GIP receptor antagonist and pharmaceutical use thereof

Abstract

A GIP receptor antagonist and the pharmaceutical use thereof. The present invention specifically relates to a compound as represented by general formula (I) or a stereoisomer, racemate, tautomer or pharmaceutically acceptable salt thereof, an intermediate thereof and a preparation method therefor, and the use thereof in the preparation of a drug for treating diabetes or obesity.

Description

A GIP receptor antagonist and its medical applications

[0001] Cross-references to related applications

[0002] This application claims priority and benefit to Chinese Patent Application No. 202510349850.0, filed March 24, 2025; Chinese Patent Application No. 202510574424.7, filed May 6, 2025; Chinese Patent Application No. 202510986822.X, filed July 17, 2025; Chinese Patent Application No. 202511530163.5, filed October 24, 2025; and Chinese Patent Application No. 202610135160.X, filed January 30, 2026, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This application relates to a compound of general formula (I) or its stereoisomers, racemates, tautomers, pharmaceutically acceptable salts, intermediates thereof, and methods of preparation thereof, as well as its use in the preparation of medicaments for treating diabetes or obesity. Background Technology

[0004] Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. Hyperglycemia is caused by a deficiency in insulin secretion or impaired biological action, or both. The long-term hyperglycemia in diabetes leads to chronic damage and dysfunction of various tissues, especially the eyes, kidneys, heart, blood vessels, and nerves. It is mainly divided into two types: Type 1 diabetes: Destruction of pancreatic beta cells leads to an absolute lack of insulin. Type 2 diabetes: Primarily characterized by insulin resistance accompanied by a relative lack of insulin, or primarily characterized by impaired insulin secretion accompanied by insulin resistance.

[0005] Drugs for type 2 diabetes can be divided into six major classes (insulin, insulin secretagogues, biguanides, glucosidase inhibitors, thiazolidinediones, and SGLT2 inhibitors), each acting through a different primary mechanism. However, with the exception of GLP-1 receptor agonists and SGLT2 inhibitors, these drugs have limited efficacy and cannot address the most critical issues: decreased cellular function and associated obesity.

[0006] Metabolic diseases such as obesity and type 2 diabetes urgently require novel treatments. While traditional GLP-1 receptor agonists (such as smegglutide) are effective, they suffer from tolerability and weight rebound after discontinuation. Small molecule GLP-1 antagonists, by inhibiting the lipogenic effects of GLP, could become potential targets for combating obesity and improving insulin resistance. GLP is an incretin hormone that promotes insulin secretion through the GLP receptor (GIPR), but its effects are glucose-dependent. Studies have found that GLP may have negative effects in obesity and insulin resistance, such as promoting fat deposition. Preclinical studies have shown that GLP receptor antagonists (such as GIP(3-30)) can effectively inhibit GLP-mediated insulin and glucagon release and reduce fat accumulation.

[0007] Small molecule GIP drugs have advantages such as oral administration and low production cost, and are an important direction for replacing peptide antagonists. Summary of the Invention

[0008] The purpose of this application is to provide a class of GIP receptor antagonists that can effectively reduce side effects, have good GIP receptor antagonistic effects, oral bioavailability, and weak inhibitory activity against CYP.

[0009] This application provides a compound of general formula (I) or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts.

[0010] Preferably, the general formula (I) is selected from the compounds shown in (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), and (Im).

[0011] Preferably, general formula (I) is selected from the compounds shown in (IA).

[0012] Preferably, general formula (I) is selected from the compounds shown in (IB).

[0013] Preferably, the general formula (I) is selected from the compounds shown in (IC).

[0014] Preferably, general formula (I) is selected from the compounds shown in (ID).

[0015] Preferably, the general formula (I) is selected from the compounds represented by (I-DD).

[0016] Preferably, general formula (I) is selected from the compounds shown in (IE).

[0017] Preferably, general formula (I) is selected from the compounds shown in (IF).

[0018] Preferably, the compound is selected from the compounds shown in (I-D1).

[0019] Preferably, the compound is selected from the compounds shown in (I-C1).

[0020] Preferably, the compound is selected from the compounds shown in (I-B1).

[0021] Preferably, the compound is selected from the compounds shown in (I-B2).

[0022] Preferably, the compound is selected from the compounds shown in (I-F1).

[0023] Preferably, the compound is selected from the compounds shown in (I-h1).

[0024] In some implementation schemes, ring B is selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-. Choose from 1 to 6 Rs b1 replace;

[0025] In some implementations, ring B is independently selected from either ring B1 or ring B2;

[0026] In some implementation schemes, rings B1 are each independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0027] In some implementation schemes, rings B2 are independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0028] Preferably, each ring B is independently selected from 1 to 6 R. b1 Replacement And at least one R b1 Selected from R b One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0029] Preferably, rings B are each independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0030] Preferably, ring B is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0031] In some implementation schemes, Y is independently selected from NR. b4 O or CR b1 R b2 ;

[0032] Preferably, Y is selected from Y1, and Y1 is selected from NR. b4 O;

[0033] Preferably, Y is selected from CR b1 R b2 ;

[0034] In some implementation schemes, b1 is independently selected from 1, 2, and 3; b2 is independently selected from 0, 1, 2, and 3.

[0035] In some implementations, the sum of b1 and b2 is selected from 2 and 3; in some implementations, the sum of b1 and b2 is selected from 3, 4, 5, and 6.

[0036] Preferably, each ring B1 is independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0037] Preferably, each ring B1 is independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0038] Preferably, each ring B1 is independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0039] More preferably, each ring B1 is independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0040] More preferably, each ring B1 is independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0041] In some implementation schemes, b1 is independently selected from 1 and 2;

[0042] In some implementations, X1 and X2 are each independently selected from O or S;

[0043] Preferably, X1 and X2 are each independently selected from O; preferably, X1 and X2 are each independently selected from S.

[0044] In some implementations, at least one of X1 and X2 is selected from S; preferably, one of X1 and X2 is selected from S and the other is selected from O; preferably, X1 is selected from S and X2 is selected from O; preferably, X1 is selected from O and X2 is selected from S.

[0045] In some implementations, L is selected from key or CR L1 R L2 ;

[0046] Preferably, each L is independently selected from a bond or CH2; preferably, each L is independently selected from a bond.

[0047] In some implementations, ring A is independently selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cycloheteroaryl, 5-6 membered heteroaryl, pyridinone, pyrimidinone, phenyl;

[0048] Preferably, ring A is selected from ring A1, and each ring A1 is independently selected from benzo[a]C. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cyclocyclic heteroaryl, pyridinone group, pyrimidinone group, 5 membered heteroaryl;

[0049] Preferably, each ring A is independently selected from ring A1, a 6-membered heteroaryl group, or a phenyl group;

[0050] Preferably, each ring A1 is independently selected from benzo[a]C. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cyclocyclic heteroaryl, pyridinone group, pyrimidinone group, 5 membered heteroaryl;

[0051] Preferably, each ring A is independently selected from ring A1, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl.

[0052] Preferably, each ring A1 is independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphene, benzocyclopentyl, benzocyclohexyl, benzocyclobutenyl, benzocyclopentenyl, benzocyclohexenyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl,

[0053] Preferably, each ring A is independently selected from ring A1,

[0054] Preferably, each ring A1 is independently selected from...

[0055] Preferably, Selected from Preferably, Selected from

[0056] Preferably, Each independently selected

[0057] Preferably, Each independently selected Preferably, Each independently selected More preferably, Each independently selected

[0058] In some implementations, the ring Cs are each independently selected from benzo[C]. 4-12 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 The ring C may be a carbocyclic group, a 5-6 membered heteroaryl group, an 8-10 membered cycloheteroaryl group, a 5-6 membered heteroaryl group, a 5-12 membered heteroaryl group, a pyridinone group, a pyrimidinone group, or a phenyl group, wherein the ring C is optionally surrounded by 1 to 5 R groups. c replace;

[0059] Preferably, ring C is selected from ring C1, and each ring C1 is independently selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 5-12Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the C1 ring is optionally surrounded by 1 to 5 R groups. c replace;

[0060] Preferably, each ring C is independently selected from ring C1, a 6-membered heteroaryl group, or a phenyl group, and the ring C is optionally surrounded by 1 to 5 R groups. c replace;

[0061] Preferably, each of the C1 rings is independently selected from benzo[a]C1. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 5-6 Monocycloalkyl, C 5-12 Bridged cycloalkyl, C 5-12 Spirocycloalkyl, C 5-12 Annular alkyl, 5-7 member monoheterocyclic alkyl, 5-7 member monoheterocyclic alkenyl, 6-12 member spiroheterocyclic alkyl, 6-12 member anheterocyclic alkyl, 6-12 member bridged heterocyclic alkyl;

[0062] Preferably, each ring C is independently selected from ring C1, phenyl, pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl, and the ring C is optionally surrounded by 1 to 5 R groups. c replace;

[0063] Preferably, each of the C1 rings is independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphene, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl, Cyclohexyl, cycloheptyl, pyrrolidinyl, piperidinyl, azacycloheptyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, morpholinyl, piperazine, azacyclohexenyl, wherein the ring C1 is optionally surrounded by 1 to 4 R... c replace;

[0064] In some implementations, s1, s3, and s5 are each independently selected from 0, 1, or 2, while s1 and s3 are not simultaneously selected from 2; s2 and s4 are each independently selected from 0 or 1; and s7 is each independently selected from 1, 2, or 3.

[0065] Preferably, each of s5 is independently selected from 0, 1, or 2;

[0066] Preferably, s7 are each independently selected from 1 and 2;

[0067] Preferably, each ring C is independently selected from ring C1, The ring C is arbitrarily divided by 1 to 4 Rs. c Replacement; preferably, each of the rings C is independently selected from...

[0068] Preferably, each ring C1 is independently selected from... The ring C1 is arbitrarily selected by 1 to 4 Rs c replace;

[0069] Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: benzo[C] 4-6 Carbocyclic groups, benzo4-6 membered heterocyclic groups;

[0070] Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted:

[0071] In some implementations, rings D are each independently selected from C. 4-12 Carbocyclic group, benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 The ring D is optionally surrounded by 1 to 5 R groups: carbocyclic, 5-6-membered heteroaryl, 8-10-membered cycloheteroaryl, 5-6-membered heteroaryl, 5-12-membered heteroaryl, pyridone, pyrimidinone, or phenyl. d replace;

[0072] Preferably, ring D is selected from ring D1, and each ring D1 is independently selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 4-12 Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the ring D1 is optionally surrounded by 1 to 5 R groups. d replace;

[0073] Preferably, each ring D is independently selected from ring D1, a 6-membered heteroaryl group, or a phenyl group, and the ring D is optionally surrounded by 1 to 5 R groups. d replace;

[0074] Preferably, each ring D is independently selected from ring D1 or phenyl, and the ring D is optionally surrounded by 1 to 5 R groups. d replace;

[0075] Preferably, each ring D1 is independently selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 4-6 Monocycloalkyl, C 5-12 Bridged cycloalkyl, C 5-12 Spirocycloalkyl, C 5-12 Annular alkyl, 5-7 member monoheterocyclic alkyl, 5-7 member monoheterocyclic alkenyl, 6-12 member spiroheterocyclic alkyl, 6-12 member anheterocyclic alkyl, 6-12 member bridged heterocyclic alkyl;

[0076] Preferably, each ring D is independently selected from ring D1, phenyl, pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl, and the ring D is optionally surrounded by 1 to 5 R groups. d replace;

[0077] Preferably, each ring D1 is independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphene, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl, Cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyrrolidinyl, piperidinyl, azacycloheptyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, morpholinyl, piperazine, azacyclohexenyl, wherein the ring D1 is optionally surrounded by 1 to 4 R... d replace;

[0078] Preferably, each ring D is independently selected from ring D1, The ring D is arbitrarily divided by 1 to 4 Rs. d Replacement; preferably, each ring D is independently selected from...

[0079] Preferably, each ring D1 is independently selected from... The ring D1 is arbitrarily selected by 1 to 4 Rs d replace;

[0080] Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: C 5-10 Bridged cycloalkyl;

[0081] Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect;

[0082] Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect;

[0083] Preferably, Each independently selected Preferably, Each individual selection is chosen independently from 1 to 4 Rs. d The following groups are substituted: Preferably, Selected from Preferably, Selected from

[0084] In some implementation schemes, R c With R d Together with the skeleton connected to it, they form ring E, and each ring E is independently selected from C. 4-10 Carbon rings, 4- to 10-membered heterocycles, wherein the ring E is optionally divided by 1 to 5 R... k replace;

[0085] Preferably, rings E are each independently selected from C. 4-8 Carbon rings, 4- to 8-membered heterocycles, wherein the ring E is optionally divided by 1 to 5 R... k replace;

[0086] Preferably, each ring E is independently selected from cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, pyrrolidinyl, piperidinyl, azircycloheptyl, azircyclooctyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, oxacyclooctyl, azircycloheptenyl, azircyclooctenyl, oxacyclopentenyl, oxacyclohexenyl, oxacycloheptenyl, oxacyclooctenyl, and oxacyclooctenyl, wherein the ring E is optionally surrounded by 1 to 4 R... k replace;

[0087] Preferably, Selected from

[0088] In some implementation schemes, R D Each is independently selected from -C(=O)OH and -C(=O)OR 1 -C(=O)NR1 R 2 -S(=O)2NHCF3,

[0089] Preferably, R D Selected from R 1D R 1D Selected from

[0090] Preferably, R D Selected from -C(=O)OH, -C(=O)OC(CH3)3, -C(=O)NH2, -S(=O)2NHCF3,

[0091] Preferably, R D Selected from -C(=O)OH;

[0092] In some implementation schemes, R 1 R 2 R b4 Each is independently selected from H and C. 1-6 Alkyl, C 1-4 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 5 R... k replace;

[0093] Preferably, R 1 R 2 R b4 Each is independently selected from H and C. 1-4 Alkyl, -C 1-2 Alkylene-OC 1-4 Alkyl, C 3-6 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 4 R... k replace;

[0094] Preferably, R 1 R 2 R b4 Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine groups are optionally separated by 1 to 4 R groups. k replace;

[0095] Preferably, R 1Each of the following groups is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0096] Preferably, R 2 Each of the following groups is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0097] Preferably, R b4 Each of the following groups is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0098] In some implementation schemes, R L1 R L2 Each is independently selected from H and C. 1-6 Alkyl, -OC 1-6 Alkyl, C 1-2 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, carbocyclic, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 5 R... k replace;

[0099] Preferably, R L1 R L2 Each is independently selected from H and C. 1-4 Alkyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 4 R... k replace;

[0100] Preferably, R L1 R L2Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, oxetyl, and aziridine are optionally separated by 1 to 4 R. k replace;

[0101] In some implementation schemes, R 1 With R 2 R L1 With R L2 Individual atoms and atoms connected to them together form C. 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0102] Preferably, R 1 With R 2 R L1 With R L2 Individual atoms and atoms connected to them together form C. 3-6 Cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0103] Preferably, R 1 With R 2 R L1 With R L2 Each individual atom and the atoms bonded to it together form cyclopropyl, cyclobutyl, oxetyl, and aziretyl groups, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziretyl groups are optionally surrounded by 1 to 4 R groups. k replace;

[0104] In some implementation schemes, R b1 R b2 R b3 Each independently selected from R b H, deuterium, halogens, CN, OH, C 1-6 Alkyl group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -OC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0105] Preferably, R b1 R b2 Rb3 Each independently selected from R b H, deuterium, halogens, CN, OH, C 1-4 Alkyl group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0106] Preferably, R b1 R b2 R b3 Each independently selected from R b H, deuterium, F, Cl, Br, I, CN, OH, methyl, ethyl, propyl, isopropyl, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, -O-methyl, -O-ethyl, -O-isopropyl, -CH2-cyclopropyl, cyclopropyl, cyclobutyl, wherein CH2, methyl, ethyl, propyl, isopropyl, cyclopropyl, and cyclobutyl are optionally divided by 1 to 4 R k replace;

[0107] Preferably, R b1 R b2 R b3 Each independently selected from R b H, deuterium, F, Cl, Br, I, CN, OH, methyl, ethyl, isopropyl, -O-methyl, cyclopropyl, cyclobutyl, wherein the methyl, ethyl, isopropyl, cyclopropyl, and cyclobutyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0108] In some implementation schemes, R b1 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group may optionally be substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0109] Preferably, R b1 Each independently selected Deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0110] Preferably, R b1 Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3,

[0111] In some implementation schemes, R b3 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group may optionally be substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0112] Preferably, R b3 Each independently selected Deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0113] In some implementation schemes, R b1 With R b2 R b1 With R b4 R b1 With R b1 Individual atoms and their connected atoms or framework together form C. 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0114] Preferably, any two non-adjacent R b1 With R b2 R b1 With R b4 R b1 With R b1 Each independent skeleton and the skeleton connected to it together form C 4-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0115] In some implementations, any two R b1Together with the atoms or framework attached to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0116] Preferably, any two R b1 Together with the atoms or framework attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxacyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, or aziridine, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxacyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, or aziridine are optionally surrounded by 1 to 4 R atoms. k replace;

[0117] As an option, any two R b1 Together with the carbon atoms or framework attached to it, they form C 3-6 cycloalkyl group, wherein the cycloalkyl group is optionally surrounded by 1 to 4 R groups k replace;

[0118] Preferably, any two R b1 Together with the carbon atom or skeleton attached thereto, they form a group optionally substituented with 1 to 4 of the following groups: cyclopropyl, cyclobutyl, wherein the substituents are selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy;

[0119] In some implementations, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0120] Preferably, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-6 Cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0121] Preferably, any two R b3 Together with the carbon atom or skeleton attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetyl, aziridine, pyrrolidinyl, or piperidinyl groups, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetyl, aziridine, pyrrolidinyl, or piperidinyl groups are optionally surrounded by 1 to 4 R atoms. k replace;

[0122] As an option, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-6 cycloalkyl group, wherein the cycloalkyl group is optionally surrounded by 1 to 4 R groups k replace;

[0123] Preferably, any two R b3 Together with the carbon atom or skeleton attached thereto, they form a group optionally substituented with 1 to 4 of the following groups: cyclopropyl, cyclobutyl, wherein the substituents are selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy;

[0124] In some implementation schemes, R b Each is independently selected from NH2, -SF5, and -NHC. 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 alkynyl group, -SC 1-6 alkyl, -OC 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0125] Preferably, R b Each is independently selected from NH2, -SF5, and -NHC. 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 alkynyl group, -SC 1-4 alkyl, -OC 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0126] Preferably, R b Each of these groups is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl. -O-cyclopropyl, wherein the methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, or cyclopropyl group is optionally surrounded by 1 to 4 R groups. k replace;

[0127] In some implementation schemes, R c R d Each is independently selected from deuterium, =O, halogen, CN, OH, NH2, -SF5, -NHC1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3 to 8-membered heterocyclic groups, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0128] Preferably, R c R d Each is independently selected from deuterium, =O, halogen, CN, OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 6-membered heterocyclic groups, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0129] Preferably, R c R dEach is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, methyl, ethyl, -S-methyl, -S-ethyl, -O -methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -O-cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl are optionally surrounded by 1 to 4 R k replace;

[0130] Preferably, R c R d Each of the following groups is independently selected from deuterium, F, Cl, Br, CN, OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl, cyclobutyl, wherein the CH2, methyl, ethyl, cyclopropyl, and cyclobutyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0131] Preferably, R c Each is independently selected from deuterium, F, Cl, Br, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl;

[0132] Preferably, R d Each is independently selected from deuterium, F, Cl, Br, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl;

[0133] In some implementation schemes, R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6Cycloalkyl, wherein the alkyl or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0134] Preferably, R c Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3, and cyclopropyl;

[0135] In some implementation schemes, R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 Cycloalkyl, wherein the alkyl or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0136] Preferably, R d Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3, and cyclopropyl;

[0137] In some implementation schemes, R d Selected from R 1d ;

[0138] In some implementation schemes, R c Selected from R 1c ;

[0139] In some implementation schemes, R d1 Each element is independently selected from halogens, OH, CN, NH2, -SF5, and C. 1-6 Alkyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6Substituents of alkoxy groups;

[0140] Preferably, R d1 Each element is independently selected from halogens, OH, CN, NH2, -SF5, and C. 1-4 Alkyl, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 6-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0141] Preferably, R d1 Each of these elements is independently selected from F, Cl, Br, I, OH, CN, NH2, -SF5, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, methyl, ethyl, -S-methyl, -S-ethyl, -O-methyl, -O-ethyl, -O-cyclopropyl, -O-cyclobutyl, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, cyclopropyl, cyclobutyl, oxacyclobutyl, aziridine, and others. The CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, and aziridine groups are optionally surrounded by 1 to 4 R groups. k replace;

[0142] Preferably, R 1c Each independently selected from -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 3- to 6-membered heterocyclic groups, NH2, -SF5, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC1-4 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace;

[0143] Preferably, R 1c Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1 Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace;

[0144] Preferably, R 1c Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1 Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace;

[0145] Preferably, R 1cSelected from -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 ,-Cyclopropyl-R d1 -Cyclobutyl-R d1 -cyclopentyl-R d1 The cyclopropyl, cyclobutyl, and cyclopentyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy groups;

[0146] Preferably, R 1c Each independently selected

[0147] In some implementation schemes, R 1d Each independently selected from -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 3- to 6-membered heterocyclic groups, NH2, -SF5, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace;

[0148] Preferably, R 1d Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace;

[0149] Preferably, R 1d Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1 Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace;

[0150] Preferably, R 1d Each is independently selected from -N(methyl)2, -N(ethyl)2,

[0151] In some implementation schemes, R A Each independently selected from R a Deuterium, O, Halogen, CN, C 1-6 Alkyl, C 2-6 alkenyl, -OC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0152] Preferably, R A Each independently selected from R a Deuterium, O, Halogen, CN, C 1-4 Alkyl, C 2-4 alkenyl, -OC1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0153] Preferably, R A Each independently selected from R a Deuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, -O-methyl, -O-ethyl, -CH2-cyclopropyl, -CH2-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, wherein CH2, methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl are optionally surrounded by 1 to 5 R. k replace;

[0154] Preferably, R A Each independently selected from R a ;

[0155] In some implementation schemes, R A Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0156] Preferably, R A Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3; in some embodiments, R a Each independently selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, C 2-6 alkynyl group, -SC 1-6 Alkyl, 3- to 10-membered heterocyclic groups, -OC 3-6 cycloalkyl, C 7-10 cycloalkyl, C 3-6 Cycloalkyl 5-6 membered heterocyclic group, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0157] Preferably, R aEach independently selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2、-C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, C 2-4 alkynyl group, -SC 1-4 Alkyl, 4-7 member monoheterocyclic, 6-10 member spirocyclic alkyl, 6-10 member anabolic alkyl, 6-10 member bridged heterocyclic alkyl, -OC 3-6 cycloalkyl, C 7-10 Spirocycloalkyl, C 7-10 Bridged cycloalkyl, C 7-10 cycloalkyl, C 3-6 Cycloalkyl 5-6 membered heterocyclic group, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0158] Preferably, R a Each independently selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2、-C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, C 2-4 alkynyl group, -SC 1-4 Alkyl, 3- to 7-membered heterocyclic groups, -OC 3-6 Cycloalkyl, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k Replace any of 1 to 4 R k replace;

[0159] Preferably, R a Each is independently selected from -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-R a1 -cyclohexyl-R a1OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, ethynyl, propynyl, propyrynyl, -S-methyl, -S-ethyl, -O-cyclopropyl, -O-cyclobutyl, oxacyclobutyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl, cyclobutylcyclopentyl, cyclopentylcyclopentyl, pyrrolidinyl, pyrrolidinyl The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethynyl, propynyl, propynyl, methyl, ethyl, oxacyclobutyl, azacyclobutyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl, cyclobutylcyclopentyl, cyclopentylcyclopentyl, pyrrolidinyl, and pyrrolidinyl are mentioned. Choose from 1 to 4 Rs k replace;

[0160] Preferably, R a Each is independently selected from -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-R a1 -cyclohexyl-R a1 , -S-methyl, -S-ethyl, -O-cyclopropyl, -O-cyclobutyl, oxetanebutyl, azironebutyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl The cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups mentioned above... Methyl, ethyl, oxetyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl Choose from 1 to 4 Rs k replace;

[0161] In some implementation schemes, R a1 Each is independently selected from NH2, -SF5, and -NHC. 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Substituents of alkoxy groups;

[0162] Preferably, R a1 Each is independently selected from NH2, -SF5, and -NHC. 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0163] Preferably, R a1 Each of these elements is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, piperidinyl, The methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziridine, pyrrolidinyl, or piperidinyl groups are optionally prefixed with 1 to 4 deuterium, F, Cl, Br, I, CN, OH, NH2, or C groups. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0164] Preferably, R a1Each of these elements is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, piperidinyl, The methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, and piperidinyl groups may optionally be substituted with 1 to 4 deuterium, F, Cl, Br, I, CN, OH, NH2, methyl, or methoxy substituents;

[0165] Preferably, R a1 Each independently selected

[0166] In some implementation schemes, R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-6 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace;

[0167] Preferably, R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-4 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace;

[0168] Preferably, R 3 R 4 Each of the following is independently selected from H, deuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, and isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally surrounded by 1 to 4 R groups. k replace;

[0169] Preferably, Selected from

[0170] Preferably, R k Each element is independently selected from deuterium, =O, halogens, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, and -NHC. 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6alkynyl group, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -OC 3-6 Carbocyclic rings, -O-3 to 7-membered heterocycles, -NH-C 3-6 Carbon rings, -NH-3 to 7-membered heterocycles, -C 1-2 Alkylene-C 3-6 Carbon ring, -C 1-2 Alkylene-3 to 7-membered heterocycles, C 3-6 Carbon rings, 3- to 7-membered heterocycles, The alkyl, alkylene, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally selected from 1 to 4 deuterium, halogen, =O, CN, OH, NH2, C 1-6 Alkyl, C 1-6 Substituents of alkoxy groups;

[0171] Preferably, R k Each element is independently selected from deuterium, =O, halogens, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, and NHC. 1-4 Alkyl, N(C) 1-4 Alkyl)2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -OC 3-6 Carbocyclic rings, -O-3 to 7-membered heterocycles, C 3-6 Carbon rings, 3- to 7-membered heterocycles, The alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic groups are optionally selected from one to four deuterium, halogen, CN, OH, NH2, C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0172] Preferably, R k Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, NH(CH3), NH(CH2CH3), N(CH3)2, N(CH2CH3)2, methyl, ethyl, propyl, isopropyl, tert-butyl, vinyl, ethynyl, methoxy, ethoxy, methylthio, -O-cyclopropyl, -O-oxacyclobutyl, -NH-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl The methyl, ethyl, propyl, isopropyl, tert-butyl, vinyl, ethynyl, methoxy, ethoxy, methylthio, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups are optionally selected from one to four of deuterium, halogens, CN, OH, NH2, and C.1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0173] Preferably, R k Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, -C(=O)OH, -C(=O)NH2, -CH2OH, methyl, ethyl, propyl, isopropyl, tert-butyl, CD3, OCD3, CH2F, CHF2, CF3, vinyl, ethynyl, methoxy, ethoxy, methylthio, -O-cyclopropyl, -O-oxacyclobutyl, -NH-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl

[0174] Preferably, R k Each is independently selected from deuterium, F, Cl, Br, -CH2OH, methyl, ethyl, isopropyl, CD3, OCD3, CH2F, CHF2, CF3, OCF3, methoxy, ethoxy, methylthio, -CH2-cyclopropyl, cyclopropyl;

[0175] In some implementations, each of b4 is independently selected from 0, 1, 2, 3, 4, 5; preferably, each of b4 is independently selected from 0, 1, 2, 3, 4; preferably, each of b4 is independently selected from 0, 1, 2, 3; preferably, each of b4 is independently selected from 0, 1, 2.

[0176] In some implementations, each of b5 is independently selected from 0, 1, 2, 3, 4, 5, 6; preferably, each of b5 is independently selected from 0, 1, 2, 3, 4; preferably, each of b5 is independently selected from 0, 1, 2, 3.

[0177] In some implementations, each of b3 is independently selected from 0, 1, 2, 3, and 4; preferably, each of b3 is independently selected from 0, 1, 2, and 3; preferably, each of b3 is independently selected from 0, 1, and 2.

[0178] In some implementations, a1 is independently selected from 0, 1, 2, 3, 4, 5, 6; preferably, a1 is independently selected from 0, 1, 2, 3, 4; preferably, a1 is independently selected from 0, 1, 2, 3.

[0179] In some implementations, a2 is independently selected from 0, 1, 2, 3, 4, 5; preferably, a2 is independently selected from 0, 1, 2, 3, 4; preferably, a2 is independently selected from 0, 1, 2, 3; preferably, a2 is independently selected from 0, 1;

[0180] In some implementations, c1 and d1 are each independently selected from 0, 1, 2, 3, and 4; preferably, c1 and d1 are each independently selected from 0, 1, 2, and 3; preferably, c1 is each independently selected from 0, 1, and 2; preferably, d1 is each independently selected from 0, 1, and 2.

[0181] In some preferred embodiments, the compounds represented by general formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (IA), (IB), (IC), (ID), (IE), or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein L is selected from the bond; and X1 is each independently selected from O or S;

[0182] X2 is independently selected from O or S; preferably, X2 is independently selected from O; R b1 Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R b3 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; and / or, R b Each independently selected C 2-4 alkenyl, C 2-4 The alkynyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R A Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R A Each independently selected from R a R a Selected from -C 3-6 cycloalkyl-R a1 ;R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6Cycloalkyl, wherein the alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R c Selected from R 1c R 1c Selected from -C 3-6 cycloalkyl-R d1 The cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 Cycloalkyl, wherein the alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R d Selected from R 1d R 1d Selected from -C 3-6 cycloalkyl-R d1 , 3 to 6-membered heterocyclic groups, wherein the cycloalkyl or heterocyclic group is optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R D Selected from -C(=O)OH; the definitions of the remaining groups are consistent with those in general formula (I);

[0183] In some preferred embodiments, the compound represented by formulas (I), (Ig), (Im), or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein ring B is selected from... * One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; L is selected from the key; Selected from Ring C is selected from 1 to 4 Rs. c The following groups are substituted: benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, phenyl; Selected from 1 to 4 Rs d The following groups are substituted: s7 are each independently selected from 1 or 2; R b1 Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R b3Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group may optionally be substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R b Each independently selected C 2-4 alkenyl, C 2-4 The alkynyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R A Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 Cycloalkyl group, wherein the alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 The cycloalkyl group is optionally substituted with one to four substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; the remaining groups are defined in the same way as those in general formula (I).

[0184] In some preferred embodiments, the compound represented by general formula (I) or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein ring B is selected from... * One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; L is selected from the key; Selected from Ring C is selected from 1 to 4 Rs. c The following groups are substituted: benzo[C] 4-6 Carbocyclic groups, benzo4-6 membered heterocyclic groups; Selected from 1 to 4 Rs d The following groups are substituted: s7 are each independently selected from 1 or 2; R b1 Each element is independently selected from deuterium, halogens, and C. 1-4Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R A Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 Cycloalkyl group, wherein the alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 The cycloalkyl group is optionally substituted with one to four substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; the remaining groups are defined in the same way as those in general formula (I).

[0185] In some preferred embodiments, the compound represented by general formula (Ih) or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein L is selected from the bond; Selected from Preferably, Selected from Ring B is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; ring C is selected from 1 to 4 Rs. c The following groups are substituted: benzo[C] 4-6 Carbocyclic, benzo4-6-membered heterocyclic, phenyl; preferably, the ring C is selected from 1 to 4 R groups. c The following groups are substituted: phenyl; ring D1 is independently selected from 1 to 4 R groups. d The following groups are substituted: C 5-10 Bridged cycloalkyl; preferably, each ring D1 is independently selected from 1 to 4 R... d The following groups are substituted: Its right side and R D Connection; R D Selected from -C(=O)OH; X1 is independently selected from O or S; X2 is independently selected from O or S; preferably, X2 is independently selected from O; R b1 Each element is independently selected from deuterium, halogens, and C.1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R b3 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; and / or, R b Each independently selected C 2-4 alkenyl, C 2-4 The alkynyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R A Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R A Each independently selected from R a R a Selected from -C 3-6 cycloalkyl-R a1 ;R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 Cycloalkyl group, wherein the alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 The cycloalkyl group is optionally substituted with one to four substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; the remaining groups are defined in the same way as those in general formula (I).

[0186] In some preferred embodiments, the compound represented by general formula (Ia) or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein L is selected from the bond; Selected from Ring B is selected from One end is connected to -C(=X1)-, and the other end is connected to -C(=X2)-; preferably, ring B is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; X1 is independently selected from O or S; X2 is independently selected from O or S; R b1 Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R b3 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; and / or, R b Each independently selected C 2-4 alkenyl, C 2-4 The alkynyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R A Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl group, wherein the alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy; and / or, R A Each independently selected from R a R a Selected from -C 3-6 cycloalkyl-R a1 ;R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 Cycloalkyl group, wherein the alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 The cycloalkyl group is optionally substituted with one to four substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; the remaining groups are defined in the same way as those in general formula (I).

[0187] In some embodiments, the "heterocyclic group", "heterocyclic", or "heteroaryl" contains 1, 2, 3, or 4 heteroatoms selected from nitrogen, oxygen, or sulfur; preferably, it contains 1 or 2 heteroatoms selected from nitrogen, oxygen, or sulfur.

[0188] Optionally, general formula (I) must satisfy at least one of the following conditions:

[0189] 1) Y is selected from Y1, and Y1 is selected from NR. b4 1) O; 2) The sum of b1 and b2 is selected from 3, 4, 5, and 6; 3) Ring B is selected from * One end is connected to -C(=X1)-, and the other end is connected to -C(=X2)-; 4) Any two non-adjacent R b1 With R b2 R b1 With R b4 R b1 With R b1 Together with the skeleton connected to it, they form C 4-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k Replacement; 5) Ring B is selected from 1 to 6 R b1 Replacement And at least one R b1 Selected from R b One end is connected to -C(=X1)-, and the other end is connected to -C(=X2)-; 6) a1 is not selected from 0, and at least one R A Selected from R a 7) Ring A is selected from ring A1, and ring A1 is selected from benzo[a]C 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 5-6 membered heterocyclic, 8-10 membered cyclocyclic heteroaryl, pyridinone group, pyrimidinone group, 5 membered heteroaryl; 8) Ring C is selected from ring C1, and ring C1 is selected from benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 5-12 Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the C1 ring is optionally surrounded by 1 to 5 R groups. c Substitution; 9) Ring D is selected from ring D1, and ring D1 is selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 4-12Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the ring D1 is optionally surrounded by 1 to 5 R groups. d Replace; 10)R c With R d Together with the connected skeleton, they form ring E, which is selected from C. 4-10 Carbon rings, 4- to 10-membered heterocycles, wherein the ring E is optionally divided by 1 to 5 R... k Replace; 11) At least one of X1 and X2 is selected from S; 12) R D Selected from R 1D R 1D Selected from 13) Ring D is at least one R d Replace, R d Selected from R 1d R 1d Selected from -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 3- to 8-membered heterocyclic groups, NH2, -SF5, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k Replacement; 14) Ring C is at least one R c Replace, R c Selected from R 1c R 1c Selected from NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 3- to 8-membered heterocyclic groups, NH2, -SF5, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace.

[0190] As a first embodiment of this application, the compounds represented by the above general formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (IA), (IB), (IC), (ID), (IE), or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, are used.

[0191] Ring A is selected from benzo[4-6] carbocyclic groups, benzo[4-6] heterocyclic groups, and benzo[5-6] heteroaryl groups. 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cycloheteroaryl, 5-6 membered heteroaryl, pyridinone, pyrimidinone, phenyl;

[0192] Alternatively, ring A is selected from ring A1, and ring A1 is selected from benzo[4-6] carbocyclic, benzo[4-6] heterocyclic, or benzo[5-6] heteroaryl[4-6] cyclocyclic. 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cyclocyclic heteroaryl, pyridinone group, pyrimidinone group, 5 membered heteroaryl;

[0193] The ring C is selected from benzo[C]. 4-12 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 The ring C may be a carbocyclic group, a 5-6 membered heteroaryl group, an 8-10 membered cycloheteroaryl group, a 5-6 membered heteroaryl group, a 5-12 membered heteroaryl group, a pyridinone group, a pyrimidinone group, or a phenyl group, wherein the ring C is optionally surrounded by 1 to 5 R groups. c replace;

[0194] Alternatively, ring C is selected from ring C1, and ring C1 is selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 5-12 Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the C1 ring is optionally surrounded by 1 to 5 R groups. c Substitution; ring D is selected from C 4-12 Carbocyclic group, benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 The ring D is optionally surrounded by 1 to 5 R groups: carbocyclic, 5-6-membered heteroaryl, 8-10-membered cycloheteroaryl, 5-6-membered heteroaryl, 5-12-membered heteroaryl, pyridone, pyrimidinone, or phenyl. d Substitution; or, ring D is selected from ring D1, which is selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 4-12 Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the ring D1 is optionally surrounded by 1 to 5 R groups. d replace;

[0195] Ring B is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-. Choose from 1 to 6 Rs b1 replace;

[0196] Y is selected independently from NR b4 O or CR b1 R b2 ;

[0197] b1 is selected from 1, 2, 3; b2 is selected from 0, 1, 2, 3; b3 is selected from 0, 1, 2, 3, 4, 5, 6;

[0198] a1 is selected from 0, 1, 2, 3, 4, 5, 6;

[0199] R D Selected from -C(=O)OH, -C(=O)OR 1 -C(=O)NR 1 R 2 -S(=O)2NHCF3,

[0200] Or, R D Selected from R 1D R 1D Selected from

[0201] X1 and X2 are each independently selected from O or S;

[0202] L is selected from either a key or CR. L1 R L2 ;

[0203] R L1 R L2 Each is independently selected from H and C. 1-6 Alkyl, -OC 1-6 Alkyl, C 1-2 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, carbocyclic, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 5 R... k replace;

[0204] As an option, R1 With R 2 R L1 With R L2 Together with the atoms bonded to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0205] R 1 R 2 R b4 Each independently selected from H and C 1-6 Alkyl, C 1-4 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 5 R... k replace;

[0206] R b1 R b2 R b3 Each independently selected from R b H, deuterium, halogens, CN, OH, C 1-6 Alkyl group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -OC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0207] R b Selected from NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 alkynyl group, -SC 1-6 alkyl, -OC 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0208] R c R d Each is independently selected from deuterium, =O, halogen, CN, OH, NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 cycloalkyl, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 -OC 3-6 cycloalkyl, -NH-C 3-6 Cycloalkyl, 3 to 8-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0209] Or, R d Selected from R 1d R 1d Selected from -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 3- to 8-membered heterocyclic groups, NH2, -SF5, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace;

[0210] Or, R c Selected from R 1c R 1c Selected from NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 3- to 8-membered heterocyclic groups, NH2, -SF5, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, -NH-C 3-6Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace;

[0211] As an option, R b1 With R b2 R b1 With R b4 R b1 With R b1 Together with the atoms or framework attached to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0212] As an option, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0213] As an option, R c With R d Together with the connected skeleton, they form ring E, which is selected from C. 4-10 Carbon rings, 4- to 10-membered heterocycles, wherein the carbon rings or heterocycles are optionally surrounded by 1 to 5 R... k replace;

[0214] R d1 Each is independently selected from halogens, OH, CN, NH2, -SF5, C 1-6 Alkyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Substituents of alkoxy groups;

[0215] R A Each independently selected from R aDeuterium, O, Halogen, CN, C 1-6 Alkyl, C 2-6 alkenyl, -OC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0216] R a Selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, C 2-6 alkynyl group, -SC 1-6 Alkyl, 3- to 10-membered heterocyclic groups, -OC 3-6 cycloalkyl, C 7-10 cycloalkyl, C 3-6 Cycloalkyl 5-6 membered heterocyclic group, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0217] R a1 Selected from NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Substituents of alkoxy groups;

[0218] R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-6 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace;

[0219] Rk Each element is independently selected from deuterium, =O, halogens, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, and -NHC. 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-NHC(=O)C 1-6 Alkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -OC 3-6 Carbocyclic rings, -O-3 to 7-membered heterocycles, -NH-C 3-6 Carbon rings, -NH-3 to 7-membered heterocycles, -C 1-2 Alkylene-C 3-6 Carbon ring, -C 1-2 Alkylene-3 to 7-membered heterocycles, C 3-6 Carbon rings, 3- to 7-membered heterocycles, The alkyl, alkylene, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally selected from 1 to 4 deuterium, halogen, =O, CN, OH, NH2, C 1-6 Alkyl, C 1-6 The alkoxy group is replaced by a substituent.

[0220] As a second embodiment of this application, the compounds represented by the above general formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (IA), (IB), (IC), (ID), (IE), (IF), or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, are used.

[0221] X1 is independently selected from O or S;

[0222] X2 is independently selected from O or S;

[0223] b4 is independently selected from 0, 1, 2, 3, 4, and 5;

[0224] b5 is selected independently from 0, 1, 2, 3, 4, 5, and 6;

[0225] a2 is independently selected from 0, 1, 2, 3, 4, and 5;

[0226] c1 and d1 are each independently selected from 0, 1, 2, 3, and 4;

[0227] Each ring B is independently selected from either ring B1 or ring B2;

[0228] Ring B1 is selected independently from each One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0229] Ring B2 is selected independently from each One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0230] Each ring A is independently selected from ring A1, a 6-membered heteroaryl group, or a phenyl group;

[0231] Each ring C is independently selected from a 1-ring, a 6-membered heteroaryl, or a phenyl group, wherein the ring C is optionally surrounded by 1 to 5 R groups. c replace;

[0232] Each ring D is independently selected from ring D1, a 6-membered heteroaryl group, or a phenyl group, wherein the ring D is optionally surrounded by 1 to 5 R groups. d replace;

[0233] Each ring A1 is independently selected from benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cyclocyclic heteroaryl, pyridinone group, pyrimidinone group, 5 membered heteroaryl;

[0234] Each of the C1 rings is independently selected from benzo[C1]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 5-6 Monocycloalkyl, C 5-12 Bridged cycloalkyl, C 5-12 Spirocycloalkyl, C 5-12 Annular alkyl, 5-7 member monoheterocyclic alkyl, 5-7 member monoheterocyclic alkenyl, 6-12 member spiroheterocyclic alkyl, 6-12 member anheterocyclic alkyl, 6-12 member bridged heterocyclic alkyl;

[0235] Each ring D1 is independently selected from benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 4-6 Monocycloalkyl, C 5-12 Bridged cycloalkyl, C 5-12 Spirocycloalkyl, C 5-12 Annular alkyl, 5-7 member monoheterocyclic alkyl, 5-7 member monoheterocyclic alkenyl, 6-12 member spiroheterocyclic alkyl, 6-12 member anheterocyclic alkyl, 6-12 member bridged heterocyclic alkyl;

[0236] As an option, R c With R d Together with the skeleton connected to it, they form ring E;

[0237] Ring E is independently selected from C 4-8 Carbon rings, 4- to 8-membered heterocycles, wherein the ring E is optionally divided by 1 to 5 R... k replace;

[0238] R L1 R L2 Each is independently selected from H and C. 1-4 Alkyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 4 R... k replace;

[0239] As an option, R 1 With R 2 R L1 With R L2 Individual atoms and atoms connected to them together form C. 3-6 Cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0240] R 1 R 2 R b4 Each independently selected from H and C 1-4 Alkyl, -C 1-2 Alkylene-OC 1-4 Alkyl, C 3-6 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 4 R... k replace;

[0241] R b1 R b2 R b3 Each independently selected from R b H, deuterium, halogens, CN, OH, C 1-4 Alkyl group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. kreplace;

[0242] As an option, any two R b1 Together with the atoms or framework attached to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0243] As an option, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-6 Cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace;

[0244] R b Each is independently selected from NH2, -SF5, and -NHC. 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 alkynyl group, -SC 1-4 alkyl, -OC 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0245] R c R d Each is independently selected from deuterium, =O, halogen, CN, OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 cycloalkyl, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 -OC 3-6 cycloalkyl, -NH-C 3-6 Cycloalkyl, 3- to 6-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0246] R d1Each is independently selected from halogens, OH, CN, NH2, -SF5, C 1-4 Alkyl, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 6-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0247] Or, R c Selected from R 1c R 1c Each independently selected from -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 3- to 6-membered heterocyclic groups, NH2, -SF5, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace;

[0248] Or, R d Selected from R 1d R 1d Each independently selected from -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 3- to 6-membered heterocyclic groups, NH2, -SF5, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace;

[0249] R A Each independently selected from R a Deuterium, O, Halogen, CN, C 1-4 Alkyl, C 2-4 alkenyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace;

[0250] R a Each independently selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2、-C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, C 2-4 alkynyl group, -SC 1-4 Alkyl, 4-7 member monoheterocyclic, 6-10 member spirocyclic alkyl, 6-10 member anabolic alkyl, 6-10 member bridged heterocyclic alkyl, -OC 3-6 cycloalkyl, C 7-10 Spirocycloalkyl, C 7-10 Bridged cycloalkyl, C 7-10 cycloalkyl, C 3-6 Cycloalkyl 5-6 membered heterocyclic group, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace;

[0251] R a1 Each is independently selected from NH2, -SF5, and -NHC. 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0252] R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-4 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace;

[0253] R k Each element is independently selected from deuterium, =O, halogens, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, and NHC. 1-4 Alkyl, N(C) 1-4 Alkyl)2、-NHC(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -OC 3-6 Carbocyclic rings, -O-3 to 7-membered heterocycles, C 3-6 Carbon rings, 3- to 7-membered heterocycles, The alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic groups are optionally selected from one to four deuterium, halogen, CN, OH, NH2, C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0254] The definitions of the remaining functional groups are the same as those in the first embodiment of this application.

[0255] As a third embodiment of this application, the compounds represented by the above general formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (IA), (IB), (IC), (ID), (IE), (IF), or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, are used.

[0256] Each ring A is independently selected from ring A1, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl.

[0257] Each ring C is independently selected from ring C1, phenyl, pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl, and the ring C is optionally surrounded by 1 to 5 R groups. c replace;

[0258] Each ring D is independently selected from ring D1, phenyl, pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl, and said ring D is optionally surrounded by 1 to 5 R groups. d replace;

[0259] R L1 R L2 Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, oxetyl, and aziridine are optionally separated by 1 to 4 R. k replace;

[0260] As an option, R 1 With R 2 R L1 With R L2 Each individual atom and the atoms bonded to it together form cyclopropyl, cyclobutyl, oxetyl, and aziretyl groups, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziretyl groups are optionally surrounded by 1 to 4 R groups. k replace;

[0261] R 1 R 2 R b4 Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine groups are optionally surrounded by 1 to 4 R groups. k replace;

[0262] R b1 R b2 R b3 Each independently selected from R b H, deuterium, F, Cl, Br, I, CN, OH, methyl, ethyl, propyl, isopropyl, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, -O-methyl, -O-ethyl, -O-isopropyl, -CH2-cyclopropyl, cyclopropyl, cyclobutyl, wherein CH2, methyl, ethyl, propyl, isopropyl, cyclopropyl, and cyclobutyl are optionally divided by 1 to 4 R k replace;

[0263] R b Each of these groups is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl. -O-cyclopropyl, wherein the methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, or cyclopropyl group is optionally surrounded by 1 to 4 R groups. k replace;

[0264] R c R d Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, methyl, ethyl, -S-methyl, -S-ethyl, -O- Methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -O-cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl are optionally surrounded by 1 to 4 R k replace;

[0265] As an option, R c With R d Together with the skeleton connected to it, they form ring E;

[0266] Or, R c Selected from R 1c R 1c Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1 Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace;

[0267] Or, R d Selected from R 1d R 1d Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1 Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace;

[0268] As an option, any two R b1 Together with the atoms or framework attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxacyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, or aziridine, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxacyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, or aziridine are optionally surrounded by 1 to 4 R atoms. k replace;

[0269] As an option, any two R b3 Together with the carbon atom or skeleton attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetyl, aziridine, pyrrolidinyl, or piperidinyl groups, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetyl, aziridine, pyrrolidinyl, or piperidinyl groups are optionally surrounded by 1 to 4 R atoms. k replace;

[0270] R A Each independently selected from R aDeuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, -O-methyl, -O-ethyl, -CH2-cyclopropyl, -CH2-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, wherein CH2, methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl are optionally surrounded by 1 to 5 R. k replace;

[0271] R a Each independently selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2、-C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, C 2-4 alkynyl group, -SC 1-4 Alkyl, 3- to 7-membered heterocyclic groups, -OC 3-6 Cycloalkyl, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k Replace any of 1 to 4 R k replace;

[0272] R a1 Each of these elements is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, piperidinyl, The methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziridine, pyrrolidinyl, or piperidinyl groups are optionally prefixed with 1 to 4 deuterium, F, Cl, Br, I, CN, OH, NH2, or C groups. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0273] R 3 R 4 Each of the following is independently selected from H, deuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, and isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally surrounded by 1 to 4 R groups. k replace;

[0274] R k Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, NH(CH3), NH(CH2CH3), N(CH3)2, N(CH2CH3)2, -NHC(=O)CH3, methyl, ethyl, propyl, isopropyl, tert-butyl, vinyl, ethynyl, methoxy, ethoxy, methylthio, -O-cyclopropyl, -O-oxacyclobutyl, -NH-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl The methyl, ethyl, propyl, isopropyl, tert-butyl, vinyl, ethynyl, methoxy, ethoxy, methylthio, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups are optionally selected from one to four of deuterium, halogens, CN, OH, NH2, and C. 1-4 Alkyl, C 1-4 Substituents of alkoxy groups;

[0275] The definitions of the remaining functional groups are the same as those in the first or second embodiment of this application.

[0276] As a fourth embodiment of this application, the compounds represented by the above general formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (IA), (IB), (IC), (ID), (IE), (IF), or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, are used.

[0277] Ring B1 is selected independently from each One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0278] As an option, any two R b1 Together with the atoms or framework attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl, or piperidinyl groups, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl, or piperidinyl groups are optionally surrounded by 1 to 4 R atoms. k replace;

[0279] As an option, any two R b3 Together with the carbon atom or skeleton attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziridine, or piperidinyl groups, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziridine, or piperidinyl groups are optionally surrounded by 1 to 4 R atoms. k replace;

[0280] The ring A1 is independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphenyl, benzocyclopentyl, benzocyclohexyl, benzocyclobutenyl, benzocyclopentenyl, benzocyclohexenyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrylalkyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrryl, pyridopyrazolyl, pyridoimidazolyl, and pyridoimidazolyl.

[0281] The ring C1 is selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphenyl, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl, and pyridoimidazolyl. Cyclohexyl, cycloheptyl, pyrrolidinyl, piperidinyl, azacycloheptyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, morpholinyl, piperazine, azacyclohexenyl, wherein the ring C1 is optionally surrounded by 1 to 4 R... c replace;

[0282] Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiophene, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl.

[0283] s1, s3, and s5 can be independently selected from 0, 1, or 2, but s1 and s3 cannot be selected from 2 at the same time;

[0284] s2 and s4 are each independently selected from 0 or 1;

[0285] Each of s7 can be independently selected from 1, 2, or 3;

[0286] The ring D1 is independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphenyl, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl, and pyridoimidazolyl. Cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyrrolidinyl, piperidinyl, azacycloheptyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, morpholinyl, piperazine, azacyclohexenyl, wherein the ring D1 is optionally surrounded by 1 to 4 R... d replace;

[0287] Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect;

[0288] More preferably, rings D1 are each independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect;

[0289] Each ring E is independently selected from cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, pyrrolyl, piperidinyl, azircycloheptyl, azircyclooctyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, oxacyclooctyl, azircycloheptenyl, azircyclooctenyl, oxacyclopentenyl, oxacyclohexenyl, oxacycloheptenyl, oxacyclooctenyl, wherein the ring E is optionally surrounded by 1 to 4 R k replace;

[0290] R a Each is independently selected from -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-R a1 -cyclohexyl-R a1OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, ethynyl, propynyl, propyrynyl, -S-methyl, -S-ethyl, -O-cyclopropyl, -O-cyclobutyl, oxacyclobutyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl, cyclobutylcyclopentyl, cyclopentylcyclopentyl, pyrrolidinyl, pyrrolidinyl The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethynyl, propynyl, propynyl, methyl, ethyl, oxacyclobutyl, azacyclobutyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl, cyclobutylcyclopentyl, cyclopentylcyclopentyl, pyrrolidinyl, and pyrrolidinyl are mentioned. Choose from 1 to 4 Rs k replace;

[0291] R d1 Each is independently selected from F, Cl, Br, I, OH, CN, NH2, -SF5, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, methyl, ethyl, -S-methyl, -S-ethyl, -O-methyl, -O-ethyl, -O-cyclopropyl, -O-cyclobutyl, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, cyclopropyl, cyclobutyl, oxacyclobutyl, aziridine, The CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, and aziridine groups are optionally surrounded by 1 to 4 R groups. k replace;

[0292] R k Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, -C(=O)OH, -C(=O)NH2, -CH2OH, -NHC(=O)CH3, methyl, ethyl, propyl, isopropyl, tert-butyl, CD3, OCD3, CH2F, CHF2, CF3, vinyl, ethynyl, methoxy, ethoxy, methylthio, -O-cyclopropyl, -O-oxacyclobutyl, -NH-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl

[0293] The definitions of the remaining functional groups are the same as those in the first, second, or third embodiments of this application.

[0294] As a fifth embodiment of this application, the compounds represented by the above general formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (IA), (IB), (IC), (ID), (IE), (IF), or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts,

[0295] b4 is independently selected from 0, 1, 2, 3, and 4;

[0296] b5 is selected independently from 0, 1, 2, 3, and 4;

[0297] b3 is independently selected from 0, 1, 2, 3, and 4;

[0298] a1 is independently selected from 0, 1, 2, 3, and 4;

[0299] a2 is independently selected from 0, 1, 2, 3, and 4;

[0300] c1 and d1 are each independently selected from 0, 1, 2, and 3;

[0301] Selected from

[0302] R D Each is independently selected from -C(=O)OH, -C(=O)OC(CH3)3, -C(=O)NH2, -S(=O)2NHCF3,

[0303] Preferably, R D Each is independently selected from -C(=O)OH;

[0304] L is independently selected from CH2 or CH3; preferably, L is independently selected from CH2.

[0305] Each ring C is independently selected from ring C1, The ring C is arbitrarily divided by 1 to 4 Rs. c replace;

[0306] Each ring D is independently selected from ring D1, The ring D is arbitrarily divided by 1 to 4 Rs. c replace;

[0307] Ring A is independently selected from ring A1,

[0308] Ring A1 is selected independently from each

[0309] Ring C1 is selected independently from each The ring C1 is arbitrarily selected by 1 to 4 Rs c replace;

[0310] Ring D1 is selected independently from each The ring D1 is arbitrarily selected by 1 to 4 Rs d replace;

[0311] Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect;

[0312] The definitions of the remaining functional groups are the same as those in the first, second, third, or fourth embodiments of this application.

[0313] As a sixth embodiment of this application, the compounds represented by the above general formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (IA), (IB), (IC), (ID), (IE), (IF), or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts,

[0314] Ring B1 is selected independently from each One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0315] Preferably, each ring B1 is independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0316] More preferably, rings B1 are each independently selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-;

[0317] b1 is selected independently from 1 and 2;

[0318] b4 is selected independently from 0, 1, 2, and 3;

[0319] b5 is selected independently from 0, 1, 2, and 3;

[0320] b3 is independently selected from 0, 1, 2, and 3;

[0321] a1 is independently selected from 0, 1, 2, and 3;

[0322] a2 is independently selected from 0, 1, 2, and 3;

[0323] Selected from

[0324] Selected from

[0325] Each independently selected Preferably, Each independently selected

[0326] Or, R d Selected from R 1d R 1d Selected from -N(methyl)2, -N(ethyl)2,

[0327] Or, R c Selected from R 1c R 1c Selected from -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 ,-Cyclopropyl-R d1 -Cyclobutyl-R d1 -cyclopentyl-R d1 The cyclopropyl, cyclobutyl, and cyclopentyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy groups;

[0328] R b1 Each independently selected H, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0329] R b3 Each independently selected H, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0330] R c R d Each of the following groups is independently selected from deuterium, F, Cl, Br, CN, OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl, cyclobutyl, wherein the CH2, methyl, ethyl, cyclopropyl, and cyclobutyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0331] As an option, R c With R d Together with the skeleton connected to it, they form ring E;

[0332] Preferably, R c Each is independently selected from deuterium, F, Cl, Br, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl;

[0333] Preferably, R d Each is independently selected from deuterium, F, Cl, Br, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl;

[0334] R A Each independently selected from R a The following substances are used: deuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, isopropyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy, cyclopropyl, cyclobutyl, -CH2-cyclopropyl, wherein CH2, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy;

[0335] R a Each is independently selected from -SF5, -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-Ra1 -cyclohexyl-R a1 , -S-methyl, -S-ethyl, -O-cyclopropyl, -O-cyclobutyl, oxetanebutyl, azironebutyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl The cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups mentioned above... Methyl, ethyl, oxetyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl Choose from 1 to 4 Rs k replace;

[0336] Preferably, R a Each independently selected from -SF5, -S-methyl, -O-cyclopropyl, The methyl, cyclopropyl, It may be optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy;

[0337] R a1 Each of these elements is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, piperidinyl, The methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, and piperidinyl groups may optionally be substituted with 1 to 4 deuterium, F, Cl, Br, I, CN, OH, NH2, methyl, or methoxy substituents;

[0338] The definitions of the remaining functional groups are the same as those in the first, second, third, fourth, or fifth embodiments of this application.

[0339] As a seventh embodiment of this application, the compound represented by the above general formulas (IB), (I-B1), (I-B2), (IC), (I-C1), (I-h1), (I-DD), (ID), (I-D1), (IF), (I-F1), or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts,

[0340] Among them, R a Selected from -C 3-6 cycloalkyl-R a1 The cycloalkyl group is optionally surrounded by 1 to 5 R groups. k Replace any of 1 to 4 R k Replacement; preferably, R a Selected from -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-R a1 ;

[0341] R a1 Each independently selected

[0342] b3 is independently selected from 0, 1, 2, 3, and 4; preferably, b3 is independently selected from 0, 1, and 2.

[0343] R b3 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R b3 Each independently selected Deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy.

[0344] As an option, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-6 cycloalkyl group, wherein the cycloalkyl group is optionally surrounded by 1 to 4 R groups k replace;

[0345] Each ring D is independently selected from ring D1 or phenyl, wherein ring D is optionally surrounded by 1 to 5 R groups. d replace;

[0346] Preferably, each ring D is independently selected from ring D1, The ring D is arbitrarily divided by 1 to 4 Rs.d replace;

[0347] Each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: C 5-12 Bridged cycloalkyl;

[0348] Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side is connected to -COOH;

[0349] More preferably, rings D1 are each independently selected from 1 to 4 R's. d The following groups are substituted: Its right side is connected to -COOH;

[0350] Each s3 is independently selected from 0, 1, or 2;

[0351] Each s5 is independently selected from 0, 1, or 2;

[0352] s2 are each independently selected from 0 or 1;

[0353] Each of s7 can be independently selected from 1, 2, or 3;

[0354] More preferably, rings D1 are each independently selected from 1 to 4 R's. d The following groups are substituted: Its right side is connected to -COOH;

[0355] Each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: benzo[C] 4-6 Carbocyclic groups, benzo4-6 membered heterocyclic groups;

[0356] Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted:

[0357] b4 is independently selected from 0, 1, 2, and 3; preferably, b4 is independently selected from 0, 1, and 2.

[0358] a2 is independently selected from 0, 1, 2, 3, and 4; preferably, a2 is independently selected from 0 and 1.

[0359] c1 is independently selected from 0, 1, and 2;

[0360] d1 is independently selected from 0, 1, and 2;

[0361] X1 is independently selected from O or S;

[0362] X2 is independently selected from O or S;

[0363] Preferably, each of X2 is independently selected from O;

[0364] R A Each element is independently selected from deuterium, halogens, and C. 1-4 The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R A Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3;

[0365] R b1 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R b1 Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3,

[0366] As an option, any two R b1 Together with the carbon atoms or framework attached to it, they form C 3-6 cycloalkyl group, wherein the cycloalkyl group is optionally surrounded by 1 to 4 R groups k replace;

[0367] R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 The alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R c Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3, and cyclopropyl;

[0368] R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6The alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R d Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3, and cyclopropyl;

[0369] R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-4 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace;

[0370] Preferably, Selected from

[0371] R k Each is independently selected from deuterium, F, Cl, Br, -CH2OH, methyl, ethyl, isopropyl, CD3, OCD3, CH2F, CHF2, CF3, OCF3, methoxy, ethoxy, methylthio, -CH2-cyclopropyl, and cyclopropyl.

[0372] This application relates to compounds or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts as shown below, wherein the compound is selected from one of the structures shown in Table E.

[0373] Table E

[0374] This application relates to a pharmaceutical composition comprising any of the above-described compounds or their stereoisomers, racemates, tautomers, pharmaceutically acceptable salts, and pharmaceutically acceptable excipients.

[0375] This application relates to a pharmaceutical composition comprising a therapeutically effective amount of the compound described above, or its stereoisomers, racemates, tautomers, pharmaceutically acceptable salts, and pharmaceutically acceptable excipients.

[0376] This application relates to the use of any of the above-mentioned compounds or their stereoisomers, racemates, tautomers, pharmaceutically acceptable salts or pharmaceutical compositions thereof in the preparation of medicaments for treating diseases related to GIPR.

[0377] This application relates to the use of any of the above-described compounds, or their stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, in the preparation of medicaments for treating and / or alleviating diabetes or obesity. This application also relates to the use of the above-described pharmaceutical compositions in the preparation of medicaments for treating and / or alleviating diabetes or obesity.

[0378] This application relates to a method for treating or alleviating a disease in mammals, the method comprising administering to a subject a therapeutically effective amount of the above-mentioned compound or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, preferably 1-1500 mg, wherein the disease is preferably diabetes or obesity.

[0379] This application relates to a method for treating or alleviating a disease in mammals, the method comprising administering to a subject a therapeutically effective amount of the above-mentioned compound or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, preferably 1-1500 mg, wherein the disease is selected from diseases related to GIPR.

[0380] Preferably, the disease is selected from diabetes [e.g., type 1 diabetes (T1D), type 2 diabetes (T2DM), prediabetes], idiopathic T1D (type 1b), latent autoimmune diabetes mellitus in adults (LADA), early-onset T2DM (EOD), adolescent-onset atypical diabetes (YOAD), adolescent-adult diabetes (MODY), malnutrition-associated diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, and kidney diseases [e.g., acute kidney disease, renal tubular dysfunction, pro-inflammatory changes in the proximal tubules, or chronic kidney disease]. Diseases (CKD), diabetic retinopathy, adipocyte dysfunction, visceral fat deposition, sleep apnea [e.g., obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urinary incontinence), eating disorders (including bulimia syndrome, bulimia nervosa, and syndromic obesity such as Prad-Willi syndrome and Budd-Bead syndrome), weight gain, such as weight gain due to the use of other medications (e.g., due to the use of steroids and / or antipsychotics, or due to the treatment of depression, or due to the use of medications that affect cognitive function), overweight, etc. Sugar addiction, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, elevated total cholesterol, high LDL (low-density lipoprotein) cholesterol and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, non-alcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction], etc. [Heart failure (HFrEF)], myocardial infarction (e.g., necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, postprandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson's disease, left ventricular hypertrophy, peripheral artery disease (PAD), macular degeneration, cataracts, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attack, restenosis, impaired glucose metabolism, impaired fasting glucose, hyperuricemia, gout, erectile dysfunction,Skin and connective tissue diseases, psoriasis, foot ulcers, ulcerative colitis, hyperapolipoprotein B hyperlipoproteinemia, Alzheimer's disease, schizophrenia, cognitive impairment, inflammatory bowel disease, short bowel syndrome, Crohn's disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addictions (e.g., alcohol, nicotine, and / or drug addiction).

[0381] In some embodiments, the pharmaceutical composition of this application may be in unit dosage form (the amount of the active pharmaceutical ingredient in a unit dosage form is also referred to as a "dosage strength").

[0382] 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., diabetes or obesity). 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 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, 1-1500 mg, 1-1200 mg, 1-1000 mg, 1-900 mg, 1-800 mg, 1-700 mg, 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, and 1-500 mg. 2-500mg, 3-500mg, 4-500mg, 5-500mg, 6-500mg, 10-500mg, 20-500mg, 25-500mg, 30-500mg, 40-500mg, 50-500mg, 60-500mg, 70-500mg, 75-500mg , 80-500mg, 90-500mg, 100-500mg, 125-500mg, 150-500mg, 200-500mg, 250-500mg, 300-500mg, 400-500mg, 5-400mg, 10-400mg, 20-400mg, 25-40 0mg, 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, 300-400mg, 1-300mg, 2-300mg, 5-300mg, 10-300mg, 20-300mg, 25-300mg, 30-300mg, 40-300mg, 50-300mg, 60-300mg, 70-300mg, 75-300mg , 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, 80-1000mg, 80-800mg.

[0383] In some embodiments, the pharmaceutical composition includes, but is not limited to, 1-1000 mg, 20-800 mg, 40-800 mg, 40-400 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, The compound of this application or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts thereof, in doses of 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, 320 mg, 400 mg, 480 mg, 500 mg, 600 mg, 640 mg, or 840 mg.

[0384] A method for treating or alleviating a disease in mammals. The method comprises administering the drug, a compound of this application, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, to a subject at a daily dose of 1-1000 mg / day. The daily dose may be a single dose or multiple doses. In some embodiments, the daily dose includes, but is not limited to, 10-1500 mg / day, 10-1000 mg / day, 10-800 mg / day, 25-800 mg / day, 50-800 mg / day, 100-800 mg / day, 200-800 mg / day, 25- 400 mg / day, 50-400 mg / day, 100-400 mg / day, 200-400 mg / day, and in some embodiments, the daily dose includes, but is not limited to, 10 mg / day, 20 mg / day, 25 mg / day, 50 mg / day, 80 mg / day, 100 mg / day, 125 mg / day, 150 mg / day, 160 mg / day, 200 mg / day, 300 mg / day, 320 mg / day, 400 mg / day, 480 mg / day, 600 mg / day, 640 mg / day, 800 mg / day, and 1000 mg / day.

[0385] This application relates to a kit that may include a single-dose or multi-dose composition containing the compound of this application or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein the amount of the compound of this application or its stereoisomers, racemates, or pharmaceutically acceptable salts is the same as the amount in the aforementioned pharmaceutical composition.

[0386] The amount of the compound or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts in this application is converted in each case to the form of free base.

[0387] General Synthesis Method 1:

[0388] General formula (Z1) and general formula (Z2) are acylated by catalytic addition of an organic base to obtain the corresponding general formula (Z3). General formula (Z3) and (Z4) are condensed with the participation of a condensing agent to obtain the corresponding general formula (Z5). General formula (Z5) is hydrolyzed under alkaline conditions to obtain the corresponding general formula (I').

[0389] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0390] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0391] The compounds in this application include their racemic, stereoisomer, tautomer, isotopic compounds, deuterated products, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals.

[0392] The carbon, hydrogen, oxygen, sulfur, nitrogen, phosphorus, F, Cl, Br, I, etc. involved in the groups and compounds described in this application include their isotopic representations. That is, the carbon, hydrogen, oxygen, sulfur, nitrogen, phosphorus, F, Cl, Br, I, etc. involved in the groups and compounds described in this application may be further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 11 C 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 15 O、 16 O、 17 O and 18 O, isotopes of sulfur include 32 S, 33 S, 34 S, 35 S and 36 S, nitrogen isotopes include 13 N、 14 N and 15 N, isotopes of fluorine include 17 F, 18 F and 19 F, isotopes of chlorine include 35 Cl、 36 Cl and 37 Cl, isotopes of bromine include 79 Br and 81 Br, an isotope of iodine, includes 123 I, 125 I, phosphorus isotopes include31 P, 32 P. In some embodiments, at the position of the deuterium substituent, the deuterium isotope abundance is greater than the natural deuterium isotope abundance (0.015%), preferably greater than 50%, more preferably greater than 60%, greater than 70%, greater than 80%, greater than 90%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 99%, greater than 99.5%, or 100%. In some cases, such as when “hydrogen” and “deuterium” appear as parallel terms, or when “hydrogen” is replaced by “deuterium”, the term “hydrogen” represents the isotope abundance of hydrogen. 1 "H", while "deuterium" represents the isotope of hydrogen. 2 H”; or it should be understood that at this position in the compound, hydrogen, existing in its natural abundance at various isotopes at that position, is replaced by deuterium, existing in its abundance at a level greater than that of the natural deuterium isotopes (e.g., deuterium abundance greater than 50%, greater than 60%, greater than 70%, greater than 80%, greater than 90%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 99%, greater than 99.5%, or 100%).

[0393] “CN” refers to cyano.

[0394] "Halogen" refers to F, Cl, Br or I.

[0395] "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".

[0396] "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, isobutyl, tert-butyl, n-pentyl, isopentyl, tert-pentyl, neopentyl, n-hexyl, and their various branched isomers; the alkyl group can be monovalent, divalent, trivalent, or tetravalent.

[0397] "Alkylene" refers to substituted or unsubstituted straight-chain and branched divalent saturated hydrocarbon groups, including -(CH2)d v - (dv is an integer from 1 to 10), alkylene examples include but are not limited to methylene, ethylene, propylene, and butylene.

[0398] "Cycloalkyl" refers to a substituted or unsubstituted saturated carbocyclic hydrocarbon group, typically having 3 to 12 carbon atoms. Cycloalkyl groups can be monocyclic, fused, bridged, or spirocyclic. Non-limiting examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutyl-cyclobutyl, cyclobutylspirobutyl, bicyclo[1.1.1]pentane, bicyclo[2.2.2]octane, adamantane, etc. Cycloalkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0399] "Heterocyclic alkyl" refers to substituted or unsubstituted saturated cyclic hydrocarbon groups containing heteroatoms, including but not limited to groups with 3 to 12 atoms, 3 to 8 atoms, containing 1 to 3 heteroatoms, or containing heteroatoms (including but not limited to N, S (=O)). dn O, Se, P, P (=O), S (=O)(=NH), Si, boron, dn is 0, 1 or 2). Heterocyclic alkyl groups can be monocyclic, fused, bridged, or spirocyclic. Heterocyclic alkyl groups can be attached to heteroatoms or carbon atoms. Non-limiting examples include epoxyethyl, aziridinepropyl, oxacyclobutyl, aziridinebutyl, tetrahydrofuranyl, tetrahydro-2H-pyranyl, dioxopentyl, dioxohexyl, pyrrolidinyl, piperidinyl, imidazoalkyl, oxazolidinyl, oxazinyl, morpholinyl, hexahydropyrimidinyl, piperazineyl, Heterocyclic alkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0400] "Cycloalkenyl" refers to a substituted or unsubstituted partially unsaturated carbocyclic hydrocarbon group, typically with 3 to 12 carbon atoms, and at least one carbon-carbon double bond within the ring, usually with 1, 2, or 3 carbon-carbon double bonds. Cycloalkenyl groups can be monocyclic, fused, bridged, or spirocyclic. Non-limiting examples include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cyclobutyl-cyclobutenyl, cyclobutenylspirocyclobutyl, etc. Cycloalkenyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0401] "Heterocyclic alkenyl" refers to a substituted or unsubstituted partially unsaturated cyclic hydrocarbon group containing heteroatoms, including but not limited to groups with 3 to 12 atoms, 3 to 8 atoms, containing 1 to 3 heteroatoms, or containing heteroatoms (including but not limited to N, S (=O)). dn The heterocyclic alkenyl group contains at least one, typically one, two, or three double bonds, and is composed of elements such as O, Se, P, P (=O), S (=O) (=NH), Si, and boron (dn is 0, 1, or 2). It can be a monocyclic, fused, bridged, or spirocyclic group. The heterocyclic alkenyl group can be attached to a heteroatom or a carbon atom; non-limiting examples include oxobutenyl, dihydropyridyl, dihydropyrroleyl, tetrahydropyridyl, tetrahydroazapyrrolyl, or azaspirooctene. The heterocyclic alkenyl group can be monovalent, divalent, trivalent, or tetravalent.

[0402] "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, 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 group can be monovalent, divalent, trivalent, or tetravalent.

[0403] "Alynyl" refers to a substituted or unsubstituted straight-chain and branched 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, and 4-pentynyl. The alkynyl group can be monovalent, divalent, trivalent, or tetravalent.

[0404] "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, and n-hexoxy.

[0405] "Carbocyclic group" or "carbocyclic ring" refers to a substituted or unsubstituted aromatic or 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, a 10- to 15-membered tricyclic ring, or a 12- to 18-membered quaternary system. The carbocyclic group can be attached to an aromatic or non-aromatic ring, and the ring can be optionally a monocyclic, fused, 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. "Carbocyclic group" or "carbon ring" can be monovalent, divalent, trivalent or tetravalent.

[0406] "Heterocyclic group" or "heterocyclic ring" refers to a substituted or unsubstituted aromatic or 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, a 10- to 15-membered tricyclic ring, or a 12- to 18-membered quaternary system, and contains one or more (including but not limited to 2, 3, 4, or 5) heteroatoms or groups containing heteroatoms (including but not limited to N, S (=O)). dn O, Se, P, P (=O), S (=O)(=NH), Si, boron, dn is 0, 1 or 2). The heterocyclic group can be attached to a heteroatom or a carbon atom, and can be attached to an aromatic ring or a non-aromatic ring. The heterocyclic group is optionally a monocyclic, bridged, fused, or spirocyclic ring. Non-limiting examples include epoxyethyl, aziridinepropyl, oxacyclobutyl, aziridinebutyl, 1,3-dioxopentyl, 1,4-dioxopentyl, 1,3-dioxahexane, aziridineheptyl, pyridinyl, furanyl, thiophene, pyranyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, piperidinyl, morpholinyl, thiomorpholinyl, 1,3-dithioyl, dihydrofuranyl, dihydropyranyl, dithiapentylcycloyl. Tetrahydrofuranyl, 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, "Heterocyclic group" or "heterocyclic" can be monovalent, divalent, trivalent or tetravalent.

[0407] "Spirocyclic" or "spirocyclic group" refers to a polycyclic group in which substituted or unsubstituted 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 heteroatoms or groups containing heteroatoms (including but not limited to N, S (=O)). dn O, Se, P, P (=O), S (=O)(=NH), Si, boron, dn is 0, 1 or 2). Non-limiting embodiments include: "Spirocyclic" or "spirocyclic group" can be monovalent, divalent, trivalent or tetravalent.

[0408] "Circular fused" or "circular fused group" refers to a polycyclic group in which each ring in a system shares a pair of adjacent atoms with 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 a circular fused system may contain 0 to 5 heteroatoms or groups containing heteroatoms (including but not limited to those selected from N, S (=O)). dn O, Se, P, P (=O), S (=O) (=NH), Si, boron, dn is 0, 1 or 2). The number of ring atoms in the 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: "Cyclone" or "cyclone base" can be monovalent, divalent, trivalent, or tetravalent.

[0409] A "bridged ring" or "bridged ring group" refers to a substituted or unsubstituted polycyclic group containing any two atoms that are not directly connected. It may contain zero or more double bonds. Any ring in a bridged ring system may contain zero to five groups selected from heteroatoms or containing heteroatoms (including but not limited to N, S (=O)). dn O, Se, P, P (=O), S (=O)(=NH), Si, boron, where dn 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: Cubicane, adamantane. "Bridged ring" or "bridged ring group" can be monovalent, divalent, trivalent, or tetravalent.

[0410] "Carbon spirocyclic", "spirocyclic carbon cyclic", "spirocarbon cyclic", or "carbon spirocyclic" refers to a spirocyclic system composed only of carbon atoms.

[0411] "Carbon fused ring", "fused cyclic carbon cyclic group", "fused carbon cyclic group" or "carbon fused cyclic group" refers to a ring system composed only of carbon atoms.

[0412] "Carbon bridged ring", "bridged ring carbon cyclo group", "bridged carbon cyclo group" or "carbon bridged ring group" refers to a ring system composed only of carbon atoms.

[0413] "Hybrid monocyclic", "monocyclic heterocyclic group" or "hybrid monocyclic group" refers to the "heterocyclic group" or "heterocyclic" in a monocyclic system.

[0414] "Hydrocyclic ring", "hydrocyclic cyclic group", "fused cyclic heterocyclic group" or "fused heterocyclic group" refers to a "fused ring" containing heteroatoms.

[0415] "Heterospirocyclic", "heterospirocyclic group", "spirocyclic heterocyclic group" or "spiroheterocyclic group" refers to a "spirocycle" containing heteroatoms.

[0416] "Hybrid-bridged ring", "hybrid-bridged ring group", "bridged ring heterocyclic group" or "bridged heterocyclic group" refers to a "bridged ring" containing heteroatoms.

[0417] "Aryl" or "aromatic ring" refers to a substituted or unsubstituted aromatic hydrocarbon group having a monocyclic or fused ring, wherein 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, 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.

[0418] "Heteroaryl" or "heteroary ring" refers to a substituted or unsubstituted aromatic hydrocarbon group containing 1 to 5 (e.g., 1, 2, 3, 4, 5) heteroatoms or groups containing heteroatoms (including but not limited to N, O, S (=O)). dn OrSe(=O) dn (dn is 0, 1, or 2), the number of ring atoms in the heteroaromatic ring includes, but is not limited to, 5 to 15, 5 to 10, or 5 to 6. The atoms C, N, S, or Se on the ring are optionally oxidized (i.e., C (=O), NO, S (=O)). dm Se (=O) dm (dm is 1, 2), non-limiting embodiments of heteroaryl groups include, but are not limited to, pyridyl, furanyl, thiophenyl, selenophenyl, pyridyl, pyranyl, N-alkylpyrrolithyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazoleyl, benzopyrazolyl, benzimidazolyl, benzopyridyl, pyrrolopyridyl, pyridinoneyl, etc. The heteroaryl ring may be fused to a saturated or unsaturated carbon ring or heterocycle, wherein the ring connected to the parent structure is an aryl ring. Non-limiting embodiments include: The heteroaryl groups mentioned in this article are defined in accordance with this definition. Heteroaryl groups can be monovalent, divalent, trivalent, or tetravalent. When divalent, trivalent, or tetravalent, the linkage site is located on an aromatic ring.

[0419] "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, =S, =NH, carbonyl, aldehyde, carboxylic acid, formate, -(CH2). dn -C(=O)-R da -O-(CH2) dn -C(=O)-R da -(CH2) dn -C(=O)-NR db R dc -(CH2) dn S(=O) dn R da -(CH2) dn -Alkenyl-R da OR dd Or -(CH2) dn -alkynyl-R da (where dn is 0, 1, or 2), arylthio, thiocarbonyl, silyl, or -NR db R dc Groups, wherein R db With R dc Independently selected from H, hydroxyl, amino, carbonyl, alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, heteroaryl, sulfonyl, trifluoromethanesulfonyl, R db With R dc It can form 3 to 6-membered heterocyclic groups, R da With R dd Each group is independently selected from aryl, heteroaryl, alkyl, alkoxy, cycloalkyl, heterocyclic, carbonyl, ester, bridged cyclic, spirocyclic, or fused cyclic groups.

[0420] "Halogenated alkyl" refers to an alkyl group that is substituted by one or more (including but not limited to 2, 3, 4, 5, or 6) halogens, wherein the alkyl group is as defined above, for example, "halogenated C 1-6 Alkyl", C 1-6 "Halogenated alkyl", etc., specific examples include but are not limited to: trifluoromethyl, 2-chloroethyl, 1,2-difluoropropyl, pentafluoroethyl, 2-bromo-3-chlorobutyl, perfluorohexyl, etc.

[0421] "Deuterated alkyl" refers to an alkyl group that has been deuterated by one or more (including but not limited to 2, 3, 4, 5 or 6) deuterium atoms. 2 H) substitution, wherein the alkyl group is as defined above, for example, "deuterated C" 1-6 Alkyl", C 1-6 "Deuterated alkyl", etc., specific examples include but are not limited to: CD3, CH2CD3, etc.

[0422] "Hydroxyalkyl" or "hydroxyalkyl" means that an alkyl group is replaced by one or more (including but not limited to 2, 3, 4, 5 or 6) hydroxyl groups, wherein the alkyl group is as defined above.

[0423] "1 to X substituents selected from..." means substituted by 1, 2, 3...X substituents selected from..., where X is any integer between 1 and 10. For example, "1 to 4 R..." k "Replace" refers to being replaced by 1, 2, 3, or 4 Rs. k Substitution. For example, "substituted by 1 to 5 substituents selected from..." means that the ring is substituted by 1, 2, 3, 4 or 5 substituents selected from... For example, "the heterobridged ring is optionally substituted by 1 to 4 substituents selected from H or F" means that the heterobridged ring is optionally substituted by 1, 2, 3 or 4 substituents selected from H or F.

[0424] The XY-membered rings (where X and Y are integers, and 3 ≤ X < Y, X < Y ≤ 20, selected from any integer between 4 and 20) include rings of the X, X+1, X+2, X+3, X+4…Y-membered elements. 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.

[0425] C x-y Carbocyclic rings (including aryl, cycloalkyl, monocyclic, spirocyclic, fused, or bridged carbocyclic rings) include C x C x+1 C x+2 C x+3 C x+4 ….C y A ring of elements (x is an integer, and 3 ≤ x < y, where y is any integer between 4 and 20), for example, "C". 3-6 "Cycloalkyl" refers to C3, C4, C5, or C6 cycloalkyl groups.

[0426] When a functional group has one or more connectable sites, any one or more of these sites can be linked to other functional groups via chemical bonds. When the chemical bond connection is non-directional and a hydrogen atom is present at the connectable site, the number of hydrogen atoms at that site decreases accordingly with the number of bonds being formed, resulting in a functional group with a corresponding valence. For example... This indicates that any connectable site on the piperidinyl group can be linked to other groups via a single chemical bond, including at least... These four connection methods, even if an H atom is drawn on -N-, This also includes For example This indicates that the R group on the piperidinyl group can be located on C or N, and at least includes [missing information]. For example, the general formula segment is: When X is selected from CH2 or NH, it means that the R group on the general formula fragment can be located on C or X. When X is selected from CH2, the general formula fragment can be... When X is selected from NH, the general formula fragment can be:

[0427] Unless otherwise stated, key This indicates that the configuration is not specified; that is, if chiral atoms are present in the chemical structure, the bond... It can be or Or simultaneously include or Two configurations. Using wedge-shaped solid line keys. and wedge-shaped dashed key The absolute configuration of the center of a solid is represented by a straight solid line key. and straight dashed key Represents the relative configuration of the solid center. (Key) This indicates that no configuration is specified, meaning it can be either Z configuration or E configuration, or both configurations can be included.

[0428] When the listed linking groups do not specify their linking direction, the linking direction includes the direction of the reading order from left to right and from right to left. For example, when ALB is selected from -MW-, it includes AMWB and AWMB.

[0429] "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.

[0430] "Pharmaceutically acceptable salt" or "its pharmaceutically acceptable salt" means that the compound of this application 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, and the free base is obtained by reacting with a non-toxic inorganic or organic acid.

[0431] "Pharmaceutical composition" refers to a mixture of one or more compounds described in this application, or their stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, and other chemical components, wherein "other chemical components" refers to pharmaceutically acceptable excipients and / or one or more other therapeutic agents. Pharmaceutically acceptable excipients include pharmaceutically acceptable carriers, pharmaceutical excipients, and functional excipients. "Carrier" refers to a material that does not cause significant irritation to organisms and does not eliminate the biological activity and properties of the administered compound.

[0432] "Prodrug" refers to a compound of this application that can be metabolized in vivo and has biological activity. The prodrug of this application is prepared by modifying the amino or carboxyl groups in the compound of this application. This modification can be performed by conventional procedures or removed in vivo to obtain the parent compound.

[0433] "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.

[0434] "Stereoisomers" refer to isomers that are produced by different spatial arrangements of atoms in a molecule, including cis-trans isomers, enantiomers, diastereomers, conformational isomers, or transisomers.

[0435] "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.

[0436] "Animals" refers to mammals, such as humans, companion animals, zoo animals, and livestock, with humans, horses, or dogs being preferred. Detailed Implementation

[0437] The following embodiments illustrate the technical solutions of this application in detail, but the scope of protection of this application includes, but is not limited to, these embodiments.

[0438] The structure of the compound was determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shifts (δ) were expressed in 10⁻¹⁰ increments. -6The unit (ppm) is given. NMR measurements were performed using a Bruker Avance III 400 and Bruker Avance 300 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0439] MS determination was performed using (Agilent 6120B (ESI) and Agilent 6120B (APCI));

[0440] HPLC determinations were performed using an Agilent 1260DAD high-performance liquid chromatograph (Zorbax SB-C18 100×4.6mm, 3.5μM).

[0441] Thin-layer chromatography silica gel plates used were from Yantai Huanghai HSGF. 254 Or Qingdao GF 254 Silica gel plates: The silica gel plates used in thin-layer chromatography (TLC) have a diameter of 0.15mm-0.20mm, while those used for TLC separation and purification of products have a diameter of 0.4mm-0.5mm.

[0442] Column chromatography typically uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier;

[0443] The starting materials for this application 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.

[0444] Example 1: Preparation of Compound 1

[0445] Step 1: Preparation of Compound 1

[0446] Dissolve 1a (CAS: 3059502-51-8, 50 mg, 0.34 mmol) in ultra-dry acetonitrile (2 mL), add N,N'-carbonyldiimidazole (57 mg, 0.35 mmol), stir at room temperature for 0.5 hours, concentrate the system to dryness, and dissolve the residue in ultra-dry N,N-dimethylacetamide (1 mL).

[0447] The mixture was added to a reaction system containing 1a-1 (105 mg, 0.30 mmol) and N-methylmorpholine (184 mg, 1.82 mmol) in N,N-dimethylacetamide (2 mL). The reaction was carried out at room temperature for 2 hours. The system was then purified by preparative liquid chromatography (PLC) of the residue (instrument: Waters 2767 PLC; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 1 (50 mg, yield 30.52%).

[0448] LCMS m / z = 486.3 [M+H] +

[0449] Example 2: Preparation of Compound 2

[0450] Step 1: Preparation of 2b

[0451] Add 10 mL of tetrahydrofuran to a three-necked flask, purge with nitrogen three times, and cool to 0 °C. Quickly add 0.93 g of dibromodifluoroethane (4.44 mmol), stir for 10 minutes in an ice bath, slowly add 0.80 g of tris(dimethylamino)phosphine (4.44 mmol), and continue stirring at 0 °C for 1 hour. Slowly add 5 mL of a tetrahydrofuran solution of 2a (1 g, 4.44 mmol), heat to 25 °C and stir for 1 hour. Add 0.23 g of zinc powder (3.55 mmol), and add 0.02 mL of tris(dimethylamino)phosphine. Transfer to 75 °C and stir for 5 hours. Add water (10 mL) to the reaction solution and separate the organic phase; extract the aqueous layer with ethyl acetate (2 × 10 mL); combine the organic phases, wash with saturated brine (2 × 10 mL), dry with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and separate by silica gel column chromatography to obtain 2b (300 mg).

[0452] Step 2: Preparation of 2c

[0453] 2b (300 mg, 1.16 mmol), tert-butyl carbamate (163 mg, 1.39 mmol), and cesium carbonate (756 mg, 2.32 mmol) were dissolved in 1,4-dioxane (5 mL). The reaction system was purged with nitrogen three times, and then Ru-Phos-G3 (48.51 mg, 0.06 mmol) was added. The reaction system was heated to 100 °C and stirred for 18 hours. After the reaction was completed, the system was diluted with water (10 mL), extracted with ethyl acetate (10 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and separated by silica gel column chromatography to obtain 2c (55 mg).

[0454] LCMS m / z = 240.2 [M-55] + ;

[0455] Step 3: 2D preparation

[0456] Dissolve 2c (55 mg, 0.24 mmol) and p-toluenesulfonic acid (61.99 mg, 0.36 mmol) in acetonitrile (3 mL). Heat the reaction mixture to 50 °C and stir for 2 hours. After the reaction is complete, concentrate the solution to obtain 2d, which can be used directly in the next step.

[0457] LCMS m / z = 196.1 [M+H] + ;

[0458] Step 4: Preparation of Compound 2

[0459] 2d (46 mg, 0.24 mmol) was dissolved in ultra-dry acetonitrile (2 mL), and N,N'-carbonyldiimidazole (38.92 mg, 0.24 mmol) was added. The mixture was stirred at room temperature for 0.5 hours and concentrated to dryness. The residue was dissolved in ultra-dry N,N-dimethylacetamide (1 mL) and added to a reaction system containing 2d-1 (CAS: 3059502-67-6, 74.48 mg, 0.24 mmol) and N-methylmorpholine (97.1 mg, 0.96 mmol) in N,N-dimethylacetamide (2 mL). The reaction was carried out at room temperature for 2 hours. The residue was purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 2 (7 mg).

[0460] LCMS m / z = 532.3 [M+H] +

[0461] 1H NMR(400MHz,DMSO-d6)δ12.90(s,1H),10.12(s,1H),8.25(s,1H),7.99(d,2H),7.83-7.66(m,6H),7.47(d,2H),7.16(d, 2H),4.52-4.43(m,1H),3.70-3.51(m,3H),3.12-2.99(m,2H),2.78-2.64(m,2H),2.25-2.14(m,1H),2.09-1.88(m,3H).

[0462] Example 3: Preparation of Compound 3

[0463] Step 1: Preparation of 3a

[0464] At 0°C, potassium tert-butoxide (2.99 g, 26.67 mmol) was added to 20 mL of tetrahydrofuran containing 9.53 g (26.67 mmol) of methyltriphenylphosphine bromide. The mixture was heated to 40°C and stirred for 1 hour. Then, 2a (2 g, 8.89 mmol) was added, and the mixture was stirred at 40°C for 5 hours. Water (100 mL) was added to the reaction mixture, and the organic phase was separated. The aqueous layer was extracted with ethyl acetate (2 × 100 mL). The organic phases were combined, washed with saturated brine (2 × 100 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 3a (1.1 g).

[0465] Step 2: Preparation of 3b

[0466] 3a (1.1 g, 4.93 mmol), tert-butyl carbamate (0.69 g, 5.92 mmol), and cesium carbonate (3.21 g, 9.86 mmol) were dissolved in 1,4-dioxane (30 mL). The reaction system was purged with nitrogen three times, and then Ru-Phos-G3 (48.51 mg, 0.06 mmol) was added. The reaction system was heated to 100 °C and stirred for 18 hours. After the reaction was completed, the system was diluted with water (50 mL), extracted with ethyl acetate (50 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and separated by silica gel column chromatography to obtain 3b (700 mg).

[0467] LCMS m / z = 204.1 [M-55] + ;

[0468] Step 3: Preparation of 3C

[0469] Dissolve 3b (259 mg, 1.0 mmol) and p-toluenesulfonic acid (258.3 mg, 1.5 mmol) in acetonitrile (5 mL). Heat the reaction mixture to 50 °C and stir for 2 hours. After the reaction is complete, concentrate the solution to obtain 3c, which can be used directly in the next step.

[0470] LCMS m / z = 160.1 [M+H] + ;

[0471] Step 4: Preparation of Compound 3

[0472] 3c (160 mg, 1.0 mmol) was dissolved in ultra-dry acetonitrile (3 mL), and N,N'-carbonyldiimidazole (162.2 mg, 1.0 mmol) was added. The mixture was stirred at room temperature for 0.5 hours, and the system was concentrated to dryness. The residue was dissolved in ultra-dry N,N-dimethylacetamide (1 mL), and added to a reaction system containing 2d-1 (310 mg, 1.0 mmol) and N-methylmorpholine (404.6 mg, 4.0 mmol) in N,N-dimethylacetamide (2 mL). The reaction was carried out at room temperature for 2 hours. The system was purified by preparative liquid chromatography (Preparative HPLC) of the residue (instrument: Waters 2767; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 3 (58 mg).

[0473] LCMS m / z = 496.2[M+H] +

[0474] 1H NMR(400MHz,DMSO-d6)δ12.83(s,1H),10.11(s,1H),8.22(s,1H),7.99(d, 2H),7.81-7.67(m,6H),7.44(d,2H),7.14(d,2H),4.83-4.78(m,2H),4.51 -4.45(m,1H),3.70-3.62(m,1H),3.57-3.48(m,1H),3.47-3.37(m,1H),3. 06-2.95(m,2H),2.78-2.67(m,2H),2.26-2.14(m,1H),2.09-1.87(m,3H).

[0475] Example 4: Preparation of Compound 4

[0476] Step 1: Preparation of Compound 4

[0477] Dissolve 4a (100 mg, 0.65 mmol) in ultradry acetonitrile (2 mL), add N,N'-thiocarbonyl diimidazole (120 mg, 0.65 mmol), stir at room temperature for 0.5 hours, concentrate the system to dryness, and dissolve the residue in ultradry N,N-dimethylacetamide (2 mL).

[0478] The mixture was added to a reaction system containing 2d-1 (200 mg, 0.64 mmol) and N-methylmorpholine (184 mg, 1.82 mmol) in N,N-dimethylacetamide (2 mL). The reaction was carried out at room temperature for 2 hours. The system was then purified by preparative liquid chromatography (HPLC) of the residue (instrument: CAS-05-PREP-HPLC K; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 10 mmol / L NH4HCO3 aqueous solution) to obtain compound 4 (171 mg).

[0479] LCMS m / z = 506.1 [M+H] +

[0480] 1 H NMR(400MHz,DMSO-d6)δ10.20(s,1H),9.12(s,1H),8.05-7.93(m,2H),7.81-7.66(m,6H),7.35-7.14( m,3H),5.10-5.00(m,1H),3.89-3.60(m,2H),3.18-3.06(m,1H),2.38-1.93(m,4H),1.29-1.13(m,6H).

[0481] Example 5: Preparation of Compound 5

[0482] Step 1: Preparation of Compound 5

[0483] 5a (100 mg, 0.74 mmol) was dissolved in ultra-dry acetonitrile (4 mL), and N,N'-carbonyldiimidazole (140 mg, 0.79 mmol) was added. The mixture was stirred at room temperature for 0.5 hours, and the system was concentrated to dryness. The residue was dissolved in ultra-dry N,N-dimethylacetamide (2 mL), and added to a reaction system containing 2d-1 (240 mg, 0.77 mmol) and N-methylmorpholine (184 mg, 1.82 mmol) in N,N-dimethylacetamide (2 mL). The reaction was carried out at room temperature for 2 hours. The system was then subjected to preparative liquid chromatography (Preparative HPLC) of the residue (instrument: Waters 2767; column: CAS-05-PREP-HPLC K; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 10 mmol / L)). Compound 5 (163 mg) was obtained by separation and purification using NH4HCO3 aqueous solution.

[0484] LCMS m / z = 488.3 [M+H] +

[0485] 1 H NMR (400MHz, DMSO-d6) δ10.16(s,1H),9.00(s,1H),8.03-7.94(m,2H),7.80-7.65(m,6H),7.34-7.25(m,2H),7. 21-7.13(m,2H),5.12-5.00(m,1H),3.89-3.58(m,2H),2.92-2.78(m,1H),2.35-1.92(m,4H),1.26-1.12(m,6H).

[0486] Example 6: Preparation of Compound 6

[0487] Step 1: Preparation of 6b

[0488] 6a (CAS: 1253787-57-3, 800.0 mg, 2.68 mmol) was dissolved in a mixed solvent of 1,4-dioxane (8 mL) and water (4 mL). 6a-1 (495.4 mg, 2.95 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (218.9 mg, 0.27 mmol), and potassium carbonate (740.8 mg, 5.36 mmol) were added sequentially. After addition, the mixture was stirred at 100 °C for 16 hours under nitrogen atmosphere. After cooling to room temperature, the mixture was extracted with ethyl acetate (20 mL × 3). The organic phase was washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (PE:EA = 10:1) to obtain 6b (260 mg).

[0489] Step 2: Preparation of 6C

[0490] 6b (260 mg, 1.00 mmol) was dissolved in methanol (5 mL), and platinum chloride (33.7 mg, 0.10 mmol) was added. After the addition was complete, the mixture was stirred at 50 °C for 16 hours under hydrogen atmosphere. After cooling to room temperature, the mixture was filtered, and the filter cake was washed with methanol (10 mL). The mixture was concentrated and purified by column chromatography (PE:EA = 5:1) to obtain 6c (162 mg, yield: 61.83%).

[0491] Step 3: Preparation of Compound 6

[0492] Compound 6 (25 mg, yield 12.02%) was obtained by reacting 6c (100 mg, 0.35 mmol) with 2d-1 (134.7 mg) according to the method in step one of Example 1.

[0493] LCMS m / z = 598.2 [M+H] +

[0494] Example 7: Preparation of Compound 7

[0495] Step 1: Preparation of 7b

[0496] 7a (40 g, 164.5 mmol) was dissolved in THF (300 mL), and a 1 M potassium tert-butoxide solution in tetrahydrofuran (246.8 mL, 246.8 mmol) was added dropwise at 0 °C. The mixture was stirred for 1 hour, followed by the addition of a tetrahydrofuran solution of methyltriphenylphosphine bromide (88.2 g, 246.8 mmol) (100 mL). The mixture was stirred at room temperature for 16 hours. The reaction was monitored by TLC until complete. The reaction was quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to obtain 7b (16 g, 40.3% yield).

[0497] Step 2: Preparation of 7c

[0498] 7b (15 g, 62.2 mmol) was dissolved in ether (150 mL), and copper-zinc alloy powder (20.1 g, 155.5 mmol) was added. Trichloroacetyl chloride (22.6 g, 124.4 mmol) and phosphorus oxychloride (13.4 g, 87.1 mmol) were added dropwise at room temperature, and the mixture was heated to 40 °C and reacted for 10 hours. The reaction solution was cooled to room temperature and quenched slowly by pouring in an aqueous sodium bicarbonate solution. The mixture was extracted with ether, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography to obtain 7c (14 g, yield 63.9%).

[0499] Step 3: Preparation of 7 days

[0500] 7c (14 g, 39.8 mmol) was dissolved in acetic acid (140 mL), and zinc powder (10.4 g, 159.1 mmol) was slowly added at 0 °C. The mixture was heated to 100 °C and reacted for 16 hours. Most of the solvent was removed by vacuum concentration, and the crude product was slowly poured into an aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate, and the organic phase was concentrated and purified by silica gel column chromatography to obtain 7d (8.4 g, 75.1% yield).

[0501] Step 4: Preparation of 7e

[0502] Add ultra-dry tetrahydrofuran (40 mL) to a three-necked flask. Under a nitrogen atmosphere and ice bath, rapidly add dibromodifluoroane (3.70 g, 17.64 mmol). Stir in an ice bath for 10 minutes. Slowly add tris(dimethylamino)phosphine (2.88 g, 17.64 mmol). After the addition is complete, continue stirring in an ice bath for 1 hour. Then, dissolve 7d (4.54 g, 16.04 mmol) in tetrahydrofuran (10 mL) and slowly add it to the system. After the addition is complete, allow the temperature to rise naturally to room temperature and react for 1 hour. Finally, add zinc powder (287.80 mg, 4.4 mmol) and add HMPA (0.3 mL). Heat to 75 °C and react for 5 hours. The reaction was quenched by adding water (50 mL), extracted with ethyl acetate (50 mL × 3), the organic phases were combined, backwashed with saturated sodium chloride aqueous solution (150 mL × 2), the organic phase was collected, dried over anhydrous sodium sulfate, filtered and concentrated to obtain crude product, and purified by silica gel column chromatography to obtain 7e (1.8 mg, yield 35.4%).

[0503] Step 5: Preparation of 7f

[0504] 7e (1.8 g, 5.68 mmol) was dissolved in tetrahydrofuran (20 mL) and methanol (10 mL), and then lithium hydroxide monohydrate (0.10 g, 2.45 mmol) dissolved in water (10 mL) was added dropwise to the system. The mixture was stirred at room temperature for 18 hours. The system was concentrated under reduced pressure to obtain a crude product, which was dissolved in water (30 mL), the pH was adjusted to 3-4 with 1 N hydrochloric acid, and ethyl acetate (30 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product 7f (1.69 g). The crude product was used directly in the next reaction without any purification.

[0505] LCMS m / z = 301.0 [MH] -

[0506] Step 6: Preparation of 7g

[0507] 7f (1.69 g, 5.58 mmol) was dissolved in dichloromethane (20 mL), followed by the sequential addition of N,N'-dicyclohexylcarbodiimide (2.32 g, 11.16 mmol) and 4-dimethylaminopyridine (2.05 g, 16.74 mmol). The mixture was stirred at room temperature for 1 hour, and finally tert-butanol (496.31 mg, 6.70 mmol) was added dropwise. The reaction was allowed to proceed for 18 hours at room temperature. The reaction was quenched with water (30 mL), and the mixture was extracted with dichloromethane (30 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain 7 g (870 mg, yield 43.44%).

[0508] Step 7: Preparation over 7 hours

[0509] 7 g (180 mg, 0.50 mmol) was dissolved in 1,4-dioxane (2.5 mL) and water (0.5 mL), followed by the sequential addition of 4-aminophenylboronic acid pinacol ester (131.45 mg, 0.60 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (40.83 mg, 0.05 mmol), and potassium carbonate (207.31 mg, 1.5 mmol). The reaction was heated under a nitrogen atmosphere for 3 hours. The reaction was quenched with water (10 mL), extracted with ethyl acetate (10 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain 7 h (135 mg, yield 45.7%).

[0510] LCMS m / z = 372.1 [M+H] +

[0511] Step 8: Preparation of 7i

[0512] 7h⁻¹ (129.32 mg, 0.47 mmol) was dissolved in dichloromethane (5 mL), followed by the addition of 7h (135 mg, 0.36 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (103.52 mg, 0.54 mmol). After the addition was complete, the reaction was carried out at room temperature under a nitrogen atmosphere for 18 hours. The reaction was confirmed to be complete by TLC. The crude product was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target product 7i (177 mg, yield 58.0%).

[0513] Step 9: Preparation of Compound 7

[0514] Compound 7 (177 mg, 0.21 mmol) was dissolved in dichloromethane (2.5 mL), and then trifluoroacetic acid (0.5 mL) was added dropwise. The reaction was carried out at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to give compound 7 (104 mg, yield 64.5%).

[0515] LCMS m / z = 574.3[M+H]+

[0516] 1H NMR(400MHz,DMSO-d6)δ13.03-12.87(brs,1H),10.10(s,1H),8.17(s,1H),8.02(s ,1H),7.85(d,1H),7.71(d,2H),7.41(d,2H),7.31(d,1H),7.25(d,2H),7.09(d,2H) ,4.52-4.45(m,1H),3.88-3.78(m,1H),3.70-3.60(m,1H),3.57-3.47(m,1H),2.92- 2.75(m,3H),2.73-2.61(m,2H),2.26-2.21(m,1H),2.10-1.88(m,3H),1.17(d,6H).

[0517] Example 8: Preparation of Compound 8

[0518] Step 1: Preparation of 8b

[0519] Dissolve 8a (5 g, 20.73 mmol) in acetonitrile (100 mL), then add tetrahydropyrrole (1.77 g, 24.88 mmol) and potassium carbonate (5.72 g, 41.39 mmol) sequentially. After the addition is complete, stir at 60 °C for 16 hours under nitrogen atmosphere, cool to room temperature, extract with ethyl acetate (50 mL × 3), wash the organic phase with saturated sodium chloride aqueous solution, dry to anhydrous sodium sulfate, concentrate, and purify by column chromatography to obtain 8b (5.94 g, yield 98.03%).

[0520] LCMS m / z = 293.2[M+H] +

[0521] Step 2: Preparation of 8c

[0522] 8b (5.94 g, 20.32 mmol) was dissolved in methanol (100 mL), and zinc powder (6.54 g, 99.98 mmol) and ammonium chloride (5.35 g, 100.02 mmol) were added. After the addition was complete, the mixture was stirred at room temperature under nitrogen for 3 hours, filtered, and the filter cake was washed with methanol (50 mL). The mixture was concentrated and purified by column chromatography to obtain 8c (2.786 g, yield: 52.26%).

[0523] LCMS m / z = 263.1 [M+H] +

[0524] Step 3: Preparation of 8 days

[0525] 8c (2 g, 7.62 mmol) was dissolved in acetonitrile (80 mL), and cuprous bromide (3.3 g, 23.00 mmol) and amyl nitrite (2.7 g, 26.18 mmol) were added sequentially. After the addition was complete, the mixture was stirred at room temperature under nitrogen for 3 hours. Water (50 mL) was added to the reaction solution, and the mixture was concentrated under reduced pressure. The aqueous layer was extracted with ethyl acetate (3 × 50 mL). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by column chromatography to obtain 8d (380 mg, yield 15.28%).

[0526] Step 4: Preparation of 8e

[0527] Dissolve 8d (380 mg, 1.16 mmol) and pinacol p-aminophenylboronic acid (214 mg, 0.95 mmol) in a mixed solution of ethylene glycol dimethyl ether (5 mL), water (2 mL), and ethanol (0.4 mL). Add tetrakis(triphenylphosphine)palladium (57 mg, 0.049 mmol) and sodium carbonate (520 mg, 4.91 mmol) sequentially. After addition, stir at 90 °C for 16 hours under nitrogen atmosphere. Cool to room temperature, extract with ethyl acetate (10 mL * 3). Wash the organic phase with saturated sodium chloride aqueous solution, dry with anhydrous sodium sulfate, concentrate, and purify by column chromatography to obtain 8e (190 mg, yield 59.06%).

[0528] LCMS m / z = 339.1 [M+H] +

[0529] Step 5: Preparation of 8f

[0530] 8e (95 mg, 0.28 mmol) and 8e-1 (87 mg, 0.30 mmol) (refer to the synthesis method in WO2024214038A1) were dissolved in dichloromethane (2 mL), and EDCI (61 mg, 0.39 mmol) was added. After the addition was complete, the mixture was stirred at room temperature under nitrogen for 16 hours and concentrated to obtain 8f, which was directly used in the next reaction.

[0531] Step 6: Preparation of Compound 8

[0532] Compound 8 was dissolved in dichloromethane (2 mL) and added to trifluoroacetic acid (1 mL). The reaction system was stirred at room temperature for 16 hours. After the reaction was completed, the residue was concentrated and purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 8 (101 mg, yield 61.41%).

[0533] LCMS m / z = 559.2 [M+H]+

[0534] Example 9: Preparation of Compound 9

[0535] Compound 9 (9 mg) was obtained by referring to the synthesis method of Example 8.

[0536] LCMS m / z = 527.3 [M+H] +

[0537] Example 10: Preparation of Compound 10

[0538] Step 1: Preparation of 10b

[0539] 10a (1.6 g, 7.21 mmol) and 2-bromo-5-nitrothiophene (1 g, 4.81 mmol) were dissolved in a mixed solution of 1,4-dioxane (40 mL) and water (0.45 mL). [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (200 mg, 0.24 mmol) and cesium fluoride (1.5 g, 9.87 mmol) were added sequentially. After addition, the mixture was stirred at 60 °C for 16 hours under nitrogen atmosphere. The mixture was cooled to room temperature and extracted with ethyl acetate (20 mL × 3). The organic phase was washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 10b (1.14 g, 77.67% yield).

[0540] LCMS m / z = 306.1 [M+H] +

[0541] Step 2: Preparation of 10C

[0542] 10b (1.14 g, 3.73 mmol) was dissolved in methanol (25 mL), and zinc powder (1.22 g, 18.65 mmol) and ammonium chloride (1.0 g, 18.65 mmol) were added. After the addition was complete, the mixture was stirred at room temperature under nitrogen for 3 hours. The mixture was filtered, and the filter cake was washed with methanol (20 mL). The mixture was concentrated and purified by column chromatography to obtain 10c (837 mg, yield: 81.41%).

[0543] LCMS m / z = 276.1 [M+H] +

[0544] Step 3: Preparation of 10 days

[0545] 10c (73 mg, 0.27 mmol) and 8e-1 (100 mg, 0.27 mmol) were dissolved in dichloromethane (3 mL), and EDCI (70 mg, 0.35 mmol) was added. After the addition was complete, the mixture was stirred at room temperature under nitrogen for 16 hours and concentrated to obtain 10d, which was directly used for the next reaction.

[0546] Step 4: Preparation of Compound 10

[0547] Compound 10 was dissolved in dichloromethane (2 mL) and added to trifluoroacetic acid (1 mL). The reaction system was stirred at room temperature for 16 hours. After the reaction was completed, the residue was concentrated and purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 10 (103 mg, yield 76.95%).

[0548] LCMS m / z = 496.2[M+H] +

[0549] Example 11: Preparation of Compound 11

[0550] Step 1: Preparation of 11b

[0551] 11a (5.0 g, 27.31 mmol) was dissolved in ultradry tetrahydrofuran (50 mL), purged three times with nitrogen, and cooled to -78 °C. A 2.5 M nBuLi THF solution (11.5 mL, 28.75 mmol) was added dropwise, and the mixture was stirred at the same temperature for 2 hours. Trimethylchlorosilane (3.15 g, 29.0 mmol) was then slowly added dropwise, and the mixture was heated to room temperature and stirred for 16 hours. Water (20 mL) was added to the reaction mixture, and the system was concentrated under reduced pressure. The aqueous layer was extracted with petroleum ether (3 × 20 mL). The combined organic phases were washed with saturated brine (2 × 20 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 11b (4.0 g, yield 83.05%).

[0552] Step 2: Preparation of 11c

[0553] Potassium tert-butoxide (4.78 g, 42.64 mmol) was dissolved in ultradry tetrahydrofuran (100 mL), purged three times with nitrogen, and cooled to -78 °C. 11b (4.0 g, 22.68 mmol) was added, followed by dropwise addition of a 2.5 M nBuLi THF solution (17.06 mL, 42.64 mmol). The mixture was stirred at the same temperature for 1 hour, and iodomethane (11.88 g, 83.69 mmol) was added dropwise. The mixture was then heated to room temperature and stirred for 16 hours. An aqueous solution of ammonium chloride (40 mL, 10% wt) was added to the reaction mixture, and the system was concentrated under reduced pressure. The aqueous layer was extracted with petroleum ether (3 × 20 mL). The combined organic phases were washed with saturated brine (2 × 20 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 11c (3.67 g, yield 84.99%).

[0554] Step 3: Preparation of 11 days

[0555] 11c (3.67 g, 19.28 mmol) was dissolved in methanol (100 mL), and NCS (3.71 g, 27.78 mmol) and lithium bromide (2.41 g, 27.75 mmol) were added. The mixture was stirred at room temperature for 2 hours. Water (20 mL) was added to the reaction solution, and the system was concentrated under reduced pressure. The aqueous layer was extracted with petroleum ether (3 × 20 mL). The combined organic phases were washed with saturated brine (2 × 20 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 11d (3.0 g, yield 78.96%).

[0556] Step 4: Preparation of 11e

[0557] 11d (200 mg, 1.01 mmol), tert-butyl carbamate (140 mg, 1.20 mmol), and cesium carbonate (650 mg, 1.99 mmol) were dissolved in 1,4-dioxane (2 mL). The reaction system was purged with nitrogen three times, and then Ru-Phos-G3 (80 mg, 0.096 mmol) was added. The reaction system was heated to 100 °C and stirred for 16 hours. After the reaction was completed, the system was diluted with water (5 mL), extracted with ethyl acetate (5 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and separated by silica gel column chromatography to obtain 11e (196 mg, yield 82.78%).

[0558] LCMS m / z = 178.2 [M-55] + ;

[0559] Step 5: Preparation of 11f

[0560] 11e (196 mg, 0.84 mmol) was dissolved in dichloromethane (2 mL) and added to a 4M hydrochloric acid-dioxane solution (2 mL). The reaction mixture was stirred at room temperature for 1 hour. After the reaction was completed, the solution was concentrated to obtain 11f (140 mg), which was directly used in the next step.

[0561] LCMS m / z = 134.1 [M+H] + ;

[0562] Step 6: Preparation of Compound 11

[0563] Compound 11 (109 mg, yield 28.34%) was obtained by reacting 11f (140 mg, 0.83 mmol) with 2d-1 (290 mg, 0.84 mmol) according to the method in step one of Example 1.

[0564] LCMS m / z = 470.3 [M+H] +

[0565] Example 12: Preparation of Compound 12

[0566] Step 1: Preparation of 12b

[0567] 12a (2.15 g, 9.99 mmol) was dissolved in dichloromethane (30 mL), and 5a (1.35 g, 9.99 mmol) and EDCI (2.0 g, 12.88 mmol) were added. The mixture was stirred at room temperature for 16 hours. Water (20 mL) was added to the reaction solution, and the system was concentrated under reduced pressure. The aqueous layer was extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, washed with saturated brine (2 × 20 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 12b (3.1 g, yield 93.36%).

[0568] Step 2: Preparation of 12C

[0569] 12b (1.0 g, 3.01 mmol) was dissolved in dichloromethane (5 mL) and added to a 4M hydrochloric acid-dioxane solution (5 mL). The reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the solution was concentrated to obtain 12c (800 mg), which was used directly in the next step.

[0570] LCMS m / z = 233.1 [M+H] + ;

[0571] Step 3: Preparation of 12 days

[0572] 12c-1 (200 mg, 0.74 mmol) and 12c (200 mg, 0.74 mmol) were purified by column chromatography according to the synthesis method in the first step of Example 1 to obtain 12d (307 mg, yield 78.35%).

[0573] LCMS m / z = 528.3 [M+H] +

[0574] Step 4: Preparation of Compound 12

[0575] Compound 12 (307 mg, 0.58 mmol) was dissolved in dichloromethane (10 mL) and then added to trifluoroacetic acid (2 mL). The reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the residue was concentrated and purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 12 (206 mg, yield 75.08%).

[0576] LCMS m / z = 472.2 [M+H] +

[0577] 1 H NMR(400MHz,DMSO-d6)δ9.92(s,1H),8.43(s,1H),8.01-7.92(m,2H),7.77-7.59(m,6H),7.55-7.48(m,2H),7.2 1-7.11(m,2H),4.54-4.42(m,1H),3.73-3.47(m,2H),2.89-2.76(m,1H),2.26-1.84(m,4H),1.24-1.09(m,6H).

[0578] Example 13: Preparation of Compound 13

[0579] Using compound 7d as a starting material, compound 13 (24 mg) was synthesized according to the synthesis method in Example 7.

[0580] LCMS m / z = 556.3 [M+H] +

[0581] Example 14: Preparation of Compound 14

[0582] Using compound 2d as a starting material, compound 14 (38 mg) was synthesized according to the synthesis method in Example 4.

[0583] LCMS m / z = 548.2 [M+H] +

[0584] Example 15: Preparation of Compound 15

[0585] Step 1: Preparation of 15b

[0586] 15a (240 mg, 1.01 mmol), tert-butyl carbamate (140 mg, 1.20 mmol), and cesium carbonate (650 mg, 1.99 mmol) were dissolved in 1,4-dioxane (5 mL). The reaction system was purged with nitrogen three times, and then Ru-Phos-G3 (85 mg, 0.10 mmol) was added. The reaction system was heated to 100 °C and stirred for 16 hours. After the reaction was completed, the system was diluted with water (5 mL), extracted with ethyl acetate (5 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and separated by silica gel column chromatography to obtain 15b (260 mg, yield 80.97%).

[0587] LCMS m / z = 318.1 [M-1] -

[0588] Step 2: Preparation of 15C

[0589] 15b (260 mg, 0.81 mmol) was dissolved in dichloromethane (3 mL) and added to a 4M hydrochloric acid-dioxane solution (3 mL). The reaction mixture was stirred at room temperature for 1 hour. After the reaction was completed, the solution was concentrated to obtain 15c (240 mg), which was used directly in the next step.

[0590] LCMS m / z = 220.1 [M+H] + ;

[0591] Step 3: Preparation of Compound 15

[0592] Compound 15 (40 mg, yield 21.60%) was obtained by reacting 15c (110 mg, 0.37 mmol) with 8e-1 (120 mg, 0.47 mmol) according to the method in step 8 of Example 7.

[0593] LCMS m / z = 496.2[M+H] +

[0594] Example 16: Preparation of Compound 16

[0595] Step 1: Preparation of 16b

[0596] 4a (2.0 g, 13.05 mmol) was dissolved in DMF (30 mL), and 12a (2.81 g, 13.05 mmol), HATU (7.44 g, 19.58 mmol), and DIPEA (3.37 g, 26.1 mmol) were added. The mixture was stirred at room temperature for 16 hours. Water (50 mL) was added to the reaction solution, and the system was concentrated under reduced pressure. The aqueous layer was extracted with ethyl acetate (3 × 50 mL). The combined organic phases were washed with saturated brine (2 × 50 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 16b (3.4 g, yield 74.32%).

[0597] Step 2: Preparation of 16C

[0598] 16b (3.4 g, 9.70 mmol) was dissolved in dichloromethane (50 mL) and added to a 4M hydrochloric acid-dioxane solution (20 mL). The reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the solution was concentrated to obtain 16c (2.2 g).

[0599] LCMS m / z = 251.2[M+H] + ;

[0600] Step 3: Preparation of 16 days

[0601] 12c-1 (200 mg, 0.74 mmol) was dissolved in ultradry acetonitrile (5 mL), and N,N'-carbonyldiimidazole (130 mg, 0.80 mmol) was added. The mixture was stirred at room temperature for 0.5 hours and concentrated to dryness. The residue was dissolved in ultradry N,N-dimethylacetamide (3 mL) and added to a reaction system containing 16c (200 mg, 0.70 mmol) and N-methylmorpholine (184 mg, 1.82 mmol) in N,N-dimethylacetamide (2 mL). The mixture was reacted at room temperature for 2 hours. Water (20 mL) was added to the reaction solution, and the aqueous layer was extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, washed with saturated brine (2 × 20 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 16d (367 mg, yield 90.58%).

[0602] Step 4: Preparation of Compound 16

[0603] Compound 16 (367 mg, 0.67 mmol) was dissolved in dichloromethane (10 mL) and then added to trifluoroacetic acid (2 mL). The reaction mixture was stirred at room temperature for 3 hours. After the reaction was completed, the residue was concentrated and purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 16 (200 mg, yield 60.74%).

[0604] LCMS m / z = 490.3[M+H] +

[0605] 1 H NMR (400MHz, DMSO-d6) δ10.16(s,1H),8.46(s,1H),8.00-7.91(m,2H),7.77-7.69(m,2H),7.68-7.60(m,4H),7.58-7.50(m,1H),7.32-7.20( m,2H),4.52-4.41(m,1H),3.73-3.62(m,1H),3.59-3.49(m,1H),3.15- 3.02(m,1H),2.24-2.13(m,1H),2.09-1.87(m,3H),1.22-1.13(m,6H).

[0606] Example 17: Preparation of Compound 17

[0607] Step 1: Preparation of 17b

[0608] 17a (0.3 g, 1.41 mmol) and 10a (345 mg, 1.55 mmol) were dissolved in a mixed solvent of dioxane (12 mL) and water (2 mL). Then, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (115 mg, 0.14 mmol) and sodium carbonate (300 mg, 2.82 mmol) were added sequentially. After the addition was complete, the mixture was stirred at 70 °C for 16 hours under nitrogen atmosphere. After cooling to room temperature, the mixture was extracted with ethyl acetate (20 mL × 3). The organic phase was washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 17b (290 mg, yield 66.32%).

[0609] LCMS m / z = 310.2[M+H] +

[0610] Step 2: Preparation of 17c

[0611] Using 17b and 8e-1 as raw materials, the synthetic method of compound 10d was used to obtain compound 17c (350 mg). The crude product was directly used for the next step.

[0612] Step 3: Preparation of Compound 17

[0613] Compound 17 (150 mg, yield 47.39%) was obtained by separation and purification using 17c as the starting material and referring to the synthesis method of compound 10. The method was followed. The chromatographic column was a Waters 2767 preparative liquid chromatography system (19 mm × 250 mm SunFire@Prep C18). The mobile phase composition was: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA).

[0614] LCMS m / z = 530.2 [M+H] +

[0615] 1 H NMR(400MHz,DMSO-d6)δ12.90(s,1H),9.52(s,1H),8.40(s,1H),8.01-7.95( m,2H),7.61-7.54(m,3H),7.46-7.39(m,1H),7.28-7.14(m,3H),4.62-4.54( m,1H),3.70-3.60(m,1H),3.53-3.46(m,1H),3.12-3.03(m,1H),2.99-2.91( m,2H),2.90-2.81(m,2H),2.21-2.10(m,1H),2.08-1.91(m,5H),1.18(d,6H).

[0616] Example 18: Preparation of Compound 18

[0617] Step 1: Preparation of 18b

[0618] 18a (200 mg, 0.88 mmol) was dissolved in DMF (4 mL), and HATU (434.98 mg, 1.14 mmol) was added. The mixture was stirred at room temperature for 10 minutes. Then, DIEA (909.85 mg, 7.04 mmol) and 4a (134.82 mg, 0.88 mmol) were added, and the mixture was stirred at room temperature for 1 hour. Water (100 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (3 × 30 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 18b (280 mg, yield 87.78%).

[0619] LCMS m / z = 307.2[M-56+H] + ;

[0620] Step 2: Preparation of 18c

[0621] 18b (280 mg, 0.77 mmol) was dissolved in dichloromethane (6 mL), and 4 M hydrochloric acid-dioxane solution (3 mL) was added. The reaction mixture was stirred at room temperature for 3 hours. After the reaction was completed, the solution was concentrated to obtain 18c (210 mg), which was used directly in the next step.

[0622] LCMS m / z = 263.1 [M+H] + ;

[0623] Step 3: Preparation of 18 days

[0624] 12c-1 (107.74 mg, 0.40 mmol) was dissolved in ultradry acetonitrile (2 mL), and N,N'-carbonyldiimidazole (64.86 mg, 0.40 mmol) was added. The mixture was stirred at room temperature for 0.5 hours, and then concentrated to dryness. The residue was dissolved in ultradry N,N-dimethylacetamide (2 mL), and added to a reaction system containing 18c (110 mg, 0.40 mmol) and N-methylmorpholine (184 mg, 1.82 mmol) in N,N-dimethylacetamide (2 mL). The reaction was carried out at room temperature for 3 hours. Water (60 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (3 × 30 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and evaporated to dryness. The purified solution was obtained by column chromatography to give 18d (190 mg, yield 70.48%).

[0625] LCMS m / z = 558.3 ​​[M+H] +

[0626] Step 4: Preparation of Compound 18

[0627] Compound 18 (190 mg, 0.28 mmol) was dissolved in dichloromethane (5 mL) and 4 M hydrochloric acid-dioxane solution (2 mL) was added. The reaction system was stirred at room temperature for 3 hours. After the reaction was completed, the mixture was concentrated, and the residue was purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 18 (84.23 mg, yield 59.16%).

[0628] LCMS m / z = 502.3 [M+H] +

[0629] 1H NMR(400MHz,DMSO-d6)δ12.82(s,1H),10.31(s,1H),8.40(s,1H),7.97(d,2H),7.76(d,2H),7.63(s,4H),7.58-7.52(m,1H),7.32-7.23(m,2H) ,4.54(s,1H),3.80-3.69(m,2H),3.14-3.06(m,1H),1.77-1.70(m,1H) ,1.68-1.61(m,1H),1.19(d,6H),0.82-0.76(m,1H),0.35-0.30(m,1H).

[0630] Example 19: Preparation of Compound 19

[0631] Compound 19 (143 mg, yield 54.86%) was obtained by the synthesis method of Example 8.

[0632] LCMS m / z = 500.2[M+H] +

[0633] 1 H NMR (400MHz, DMSO-d6) δ10.15(s,1H),8.19(s,1H),7.96-7.76(m,4H),7.45-7.36(m,3H),7.32-7.24(m,1H),7.13-7.03(m,2H),5.17(s,2 H),4.51-4.39(m,1H),3.69-3.59(m,1H),3.55-3.46(m,1H),2.85-2.75(m,1H),2.24-2.12(m,1H),2.09-1.87(m,3H),1.21-1.12(m,6H).

[0634] Example 20: Preparation of Compound 20

[0635] Compound 20 (50 mg, yield 20.54%) was obtained by the synthesis method of Example 8.

[0636] LCMS m / z = 518.2 [M+H] +

[0637] 1H NMR(400MHz,DMSO-d6)δ10.16(s,1H),8.40(s,1H),7.96-7.78(m,4H),7.46-7.35(m,2H),7.33-7.09(m,3H),5.17(s,2H),4.52- 4.39(m,1H),3.69-3.60(m,1H),3.57-3.45(m,1H),3.12-3.00(m,1H),2.26-2.12(m,1H),2.09-1.86(m,3H),1.22-1.11(m,6H).

[0638] Example 21: Preparation of compound 21

[0639] Step 1: Preparation of 21b

[0640] 21a (3 g, 14.13 mmol) and 21a-1 (2.54 g, 15.54 mmol) were dissolved in DCM (40 mL), and EDCI (4.06 g, 21.20 mmol) and DMAP (0.35 g, 2.83 mmol) were added. The mixture was stirred at 25 °C for 3 hours. The reaction solution was quenched with an aqueous sodium bicarbonate solution (50 mL), and extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 21b (3.3 g, yield 58.80%).

[0641] LCMS m / z = 358.1 [M+H] + ;

[0642] Step 2: Preparation of 21c

[0643] 4,4'-di-tert-butyl-N-cyano-[2,2'-bipyridine]-6-carbamate (0.38 g, 1.12 mmol) and ethylene glycol dimethyl ether nickel bromide (0.35 g, 1.12 mmol) were mixed in a three-necked flask to prepare a catalyst solution, which was purged with nitrogen three times. Then, dry DMA (3 mL) and dry THF (3 mL) were added, and the mixture was purged with nitrogen three times again. The mixture was stirred at room temperature for 15 minutes to prepare the catalyst solution. 21b (2 g, 5.60 mmol), 21b-1 (1.34 g, 5.60 mmol) and zinc powder (0.37 g, 11.2 mmol) were dispersed in THF (27 mL), purged with nitrogen three times, and the catalyst solution was added, followed by three more nitrogen purgings. The reaction mixture was stirred at room temperature for 20 hours. After the reaction was completed, DCM (30 mL) was added for dispersion, and the mixture was concentrated with silica gel and separated by silica gel column chromatography to obtain 21c (1.1 g, yield 66.98%).

[0644] LCMS m / z = 279.1 [M+H]+ ;

[0645] Step 3: Preparation of Compound 21

[0646] Compound 21 (8.97 mg) was obtained from 21c (500 mg, 1.70 mmol) according to the method in Example 15.

[0647] LCMS m / z = 504.4 [M+H] +

[0648] Example 22: Preparation of compound 22

[0649] Step 1: Preparation of 22b

[0650] 22a (400 mg, 3.00 mmol) and calcium carbonate (450.41 mg, 4.50 mmol) were dispersed in DCM (8 mL) and MeOH (4 mL). Benzyltrimethyldichloroiodate ammonium (1.04 g, 3.00 mmol) was added at 0 °C, and the mixture was stirred overnight at 25 °C. The reaction mixture was quenched with an aqueous sodium bicarbonate solution (20 mL), and extracted with ethyl acetate (4 × 30 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 22b (830 mg, yield 90.49%).

[0651] LCMS m / z = 260.0 [M+H] + ;

[0652] Step 2: Preparation of 22c

[0653] 22b (400 mg, 1.31 mmol) and 10a (378.15 mg, 1.70 mmol) were dispersed in 1,4-dioxane (6 mL) and water (0.6 mL). Sodium carbonate (416.54 mg, 3.93 mmol) and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (106.98 mg, 0.13 mmol) were added. After purging with nitrogen three times, the mixture was stirred overnight at 80 °C. 100–200 mesh silica gel was added to the reaction mixture, and the solution was concentrated under reduced pressure and separated by silica gel column chromatography to obtain 22c (140 mg, yield 16.60%).

[0654] LCMS m / z = 310.1 [M+H] + ;

[0655] Step 3: Preparation of 22 days

[0656] 22c (140 mg, 0.22 mmol) and 8e-1 (64.75 mg, 0.22 mmol) were dissolved in DCE (5 mL), and EDCI (59.04 g, 0.31 mmol) was added. The mixture was stirred overnight at 25 °C. The reaction solution was quenched with water (10 mL) and extracted with ethyl acetate (4 × 30 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 22d (131 mg, yield 88.77%).

[0657] LCMS m / z = 584.3 [MH] - ;

[0658] Step 4: Preparation of Compound 22

[0659] Compound 22 (131 mg, 0.19 mmol) was dissolved in DCM (3 mL), and TFA (1 mL) was added. The mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure and then purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 22 (62.7 mg, yield 61.24%).

[0660] LCMS m / z = 530.2 [M+H] + ;

[0661] 1 H NMR(400MHz,DMSO-d6)δ12.93(s,1H),10.24(s,1H),8.41(s,1H),8.18-8.14(m,1H ),8.09-8.04(m,2H),7.98-7.93(m,1H),7.80-7.73(m,2H),7.45-7.38(m,2H),7.28 -7.23(m,1H),7.20-7.14(m,2H),4.76-7.71(m,1H),3.70-3.62(m,1H),3.57-3.50( m,1H),3.12-3.03(m,1H),2.24-2.17(m,1H),2.08-1.97(m,3H),1.21-1.15(m,6H).

[0662] Example 23: Preparation of compound 23

[0663] Using compound 23a as a starting material, compound 23 (114.9 mg) was synthesized according to the synthesis method of Example 22.

[0664] LCMS m / z = 514.2 [MH] - ;

[0665] Example 24: Preparation of compound 24

[0666] Step 1: Preparation of 24a

[0667] 21d (350 mg, 0.97 mmol) was dissolved in dichloromethane (2 mL) and added to a 4M hydrochloric acid-dioxane solution (2 mL). The reaction mixture was stirred at room temperature for 1 hour. After the reaction was completed, the solution was concentrated to obtain 24a (221 mg).

[0668] LCMS m / z = 260.2[M+H] + ;

[0669] Step 2: Preparation of 24b

[0670] 24a (80 mg, 0.40 mmol) was dissolved in ultradry acetonitrile (2 mL), and N,N'-carbonyldiimidazole (70 mg, 0.40 mmol) was added. The mixture was stirred at room temperature for 0.5 hours, and then concentrated to dryness. The residue was dissolved in ultradry N,N-dimethylacetamide (2 mL), and added to a reaction system containing 18c (60 mg, 0.20 mmol) and N-methylmorpholine (280 mg, 2.73 mmol) in N,N-dimethylacetamide (2 mL). The reaction was carried out at room temperature for 16 hours. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (3 × 30 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated to dryness, and purified by column chromatography to give 24b (112 mg, yield 64.41%).

[0671] LCMS m / z = 548.3 [M+H] +

[0672] Step 3: Preparation of Compound 24

[0673] Compound 24b (100 mg, 0.18 mmol) was dissolved in a 4:1:1 volumetric mixture (6 mL) of tetrahydrofuran (4 mL), methanol (1 mL), and water (1 mL), and lithium hydroxide monohydrate (22 mg, 0.54 mmol) was added. The reaction mixture was stirred at 40 °C for 3 hours. The reaction solution was concentrated, and the residue was purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) to obtain compound 24 (84 mg, yield 86.21%).

[0674] LCMS m / z = 534.3 [M+H]+ ;

[0675] 1 H NMR(400MHz,DMSO-d6)δ12.11-11.04(br,1H),10.28(s,1H),8.13(s,1H), 7.60-7.45(m,1H),7.38-7.32(m,2H),7.30-7.21(m,2H),7.18-7.12(m,2H) ,4.50(s,1H),3.78-3.60(m,2H),3.17-3.01(m,1H),1.80-1.69(m,12H),1 .65-1.56(s,1H),1.19-1.18(d,6H),0.81-0.72(m,1H),0.31-0.25(m,1H).

[0676] Example 25: Preparation of Compound 25

[0677] Step 1: Preparation of 25a

[0678] 12a (41 mg, 0.19 mmol) and HATU (86.69 mg, 0.23 mmol) were dissolved in DMF (1.5 mL) and stirred at room temperature for 10 minutes. Then, 24a (50 mg, 0.19 mmol) and DIEA (122.78 mg, 0.95 mmol) were added and stirred overnight at room temperature. The reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 25a (50 mg, yield 56.80%).

[0679] LCMS m / z = 357.2[M - Boc + H] + ;

[0680] Step 2: Preparation of 25b

[0681] 25a (50 mg, 0.11 mmol) was dissolved in DCM (1.5 mL), and TFA (0.5 mL) was added. The reaction mixture was stirred at room temperature for 2 hours. After the reaction was completed, the solution was concentrated, dissolved in dry DCM, and concentrated again to obtain 25b (38 mg).

[0682] LCMS m / z = 357.2 [M+H] + ;

[0683] Step 3: Preparation of compound 25c

[0684] 4a (16.85 mg, 0.11 mmol) and TCDI (19.60 mg, 0.11 mmol) were dissolved in ACN (1 mL), stirred at 30 °C for 1 hour, and concentrated to dryness. The solutions were then dissolved again in DMA (1 mL), followed by the addition of NMM (92 mg, 0.91 mmol) and 25b (38 mg, 0.11 mmol). The mixture was stirred overnight at room temperature. The reaction solution was quenched with water (20 mL) and extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 25c (10 mg, yield 16.66%).

[0685] LCMS m / z = 550.1 [MH] - ;

[0686] Step 4: Preparation of Compound 25

[0687] Compound 25 (10 mg, 0.018 mmol) was dissolved in THF (1 mL) and MeOH (0.4 mL), and LiOH·H2O (7.55 mg, 0.18 mmol) and H2O (0.3 mL) were added. The mixture was stirred overnight at room temperature. After the reaction was complete, the solution was concentrated and purified by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 5 mmol / L NH4OAc) to obtain compound 25 (3.4 mg, yield 35.60%).

[0688] LCMS m / z = 536.3 [MH] - ;

[0689] 1 H NMR (400MHz, DMSO-d6) δ11.98(s,1H),9.93(s,1H),9.07(s,1H),7.52-7.45(m,2H),7.31-7.16(m,5H),5.04-4.98(m,1H),3.84-3.75(m ,1H),3.70-3.61(m,1H),3.16-3.08(m,1H),2.29-2.19(m,1H),2.14-2.00(m,2H),1.98-1.91(m,1H),1.83-1.71(m,12H),1.21(d,6H).

[0690] Example 26: Preparation of Compound 26

[0691] Compound 26 was obtained from compound 24a as a raw material, referring to Example 4.

[0692] LCMS m / z = 550.3 [M+H] + ;

[0693] Example 27: Preparation of Compound 27

[0694] Compound 27 was obtained from compound 27a as a raw material, according to Example 18.

[0695] LCMS m / z = 504.3 [M+H] +

[0696] Example 28: Preparation of Compound 28

[0697] Step 1: Preparation of 28b

[0698] 28a (synthetic method referred to WO2022 / 66774,2022,A1) (140 mg, 0.53 mmol) and HATU (302.28 mg, 0.80 mmol) were dissolved in DMF (3 mL) and stirred at room temperature for 10 minutes. Then, 12c-1 (142.75 mg, 0.53 mmol) and DIEA (205.49 mg, 1.59 mmol) were added and stirred at room temperature overnight. The reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain 28b (240 mg, yield 87.7%).

[0699] Step 2: Preparation of 28c

[0700] 28b (240 mg, 0.47 mmol) was dissolved in DCM (1.5 mL), and TFA (0.5 mL) was added. The reaction mixture was stirred at room temperature for 2 hours. After the reaction was completed, the solution was concentrated and passed through a column (DCM / MeOH = 10 / 1) to give 28c (147 mg, yield 87.95%).

[0701] LCMS m / z = 359.2 [M+H] + ;

[0702] Step 3: Preparation of Compound 28

[0703] 4a (26 mg, 0.17 mmol) and CDI (27.57 mg, 0.17 mmol) were dissolved in ACN (1 mL), stirred at 30 °C for 1 hour, and concentrated to dryness. The solutions were then dissolved again in DMA (1 mL), followed by the addition of NMM (85.98 mg, 0.85 mmol) and 28c (50 mg, 0.14 mmol). The mixture was stirred overnight at room temperature. The reaction solution was quenched with water (20 mL), and extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

[0704] Compound 28 (32 mg, yield 35.08%) was obtained by preparative liquid chromatography (instrument: Waters 2767 preparative liquid chromatography; column: SunFire@Prep C18 (19 mm × 250 mm); mobile phase composition: mobile phase A: acetonitrile / mobile phase B: water (containing 0.1% TFA) separation and purification.

[0705] LCMS m / z = 538.1 [M+H] +

[0706] 1 H NMR(400MHz,DMSO-d6)δ12.89(s,1H),10.27(s,1H),8.57(s,1H),7.99(d,2H),7.78(d,2H),7.72(s,4H),7.43-7.36(m,1H) ,7.27-7.22(m,1H),7.21-7.15(m,1H),4.79-4.72(m,1H),4.33(s,2H),3.14-2.97(m,2H),2.69-2.60(m,1H),1.18(d,6H).

[0707] Example 29: Preparation of compound 29

[0708] Using compound 28a as a starting material, compound 29 (22 mg) was synthesized according to the synthesis method of Example 12.

[0709] LCMS m / z = 538.2 [M+H] +

[0710] 1H NMR(400MHz,DMSO-d6)δ12.83(s,1H),10.25(s,1H),8.63(s,1H),7.98(d,2H),7.77(d,2H),7.66(s,4H),7.55-7.48 (m,1H),7.31-7.22(m,2H),4.77-4.69(m,1H),4.43-4.30(m,2H),3.15-2.96(m,2H),2.67-2.59(m,1H),1.19(d,6H).

[0711] Referring to the synthesis method of the above embodiments, the embodiments in the following table are synthesized:

[0712] Biological test example 1:

[0713] Determination of the GIPR inhibitory activity of the compound

[0714] Human GIPR cells were passaged and cultured until approximately 80% confluence was achieved. Cells were then digested with dissociation buffer. After centrifugation, the culture medium was removed, and the cells were resuspended in 1×Stimulation Buffer (prepared according to the cAMP kit). After cell count, the cells were seeded into 384-well plates. A specific volume of the diluted compound was added to the corresponding well, and the plates were incubated at 37°C for 30 minutes. Then, a specific volume of the agonist solution prepared with 1×Stimulation Buffer was added to the corresponding well, and after centrifugation, all cells were incubated at 37°C for 30 minutes to induce cAMP production. The cAMP kit was then used for detection. The detection reagents were prepared according to the kit instructions. Eu-cAMP was diluted to the working concentration with detection buffer, and a specific volume was added to the corresponding well. Ultra-anti-cAMP was then diluted to the working concentration with detection buffer, and a specific volume was added to the corresponding well. After centrifugation, the plates were incubated at room temperature for 1 hour. After incubation, the readings at 665 nm and 620 nm under 330 nm excitation were detected using a multi-functional microplate reader. The data were then exported, and the IC50 of the compound was calculated using a GraphPad nonlinear fitting formula. 50 .

[0715] The results of the biological tests are shown in Table 1:

[0716] Table 1

[0717] A < 10nM

[0718] Conclusion: The compounds of this application, such as the compounds in the examples, have good inhibitory activity against the GIP receptor.

[0719] Biological Test Example 2: Rat Pharmacokinetic Test

[0720] Experimental animals: SD rats, 180-200g, 6 rats / compound.

[0721] Experimental design: On the day of the experiment, SD rats were randomly divided into groups according to their body weight. They were fasted for 12-14 hours before administration but allowed free access to water, and were fed 4 hours after administration.

[0722] Table 2. Dosage Information Note: For injection: 5% DMA + 5% Solutol + 90% Saline or 10% DMA + 10% Solutol + 80% Saline; For gavage: 5% DMSO + 5% Solutol + 90% 0.5% MC.

[0723] (DMA: dimethylacetamide; Solutol: polyethylene glycol-15-hydroxystearate; Saline: physiological saline; MC: methylcellulose)

[0724] Blood samples of 60 μL were collected via the orbital cavity before and after isoflurane anesthesia, placed in EDTAK2 centrifuge tubes, and centrifuged at 5000 rpm for 10 min to collect plasma. Blood collection time points for both the intravenous and gavage groups were 0, 5, 15, 30 min, 1, 2, 4, 6, 8, and 24 h. All samples were stored at -80℃ before analysis and quantitative analysis was performed using LC-MS / MS.

[0725] Table 2-1 Pharmacokinetic results of the test compounds in rats

[0726] Reference compound 1 is

[0727] Conclusion: The compounds of this application, such as the compounds in the examples, have higher exposure levels and better oral performance in rats, which are significantly superior to control compound 1.

[0728] Biological Test Example 3: CYP450 Enzyme Inhibition Test

[0729] The aim of this study was to evaluate the effects of test substances on the activities of five isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) of human liver microsomal cytochrome P450 (CYP) using an in vitro assay system. Specific probe substrates for CYP450 isoenzymes were co-incubated with human liver microsomes and different concentrations of the test substances. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) was added to initiate the reaction. After the reaction, the metabolites produced by the specific substrates were quantitatively detected by liquid chromatography-tandem mass spectrometry (LC-MS / MS) after sample processing, and the changes in CYP enzyme activity were measured. The IC50 values ​​were calculated. 50 The value is used to evaluate the inhibitory potential of the test substance against each CYP enzyme subtype.

[0730] Conclusion: The compounds of this application, such as those in the examples, exhibit weak CYP inhibition. Specifically, compounds 4, 5, and 25 show IC50 inhibition against five CYP isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). 50 Greater than 30 μM.

[0731] Biological Test Example 4: UGT1A1 Inhibitory Activity Test

[0732] This experiment evaluated the inhibitory potential of test substances on UGT1A1 using recombinant human UGT1A1 enzyme. Bilirubin, a probe substrate for the UGT1A1 enzyme, was co-incubated with recombinant human UGT1A1 enzyme and different concentrations (0–10 μM) of the test substances. Uridine diphosphate glucuronide (UDPGA) was added to initiate the reaction. After the reaction, the samples were processed, and specific metabolites produced by bilirubin were quantitatively detected using liquid chromatography-tandem mass spectrometry (LC-MS / MS). Changes in UGT1A1 enzyme activity were measured, and the IC50 was calculated. 50 The value is used to evaluate the inhibitory potential of the test substance on each UGT1A1 enzyme.

[0733] Conclusion: The compounds of this application, such as the compounds in the examples, have weaker UGT1A1 inhibition and a lower risk of hepatotoxicity.

[0734] Biological Test Example 5: Mouse Pharmacokinetic Test

[0735] Test animals: C57 BL / 6J mice, 22-25g, 6 mice per test compound.

[0736] Experimental design: On the day of the experiment, C57 mice were randomly divided into groups according to body weight. They were fasted for 12-14 hours before administration but allowed free access to water, and were fed 4 hours after administration.

[0737] Table 3. Dosage Information Note: For injection: 5% DMA + 5% Solutol + 90% Saline or 10% DMA + 10% Solutol + 80% Saline; For gavage: 5% DMSO + 5% Solutol + 90% 0.5% MC.

[0738] Blood samples of 0.06 mL were collected via the orbital cavity before and after isoflurane anesthesia, placed in EDTAK2 centrifuge tubes, and centrifuged at 5000 rpm for 10 min at 4°C to collect plasma. Blood collection time points for both the intravenous and gavage groups were 0, 5, 15, 30 min, 1, 2, 4, 7, and 24 h. All samples were stored at -60°C before analysis and quantitative analysis was performed using LC-MS / MS.

[0739] Conclusion: The compounds of this application, such as the compounds in the examples, have good pharmacokinetic properties in mice.

[0740] Biological Test Example 6: Pharmacokinetic Test in Beagle Dogs

[0741] Test animals: Male beagles, weighing approximately 8–11 kg, 6 per test compound, purchased from Beijing Mars Biotechnology Co., Ltd.

[0742] Experimental Methods: On the day of the experiment, beagles were randomly grouped according to their body weight. They were fasted for 12–14 hours prior to administration but allowed free access to water. Food was given 4 hours after administration. Administration was performed according to Table 4.

[0743] Table 4. Dosage Information Note: The solvent for oral administration is 0.5% MC.

[0744] Blood samples (1 ml) were collected via jugular or limb veins before and after drug administration and placed in EDTAK2 centrifuge tubes. Plasma was collected by centrifugation at 5000 rpm and 4°C for 10 min. Blood collection time points for both the intravenous and gavage groups were: 0, 5, 15, 30 min, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h. All samples were stored at -80°C before analysis and quantitative analysis was performed using LC-MS / MS.

[0745] Conclusion: The compounds of this application, such as the compounds in the examples, have good canine pharmacokinetic properties.

[0746] Biological Test Example 7: Monkey Pharmacokinetic Test

[0747] Test animals: male cynomolgus monkeys, 3-5 kg, 5 animals per test compound.

[0748] Experimental method: On the day of the experiment, monkeys were randomly divided into groups according to their body weight. They were fasted for 14-18 hours before administration but allowed free access to water. They were fed 4 hours after administration.

[0749] Table 5. Dosage Information Note: Injection solvent: 10% DMA + 5% Solutol + 85% Saline; Gavage solvent: 5% DMSO + 5% Solutol + 90% 0.5% MC

[0750] *Dosage is calculated based on free base.

[0751] Blood samples of 1.0 mL were collected from venous sites in the extremities before and after drug administration and placed in EDTAK2 centrifuge tubes. Plasma was collected by centrifugation at 5000 rpm and 4°C for 10 min. Blood collection time points for both the intravenous and gavage groups were: 0, 5 min, 15 min, 30 min, 1, 2, 4, 6, 8, 10, 12, 24 h, and 48 h. All samples were stored at -60°C before analysis and quantitative analysis was performed using LC-MS / MS.

[0752] Table 5-1 Pharmacokinetic results of the test compounds in monkeys

[0753] Conclusion: The compounds of this application, such as the compounds in the examples, have good pharmacokinetic properties in monkeys.

[0754] Biological Test Example 8: Effects of GIPR Antagonists on Obese Mice

[0755] An obese mouse model was induced by feeding transgenic mice expressing the human GIP receptor (GIPR) with a high-fat diet. The successfully induced obese mice were randomly assigned to two groups: the drug treatment group received a GIPR antagonist and a GLP-1R agonist, administered continuously for a certain period while measuring experimental indicators such as body weight. At the endpoint of administration, the weight-loss potential of the compounds was assessed using indicators such as changes in body weight.

[0756] Conclusion: The compounds of this application, such as those in the examples, have good weight loss effects in obese mouse models.

Claims

1. A compound or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein the compound is selected from compounds represented by general formula (I). Ring A is selected from benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cycloheteroaryl, 5-6 membered heteroaryl, pyridinone, pyrimidinone, phenyl; Alternatively, ring A is selected from ring A1, and ring A1 is selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cyclocyclic heteroaryl, pyridinone group, pyrimidinone group, 5 membered heteroaryl; The ring C is selected from benzo[C]. 4-12 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 The ring C may be a carbocyclic group, a 5-6 membered heteroaryl group, an 8-10 membered cycloheteroaryl group, a 5-6 membered heteroaryl group, a 5-12 membered heteroaryl group, a pyridinone group, a pyrimidinone group, or a phenyl group, wherein the ring C is optionally surrounded by 1 to 5 R groups. c replace; Alternatively, ring C is selected from ring C1, and ring C1 is selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 5-12 Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the C1 ring is optionally surrounded by 1 to 5 R groups. c replace; Ring D is selected from C 4-12 Carbocyclic group, benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 The ring D is optionally surrounded by 1 to 5 R groups: carbocyclic, 5-6-membered heteroaryl, 8-10-membered cycloheteroaryl, 5-6-membered heteroaryl, 5-12-membered heteroaryl, pyridone, pyrimidinone, or phenyl. d replace; Alternatively, ring D is selected from ring D1, and ring D1 is selected from benzo[C]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 4-12 Cycloalkyl, 5-12-membered heterocyclic alkyl, 5-12-membered heterocyclic alkenyl, wherein the ring D1 is optionally surrounded by 1 to 5 R groups. d replace; Ring B is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-. Choose from 1 to 6 Rs b1 replace; Y is selected independently from NR b4 O or CR b1 R b2 ; b1 is selected from 1, 2, 3; b2 is selected from 0, 1, 2, 3; b3 is selected from 0, 1, 2, 3, 4, 5, 6; a1 is selected from 0, 1, 2, 3, 4, 5, 6; R D Selected from -C(=O)OH, -C(=O)OR 1 -C(=O)NR 1 R 2 -S(=O)2NHCF3, Or, R D Selected from R 1D R 1D Selected from X1 and X2 are each independently selected from O or S; L is selected from either a key or CR. L1 R L2 ; R L1 R L2 Each is independently selected from H and C. 1-6 Alkyl, -OC 1-6 Alkyl, C 1-2 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, carbocyclic, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 5 R... k replace; As an option, R 1 With R 2 R L1 With R L2 Individual atoms and atoms connected to them together form C. 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace; R 1 R 2 R b4 Each independently selected from H and C 1-6 Alkyl, C 1-4 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 5 R... k replace; R b1 R b2 R b3 Each independently selected from R b H, deuterium, halogens, CN, OH, C 1-6 Alkyl group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -OC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace; R b Selected from NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 alkynyl group, -SC 1-6 alkyl, -OC 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace; R c R d Each is independently selected from deuterium, =O, halogen, CN, OH, NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 cycloalkyl, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 -OC 3-6 cycloalkyl, -NH-C 3-6 Cycloalkyl, 3 to 8-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace; Or, R d Selected from R 1d R 1d Selected from -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 3- to 8-membered heterocyclic groups, NH2, -SF5, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace; Or, R c Selected from R 1c R 1c Selected from NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, -C 0-4 Alkylene-C 3-6 cycloalkyl-R d1 3- to 8-membered heterocyclic groups, NH2, -SF5, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace; As an option, R b1 With R b2 R b1 With R b4 R b1 With R b1 Individual atoms and their connected atoms or framework together form C. 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace; As an option, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace; As an option, R c With R d Together with the connected skeleton, they form ring E, which is selected from C. 4-10 Carbon rings, 4- to 10-membered heterocycles, wherein the carbon rings or heterocycles are optionally surrounded by 1 to 5 R... k replace; R d1 Each is independently selected from halogens, OH, CN, NH2, -SF5, C 1-6 Alkyl, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Substituents of alkoxy groups; R A Each independently selected from R a Deuterium, O, Halogen, CN, C 1-6 Alkyl, C 2-6 alkenyl, -OC 1-6 Alkyl, -C 1-4 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace; R a Selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, C 2-6 alkynyl group, -SC 1-6 Alkyl, 3- to 10-membered heterocyclic groups, -OC 3-6 cycloalkyl, C 7-10 cycloalkyl, C 3-6 Cycloalkyl 5-6 membered heterocyclic group, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace; R a1 Selected from NH2, -SF5, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 2-6 alkenyl, C 2-6 Alkyne group, -C(=O)NHC 1-6 Alkyl group, -NHC(=O)C 1-6 Alkyl, -SC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Substituents of alkoxy groups; R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-6 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace; R k Each element is independently selected from deuterium, =O, halogens, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, and -NHC. 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-NHC(=O)C 1-6 Alkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -OC 3-6 Carbocyclic rings, -O-3 to 7-membered heterocycles, -NH-C 3-6 Carbon rings, -NH-3 to 7-membered heterocycles, -C 1-2 Alkylene-C 3-6 Carbon ring, -C 1-2 Alkylene-3 to 7-membered heterocycles, C 3-6 Carbon rings, 3- to 7-membered heterocycles, The alkyl, alkylene, alkenyl, alkynyl, carbocyclic, or heterocyclic group is optionally selected from 1 to 4 deuterium, halogen, =O, CN, OH, NH2, C 1-6 Alkyl, C 1-6 The alkoxy group is replaced by a substituent.

2. The compound according to claim 1, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein the compound is selected from the compounds shown in (Ih), (I), (Ia), (Ib), (Ic), (Ie), (If), (Ig), (Ii), (Ij), (Ik), and (Im). X1 is independently selected from O or S; X2 is independently selected from O or S; b4 is independently selected from 0, 1, 2, 3, 4, and 5; b5 is selected independently from 0, 1, 2, 3, 4, 5, and 6; a2 is independently selected from 0, 1, 2, 3, 4, and 5; c1 and d1 are each independently selected from 0, 1, 2, 3, and 4; Each ring B is independently selected from either ring B1 or ring B2; Ring B1 is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; Ring B2 is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; Each ring A is independently selected from ring A1, a 6-membered heteroaryl group, or a phenyl group; Each ring C is independently selected from a 1-ring, a 6-membered heteroaryl, or a phenyl group, wherein the ring C is optionally surrounded by 1 to 5 R groups. c replace; Each ring D is independently selected from ring D1, a 6-membered heteroaryl group, or a phenyl group, wherein the ring D is optionally surrounded by 1 to 5 R groups. d replace; Preferably, each ring D is independently selected from ring D1 or phenyl, and the ring D is optionally surrounded by 1 to 5 R groups. d replace; Each ring A1 is independently selected from benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl and 5-6 membered heterocyclic, 8 to 10 membered cyclocyclic heteroaryl, pyridinone group, pyrimidinone group, 5 membered heteroaryl; Each of the C1 rings is independently selected from benzo[C1]. 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 5-6 Monocycloalkyl, C 5-12 Bridged cycloalkyl, C 5-12 Spirocycloalkyl, C 5-12 Annular alkyl, 5-7 member monoheterocyclic alkyl, 5-7 member monoheterocyclic alkenyl, 6-12 member spiroheterocyclic alkyl, 6-12 member anheterocyclic alkyl, 6-12 member bridged heterocyclic alkyl; Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: benzo[C] 4-6 Carbocyclic groups, benzo4-6 membered heterocyclic groups; Each ring D1 is independently selected from benzo[C] 4-6 Carbocyclic, benzo4-6 membered heterocyclic, 5-6 membered heteroaryl, benzo[a]C 4-6 Carbocyclic, 5-6 membered heteroaryl, 8-10 membered cyclocyclic heteroaryl, pyridinone, pyrimidinone, 5 membered heteroaryl, C 4-6 Monocycloalkyl, C 5-12 Bridged cycloalkyl, C 5-12 Spirocycloalkyl, C 5-12 Annular alkyl, 5-7 member monoheterocyclic alkyl, 5-7 member monoheterocyclic alkenyl, 6-12 member spiroheterocyclic alkyl, 6-12 member anheterocyclic alkyl, 6-12 member bridged heterocyclic alkyl; Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: C 5-12 Bridged cycloalkyl; As an option, R c With R d Together with the skeleton connected to it, they form ring E; Ring E is independently selected from C 4-8 Carbon rings, 4- to 8-membered heterocycles, wherein the ring E is optionally divided by 1 to 5 R... k replace; R L1 R L2 Each is independently selected from H and C. 1-4 Alkyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-OC 1-4 Alkyl, C 3-7 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 4 R... k replace; As an option, R 1 With R 2 R L1 With R L2 Together with their respective independent atoms, they form C 3-6 Cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace; R 1 R 2 R b4 Each independently selected from H and C 1-4 Alkyl, -C 1-2 Alkylene-OC 1-4 Alkyl, C 3-6 Cycloalkyl, 4- to 7-membered heterocyclic alkyl, wherein the alkyl, alkylene, cycloalkyl or heterocyclic alkyl is optionally surrounded by 1 to 4 R... k replace; R b1 R b2 R b3 Each independently selected from R b H, deuterium, halogens, CN, OH, C 1-4 Alkyl group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace; As an option, any two R b1 Together with the atoms or framework attached to it, they form C 3-8 Cycloalkyl, 4- to 8-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace; As an option, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-6 Cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally surrounded by 1 to 5 R... k replace; R b Each is independently selected from NH2, -SF5, and -NHC. 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 alkynyl group, -SC 1-4 alkyl, -OC 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace; R c R d Each is independently selected from deuterium, =O, halogen, CN, OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 cycloalkyl, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 -OC 3-6 cycloalkyl, -NH-C 3-6 Cycloalkyl, 3- to 6-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace; R d1 Each is independently selected from halogens, OH, CN, NH2, -SF5, C 1-4 Alkyl, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 6-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups; Or, R c Selected from R 1c R 1c Each independently selected from -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 3- to 6-membered heterocyclic groups, NH2, -SF5, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace; Or, R d Selected from R 1d R 1d Each independently selected from -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2, -C 0-2 Alkylene-C 3-6 cycloalkyl-R d1 3- to 6-membered heterocyclic groups, NH2, -SF5, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, -NH-C 3-6 Cycloalkyl, wherein the alkyl, alkenyl, ynyl, cycloalkyl, or heterocyclic group is optionally selected to have 1 to 5 R groups. k replace; R A Each independently selected from R a Deuterium, O, Halogen, CN, C 1-4 Alkyl, C 2-4 alkenyl, -OC 1-4 Alkyl, -C 1-2 Alkylene-C 3-6 cycloalkyl, C 3-6 Cycloalkyl, wherein the alkyl, alkylene, alkenyl, or cycloalkyl group is optionally surrounded by 1 to 5 R groups. k replace; R a Each independently selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2、-C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, C 2-4 alkynyl group, -SC 1-4 Alkyl, 4-7 member monoheterocyclic, 6-10 member spirocyclic alkyl, 6-10 member anabolic alkyl, 6-10 member bridged heterocyclic alkyl, -OC 3-6 cycloalkyl, C 7-10 Spirocycloalkyl, C 7-10 Bridged cycloalkyl, C 7-10 cycloalkyl, C 3-6 Cycloalkyl 5-6 membered heterocyclic group, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k replace; R a1 Each is independently selected from NH2, -SF5, and -NHC. 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 2-4 alkenyl, C 2-4 Alkyne group, -C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, -SC 1-4 Alkyl, C 3-6 cycloalkyl, -OC 3-6 cycloalkyl, 3- to 8-membered heterocyclic groups The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic groups are optionally surrounded by 1 to 4 deuterium, halogen, CN, OH, NH2, or C atoms. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups; R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-4 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace; R k Each element is independently selected from deuterium, =O, halogens, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, and NHC. 1-4 Alkyl, N(C) 1-4 Alkyl)2、-NHC(=O)C 1-4 Alkyl, C 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, -OC 1-4 Alkyl, -SC 1-4 Alkyl, -OC 3-6 Carbocyclic rings, -O-3 to 7-membered heterocycles, C 3-6 Carbon rings, 3- to 7-membered heterocycles, The alkyl, alkenyl, alkynyl, carbocyclic, or heterocyclic groups are optionally selected from one to four deuterium, halogen, CN, OH, NH2, C 1-4 Alkyl, C 1-4 The alkoxy group is replaced by a substituent.

3. The compound according to claim 1 or 2, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts. Each ring A is independently selected from ring A1, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl. Each ring C is independently selected from ring C1, phenyl, pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl, and the ring C is optionally surrounded by 1 to 5 R groups. c replace; Each ring D is independently selected from ring D1, phenyl, pyridyl, pyrimidinyl, pyrazinyl, or pyridazinyl, and said ring D is optionally surrounded by 1 to 5 R groups. d replace; R L1 R L2 Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, oxetyl, and aziridine are optionally separated by 1 to 4 R. k replace; As an option, R 1 With R 2 R L1 With R L2 Each individual atom and the atoms bonded to it together form cyclopropyl, cyclobutyl, oxetyl, and aziretyl groups, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziretyl groups are optionally surrounded by 1 to 4 R groups. k replace; R 1 R 2 R b4 Each of the following is independently selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, oxetyl, and aziridine groups are optionally surrounded by 1 to 4 R groups. k replace; R b1 R b2 R b3 Each independently selected from R b H, deuterium, F, Cl, Br, I, CN, OH, methyl, ethyl, propyl, isopropyl, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, -O-methyl, -O-ethyl, -O-isopropyl, -CH2-cyclopropyl, cyclopropyl, cyclobutyl, wherein CH2, methyl, ethyl, propyl, isopropyl, cyclopropyl, and cyclobutyl are optionally prefixed with 1 to 4 R. k replace; R b Each of these groups is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl. -O-cyclopropyl, wherein the methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, or cyclopropyl group is optionally surrounded by 1 to 4 R groups. k replace; R c R d Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, methyl, ethyl, -S-methyl, -S-ethyl, -O -methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -O-cyclobutyl, -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl are optionally surrounded by 1 to 4 R k replace; As an option, R c With R d Together with the skeleton connected to it, they form ring E; Or, R c Selected from R 1c R 1c Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1 Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace; Or, R d Selected from R 1d R 1d Each of the following is independently selected from F, Cl, Br, I, NH2, -SF5, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 -NH-cyclopropyl, -NH-cyclobutyl, cyclopropyl-R d1 Cyclobutyl-R d1 , cyclopentyl-R d1 Cyclohexyl-R d1 Oxycyclic butyl, aziridine, pyrrolidinyl, wherein CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxycyclic butyl, aziridine, pyrrolidinyl are optionally surrounded by 1 to 4 R k replace; As an option, any two R b1 Together with the atoms or framework attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxacyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, or aziridine, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxacyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, or aziridine are optionally surrounded by 1 to 4 R atoms. k replace; As an option, any two R b3 Together with the carbon atom or skeleton attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetyl, aziridine, pyrrolidinyl, or piperidinyl groups, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetyl, aziridine, pyrrolidinyl, or piperidinyl groups are optionally surrounded by 1 to 4 R atoms. k replace; R A Each independently selected from R a Deuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, -O-methyl, -O-ethyl, -CH2-cyclopropyl, -CH2-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, wherein CH2, methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl are optionally surrounded by 1 to 5 R. k replace; R a Each independently selected from -C 3-6 cycloalkyl-R a1 OH, NH2, -SF5, -NHC 1-4 Alkyl, -N(C) 1-4 Alkyl)2、-C(=O)NHC 1-4 Alkyl group, -NHC(=O)C 1-4 Alkyl, C 2-4 alkynyl group, -SC 1-4 Alkyl, 3- to 7-membered heterocyclic groups, -OC 3-6 Cycloalkyl, wherein the alkyl, alkynyl, cycloalkyl, or heterocyclic group is optionally surrounded by 1 to 5 R groups. k Replace any of 1 to 4 R k replace; R a1 Each of these elements is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, piperidinyl, The methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziridine, pyrrolidinyl, or piperidinyl groups are optionally prefixed with 1 to 4 deuterium, F, Cl, Br, I, CN, OH, NH2, or C groups. 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Substituents of alkoxy groups; R 3 R 4 Each of the following is independently selected from H, deuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, and isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally surrounded by 1 to 4 R groups. k replace; R k Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, -C(=O)OH, -C(=O)NH2, NH2, NH(CH3), NH(CH2CH3), N(CH3)2, N(CH2CH3)2, -NHC(=O)CH3, methyl, ethyl, propyl, isopropyl, tert-butyl, vinyl, ethynyl, methoxy, ethoxy, methylthio, -O-cyclopropyl, -O-oxacyclobutyl, -NH-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl The methyl, ethyl, propyl, isopropyl, tert-butyl, vinyl, ethynyl, methoxy, ethoxy, methylthio, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups are optionally selected from one to four of deuterium, halogens, CN, OH, NH2, and C. 1-4 Alkyl, C 1-4 The alkoxy group is replaced by a substituent.

4. The compound according to claims 1 to 3, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein, Ring B1 is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; As an option, any two R b1 Together with the atoms or framework attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl, or piperidinyl groups, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, azacyclobutyl, or piperidinyl groups are optionally surrounded by 1 to 4 R atoms. k replace; As an option, any two R b3 Together with the carbon atom or skeleton attached thereto, they form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziridine, or piperidinyl groups, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziridine, or piperidinyl groups are optionally surrounded by 1 to 4 R atoms. k replace; The ring A1 is independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphene, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, benzocyclobutenyl, benzocyclopentenyl, benzocyclohexenyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl, and pyridoimidazolyl. The C1 rings are independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphenyl, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl, and pyridoimidazolyl. Cyclohexyl, cycloheptyl, pyrrolidinyl, piperidinyl, azacycloheptyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, morpholinyl, piperazine, azacyclohexenyl The ring C1 is arbitrarily selected by 1 to 4 Rs c replace; Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiophene, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl. s1, s3, and s5 can be independently selected from 0, 1, or 2, but s1 and s3 cannot be selected from 2 at the same time; s2 and s4 are each independently selected from 0 or 1; Each of s7 can be independently selected from 1, 2, or 3; The ring D1 is independently selected from pyrazolyl, imidazolyl, thiophene, furanyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyridinone, pyrimidinone, benzofuranyl, indolyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzooxazolyl, benzothiaphenyl, benzocyclopentyl, benzocyclohexyl, 1,3-benzodioxolanecycloyl, benzotetrahydrofuranyl, benzopyrrolidinyl, benzopiperidinyl, benzotetrahydropyranyl, quinolinyl, isoquinolinyl, pyridopyrrolidinyl, pyridopyrazolyl, pyridoimidazolyl, and pyridoimidazolyl. Cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyrrolidinyl, piperidinyl, azacycloheptyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, morpholinyl, piperazine, azacyclohexenyl, wherein the ring D1 is optionally surrounded by 1 to 4 R... d replace; Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect; More preferably, rings D1 are each independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect; Each ring E is independently selected from cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, pyrrolyl, piperidinyl, azircycloheptyl, azircyclooctyl, oxacyclopentyl, oxacyclohexyl, oxacycloheptyl, oxacyclooctyl, azircycloheptenyl, azircyclooctenyl, oxacyclopentenyl, oxacyclohexenyl, oxacycloheptenyl, oxacyclooctenyl, wherein the ring E is optionally surrounded by 1 to 4 R k replace; R a Each is independently selected from -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-R a1 -cyclohexyl-R a1 OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, ethynyl, propynyl, propyrynyl, -S-methyl, -S-ethyl, -O-cyclopropyl, -O-cyclobutyl, oxacyclobutyl, aziridine, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl, cyclobutylcyclopentyl, cyclopentylcyclopentyl, pyrrolidinyl, pyrrolidinyl The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethynyl, propynyl, propynyl, methyl, ethyl, oxacyclobutyl, azacyclobutyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl, cyclobutylcyclopentyl, cyclopentylcyclopentyl, pyrrolidinyl, and pyrrolidinyl are mentioned. Choose from 1 to 4 Rs k replace; R d1 Each is independently selected from F, Cl, Br, I, OH, CN, NH2, -SF5, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, methyl, ethyl, -S-methyl, -S-ethyl, -O-methyl, -O-ethyl, -O-cyclopropyl, -O-cyclobutyl, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(ethyl)2, cyclopropyl, cyclobutyl, oxacyclobutyl, aziridine, The CH2, methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, and aziridine groups are optionally surrounded by 1 to 4 R groups. k replace; R k Each is independently selected from deuterium, =O, F, Cl, Br, I, CN, OH, -C(=O)OH, -C(=O)NH2, -CH2OH, -NHC(=O)CH3, methyl, ethyl, propyl, isopropyl, tert-butyl, CD3, OCD3, CH2F, CHF2, CF3, vinyl, ethynyl, methoxy, ethoxy, methylthio, -O-cyclopropyl, -O-oxacyclobutyl, -NH-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl 5. The compound according to claims 1 to 4, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein, b4 is independently selected from 0, 1, 2, 3, and 4; b5 is selected independently from 0, 1, 2, 3, and 4; b3 is independently selected from 0, 1, 2, 3, and 4; a1 is independently selected from 0, 1, 2, 3, and 4; a2 is independently selected from 0, 1, 2, 3, and 4; c1 and d1 are each independently selected from 0, 1, 2, and 3; Selected from R D Each is independently selected from -C(=O)OH, -C(=O)OC(CH3)3, -C(=O)NH2, -S(=O)2NHCF3, Preferably, R D Selected from -C(=O)OH; L is independently selected from CH2 or CH3; preferably, L is independently selected from CH2. Each ring C is independently selected from ring C1, The ring C is arbitrarily divided by 1 to 4 Rs. c replace; Each ring D is independently selected from ring D1, The ring D is arbitrarily divided by 1 to 4 Rs. d replace; Ring A is independently selected from ring A1, Ring A1 is selected independently from each Ring C1 is selected independently from each The ring C1 is arbitrarily selected by 1 to 4 Rs c replace; Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: Ring D1 is selected independently from each The ring D1 is arbitrarily selected by 1 to 4 Rs d replace; Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side and R D connect.

6. The compound according to claims 1 to 5, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein, Ring B1 is selected independently from each One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; Preferably, each ring B1 is independently selected from... One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; b1 is selected independently from 1 and 2; b4 is selected independently from 0, 1, 2, and 3; b5 is selected independently from 0, 1, 2, and 3; b3 is independently selected from 0, 1, 2, and 3; a1 is independently selected from 0, 1, 2, and 3; a2 is independently selected from 0, 1, 2, and 3; Selected from Selected from Each independently selected Preferably, Each independently selected Or, R d Each independently selected from R 1d R 1d Selected from -N(methyl)2, -N(ethyl)2, Or, R c Selected from R 1c R 1c Each is independently selected from -CH2-cyclopropyl-R d1 -CH2-cyclobutyl-R d1 ,-Cyclopropyl-R d1 -Cyclobutyl-R d1 -cyclopentyl-R d1 The cyclopropyl, cyclobutyl, and cyclopentyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy groups; R b1 Each independently selected H, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy. R b3 Each independently selected H, deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy. R c R d Each of the following groups is independently selected from deuterium, F, Cl, Br, CN, OH, NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl, cyclobutyl, wherein the CH2, methyl, ethyl, cyclopropyl, and cyclobutyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; As an option, R c With R d Together with the skeleton connected to it, they form ring E; Preferably, R c Each is independently selected from deuterium, F, Cl, Br, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl; Preferably, R d Each is independently selected from deuterium, F, Cl, Br, methyl, ethyl, CD3, OCD3, CH2F, CHF2, CF3, -O-methyl, -O-ethyl, -O-cyclopropyl, -CH2-cyclopropyl, cyclopropyl; R A Each of the following groups is independently selected from deuterium, F, Cl, Br, I, CN, methyl, ethyl, propyl, isopropyl, CD3, OCD3, CH2F, CHF2, CF3, methoxy, cyclopropyl, cyclobutyl, and -CH2-cyclopropyl, wherein the CH2, methyl, ethyl, propyl, isopropyl, cyclopropyl, and cyclobutyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy. Or, R A Each independently selected from R a ; R a Each is independently selected from -SF5, -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-R a1 -cyclohexyl-R a1 , -S-methyl, -S-ethyl, -O-cyclopropyl, -O-cyclobutyl, oxetanebutyl, azironebutyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl The cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups mentioned above... Methyl, ethyl, oxetyl, aziridine, pyrrolyl, piperidinyl, morpholinyl, piperazine, tetrahydrofuranyl, tetrahydropyranyl Choose from 1 to 4 Rs k replace; Preferably, R a Each independently selected from -SF5, -S-methyl, -O-cyclopropyl, The methyl, cyclopropyl, It may be optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; R a1 Each of these elements is independently selected from NH2, -SF5, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(ethyl)2, -C(=O)NH-methyl, -C(=O)NH-ethyl, -NHC(=O)methyl, -NHC(=O)ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, piperidinyl, The methyl, ethyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, -S-methyl, -S-ethyl, -O-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxacyclobutyl, aziroxybutyl, pyrrolidinyl, and piperidinyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, I, CN, OH, NH2, methyl, and methoxy groups.

7. The compound according to claim 1, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein the compound is selected from the compounds shown in (I-B2), (I-B1), (IB), (IC), (I-Cl), (I-h1), (I-DD), (I-D1), (IF), and (I-F1). in, R a Selected from -C 3-6 cycloalkyl-R a1 The cycloalkyl group is optionally surrounded by 1 to 5 R groups. k Replace any of 1 to 4 R k Replacement; preferably, R a Selected from -cyclopropyl-R a1 -Cyclobutyl-R a1 -cyclopentyl-R a1 ; R a1 Each independently selected Wherein, each of b3 is independently selected from 0, 1, 2, 3, and 4; preferably, each of b3 is independently selected from 0, 1, and 2; R b3 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R b3 Each independently selected Deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, wherein the methyl, ethyl, propyl, and isopropyl groups are optionally substituted by 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy. As an option, any two R b3 Together with the carbon atoms or framework attached to it, they form C 3-6 cycloalkyl group, wherein the cycloalkyl group is optionally surrounded by 1 to 4 R groups k replace; Each ring D is independently selected from ring D1 or phenyl, wherein ring D is optionally surrounded by 1 to 5 R groups. d replace; Preferably, each ring D is independently selected from ring D1, The ring D is arbitrarily divided by 1 to 4 Rs. d replace; Each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: C 5-12 Bridged cycloalkyl; Preferably, each ring D1 is independently selected from 1 to 4 R's. d The following groups are substituted: Its right side is connected to -COOH; More preferably, rings D1 are each independently selected from 1 to 4 R's. d The following groups are substituted: Its right side is connected to -COOH; Each s3 is independently selected from 0, 1, or 2; Each s5 is independently selected from 0, 1, or 2; s2 are each independently selected from 0 or 1; Each of s7 can be independently selected from 1, 2, or 3; More preferably, rings D1 are each independently selected from 1 to 4 R's. d The following groups are substituted: Its right side is connected to -COOH; Ring B is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; Preferably, ring B is selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; Preferably, Selected from One end is connected to -C (=X1)-, and the other end is connected to -C (=X2)-; Each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: benzo[C] 4-6 Carbocyclic groups, benzo4-6 membered heterocyclic groups; Preferably, each ring C1 is independently selected from 1 to 4 R's. c The following groups are substituted: b4 is independently selected from 0, 1, 2, and 3; preferably, b4 is independently selected from 0, 1, and 2. a2 is independently selected from 0, 1, 2, 3, and 4; preferably, a2 is independently selected from 0 and 1. c1 is independently selected from 0, 1, and 2; d1 is independently selected from 0, 1, and 2; X1 is independently selected from O or S; X2 is independently selected from O or S; Preferably, each of X2 is independently selected from O; R A Each element is independently selected from deuterium, halogens, and C. 1-4 The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R A Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3; R b1 Each element is independently selected from deuterium, halogens, and C. 1-4 alkyl, The alkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R b1 Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3, As an option, any two R b1 Together with the carbon atoms or framework attached to it, they form C 3-6 cycloalkyl group, wherein the cycloalkyl group is optionally surrounded by 1 to 4 R groups k replace; R c Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 The alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R c Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3, and cyclopropyl; R d Each element is independently selected from deuterium, halogens, and C. 1-4 Alkyl, C 3-6 The alkyl group or cycloalkyl group is optionally substituted with 1 to 4 substituents selected from deuterium, F, Cl, Br, CN, OH, methyl, CD3, OCD3, CH2F, CHF2, CF3, and methoxy; preferably, R d Each is independently selected from deuterium, F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, CD3, CH2F, CHF2, CF3, and cyclopropyl; R 3 R 4 Each element is independently selected from H, deuterium, halogens, CN, and C. 1-4 Alkyl groups, wherein the alkyl group is optionally surrounded by 1 to 4 R groups. k replace; Preferably, Selected from R k Each is independently selected from deuterium, F, Cl, Br, -CH2OH, methyl, ethyl, isopropyl, CD3, OCD3, CH2F, CHF2, CF3, OCF3, methoxy, ethoxy, methylthio, -CH2-cyclopropyl, and cyclopropyl.

8. The compound according to claim 1, or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, wherein the compound is selected from one of the structures shown in Table E.

9. A pharmaceutical composition comprising the compound of any one of claims 1-8 or its stereoisomers, racemates, tautomers, pharmaceutically acceptable salts, and pharmaceutically acceptable excipients, preferably, the pharmaceutical composition comprising 1-1500 mg of the compound of any one of claims 1-8 or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts.

10. The use of the compound or its stereoisomer, racemate, tautomer, pharmaceutically acceptable salt, or pharmaceutical composition according to any one of claims 1-8 in the preparation of a medicament for treating diseases related to GIPR, preferably, wherein the disease is selected from diabetes [e.g., type 1 diabetes (T1D), type 2 diabetes (T2DM), prediabetes], idiopathic T1D (type 1b), latent autoimmune diabetes mellitus in adults (LADA), early-onset T2DM (EOD), adolescent-onset atypical diabetes (YOAD), adolescent-adult diabetes mellitus (MODY), malnutrition-associated diabetes, gestational diabetes mellitus, hyperglycemia, insulin resistance, liver disease, etc. Visceral insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disease, renal tubular dysfunction, pro-inflammatory changes in the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral fat deposition, sleep apnea [e.g., obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urinary incontinence), eating disorders (including bulimia syndrome, bulimia nervosa, and syndromic obesity such as Prad-Willi syndrome and Budd-Bead syndrome), weight gain, such as weight gain due to the use of other medications (e.g., due to the use of steroids). Caused by alcohol and / or antipsychotic medications, or by treatment of depression, or by the use of medications that affect cognitive function; overweight; excessive sugar intake; dyslipidemia [including hyperlipidemia, hypertriglyceridemia, elevated total cholesterol, high LDL (low-density lipoprotein) cholesterol and low HDL (high-density lipoprotein) cholesterol]; hyperinsulinemia; non-alcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma]; cardiovascular disease; atherosclerosis (including coronary artery disease); peripheral vascular disease; hypertension; endothelial dysfunction; impaired vascular compliance; heart failure [e.g. congestive heart failure, reduced ejection fraction] Heart failure with reduced ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), myocardial infarction (e.g., necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, postprandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson's disease, left ventricular hypertrophy, peripheral artery disease (PAD), macular degeneration, cataracts, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attack, restenosis, impaired glucose metabolism, impaired fasting glucose, hyperuricemia, gout, erectile dysfunction.Skin and connective tissue diseases, psoriasis, foot ulcers, ulcerative colitis, hyperapolipoprotein B hyperlipoproteinemia, Alzheimer's disease, schizophrenia, cognitive impairment, inflammatory bowel disease, short bowel syndrome, Crohn's disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addictions (e.g., alcohol, nicotine, and / or drug addiction).

11. A method for treating or alleviating a disease in a mammal, the method comprising administering to a subject a therapeutically effective amount of the compound of any one of claims 1-8 or its stereoisomers, racemates, tautomers, or pharmaceutically acceptable salts, preferably 1-1500 mg, wherein the disease is selected from diseases associated with GIPR, preferably, the disease is selected from diabetes [e.g., type 1 diabetes (T1D), type 2 diabetes (T2DM), prediabetes], idiopathic T1D (type 1b), latent autoimmune diabetes mellitus in adults (LADA), early-onset T2DM (EOD), adolescent-onset atypical diabetes (YOAD), and adolescent-adult diabetes mellitus (MODY). Malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney diseases [e.g., acute kidney disease, renal tubular dysfunction, pro-inflammatory changes in the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral fat deposition, sleep apnea [e.g., obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urinary incontinence), eating disorders (including bulimia syndrome, bulimia nervosa, and syndromic obesity such as Prad-Willi syndrome and Budd-Bead syndrome), weight Increased risk factors include weight gain due to the use of other medications (e.g., steroid and / or antipsychotic medications, treatment of depression, or medications affecting cognitive function), overweight, excessive sugar consumption, dyslipidemia (including hyperlipidemia, hypertriglyceridemia, elevated total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol), hyperinsulinemia, non-alcoholic fatty liver disease (NAFLD, including related conditions such as steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma), cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, and vascular malformation. Impaired resuscitation, heart failure [e.g., congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g., necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, postprandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson's disease, left ventricular hypertrophy, peripheral artery disease (PAD), macular degeneration, cataracts, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attack, restenosis, impaired glucose metabolism,Impaired fasting glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue diseases, psoriasis, foot ulcers, ulcerative colitis, hyperapolipoprotein B hyperglycemia, Alzheimer's disease, schizophrenia, cognitive impairment, inflammatory bowel disease, short bowel syndrome, Crohn's disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addictions (e.g., alcohol, nicotine, and / or drug addiction).

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