 6 Each is independently selected from H, F, Cl, Br, CF3, methyl, or ethyl; R 1 R 2 R 4 The definition is the same as that in the fifth embodiment of the present invention.

[0023] As an eleventh embodiment of the present invention, the compounds represented by the aforementioned general formulas (Id-3) and (Id-4), or their stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, Ring B is selected from oxetyl, oxetyl, oxetyl, thiophene, azirone, pyrrolyl, piperidinyl, morpholinyl, piperazine, wherein ring B is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, CF3, OH, =O, cyano, NH2, -C(=O)CH3, methyl, ethyl, methoxy, or ethoxy; R 7 Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R 7 R 7 When substituted, it may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl or piperazine; R 1 R 2 R 4 The definition is the same as in the sixth embodiment of the present invention. As the twelfth embodiment of the present invention, the compound represented by the aforementioned general formula (Id-3) or general formula (Id-4), or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, R 4 Selected from , , wherein R 4 It may be optionally substituted with one, two or three substituents selected from F, Cl, Br, I, OH, cyano, methyl, ethyl, methoxy or ethoxy; The definitions of the remaining groups are the same as in any of the ninth, tenth, and eleventh embodiments of the present invention.

[0024] As a thirteenth embodiment of the present invention, the compound or its stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal represented by the following general formula (Id-5) (Id-5) Selected from , , ; R 1 Selected from -OCH3 or -OCD3; R 2 Selected from -CH3 or -CD3; n is selected from 1, 2, or 3.

[0025] As the fourteenth embodiment of the present invention, the compound or its stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal represented by the following general formula (Id-6) (Id-6) Selected from , , ; R 1 Selected from -OCH3 or -OCD3; R 2 Selected from -CH3 or -CD3.

[0026] As a fifteenth embodiment of the present invention, the compound or its stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal represented by the following general formulas (Id-7) and (Id-8) are used. (Id-7) (Id-8) Selected from , , ; R 1 Selected from -OCH3 or -OCD3; R 2 Selected from -CH3 or -CD3.

[0027] As a sixteenth embodiment of the present invention, the compound of general formula (I) is selected from the compounds shown in general formula (Id-3-a), general formula (Id-5-a), general formula (Id-6-a), general formula (Id-7-a), and general formula (Id-8-a). (Id-3-a) (Id-5-a) (Id-6-a) (Id-7-a) (Id-8-a) The definitions of each group in general formula (Id-3-a) are the same as those in general formula (Id-3); The definitions of each group in general formula (Id-5-a) are the same as those in general formula (Id-5); The definitions of each group in general formula (Id-6-a) are the same as those in general formula (Id-6); The definitions of each group in general formula (Id-7-a) are the same as those in general formula (Id-7); The definitions of each group in general formula (Id-8-a) are the same as those in general formula (Id-7).

[0028] This invention relates to a compound or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or eutectics, wherein the compound is selected from one of the structures in Table E-1.

[0029] Table E-1

[0030]

[0031]

[0032]

[0033]

[0034]

[0035]

[0036]

[0037]

[0038]

[0039]

[0040]

[0041]

[0042]

[0043]

[0044]

[0045]

[0046]

[0047]

[0048]

[0049] .

[0050] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4) or (Ie), R 1 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy group, -C(=O)C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0051] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4) or (Ie), R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy group, -C(=O)C 1-4 Alkyl group, -S (=O) p C1-4 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0052] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4) or (Ie), R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthio, -WR 1d C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0053] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4) or (Ie), R 1 Selected from R 1A .

[0054] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4) or (Ie), R 1 Each group is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, eththio, cyclopropyl, cyclobutyl, or -WR. 1d The methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, ethio, cyclopropyl, and cyclobutyl groups are optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0055] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4) or (Ie), R 1 Each of the following groups is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, eththio, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl The ethyl, propynyl, propynyl, methylthio, ethylthio, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl may be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrrolidinyl.

[0056] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2) or (Ie), R 1Each is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, -OCD3, CD3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, ethynyl, -CH2-cyclopropyl, or -O-cyclopropyl.

[0057] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2) or (Ie), R 1 Selected from H, F, Cl, Br, I, -OCD3, CD3, methyl, ethyl, propyl, methoxy, ethoxy, isopropoxy, cyclopropyl, -CH2-cyclopropyl, or -O-cyclopropyl.

[0058] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4) or (Ie), R 1 Each is independently selected from -OCH2F, -OCHF2, -OCF3, , .

[0059] This invention relates to some embodiments of general formulas (Id-1), (Id-2), (Id-3), (Id-4), R 1 Selected from H, F, Cl, Br, I, -OCD3, CD3, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, -CH2-C 3-6 cycloalkyl or -OC 3-6 Cycloalkyl.

[0060] This invention relates to some embodiments of general formula (I) or (If), R 1A The group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further composed of 0 to 2 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0061] This invention relates to some embodiments of general formula (I) or (If), R 1A The group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further substituted by 0 to 2 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, azacyclobutyl or pyrrolidinyl.

[0062] The present invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id) or (Ie), where W is selected from O or S.

[0063] The present invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Ie) or (If), where n is selected from 0, 1, 2.

[0064] The present invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Ie) or (If), where p is selected from 0, 1, 2.

[0065] This invention relates to some embodiments of general formulas (I), (Ia), and (Ib), wherein X1 and X2 are each independently selected from N or CR. 3 .

[0066] This invention relates to some embodiments of general formulas (I), (Ia), and (Ib), where X1 is selected from CR. 3 X2 is selected from CR 3 .

[0067] This invention relates to some embodiments of general formulas (I), (Ia), and (Ib), where X1 is selected from N and X2 is selected from CR. 3 .

[0068] This invention relates to some embodiments of general formulas (I), (Ia), and (Ib), where X1 is selected from CR. 3 X2 is selected from N.

[0069] The present invention relates to some embodiments of general formulas (I), (Ia), and (Ib), wherein X1 and X2 are each independently selected from N.

[0070] This invention relates to some embodiments of general formula (I), where Y is selected from NR. 7 or C(R) 7 )2.

[0071] This invention relates to some embodiments of general formula (I), where Y is selected from NR. 7A .

[0072] This invention relates to some embodiments of general formula (I), where Y is selected from C(R) 7a )2.

[0073] This invention relates to some embodiments of general formula (I), where Y is selected from C(R) 7B 2. This invention relates to some embodiments of general formula (I), Selected from , or .

[0074] This invention relates to some embodiments of general formulas (Ia), (Ib), (Id), or (Ie). Selected from , or .

[0075] This invention relates to some embodiments of the general formula (If). Selected from or .

[0076] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 3 Each is independently selected from H, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0077] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 3 Each is independently selected from H, halogen, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-4 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted, wherein the heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0078] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 3 Each of the following is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0079] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 3 Each of the following groups is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, cyano.

[0080] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 3 Each is independently selected from H, methyl, or ethyl.

[0081] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 2 Selected from halogens, C 1-6 Alkyl or C 1-6 Alkoxy group, wherein the alkyl group is optionally further substituted with 0 to 4 substituents selected from H, D, halogen, OH, cyano or NH2.

[0082] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 2 Selected from halogens, C 1-4 Alkyl or C 1-4 Alkoxy group, wherein the alkyl group is optionally further substituted with 0 to 4 substituents selected from H, D, halogen, OH, cyano or NH2.

[0083] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 2The group is selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, cyano, or NH2.

[0084] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 2 Selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy.

[0085] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 2 Each is independently selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl.

[0086] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 2 Selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl.

[0087] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Id-5), (Ie), or (If), R 2 Each is independently selected from CD3, CHD2, and CH2D.

[0088] This invention relates to some embodiments of general formulas (Id-1) and (Id-2), R 2 Selected from F, Cl, Br, I, C 1-4 alkyl.

[0089] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6 Alkyl or C 1-6Alkyl group, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0090] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl or C 1-4 alkoxy groups, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0091] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 6 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0092] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 6 Each of the following groups is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, or -CH2OH.

[0093] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 6 Each is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy.

[0094] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 6 Each is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, and isopropyl.

[0095] This invention relates to some embodiments of general formula (I), where R is selected from H, C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 Alkyl groups are substituted.

[0096] This invention relates to some embodiments of general formula (I), where R is selected from H, C 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0097] The present invention relates to some embodiments of general formula (I), wherein R is selected from H, methyl, ethyl, propyl or isopropyl, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl or CF3.

[0098] This invention relates to some embodiments of general formula (I), where R is selected from H.

[0099] This invention relates to some embodiments of general formulas (I), (Ib), (Ic), (Id), (Id-1), (Id-3), (Id-4) or (If), R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0100] This invention relates to some embodiments of general formulas (I), (Ib), (Ic), (Id), (Id-1), (Id-3), (Id-4) or (If), R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl, C 1-4Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-6 A carbocyclic or 3- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0101] This invention relates to some embodiments of general formulas (I), (Ib), (Ic), (Id), (Id-1), (Id-3), (Id-4) or (If), R 7 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, Ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxazine, oxazine-butyl, oxazine-pentyl, oxazine-hexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0102] This invention relates to some embodiments of general formulas (I), (Ib), (Ic), (Id), (Id-1), (Id-3), (Id-4) or (If), R 7 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl The pyridyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, propynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrrolidinyl.

[0103] This invention relates to some embodiments of general formulas (I), (Ib), (Ic) or (If), R 7Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH 2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxygen Heterocyclohexyl, pyrazolyl, pyrroloyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein cyclopropyl, cyclobutyl, cyclopentyl, azirrobutyl, pyrroloalkyl, piperidinyl, morpholinyl, piperazinyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroloyl, imidazolyl, furanyl, thiophenyl, ... The thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, propynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrrolidinyl; This invention relates to some embodiments of general formula (I), R 7 Selected from R 7A R 7B Or R 7a .

[0104] This invention relates to some embodiments of general formula (I), R 7 Selected from R 7’ .

[0105] This invention relates to some embodiments of general formula (Id-1), R 7 Selected from H, methoxymethyl, methoxyethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, oxacyclobutyl, oxacyclopentyl, and oxacyclohexyl.

[0106] This invention relates to some embodiments of general formula (Id-1), R 7The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziroxybutyl, aziroxypentyl, aziroxyhexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziroxybutyl, aziroxypentyl, aziroxyhexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, and methoxy.

[0107] This invention relates to some embodiments of general formula (Id-2), where 2 R 7B Together with the carbon atoms connected to it, they form the following ring: , , , , , , .

[0108] This invention relates to some embodiments of general formula (Id-1), R 7 Selected from methoxymethyl, methoxyethyl, C 2-4 alkynyl group, C 3-6 Cycloalkyl or 4- to 7-membered heterocyclic compounds.

[0109] This invention relates to some embodiments of general formula (Id-2), where 2 R 7B Together with the carbon atoms connected thereto, they form 4 to 7-membered heterocycles (preferably 4 to 6-membered heterocycles).

[0110] This invention relates to some embodiments of general formula (Ia), R 7A Selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridyl, pyrazinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0111] This invention relates to some embodiments of general formula (Ia), R 7A Selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl, pyrazolyl, pyrroleyl, or imidazoleyl The group may be further substituted with 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl or cyclobutyl.

[0112] This invention relates to some embodiments of general formula (Ia), R 7A Selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -CH2CH2OCH3, -CH2CF3, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, or imidazolyl.

[0113] This invention relates to some embodiments of general formula (Ie), R 7a Each is independently selected from R d F, Cl, Br, I, vinyl, ethynyl, propynyl, propyrynyl, -C(=O)R 1d -S(=O)2R 1dCyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the vinyl, ethynyl, propynyl, propargyl, or cyclopropyl groups are... Cyclobutyl, cyclopentyl, azacyclobutyl, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl may optionally be further composed of 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0114] This invention relates to some embodiments of general formula (Ie), R 7a Each is independently selected from R d F, Cl, Br, I, vinyl, ethynyl, propynyl, propyrynyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the vinyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, pyrroleyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, pyrroleyl, piperidinyl, py ... Cyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroloyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, aziridine or pyrroloalkyl.

[0115] This invention relates to some embodiments of general formula (Ie), R 7a Selected from F, Cl, Br, I, CF3, -CH2F, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O) -phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl.

[0116] This invention relates to some embodiments of general formula (Ie), R d Each of the following is independently selected from methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy groups are further selected by one to three groups selected from halogen, ethynyl, and C. 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 Substituents of cycloalkyl or 3 to 8-membered heterocyclic groups.

[0117] This invention relates to some embodiments of general formula (Ie), R d Each of the following groups is independently selected from methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy groups are further substituted by 1 to 3 substituents selected from F, Cl, Br, I, ethynyl, methoxy, ethoxy, CF3, -CH2F, cyclopropyl, cyclobutyl, aziridine, or pyrrolidinyl.

[0118] This invention relates to some embodiments of general formulas (I), (Id), (Id-1), and (Id-2), in which two R7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0119] This invention relates to some embodiments of general formulas (I), (Id), (Id-1), and (Id-2), in which two R 7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0120] This invention relates to some embodiments of general formulas (I), (Id), (Id-1), and (Id-2), in which two R 7 Together with the carbon atom attached thereto, it forms an oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group, wherein the oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group is optionally further composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0121] This invention relates to some embodiments of formula (I) or (Ib), where R at adjacent positions 6 With R 7 Double bonds can be formed.

[0122] This invention relates to some embodiments of general formulas (I), (Id), (Id-1), and (Id-2), in which two R 6 Together with the atoms attached to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0123] This invention relates to some embodiments of general formulas (I), (Id), (Id-1), and (Id-2), in which two R 6 Together with the atoms attached to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0124] This invention relates to some embodiments of general formula (I) or (Id), in which two R 6 Together with the atoms attached to it, it forms cyclobutyl, cyclopentyl, cyclohexyl, oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine.

[0125] This invention relates to some embodiments of general formula (I), Selected from , or , It indicates a single bond or a double bond, and contains only one double bond.

[0126] This invention relates to some embodiments of general formula (I), Selected from , , , or Above it is R 4 Connected.

[0127] This invention relates to some embodiments of general formulas (I), (Ic), (Id), (Id-1), (Id-2), or (If). Selected from the excerpt in the table below, above which is R 4 Connected, .

[0128] This invention relates to some embodiments of general formulas (Id-3) and (Id-4), wherein ring B is selected from 3-6 membered heterocyclic groups, wherein the heterocyclic group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, -C(=O)R. 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0129] This invention relates to some embodiments of general formulas (Id-3) and (Id-4), wherein ring B is selected from 3-6 membered heterocyclic alkyl groups, wherein the heterocyclic alkyl group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group or heteroalkyl group contains 1 to 4 heteroatoms selected from O, S or N.

[0130] This invention relates to some embodiments of general formulas (Id-3) and (Id-4), wherein ring B is selected from oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine, wherein the oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0131] This invention relates to some embodiments of general formula (Id-3), wherein ring B is selected from oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine, wherein the oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, CF3, OH, =O, cyano, NH2, -C(=O)CH3, methyl, ethyl, methoxy, or ethoxy.

[0132] This invention relates to some embodiments of general formula (Id-4), R 6 Each element is independently selected from H, halogens, OH, NH2, and C. 1-4 Alkyl or C 1-4 Alkyl groups, wherein the alkyl or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0133] This invention relates to some embodiments of general formula (Id-4), R 6 Each is independently selected from H, F, Cl, Br, CF3, methyl, and ethyl.

[0134] This invention relates to some embodiments of general formula (Id-4), R 7 Selected from C 2-4 alkynyl group, C 3-6 Carbocyclic groups, 3- to 8-membered heterocyclic groups, R 7 Selected from H, halogens, OH, -NR1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d The alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0135] This invention relates to some embodiments of general formula (Id-4), R 7 Selected from C 2-4 alkynyl, phenyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycloalkyl or 5- to 6-membered heteroaryl, R 7 Selected from H, halogens, OH, -NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)C 1-4 Alkyl group, -S(=O)2C 1-4 Alkyl groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, phenyl, cycloalkyl, heteroaryl, or heterocycloalkyl group is optionally further selected from 0 to 4 elements chosen from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heteroalkyl, heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0136] This invention relates to some embodiments of general formula (Id-4), R 7 Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R 7 R 7 When substituted, it may be further replaced by 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0137] This invention relates to some embodiments of general formula (Id-4), R 7Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R 7 R 7 When substituted, it may optionally be further substituted with 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine.

[0138] This invention relates to some embodiments of general formula (Id-4), R 7 Selected from ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, and cyclopentyl, wherein the propynyl, propynyl, cyclopropyl, cyclobutyl, and cyclopentyl groups are optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, methyl, ethyl, methoxy, ethoxy, and cyclopropyl, R 7 The group is selected from H, F, OH, NH2, methyl, ethyl, methoxy, ethoxy, wherein the methyl, ethyl, methoxy, ethoxy group is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, methyl, ethyl, methoxy, or ethoxy.

[0139] The present invention relates to some embodiments of general formulas (Id-3) and (Id-4), wherein X1 is selected from N or CH, X2 is selected from N or CH, wherein the CH is optionally substituted with one methyl or ethyl molecule.

[0140] This invention relates to some embodiments of general formulas (Id-3) and (Id-4), where X1 is selected from CH and X2 is selected from CH.

[0141] This invention relates to some embodiments of general formula (Id-4). Choose from one of the following structures: .

[0142] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4 Selected from C 5-12 Carbocyclic groups, 5- to 12-membered heterocyclic groups, C 6-12 aryl or 5 to 12-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The substitution, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0143] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4 Selected from C 5-7 Monocyclic carbocyclic group, C 5-12 fused carbonyl group, C 5-12 Spirocyclic carbocyclic group, C 5-12 5- to 7-membered bridged carbide ring groups, 5- to 12-membered monocyclic heterocyclic groups, 5- to 12-membered fused ring heterocyclic groups, 5- to 12-membered spirocyclic heterocyclic groups, or 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N.

[0144] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4 Selected from C 5-6 Monocyclic carbocyclic group, C 5-10 fused carbonyl group, C 5-11 Spirocyclic carbocyclic group, C 5-12 5- to 6-membered bridged carbide ring groups, 5- to 10-membered fused ring heterocyclic groups, 5- to 11-membered spirocyclic heterocyclic groups, 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N.

[0145] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4 Each of the following groups is independently selected from cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrazolyl, pyrimidinyl, or naphthidinyl, wherein the cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrimidinyl, or naphthidinyl is optionally further divided by 0 to 4 R groups. 5 replace.

[0146] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4 Each independently selected , , , , or .

[0147] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4 Each independently selected , , .

[0148] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4 Selected from , , wherein R 4 It may be further substituted with 0, 1, 2 or 3 substituents selected from F, Cl, Br, I, OH, cyano, methyl, ethyl, methoxy or ethoxy.

[0149] This invention relates to some embodiments of general formulas (Id-1), (Id-2), (Id-3), and (Id-4), R 4 Selected from , wherein R 4 The radical can be further selected from 0, 1, 2 or 3 of the following groups: F, Cl, Br, I, OH, cyano, C. 1-4 Alkyl, C 1-4 The alkoxy group is replaced by a substituent.

[0150] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl or 4- to 12-membered heterocyclic groups, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N.

[0151] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N.

[0152] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 3-6 Cycloalkyl or 4- to 6-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N.

[0153] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 5 Each is independently selected from H, F, Cl, Br, I, OH, cyano, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -COOH, -CH2OH, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2OH, , , -C(=O)NH2, -C(=O)NHOH, -S(=O)2NHC(=O)CH3, -C(=O)NHS(=O)2CH3, pyrazolyl, tetrazolyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, pyrazolyl, tetrazolyl are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, or cyclobutyl.

[0154] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1c Selected from OH, NH2, C 1-6 Alkoxy, NHC 1-4 Alkyl or N(C) 1-4 Alkyl)2.

[0155] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1c Selected from OH, NH2, C 1-4 Alkoxy, NHC 1-4 Alkyl or N(C) 1-4 Alkyl)2.

[0156] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1c Selected from OH, NH2, methoxy, ethoxy, NHCH3, N(CH3)2.

[0157] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4a R 4b Each group is independently selected from H, OH, cyano, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0158] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4a R 4b Each group is independently selected from H, OH, cyano, NH2, and C. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10 aryl or 5- to 6-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0159] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4c R 4d Each is independently selected from H, OH, and C. 1-6 Alkyl, C 1-6 Alkoxy, -NR 1a R 1b -OR 1d -C 3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0160] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4c R 4d Each is independently selected from H, OH, and C. 1-4 Alkyl, C 1-4 Alkoxy, -NR 1a R 1b -OR 1d C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N.

[0161] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 12-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0162] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy or C 3-6 Cycloalkyl groups, 5- to 10-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0163] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4a R 4b R 4c R 4d Each of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0164] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4a R 4b R 4c R 4d Each of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, or CF3.

[0165] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 4e R 4f Each is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl.

[0166] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1d Each is independently selected from H and C 1-6 Alkyl, C 3-8 A carbocyclic or 4- to 10-membered heterocyclic group, wherein the alkyl, carbocyclic, or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0167] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1d Each is independently selected from H and C 1-4 Alkyl, C 3-6A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, carbocyclic or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0168] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1d Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl is optionally selected from 0 to 4 of the following: H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0169] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1d Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl is optionally substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, azircyclobutyl, or pyrrolidinyl.

[0170] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1d Each is independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolyl, phenyl, -CH2-cyclopropyl or -CH2-cyclobutyl.

[0171] This invention relates to some embodiments of general formula (I), R 8 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0172] This invention relates to some embodiments of general formula (I), R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0173] This invention relates to some embodiments of general formula (I), R 8 R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthioyl, wherein the alkyl, alkenyl, alkoxy, or alkylthioyl group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0174] This invention relates to some embodiments of general formula (I), R 8 R 9 Or R 10 Each is independently selected from H, F, Cl, Br, I, OH, cyano, CF3, NH2, methyl, and ethyl.

[0175] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1a R 1b Each is independently selected from H and C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituted group is a cycloalkyl or a 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N.

[0176] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R1a R 1b Each is independently selected from H and C 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0177] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1a R 1b Each is independently selected from H, methyl, ethyl, propyl, or isopropyl, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl groups are substituted.

[0178] This invention relates to some embodiments of general formulas (I), (Ia), (Ib), (Ic), (Id), (Id-1), (Id-2), (Id-3), (Id-4), (Ie), or (If), R 1a R 1b Each of the groups is independently selected from H, methyl, ethyl, propyl, or isopropyl, wherein the methyl, ethyl, propyl, or isopropyl groups are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, and -CH2OH.

[0179] This invention relates to some embodiments of general formula (I), where Y is selected from C(R) 7 )2, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, cyano C 1-6 Alkyl or unsubstituted C 1-6 alkoxy group, and two R groups 7 For the carbon atom attached to it to not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1) R 1 Selected from C 2-6 alkynyl group, C 3-6 Cycloalkyl-substituted C 1-6 Alkyl, 3- to 8-membered heterocyclic substituted C 1-6 Alkyl, -WC 3-8 A carbocyclic or -W-4 to 10-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N.

[0180] This invention relates to some embodiments of general formula (I), where Y is selected from C(R) 7 )2, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-4 Alkyl, hydroxyl C 1-4 Alkyl, cyano C 1-4 Alkyl or unsubstituted C 1-4 alkoxy group, and two R groups 7 For the carbon atom attached to it to not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1)R 1 Selected from C 2-4 alkynyl group, C 3-6Cycloalkyl-substituted C 1-4 Alkyl, 3- to 8-membered heterocyclic substituted C 1-4 Alkyl, -WC 3-6 A carbocyclic or -W-4 to 8-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic group is replaced by a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N.

[0181] This invention relates to a pharmaceutical composition comprising the compound or its stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal, and a pharmaceutically acceptable carrier.

[0182] This invention relates to the use of a compound or its stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal, or a pharmaceutical composition or formulation of the present invention in the preparation of a medicament for treating diseases related to complement factor B activity or expression levels, preferably in the preparation of a medicament for kidney diseases.

[0183] This invention relates to a pharmaceutical composition or pharmaceutical formulation comprising a therapeutically effective amount of the compound or its stereoisomer, deuterated derivative, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal, and pharmaceutical excipient. The pharmaceutical composition may be in unit dosage form (the amount of the active ingredient in a unit dosage form is also referred to as a "dosage strength").

[0184] The present invention also provides a method for treating diseases in mammals, comprising administering to the mammal a therapeutically effective amount of the compound or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals or pharmaceutical compositions described herein. In some embodiments, the mammals described in the present invention include humans.

[0185] The term "effective amount" or "therapeutic effective amount" as used in this application means that administering a sufficient amount of the compound disclosed in this application will alleviate, to some extent, one or more symptoms of the disease or condition being treated (e.g., kidney disease). In some embodiments, the result is a reduction and / or mitigation of the signs, symptoms, or causes of the disease, or any other desired alteration of the biological system. For example, an "effective amount" for therapeutic use is the amount of a composition comprising the compound disclosed in this application required to provide a clinically significant reduction in disease symptoms.Examples of therapeutically effective doses include, but are not limited to, 1-600 mg, 2-600 mg, 3-600 mg, 4-600 mg, 5-600 mg, 6-600 mg, 10-600 mg, 20-600 mg, 25-600 mg, 30-600 mg, 40-600 mg, 50-600 mg, 60-600 mg, 70-600 mg, 75-600 mg, 80-600 mg, 90-600 mg, 100-600 mg, 200-600 mg, 1-500 mg, 2-500 mg, 3-500 mg, 4-500 mg, 5-500 mg, 6... -500mg, 10-500mg, 20-500mg, 25-500mg, 30-500mg, 40-500mg, 50-500mg, 60-500mg, 70-500mg, 75-500mg, 80-500mg, 90-500mg, 100-5 00mg, 125-500mg, 150-500mg, 200-500mg, 250-500mg, 300-500mg, 400-500mg, 5-400mg, 10-400mg, 20-400mg, 25-400mg, 30-400mg, 40- 400mg,50-400mg,60-400mg,70-400mg,75-400mg,80-400mg,90-400mg,100-400mg,125-400mg,150-400mg,200-400mg,250-400mg,3 00-400mg, 1-300mg, 2-300mg, 5-300mg, 10-300mg, 20-300mg, 25-300mg, 30-300mg, 40-300mg, 50-300mg, 60-300mg, 70-300mg, 75-300m g, 80-300mg, 90-300mg, 100-300mg, 125-300mg, 150-300mg, 200-300mg, 250-300mg, 1-200mg, 2-200mg, 5-200mg, 10-200mg, 20-200mg , 25-200mg, 30-200mg, 40-200mg, 50-200mg, 60-200mg, 70-200mg, 75-200mg, 80-200mg, 90-200mg, 100-200mg, 125-200mg, 150-200mg.

[0186] In some embodiments, the pharmaceutical composition includes, but is not limited to, 1-600 mg, 20-400 mg, 25-200 mg, 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 300 mg of the compound of the present invention or its stereoisomers, deuterated products, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals.

[0187] In some embodiments, the pharmaceutical composition can be formulated for specific routes of administration, such as oral administration, parenteral administration, and rectal administration. Additionally, the pharmaceutical compositions of the present invention can be formulated in solid form (including but not limited to capsules, tablets, pills, granules, powders, or suppositories) or liquid form (including but not limited to solutions, suspensions, or emulsions).

[0188] A method for treating a disease in a mammal, the method comprising administering to a subject a therapeutically effective amount of the compound of the present invention or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals, preferably 1-600 mg, wherein the disease is preferably a kidney disease.

[0189] A method for treating a disease in mammals, the method comprising administering a medicament, the present invention compound or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, to a subject at a daily dose of 1-800 mg / day, said daily dose being a single dose or multiple doses, and in some embodiments, the daily dose including but not limited to 10-800 mg / day, 25-800 mg / day, 50-800 mg / day, 100-800 mg / day, etc. In some embodiments, the daily dose includes, but is not limited to, 10 mg / day, 20 mg / day, 25 mg / day, 50 mg / day, 100 mg / day, 125 mg / day, 150 mg / day, 200 mg / day, 400 mg / day, 600 mg / day, and 800 mg / day.

[0190] This invention relates to a kit that may include a single-dose or multi-dose composition comprising the compound of the present invention or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the amounts of the compound of the present invention or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals are the same as those in the aforementioned pharmaceutical composition.

[0191] In this invention, the amounts of the compound or its stereoisomers, deuterated products, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or eutectics of this invention are converted in each case as free bases.

[0192] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0193] The carbon, hydrogen, oxygen, sulfur, nitrogen, or F, Cl, Br, I involved in the groups and compounds described in this invention include their isotopes, and the carbon, hydrogen, oxygen, sulfur, or nitrogen involved in the groups and compounds described in this invention may optionally be further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 12 C 13 C and 14 C, the isotopes of hydrogen include protium (H), deuterium (D, also called heavy hydrogen), and tritium (T, also called superheavy hydrogen), and the isotopes of oxygen include 16 O、 17 O and 18 O, isotopes of sulfur include 32 S, 33 S, 34 S and 36 S, nitrogen isotopes include 14 N and 15 N, isotopes of fluorine include 17 F and 19 F, isotopes of chlorine include 35 Cl and 37 Cl, isotopes of bromine include 79 Br and 81 Br.

[0194] "Halogen" refers to F, Cl, Br or I.

[0195] "Halogen-substituted" refers to substitution with F, Cl, Br, or I, including but not limited to 1 to 10 substituents selected from F, Cl, Br, or I, 1 to 6 substituents selected from F, Cl, Br, or I, and 1 to 4 substituents selected from F, Cl, Br, or I. "Halogen-substituted" is abbreviated as "halogenated".

[0196] "alkyl" refers to a substituted or unsubstituted straight-chain or branched saturated aliphatic hydrocarbon group, including but not limited to alkyl groups with 1 to 20 carbon atoms, alkyl groups with 1 to 8 carbon atoms, alkyl groups with 1 to 6 carbon atoms, and alkyl groups with 1 to 4 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 their various branched isomers. Alkyl groups used herein are defined in accordance with this definition. Alkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0197] "Heteroalkyl" refers to a substituted or unsubstituted alkyl group in which one or more carbon atoms (including but not limited to 2, 3, 4, 5, or 6) are replaced by heteroatoms (including but not limited to N, O, or S). Non-limiting examples include -X(CH2)vX(CH2)vX(CH2)vH (v is an integer from 1 to 5, X is independently selected from bonds or heteroatoms, heteroatoms include but are not limited to N, O, or S, and at least one X is selected from heteroatoms, and the N or S in the heteroatoms can be oxidized to various oxidation states). Heteroalkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0198] "Alkylene" refers to substituted or unsubstituted straight-chain and branched divalent saturated hydrocarbon groups, including -(CH2). v - (v is an integer from 1 to 10), alkylene examples include, but are not limited to, methylene, ethylene, propylene, and butylene.

[0199] "Heteroalkylene" refers to a substituted or unsubstituted alkylene group in which one or more carbon atoms (including but not limited to 2, 3, 4, 5, or 6) are replaced by heteroatoms (including but not limited to N, O, or S). Non-limiting examples include -X(CH2)vX(CH2)vX(CH2)v-, where v is an integer from 1 to 5, and each X is independently selected from N, O, or S, and at least one X is selected from N, O, or S.

[0200] "Cycloalkyl" refers to a substituted or unsubstituted saturated carbocyclic hydrocarbon group, typically having 3 to 10 carbon atoms. Non-limiting examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. The cycloalkyl group used herein is defined as described above. Cycloalkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0201] "Heterocyclic alkyl" refers to a substituted or unsubstituted saturated cyclic hydrocarbon group containing heteroatoms, including but not limited to 3 to 10 atoms or 3 to 8 atoms, containing 1 to 3 heteroatoms selected from N, O, or S. The selectively substituted N or S in the ring of the heterocyclic alkyl group can be oxidized to various oxidation states. Heterocyclic alkyl groups can be attached to heteroatoms or carbon atoms, and can be attached to aromatic or non-aromatic rings. They can be connected to bridged or spirocyclic rings. Non-limiting examples include epoxyethyl, azirropropyl, oxacyclobutyl, azirrobutyl, tetrahydrofuranyl, and tetrahydro-2-dihydrocarbonyl. H -Pyranyl, dioxolane, dioxane, pyrrolidinyl, piperidinyl, imidazoalkyl, oxazolidinyl, oxazinyl, morpholinyl, hexahydropyrimidinyl, piperazinyl. Heterocyclic alkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0202] "Alkenyl" refers to a substituted or unsubstituted straight-chain and branched unsaturated hydrocarbon group having at least one, typically one, two, or three, carbon-carbon double bonds. The main chain has, but is not limited to, 2 to 10, 2 to 6, or 2 to 4 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, etc. Alkenyl groups include 1-butenyl, 2-methyl-3-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 1-octenyl, 3-octenyl, 1-nonenyl, 3-nonenyl, 1-decenyl, 4-decenyl, 1,3-butadiene, 1,3-pentadiene, 1,4-pentadiene, and 1,4-hexadiene, etc. The alkenyl groups used in this article are defined in accordance with this definition. Alkenyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0203] "Alynyl" refers to a substituted or unsubstituted straight-chain and branched monovalent unsaturated hydrocarbon group having at least one, typically one, two, or three, carbon-carbon triple bonds. The main chain comprises 2 to 10 carbon atoms, including but not limited to having 2 to 6 carbon atoms on the main chain, or 2 to 4 carbon atoms on the main chain. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3... -Pentynyl, 4-pentynyl, 1-methyl-1-butynyl, 2-methyl-1-butynyl, 2-methyl-3-butynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-1-pentynyl, 2-methyl-1-pentynyl, 1-hepynyl, 2-hepynyl, 3-hepynyl, 4-hepynyl, 1-octyynyl, 3-octyynyl, 1-nonynyl, 3-nonynyl, 1-decynyl, 4-decynyl, etc. The ynyl group can be monovalent, divalent, trivalent, or tetravalent.

[0204] "Alkoxy" refers to a substituted or unsubstituted -O-alkyl group. Non-limiting examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexoxy, cyclopropoxy, and cyclobutoxy.

[0205] "Carbocyclic group" or "carbocyclic ring" refers to a substituted or unsubstituted aromatic ring or a substituted or unsubstituted saturated or unsaturated non-aromatic ring. The aromatic or non-aromatic ring can be a 3- to 8-membered monocyclic, 4- to 12-membered bicyclic, or 10- to 15-membered tricyclic system. The carbocyclic group can be attached to the aromatic or non-aromatic ring, which may be selected as a monocyclic, bridged, or spirocyclic ring. Non-limiting examples include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, 1-cyclopentyl-1-enyl, 1-cyclopentyl-2-enyl, 1-cyclopentyl-3-enyl, cyclohexyl, 1-cyclohexyl-2-enyl, 1-cyclohexyl-3-enyl, cyclohexenyl, benzene ring, naphthalene ring, etc. , , , or "Carbocyclic group" or "carbon ring" can be monovalent, divalent, trivalent or tetravalent.

[0206] "Heterocyclic group" or "heterocyclic" refers to a substituted or unsubstituted aromatic ring or a substituted or unsubstituted saturated or unsaturated non-aromatic ring. The aromatic or non-aromatic ring can be a 3- to 8-membered monocyclic ring, a 4- to 12-membered bicyclic ring, or a 10- to 15-membered tricyclic system, and contains one or more (including but not limited to 2, 3, 4, or 5) heteroatoms selected from N, O, or S. The N and S selectively substituted in the ring of the heterocyclic group can be oxidized to various oxidation states. Heterocyclic groups can be attached to heteroatoms or carbon atoms, and can be attached to aromatic or non-aromatic rings. They can be connected to bridged or spirocyclic rings. Non-limiting examples include epoxyethyl, azirropropyl, oxacyclobutyl, azirrobutyl, 1,3-dioxopentyl, 1,4-dioxopentyl, 1,3-dioxohexyl, azirroheptyl, pyridinyl, furanyl, thiophene, pyranyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, piperidinyl, morpholinyl, thiomorpholinyl, 1,3-dithial, dihydrofuranyl, dihydropyranyl, dithiapentylcycloalkyl, tetrahydro Furanyl, tetrahydropyrrolyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydropyranyl, benzimidazolyl, benzopyridyl, pyrrolopyridyl, benzodihydrofuranyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl, pyrazinyl, indazolyl, benzothiophene, benzofuranyl, benzopyrrolyl, benzimidazolyl, benzothiazolyl, benzooxazolyl, benzopyridyl, benzopyrimidinyl, benzopyrazinyl, piperazinyl, azabicyclo[3.2.1]octyl, azabicyclo[5.2.0]nonyl, oxatricyclo[5.3.1.1]dodecyl, azaadamantyl, oxaspiro[3.3]heptyl, , , , , , , , , , , , , or "Heterocyclic group" or "heterocyclic ring" can be monovalent, divalent, trivalent or tetravalent.

[0207] "Spirocyclic" or "spirocyclic group" refers to a polycyclic group in which substituted or unsubstituted monocyclic rings share a single atom (called a spiro atom). The number of ring atoms in a spirocyclic system includes, but is not limited to, 5 to 20, 6 to 14, 6 to 12, or 6 to 10. One or more rings may contain 0 or more (including but not limited to 1, 2, 3, or 4) double bonds, and optionally may contain 0 to 5 double bonds selected from N, O, or S (=O). n heteroatoms.

[0208] "Spirocyclic" or "spirocyclic group" can be monovalent, divalent, trivalent or tetravalent.

[0209] "Burying" or "burying group" refers to a polycyclic group in which each ring in the system shares a pair of adjacent atoms with the other rings in the system. One or more rings may contain zero or more (including but not limited to 1, 2, 3 or 4) double bonds and may be substituted or unsubstituted. Each ring in the burying system may contain 0 to 5 heteroatoms or groups containing heteroatoms (including but not limited to those selected from N, S (=O)). n Or O, where n is 0, 1, or 2). The number of ring atoms in a cyclic system includes, but is not limited to, 5 to 20, 5 to 14, 5 to 12, and 5 to 10. Non-limiting examples include: , , , A "cyclic compound" or "cyclic base" can be monovalent, divalent, trivalent, or tetravalent.

[0210] A “bridged ring” or “bridged ring group” refers to a substituted or unsubstituted polycyclic group containing any two atoms that are not directly connected, and may contain zero or more double bonds. In a cyclic system, any ring may contain 0 to 5 groups selected from heteroatoms or containing heteroatoms (including but not limited to N, S(=O)n, or O, where n is 0, 1, or 2). The number of ring atoms includes, but is not limited to, 5 to 20, 5 to 14, 5 to 12, or 5 to 10. Non-limiting examples include… , , , , , cuboethane, adamantane. "Bridged ring" or "bridged ring group" can be monovalent, divalent, trivalent or tetravalent.

[0211] "Carbon spirocyclic", "spirocyclic carbocyclic", "spirocarbon cyclic", or "carbon spirocyclic" refers to a spirocyclic system composed only of carbon atoms. The definitions of "carbon spirocyclic", "spirocyclic carbocyclic", "spirocarbon cyclic", or "carbon spirocyclic" used in this article are consistent with those for spirocyclic systems.

[0212] "Carbon fused ring", "fused cyclic carbocyclic group", "fused carbon cyclic group" or "carbon fused cyclic group" refers to a "fused ring" composed only of carbon atoms. The definitions of "carbon fused ring", "fused cyclic carbocyclic group", "fused carbon cyclic group" or "carbon fused cyclic group" used in this article are consistent with those of fused rings.

[0213] "Carbon-bridged ring," "bridged ring carbonyl group," "bridged carbonyl group," or "carbon-bridged ring group" refers to a "bridged ring" composed only of carbon atoms in a ring system. The definitions of "carbon-bridged ring," "bridged ring carbonyl group," "bridged carbonyl group," or "carbon-bridged ring group" used in this article are consistent with those for bridged rings.

[0214] "Hybrid monocyclic", "monocyclic heterocyclic group" or "hybrid monocyclic group" refers to the "heterocyclic group" or "heterocyclic" of a monocyclic system. The definition of heterocyclic group, "monocyclic heterocyclic group" or "hybrid monocyclic group" in this article is consistent with that of heterocycle.

[0215] "Hypercyclic ring", "hypercyclic cyclic group", "fused cyclic heterocyclic group" or "hypercyclic cyclic group" refers to a "fused ring" containing heteroatoms. The definitions of heterocyclic ring, "hypercyclic cyclic group", "fused cyclic heterocyclic group" or "hypercyclic cyclic group" used in this article are consistent with those of fused ring.

[0216] "Heterospirocyclic", "heterospirocyclic group", "spirocyclic heterocyclic group" or "heterospirocyclic group" refers to a "spirocycle" containing heteroatoms. The definitions of heterospirocyclic, "heterospirocyclic group", "spirocyclic heterocyclic group" or "heterospirocyclic group" used in this article are consistent with those for spirocycles.

[0217] "Hybrid-bridged ring," "hybrid-bridged ring-based group," "bridged-ring heterocyclic group," or "hybrid-bridged ring-based group" refers to a "bridged ring" containing heteroatoms. The terms "hybrid-bridged ring," "hybrid-bridged ring-based group," "bridged-ring heterocyclic group," or "hybrid-bridged ring-based group" used in this article are defined in the same way as "bridged ring."

[0218] "Aryl" or "aromatic ring" refers to a substituted or unsubstituted aromatic hydrocarbon group having a monocyclic or fused ring. The number of ring atoms in the aromatic ring includes, but is not limited to, 6 to 18, 6 to 12, or 6 to 10 carbon atoms. The aryl ring can be fused to a saturated or unsaturated carbon ring or heterocycle, wherein the ring connected to the parent structure is the aryl ring. Non-limiting embodiments include benzene rings, naphthalene rings, etc. The "aryl" or "aryl ring" can be monovalent, divalent, trivalent, or tetravalent. When it is divalent, trivalent, or tetravalent, the linking site is located on the aryl ring.

[0219] "Heteroaryl" or "heteroary ring" refers to a substituted or unsubstituted aromatic hydrocarbon group containing 1 to 5 heteroatoms or a group containing heteroatoms (including but not limited to N, O, or S (=O)). n (where n is 0, 1, or 2), and the number of ring atoms in the heteroaryl ring includes, but is not limited to, 5 to 15, 5 to 10, or 5 to 6. Non-limiting embodiments of heteroaryl groups include, but are not limited to, pyridyl, furanyl, thiophene, pyridyl, pyranyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, benzopyrazole, benzimidazole, benzopyridine, pyrrolopyridine, etc. The heteroaryl ring can be fused to a saturated or unsaturated carbon ring or heterocycle, wherein the ring connected to the parent structure is a heteroaryl ring. Non-limiting embodiments include... and The definition of heteroaryl groups used in this paper is consistent with that in this paper. Heteroaryl groups can be monovalent, divalent, trivalent, or tetravalent. When they are divalent, trivalent, or tetravalent, the linking site is located on the heteroaryl ring.

[0220] "5-membered fused heteroaromatic ring" refers to a 5-membered fused heteroaromatic ring in which at least one of the two fused rings contains one or more heteroatoms (including but not limited to O, S or N), and the entire group is aromatic. Non-limiting examples include pyrrolopyrrolo ring, pyrazolopyrrolo ring, pyrazolopyrazole ring, pyrrolofuran ring, pyrazolofuran ring, pyrrolothiophene ring, and pyrazolothiophene ring.

[0221] "5-6-membered heteroaryl ring" refers to a 5-6-membered fused heteroaryl ring in which at least one of the two fused rings contains one or more heteroatoms (including but not limited to O, S or N), and the entire group is aromatic. Non-limiting examples include benzo5-membered heteroaryl and 6-membered heteroaryl-5-membered heteroaryl ring.

[0222] "Substituted" or "substituted" means substituted by one or more (including but not limited to 2, 3, 4, or 5) substituents, including but not limited to H, F, Cl, Br, I, alkyl, cycloalkyl, alkoxy, haloalkyl, thiol, hydroxyl, nitro, mercapto, amino, cyano, isocyano, aryl, heteroaryl, heterocyclic, bridged cyclic, spirocyclic, fused cyclic, hydroxyalkyl, =O, carbonyl, aldehyde, carboxylic acid, formate, -(CH2). m -C(=O)-R a -O-(CH2) m -C(=O)-R a -(CH2) m -C(=O)-NR b R c -(CH2) m S(=O) n R a -(CH2) m -Alkenyl-R a OR d Or -(CH2) m -alkynyl-R a (where m and n are 0, 1, or 2), arylthio, thiocarbonyl, silyl, or -NR b R c Groups, wherein R b With R c Independently selected from H, hydroxyl, amino, carbonyl, alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, heteroaryl, sulfonyl, trifluoromethanesulfonyl, R b With R c It can form five- or six-membered cycloalkyl or heterocyclic groups.

[0223] "Contains 1 to 5 heteroatoms selected from O, S or N" means that it contains 1, 2, 3, 4 or 5 heteroatoms selected from O, S or N.

[0224] "Substituted with 0 to X substituents" means substituted by 0, 1, 2, 3...X substituents, where X is any integer selected from 1 to 10. For example, "Substituted with 0 to 4 substituents" means substituted by 0, 1, 2, 3, or 4 substituents. Similarly, "Substituted with 0 to 5 substituents" means substituted by 0, 1, 2, 3, 4, or 5 substituents. And "The heterobridged ring may be further substituted by 0 to 4 substituents selected from H or F" means the heterobridged ring may be further substituted by 0, 1, 2, 3, or 4 substituents selected from H or F.

[0225] The XY-membered rings (where X is an integer less than Y and greater than 3, and Y is any integer between 4 and 12) include rings of the X+1, X+2, X+3, X+4…Y-membered types. These rings include heterocyclic rings, carbocyclic rings, aromatic rings, aryl groups, heteroaryl groups, cycloalkyl groups, heteromonocyclic rings, heterofused rings, heterospirocyclic rings, or heterobridged rings. For example, "4-7-membered heteromonocyclic rings" refers to heteromonocyclic rings of 4, 5, 6, or 7 members, and "5-10-membered heterofused rings" refers to heterofused rings of 5, 6, 7, 8, 9, or 10 members.

[0226] "Optional" or "optionally" means that the event or environment described below may but does not have to occur, and the description includes the possibility or possibility that the event or environment may or may not occur. For example, "optionally substituted F alkyl" means that the alkyl group may but does not have to be substituted with F, and the description includes the case where the alkyl group is substituted with F and the case where the alkyl group is not substituted with F.

[0227] "Pharmaceutically acceptable salt" or "its pharmaceutically acceptable salt" means that the compound of the present invention retains the bioavailability and properties of a free acid or a free base, and that the free acid is obtained by reacting with a non-toxic inorganic or organic base, wherein the free base is obtained by reacting with a non-toxic inorganic or organic acid.

[0228] "Pharmaceutical composition" refers to a mixture of one or more compounds described in this invention, or stereoisomers, tautomers, deuterated compounds, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals, and other chemical components, wherein "other chemical components" refers to pharmaceutically acceptable carriers, excipients, and / or one or more other therapeutic agents.

[0229] "Carrier" refers to a material that does not cause significant stimulation to an organism and does not eliminate the biological activity and properties of the compound given.

[0230] "Excipients" are inert substances added to a pharmaceutical composition to facilitate administration of the compound. Non-limiting examples include calcium carbonate, calcium phosphate, sugar, starch, cellulose derivatives (including microcrystalline cellulose), gelatin, vegetable oils, polyethylene glycols, diluents, granulating agents, lubricants, binders, and disintegrants.

[0231] "Product specification" refers to the weight of the active pharmaceutical ingredient contained in each vial, tablet, or other unit of preparation.

[0232] "Prodrug" refers to a compound of the present invention that can be metabolized in vivo and converted into a biologically active compound. The prodrug of the present invention is prepared by modifying the amino or carboxyl groups in the compound of the present invention. This modification can be performed through conventional procedures or removed in vivo to obtain the parent compound. When the prodrug of the present invention is administered to a mammalian individual, the prodrug is cleaved to form free amino or carboxyl groups.

[0233] "Co-crystal" refers to a crystal formed by the bonding of an active pharmaceutical ingredient (API) and a co-crystal form (CCF) through hydrogen bonds or other non-covalent bonds. Both API and CCF are solids at room temperature in their pure states, and a fixed stoichiometric ratio exists between the components. Co-crystal is a multi-component crystal, encompassing both binary co-crystals formed between two neutral solids and multi-component co-crystals formed between a neutral solid and a salt or solvate.

[0234] "Animals" refers to mammals, such as humans, companion animals, zoo animals, and livestock, with humans, horses, or dogs being preferred.

[0235] "Stereoisomers" are isomers that are produced by different spatial arrangements of atoms in a molecule, including cis-trans isomers, enantiomers, and conformational isomers.

[0236] "Tautomers" refer to functional group isomers that are produced by the rapid movement of an atom in two positions within a molecule, such as keto-enol isomers and amide-imine alcohol isomers.

[0237] IC 50 "It refers to the concentration of a drug or inhibitor required to inhibit a specified biological process (or a component of that process, such as an enzyme, receptor, or cell) by half." Detailed Implementation

[0238] The following embodiments illustrate the technical solution of the present invention in detail, but the scope of protection of the present invention includes, but is not limited to, these embodiments.

[0239] The structure of the compounds was determined 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 Bruker Avance III 400 and Bruker Avance 300 NMR spectrometers in the following solvents: deuterated dimethyl sulfoxide (DMSO-d₆), deuterated chloroform (CDCl₃), and deuterated methanol (CD₃OD). Tetramethylsilane (TMS) was used as the internal standard. MS determination was performed using (Agilent 6120B (ESI) and Agilent 6120B (APCI)); HPLC determinations were performed using an Agilent 1260DAD high-performance liquid chromatograph (Zorbax SB-C18 100 × 4.6 mm, 3.5 μM). Thin-layer chromatography (TLC) uses Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The silica gel plates used for TLC have a diameter of 0.15 mm to 0.20 mm, and the diameter of the plates used for TLC separation and purification is 0.4 mm to 0.5 mm. Column chromatography typically uses Yantai Huanghai silica gel with a mesh size of 200-300 as the carrier.

[0240] The known starting materials of this invention can be synthesized using or according to methods known in the art, or can be purchased from companies such as Titan Technology, Anaiji Chemical, Shanghai Demo, Chengdu Kelong Chemical, Shaoyuan Chemical Technology, and Bailingwei Technology.

[0241] Tf: Trifluoromethanesulfonyl. Boc: Tert-butoxycarbonyl. Ts: p-Toluenesulfonyl. Cbz: Benzyloxycarbonyl.

[0242] TMS: Trimethylsilyl.

[0243] Chemical bond wavy lines The stereoisomers representing the connecting atoms are R or S.

[0244] DMA: Dimethylacetamide; Solutol: Polyethylene glycol-15-hydroxystearate; Saline: Physiological saline; MC: Methylcellulose solution Example 1: Trifluoroacetate of 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid (compound 1-A) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid trifluoroacetate Trifluoroacetate of 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid (compound 1-B) 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0245]

[0246] Step 1: (S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethylene)piperidine-1-carboxylic acid benzyl ester (1b) benzyl (S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethylene)piperidine-1-carboxylate

[0247] Methoxymethyltriphenylphosphine chloride (970 mg, 2.83 mmol) was added to 40 mL of ultra-dry THF, cooled in an ice-water bath, and slowly added dropwise in a 1 mol / L potassium tert-butoxide tetrahydrofuran solution (3.3 mL) under a nitrogen atmosphere. The mixture was stirred at 0 °C for 30 min, and then a tetrahydrofuran solution (5 mL) of (S)-2-(4-(methoxycarbonyl)phenyl)-4-oxopiperidin-1-carboxylic acid benzyl ester (0.8 g, 2.18 mmol) (1a) (synthetic method see WO2020016749) was added. The mixture was reacted at room temperature for 16 h. Add 50 mL of ethyl acetate to the reaction system, wash with 50 mL of saturated ammonium chloride aqueous solution, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then purify the crude product by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to obtain (S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethylene)piperidine-1-carboxylic acid benzyl ester (1b) (550 mg, yield: 64%).

[0248] LCMS m / z = 396.1 [M+1] + Step 2: Maleate of methyl 4-((2S)-4-(methoxymethyl)piperidin-2-yl)benzoate (1c) methyl 4-((2S)-4-(methoxymethyl)piperidin-2-yl)benzoate maleate

[0249] (S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethylene)piperidin-1-carboxylate benzyl ester (1b) (550 mg, 1.39 mmol) was dissolved in 10 mL of methanol, and 0.2 g of 10% palladium on carbon was added. The mixture was stirred at room temperature for 16 h under a hydrogen atmosphere. The reaction system was filtered under reduced pressure, and the filtrate was concentrated under reduced pressure to obtain a crude product (350 mg). The crude product (350 mg) was dissolved in 20 mL of isopropyl acetate, and maleic acid (77 mg, 0.66 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure to obtain the maleate salt of crude methyl 4-((2S)-4-(methoxymethyl)piperidin-2-yl)benzoate (1c) (430 mg).

[0250] Step 3: 5-Methoxy-4-(((2S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethyl)piperidin-1-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (1d) tert-butyl 5-methoxy-4-(((2S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethyl)piperidin-1-yl)methyl)-7-methyl-1H-indole-1-carboxylate

[0251] The maleate (430 mg) of the crude product methyl 4-((2S)-4-(methoxymethyl)piperidin-2-yl)benzoate (1c) was dissolved in 10 mL of ethanol, and tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (385 mg, 1.33 mmol) (synthetic method see WO2015009616) was added, along with 10 mg of Ir(CO)2acac (CAS: 14023-80-4). The mixture was heated to 75 °C and reacted under a hydrogen balloon atmosphere for 48 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1) to give tert-butyl 5-methoxy-4-(((2S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethyl)piperidin-1-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid (1d) (340 mg, two-step yield from compound 1b: 46%).

[0252] LCMS m / z = 537.5 [M+1] + Step 4: Trifluoroacetate of 4-((2S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid (compound 1) 4-((2S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0253] 5-Methoxy-4-(((2S)-2-(4-(methoxycarbonyl)phenyl)-4-(methoxymethyl)piperidin-1-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (1d) (340 mg, 0.63 mmol) was dissolved in 10 mL of methanol, and solid potassium carbonate (410 mg, 2.97 mmol) was added. The mixture was heated to 85 °C and refluxed for 3 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain a crude product (750 mg). The crude product (750 mg) was dissolved in a mixed solvent of 10 mL THF, 5 mL methanol and 2 mL water, and lithium hydroxide monohydrate (250 mg, 5.95 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure, and the crude product was subjected to Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare a sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the product with a 5% gradient (elution time 15 min), and the solution was lyophilized to obtain 180 mg of trifluoroacetate of 4-((2S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid (compound 1).

[0254] LCMS m / z = 423.2 [M+1] + Step 5: Trifluoroacetate of 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid (compound 1-A) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid trifluoroacetate Trifluoroacetate of 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid (compound 1-B) 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(methoxymethyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0255] The trifluoroacetate salts of compound 1 were prepared by high-performance liquid chromatography (HPLC) to obtain the trifluoroacetates of compounds 1-a and 1-b. The preparation conditions were as follows: Instrumentation and column: A Waters 350 preparative HPLC system was used, with a DAICELCHIRALCEL AD column. Mobile phase: supercritical CO2 / ethanol, with isogradient elution: supercritical CO2 / ethanol = 60 / 40, flow rate: 100 mL / min. Analytical methods for compounds 1-a and 1-b: Instrument: SHIMADZU LC-30AD SFC column: Chiralpak AD-3 50×4.6 mm, ID, 3 μm; mobile phase A: sCO2 (supercritical CO2); mobile phase B: isopropanol (containing 0.05% diethylamine); column temperature: 35 ℃; flow rate: 3 mL / min; wavelength: 220 nm; elution program: mobile phase A:B: 95:5-60:40.

[0256] Retention time of compound 1-a: 2.009 min; NMR spectrum of trifluoroacetate of compound 1-a: 1H NMR (400 MHz, CD3OD) δ 8.20 – 8.05 (m, 2H), 7.70 – 7.54 (m, 2H), 7.34 – 7.26 (m, 1H), 6.80 – 6.70 (m, 1H), 6.40 – 6.20 (m, 1H), 4.65 – 4.43(m, 1H), 4.40 – 4.22 (m, 1H), 4.15 – 3.95 (m, 1H), 3.79 – 3.64 (m, 5H), 3.44(s, 3H), 3.37 – 3.31 (m, 2H), 2.53 – 2.47 (m, 3H), 2.40 – 1.77 (m, 5H). LCMS m / z = 423.2 [M+1] + Retention time of compound 1-b: 2.339 min.

[0257] NMR spectrum of trifluoroacetate of compound 1-b: 1 H NMR (400 MHz, CD3OD) δ 8.28 – 8.16 (m, 2H), 7.79 – 7.64 (m, 2H), 7.37 – 7.29 (m, 1H), 6.76 (s, 1H), 6.33 (s, 1H), 4.65 – 4.47 (m, 1H), 4.45 –4.27 (m, 1H), 4.23 – 4.05 (m, 1H), 3.75 (s, 3H), 3.65 – 3.50 (m, 1H), 3.45 –3.28 (m, 6H), 2.51 (s, 3H), 2.25 – 2.05 (m, 2H), 2.00 – 1.75 (m, 2H), 1.74 –1.50 (m, 1H). LCMS m / z = 423.2 [M+1] + Compound 1-a or compound 1-b is one of the isomers of compound 1-A or compound 1-B, respectively.

[0258] Example 2: Trifluoroacetate of 4-[(5R,7S)-8-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-1-oxa-8-azaspiro[4.5]dec-7-yl]benzoic acid (compound 2-A) 4-[(5R,7S)-8-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-1-oxa-8-azaspiro[4.5]decan-7-yl]benzoic acid trifluoroacetate Trifluoroacetate of 4-[(5S,7S)-8-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-1-oxa-8-azaspiro[4.5]dec-7-yl]benzoic acid (compound 2-B) 4-((5S,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid trifluoroacetate

[0259]

[0260] 1. Synthesis of intermediates 2b-a (diasteretype 1) and 2b-b (diasteretype 2):

[0261] Under a nitrogen atmosphere, propynyloxytrimethylsilane (0.90 mL, 5.86 mmol) and anhydrous tetrahydrofuran (6 mL) were added to the reaction flask, respectively, and then the system was cooled to 0 °C. o C. At this temperature, slowly add 6 mL of tetrahydrofuran solution of magnesium ethyl bromide (1.0 mol / L) dropwise to the reaction flask. After the addition is complete, at 0°C... o Stirring continued for 30 min at C, then the mixture was brought to room temperature and stirred for another 90 min. The reaction system was cooled to 0 °C, and then a tetrahydrofuran solution (6 mL) of (S)-2-(4-(methoxycarbonyl)phenyl)-4-oxopiperidin-1-carboxylic acid benzyl ester (1.1 g, 3.0 mmol) (1a) (synthetic method see WO2020016749) was slowly added dropwise, and the mixture was stirred at 0 °C. oThe reaction was carried out at C for 3 h, and then the reaction system was slowly restored to room temperature and the reaction was continued at room temperature for 96 h. The reaction solution was cooled to 0 °C, and the reaction was quenched by slowly adding 20 mL of saturated ammonium chloride solution. After the addition was completed, the system was restored to room temperature and stirred for 2 h. Then, it was extracted with ethyl acetate (30 mL × 3), the organic phase was washed with 20 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (ethyl acetate / petroleum ether (v / v) = 1:1) to give intermediate 2b-a (diastereomer 1) (0.47 g, yield: 37%, Rf = 0.25) and 2b-b (diastereomer 2) (0.24 g, yield: 19%, Rf = 0.20).

[0262] 2. Synthesis of compound 2-a (diastereomer 1): Step 1: Methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate [2c-a (diasteretype 1)] methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate

[0263] Intermediate 2b-a (diastereomer 1) (1.50 g, 3.54 mmol) was dissolved in 10 mL of methanol, and 10% palladium on carbon (750 mg) was added. The mixture was reacted under a hydrogen balloon atmosphere for 5 h. The reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain crude methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate [2c-a (diastereomer 1)] (1.0 g).

[0264] LCMS m / z = 294.1 [M+1] + Step 2: (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid tert-butyl ester [2d-a (diasteretype 1)] tert-butyl (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0265] The crude product methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate [2c-a (diastereomer 1)] (1.0 g) was dissolved in 10 mL of dichloromethane, and 1 mL of anhydrous methanol and triethylamine (1.03 g, 10.2 mmol) were added sequentially, followed by Boc2O (1.48 g, 6.78 mmol). After the addition was complete, the reaction was carried out at room temperature for 4 h. Add 20 mL of water and 20 mL of dichloromethane to the reaction solution, separate the layers, wash the organic layer with 10 mL of saturated sodium chloride solution, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and then purify the residue by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 2:3) to give (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid tert-butyl ester [2d-a (diastereomer 1)] (0.800 g, two-step yield from intermediate 2b-a (diastereomer 1): 57%).

[0266] Step 3: (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylic acid tert-butyl ester [2e-a (diastereomer 1)] tert-butyl (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylate

[0267] (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid tert-butyl ester [2d-a (diastereomer 1)] (0.650 g, 1.65 mmol) was dissolved in 10 mL of dichloromethane, and triethylamine (0.501 g, 4.95 mmol) and DMAP (0.020 g, 0.164 mmol) were added sequentially, followed by p-toluenesulfonyl chloride (0.629 g, 3.30 mmol). After the addition was complete, the reaction was carried out at room temperature for 16 h. Add 20 mL of water and 50 mL of ethyl acetate to the reaction solution, separate the layers, wash the organic layer with 20 mL of saturated sodium chloride solution, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and purify the crude product by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 9:1) to obtain (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylic acid tert-butyl ester [2e-a (diastereomer 1)] (0.360 g, yield: 58%).

[0268] 1H NMR (400 MHz, CDCl3) δ 7.97 (d, 2H), 7.28 (d, 2H), 5.38 – 5.30 (m,1H), 4.14 – 4.04 (m, 1H), 3.90 (s, 3H), 3.63 – 3.54 (m, 1H), 3.54 – 3.45 (m,1H), 3.30 – 3.19 (m, 1H), 2.37 – 2.29 (m, 1H), 1.99 – 1.78 (m, 3H), 1.78 –1.55 (m, 4H), 1.41 (s, 9H). LCMS m / z = 398.2 [M+23] + Step 4: 4-[(7S)-1-oxa-8-azaspiro[4.5]dec-7-yl]methyl benzoate [2f-a (diastereomer 1)] hydrochloride methyl 4-((7S)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoate hydrochloride

[0269] (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylic acid tert-butyl ester [2e-a (diastereomer 1)] (0.350 g, 0.93 mmol) was dissolved in 5 mL of dichloromethane, and 5 mL of 4 mol / L 1,4-dioxane hydrochloride solution was added. The mixture was stirred at room temperature for 4 h. The reaction solution was concentrated under reduced pressure to obtain crude methyl 4-[(7S)-1-oxa-8-azaspiro[4.5]dec-7-yl]benzoate [2f-a (diastereomer 1)] hydrochloride (0.290 g).

[0270] LCMS m / z = 276.2 [M+1] + Step 5: 5-Methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [2g-a (diastereomer 1)] tert-butyl 5-methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decan-8-yl)methyl)-7-methyl-1H-indole-1-carboxylate

[0271] The crude product methyl 4-[(7S)-1-oxa-8-azaspiro[4.5]dec-7-yl]benzoate [2f-a (diastereomer 1)] hydrochloride (0.290 g) was dissolved in 10 mL of anhydrous ethanol, and tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (270 mg, 0.93 mmol) (synthetic method see WO2015009616) was added. Nitrogen gas was purged three times, and 10 mg of Ir(CO)2acac was added. Hydrogen gas was purged three times. The temperature was raised to 75 °C, and the reaction was carried out under a hydrogen balloon atmosphere for 24 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 85:15) to give 5-methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [2g-a (diastereomer 1)] (0.170 g, two-step yield from compound 2e-a (diastereomer 1): 33%).

[0272] 1 H NMR (400 MHz, CDCl3) δ 8.04 (d, 2H), 7.60 (d, 2H), 7.47 (d, 1H), 6.68 – 6.62 (m, 2H), 3.91 (s, 3H), 3.83 – 3.71 (m, 5H), 3.59 (d, 1H), 3.25(d, 1H), 3.21 (dd, 1H), 2.92 – 2.83 (m, 1H), 2.58 (s, 3H), 2.10 – 2.00 (m,1H), 1.99 – 1.65 (m, 7H), 1.61 (s, 9H), 1.53 – 1.43 (m, 1H). LCMS m / z = 549.3 [M+1] + Step 6: Trifluoroacetate of 4-((7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid [compound 2-a (diastereomer 1)] 4-((7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid trifluoroacetate

[0273] 5-Methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [2 g-a (diastereomer 1)] (0.160 g, 0.29 mmol) was dissolved in 10 mL of anhydrous methanol, and solid potassium carbonate (0.200 g, 1.45 mmol) was added. After the addition was complete, the mixture was heated to 75 °C and refluxed for 3 h. The reaction solution was cooled to room temperature, and 10 mL of tetrahydrofuran, 2 mL of water, and 2 mL of methanol were added sequentially. Then, lithium hydroxide monohydrate (0.120 g, 2.9 mmol) was added, and the reaction was carried out at room temperature for 16 h. The reaction solution was concentrated under reduced pressure. 10 mL of water was added to the residue, and the pH was adjusted to 8 by adding 0.1 mol / L citric acid aqueous solution dropwise. The solution was then passed through Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC system, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the solution with a 5% gradient (elution time 15 min), and the solution was lyophilized to obtain 0.100 g of trifluoroacetate of 4-((7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid [compound 2-a (diastereomer 1)].

[0274] 1H NMR (400 MHz, CD3OD) δ 8.23 ​​(d, 2H), 7.74 (d, 2H), 7.33 (d, 1H), 6.77 (s, 1H), 6.34 (d, 1H), 4.62 (d, 1H), 4.34 (d, 1H), 4.20 (d, 1H), 3.90 –3.79 (m, 2H), 3.76 (s, 3H), 3.65 – 3.55 (m, 1H), 3.43 – 3.34 (m, 1H), 2.51(s, 3H), 2.34 – 2.23 (m, 1H), 2.23 – 1.98 (m, 6H), 1.92 – 1.82 (m, 1H). LCMS m / z = 435.3 [M+1] + Compound 2-a (diastere 1) is one of the isomers of compound 2-A or compound 2-B.

[0275] 3. Synthesis of compound 2-b (diastereomer 2): Step 1: Methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate [2c-b (diastere-2)] methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate

[0276] Intermediate 2b-b (diastereomer 2) (0.700 g, 1.65 mmol) was dissolved in 10 mL of methanol, and 10% palladium on carbon (350 mg) was added. The mixture was reacted under a hydrogen balloon atmosphere for 5 h. The reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain crude methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate [2c-b (diastereomer 2)] (0.480 g).

[0277] LCMS m / z = 294.1 [M+1] + Step 2: (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid tert-butyl ester [2d-b (diastere-2)] tert-butyl (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0278] The crude product methyl 4-((2S)-4-hydroxy-4-(3-hydroxypropyl)piperidin-2-yl)benzoate [2c-b (diastereomer 2)] (0.480 g) was dissolved in 10 mL of dichloromethane, and 1 mL of anhydrous methanol and triethylamine (0.500 g, 4.94 mmol) were added sequentially, followed by Boc2O (0.720 g, 3.30 mmol). After the addition was complete, the mixture was reacted at room temperature for 4 h. Add 20 mL of water and 20 mL of dichloromethane to the reaction solution, separate the layers, wash the organic layer with 10 mL of saturated sodium chloride solution, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and purify the residue by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 2:3) to give (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid tert-butyl ester [2d-b (diastereomer 2)] (0.320 g, two-step yield from intermediate 2b-b (diastereomer 2): 49%).

[0279] Step 3: (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylic acid tert-butyl ester [2e-b (diastereomer 2)] tert-butyl (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylate

[0280] (2S)-4-hydroxy-4-(3-hydroxypropyl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid tert-butyl ester [2d-b (diastereomer 2)] (0.320 g, 0.81 mmol) was dissolved in 10 mL of dichloromethane, followed by the addition of triethylamine (0.250 g, 2.47 mmol) and DMAP (0.010 g, 0.0820 mmol), and then p-toluenesulfonyl chloride (0.310 g, 1.63 mmol). The reaction was carried out at room temperature for 16 h after the addition was complete. Add 20 mL of water and 50 mL of ethyl acetate to the reaction solution, separate the layers, wash the organic layer with 20 mL of saturated sodium chloride solution, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and purify the crude product by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 9:1) to obtain (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylic acid tert-butyl ester [2e-b (diastereomer 2)] (0.160 g, yield: 53%).

[0281] 1 H NMR (400 MHz, CDCl3) δ 7.99 (d, 2H), 7.28 – 7.23 (m, 2H), 5.37 (t,1H), 4.25 – 4.15 (m, 1H), 3.91 (s, 3H), 3.79 (t, 2H), 3.18 – 3.08 (m, 1H), 2.17 – 2.12 (m, 2H), 1.85 – 1.72 (m, 3H), 1.66 – 1.56 (m, 1H), 1.44 – 1.31 (m, 10H), 1.30 – 1.17 (m, 1H). Step 4: 4-[(7S)-1-oxa-8-azaspiro[4.5]dec-7-yl]methyl benzoate [2f-b (diastereomer 2)] hydrochloride methyl 4-((7S)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoate hydrochloride

[0282] (7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylic acid tert-butyl ester [2e-b (diastereomer 2)] (0.160 g, 0.426 mmol) was dissolved in 5 mL of dichloromethane, and 5 mL of 4 mol / L 1,4-dioxane hydrochloride solution was added. The mixture was stirred at room temperature for 4 h. The reaction solution was concentrated under reduced pressure to obtain crude methyl 4-[(7S)-1-oxa-8-azaspiro[4.5]dec-7-yl]benzoate [2f-b (diastereomer 2)] hydrochloride (0.130 g).

[0283] LCMS m / z = 276.2 [M+1] + Step 5: 5-Methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [2g-b (diastereomer 2)] tert-butyl 5-methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decan-8-yl)methyl)-7-methyl-1H-indole-1-carboxylate

[0284] The crude product methyl 4-[(7S)-1-oxa-8-azaspiro[4.5]dec-7-yl]benzoate [2f-b (diastereomer 2)] hydrochloride (0.130 g) was dissolved in 10 mL of anhydrous ethanol. 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (144 mg, 0.50 mmol) (synthetic method see WO2015009616) was added, nitrogen gas was purged three times, 10 mg of Ir(CO)2acac was added, hydrogen gas was purged three times, the temperature was raised to 75 °C, and the reaction was carried out under a hydrogen balloon atmosphere for 24 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 85:15) to give 5-methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [2g-b (diastereomer 2)] (0.09 g, two-step yield from compound 2e-b (diastereomer 2): 39%).

[0285] LCMS m / z = 549.3 [M+1] + Step 6: Trifluoroacetate of 4-((7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid [compound 2-b (diastereomer 2)] 4-((7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid trifluoroacetate

[0286] 5-Methoxy-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [2 g-b (diastereomer 2)] (0.090 g, 0.16 mmol) was dissolved in 10 mL of anhydrous methanol, and solid potassium carbonate (0.11 g, 0.80 mmol) was added. After the addition was complete, the mixture was heated to 75 °C and refluxed for 3 h. The reaction solution was cooled to room temperature, and 10 mL of tetrahydrofuran, 2 mL of water, and 2 mL of methanol were added sequentially. Then, lithium hydroxide monohydrate (0.067 g, 1.6 mmol) was added, and the reaction was carried out at room temperature for 16 h. The reaction solution was concentrated under reduced pressure. 10 mL of water was added to the residue, and the pH was adjusted to 8 by adding 0.1 mol / L citric acid aqueous solution dropwise. The solution was then passed through Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC system, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the compound with a 5% gradient (elution time 15 min), and the lyophilized product was 0.045 g of trifluoroacetate of 4-((7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid [compound 2-b (diastereomer 2)].

[0287] 1H NMR (400 MHz, CD3OD) δ 8.22 (d, 2H), 7.74 (d, 2H), 7.33 (d, 1H), 6.77 (s, 1H), 6.36 (d, 1H), 4.83 – 4.70 (m, 1H), 4.34 (d, 1H), 4.22 (d, 1H),4.00 –3.86 (m, 2H), 3.76 (s, 3H), 3.63 – 3.52 (m, 1H), 3.50 – 3.40 (m, 1H),2.51 (s, 3H), 2.31 – 2.20 (m, 1H), 2.10 – 1.92 (m, 4H), 1.90 – 1.77 (m, 3H). LCMS m / z = 435.3 [M+1] + Compound 2-b (diastere 2) is one of the isomers of compound 2-A or compound 2-B.

[0288] Example 3: Trifluoroacetate of 4-[(2S,4S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid (compound 3) 4-[(2S,4S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid trifluoroacetate

[0289]

[0290] Step 1: (2S,4S)-4-(2-methoxyethoxy)-2-(4-((2-methoxyethoxy)carbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (3b) benzyl (2S,4S)-4-(2-methoxyethoxy)-2-(4-((2-methoxyethoxy)carbonyl)phenyl)piperidine-1-carboxylate

[0291] (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (3a) (0.300 g, 0.81 mmol) (synthetic method see WO2020016749) and 1-bromo-2-methoxyethane (0.370 g, 2.66 mmol) were dissolved in 3 mL DMF, and 60% sodium hydride (0.072 g) was added at room temperature. After the addition was complete, the reaction was carried out at room temperature for 16 h. At room temperature, 2 mL of water was slowly added to the reaction solution to quench the reaction, followed by extraction with 10 mL of ethyl acetate. The mixture was separated, and the organic phase was washed with 5 mL of saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was then purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 85:15) to give (2S,4S)-4-(2-methoxyethoxy)-2-(4-((2-methoxyethoxy)carbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (3b) (0.180 g, yield: 47%).

[0292] Step 2: Maleate of 2-methoxyethyl 4-[(2S,4S)-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid (3c) 2-methoxyethyl 4-[(2S,4S)-4-(2-methoxyethoxy)piperidin-2-yl]benzoatemaleate

[0293] (2S,4S)-4-(2-methoxyethoxy)-2-(4-((2-methoxyethoxy)carbonyl)phenyl)piperidin-1-carboxylic acid benzyl ester (3b) (0.180 g, 0.382 mmol) was dissolved in 5 mL of methanol, and 30 mg of 10% palladium on carbon was added. The mixture was reacted at room temperature for 2 h under a hydrogen balloon atmosphere. The reaction system was filtered, and the filter cake was washed with 5 mL of methanol. The filtrates were combined and concentrated under reduced pressure to obtain crude 4-[(2S,4S)-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid 2-methoxyethyl ester (3c) (0.128 g). The crude product 2-methoxyethyl 4-[(2S,4S)-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid (3c) (0.128 g) was dissolved in 5 mL of isopropyl acetate, 1 mL of anhydrous methanol was added, and maleic acid (0.044 g, 0.38 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction solution was concentrated under reduced pressure to obtain the maleate (0.173 g) of the crude product 2-methoxyethyl 4-[(2S,4S)-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid (3c).

[0294] Step 3: 5-Methoxy-4-{[(2S,4S)-4-(2-methoxyethoxy)-2-(4-[(2-methoxyethoxy)carbonyl]phenyl)piperidin-1-yl]methyl}-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (3d) tert-butyl 5-methoxy-4-{[(2S,4S)-4-(2-methoxyethoxy)-2-(4-[(2-methoxyethoxy)carbonyl]phenyl)piperidin-1-yl]methyl}-7-methyl-1H-indole-1-carboxylate

[0295] The maleate (0.173 g) of the crude product 4-[(2S,4S)-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid 2-methoxyethyl ester (3c) was dissolved in 10 mL of anhydrous ethanol. 4-Formyl-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (0.140 g, 0.484 mmol) (synthetic method see WO2015009616) was added, nitrogen gas was purged three times, 5 mg of Ir(CO)2acac was added, hydrogen gas was purged three times, the temperature was raised to 75 °C, and the reaction was carried out under a hydrogen balloon atmosphere for 24 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 85:15) to give 5-methoxy-4-{[(2S,4S)-4-(2-methoxyethoxy)-2-(4-[(2-methoxyethoxy)carbonyl]phenyl)piperidin-1-yl]methyl}-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (3d) (0.130 g, two-step yield from compound 3b: 56%).

[0296] LCMS m / z = 611.3 [M+1] + Step 4: Trifluoroacetate of 4-[(2S,4S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid (compound 3) 4-[(2S,4S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid trifluoroacetate

[0297] 5-Methoxy-4-{[(2S,4S)-4-(2-methoxyethoxy)-2-(4-[(2-methoxyethoxy)carbonyl]phenyl)piperidin-1-yl]methyl}-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (3d) (0.130 g, 0.213 mmol) was dissolved in 10 mL of anhydrous methanol, and solid potassium carbonate (0.147 g, 1.06 mmol) was added. After the addition was complete, the temperature was raised to 75 °C and the reaction was carried out for 3 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and 10 mL of water was added to the residue. The pH was adjusted to 8 by adding 0.1 mol / L citric acid aqueous solution dropwise. The solution was then passed through Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC, Sunfire C18, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare a sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the product with a 5% gradient (elution time 15 min), and the solution was lyophilized to obtain 0.022 g of trifluoroacetate of 4-[(2S,4S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-(2-methoxyethoxy)piperidin-2-yl]benzoic acid (compound 3).

[0298] 1 H NMR (400 MHz, CD3OD) δ 8.23 ​​(d, 2H), 7.74 (d, 2H), 7.34 (d, 1H), 6.77 (s, 1H), 6.37 (d, 1H), 4.89 – 4.81 (m, 1H), 4.33 (d, 1H), 4.23 (d, 1H),3.92 – 3.82 (m, 1H), 3.76 (s, 3H), 3.73 – 3.54 (m, 5H), 3.46 (s, 3H), 3.43 –3.30 (m, 1H), 2.51 (s, 3H), 2.34 – 2.18 (m, 2H), 2.16 – 2.05 (m, 1H), 2.05 –1.91 (m, 1H). LCMS m / z = 453.3 [M+1] + Example 4: 4-((2S,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid (compound 4) 4-((2S,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid

[0299]

[0300] Step 1: (2S,4S)-4-(cyclopropylmethoxy)-2-(4-((cyclopropylmethoxy)carbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (4a-1) benzyl (2S,4S)-4-(cyclopropylmethoxy)-2-(4-((cyclopropylmethoxy)carbonyl)phenyl)piperidine-1-carboxylate (2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (4a-2) benzyl (2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0301] (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (3a) (400 mg, 1.08 mmol) (synthetic method see WO2020016749) was added to 10 mL of DMF, cooled to 0 °C, 60% sodium hydride (95 mg) was added, stirring was continued for 1 h, (bromomethyl)cyclopropane (321 mg, 2.38 mmol) was added, and the mixture was heated to room temperature and reacted for 16 h. At room temperature, 20 mL of water was slowly added to the reaction solution to quench the reaction, followed by extraction with 50 mL of ethyl acetate. The mixture was separated, and the organic phase was washed with 50 mL of saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to obtain a mixture (450 mg) of (2S,4S)-4-(cyclopropylmethoxy)-2-(4-((cyclopropylmethoxy)carbonyl)phenyl)piperidine-1-carboxylate benzyl ester (4a-1) and (2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate benzyl ester (4a-2).

[0302] The LCMS m / z of compound (4a-1) is 464.2 [M+1]. + The LCMS m / z of compound (4a-2) is 424.2 [M+1]. + Step 2: Maleate of 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)benzoate cyclopropyl methyl ester (4b-1) cyclopropylmethyl 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)benzoate maleate 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)methyl benzoate (4b-2) maleate methyl 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)benzoatemaleate

[0303] The mixture (450 mg) of (2S,4S)-4-(cyclopropylmethoxy)-2-(4-((cyclopropylmethoxy)carbonyl)phenyl)piperidine-1-carboxylate (4a-1) and (2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate (4a-2) was dissolved in 10 mL of methanol, and 90 mg of 10% palladium on carbon was added. The mixture was stirred at room temperature for 5 h under a hydrogen atmosphere. The reaction system was filtered under reduced pressure, and the filtrate was concentrated under reduced pressure to obtain a crude product (320 mg). The crude product (320 mg) was dissolved in 10 mL of isopropyl acetate, and maleic acid (77 mg, 0.66 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure to obtain a mixture (420 mg) of crude 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)benzoic acid cyclopropyl methyl ester (4b-1) maleate and crude 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)benzoic acid methyl ester (4b-2) maleate.

[0304] Step 3: 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-((cyclopropylmethoxy)carbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (4c-1) tert-butyl 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-((cyclopropylmethoxy)carbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (4c-2) tert-butyl 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

[0305] The mixture (420 mg) of the maleate of crude 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)benzoate cyclopropyl methyl ester (4b-1) and the maleate of 4-((2S,4S)-4-(cyclopropylmethoxy)piperidin-2-yl)benzoate methyl ester (4b-2) was dissolved in 10 mL of ethanol, and 350 mg (1.2 mmol) of 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (synthetic method see WO2015009616) was added, followed by 35 mg of Ir(CO)2acac. The mixture was heated to 75 °C and reacted under a hydrogen balloon atmosphere for 16 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1) to obtain a mixture (130 mg) of tert-butyl 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-(((cyclopropylmethoxy)carbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid (tert-butyl ester) and 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid (tert-butyl ester) (4c-2).

[0306] The LCMS m / z of compound (4c-1) is 603.3 [M+1]. + The LCMS m / z of compound (4c-2) is 563.3 [M+1]. + Step 4: 4-((2S,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid (compound 4) 4-((2S,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid

[0307] The mixture (130 mg) of the above-mentioned tert-butyl 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-(((cyclopropylmethoxy)carbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid (tert-butyl ester) and 4-(((2S,4S)-4-(cyclopropylmethoxy)-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid (tert-butyl ester) (4c-2) was dissolved in 10 mL of methanol, and solid potassium carbonate (149 mg, 1.08 mmol) was added. The mixture was heated to 85 °C and refluxed for 3 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in a mixed solvent of 10 mL THF, 5 mL methanol, and 2 mL water. Lithium hydroxide monohydrate (181 mg, 4.3 mmol) was added, and the mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure, and the crude product was subjected to Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC system; Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide, and filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: acetonitrile / aqueous solution containing 5 mmol / L ammonium acetate. Gradient elution method: Acetonitrile was used to elute 60% of the compound with a 5% gradient (elution time 15 min), and the lyophilized compound was 4-((2S,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid (compound 4) (5 mg).

[0308] 1 H NMR (400 MHz, CD3OD) δ 8.10 (d, 2H), 7.60 (d, 2H), 7.28 (d, 1H), 6.73 (s, 1H), 6.32 (s, 1H), 4.70 – 4.40 (m, 1H), 4.32 – 4.14 (m, 1H), 4.09 –3.90 (m, 1H), 3.88 – 3.79 (m, 1H), 3.75 (s, 3H), 3.42 – 3.34 (m, 2H), 3.30 –3.14 (m, 2H), 2.49 (s, 3H), 2.26 – 2.10 (m, 2H), 2.06 – 1.90 (m, 2H), 1.19 –1.04 (m, 1H), 0.64 – 0.50 (m, 2H), 0.31 – 0.22 (m, 2H). LCMS m / z = 449.2 [M+1] + Example 5: Trifluoroacetate of 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 5 (diastere-1)] 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0309]

[0310] Step 1: (S)-4-cyclopropylidene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (5a) benzyl (S)-4-cyclopropylidene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0311] (3-bromopropyl)triphenylphosphine bromide (12.2 g, 26.3 mmol) was added to 100 mL of ultra-dry THF, cooled in an ice-water bath, and potassium tert-butoxide solid (5.9 g, 52.6 mmol) was slowly added under a nitrogen atmosphere. The mixture was stirred at 0 °C for 45 min, and then a tetrahydrofuran solution (20 mL) of (S)-2-(4-(methoxycarbonyl)phenyl)-4-oxopiperidin-1-carboxylic acid benzyl ester (8.0 g, 21.8 mmol) (1a) (synthetic method see WO2020016749) was added. The mixture was reacted at room temperature for 16 h. 100 mL of ethyl acetate was added to the reaction system, washed with 100 mL of saturated ammonium chloride aqueous solution, dried over anhydrous sodium sulfate, and the crude product was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to give (S)-4-cyclopropylidene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (5a) (5.5 g, yield: 64%).

[0312] LCMS m / z = 392.2 [M+1] + Step 2: (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (5b) benzyl (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0313] (S)-4-cyclopropylidene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate (5a) (3.7 g, 9.45 mmol) was added to 50 mL of ultra-dry DMF. Under a nitrogen atmosphere, benzylbenzenesulfonyl hydrazine solid (8.2 g, 47.6 mmol) was added, and the mixture was heated to 100 °C and reacted for 16 h. The reaction solution was cooled to room temperature, and 100 mL of ethyl acetate was added. The organic phase was washed three times with 100 mL of saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to obtain (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate (5b) (2.0 g, yield: 54%).

[0314] Rf value of compound 5b: 0.27 (eluent: ethyl acetate / petroleum ether (v / v) = 1:10) NMR of compound 5b: 1 H NMR (400 MHz, CDCl3) δ 8.01 – 7.91 (m, 2H), 7.36 – 7.21 (m, 5H), 7.20 – 7.10 (m, 2H), 5.12 – 5.00 (m, 3H), 4.18 – 4.02 (m, 1H), 3.91 (s, 3H),3.42 – 3.28 (m, 1H), 2.20 – 2.08 (m, 1H), 2.04 – 1.83 (m, 2H), 1.56 – 1.44(m, 1H), 0.98 – 0.84 (m, 1H), 0.46 – 0.21 (m, 3H), 0.10 – 0.01 (m, 2H).

[0315] LCMS m / z = 394.2 [M+1] + Based on the hydrogens at positions C1 and C3 of the final product compound 5 1 H-1 H NOESY verification confirmed that compound 5b has the structure 5b-B.

[0316] Step 3: Maleate of 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c (diastereomer 1)] methyl 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate maleate

[0317] (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate benzyl ester (5b) (2.0 g, 5.08 mmol) was dissolved in 50 mL of acetonitrile, and trimethyliodosilane (5.1 g, 25.5 mmol) was slowly added dropwise. The mixture was stirred at room temperature for 30 min. 100 mL of water was added to the reaction system, and the pH of the system was adjusted to 3-4 with 1 mol / L dilute hydrochloric acid. The organic phase was extracted with 50 mL of ethyl acetate, and the pH of the aqueous phase was adjusted to 10 with 1 mol / L sodium hydroxide solution. The mixture was extracted three times with 100 mL of dichloromethane, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give compound 5c (diastereomer 1) (1.0 g). Compound 5c (diastereomer 1) (1.0 g, 3.86 mmol) was dissolved in 20 mL of isopropyl acetate, and maleic acid (267 mg, 2.3 mmol) was added. The mixture was reacted at room temperature for 16 h. The reaction system was concentrated under reduced pressure to obtain crude maleate of methyl 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c (diastereomer 1)] (1.2 g).

[0318] LCMS m / z = 260.2 [M+1] + NMR of compound 5c (diastereomer 1): 1H NMR (400 MHz, CDCl3) δ 8.03 – 7.94 (m, 2H), 7.50 – 7.41 (m, 2H), 3.91 (s, 3H), 3.62 (dd, 1H), 3.28 – 3.19 (m, 1H), 2.79 – 2.66 (m, 1H), 2.39(br.s, 1H), 1.99 – 1.75 (m, 2H), 1.50 – 1.22 (m, 2H), 0.86 – 0.70 (m, 1H),0.64 – 0.50 (m, 1H), 0.46 – 0.32 (m, 2H), 0.15 – 0.04 (m, 2H). Based on the hydrogens at positions C1 and C3 of the final product compound 5 1 H- 1 H NOESY confirmed that compound 5c (diastere 1) has the structure 5c-B.

[0319] Step 4: 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [5d (diastereomer 1)] tert-butyl 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

[0320] The maleate (1.2 g) of the crude product 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c (diastereomer 1)] was dissolved in 50 mL of ethanol, and tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (1.23 g, 4.25 mmol) (synthetic method see WO2015009616) was added, followed by 135 mg of Ir(CO)2acac. The mixture was heated to 75 °C and reacted under a hydrogen balloon atmosphere for 16 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1) to give 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [5d (diastereomer 1)] (800 mg, yield: 35%).

[0321] LCMS m / z = 533.3 [M+1] + Based on the hydrogens at positions C1 and C3 of the final product compound 5 1 H- 1 H NOESY verification confirmed that compound 5d (diastere-1) has the structure 5d-B.

[0322] Step 5: Trifluoroacetate of 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 5 (diastereomer 1)] 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0323] 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [5d (diastereomer 1)] (740 mg, 1.39 mmol) was dissolved in 10 mL of methanol, and solid potassium carbonate (960 mg, 6.95 mmol) was added. The mixture was heated to 80 °C and refluxed for 3 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in a mixed solvent of 10 mL THF and 2 mL water, and lithium hydroxide monohydrate (588 mg, 14.01 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure, and the crude product was subjected to Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare a sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the product with a 5% gradient (elution time 15 min), and the solution was lyophilized to obtain trifluoroacetate (480 mg) of 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 5 (diastereomer 1)].

[0324] 1 H NMR (400 MHz, CD3OD) δ 8.23 ​​(d, 2H), 7.73 (d, 2H), 7.33 (d, 1H), 6.77 (s, 1H), 6.33 (d, 1H), 4.48 (dd, 1H), 4.38 – 4.31 (m, 1H), 4.17 – 4.09(m, 1H), 3.76 (s, 3H), 3.62 – 3.53 (m, 1H), 3.30 – 3.21 (m, 1H), 2.51 (s,3H), 2.25 – 2.11 (m, 1H), 2.05 – 1.88 (m, 2H), 1.78 – 1.60 (m, 1H), 1.21 –1.05 (m, 1H), 0.65 – 0.53 (m, 1H), 0.51 – 0.39 (m, 2H), 0.24 – 0.14 (m, 2H). LCMS m / z = 419.2 [M+1] + Compound 5 (diastereomer 1) has significant hydrogen ions at C1 and C3 on the piperidine ring of its trifluoroacetate salt. 1 H- 1 The H NOESY signal confirms that the configuration of compound 5 (diastereomer 1) is as shown in the following formula:

[0325] Based on the trifluoroacetate NMR analysis of compound 5 (diastere 1), compound 5 (diastere 1) is structure 5-B.

[0326] Example 5-1: Trifluoroacetate of 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 5-1 (diastere-2)] 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0327]

[0328] Step 1: (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (5b-1) benzyl (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0329] (S)-4-cyclopropylidene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate (5a) (3.7 g, 9.45 mmol) was added to 50 mL of ultra-dry DMF. Under a nitrogen atmosphere, benzylbenzenesulfonyl hydrazine solid (8.2 g, 47.6 mmol) was added, and the mixture was heated to 100 °C and reacted for 16 h. The reaction solution was cooled to room temperature, and 100 mL of ethyl acetate was added. The organic phase was washed three times with 100 mL of saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 15:1) to obtain (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate (5b-1) (0.7 g, yield: 19%).

[0330] Rf value of compound 5b-1: 0.36 (eluent: ethyl acetate / petroleum ether (v / v) = 1:10) NMR of compound 5b-1: 1 H NMR (400 MHz, CDCl3) δ 8.04 – 7.90 (m, 2H), 7.50 – 7.10 (m, 7H), 5.75 – 5.45 (m, 1H), 5.19 (s, 2H), 4.40 – 4.05 (m, 1H), 3.85 (s, 3H), 2.84 – 2.66 (m, 1H), 2.54 – 2.33 (m, 1H), 1.84 – 1.55 (m, 2H), 1.45 – 1.18 (m, 1H), 0.72 – 0.27 (m, 4H), 0.09 – -0.06 (m, 2H). Based on the hydrogen atoms at the C1 and C6 positions of the piperidine ring and the cyclopropyl group of the final product compound 5-1 1 H- 1 H NOESY verification confirmed that compound 5b-1 has the structure 5b-A.

[0331]

[0332] LCMS m / z = 394.2 [M+1] + Step 2: Maleate of 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c-1 (diastereomer 2)] methyl 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate maleate

[0333] (2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (5b-1) (1.0 g, 2.54 mmol) was dissolved in 10 mL of acetonitrile, and trimethyliodosilane (2.54 g, 12.7 mmol) was slowly added dropwise. The mixture was stirred at room temperature for 30 min. 10 mL of methanol was added to the reaction system, and the pH was adjusted to 2-3 with 2 mol / L dilute hydrochloric acid. The organic phase was extracted with 20 mL of ethyl acetate, and the aqueous phase was adjusted to pH 10 with 2 mol / L sodium hydroxide solution. The mixture was extracted three times with 100 mL of dichloromethane, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give compound 5c-1 (diastereomer 2) (0.6 g). Compound 5c-1 (diastereomer 2) (0.6 g, 2.31 mmol) was dissolved in 10 mL of isopropyl acetate, and maleic acid (270 mg, 2.33 mmol) was added. The reaction was carried out at room temperature for 16 h. The reaction system was concentrated under reduced pressure to give crude methyl 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c-1 (diastereomer 2)] maleate (0.85 g).

[0334] Based on the hydrogen atoms at the C1 and C6 positions of the piperidine ring and the cyclopropyl group of the final product compound 5-1 1 H- 1 H NOESY verification confirmed that compound 5c-1 (diastereomer 2) has the structure 5c-A.

[0335] Step 3: 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [5d-1 (diastereomer 2)] tert-butyl 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

[0336] The maleate of 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c-1 (diastereomer 2)] (0.85 g) was dissolved in 10 mL of ethanol, and tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (0.67 g, 2.32 mmol) (synthetic method see WO2015009616) was added, followed by 80 mg of Ir(CO)2acac. The mixture was heated to 80 °C and reacted under a hydrogen balloon atmosphere for 16 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 15:1) to give 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [5d-1 (diastereomer 2)] (850 mg, yield: 69%).

[0337] Compound 5d-1 (diastereomer 2) NMR: 1 H NMR (400 MHz, CDCl3) δ 8.08 – 7.96 (m, 2H), 7.67 – 7.56 (m, 2H), 7.48 (d, 1H), 6.71 (d, 1H), 6.67 (s, 1H), 3.91 (s, 3H), 3.80 (s, 3H), 3.74 –3.64 (m, 1H), 3.60 – 3.50 (m, 1H), 3.44 – 3.33 (m, 1H), 2.76 – 2.65 (m, 1H), 2.59 (s, 3H), 2.45 – 2.32 (m, 1H), 1.96 – 1.50 (m, 13H), 1.23 – 1.10 (m, 1H), 0.90 – 0.75 (m, 1H), 0.57 – 0.41 (m, 2H), 0.10 – 0.01 (m, 2H). LCMS m / z = 533.3 [M+1] + Based on the hydrogen atoms at the C1 and C6 positions of the piperidine ring and the cyclopropyl group of the final product compound 5-1 1 H- 1 H NOESY verification confirmed that compound 5d-1 (diastereomer 2) has the structure 5d-A.

[0338] Step 4: Trifluoroacetate of 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 5-1 (diastereomer 2)] 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0339] 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [5d-1 (diastereomer 2)] (850 mg, 1.596 mmol) was dissolved in 10 mL of methanol, and solid potassium carbonate (1.1 g, 7.96 mmol) was added. The mixture was heated to 80 °C and refluxed for 3 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in a mixed solvent of 10 mL THF and 2 mL water, and lithium hydroxide monohydrate (670 mg, 15.97 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure, and the crude product was subjected to Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare a sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the product with a 5% gradient (elution time 15 min), and the product was lyophilized to obtain 400 mg of trifluoroacetate of 4-((2S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 5-1 (diastereomer 2)].

[0340] 1H NMR (400 MHz, CD3OD) δ 8.29 – 8.18 (m, 2H), 7.79 – 7.72 (m, 2H), 7.37 – 7.32 (m, 1H), 6.78 (s, 1H), 6.38 (d, 1H), 4.83 – 4.78 (m, 1H), 4.41 – 4.32 (m, 1H), 4.30 – 4.20 (m, 1H), 3.77 (s, 3H), 3.65 – 3.42 (m, 2H), 2.51 (s, 3H), 2.40 – 2.25 (m, 1H), 2.18 – 2.02 (m, 2H), 1.98 – 1.82 (m, 1H), 1.52– 1.38 (m, 1H), 1.18 – 1.04 (m, 1H), 0.72 – 0.60 (m, 2H), 0.25 – 0.17 (m, 2H). LCMS m / z = 419.2 [M+1] + Compound 5-1 (diastereomer 2) exhibits significant hydrogen spectroscopy at the C1 and C6 positions of the trifluoroacetate piperidine ring. 1 H- 1 The HNOESY signal confirms that the configuration of compound 5-1 (diastereomer 2) is as shown in the following formula:

[0341] Based on the trifluoroacetate NMR analysis of compound 5-1 (diastere 2), compound 5-1 (diastere 2) is structure 5-A.

[0342] Example 6: Trifluoroacetate of 4-((7S)-8-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid (compound 6) 4-((7S)-8-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid trifluoroacetate

[0343]

[0344] Step 1: 4-Formyl-5-trideuterated methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (6b) tert-butyl 4-formyl-5-trideuterio methoxy-7-methyl-1H-indole-1-carboxylate

[0345] 4-Formyl-5-hydroxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (6a) (synthetic method see WO2020016749) (0.3 g, 1.09 mmol) was dissolved in 5 mL DMF, and solid potassium carbonate (0.2 g, 1.45 mmol) was added, followed by deuterated iodomethane (0.32 g, 2.21 mmol). After the addition was complete, the reaction was carried out at room temperature for 3 h. 10 mL of water and 20 mL of ethyl acetate were added to the reaction solution, and the mixture was separated. The organic layer was washed with 10 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate / petroleum ether (v / v) = 1:9) to give 4-formyl-5-trideuterated methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (6b) (0.3 g, yield: 94%).

[0346] 1 H NMR (400 MHz, CDCl3) δ 10.63 (s, 1H), 7.62 (d, 1H), 7.47 (d, 1H), 6.73 (s, 1H), 2.68 (s, 3H), 1.63 (s, 9H). LCMS m / z = 293.1 [M+1] + Step 2: 5-(methoxy-d3)-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (6c) tert-butyl 5-(methoxy-d3)-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]decan-8-yl)methyl)-7-methyl-1H-indole-1-carboxylate

[0347] Add 50 mL of dichloromethane to the above crude product methyl 4-[(7S)-1-oxa-8-azaspiro[4.5]dec-7-yl]benzoate [2f-b (diastereomer 2)] hydrochloride (200 mg), adjust the pH to 9 with saturated sodium bicarbonate solution, separate the organic phase, concentrate under reduced pressure, dissolve the residue in 4 mL of tetrahydrofuran, add 1 mL of anhydrous methanol, add maleic acid (0.034 g, 0.292 mmol), heat to 50 °C and stir for 1 h. Cool the reaction solution to room temperature and concentrate under reduced pressure to obtain crude product (0.194 g). The crude product (0.194 g) was dissolved in 10 mL of anhydrous ethanol, and tert-butyl 4-formyl-5-trideuterated methoxy-7-methyl-1H-indole-1-carboxylic acid (6b) (0.17 g, 0.58 mmol) was added. Nitrogen gas was purged three times, and 6 mg of Ir(CO)2acac was added. Hydrogen gas was purged three times, and the temperature was raised to 75 °C. The mixture was then reacted under a hydrogen balloon atmosphere for 24 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-85:15) to give 5-(methoxy-d3)-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (6c) (0.17 g, yield: 53%).

[0348] LCMS m / z = 552.3 [M+1] + Step 3: Trifluoroacetate of 4-((7S)-8-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid (compound 6) 4-((7S)-8-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid trifluoroacetate

[0349] 5-(methoxy-d3)-4-(((7S)-7-(4-(methoxycarbonyl)phenyl)-1-oxa-8-azaspiro[4.5]dec-8-yl)methyl)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester (6c) (0.14 g, 0.25 mmol) was dissolved in 10 mL of anhydrous methanol, and solid potassium carbonate (0.17 g, 1.23 mmol) was added. After the addition was complete, the mixture was heated to 75 °C and refluxed for 3 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure. 10 mL of tetrahydrofuran, 2 mL of water, and 2 mL of methanol were added to the residue in sequence, followed by lithium hydroxide monohydrate (0.1 g, 2.38 mmol). The mixture was reacted at room temperature for 16 h. The reaction solution was concentrated under reduced pressure. 10 mL of water was added to the residue, and the pH was adjusted to 8 by adding 0.1 mol / L citric acid aqueous solution dropwise. The solution was then passed through Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC system, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide, and filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the compound with a 5% gradient (elution time 15 min), and the lyophilized product was 0.085 g of trifluoroacetate of 4-((7S)-8-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid (compound 6).

[0350] 1 H NMR (400 MHz, CD3OD) δ 8.22 (d, 2H), 7.75 (d, 2H), 7.33 (d, 1H), 6.76 (s, 1H), 6.36 (d, 1H), 4.83 – 4.70 (m, 1H), 4.34 (d, 1H), 4.22 (d, 1H), 4.00 – 3.86 (m, 2H), 3.63 – 3.40 (m, 2H), 2.51 (s, 3H), 2.31 – 2.20 (m, 1H), 2.10 – 1.92 (m, 4H), 1.90 – 1.77 (m, 3H). LCMS m / z = 438.2 [M+1] + Compound 6 is one of the isomers of structure 6-A or 6-B.

[0351] Example 7: Trifluoroacetate of 4-((2S)-4-cyclopropyl-1-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 7 (diastere-1)] 4-((2S)-4-cyclopropyl-1-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0352]

[0353] Step 1: 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-(methoxy-d3)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [7a (diastereomer 1)] tert-butyl 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-(methoxy-d3)-7-methyl-1H-indole-1-carboxylate

[0354] Compound 5c (diastereomer 1) (162 mg, 0.625 mmol) was dissolved in 5 mL of isopropyl acetate, and maleic acid (73 mg, 0.628 mmol) was added. The reaction was carried out at room temperature for 1 h. The reaction system was concentrated under reduced pressure to give crude methyl 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c (diastereomer 1)] maleate (235 mg). The maleate (235 mg) of the crude product 4-((2S)-4-cyclopropylpiperidin-2-yl)benzoate [5c (diastereomer 1)] was dissolved in 10 mL of ethanol, and tert-butyl 4-formyl-5-trideuterated methoxy-7-methyl-1H-indole-1-carboxylate (6b) (165 mg, 0.564 mmol) was added. 20 mg of Ir(CO)2acac was added, the mixture was purged with hydrogen three times, the temperature was raised to 80 °C, and the reaction was carried out under a hydrogen balloon atmosphere for 16 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1) to give 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-(methoxy-d3)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [7a (diastereomer 1)] (200 mg, yield: 60%).

[0355] LCMS m / z = 536.3 [M+1] + Based on the hydrogens at positions C1 and C3 of the final product compound 5 1 H- 1 H NOESY confirmed that compound 7a (diastere 1) has the structure 7a-B.

[0356] Step 2: Trifluoroacetate of 4-((2S)-4-cyclopropyl-1-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 7 (diastere-1)] 4-((2S)-4-cyclopropyl-1-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid trifluoroacetate

[0357] 4-(((2S)-4-cyclopropyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-(methoxy-d3)-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [7a (diastereomer 1)] (200 mg, 0.37 mmol) was dissolved in 5 mL of methanol, and solid potassium carbonate (257 mg, 1.86 mmol) was added. The mixture was heated to 80 °C and refluxed for 3 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in a mixed solvent of 5 mL THF and 1 mL water, and lithium hydroxide monohydrate (155 mg, 3.7 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure, and the crude product was subjected to Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare a sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the product with a 5% gradient (elution time 15 min), and the product was lyophilized to obtain trifluoroacetate (125 mg) of 4-((2S)-4-cyclopropyl-1-((5-(methoxy-d3)-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 7 (diastereomer 1)].

[0358] 1 H NMR (400 MHz, CD3OD) δ 8.28 – 8.18 (m, 2H), 7.77 – 7.68 (m, 2H), 7.36 – 7.30 (m, 1H), 6.77 (s, 1H), 6.32 (d, 1H), 4.48 (dd, 1H), 4.40 – 4.29(m, 1H), 4.18 – 4.08 (m, 1H), 3.62 – 3.52 (m, 1H), 3.30 – 3.21 (m, 1H), 2.51(s, 3H), 2.25 – 2.12 (m, 1H), 2.09 – 1.85 (m, 2H), 1.79 – 1.60 (m, 1H), 1.20– 1.03 (m, 1H), 0.67 – 0.53 (m, 1H), 0.52 – 0.40 (m, 2H), 0.26 – 0.12 (m, 2H). LCMS m / z = 422.2 [M+1] + Based on the hydrogens at positions C1 and C3 of the final product compound 5 1 H- 1 H NOESY verification confirmed that compound 7 (diastere 1) is structure 7-B.

[0359] Example 8: Formate of 4-((2S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 8 (diastereomer 1)] 4-((2S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid formate

[0360]

[0361] Step 1: (S)-4-cyclobutylene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (8b) benzyl (S)-4-cyclobutylidene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0362] (4-Bromobutyl)triphenylphosphine bromide (7.8 g, 16.31 mmol) was added to 60 mL of ultra-dry THF, cooled to 0 °C, and solid potassium tert-butoxide (3.7 g, 32.97 mmol) was slowly added under a nitrogen atmosphere. The mixture was stirred at 0 °C for 45 min, and then a tetrahydrofuran solution (20 mL) of (S)-2-(4-(methoxycarbonyl)phenyl)-4-oxopiperidin-1-carboxylic acid benzyl ester (5.0 g, 13.6 mmol) (1a) (synthetic method see WO2020016749) was added. The mixture was heated to 35 °C and reacted for 16 h. Add 100 mL of saturated ammonium chloride aqueous solution to the reaction system, extract twice with 100 mL of ethyl acetate, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and purify the crude product by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1) to obtain (S)-4-cyclobutylene-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (8b) (2.8 g, yield: 51%).

[0363] LCMS m / z = 406.2 [M+1]+ Step 2: Maleate of 4-((2S)-4-cyclobutylpiperidin-2-yl)benzoate [8c (diastereomer 1)] methyl 4-((2S)-4-cyclobutylpiperidin-2-yl)benzoate maleate

[0364] (S)-4-cyclobutylidene-2-(4-(methoxycarbonyl)phenyl)piperidin-1-carboxylate benzyl ester (8b) (1.4 g, 3.45 mmol) was dissolved in 20 mL of tetrahydrofuran, and 430 mg of 10% palladium on carbon was added. The mixture was reacted at 35 °C for 16 h under a hydrogen atmosphere. The reaction mixture was filtered under reduced pressure, and the filtrate was concentrated under reduced pressure to give compound 8c (diastereomer 1) (640 mg). Compound 8c (diastereomer 1) (560 mg) was dissolved in 20 mL of isopropyl acetate, and maleic acid (237 mg, 2.04 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to give crude methyl 4-((2S)-4-cyclobutylpiperidin-2-yl)benzoate [8c (diastereomer 1)] maleate (700 mg).

[0365] NMR of compound 8c (diastereomer 1): 1 H NMR (400 MHz, CDCl3) δ 8.02 – 7.94 (m, 2H), 7.47 – 7.39 (m, 2H), 3.90 (s, 3H), 3.63 (dd, 1H), 3.28 – 3.19 (m, 1H), 2.83 – 2.70 (m, 1H), 2.15 –1.56 (m, 10H), 1.49 – 1.35 (m, 1H), 1.14 – 0.92 (m, 2H). Compound 8c (diastere 1) is one of the isomers of structure 8c-A or 8c-B.

[0366] Step 3: 4-(((2S)-4-cyclobutyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [8d (diastereomer 1)] tert-butyl 4-(((2S)-4-cyclobutyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

[0367] The maleate (700 mg) of the crude product 4-((2S)-4-cyclobutylpiperidin-2-yl)benzoate [8c (diastereomer 1)] was dissolved in 15 mL of ethanol, and tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (650 mg, 2.25 mmol) (synthetic method see WO2015009616) was added, along with 70.8 mg of Ir(CO)2acac. The mixture was heated to 75 °C and reacted under a hydrogen balloon atmosphere for 16 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1) to give 4-(((2S)-4-cyclobutyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [8d (diastereomer 1)] (750 mg, yield: 61%).

[0368] Compound 8d (diastere-1) is one of the isomers of structure 8d-A or 8d-B.

[0369] Step 4: Formate of 4-((2S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 8 (diastereomer 1)] 4-((2S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid formate

[0370] 4-(((2S)-4-cyclobutyl-2-(4-(methoxycarbonyl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylic acid tert-butyl ester [8d (diastereomer 1)] (600 mg, 1.097 mmol) was dissolved in 10 mL of methanol, and solid potassium carbonate (760 mg, 5.5 mmol) was added. The mixture was heated to 80 °C and refluxed for 3 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in a mixed solvent of 10 mL THF and 2 mL water, and lithium hydroxide monohydrate (470 mg, 11.20 mmol) was added. The mixture was stirred at room temperature for 16 h. The reaction system was concentrated under reduced pressure, and the crude product was subjected to Pre-HPLC (instrument and preparative column: SHIMADZU LC-20AP & SHIMADZU SPD-20A preparative HPLC, YMCTriart C18, 7 μm, inner diameter × length = 50 mm × 250 mm). Preparation method: The crude product was dissolved in methanol and dimethyl sulfoxide and filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: acetonitrile / water (containing 0.225% formic acid). Gradient elution method: Acetonitrile was used to elute 53% by a 23% gradient (elution time 18 min), and the solution was lyophilized to obtain 500 mg of formate of 4-((2S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [compound 8 (diastereomer 1)].

[0371] 1 H NMR (400 MHz, CD3OD) δ 8.35 (s, 1H), 8.21 – 8.13 (m, 2H), 7.72 – 7.60 (m, 2H), 7.35 – 7.28 (m, 1H), 6.75 (s, 1H), 6.37 – 6.24 (m, 1H), 4.62 – 4.27 (m, 2H), 4.19 – 4.05 (m, 1H), 3.80 – 3.68 (m, 3H), 3.62 – 3.42 (m, 1H), 3.39 – 3.21 (m, 1H), 2.50 (s, 3H), 2.30 – 1.20 (m, 12H). LCMS m / z = 433.3 [M+1] + Compound 8 (diastere 1) is one of the isomers of structure 8-A or 8-B.

[0372] Example 9: 4-((2S)-4-(azacyclobut-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid [Compound 9 (diasteretype 1)] 4-((2S)-4-(azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid

[0373] Step 1: (2S)-4-(azacyclobut-1-yl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylic acid benzyl ester (9a) benzyl (2S)-4-(azetidin-1-yl)-2-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

[0374] (S)-2-(4-(methoxycarbonyl)phenyl)-4-oxopiperidin-1-carboxylic acid benzyl ester (1.5 g, 4.08 mmol) (1a) (synthetic method see WO2020016749) was dissolved in 30 mL THF, and aziridine (0.47 g, 8.23 ​​mmol) and acetic acid (0.7...

Claims

1. A compound or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals, wherein the compound is selected from the compounds of general formula (I). 2.R 1 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy group, -C(=O)C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituent is a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the 3- to 10-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; p is selected from 0, 1, or 2; n is selected from 0, 1, or 2; W is selected from O or S; R 2 Selected from halogens, C 1-6 Alkyl or C 1-6 Alkoxy group, wherein the alkyl or alkoxy group is optionally further substituted by 0 to 4 substituents selected from H, D, halogen, OH, cyano or NH2; X1 and X2 are each independently selected from N or CR. 3 ; Y is selected from NR 7 or C(R) 7 )2; R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6 Alkyl or C 1-6 alkoxy groups, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituent is a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the 3- to 10-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; As an option, two R 7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic group is substituted, wherein the 3- to 6-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; As an option, R at adjacent positions 6 With R 7 Double bonds can be formed; As an option, two R 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 3 Each is independently selected from H, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 1c Selected from OH, NH2, C 1-6 Alkoxy, NHC 1-4 Alkyl or N(C) 1-4 Alkyl)2; R is selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 Substituents of alkyl groups; R 4 Selected from C 5-12 Carbocyclic groups, 5- to 12-membered heterocyclic groups, C 6-12 aryl or 5 to 12-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further surrounded by 0 to 4 R groups. 5 The substitution, wherein the heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl or 4- to 12-membered heterocyclic groups, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; R 4a R 4b Each group is independently selected from H, OH, cyano, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3 to 8-membered heterocyclic group is substituted, wherein the 4 to 10-membered heterocyclic group or 3 to 8-membered heterocyclic group or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 4c R 4d Each is independently selected from H, OH, and C. 1-6 Alkyl, C 1-6 Alkoxy, -NR 1a R 1b -OR 1d -C 3-8 Carbocyclic groups, 4- to 10-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3 to 8-membered heterocyclic group is substituted, wherein the 4 to 10-membered heterocyclic group or 3 to 8-membered heterocyclic group or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 12-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 1a R 1b Each is independently selected from H and C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 1d Each is independently selected from H and C 1-6 Alkyl, C 3-8 A carbocyclic or 4- to 10-membered heterocyclic group, wherein the alkyl, carbocyclic, or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic group is substituted, wherein the 4- to 10-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 8 Selected from H, halogen, OH, cyano, NH2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl group, -S (=O) p C 1-6 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituent is a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the 3- to 10-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-8 A carbocyclic or 3- to 10-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The substituent is a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the 3- to 10-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; When Y is selected from C(R) 7 )2, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, cyano C 1-6 Alkyl or unsubstituted C 1-6 alkoxy group, and two R groups 7 When the carbon atom attached to it does not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1) R 1 Selected from C 2-6 alkynyl group, C 3-6 Cycloalkyl-substituted C 1-6 Alkyl, 3- to 8-membered heterocyclic substituted C 1-6 Alkyl, -WC 3-8 A carbocyclic or -W-4 to 10-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic group is substituted, wherein the 4- to 10-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-6 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-6 Alkyl, hydroxyl substituted C 1-6 alkyl or cyano-substituted C 1-6 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N.

3. The compound or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals according to claim 1. R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy group, -C(=O)C 1-4 Alkyl group, -S (=O) p C 1-4 Alkyl, -WR 1d -CH2NHC(O)C 1-4 Alkyl group, -CH2C(=O)R 1c -OCH2C(=O)R 1c C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The 4 to 8-membered heterocyclic group is replaced by a substituent of a cycloalkyl or 3 to 8-membered heterocyclic group, wherein the 4 to 8-membered heterocyclic group or the 3 to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 2 Selected from halogens, C 1-4 Alkyl or C 1-4 Alkyl group, wherein the alkyl group or alkoxy group is optionally further substituted with 0 to 4 substituents selected from H, D, halogen, OH, cyano or NH2; X1 and X2 are each independently selected from N or CR. 3 ; R 6 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl or C 1-4 alkoxy groups, wherein the alkyl group or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 7 Each is independently selected from H, halogen, OH, -NR 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d C 3-6 A carbocyclic or 3- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic groups are substituted, wherein each of the 3- to 8-membered heterocyclic groups contains 1 to 4 heteroatoms selected from O, S or N; As an option, two R 7 Together with the carbon atom attached thereto, a 3-6 membered heterocyclic group is formed, wherein the heterocyclic group is optionally further surrounded by 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic group is substituted, wherein the 3- to 6-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; As an option, R at adjacent positions 6 With R 7 Double bonds can be formed; As an option, two R 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 3 Each is independently selected from H, halogen, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -CH2C(=O)R 1c -S(=O) p C 1-4 Alkyl group, -CH2NHC(O)C 1-4 Alkyl group, -OCH2C(=O)R 1c C 3-6 Carbocyclic or 5- to 6-membered heteroaryl, wherein the alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 Alkynyl, carbocyclic, or heteroaryl groups may be further decorated with 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted, wherein the heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; R 1c Selected from OH, NH2, C 1-4 Alkoxy, NHC 1-4 Alkyl or N(C) 1-4 Alkyl)2; R is selected from H and C. 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 4 Selected from C 5-7 Monocyclic carbocyclic group, C 5-12 fused carbonyl group, C 5-12 Spirocyclic carbocyclic group, C 5-12 5- to 7-membered bridged carbide ring groups, 5- to 12-membered monocyclic heterocyclic groups, 5- to 12-membered fused ring heterocyclic groups, 5- to 12-membered spirocyclic heterocyclic groups, or 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N; R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; R 4a R 4b Each group is independently selected from H, OH, cyano, NH2, and C. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10 aryl or 5- to 6-membered heteroaryl, wherein the alkyl, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The 4 to 8-membered heterocyclic group or the 3 to 8-membered heterocyclic group or the heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N. R 4c R 4d Each is independently selected from H, OH, and C. 1-4 Alkyl, C 1-4 Alkoxy, -NR 1a R 1b -OR 1d C 3-6 Carbocyclic groups, 4- to 8-membered heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the alkyl, alkoxy, carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The 4 to 8-membered heterocyclic group or the 3 to 8-membered heterocyclic group or the heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N. R 4e R 4f Each is independently selected from H, OH, and -NR. 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy or C 3-6 Cycloalkyl groups, 5- to 10-membered heterocyclic groups, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 1a R 1b Each is independently selected from H and C 1-4 Alkyl groups, wherein the alkyl group is optionally composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 1d Each is independently selected from H and C 1-4 Alkyl, C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, carbocyclic or heterocyclic group is optionally composed of 0 to 4 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The 4 to 8-membered heterocyclic group is replaced by a substituent of a cycloalkyl or 3 to 8-membered heterocyclic group, wherein the 4 to 8-membered heterocyclic group or the 3 to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 8 R 9 Or R 10 Each group is independently selected from H, halogen, OH, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthioyl, wherein the alkyl, alkenyl, alkoxy, or alkylthioyl group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; When Y is selected from C(R) 7 )2, R 7 Selected from H, OH, -NR 1a R 1b Unreplaced C 1-4 Alkyl, hydroxyl C 1-4 Alkyl, cyano C 1-4 Alkyl or unsubstituted C 1-4 alkoxy group, and two R groups 7 When the carbon atom attached to it does not form a 3-6 membered heterocyclic group, one of the following conditions must be met: 1)R 1 Selected from C 2-4 alkynyl group, C 3-6 Cycloalkyl-substituted C 1-4 Alkyl, 3- to 8-membered heterocyclic substituted C 1-4 Alkyl, -WC 3-6 A carbocyclic or -W-4 to 8-membered heterocyclic group, wherein the alkynyl, alkyl, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The substituent is a cycloalkyl or 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group or 4- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 2) R at adjacent positions 6 With R 7 Formation of double bonds; 3) Two Rs 6 Together with the atoms bonded to it, they form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally further composed of 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 The alkyl group is substituted with a substituent, wherein the heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; 4) X2 is selected from N.

4. The compound or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals according to claim 2. R 1 Selected from H, halogen, OH, cyano, NH2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkylthio, -WR 1d C 3-6 A carbocyclic or 4- to 8-membered heterocyclic group, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The 4 to 8-membered heterocyclic group is replaced by a substituent of a cycloalkyl or 3 to 8-membered heterocyclic group, wherein the 4 to 8-membered heterocyclic group or the 3 to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 2 The group is selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, I, OH, cyano or NH2. R 3 Each of the following is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 6 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further selected by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R is selected from H, methyl, ethyl, propyl or isopropyl, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl or CF3; R 4 Selected from C 5-6 Monocyclic carbocyclic group, C 5-10 fused carbonyl group, C 5-11 Spirocyclic carbocyclic group, C 5-12 5- to 6-membered bridged carbide ring groups, 5- to 10-membered fused ring heterocyclic groups, 5- to 11-membered spirocyclic heterocyclic groups, 5- to 12-membered bridged ring heterocyclic groups, C 6-10 aryl or 5 to 10-membered heteroaryl, wherein the carbocyclic, heterocyclic, aryl, or heteroaryl group is optionally further divided by 0 to 4 R groups. 5 The heterocyclic or heteroaryl group is replaced by 1 to 4 heteroatoms selected from O, S or N; R 5 Each group is independently selected from H, halogen, OH, cyano, -C(=O)R 4e -S(=O)2R 4e -CH2C(=O)R 4e -C(=O)NHS(=O)2R 4e -C(=O)NR 4e R 4f -S(=O)2NHC(=O)R 4e -S(=O)2NR 4e R 4f -P(O)R 4c R 4d , , C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 3-6 Cycloalkyl or 4- to 6-membered heterocyclic group, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally further surrounded by 0 to 4 H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl or C 3-6 The heterocyclic group is substituted by a cycloalkyl substituent, wherein the heterocyclic group contains 1 to 5 heteroatoms selected from O, S or N; R 4a R 4b R 4c R 4d Each of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl is optionally further selected from 0 to 4 of the following: H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 1a R 1b Each is independently selected from H, methyl, ethyl, propyl, or isopropyl, wherein the methyl, ethyl, propyl, or isopropyl group is optionally further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 4e R 4f Each is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl; R 1d Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl is optionally selected from 0 to 4 of the following: H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 8 R 9 Or R 10 Each is independently selected from H, F, Cl, Br, I, OH, cyano, CF3, NH2, methyl, and ethyl.

5. The compound according to claim 3, or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound is selected from compounds of general formulas (Ia), (Ib), (Ic), (Id), (Ie), or (If).

6. n is independently selected from 0, 1, or 2; R 3 Each of the following groups is independently selected from H, F, Cl, Br, I, cyano, methyl, ethyl, propyl, isopropyl, -CH2C(=O)OH, -CH2C(=O)NH2, wherein the methyl, ethyl, propyl or isopropyl group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, cyano. R 6 Each of the following groups is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, or isopropoxy group is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, or -CH2OH; R 7 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, Ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxazine, oxazine-butyl, oxazine-pentyl, oxazine-hexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 7A Selected from H, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridyl, pyrazinyl, pyrazinyl, or pyrimidinyl, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl, pyrazolyl, pyrroleyl, imidazoleyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 7a Each is independently selected from R d F, Cl, Br, I, vinyl, ethynyl, propynyl, propyrynyl, -C(=O)R 1d -S(=O)2R 1d Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl, wherein the vinyl, ethynyl, propynyl, propargyl, or cyclopropyl groups are... Cyclobutyl, cyclopentyl, azacyclobutyl, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, imidazolyl, furanyl, thiophene, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, or pyrimidinyl may optionally be further composed of 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R d Each of the following is independently selected from methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy, wherein the methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, and isopropoxy groups are further selected by one to three groups selected from halogen, ethynyl, and C. 2-4 alkynyl group, C 1-4 Alkoxy, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 Substituted with cycloalkyl or 3 to 8-membered heterocyclic groups; (Ib) It indicates a single bond or a double bond, and contains only one double bond; In (Id), as a choice, the two Rs 7 Together with the carbon atom attached thereto, it forms an oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group, wherein the oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine group is optionally further composed of 0 to 4 atoms selected from H, halogen, OH, =O, cyano, -C(=O)R 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; Or in (Id), two Rs 6 Together with the atoms attached thereto, they form cyclobutyl, cyclopentyl, cyclohexyl, oxecyclobutyl, oxecyclopentyl, oxecyclohexyl, thiocyclopentyl, aziroxybutyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazineyl. R 1A The group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further composed of 0 to 2 elements selected from H, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 1 Each group is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, eththio, cyclopropyl, cyclobutyl, or -WR. 1d The methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propargyl, methylthio, ethio, cyclopropyl, and cyclobutyl groups are optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, and C. 1-4 Alkyl, C 2-4 alkynyl group, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 4 Each of the following groups is independently selected from cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrazolyl, pyrimidinyl, or naphthidinyl, wherein the cyclopentyl, cyclohexyl, benzocyclohexyl, benzocyclopentyl, phenyl, naphthyl, pyridyl, pyrimidinyl, or naphthidinyl is optionally further divided by 0 to 4 R groups. 5 replace; R 4a R 4b R 4c R 4d Each of the following is independently selected from H, OH, NH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, or cyclobutyl is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, or CF3; R 1d Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, oxecyclobutyl, azircyclobutyl, pyrrolidinyl, or phenyl is optionally substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, azircyclobutyl, or pyrrolidinyl.

7. The compound according to claim 4, or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound is selected from the compounds of general formula (Id). R 4 Each independently selected , , , , or ; Or R 4 Each independently selected , , ; R 5 Each is independently selected from H, F, Cl, Br, I, OH, cyano, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -COOH, -CH2OH, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2OH, , , -C(=O)NH2, -C(=O)NHOH, -S(=O)2NHC(=O)CH3, -C(=O)NHS(=O)2CH3, pyrazolyl, tetrazolyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, pyrazolyl, tetrazolyl are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl or cyclobutyl; Selected from , or ; R 1 Each is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, -OCD3, CD3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, ethynyl, -CH2-cyclopropyl, or -O-cyclopropyl; Or R 1 Each is independently selected from -OCH2F, -OCHF2, -OCF3, , ; R 2 Each is independently selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; Or R 2 Each is independently selected from CD3, CHD2, and CH2D; R 3 Each is independently selected from H, methyl, or ethyl; Selected from the excerpt in the table below, above which is R 4 Connected, 8. The compound according to claim 4, or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound is selected from compounds of general formulas (Ia), (Ib), (Ic), (Ie), or (If). Selected from , or ; #imgpt85# is selected from #imgpt86# or #imgpt87#; R 1A The group is selected from ethynyl, propynyl, propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxacyclobutyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, wherein the ethynyl, propynyl, propynyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -CH2- is optionally further substituted by 0 to 2 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, ethynyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, cyclobutyl, azacyclobutyl or pyrrolidinyl; R 1 Each is independently selected from H, F, Cl, Br, I, OH, cyano, NH2, -OCD3, CD3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, cyclopropyl, ethynyl, -CH2-cyclopropyl, or -O-cyclopropyl; Or R 1 Each can be independently selected from -OCH2F, -OCHF2, -OCF3, #imgpt88#, and #imgpt89#; R 2 Each is independently selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; Or R 2 Each is independently selected from CD3, CHD2, and CH2D; R 3 Each is independently selected from H, methyl, or ethyl; R 4 Each character is independently selected from #imgpt90#, #imgpt91#, #imgpt92#, #imgpt93#, #imgpt94#, or #imgpt95#. R 5 Each is independently selected from H, F, Cl, Br, I, OH, cyano, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, -COOH, -CH2OH, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2OH, #imgpt96#, #imgpt97#, #imgpt98#, -C(=O)NH2, -C(=O)NHOH, -S(=O)2N HC(=O)CH3, -C(=O)NHS(=O)2CH3, pyrazolyl, tetrazolyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, pyrazolyl, and tetrazolyl groups are optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, I, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, CF3, -CH2F, -CH2OH, cyclopropyl, or cyclobutyl. In (Ia), #imgpt99# is selected from #imgpt100#, and its upper part is R. 4 Connected; In (Ib), #imgpt101# is selected from #imgpt102# or #imgpt103#, and its upper part is R. 4 Connected; In (Ic) or (If), #imgpt104# is selected from #imgpt105#, and above it is R. 4 Connected; In (Ie), #imgpt106# is selected from #imgpt107#, and its upper part is R. 4 Connected; R 6 Each is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, and isopropyl. R 7 Each of the following is independently selected from H, F, Cl, Br, I, OH, NH2, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, imidazolyl, furanyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl; R 7A Selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, tert-butyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -CH2CH2OCH3, -CH2CF3, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O)-phenyl, -S(=O)2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, or imidazolyl; R 7a Selected from F, Cl, Br, I, CF3, -CH2F, vinyl, ethynyl, propynyl, propynyl, -CH2-propynyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-azacyclobutyl, -CH2OCH3, -OCH2CH2OCH3, -CH2CH2OCH3, -CH2CF3, -OCH2-cyclopropyl, -C(=O)CH3, -C(=O)-cyclopropyl, -C(=O) -phenyl, -S(=O)2CH3, -S(=O)2CH2CH3, -S(=O)2-cyclopropyl, -S(=O)2-CH2-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl or pyrimidinyl.

9. The compound according to claim 4, or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or eutectics, wherein the compound of general formula (Id) is selected from compounds of general formula (Id-1) or general formula (Id-2). #imgpt108##imgpt109# 10.R 4 Selected from #imgpt110# and #imgpt111#, wherein R 4 Optionally further substituted with 0, 1, 2 or 3 substituents selected from F, Cl, Br, I, OH, cyano, methyl, ethyl, methoxy or ethoxy; R 1 Selected from H, F, Cl, Br, I, -OCD3, CD3, methyl, ethyl, propyl, methoxy, ethoxy, isopropoxy, cyclopropyl, -CH2-cyclopropyl, or -O-cyclopropyl; Or R 1 Each is independently selected from -OCH2F, -OCHF2, -OCF3, #imgpt112#, #imgpt113#; R 2 Selected from F, Cl, Br, I, methyl, ethyl, propyl, and isopropyl; Or R 2 Each is independently selected from CD3, CHD2, and CH2D; R 7 The molecule is selected from methoxymethyl, methoxyethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, ethynyl, propynyl, or propynyl is optionally further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, and methoxy. 2 Rs 7B Together with the carbon atoms connected to it, they form the following rings: #imgpt114#, #imgpt115#, #imgpt116#, #imgpt117#, #imgpt118#, #imgpt119#, #imgpt120#.

11. The compound according to claim 2, or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound of formula (I) is selected from the compounds shown in formulas (Id-3) and (Id-4). #imgpt121#(Id-3) #imgpt122#(Id-4) #imgpt123# is selected from either a single bond or a double bond. When selected from a double bond, R 7’ It does not exist, and at most one of #imgpt124# in the general formula (Id-4) is selected from a double bond; Ring B is selected from 3-6 membered heterocyclic groups, wherein the heterocyclic group is optionally further surrounded by 0 to 4 groups selected from H, halogen, OH, =O, cyano, -C(=O)R. 1d -S(=O)2R 1d NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic group is substituted, wherein the 3- to 6-membered heterocyclic group or the 3- to 8-membered heterocyclic group contains 1 to 4 heteroatoms selected from O, S or N; R 6 Each element is independently selected from H, halogens, OH, NH2, and C. 1-4 Alkyl or C 1-4 Alkyl groups, wherein the alkyl or alkoxy group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 7 Selected from C 2-4 alkynyl group, C 3-6 Carbocyclic groups, 3- to 8-membered heterocyclic groups, R 7 Selected from H, halogens, OH, -NR 1a R 1b C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)R 1d -S(=O)2R 1d The alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally further selected from 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic groups are substituted, wherein each of the 3- to 8-membered heterocyclic groups contains 1 to 4 heteroatoms selected from O, S or N.

12. The compound of claim 8 or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals. X1 is selected from N or CH, X2 is selected from N or CH, wherein the CH is optionally substituted with one methyl or ethyl molecule; Ring B is selected from 3-6 membered heterocyclic alkyl groups, wherein the heterocyclic alkyl group is optionally further divided by 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic or heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 7 Selected from C 2-4 alkynyl, phenyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycloalkyl or 5- to 6-membered heteroaryl, R 7 Selected from H, halogens, OH, -NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, -C(=O)C 1-4 Alkyl group, -S(=O)2C 1-4 Alkyl groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, phenyl, cycloalkyl, heteroaryl, or heterocycloalkyl group is optionally further selected from 0 to 4 elements chosen from H, D, halogen, OH, =O, cyano, NH2, C. 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic alkyl, heterocyclic or heteroaryl group contains 1 to 4 heteroatoms selected from O, S or N; Preferably, Ring B is selected from oxetyl, oxetyl, oxetylhexyl, thiophene, azirone, pyrrolyl, piperidinyl, morpholinyl, or piperazine, wherein the oxetyl, oxetyl, oxetyl, thiophene, azirone, pyrrolyl, piperidinyl, morpholinyl, or piperazine may optionally be further selected from 0 to 4 groups selected from H, halogen, OH, =O, cyano, NH2, -C(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Substituents of alkyl groups; R 7 Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R 7 R 7 When substituted, it may be further replaced by 0 to 4 groups selected from H, D, halogen, OH, =O, cyano, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkyl-substituted C 2-4 alkenyl, C 1-4 Alkyl-substituted C 2-4 alkynyl group, C 1-4 alkyl oxygen-substituted C 1-4 alkoxy- or halogen-substituted C 1-4 Alkyl, hydroxyl substituted C 1-4 alkyl and cyano substituted C 1-4 Alkyl, C 3-6 The cyclic alkyl or 3- to 8-membered heterocyclic substituents are substituted, wherein the heterocyclic substituent contains 1 to 4 heteroatoms selected from O, S or N; R 6 Each is independently selected from H, F, Cl, Br, CF3, methyl, or ethyl; R 1 R 2 R 4 The definition is the same as in claim 5.

13. The compound of claim 9 or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals. Ring B is selected from oxetyl, oxetyl, oxetylhexyl, thiophene, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine, wherein the oxetyl, oxetyl, oxetyl, thiophene, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, or piperazine is optionally further substituted by 0 to 4 substituents selected from H, F, Cl, Br, CF3, OH, =O, cyano, NH2, -C(=O)CH3, methyl, ethyl, methoxy, or ethoxy. R 7 Selected from one of the following groups, substituted or unsubstituted: ethynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl, pyrazolyl, pyrroleyl, imidazolyl, furanyl, thiophenyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, 1,2,4-oxadiazolyl, pyridinyl, pyrazinyl, pyrazinyl, or pyrimidinyl, R 7 Selected from H, F, OH, NH2, or one of the following groups, substituted or unsubstituted: methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, vinyl, ethynyl, propynyl, or propargyl, when R 7 R 7 When substituted, it may optionally be further substituted by 0 to 4 substituents selected from H, D, F, Cl, Br, CF3, OH, =O, cyano, NH2, methyl, ethyl, methoxy, ethoxy, ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl or piperazine; R 1 R 2 R 4 The definition is the same as in claim 6.

14. The compound of claim 8 or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals. R 4 Selected from #imgpt125# and #imgpt126#, wherein R 4 It may be optionally substituted with one, two or three substituents selected from F, Cl, Br, I, OH, cyano, methyl, ethyl, methoxy or ethoxy.

15. The compound according to claim 10, or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound is selected from compounds of general formula (Id-5). #imgpt127#(Id-5) #imgpt128# is selected from #imgpt129#, #imgpt130#, and #imgpt131#; R 1 Selected from -OCH3 or -OCD3; R 2 Selected from -CH3 or -CD3; n is selected from 1, 2, or 3.

16. The compound according to claim 2, or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, wherein the compound is selected from compounds of general formula (Id-7) and general formula (Id-8). #imgpt132#(Id-7) #imgpt133#(Id-8) #imgpt134# is selected from #imgpt135#, #imgpt136#, and #imgpt137#; R 1 Selected from -OCH3 or -OCD3; R 2 Selected from -CH3 or -CD3.

17. The compound of claim 1 or its stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or eutectics, wherein the compound is selected from one of the structures shown in Table E-1.

18. A pharmaceutical composition comprising the compound or stereoisomer of any one of claims 1-14, a deuterated product, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or cocrystal, and a pharmaceutically acceptable carrier.

19. A pharmaceutical composition or pharmaceutical preparation comprising 1-600 mg of the compound or its stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or eutectic and pharmaceutical excipient as described in any one of claims 1-14.

20. The use of the compound or stereoisomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or cocrystal of any one of claims 1-14, or the pharmaceutical composition of any one of claims 15-16, in the preparation of a medicament for treating diseases (preferably kidney diseases) related to complement factor B activity or expression.

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