Carboxyl-containing heterocyclic derivative modulator, preparation method therefor and use thereof

Abstract

The present invention relates to a carboxyl-containing heterocyclic derivative modulator, a preparation method therefor, and the use thereof. In particular, the present invention relates to a compound as represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and the use thereof as a modulator in the preparation of a drug for treating diabetes, obesity, NASH, renal diseases, and related conditions thereof, wherein each substituent in general formula (I) is as defined in the description.

Description

Carboxyl-containing heterocyclic derivative modifiers, their preparation methods and applications Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to a carboxyl-containing heterocyclic derivative regulator, its preparation method, and its application. Background Technology

[0002] Glucose-dependent insulinotropic polypeptide (GIP) is an incretin composed of 42 amino acids. It is primarily generated by the cleavage of GIP precursor protein by prohormone convertase 1 / 3 (PC1 / 3) in intestinal K cells. Its receptor, GIPR, is widely distributed in various tissues, including the pancreas, stomach, adipose tissue, lung, heart, bone, vascular endothelium, and parts of the brain. After binding to its receptor, GIP activates adenylate cyclase, increasing intracellular cAMP levels, activating downstream PKA and EPAC2, promoting insulin release, and desensitizing and inducing receptor endocytosis by recruiting β-arrestin. Downstream, the ERK pathway promotes cell proliferation. GIP exerts its physiological functions in multiple tissues, enhancing glucose-dependent insulin secretion to regulate postprandial blood glucose levels, maintaining glycemic homeostasis by regulating insulin and glucagon release, inhibiting food intake, promoting glucose uptake in white adipose tissue, increasing lipase activity, and promoting lipid synthesis and degradation, among other things. Natural GIP is rapidly cleaved in vivo by dipeptidyl peptidase 4 (DPP4). GIP was one of the first incretins discovered, but current research on another incretin—glucagon-like peptide-1 (GLP-1)—far surpasses that on GIP. In recent years, numerous preclinical and clinical studies have confirmed that GIPR is also a very promising target; inhibiting GIPR activity can reduce weight and has broad market prospects in the fields of obesity and metabolic diseases.

[0003] In preclinical animal models, multiple studies have demonstrated the effectiveness of inhibiting GIPR activity in treating obesity and metabolic diseases. GIPR knockout mice have a protective effect against obesity induced by a high-fat diet, the GIPR antagonist (Pro3) GIP can reduce the body weight of obese mice fed a high-fat diet, and the GIPR inhibitory antibody Gipg013 can also lead to weight loss in mice. In clinical studies, GIP antibody conjugated with the GLP-1 peptide AMG133 has also shown stronger weight-reducing efficacy than the GLP-1 peptide.

[0004] GIPR antagonists are a highly promising target, potentially used as monotherapy or in combination with other drugs (such as GLP-1R agonists). The most advanced clinical candidate for this target, AMG133, is a GIPR antibody drug that requires subcutaneous administration, leading to poor patient compliance. Currently, no small molecule GIPR antagonists have entered clinical trials. There is a significant clinical need to develop new small molecule GIPR antagonists. Lower-cost, better-compliant oral small molecule GIPR antagonists have the potential to treat various metabolic diseases and possess a broad market prospect. They are expected to provide more treatment options for patients with diabetes, obesity, and NASH in the future. Summary of the Invention

[0005] The object of this invention is to provide a compound of general formula (I) or a pharmaceutically acceptable salt thereof:

[0006] in:

[0007] M1 or M2 are each independently selected from CH or N;

[0008] L1, L2, or L3 are each independently selected from the bond, -C(O)-, or -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O)n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C = CR 22 R 33 -、-R 11 C = CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group(NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally substituted with one or more of the following substituents: halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl.

[0009] Alternatively, L1 and L2 may form heterocyclic groups with the atoms they are attached to;

[0010] Ring A, ring B, or ring D are each independently selected from cycloalkyl, heterocyclic, aryl, or heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, alkenylcarboxyl, or alkynylcarboxyl groups.

[0011] R 11 R 22 Or R 33Each of the following groups is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0012] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl groups are optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl or carboxyl groups.

[0013] Alternatively, any two atoms connected to R1, R2, R3, and R4 may form a cycloalkyl, heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0014] Alternatively, when y is 2, 3, or 4, the two R2 atoms connected to them form a cycloalkyl, heterocyclic, or aryl group, wherein the cycloalkyl, heterocyclic, or aryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0015] R 31 R 32 R 33 R aa R bb Or R cc Each of the following is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0016] Or, R aa R bb It forms cycloalkyl or heterocyclic groups with the atoms attached to it;

[0017] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0018] n1 or n2 can be 0, 1, 2 or 3 independently;

[0019] n3 can be 0, 1, 2 or 3 independently;

[0020] n4 or m2 are each independently 0, 1, or 2; and

[0021] m1 can be 0, 1, 2 or 3 independently;

[0022] The conditions are:

[0023] When M1 is N, M2 is CH, and ring A is pyridine, pyrazole, phenyl, or... Ring B is pyridine, phenyl, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, acetamido, and when R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not phenyl or pyridine.

[0024] In certain embodiments of the invention, a compound of general formula (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (II-8), (II-9), (II-10), (II-11), (II-12), (II-13) or (II-14) or a pharmaceutically acceptable salt thereof is provided:

[0025] in:

[0026] It can be a single bond or a double bond;

[0027] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0028] L1, L2, or L3 are each independently selected from the bond, -C(O)-, or -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11-、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C=CR 22 R 33 -、-R 11 C=CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 )n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group(NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally substituted with one or more of the following substituents: halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl.

[0029] Alternatively, L1 and L2 may form heterocyclic groups with the atoms they are attached to;

[0030] Ring A, ring B, ring C, or ring D are each independently selected from cycloalkyl, heterocyclic, aryl, or heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, alkenylcarboxyl, or alkynylcarboxyl groups.

[0031] Alternatively, ring C does not exist;

[0032] R 11 R 22 Or R 33 Each of the following groups is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0033] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl groups are optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl or carboxyl groups.

[0034] And at least one R4 is selected from a carboxyl group;

[0035] Alternatively, any two atoms connected to R1, R2, R3, and R4 may form a cycloalkyl, heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0036] Alternatively, when y is 2, 3, or 4, the two R2 atoms connected to them form a cycloalkyl, heterocyclic, or aryl group, wherein the cycloalkyl, heterocyclic, or aryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0037] R 31 R 32 R 33 R aa R bb Or R cc Each of the following is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0038] Or, R aa R bb It forms cycloalkyl or heterocyclic groups with the atoms attached to it;

[0039] x, y, and z are each independently 0, 1, 2, 3, or 4;

[0040] t is 1, 2, 3, or 4;

[0041] n1 or n2 can be 0, 1, 2 or 3 independently;

[0042] n3 can be 0, 1, 2 or 3 independently;

[0043] n4 or m2 are each independently 0, 1 or 2;

[0044] m1 can be 0, 1, 2 or 3 independently;

[0045] n5 or n6 are each independently 1, 2 or 3; and

[0046] n7 can be 0, 1, 2, or 3;

[0047] The conditions are:

[0048] (1) In general formula (II-1), X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, phenyl, When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, acetamido, and when R4 is selected from 1, 2 or 3 substituents from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not phenyl or pyridine.

[0049] (2) In general formula (II-6), X0, X1, X2, X3, and X4 are each independently selected from CH or N; X5, X6, X7, X8, and X9 are each independently selected from CH or N; L1 is -NHC(O)-; L2 is -C(O)NH-; L3 is a bond; L1 and L2 do not form heterocyclic groups with the atoms they are attached to; ring D is phenyl or pyridine; n1 is 2; n2 is 0; R1 is selected from 1, 2, or 3 substituents from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy; R2 is selected from one or more substituents from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido; and R4 is selected from 1, 2, or 3 substituents from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2; ring C is not a bond. in This indicates that it is connected to L1. Indicates connection to L2;

[0050] (3) In general formula (II-2), X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is phenyl or pyridine, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, then ring A is not pyridine, pyrazole, phenyl, or

[0051] In some embodiments of the invention, general formula (II-5) is further a compound represented by general formula (II-5A) or a pharmaceutically acceptable salt thereof:

[0052] In some embodiments of the invention, a compound of general formula (II-5B) or a pharmaceutically acceptable salt thereof is provided:

[0053] in:

[0054] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0055] L1, L2, or L3 are each independently selected from the bond, -C(O)-, or -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 )n3 -、 -NR 11 -、 -(CR 22 R 33 ) n3 NR 11 -、 -NR 11 (CR 22 R 33 ) n3 -、 -S(O) n4 -、 -NR 11 S(O) n4 -、 -S(O) n4 NR 11 -、 -NR 11 C=NR 22 -、 -NR 11 C=CR 22 R 33 -、 -R 11 C=CR 22 -、 -NR 11 C(O)C(O)-、 -C(O)C(O)NR 11 -、 -(CR 22 R 33 ) n3 C(O)-、 -C(O)(CR 22 R 33 ) n3 -、 -NR 11 (CR 22 R 33 ) n3 C(O)-、 -C(O)(CR 22 R 33 ) n3 NR 11 -、 -C(O)NR 11 (CR 22 R 33 ) n3 -、 -(CR 22 R 33 ) n3 NR 11 C(O)-、 -(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、 -NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、 -(NR 11 )3 - 10 - membered heteroaryl group -、 - 3 - 10 - membered heteroaryl group (NR 11)-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group(NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally substituted with one or more of the following substituents: halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl.

[0056] Alternatively, L1 and L2 may form heterocyclic groups with the atoms they are attached to;

[0057] Ring A, ring B, ring C, or ring D are each independently selected from cycloalkyl, heterocyclic, aryl, or heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, alkenylcarboxyl, or alkynylcarboxyl groups.

[0058] Alternatively, ring C does not exist;

[0059] R 11 R 22 Or R 33Each of the following groups is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0060] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl groups are optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl or carboxyl groups.

[0061] And at least one R4 is selected from a carboxyl group;

[0062] Alternatively, any two atoms connected to R1, R2, R3, and R4 may form a cycloalkyl, heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0063] Alternatively, when y is 2, 3, or 4, the two R2 atoms connected to them form a cycloalkyl, heterocyclic, or aryl group, wherein the cycloalkyl, heterocyclic, or aryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0064] R 31 R 32 R 33 R aa R bb Or R cc Each of the following is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0065] Or, R aa R bb It forms cycloalkyl or heterocyclic groups with the atoms attached to it;

[0066] x, y, and z are each independently 0, 1, 2, 3, or 4;

[0067] t is 1, 2, 3, or 4;

[0068] n1 or n2 can be 0, 1, 2 or 3 independently;

[0069] n3 can be 0, 1, 2 or 3 independently;

[0070] n4 or m2 are each independently 0, 1 or 2;

[0071] m1 can be 0, 1, 2 or 3 independently;

[0072] n5 or n6 are each independently 1, 2 or 3; and

[0073] n7 can be 0, 1, 2, or 3.

[0074] In some embodiments of the invention, general formula (II-5B) is further a compound represented by general formula (II-5C) or a pharmaceutically acceptable salt thereof:

[0075] In certain embodiments of the invention, for compounds of general formula (II-1) or their pharmaceutically acceptable salts:

[0076] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0077] Ring D is selected from C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents in the alkyl group, -SF5 or -SCF3 are substituted;

[0078] L1, L2, or L3 are each independently selected from the bond, -C(O)-, or -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C = CR 22 R 33 -、-R 11 C = CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 3-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted;

[0079] R 11 R 22 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3The alkyl halogroup is substituted by one or more substituents;

[0080] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa Rbb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally further converted by halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution;

[0081] R 31 R 32 R 33 R aa R bb Or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1- 6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally halogenated, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution;

[0082] Or, R aa R bb Forming C with the attached atoms 3-15 Cycloalkyl or containing 1-5 3-15 membered heterocyclic groups selected from N, O or S heteroatoms;

[0083] Ring B is selected from C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-4 N, O, S, P or B atoms, C6-14 Aryl or 5-14 membered heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 A aryl group or a 5-14 membered heteroaryl group containing 1-4 N, O, S, P or B atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample;

[0084] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0085] n1 or n2 are each independently 0, 1 or 2;

[0086] n3 can be 0, 1, 2 or 3 independently;

[0087] n4 or m2 are each independently 0, 1, or 2; and

[0088] m1 can be 0, 1, 2 or 3 independently;

[0089] The conditions are:

[0090] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, benzene ring, etc. When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano or acetamido, and R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not a benzene ring or a pyridine ring.

[0091] In certain embodiments of the invention, for compounds of general formula (II-1) or their pharmaceutically acceptable salts:

[0092] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0093] Ring D is selected from C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0094] L1, L2, or L3 are each independently selected from the following bonds: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-.

[0095] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R31 、-NR 31 (CR aa R bb ) m1 R 32 、-S(CR aa R bb ) m1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) m1 C(O)NR 31 R 32 、-(CH2) m1 P(O)R 31 R 32 、-(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb )m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0096] R 31 R 32 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0097] R aa R bb Or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0098] Or, R aa R bb Forming C with the attached atoms 3-10 Cycloalkyl groups or containing 1-4 3-10 membered heterocyclic groups selected from N, O or S heteroatoms;

[0099] Ring B is selected from C 3-8Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, 5-8 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 A aryl group, a 5-8 membered mono-heteroaryl group containing 1-4 N, O, S, P, or B atoms, or an 8-14 membered fused heteroaryl group containing 1-4 N, O, S, P, or B atoms, optionally prefixed with an oxo group, a thio group, a halogen, an amino group, a hydroxyl group, a cyano group, a nitro group, or a C group. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R3, -(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa Rbb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample;

[0100] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0101] n1 or n2 are each independently 0, 1 or 2;

[0102] n3 can be 0, 1, 2 or 3 independently;

[0103] n4 or m2 are each independently 0, 1, or 2; and

[0104] m1 can be 0, 1, 2 or 3 independently;

[0105] The conditions are:

[0106] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, benzene ring, etc. When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano or acetamido, and R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not a benzene ring or a pyridine ring.

[0107] In certain embodiments of the invention, for compounds of general formula (II-1) or their pharmaceutically acceptable salts:

[0108] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0109] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0110] L1, L2, or L3 are each independently selected from the following bonds: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-.

[0111] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb )m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0112] R 31 R 32 Or R 33 Each group is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl group is optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0113] R aa R bb Or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy.

[0114] Or, R aa R bb Forming C with the attached atoms 3-6 Cycloalkyl or containing 1-4 4-6 membered heterocyclic groups selected from N, O or S heteroatoms;

[0115] Ring B is selected from C 3-6 Monocycloalkyl, C 6-14 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-8 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, 5-6 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-6 Monocycloalkyl, C 6-14Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-8 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 A aryl group, a 5-6 member mono-heteroaryl group containing 1-4 N, O, S, P, or B atoms, or an 8-14 member fused heteroaryl group containing 1-4 N, O, S, P, or B atoms, optionally prefixed with an oxo group, a thio group, a halogen, an amino group, a hydroxyl group, a cyano group, a nitro group, or a C group. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb COOH, -S(O) m2 R 32 -S(O)(=NR) cc )R 32 -BR 31 R 32 、-(NR 31 )C(O)R 32 -C(O)C(O)R 31 -C(O)NR 31 R 32 or -S(O) m2 NR 31 R 32 One or more substituents are substituted in the sample;

[0116] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0117] n1 or n2 are each independently 0, 1 or 2;

[0118] n3 can be 0, 1, 2 or 3 independently;

[0119] n4 or m2 are each independently 0, 1, or 2; and

[0120] m1 can be 0, 1, 2 or 3 independently;

[0121] The conditions are:

[0122] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, benzene ring, etc. When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano or acetamido, and R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not a benzene ring or a pyridine ring.

[0123] In certain embodiments of the invention, for compounds of general formula (II-1) or their pharmaceutically acceptable salts:

[0124] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0125] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0126] L1 or L2 are each independently selected from -NHC(O)-, -C(O)NH-, -NHC(S)- or -C(S)NH-;

[0127] L3 is selected from the key;

[0128] R1, R2, R3, or R4 are each independently selected from hydrogen, fluorine, chlorine, bromine, amino, oxo, methylamino, dimethylamino, hydroxyl, cyano, nitro, carboxyl, methyl, ethyl, isopropyl, tert-butyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, difluorovinyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, cyclopropoxy, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SF5, -B(OH)2, -SCF3, -CH2COOH, -S(O)OH.

[0129] Cycloyl B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, Optional radicals include hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -(CH=CH)COOH, -B(OH)2, -CH2COOH, and -S(O)OH. One or more substituents are substituted in the sample;

[0130] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0131] n1 or n2 are each independently 0, 1 or 2;

[0132] n3 can be 0, 1, 2 or 3 independently;

[0133] n4 or m2 are each independently 0, 1, or 2; and

[0134] m1 can be 0, 1, 2 or 3 independently;

[0135] The conditions are:

[0136] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, benzene ring, etc. When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano or acetamido, and R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not a benzene ring or a pyridine ring.

[0137] In certain embodiments of the invention, for compounds of general formula (II-1) or their pharmaceutically acceptable salts:

[0138] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0139] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0140] L1 or L2 are each independently selected from -NHC(O)-, -C(O)NH-, -NHC(S)- or -C(S)NH-;

[0141] L3 is selected from the key;

[0142] R1, R2, R3, or R4 are each independently selected from hydrogen, fluorine, carboxyl, methyl, isopropyl, methoxy, trifluoromethyl, -SF5, -B(OH)2.

[0143] Ring B is selected from phenyl, Optional radicals include hydrogen, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -B(OH)2, or... One or more substituents are substituted in the sample;

[0144] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0145] n1 or n2 are each independently 0, 1 or 2;

[0146] n3 can be 0, 1, 2 or 3 independently;

[0147] n4 or m2 are each independently 0, 1, or 2; and

[0148] m1 can be 0, 1, 2 or 3 independently;

[0149] The conditions are:

[0150] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, benzene ring, etc. When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano or acetamido, and R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not a benzene ring or a pyridine ring.

[0151] In certain embodiments of the invention, for compounds of general formula (II-2) or their pharmaceutically acceptable salts:

[0152] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0153] Ring D is selected from C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents in the alkyl group, -SF5 or -SCF3 are substituted;

[0154] L1, L2, or L3 are each independently selected from the bond, -C(O)-, or -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C = CR 22 R 33 -、-R 11 C = CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11(CR 22 R 33 ) n3 3-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted;

[0155] R 11 R 22 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0156] R1, R2, R3, or R4 are each independently selected from halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally further converted by halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution;

[0157] Alternatively, R3 and R4 form 3-12 membered heterocyclic groups with the atoms they are attached to, which can optionally be further reacted with halogens, amino groups, hydroxyl groups, oxo groups, cyano groups, nitro groups, C groups, etc. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution;

[0158] Alternatively, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3-12 Cycloalkyl, 3-12 membered heterocyclic or C 6-12 Aryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic or C 6-12 Aryl group, optionally further reacted with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6- 12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution;

[0159] R 31 R 32 R 33 R aa R bb Or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1- 6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally halogenated, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution;

[0160] Or, R aa R bb Forming C with the attached atoms 3-15 Cycloalkyl or containing 1-5 3-15 membered heterocyclic groups selected from N, O or S heteroatoms;

[0161] Ring A is selected from C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0162] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0163] n1 or n2 are each independently 0, 1 or 2;

[0164] n3 can be 0, 1, 2 or 3 independently;

[0165] n4 or m2 are each independently 0, 1, or 2; and

[0166] m1 can be 0, 1, 2 or 3 independently;

[0167] The conditions are:

[0168] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is a benzene ring or a pyridine ring, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, ring A is not a pyridine ring, benzene ring, or

[0169] In certain embodiments of the invention, for compounds of general formula (II-2) or their pharmaceutically acceptable salts:

[0170] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0171] Ring D is selected from C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0172] L1, L2, or L3 are each independently selected from the bond, -C(O)-, or -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C = CR22 R 33 -、-R 11 C = CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 3-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted;

[0173] R 11R 22 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0174] R1, R2, R3, or R4 are each independently selected from halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2- 4-Alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0175] Alternatively, R3, R4, and the atoms attached to them form a 3-10 membered heterocyclic group containing 1-4 N, O, or S atoms, optionally surrounded by a halogen, amino, hydroxyl, oxo, cyano, nitro, or C atom. 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0176] Alternatively, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, or C 6-10 Aryl, the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, or C 6-10 aryl, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0177] R 31 R 32 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0178] R aa R bb Or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0179] Or, R aa R bb Forming C with the attached atoms 3-10 Cycloalkyl groups or containing 1-4 3-10 membered heterocyclic groups selected from N, O or S heteroatoms;

[0180] Ring A is selected from C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0181] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0182] n1 or n2 are each independently 0, 1 or 2;

[0183] n3 can be 0, 1, 2 or 3 independently;

[0184] n4 or m2 are each independently 0, 1, or 2; and

[0185] m1 can be 0, 1, 2 or 3 independently;

[0186] The conditions are:

[0187] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is a benzene ring or a pyridine ring, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, ring A is not a pyridine ring, benzene ring, or

[0188] In certain embodiments of the invention, for compounds of general formula (II-2) or their pharmaceutically acceptable salts:

[0189] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0190] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0191] L1, L2, or L3 are each independently selected from the following bonds: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-.

[0192] R1, R2, R3, or R4 are each independently selected from halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2- 4-Alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R31 、-NR 31 (CR aa R bb ) m1 R 32 、-S(CR aa R bb ) m1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) m1 C(O)NR 31 R 32 、-(CH2) m1 P(O)R 31 R 32 、-(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb )m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0193] Alternatively, R3, R4, and the atoms attached to them form a 3-10 membered heterocyclic group containing 1-4 N, O, or S atoms, optionally surrounded by a halogen, amino, hydroxyl, oxo, cyano, nitro, or C atom. 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0194] Alternatively, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, or C 6-10 Aryl, the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, or C 6-10 aryl, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0195] R 31 R 32 Or R 33 Each group is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl group is optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0196] R aa R bb Or R ccEach is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy.

[0197] Or, R aa R bb Forming C with the attached atoms 3-6 Cycloalkyl or containing 1-4 4-6 membered heterocyclic groups selected from N, O or S heteroatoms.

[0198] Ring A is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0199] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0200] n1 or n2 are each independently 0, 1 or 2;

[0201] n3 can be 0, 1, 2 or 3 independently;

[0202] n4 or m2 are each independently 0, 1, or 2; and

[0203] m1 can be 0, 1, 2 or 3 independently;

[0204] The conditions are:

[0205] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is a benzene ring or a pyridine ring, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, ring A is not a pyridine ring, benzene ring, or

[0206] In certain embodiments of the invention, for compounds of general formula (II-2) or their pharmaceutically acceptable salts:

[0207] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0208] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0209] L1, L2, or L3 are each independently selected from the following bonds: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-.

[0210] R1, R2, R3, R4, or R5 are each independently selected from fluorine, chlorine, bromine, amino, oxo, methylamino, dimethylamino, hydroxyl, cyano, nitro, carboxyl, methyl, ethyl, isopropyl, tert-butyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, difluorovinyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, cyclopropoxy, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SF5, -B(OH)2, -SCF3, -CH2COOH, -S(O)OH.

[0211] Alternatively, R3, R4 and the atoms they are bonded to form

[0212] Alternatively, when y is 2, 3 or 4, the two R2 atoms connected to them form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl groups;

[0213] Cycloyl A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally substituted with one or more substituents selected from fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl;

[0214] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0215] n1 or n2 are each independently 0, 1 or 2;

[0216] n3 can be 0, 1, 2 or 3 independently;

[0217] n4 or m2 are each independently 0, 1, or 2; and

[0218] m1 can be 0, 1, 2 or 3 independently;

[0219] The conditions are:

[0220] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is a benzene ring or a pyridine ring, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, ring A is not a pyridine ring, benzene ring, or

[0221] In certain embodiments of the invention, for compounds of general formula (II-2) or their pharmaceutically acceptable salts:

[0222] X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0223] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution;

[0224] L1 or L2 are each independently selected from -NHC(O)-, -C(O)NH-, -NHC(S)- or -C(S)NH-;

[0225] L3 is selected from the key;

[0226] R1, R2, R3, R4, or R5 are each independently selected from fluorine, carboxyl, methyl, isopropyl, methoxy, trifluoromethyl, -SF5, -B(OH)2.

[0227] Ring A is selected from Optionally substituted with one or more substituents selected from fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl;

[0228] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0229] n1 or n2 are each independently 0, 1 or 2;

[0230] n3 can be 0, 1, 2 or 3 independently;

[0231] n4 or m2 are each independently 0, 1, or 2; and

[0232] m1 can be 0, 1, 2 or 3 independently;

[0233] The conditions are:

[0234] When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is a benzene ring or a pyridine ring, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, ring A is not a pyridine ring, benzene ring, or

[0235] In certain embodiments of the invention, a compound of general formula (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), (III-8), (III-9), (III-10), (III-11), or (III-12) or a pharmaceutically acceptable salt thereof is provided:

[0236] in:

[0237] It can be a single bond or a double bond;

[0238] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0239] L1 or L2 are each independently selected from the bond, -C(O)-, and -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11-、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C=CR 22 R 33 -、-R 11 C=CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 )n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group(NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally substituted with one or more of the following substituents: halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl.

[0240] Alternatively, L1 and L2 may form heterocyclic groups with the atoms they are attached to;

[0241] Ring A, ring B, ring C, or ring D are each independently selected from cycloalkyl, heterocyclic, aryl, or heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, alkenylcarboxyl, or alkynylcarboxyl groups.

[0242] Alternatively, ring C does not exist;

[0243] R 11 R 22 Or R 33 Each of the following groups is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0244] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl groups are optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl or carboxyl groups.

[0245] And at least one R4 is selected from a carboxyl group;

[0246] Alternatively, any two atoms connected to R1, R2, R3, and R4 may form a cycloalkyl, heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0247] Alternatively, when y is 2, 3, or 4, the two R2 atoms connected to them form a cycloalkyl, heterocyclic, or aryl group, wherein the cycloalkyl, heterocyclic, or aryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0248] R 31 R 32 R 33 R aa R bb Or R cc Each of the following is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0249] Or, R aa R bb It forms cycloalkyl or heterocyclic groups with the atoms attached to it;

[0250] x, y, and z are each independently 0, 1, 2, 3, or 4;

[0251] t is 1, 2, 3, or 4;

[0252] n1 or n2 are each independently 0, 1 or 2;

[0253] n3 can be 0, 1, 2 or 3 independently;

[0254] n4 or m2 are each independently 0, 1, or 2; and

[0255] m1 can be 0, 1, 2 or 3 independently.

[0256] In some embodiments of the invention, a compound of general formula (III-2A) or a pharmaceutically acceptable salt thereof is provided:

[0257] in:

[0258] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0259] L1 or L2 are each independently selected from the bond, -C(O)-, and -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C = CR 22 R 33 -、-R 11 C = CR22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11C(O))4-10 heterocyclic group-,-4-10 heterocyclic group(NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally substituted with one or more of the following substituents: halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl.

[0260] Alternatively, L1 and L2 may form heterocyclic groups with the atoms they are attached to;

[0261] Ring A, ring B, ring C, or ring D are each independently selected from cycloalkyl, heterocyclic, aryl, or heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, alkenylcarboxyl, or alkynylcarboxyl groups.

[0262] Alternatively, ring C does not exist;

[0263] R 11 R 22 Or R 33 Each of the following groups is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0264] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, -O(CR) aa R bb )m1 R 31 、-NR 31 (CR aa R bb ) m1 R 32 、-S(CR aa R bb ) m1 R 31 、-OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 、N=S=OR 31 R 32 、N(R 31 )=S=OR 32 -、-(CH2) m1 C(O)NR 31 R 32 、-(CH2) m1 P(O)R 31 R 32 、-(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa Rbb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 C(O)C(O)R 31 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl groups are optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl or carboxyl groups.

[0265] And at least one R4 is selected from a carboxyl group;

[0266] Alternatively, any two atoms connected to R1, R2, R3, and R4 may form a cycloalkyl, heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0267] Alternatively, when y is 2, 3, or 4, the two R2 atoms connected to them form a cycloalkyl, heterocyclic, or aryl group, wherein the cycloalkyl, heterocyclic, or aryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups.

[0268] R 31 R 32 R 33 Raa R bb Or R cc Each of the following is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl;

[0269] Or, R aa R bb It forms cycloalkyl or heterocyclic groups with the atoms attached to it;

[0270] x, y, and z are each independently 0, 1, 2, 3, or 4;

[0271] t is 1, 2, 3, or 4;

[0272] n1 or n2 are each independently 0, 1 or 2;

[0273] n3 can be 0, 1, 2 or 3 independently;

[0274] n4 or m2 are each independently 0, 1, or 2; and

[0275] m1 can be 0, 1, 2 or 3 independently.

[0276] In certain embodiments of the invention, for compounds of general formula (III-1) or their pharmaceutically acceptable salts:

[0277] X5, X6, X7, X8, or X9 are each independently selected from C or N;

[0278] Ring D is selected from C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0279] L1 or L2 are each independently selected from bonds, C(O), and NR. 11 C(O), C(O)NR 11 、(CR 22 R 33 ) n3 C(O)NR 11 NR 11 C(O)NR 22 、(CR 22 R 33 ) n3 NR 11 、(CR 22 R 33 ) n3 NR 11 NR 11 (CR 22 R 33 ) n3 S(O) n4 NR 11 S(O) n4 S(O) n4 NR 11 Or O;

[0280] R 11 R 22 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0281] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-3 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -N(CR) aa R bb ) m1 R 31 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb )m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH or The amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0282] R 31 R 32 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0283] R aa R bb Or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0284] Ring B is selected from C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-14 Aryl or 5-14 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-14 A aryl group or a 5-14 membered heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH or One or more substituents are substituted in the sample;

[0285] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0286] n1 or n2 are each independently 0, 1 or 2;

[0287] n3 can be 0, 1, 2 or 3 independently;

[0288] n4 or m2 are each independently 0, 1, or 2; and

[0289] m1 can be 0, 1, 2 or 3 independently;

[0290] The conditions are:

[0291] When X5, X6, X7, X8, and X9 are each independently selected from C or N, L1 is NHC(O), L2 is C(O)NH, and ring B is pyridine, benzene ring, or... When both n1 and n2 are 1, ring D is neither a benzene ring nor a pyridine ring.

[0292] In certain embodiments of the invention, for compounds of general formula (III-1) or their pharmaceutically acceptable salts:

[0293] X5, X6, X7, X8, or X9 are each independently selected from C or N;

[0294] Ring D is selected from C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0295] L1 or L2 are each independently selected from bonds, C(O), and NR. 11 C(O), C(O)NR 11 、(CR 22 R 33 ) n3 C(O)NR 11 NR 11 C(O)NR 22 、(CR 22 R 33 ) n3 NR 11 、(CR 22 R 33) n3 NR 11 NR 11 (CR 22 R 33 ) n3 S(O) n4 NR 11 S(O) n4 S(O) n4 NR 11 Or O;

[0296] R 11 R 22 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0297] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-3 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -N(CR) aa R bb ) m1 R 31 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb )m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH or The amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0298] R 31 R 32 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, or propoxy groups are optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0299] R aa R bb Or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy.

[0300] Ring B is selected from C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, 8-14 member fused heteroaryl containing 1-3 N, O or S atoms, carboxyl, -(CR aa =CR bb ) m1 COOH or The C mentioned 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-14 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0301] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0302] n1 or n2 are each independently 0, 1 or 2;

[0303] n3 can be 0, 1, 2 or 3 independently;

[0304] n4 or m2 are each independently 0, 1, or 2; and

[0305] m1 can be 0, 1, 2 or 3 independently;

[0306] The conditions are:

[0307] When X5, X6, X7, X8, and X9 are each independently selected from C or N, L1 is NHC(O), L2 is C(O)NH, and ring B is pyridine, benzene ring, or... When both n1 and n2 are 1, ring D is neither a benzene ring nor a pyridine ring.

[0308] In certain embodiments of the invention, for compounds of general formula (III-1) or their pharmaceutically acceptable salts:

[0309] X5, X6, X7, X8, or X9 are each independently selected from C or N;

[0310] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0311] L1 or L2 are each independently selected from bonds, C(O), and NR. 11 C(O), C(O)NR 11 、(CR 22 R 33 ) n3 C(O)NR 11 NR 11 C(O)NR 22、(CR 22 R 33 ) n3 NR 11 、(CR 22 R 33 ) n3 NR 11 NR 11 (CR 22 R 33 ) n3 S(O) n4 NR 11 S(O) n4 S(O) n4 NR 11 Or O;

[0312] R 11 R 22 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0313] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-3 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -N(CR) aa R bb ) m1 R 31 -S(CR) aa R bb ) m1 R31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH or The amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0314] R 31 R 32 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, or propoxy groups are optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0315] R aa R bb Or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy.

[0316] Ring B is selected from C 3-6 Monocycloalkyl, C 6-14 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-14 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-14 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 aryl, 5-6 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-14 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Substitution with one or more substituents, such as alkyl, carboxyl, or (CH=CH)COOH;

[0317] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0318] n1 or n2 are each independently 0, 1 or 2;

[0319] n3 can be 0, 1, 2 or 3 independently;

[0320] n4 or m2 are each independently 0, 1, or 2; and

[0321] m1 can be 0, 1, 2 or 3 independently;

[0322] The conditions are:

[0323] When X5, X6, X7, X8, and X9 are each independently selected from C or N, L1 is NHC(O), L2 is C(O)NH, and ring B is pyridine, benzene ring, or... When both n1 and n2 are 1, ring D is neither a benzene ring nor a pyridine ring.

[0324] In certain embodiments of the invention, for compounds of general formula (III-1) or their pharmaceutically acceptable salts:

[0325] X5, X6, X7, X8, or X9 are each independently selected from C or N;

[0326] Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0327] L1 or L2 are each independently selected from bonds, C(O), and NR. 11 C(O), C(O)NR 11 、(CR 22 R 33 ) n3 C(O)NR 11 NR 11 C(O)NR 22 、(CR 22 R 33 ) n3 NR11 、(CR 22 R 33 ) n3 NR 11 NR 11 (CR 22 R 33 ) n3 S(O) n4 NR 11 S(O) n4 S(O) n4 NR 11 Or O;

[0328] R 11 R 22 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0329] R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-3 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -N(CR) aa R bb ) m1 R 31 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH or The amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0330] R 31 R 32 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, or propoxy groups are optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents;

[0331] R aa R bb Or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy.

[0332] Cycloyl B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, It may be optionally substituted with one or more of the following substituents: hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, carboxyl, or (CH=CH)COOH;

[0333] x, y, z and t are each independently 0, 1, 2, 3 or 4;

[0334] n1 or n2 are each independently 0, 1 or 2;

[0335] n3 can be 0, 1, 2 or 3 independently;

[0336] n4 or m2 are each independently 0, 1, or 2; and

[0337] m1 can be 0, 1, 2 or 3 independently;

[0338] The conditions are:

[0339] When X5, X6, X7, X8, and X9 are each independently selected from C or N, L1 is NHC(O), L2 is C(O)NH, and ring B is pyridine, benzene ring, or... When both n1 and n2 are 1, ring D is neither a benzene ring nor a pyridine ring.

[0340] In certain preferred embodiments of the present invention, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O or S atoms, 6-11 membered fused heterocyclic groups containing 1-3 N, O or S atoms, 5-11 membered spirocyclic groups containing 1-3 N, O or S atoms, or 6-11 membered bridged heterocyclic groups containing 1-3 N, O or S atoms.

[0341] In certain preferred embodiments of the present invention, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O or S atoms, 5-9 membered spirocyclic groups containing 1-3 N, O or S atoms, or 6-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms.

[0342] In certain preferred embodiments of the present invention, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-9 Spirocycloalkyl, C 5-10Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O or S atoms, 5-9 membered spirocyclic groups containing 1-3 N, O or S atoms, or 6-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms.

[0343] In certain preferred embodiments of the present invention, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O or S atoms, or 6-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms.

[0344] In certain preferred embodiments of the present invention, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O or S atoms, or 6-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms.

[0345] In certain preferred embodiments of the present invention, cycloD is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ...

[0346] In certain preferred embodiments of the invention, general formula (II-1) is further a compound of general formulas (IV-2), (IV-2A), (IV-4) or a pharmaceutically acceptable salt thereof; general formula (II-2) is further a compound of general formulas (IV-1), (IV-1A) or a pharmaceutically acceptable salt thereof; general formula (II-3) is further a compound of general formulas (IV-3), (IV-3A), (IV-5) or a pharmaceutically acceptable salt thereof; general formula (II-5) or (II-5A) is further a compound of general formulas (IV-1), (IV-2) or a pharmaceutically acceptable salt thereof; general formula (II-5B) or (II-5C) is further a compound of general formulas (IV-1A), (IV-2A) or a pharmaceutically acceptable salt thereof; and general formula (II-7) is further a compound of general formulas (IV-4), (IV-5), (IV-6) or a pharmaceutically acceptable salt thereof.

[0347] in:

[0348] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N.

[0349] In certain preferred embodiments of the invention, general formula (IV-1) is further a compound of general formula (V-1) or (V-7) or a pharmaceutically acceptable salt thereof; general formula (IV-2) is further a compound of general formula (V-1), (V-3), or (V-5) or a pharmaceutically acceptable salt thereof; general formula (IV-3) is further a compound of general formula (V-2), (V-4), (V-6), or (V-8) or a pharmaceutically acceptable salt thereof; general formula (IV-4) is further a compound of general formula (V-9) or (V-10) or a pharmaceutically acceptable salt thereof; and general formula (IV-5) is further a compound of general formula (V-11) or a pharmaceutically acceptable salt thereof.

[0350] In certain preferred embodiments of the invention, general formula (V-1) is further a compound represented by general formula (V-1A) or a pharmaceutically acceptable salt thereof, general formula (V-2) is further a compound represented by general formula (V-2A) or a pharmaceutically acceptable salt thereof, general formula (V-3) is further a compound represented by general formula (V-3A) or a pharmaceutically acceptable salt thereof, general formula (V-4) is further a compound represented by general formula (V-4A) or a pharmaceutically acceptable salt thereof, general formula (V-5) is further a compound represented by general formula (V-5A) or a pharmaceutically acceptable salt thereof, and general formula (V-6) is further a compound represented by general formula (V-1A) or a pharmaceutically acceptable salt thereof. Compounds of formula (V-6A) or their pharmaceutically acceptable salts, general formula (V-7) further being compounds of general formula (V-7A) or their pharmaceutically acceptable salts, general formula (V-8) further being compounds of general formula (V-8A) or their pharmaceutically acceptable salts, general formula (V-9) further being compounds of general formula (V-9A) or their pharmaceutically acceptable salts, general formula (V-10) further being compounds of general formula (V-10A) or their pharmaceutically acceptable salts, general formula (V-11) further being compounds of general formula (V-11A) or their pharmaceutically acceptable salts:

[0351] In certain preferred embodiments of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0352] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0353] L1 or L2 are each independently selected from the following: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-.

[0354] R1, R2, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, oxo, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -NR 31 (CR aa R bb ) m1 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 BR 31 R 32 、-(CR aa R bb ) m1 C(O)R31 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, optionally prefixed with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3One or more substituents in the alkyl group are substituted;

[0355] R 31 R 32 R aa Or R bb Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2- 3-olefin, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1- 3 alkyl groups;

[0356] x, y, and t are each independently 0, 1, 2, 3, or 4;

[0357] m1 can be 0, 1, 2, or 3;

[0358] m2 can be 0, 1, or 2.

[0359] In certain preferred embodiments of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0360] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0361] L1 or L2 are each independently selected from the following: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-.

[0362] R1, R2, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, oxo, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -NR 31 (CR aa R bb ) m1 R 32 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 BR 31 R 32 、-(CR aa R bb ) m1 C(O)R 31 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O)m2 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, optionally prefixed with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted;

[0363] And at least one R4 is selected from a carboxyl group;

[0364] R 31 R 32 R aa Or R bb Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2- 3-olefin, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1- 3 alkyl groups;

[0365] x and y are each independently 0, 1, 2, 3 or 4;

[0366] t is 1, 2, 3, or 4;

[0367] m1 can be 0, 1, 2, or 3;

[0368] m2 can be 0, 1, or 2.

[0369] In a further preferred embodiment of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0370] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0371] L1 or L2 is independently selected from -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-,

[0372] R1 is selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, propynyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl or -SF5;

[0373] R2 is selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0374] R4 is selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, carboxyl, -(CH=CH)COOH, -B(OH)2, -CH2COOH, -S(O)OH.

[0375] x, y, and t are each independently 0, 1, 2, or 3.

[0376] In a further preferred embodiment of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0377] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0378] L1 or L2 is independently selected from -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-,

[0379] R1 is selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, propynyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl or -SF5;

[0380] R2 is selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0381] R4 is selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, carboxyl, -(CH=CH)COOH, -B(OH)2, -CH2COOH, -S(O)OH.

[0382] And at least one R4 is selected from a carboxyl group;

[0383] x and y are each independently 0, 1, 2 or 3;

[0384] t is selected from 1, 2, or 3.

[0385] In certain preferred embodiments of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0386] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0387] L1 or L2 are each independently selected from -NHC(O)- or -C(O)NH-;

[0388] R1, R2, or R4 are each independently selected from hydrogen, methyl, methoxy, carboxyl, or...

[0389] x, y, and t are each independently 0, 1, 2, or 3.

[0390] In certain preferred embodiments of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0391] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0392] L1 or L2 are each independently selected from -NHC(O)- or -C(O)NH-;

[0393] R1, R2, or R4 are each independently selected from hydrogen, methyl, methoxy, carboxyl, or... And at least one R4 is selected from a carboxyl group;

[0394] x and y are each independently 0, 1, 2 or 3;

[0395] t is selected from 1, 2, or 3.

[0396] In certain preferred embodiments of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0397] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0398] L1 or L2 are each independently selected from -NHC(O)- or -C(O)NH-;

[0399] R1, R2, or R4 are each independently selected from hydrogen, methyl, methoxy, or carboxyl groups;

[0400] x, y, and t are each independently 0, 1, 2, or 3.

[0401] In certain preferred embodiments of the present invention, for general formulas (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), (V-11), (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A) or (V-11A), wherein:

[0402] X0, X1, X2, X3, X4, X5, X6, X7, X8, or X9 are each independently selected from CH or N;

[0403] L1 or L2 are each independently selected from -NHC(O)- or -C(O)NH-;

[0404] R1, R2, or R4 are each independently selected from hydrogen, methyl, methoxy, or carboxyl, and at least one R4 is selected from carboxyl.

[0405] x and y are each independently 0, 1, 2 or 3;

[0406] t is selected from 1, 2, or 3.

[0407] In some embodiments of the present invention Selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, or -SCF3.

[0408] In certain preferred embodiments of the present invention Selected from It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0409] In certain preferred embodiments of the present invention Selected from Optionally substituted with one or more substituents selected from hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl, wherein This indicates that it is connected to L1. This indicates that it is connected to L2.

[0410] In some embodiments of the present invention Selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, or -SCF3.

[0411] In certain preferred embodiments of the present invention Selected from It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0412] In certain preferred embodiments of the present invention Selected from Optionally substituted with one or more substituents selected from hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl, wherein This indicates that it is connected to L1. This indicates that it is connected to L2.

[0413] In some embodiments of the present invention, L1, L2, or L3 are each independently selected from bond, -C(O)-, -NR 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR 11 C=NR 22 -、-NR 11 C = CR 22 R 33 -、-R 11 C = CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11-、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group(NR) 11 C(O))-、-(NR 11(CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally converted by a halogen, amino, hydroxyl, oxo, cyano, nitro, or C group. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1- 6-alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents of aryl or 5-12 heteroaryl groups are used for substitution.

[0414] In some embodiments of the invention, L1, L2 and the atoms attached to them form 3-12 membered heterocyclic groups, optionally surrounded by halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6- 12 One or more substituents of aryl or 5-12 heteroaryl groups are used for substitution.

[0415] In some embodiments of the present invention, R 11 R 22 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1- 6-hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally surrounded by hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 It is replaced by one or more substituents of a haloalkyl group.

[0416] In a preferred embodiment of the present invention, L1, L2, or L3 are each independently selected from bond, -C(O)-, -NR. 11 C(O)-、-C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)NR 11 -、-NR 11 C(O)(CR 22 R 33 ) n3 -、-NR 11 C(O)NR 22 -、-C(S)-、-NR 11 C(S)-、-C(S)NR 11 -、-(CR 22 R 33 ) n3 C(S)NR 11 -、-NR 11 C(S)NR 22 -、-(CR 22 R 33 ) n3 -、-NR 11 -、-(CR 22 R 33 ) n3 NR 11 -、-NR 11 (CR 22 R 33 ) n3 -、-S(O) n4 -、-NR 11 S(O) n4 -、-S(O) n4 NR 11 -、-NR11 C=NR 22 -、-NR 11 C = CR 22 R 33 -、-R 11 C = CR 22 -、-NR 11 C(O)C(O)-、-C(O)C(O)NR 11 -、-(CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 -、-NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11 (CR 22 R 33 ) n33-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in a haloalkyl group are substituted.

[0417] In a preferred embodiment of the invention, L1, L2 and their adjacent atoms form a 5-12 membered heterocyclic group containing 1-6 N, O or S atoms, optionally coated with a halogen, hydroxyl group, oxo group, or C group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in a haloalkyl group are substituted.

[0418] In a preferred embodiment of the present invention, R 11 R 22 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1- 3-hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2- 4-Alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 It is replaced by one or more substituents of a haloalkyl group.

[0419] In a preferred embodiment of the present invention, R 11 R 22 Or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 It is replaced by one or more substituents of a haloalkyl group.

[0420] In a preferred embodiment of the present invention, L1, L2, or L3 are each independently selected from the following bonds: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-, -NHC(O)CH2-, -CH2NHC(O)NH-,

[0421] In a preferred embodiment of the present invention, L1, L2 and the atoms connected to them form It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0422] In a preferred embodiment of the present invention, L1 or L2 is independently selected from -NHC(O)-, -C(O)NH-, -NHC(S)-, -C(S)NH-, -CH2C(O)NH-, -CH2NHC(O)-, or

[0423] In a preferred embodiment of the present invention, L1 or L2 is independently selected from -NHC(O)- or -C(O)NH-.

[0424] In a preferred embodiment of the present invention, L3 is selected from a bond.

[0425] In some embodiments of the present invention, R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -CR aa =CR aa R bb 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1- 6-hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally further converted by halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents of aryl or 5-12 heteroaryl groups are used for substitution.

[0426] In some embodiments of the present invention, R3, R4 and the atoms connected to them form C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, optionally further bonded by hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1- 6-alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents of aryl or 5-12 heteroaryl groups are used for substitution.

[0427] In some embodiments of the invention, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3- 14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, optionally further bonded by hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylinyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3- 12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents of aryl or 5-12 heteroaryl groups are used for substitution.

[0428] In some embodiments of the present invention, R 31 R 32 R 33 R aa R bb Or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally halogenated, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1- 6-Hydroalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents of aryl or 5-12 heteroaryl groups are used for substitution.

[0429] In some embodiments of the present invention, R aa R bbForming C with the attached atoms 3-15 Cycloalkyl or containing 1-5 3-15 membered heterocyclic groups selected from N, O or S heteroatoms.

[0430] In a preferred embodiment of the present invention, R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa Rbb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH, -CR aa =CR aa R bb 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0431] In a preferred embodiment of the present invention, R3, R4 and the atoms connected to them form C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally coated with hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, or C. 1-3 Alkyl, C 2- 4-Alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0432] In a preferred embodiment of the invention, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3- 10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally coated with hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, or C. 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution.

[0433] In a preferred embodiment of the present invention, R 31 R 32 Or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1- 3-hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 It is replaced by one or more substituents of a haloalkyl group.

[0434] In a preferred embodiment of the present invention, R aa R bb Or Rcc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1- 3-hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 It is replaced by one or more substituents of a haloalkyl group.

[0435] In a preferred embodiment of the present invention, R aa R bb Forming C with the attached atoms 3-10 Cycloalkyl or containing 1-4 3-10 membered heterocyclic groups selected from N, O or S heteroatoms.

[0436] In a preferred embodiment of the present invention, R 31 R 32 Or R 33 Each group is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl group is optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1- It is substituted by one or more substituents of a 3-haloalkyl group.

[0437] In a preferred embodiment of the present invention, R aa R bb Or R ccEach is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy.

[0438] In a preferred embodiment of the present invention, R aa R bb Forming C with the attached atoms 3-6 Cycloalkyl or containing 1-4 4-6 membered heterocyclic groups selected from N, O or S heteroatoms.

[0439] In a preferred embodiment of the present invention, R aa R bb It forms pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups with the attached atoms. It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0440] In a preferred embodiment of the present invention, R1, R2, R3, or R4 are each independently selected from hydrogen, fluorine, chlorine, bromine, amino, oxo, methylamino, dimethylamino, hydroxy, cyano, nitro, carboxyl, methyl, ethyl, isopropyl, tert-butyl, n-butyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, difluorovinyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, cyclopropoxy, hydroxymethyl, hydroxyethyl, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SF5, -B(OH)2, -SCF3, -CH2COOH, -S(O)OH, -C(O)NH2.

[0441] In a preferred embodiment of the present invention, R3, R4 and the atoms connected to them form It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0442] In a preferred embodiment of the invention, when y is 2, 3 or 4, the two R2 atoms connected to them form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl.

[0443] In a preferred embodiment of the present invention, R1, R2, R3, or R4 are each independently selected from hydrogen, fluorine, carboxyl, methyl, isopropyl, methoxy, trifluoromethyl, -SF5, -B(OH)2, etc.

[0444] In a preferred embodiment of the present invention, R1, R2, R3, or R4 are each independently selected from hydrogen, fluorine, carboxyl, methyl, isopropyl, methoxy, trifluoromethyl, -SF5, -B(OH)2, etc. And at least one R4 is selected from carboxyl groups.

[0445] In a preferred embodiment of the present invention, R1, R2, R3, or R4 are each independently selected from hydrogen, carboxyl, methyl, methoxy, or...

[0446] In a preferred embodiment of the present invention, R1, R2, R3 or R4 are each independently selected from hydrogen, carboxyl, methyl or methoxy.

[0447] In a preferred embodiment of the present invention, at least one R4 is selected from a carboxyl group.

[0448] In a preferred embodiment of the present invention, R1, R2, R3, or R4 are each independently selected from hydrogen, carboxyl, methyl, methoxy, or... And at least one R4 is selected from carboxyl groups.

[0449] In a preferred embodiment of the invention, R1, R2, R3 or R4 are each independently selected from hydrogen, carboxyl, methyl or methoxy, and at least one R4 is selected from carboxyl.

[0450] In some embodiments of the present invention, ring A is selected from C. 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 Aryl or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P or B atoms, optionally surrounded by hydrogen, halogen, amino, hydroxyl, mercapto, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-14Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, carboxyl, -S(CR) aa R bb ) m1 R 31 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 One or more substituents are substituted in the sample.

[0451] In a preferred embodiment of the present invention, ring A is selected from C. 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, or C. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in an alkyl group are substituted.

[0452] In a preferred embodiment of the present invention, ring A is selected from C. 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally surrounded by hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1- One or more substituents in the 3 alkyl group are substituted.

[0453] In a preferred embodiment of the present invention, ring A is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1- One or more substituents in the 3 alkyl group are substituted.

[0454] In a preferred embodiment of the present invention, ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and... The radical can be optionally covered by hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl. One or more substituents are substituted in the sample.

[0455] In a preferred embodiment of the present invention, ring A is selected from... It may optionally be substituted with one or more of the following substituents: hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0456] In a preferred embodiment of the present invention, ring A is selected from...

[0457] In a preferred embodiment of the present invention, ring A is selected from...

[0458] In some embodiments of the present invention, ring B is selected from C. 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14Aryl or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P or B atoms, optionally surrounded by hydrogen, halogen, amino, hydroxyl, mercapto, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, carboxyl, -S(CR) aa R bb ) m1 R 31 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample.

[0459] In a preferred embodiment of the present invention, ring B is selected from C.3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl or 5-14 membered heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 A aryl group or a 5-14 membered heteroaryl group containing 1-4 N, O, S, P or B atoms, optionally surrounded by hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample.

[0460] In a preferred embodiment of the present invention, ring B is selected from C. 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, 5-8 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, a 5-8 membered mono-heteroaryl containing 1-4 N, O, S, P or B atoms, or an 8-14 membered fused heteroaryl containing 1-4 N, O, S, P or B atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample.

[0461] In a preferred embodiment of the present invention, ring B is selected from C. 3-6 Monocycloalkyl, C 6-14 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P, or B atoms, 5-9 membered spirocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P, or B atoms, C 6-14 Aryl, 5-6 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-6 Monocycloalkyl, C 6-14 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P, or B atoms, 5-9 membered spirocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P, or B atoms, C 6-14 Aryl, a 5-6 membered mono-heteroaryl containing 1-4 N, O, S, P or B atoms, or an 8-14 membered fused heteroaryl containing 1-4 N, O, S, P or B atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb COOH, -S(O) m2 R 32 -S(O)(=NR) cc )R 32 -BR 31 R 32 、-(NR 31 )C(O)R 32 -C(O)C(O)R 31 -C(O)NR 31 R 32 or -S(O) m2 NR 31 R 32 One or more substituents are substituted in the sample.

[0462] In a preferred embodiment of the present invention, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, The following groups are optionally covered: hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -(CH=CH)COOH, -B(OH)2, -CH2COOH, -S(O)OH, -C(O)NH2. One or more substituents are substituted in the sample.

[0463] In a preferred embodiment of the present invention, ring B is selected from cyclohexyl, phenyl, ... Optional radicals include hydrogen, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -B(OH)2, or... One or more substituents are substituted in the sample.

[0464] In a preferred embodiment of the present invention, ring B is selected from cyclohexyl, phenyl, ...

[0465] In some embodiments of the present invention, ring C is selected from C. 3-14 Cycloalkyl groups, containing 1-5 3-14 membered heterocyclic groups selected from N, O, S, P, B, or Si atoms, C6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 Aryl or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P or B atoms, optionally surrounded by hydrogen, halogen, amino, hydroxyl, mercapto, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1- 6-alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, carboxyl, -S(CR) aa R bb ) m1 R 31 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 One or more substituents are substituted in the sample.

[0466] In some embodiments of the present invention, ring C is absent.

[0467] In a preferred embodiment of the present invention, ring C is selected from C. 3-10 Cycloalkyl groups, 3-12 membered heterocyclic groups containing 1-5 N, O, S, P, B or Si atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-12 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, or C. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 2-3 Haloalkenyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl or -S(CR) aa R bb ) m1 R 31 One or more substituents are substituted in the sample.

[0468] In a preferred embodiment of the present invention, ring C is selected from C. 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P, B or Si atoms, 4-12 membered fused heterocyclic groups containing 1-5 N, O or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P, B or Si atoms, 4-12 membered fused heterocyclic groups containing 1-5 N, O or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally surrounded by hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 2-3 Haloalkenyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C1-3 Alkyl or -S(CR) aa R bb )R 31 One or more substituents are substituted in the sample.

[0469] In a preferred embodiment of the present invention, ring C is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P, B or Si atoms, 6-12 membered fused heterocyclic groups containing 1-5 N, O or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P, B or Si atoms, 6-12 membered fused heterocyclic groups containing 1-5 N, O or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl, 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 2-3 Haloalkenyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl or -SR 31 One or more substituents are substituted in the sample.

[0470] In a preferred embodiment of the present invention, cycloC is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and... It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, or -SCF3.

[0471] In a preferred embodiment of the present invention, ring C is selected from... It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

[0472] In some embodiments of the present invention, ring D is selected from C. 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 Aryl or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P or B atoms, optionally surrounded by hydrogen, halogen, amino, hydroxyl, mercapto, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, carboxyl, -S(CR) aa R bb ) m1 R 31 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 One or more substituents are substituted in the sample.

[0473] In a preferred embodiment of the present invention, ring D is selected from C. 3-10 Cycloalkyl groups, 3-12 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-12 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, or C. 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-10 One or more substituents of cycloalkyl, -SF5 or -SCF3 are used for substitution.

[0474] In a preferred embodiment of the present invention, ring D is selected from C. 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-12 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-12 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally surrounded by hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-8 One or more of the following substituents are selected from cycloalkyl, -SF5, or -SCF3: substituted.

[0475] In a preferred embodiment of the present invention, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-11 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 Polycyclic alkyl, C 5-9 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-11 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-6 One or more of the following substituents are selected from cycloalkyl, -SF5, or -SCF3: substituted.

[0476] In a preferred embodiment of the present invention, cycloD is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyridine, pyrimidine, pyridazine, etc. Optional radicals include hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, n-butyl, propynyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, -SF5, -SCF3. One or more substituents are substituted in the sample.

[0477] In a preferred embodiment of the present invention, ring D is selected from cyclobutyl, cyclohexyl, phenyl, Optional radicals include hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, propynyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, -SF5, or One or more substituents are substituted in the sample.

[0478] The present invention further provides a compound of general formula (MA) or a pharmaceutically acceptable salt thereof:

[0479] in:

[0480] P1 is selected from a carboxyl protecting group;

[0481] L1 is -NHC(O)-;

[0482] Ring D is selected from

[0483] n1 is 1, n2 is 1;

[0484] The definitions of R1, R2, x, and y are as described in general formula (III-1).

[0485] In certain preferred embodiments of the present invention, P1 is selected from methyl, ethyl, isopropyl, tert-butyl, or benzyl.

[0486] The present invention further provides a method for preparing a compound of the general formula as described above or a pharmaceutically acceptable salt thereof, comprising the following steps:

[0487] in:

[0488] The definitions of rings B, D, R1, R2, R3, R4, L1, X5, X6, X7, X8, X9, x, y, z, and t are as described in general formula (III-1); L2 is -C(O)NH-;

[0489] General formulas (M-1A) and (M-1B) react under the action of a condensing agent and a base to give general formula (III-1).

[0490] In some preferred embodiments of the present invention, the condensing agent in the preparation method is selected from EDCI, DIC, DCC, TBTU, HATU, HBTU, HCTU, DEPBT, PyBOP, or PyAOP.

[0491] In some preferred embodiments of the present invention, the alkali used in the preparation method is selected from DIEA, TEA, NMP, DBU or DABCO.

[0492] In some preferred embodiments of the present invention, the condensing agent in the preparation method is selected from EDCI or HATU, and the alkali is selected from DIEA.

[0493] In some preferred embodiments of the present invention, the preparation method, when at least one R4 is selected from C(O)O-PG1, further includes a step of removing the protecting group PG1 under the action of acid or base.

[0494] In certain preferred embodiments of the present invention, in the step of removing the protecting group PG1 under the action of acid or base, PG1 is selected from methyl, ethyl, isopropyl, tert-butyl, or benzyl; the base is selected from LiOH, NaOH, KOH, or Cs2CO3; and the acid is selected from hydrochloric acid, formic acid, acetic acid, MSA, or TFA.

[0495] In certain preferred embodiments of the present invention, in the step of removing the protecting group PG1 under the action of acid or base, PG1 is selected from methyl or tert-butyl; the base is selected from LiOH; and the acid is selected from MSA or TFA.

[0496] The present invention further provides a method for preparing a compound of the general formula as described above or a pharmaceutically acceptable salt thereof, comprising the following steps:

[0497] in:

[0498] The definitions of rings B, D, R1, R2, R3, R4, L2, X5, X6, X7, X8, X9, x, y, z, and t are as described in general formula (III-1); L1 is -NHC(O)-;

[0499] General formulas (M-2A) and (M-2B) react with a carbonylating agent and a base to give general formula (III-1).

[0500] In some preferred embodiments of the present invention, the carbonylating agent in the preparation method is selected from CDI, triphosgene, diester carbonate or isocyanate.

[0501] In some preferred embodiments of the present invention, the alkali used in the preparation method is selected from DIEA, TEA, NMP, DBU, DABCO or NMM.

[0502] In some preferred embodiments of the present invention, the carbonylating agent in the preparation method is selected from CDI or triphosgene, and the base is selected from TEA, DBU or NMM.

[0503] In some preferred embodiments of the present invention, the preparation method, when at least one R4 is selected from C(O)O-PG1, further includes a step of removing the protecting group PG1 under the action of acid or base.

[0504] In certain preferred embodiments of the present invention, in the step of removing the protecting group PG1 under the action of acid or base, PG1 is selected from methyl, ethyl, isopropyl, tert-butyl, or benzyl; the base is selected from LiOH, NaOH, KOH, or Cs2CO3; and the acid is selected from hydrochloric acid, formic acid, acetic acid, MSA, or TFA.

[0505] In certain preferred embodiments of the present invention, in the step of removing the protecting group PG1 under the action of acid or base, PG1 is selected from methyl or tert-butyl; the base is selected from LiOH; and the acid is selected from MSA or TFA.

[0506] The present invention further relates to a pharmaceutical composition comprising a therapeutically effective dose of any of the shown general formula compounds, their stereoisomers or pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0507] In some embodiments of the invention, the pharmaceutical composition, based on free base, comprises 0.1% to 95% by weight of the compound, its stereoisomers, or a pharmaceutically acceptable salt thereof, preferably 5% to 70%, for example 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5%.

[0508] In some embodiments of the invention, the pharmaceutical composition is selected from tablets, capsules, liquid formulations or injections, preferably also containing a filler, optionally a disintegrant, or further containing one or more of a flow aid or lubricant.

[0509] In some embodiments of the present invention, the pharmaceutical composition is an immediate-release formulation or a sustained-release formulation.

[0510] In some embodiments of the invention, the unit dose of the pharmaceutical composition, calculated as free base, of the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof is 1-1000 mg, preferably 1-500 mg, or preferably 1 mg, 2 mg, 3 mg, 5 mg, 10 mg, 20 mg, 40 mg, 50 mg, 60 mg, 80 mg, 100 mg, 200 mg, 300 mg, 400 mg, or 500 mg.

[0511] In some embodiments of the invention, the compound or a pharmaceutically acceptable salt thereof may be administered by any convenient method, such as oral, parenteral, oral, sublingual, nasal, rectal, intrathecal, or transdermal administration, and accordingly modified pharmaceutical compositions.

[0512] In some embodiments of the invention, the compound or a pharmaceutically acceptable salt thereof may be formulated into liquid or solid dosage forms, such as syrups, suspensions, emulsions, tablets, capsules, powders, granules, or lozenges.

[0513] The present invention further relates to the use of any of the compounds of the general formula shown or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof, in the preparation of a medicament for treating diseases related to GIPR.

[0514] The present invention further relates to compounds of the general formula or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the preparation of treatments for diabetes, obesity, NASH, kidney disease and related conditions, more preferably type I diabetes, type II diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease, renal tubular dysfunction, proximal tubular pro-inflammatory changes, chronic kidney disease, diabetic retinopathy, obesity, glomerulosclerosis, chronic renal failure, metabolic syndrome, obesity or NASH.

[0515] The present invention further relates to a compound of the general formula or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in a method for preparing a medicament for treating GIPR-related and related diseases.

[0516] The present invention also relates to a method for treating, preventing, and / or treating diseases associated with GIPR, comprising administering to a patient a therapeutically effective dose of a compound of the general formula, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0517] The present invention also provides a method for treating disease conditions using the compounds or pharmaceutical compositions of the present invention, including but not limited to conditions related to GIPR.

[0518] The present invention also relates to a method for treating GIPR-related diseases in mammals, comprising administering to the mammal a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate, or derivative thereof.

[0519] Detailed description of the invention

[0520] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0521] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight-chain or branched group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 8 carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms, and most preferably an alkyl group containing 1 to 3 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2, 3-Dimethylpentyl, 2,4-Dimethylpentyl, 2,2-Dimethylpentyl, 3,3-Dimethylpentyl, 2-Ethylpentyl, 3-Ethylpentyl, n-Octyl, 2,3-Dimethylhexyl, 2,4-Dimethylhexyl, 2,5-Dimethylhexyl, 2,2-Dimethylhexyl, 3,3-Dimethylhexyl, 4,4-Dimethylhexyl, 2-Ethylhexyl, 3-Ethylhexyl, 4-Ethylhexyl, 2-Methyl-2-Ethylpentyl, 2-Methyl-3-Ethylpentyl, n-Nonyl, 2-Methyl-2-Ethylhexyl, 2-Methyl-3-Ethylhexyl, 2,2-Diethylpentyl, n-Decyl, 3,3-Diethylhexyl, 2,2-Diethylhexyl, and their various branched isomers, etc. More preferably, lower alkyl groups containing 1 to 6 carbon atoms are used. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, etc. Alkyl groups can be substituted or unsubstituted. When substituted, the substituents can be substituted at any usable connection point. The substituents are preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl, or carboxylic acid ester groups. The present invention preferably uses methyl, ethyl, isopropyl, tert-butyl, haloalkyl, alkoxy-substituted alkyl, and hydroxy-substituted alkyl.

[0522] The term "alkylene" refers to an alkyl group in which one hydrogen atom is further substituted, for example: "methylene" refers to -CH2-, "ethylene" refers to -(CH2)2-, "propylene" refers to -(CH2)3-, "butylene" refers to -(CH2)4-, etc. The term "alkenyl" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon double bond, such as vinyl, 1-propenyl, 2-propenyl, 1-, 2-, or 3-butenyl, etc. Alkenyl groups can be substituted or unsubstituted; when substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, and heterocycloalkylthio.

[0523] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, wherein the cycloalkyl ring contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, and more preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, cyclooctyl, etc.; polycyclic cycloalkyl groups include spirocyclic, fused-ring, and bridged-ring cycloalkyl groups, preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, and cycloheptyl.

[0524] The term "spirocycloalkyl" refers to a polycyclic group consisting of 5 to 20 quintile rings sharing a single carbon atom (called a spiro atom), which may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Preferably, it is 6 to 14 quintiles, more preferably 7 to 10 quintiles. Spirocycloalkyl groups are classified into monospirocycloalkyl, bispirocycloalkyl, or polyspirocycloalkyl groups based on the number of shared spiro atoms between the rings, with monospirocycloalkyl and bispirocycloalkyl groups being preferred. More preferably, it is a 3 / 6, 3 / 5, 4 / 4, 4 / 5, 4 / 6, 5 / 5, or 5 / 6 quintile monospirocycloalkyl group. Non-limiting examples of spirocycloalkyl groups include:

[0525] wait;

[0526] It also includes spirocyclic alkyl groups that share a spiro atom with a heterocyclic alkyl group, and non-limiting examples include:

[0527] wait.

[0528] The term "fused-ring alkyl" refers to a 5- to 20-membered polycyclic carbon group in which each ring in the system shares an adjacent pair of carbon atoms with other rings in the system, wherein one or more rings may contain one or more double bonds, but no ring has a fully conjugated π-electron system. Preferably, it is 6- to 14-membered, more preferably 7- to 10-membered. Depending on the number of constituent rings, it can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic fused-ring alkyl, preferably bicyclic or tricyclic, more preferably 5-membered / 5-membered or 5-membered / 6-membered bicyclic alkyl. Non-limiting examples of fused-ring alkyl include:

[0529] wait.

[0530] The term "bridged cycloalkyl" refers to a 5- to 20-membered polycyclic carbon group in which any two rings share two non-directly bonded carbon atoms. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Preferably, it is 6- to 14-membered, more preferably 7- to 10-membered. Depending on the number of rings, it can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic bridged cycloalkyl, preferably bicyclic, tricyclic, or tetracyclic, and more preferably bicyclic or tricyclic. Non-limiting examples of bridged cycloalkyl groups include:

[0531] The cycloalkyl ring may be fused to an aryl, heteroaryl, or heterocycloalkyl ring, wherein the ring connected to the parent structure is a cycloalkyl group, and non-limiting examples include indanyl, tetrahydronaphthyl, benzocycloheptyl, etc. The cycloalkyl group may be optionally substituted or unsubstituted; when substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl, or carboxylic acid ester group.

[0532] The term "heterocyclic group" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, one or more of which are selected from nitrogen, oxygen, boron, silicon, S(O). m Heteroatoms of P(O)n (where m is an integer from 0 to 2) or P(O)n (where n is an integer from 0 to 2), but excluding the ring portion of -OO-, -OS-, or -SS-, with the remaining ring atoms being carbon. Preferably, it contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms; more preferably, it contains 3 to 8 ring atoms; most preferably, it contains 3 to 8 ring atoms; even more preferably, it contains a 3-8 membered heterocyclic group containing 1 to 3 nitrogen atoms, optionally substituted with 1 to 2 oxygen atoms, sulfur atoms, or oxo groups, including nitrogen-containing monocyclic heterocyclic groups, nitrogen-containing spirocyclic groups, or nitrogen-containing fused heterocyclic groups.

[0533] Non-limiting examples of monocyclic heterocyclic groups include pyrrolyl, imidazoyl, tetrahydrofuranyl, tetrahydrothiophenyl, dihydroimidazoyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, acrylonitrile, 1,4-diazaheptanyl, pyranyl, etc., preferably pyrrolyl, morpholinyl, piperidinyl, acrylonitrile, 1,4-diazaheptanyl, and piperazinyl. Polycyclic heterocyclic groups include spirocyclic, fused-ring, and bridged-ring heterocyclic groups; wherein the spirocyclic, fused-ring, and bridged-ring heterocyclic groups involved are optionally connected to other groups by single bonds, or further cyclically linked to other cycloalkyl, heterocyclic, aryl, and heteroaryl groups by any two or more atoms on the ring.

[0534] The term "spiroheterocyclic group" refers to a polycyclic heterocyclic group consisting of 5 to 20 member monocyclic rings sharing a single atom (called a spiro atom), wherein one or more ring atoms are selected from nitrogen, oxygen, boron, silicon, and S(O). m Heteroatoms of type P(O)n (where m is an integer from 0 to 2) or P(O)n (where n is an integer from 0 to 2), with the remaining ring atoms being carbon. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Preferably, it is 6 to 14-membered, more preferably 7 to 10-membered. Spirocyclic groups are classified into monospirocyclic, bispirocyclic, or multispirocyclic groups based on the number of shared spiro atoms between rings, preferably monospirocyclic and bispirocyclic groups. More preferably, it is a 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered, or 5-membered / 6-membered monospirocyclic group. Non-limiting examples of spirocyclic groups include:

[0535] wait.

[0536] The term "fused heterocyclic group" refers to a 5- to 20-membered polycyclic heterocyclic group in which each ring in the system shares an adjacent pair of atoms with the other rings in the system. One or more rings may contain one or more double bonds, but no ring has a fully conjugated π-electron system. One or more ring atoms are selected from nitrogen, oxygen, boron, silicon, and S(O). m The heteroatoms are either P(O)n (where m is an integer from 0 to 2) or P(O)n (where n is an integer from 0 to 2), and the remaining ring atoms are carbon. Preferably, they are 6 to 14-membered, more preferably 7 to 10-membered. Depending on the number of rings, they can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic fused heterocyclic groups, preferably bicyclic or tricyclic, more preferably 5-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclic groups. Non-limiting examples of fused heterocyclic groups include:

[0537] wait.

[0538] The term "bridged heterocyclic group" refers to a 5- to 14-membered polycyclic heterocyclic group in which any two rings share two non-directly connected atoms. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. One or more ring atoms are selected from nitrogen, oxygen, boron, silicon, and S(O). m The heteroatom is either P(O)n (where m is an integer from 0 to 2) or P(O)n (where n is an integer from 0 to 2), and the remaining ring atoms are carbon. Preferably, it is 6 to 14-membered, more preferably 7 to 10-membered. Depending on the number of rings, it can be classified as a bicyclic, tricyclic, tetracyclic, or polycyclic bridged heterocyclic group, preferably bicyclic, tricyclic, or tetracyclic, and more preferably bicyclic or tricyclic. Non-limiting examples of bridged heterocyclic groups include:

[0539] wait.

[0540] The heterocyclic ring may be fused to an aryl, heteroaryl, or cycloalkyl ring, wherein the ring connected to the parent structure is a heterocyclic group, and non-limiting examples include:

[0541] wait.

[0542] The heterocyclic group can be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl, or carboxylic acid ester group.

[0543] The term "aryl" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., a ring sharing adjacent carbon atom pairs) group having a conjugated π-electron system, preferably 6- to 12-membered, such as phenyl and naphthyl. More preferably phenyl. The aryl ring may be fused to a heteroaryl, heterocyclic, or cycloalkyl ring, including benzo5- to 10-membered heteroaryl, benzo3- to 8-membered cycloalkyl, and benzo3- to 8-membered heteroalkyl, preferably benzo5- to 6-membered heteroaryl, benzo3- to 6-membered cycloalkyl, and benzo3- to 6-membered heteroalkyl, wherein the heterocyclic group is a heterocyclic group containing 1-3 nitrogen, oxygen, and sulfur atoms; or may further include a ternary nitrogen-containing fused ring containing a benzene ring.

[0544] The ring connected to the parent structure is an aryl ring, and non-limiting examples include:

[0545] wait.

[0546] The aryl group can be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylic acid ester group.

[0547] The term "heteroaryl" refers to a heteroaryl system comprising 1 to 4 heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. The heteroaryl group is preferably 5 to 12-membered, more preferably 5- or 6-membered, such as imidazolyl, furanyl, thiophene, thiazolyl, pyrazolyl, oxazolyl, pyrroleyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, thiadiazole, pyrazinyl, etc., preferably triazolyl, thiophene, imidazolyl, pyrazolyl, oxazolyl, pyrimidinyl, or thiazolyl; more preferably pyrazolyl, pyrroleyl, and oxazolyl. The heteroaryl ring may be fused to an aryl, heterocyclic, or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaryl ring, and non-limiting examples include:

[0548] wait.

[0549] The heteroaryl group can be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylic acid ester group.

[0550] The term "alkoxy" refers to -O- (alkyl) and -O- (unsubstituted cycloalkyl), where alkyl is defined as described above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, and cyclohexoxy. Alkoxy groups can be optionally substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl, or carboxylic acid ester group.

[0551] "Halogenated alkyl" refers to an alkyl group that has been substituted with one or more halogens, wherein the alkyl group is as defined above.

[0552] "Haloalkoxy" refers to an alkoxy group that has been substituted by one or more halogens, wherein the alkoxy group is as defined above.

[0553] "Hydroxyalkyl" refers to an alkyl group that has been replaced by a hydroxyl group, where the alkyl group is as defined above.

[0554] "Alkenyl" refers to an alkenyl group, also known as an olefinic group, which is a straight-chain or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon double bond, and the carbon-carbon double bond can be located anywhere within the alkenyl group. Alkenyl groups have a carbon density of 2 to 20 carbon atoms. 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12 ), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ), 2 to 4 (C 2-4 ) or 2 to 3 (C 2-3 A straight-chain or branched unsaturated hydrocarbon group containing 1 carbon atom. Non-limiting examples of alkenyl groups include: The alkenyl group described therein may be further substituted with other related groups, such as: alkyl, alkenyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylic acid ester group.

[0555] "Alynyl" refers to (CH≡C-) that contains at least one carbon-carbon triple bond, which can be located anywhere within the alkynyl group, and at least one carbon-carbon double bond, which can be located anywhere within the alkenyl group. The alkynyl group has 2 to 20 carbon atoms. 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12 ), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ), 2 to 4 (C 2-4 ) or 2 to 3 (C 2- 3) A straight-chain or branched unsaturated hydrocarbon group containing one carbon atom. Non-limiting examples of alkynyl groups include: The alkynyl group may be further substituted with other related groups, such as alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylic acid ester group.

[0556] The term "alkenyl carbonyl" refers to -C(O)-(alkenyl), where alkenyl is defined as described above. Non-limiting examples of alkenyl carbonyl include vinyl carbonyl, propenyl carbonyl, and butenyl carbonyl. Alkenyl carbonyl can be optionally substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl, or carboxylic acid ester.

[0557] "Hydroxy" refers to the -OH group.

[0558] "Halogen" refers to fluorine, chlorine, bromine, or iodine.

[0559] "Amino" refers to -NH2.

[0560] “Cyano” refers to -CN.

[0561] "Nitro" refers to -NO2.

[0562] "Carbonyl" refers to -C(O)-.

[0563] "Carboxyl group" refers to -C(O)OH.

[0564] "THF" refers to tetrahydrofuran.

[0565] “EtOAc” refers to ethyl acetate.

[0566] “MeOH” refers to methanol.

[0567] "DMF" refers to N,N-dimethylformamide.

[0568] "TFA" refers to trifluoroacetic acid.

[0569] “MeCN” refers to Yi Qing.

[0570] “DMA” stands for N,N-dimethylacetamide.

[0571] “Et2O” refers to diethyl ether.

[0572] “DCE” refers to 1,2-dichloroethane.

[0573] "DIPEA" refers to N,N-diisopropylethylamine.

[0574] “NBS” refers to N-bromosuccinimide.

[0575] “NIS” refers to N-iodosuccinimide.

[0576] “DIEA” refers to N,N-diisopropylethylamine.

[0577] “EDCI” refers to 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride.

[0578] “DIC” refers to N,N'-diisopropylcarbodiimide.

[0579] “DCC” refers to N,N'-dicyclohexylcarboimide.

[0580] “TBTU” refers to O-benzotriazole-N,N,N',N'-tetramethylureatetrafluoroboric acid.

[0581] “HATU” refers to 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate.

[0582] “HBTU” refers to benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate.

[0583] “HCTU” refers to 6-chlorobenzotriazole-1,1,3,3-tetramethylurea hexafluorophosphate.

[0584] “DEPBT” refers to 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazine-4-one.

[0585] “PyBOP” refers to benzotriazol-1-yl-oxytripyrrolidinyl phosphate hexafluorophosphate.

[0586] “PyAOP” refers to hexafluorophosphate (7-azabenzotriazole-1-oxy)tripyrrolidinephosphide.

[0587] "TEA" refers to triethylamine.

[0588] “NMP” refers to N-methylpyrrolidone.

[0589] “DBU” refers to 1,8-diazahexacyclic[5,4,0]undecene-7.

[0590] “DABCO” refers to 1,4-diazabicyclo[2.2.2]octane.

[0591] “CDI” refers to N,N'-carbonyldiimidazole.

[0592] “NMM” refers to N-methylmorpholine.

[0593] “MSA” stands for melanin.

[0594] This indicates that the site is selected from either a single bond or a double bond.

[0595] “N / A” means not detected.

[0596] The different terms such as "X is selected from A, B, or C", "X is selected from A, B, and C", "X is A, B, or C", and "X is A, B, and C" all express the same meaning, that is, X can be any one or more of A, B, and C.

[0597] All hydrogen atoms described in this invention can be replaced by their isotope deuterium, and any hydrogen atom in the compounds of the embodiments of this invention can also be replaced by a deuterium atom.

[0598] The compounds of this invention include all pharmaceutically acceptable isotopically labeled compounds, wherein one or more atoms of the compounds disclosed herein are replaced by atoms having the same atomic number but a different atomic mass or mass number than those commonly found. Examples of isotopes that may be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, and examples of isotopes include tritium, etc.

[0599] "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 absence of such event or environment. For example, "optionally alkyl-substituted heterocyclic group" means that the alkyl group may but does not have to be present, and the description includes cases where the heterocyclic group is substituted with an alkyl group and cases where the heterocyclic group is not substituted with an alkyl group.

[0600] "Substituted" refers to one or more hydrogen atoms in a group, preferably up to five, and more preferably one to three hydrogen atoms, which are independently substituted by the corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without much effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom having an unsaturated bond (such as an alkene).

[0601] "Pharmaceutical composition" means a mixture containing one or more of the compounds described herein or their physiologically / pharmacologically acceptable salts or prodrugs, along with other chemical components, such as physiologically / pharmacologically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and the exertion of its biological activity.

[0602] "Pharmaceutical acceptable salt" or "medicinal salt" refers to the salts of the compounds of this invention, which are safe and effective when used in mammals and have the appropriate biological activity.

[0603] The compounds of this invention, such as those of formulas (I) to (V-11A) or specific compounds, are intended to include one or more of the following: a free base of the compound or a pharmaceutically acceptable salt thereof, a stereoisomer, or a mixture of two or more stereoisomers. A stereoisomer is a compound that differs only in its spatial arrangement. Stereoisomers include all diastereomers and enantiomers of the compound. An enantiomer is a stereoisomer that is a mirror image of another. A diastereomer is a stereoisomer having two or more distinct chiral centers that are not mirror images of each other. Detailed Implementation

[0604] Example

[0605] 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 ohms. -6 The unit (ppm) is given. NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0606] MS measurements were performed using a Finnigan LCQAd (ESI) mass spectrometer (manufacturer: Thermo, model: Finnigan LCQ advantage MAX).

[0607] HPLC determinations were performed using an Agilent 1200DAD high-performance liquid chromatograph (Sunfire C18 150×4.6mm column) and a Waters 2695-2996 high-performance liquid chromatograph (Gimini C18 150×4.6mm column).

[0608] Mean inhibition rate of kinases and IC 50 The values ​​were determined using a NovoStar microplate reader (BMG GmbH, Germany).

[0609] Thin-layer chromatography silica gel plates are Yantai Huanghai HSGF254 or Qingdao GF254. The silica gel plates used in thin-layer chromatography (TLC) have a diameter of 0.15 mm to 0.2 mm, and the diameter of the silica gel plates used for thin-layer chromatography separation and purification products is 0.4 mm to 0.5 mm.

[0610] Column chromatography typically uses Yantai Huanghai silica gel with a mesh size of 200-300 as the carrier.

[0611] The known starting materials of this invention can be synthesized using or according to methods known in the art, or can be purchased from companies such as ABCR GmbH & Co. KG, Acros Organics, Aldrich Chemical Company, Accela ChemBio Inc, and Darui Chemicals.

[0612] Unless otherwise specified in the examples, the reactions can be carried out under an argon or nitrogen atmosphere.

[0613] Argon or nitrogen atmosphere refers to a reaction flask connected to an argon or nitrogen gas balloon with a volume of approximately 1L.

[0614] A hydrogen atmosphere refers to a reaction vessel connected to a hydrogen balloon with a volume of approximately 1L.

[0615] The pressurized hydrogenation reaction was performed using a Parr 3916EKX hydrogenator and a Qinglan QL-500 hydrogen generator or an HC2-SS hydrogenator.

[0616] The hydrogenation reaction is usually carried out under vacuum, filled with hydrogen gas, and repeated 3 times.

[0617] The microwave reaction was performed using a CEM Discover-S 908860 microwave reactor.

[0618] Unless otherwise specified in the examples, "solution" refers to an aqueous solution.

[0619] Unless otherwise specified in the examples, the reaction temperature is room temperature, which is 20℃~30℃.

[0620] The reaction process in the examples was monitored using thin-layer chromatography (TLC). The developing solvent systems used in the reactions were: A: dichloromethane and methanol system, B: n-hexane and ethyl acetate system, C: petroleum ether and ethyl acetate system, and D: acetone. The volume ratio of the solvents was adjusted according to the polarity of the compounds.

[0621] The eluent systems for column chromatography and the developing solvent systems for thin-layer chromatography used to purify the compounds include: A: dichloromethane and methanol system, B: n-hexane and ethyl acetate system, and C: dichloromethane and acetone system. The volume ratio of the solvents is adjusted according to the polarity of the compounds, and small amounts of basic or acidic reagents such as triethylamine and acetic acid can also be added for adjustment.

[0622] Synthetic intermediate 1

[0623] ((3-Fluoro-4-isopropylphenyl)carbamoyl)-D-proline

[0624] first step

[0625] 4-Bromo-3-fluoroaniline (10.00 g, 52.63 mmol), pinacol isopropenylborate (17.69 g, 105.26 mmol), potassium carbonate (21.82 g, 157.88 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (1.16 g, 1.58 mmol) were dissolved in 1,4-dioxane (100 mL) and water (10 mL). The mixture was purged with nitrogen three times, and the reaction mixture was stirred at 90 °C for 16 hours. The reaction was cooled to room temperature, quenched with water (100 mL), and extracted with ethyl acetate (100 mL x 3). The organic phase was dried, concentrated, and the residue was purified by silica gel column chromatography (elution system THF / PE = 0-40%) to give 3-fluoro-4-(prop-1-en-2-yl)aniline (14.30 g, 55% purity), yield: 98.8%. MS m / z (ESI): 152 [M+H] +

[0626] Step 2

[0627] 3-Fluoro-4-(prop-1-en-2-yl)aniline (14.30 g, 55% purity, 52.02 mmol) and 5% wet palladium / carbon (6.32 g) were dissolved in methanol (150 mL), and formic acid (5 mL) was added. The mixture was purged three times with a hydrogen balloon and stirred at 20 °C for 16 hours. The mixture was filtered through diatomaceous earth, washed with methanol (50 mL), and concentrated. The residue was purified by silica gel column chromatography (elution system THF / PE = 0-30%) to give 3-fluoro-4-isopropylaniline (7.0 g, 45.75 mmol), yield: 87.8%. MS m / z (ESI): 154 [M+H] +

[0628] Step 3

[0629] Under ice-water bath cooling, 3-fluoro-4-(prop-1-en-2-yl)aniline (4.00 g, 26.11 mmol) was added to a carbonyl diimidazole (4.23 g, 26.11 mmol) solution in acetonitrile (70 mL). After 5 minutes, the mixture was heated to 20 °C and stirred for 2 hours. Subsequently, the reaction solution was removed under reduced pressure, and then dissolved in tetrahydrofuran (50 mL). N-methylmorpholine and D-proline were added sequentially. After stirring at 20 °C for 6 hours until the reaction was complete, the reaction was quenched with sodium bicarbonate (50 mL), extracted with diethyl ether (30 mL x 2), the aqueous phase was adjusted to pH 2–3 with 6N hydrochloric acid, and then extracted with ethyl acetate (50 mL x 3). The organic phase was dried and concentrated to give 3-fluoro-4-isopropylaniline (6.20 g, 95% purity, 20.01 mmol), yield: 76.6%. MS m / z(ESI): 295 [M+H] +

[0630] Synthetic intermediate 2

[0631] (R)-N-(3-fluoro-4-isopropylphenyl)pyrrole-2-carboxamide

[0632] first step

[0633] 3-Fluoro-4-isopropylaniline (150 mg, 0.98 mmol), tert-butyloxycarbonyl-D-proline (211 mg, 0.98 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbamoyldiimide hydrochloride (188 mg, 0.98 mmol) were dissolved in dichloromethane (10 mL) and stirred at 20 °C for 6 hours. The reaction mixture was quenched with water (100 mL), extracted with dichloromethane (30 mL x 3), dried over the organic phase, and concentrated to give crude (R)-2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carboxylic acid tert-butyl ester (351 mg). MS m / z (ESI): 351 [M+H] +

[0634] Step 2

[0635] To a solution of (R)-2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carboxylic acid tert-butyl ester (350 mg) in dichloromethane (10 mL), trifluoroacetic acid (2 mL) was added, and the mixture was stirred at 20 °C for 2 hours. The reaction solution was concentrated under reduced pressure to give the crude product (R)-N-(3-fluoro-4-isopropylphenyl)pyrrole-2-carboxamide (370 mg). MS m / z (ESI): 251 [M+H] +

[0636] Example A

[0637] 4-[4-({[1-({[4-(propyl-2-yl)phenyl]amino}carbonyl)azacyclohepta-2-yl]carbonyl}amino)phenyl]benzoic acid

[0638] Step 1: 2-(4-aminophenyl)benzoic acid-2-methylpropyl-2-yl ester

[0639] 4-Bromoaniline (2.06 g, 12 mmol) and (4-(tert-butoxycarbonyl)phenyl)boronic acid (2.66 g, 12 mmol) were dissolved in 1'-4-Dioxane (50 mL) and Water (10 mL). Under nitrogen protection, bis(triphenylphosphine)palladium dichloride (421 mg, 0.6 mmol) and potassium phosphate (6.36 g, 30 mmol) were added. The mixture was stirred at 90 °C for 5 hours. The mixture was evaporated to dryness, the reaction was quenched with saturated brine (100 mL), and extracted with ethyl acetate (50 mL × 3). The organic phases were combined, washed with saturated brine (50 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by rapid silica gel chromatography (petroleum ether:ethyl acetate = 100:0 to 50:50 elution) to give the target product (2.74 g, yield: 85%). MS m / z (ESI): 270.1 [M+H] + .

[0640] Step 2: 2-({[4-(4-{[(2-methylprop-2-yl)oxy]carbonyl}phenyl)phenyl]amino}carbonyl)azacycloheptane-1-carboxylic acid-2-methylprop-2-yl ester)

[0641] 2-Methylpropyl-2-yl 4-(4-aminophenyl)benzoate (2.5 g, 9.29 mmol), 1-{[(2-methylpropyl-2-yl)oxy]carbonyl}azacycloheptane-2-carboxylic acid (2.7 g, 11.1 mmol), and N,N-diisopropylethylamine (2.99 g, 23.2 mmol, 3.82 mL) were dissolved in N,N-dimethylformamide (20 mL). Under nitrogen protection, 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (4.59 g, 12 mmol) was added. The mixture was stirred at 25 °C for 12 hours. The mixture was then extracted with 150 mL of saturated brine and ethyl acetate (50 mL × 3). The organic phases were combined, washed successively with 50 mL of saturated brine (50 mL × 4), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by rapid silica gel chromatography (elution with petroleum ether:ethyl acetate = 100:0 to 60:40) to give the target product (3.8 g, yield: 83%). MS m / z (ESI): 495.3 [M+H] + .

[0642] Step 3: 4-{4-[(azacycloheptan-2-ylcarbonyl)amino]phenyl}benzoic acid

[0643] 2-({[4-(4-{[(2-methylprop-2-yl)oxy]carbonyl}phenyl)phenyl]amino}carbonyl)azacycloheptan-1-carboxylic acid-2-methylprop-2-yl ester (3.1 g, 6.3 mmol) was dissolved in dichloromethane (10 mL). Under ice-water bath cooling and nitrogen protection, dioxane hydrochloride (4 M, 30 mL) was added. The mixture was stirred at 0 °C for 3 hours. The reaction solution was evaporated to dryness, and the crude product (2.2 g) was used directly in the next step. MS m / z (ESI): 339.2 [M+H] + .

[0644] Step 4: 4-[4-({[1-({[4-(prop-2-yl)phenyl]amino}carbonyl)azacyclohepta-2-yl]carbonyl}amino)phenyl]benzoic acid

[0645] 4-{4-[(azacyclohepta-2-ylcarbonyl)amino]phenyl}benzoic acid (0.5 g, 1.48 mmol) and N-methylmorpholine (448 mg, 4.4 mmol) were dissolved in tetrahydrofuran (20 mL). Under ice-water bath cooling and nitrogen protection, 4-isocyano-1-(propane-2-yl)benzene (238 mg, 1.48 mmol) was added. The mixture was stirred at 25 °C for 4 hours. The reaction was quenched with saturated brine (5 mL). The mixture was separated, the organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product was separated by preparative high-performance liquid chromatography (HPLC) to obtain the final product (273 mg, yield: 37%). MS m / z (ESI): 500.2 [M+H] + .

[0646] Step 5: 4-[4-({[(2R)-1-({[4-(prop-2-yl)phenyl]amino}carbonyl)azacyclohepta-2-yl]carbonyl}amino)phenyl]benzoic acid and 4-[4-({[(2S)-1-({[4-(prop-2-yl)phenyl]amino}carbonyl)azacyclohepta-2-yl]carbonyl}amino)phenyl]benzoic acid

[0647] The target product was obtained by chiral separation using SFC (supercritical fluid chromatography). MS m / z (ESI): 500.2 [M+H] + Examples 2-47 refer to the synthesis method of Example A.

[0648] Example B: 4'-(4-(((3-fluoro-4-isopropylphenyl)amino)methyl)-7-methyl-6,7-dihydro-5H-cyclopentadien[b]pyridin-2-yl)-[1,1'-biphenyl]-4-carboxylic acid

[0649] Step 1: N-((2-bromo-7-methyl-6,7-dihydro-5H-cyclopentadieno[b]pyridin-4-yl)methyl)-3-fluoro-4-isopropylaniline

[0650] The synthesis of the starting material 2-bromo-7-methyl-6,7-dihydro-5H-cyclopentadieno[b]pyridine-4-carboxaldehyde is based on patent WO2023151636A1. 2-bromo-7-methyl-6,7-dihydro-5H-cyclopentadieno[b]pyridine-4-carboxaldehyde (2.4 g, 10 mmol) and 3-fluoro-4-isopropylaniline (1.53 g, 10 mmol) were dissolved in dichloromethane (50 mL), and sodium borohydride acetate (0.76 g, 20 mmol) was added. The mixture was stirred at 25 °C for 12 hours. The reaction was cooled to 0 °C, quenched with saturated ammonium chloride solution (30 mL), extracted with dichloromethane (50 mL × 3), the organic phases were combined, washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by rapid silica gel chromatography (elution with petroleum ether: ethyl acetate = 100:0 to 50:50) to give the target product (3.2 g, yield: 85%). MS m / z (ESI): 377.1 [M+H] + .

[0651] Step 2: Methyl 4'-(4-((((3-fluoro-4-isopropylphenyl)amino)methyl)-7-methyl-6,7-dihydro-5H-cyclopentadien[b]pyridin-2-yl)-[1,1'-biphenyl]-4-carboxylic acid ester

[0652] N-((2-bromo-7-methyl-6,7-dihydro-5H-cyclopentadieno[b]pyridin-4-yl)methyl)-3-fluoro-4-isopropylaniline (3.0 g, 8 mmol) and methyl 4'-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentane-2-yl)-[1,1'-biphenyl]-4-carboxylic acid ester (3.4 g, 10 mmol) were dissolved in 1',4-Dioxane (50 mL) and Water (10 mL). Under nitrogen protection, bis(triphenylphosphine)palladium dichloride (280 mg, 0.4 mmol) and potassium phosphate (4.2 g, 20 mmol) were added. The mixture was stirred at 90 °C for 5 hours. The mixture was evaporated to dryness, the reaction was quenched with saturated brine (100 mL), extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated brine (50 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by rapid silica gel chromatography (elution with petroleum ether: ethyl acetate = 100:0 to 50:50) to give the target product (3.2 g, yield: 78%). MS m / z (ESI): 509.3 [M+H] + .

[0653] Step 3: 4'-(4-(((3-fluoro-4-isopropylphenyl)amino)methyl)-7-methyl-6,7-dihydro-5H-cyclopentadien[b]pyridin-2-yl)-[1,1'-biphenyl]-4-carboxylic acid

[0654] Methyl 4'-(4-((((3-fluoro-4-isopropylphenyl)amino)methyl)-7-methyl-6,7-dihydro-5H-cyclopentadien[b]pyridin-2-yl)-[1,1'-biphenyl]-4-carboxylic acid ester (0.5 g, 1 mmol) was dissolved in THF (5 mL) and water (2 mL), and LiOH (72 mg, 3 mmol) was added. The mixture was stirred at 25 °C for 4 hours. The pH was adjusted to neutral with 1 N HCl solution, and the mixture was extracted with ethyl acetate (30 mL × 3). The organic phases were combined, washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was separated by preparative high performance liquid chromatography to obtain the product (356 mg, yield: 72%). MS m / z (ESI): 494.2 [M+H] + .

[0655] Step 4: (R)-4'-(4-(((3-fluoro-4-isopropylphenyl)amino)methyl)-7-methyl-6,7-dihydro-5H-cyclopentadien[b]pyridin-2-yl)-[1,1'-biphenyl]-4-carboxylic acid and (S)-4'-(4-(((3-fluoro-4-isopropylphenyl)amino)methyl)-7-methyl-6,7-dihydro-5H-cyclopentadien[b]pyridin-2-yl)-[1,1'-biphenyl]-4-carboxylic acid

[0656] The target product was obtained by chiral separation using SFC (supercritical fluid chromatography). MS m / z (ESI): 494.2 [M+H] + .

[0657] Examples 10-45 refer to the synthesis method of Example B.

[0658] Example C

[0659] (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)azacycloheptane-2-carboxamide)phenyl)-6-methyl-2-pyridinic acid

[0660] first step

[0661] Under nitrogen protection, 1-a (896 mg, 4.09 mmol), tert-butyl 5-bromo-6-methylpyridinecarboxylate (1.12 g, 4.11 mmol), palladium dichloride (287 mg, 0.409 mmol), and tripotassium phosphate (2.61 g, 12.3 mmol) were dissolved in 1,4-dioxane (20 mL) and water (5 mL), and the mixture was heated to 90 °C and stirred for 16 hours. After cooling to room temperature, a saturated ammonium chloride solution (100 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (2 x 100 mL). The organic phase was dried, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give tert-butyl 5-(4-aminophenyl)-6-methylpyridine-2-carboxylate 1-b (755 mg), yield: 64.8%. MS m / z (ESI): 284.2 [M+H] + .

[0662] Step 2

[0663] 1-b (284 mg, 1 mmol), (R)-1-(tert-butoxycarbonyl)azacycloheptane-2-carboxylic acid (291.6 mg, 4.11 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (249 mg, 1.3 mmol) were dissolved in dichloromethane (10 mL) and stirred at room temperature for 16 hours. Water (20 mL) was added to the reaction mixture, followed by extraction with dichloromethane (2 x 30 mL). The organic phase was dried, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give (R)-2-((4-(6-(tert-butoxycarbonyl)-2-methylpyridin-3-yl)phenyl)carboxamide)azacycloheptane-1-carboxylic acid tert-butyl ester 1-c (350 mg), yield: 68.8%. MS m / z (ESI): 510.3 [M+H] + .

[0664] Step 3

[0665] At room temperature, 1-c (350 mg, 0.687 mmol) was dissolved in 1,4-dioxane (5 mL), and 1,4-dioxane hydrochloride solution (4 M, 3.5 mL) was slowly added dropwise with stirring. After the addition was complete, the reaction was continued to be stirred at room temperature for 2 hours. The reaction solution was concentrated, and the residue was dissolved in methanol. The pH was then adjusted to 8 with saturated sodium bicarbonate solution, and purified by silica gel column chromatography (elution system A) to give (R)-5-(4-(azacycloheptan-2-carboxamide)phenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester 1-d (280 mg), yield: 91.6%. MS m / z (ESI): 410.2 [M+H] + .

[0666] Step 4

[0667] At room temperature, 3-fluoro-4-isopropylaniline (56.1 mg, 0.366 mmol) and triethylamine (37 mg, 0.366 mmol) were dissolved in acetonitrile (5 mL), and N,N'-carbonyldiimidazole (350 mg, 0.687 mmol) was added with stirring. The reaction was stirred at room temperature for half an hour, and the reaction solution was concentrated. The residue was dissolved in acetonitrile (2 mL) and added dropwise to acetonitrile (5 mL) containing 1-d (150 mg, 0.366 mmol) and triethylamine (185 mg, 1.83 mmol). The reaction was stirred at room temperature for another hour. Water (10 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (2 x 30 mL). The organic phase was dried and purified by silica gel column chromatography (elution system A) to give (R)-5-(4-(1-((3-fluoro-4-isopropylaniline)carbamoyl)azacycloheptane-2-carboxamide)phenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester 1-e (280 mg), yield: 91.6%. MS m / z (ESI): 589.3 [M+H] + .

[0668] Step 5

[0669] At room temperature, methanesulfonic acid (80 mg, 0.83 mmol) was added to a 1-e (150 mg, 0.166 mmol) solution in hexafluoroisopropanol (2 mL). The reaction was stirred at room temperature for 1 hour. The reaction solution was concentrated, and the residue was suspended in acetonitrile (1 mL) and water (2 mL). The filtered solid was purified by preparative HPLC (formic acid system) to obtain (R)-5-(4-(1-((3-fluoro-4-isopropylaniline)carbamoyl)azacycloheptane-2-carboxamide)phenyl)-6-methylpyridine-2-carboxylic acid (36 mg), yield: 40.8%. MS m / z (ESI): 533.2 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ10.13(s,1H),8.47(s,1H),7.92(d,1H),7.78-7.68(m,3H),7.48-7.33(m,3H),7.26(dd,1H),7.17(t,1H),4.76(dd,1H) ,3.96(d,1H),3.07(p,1H),2.50(s,3H),2.34(dt,1H),1.95-1.68(m,1H ),1.85-1.66(m,3H),1.51-1.39(d,1H),1.38-1.21(m,3H),1.18(d,6H).

[0670] Example D

[0671] (R)-5-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carbamoyl)phenyl)-6-methylpyridine-2-carboxylic acid

[0672] first step

[0673] To a solution of 5-bromo-6-methylpyridine-2-carboxylic acid (5.00 g, 23.14 mmol) in pyridine (100 mL) and tert-butanol (50 mL), p-toluenesulfonyl chloride (13.24 g, 69.43 mmol) was added, and the mixture was stirred at 20 °C for 4 hours. The reaction mixture was quenched with water (200 mL), extracted with 2N hydrochloric acid (100 mL), and methyl tert-butyl ether (150 mL x 3). The mixture was washed with 1N sodium hydroxide solution, dried over the organic phase, and concentrated to obtain crude tert-butyl 5-bromo-6-methylpyridine-2-carboxylic acid (6.50 g). MS m / z (ESI): 272 [M+H] +

[0674] Step 2

[0675] Crude tert-butyl 5-bromo-6-methylpyridine-2-carboxylate (6.50 g), pinacol ester of aminophenylboronic acid (5.23 g, 23.33 mmol), potassium carbonate (6.60 g, 47.77 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (873 mg, 1.19 mmol) were dissolved in 1,4-dioxane (100 mL) and water (10 mL). The mixture was purged with nitrogen three times, and the reaction mixture was stirred at 90 °C for 16 hours. The reaction was cooled to room temperature, quenched with water (100 mL), extracted with ethyl acetate (100 mL x 3), dried over the organic phase, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give tert-butyl 5-(4-aminophenyl)-6-methylpyridine-2-carboxylate (7.20 g, 90% purity), yield: 95.4%. MS m / z(ESI): 285 [M+H] +

[0676] Step 3

[0677] A solution of tert-butyl 5-(4-aminophenyl)-6-methylpyridine-2-carboxylate (284 mg, 1.00 mmol) and N,N'-carbodiimidazole (162 mg, 1.00 mmol) in acetonitrile (10 mL) was stirred at 20 °C for 1 hour and concentrated under reduced pressure. A solution of crude (R)-N-(3-fluoro-4-isopropylphenyl)pyrrole-2-carboxamide (370 mg) and N-methylmorpholine (500 mg, 5.00 mmol) in tetrahydrofuran (10 mL) was added, and the mixture was stirred at 20 °C for 6 hours. The reaction solution was quenched with water (10 mL), and the pH was adjusted to 5 with 2N hydrochloric acid (3 mL). Extraction was performed with ethyl acetate (20 mL x 3). The organic phase was dried and concentrated to obtain crude (550 mg) of (R)-5-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester. MS m / z (ESI): 561 [M+H] +

[0678] Step 4

[0679] Crude tert-butyl 5-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carbamate)phenyl)-6-methylpyridine-2-carboxylic acid (tert-butyl ester) (550 mg) was dissolved in trifluoroacetic acid (3 mL) and dichloromethane (3 mL), and the reaction was stirred at 20 °C for 4 hours until complete. The crude product was concentrated under reduced pressure and purified by preparative HPLC (formic acid system) to give (R)-5-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carbamate)phenyl)-6-methylpyridine-2-carboxylic acid (147 mg), yield: 30.4%. MS m / z (ESI): 505 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ13.03(br s,1H),10.12(s,1H),8.46(s,1H),7.91(d,J=7.88Hz,1H),7.75(d,J=7.88Hz,1H),7. 65(d,J=8.63Hz,2H),7.51-7.58(m,1H),7.32(d,J=8.63Hz,2H),7.22-7.30(m,2H),4. 46(dd,J=8.19,3.69Hz,1H),3.62-3.74(m,1H),3.51-3.60(m,1H),3.10(spt,J=6.92H z,1H),2.51(s,3H),2.14-2.25(m,1H),1.88-2.09(m,3H),1.18(d,J=6.88Hz,6H)ppm.

[0680] Example E

[0681] (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)thiocarbamoyl)pyrrolo-2-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid

[0682] first step

[0683] 5-(4-aminophenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester (800 mg, 2.81 mmol), tert-butoxycarbonyl-D-proline (666 mg, 3.09 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (593 mg, 3.09 mmol) were dissolved in acetonitrile (20 mL) and stirred at 20 °C for 6 hours. After the reaction was complete, the reaction solution was concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give (R)-5-(4-(1-(tert-butoxycarbonyl)pyrrolo-2-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester (1.10 g), yield 80.6%. MS m / z (ESI): 482 [M+H] + .

[0684] Step 2

[0685] To a solution of (R)-5-(4-(1-(tert-butyloxycarbonyl)pyrrolo-2-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester (1.10 g, 2.29 mmol) in dichloromethane (20 mL), trifluoroacetic acid (3 mL) was added, and the mixture was stirred at 20 °C for 2 hours. The reaction solution was concentrated under reduced pressure to give the crude product (R)-6-methyl-5-(4-(pyrrolo-2-carboxamido)phenyl)pyridine-2-carboxylic acid tert-butyl ester (1.58 g). MS m / z (ESI): 382 [M+H] +

[0686] Step 3

[0687] A solution of 3-fluoro-4-isopropylaniline (150 mg, 0.98 mmol) and 1,1'-thiocarbamodiimidazole (174 mg, 0.98 mmol) in acetonitrile (10 mL) was stirred at 20 °C for 1 hour and concentrated under reduced pressure. A solution of crude (R)-6-methyl-5-(4-(pyrrolo-2-carbamoyl)phenyl)pyridine-2-carboxylic acid tert-butyl ester (700 mg) and N-methylmorpholine (500 mg, 5.00 mmol) in tetrahydrofuran (10 mL) was added, and the mixture was stirred at 20 °C for 6 hours. After the reaction was complete, the reaction solution was concentrated, and the residue was purified by silica gel column chromatography (elution system A) to obtain (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)thiocarbamoyl)pyrrolo-2-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester (490 mg), yield 84.2%. MS m / z (ESI): 576 [M+H] +

[0688] Step 4

[0689] (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)thiocarbamoyl)pyrrolo-2-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid tert-butyl ester (490 mg, 0.85 mmol) was dissolved in trifluoroacetic acid (5 mL) and dichloromethane (5 mL), and the reaction was stirred at 20 °C for 4 hours until complete. The crude product was concentrated under reduced pressure and purified by preparative HPLC (formic acid system) to (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)thiocarbamoyl)pyrrolo-2-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid (115.7 mg), yield: 25.2%. MS m / z (ESI): 520 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ13.07(br s,1H),10.24(s,1H),9.13(s,1H),7.93(d,J=7.88Hz,1H),7.71-7.78(m,3H),7.40(d,J=8.63Hz,2H),7.16-7.33(m,3H),5.05(dd,J=8.32,2. 69Hz,1H),3.63-3.72(m,1H),3.12(spt,J=6.92Hz,1H),2.22-2.35(m,1H),1.95-2.18(m,3H),1.55–1.65(m,4H),1.21(d,J=7.00Hz,6H)ppm.

[0690] Example F

[0691] (R)-4-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)-2,3-dihydrobenzofuran-7-carboxylic acid

[0692] first step

[0693] Under a nitrogen atmosphere at -78°C, lithium diisopropylamino (18.17 mL, 18.17 mmol) was added to a tetrahydrofuran (100 mL) solution of tert-butyl 4-bromo-2-fluorobenzoate (5.0 g, 18.17 mmol) and stirred for 30 minutes. Ethylene oxide (6.06 mL, 18.17 mmol) was then added, and the mixture was stirred at -78°C for another 30 minutes, followed by a slow increase to 20°C over 4 hours. The reaction mixture was quenched with sodium bicarbonate solution (100 mL), extracted with ethyl acetate (30 mL x 3), dried over dryness, concentrated, and the residue purified by silica gel column chromatography to give tert-butyl 4-bromo-2,3-dihydrobenzofuran-7-carboxylate (2.00 g, 6.35 mmol), yield: 35.0%. MS m / z (ESI): 299.0 [M+H] +

[0694] Step 2

[0695] Under a nitrogen atmosphere, tert-butyl 4-bromo-2,3-dihydrobenzofuran-7-carboxylate (1.00 g, 3.34 mmol), pinacol 4-aminophenylboronic acid (732 mg, 3.34 mmol), potassium carbonate (1.39 g, 10.03 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (245 mg, 0.33 mmol) were dissolved in 1,4-dioxane (30 mL) and water (6 mL). The nitrogen atmosphere was purged three times, and the reaction system was stirred at 90 °C for 16 hours. The reaction was cooled to room temperature, quenched with water (100 mL), extracted with ethyl acetate (100 mL x 3), dried over the organic phase, concentrated, and the residue was purified by silica gel column chromatography to give tert-butyl 4-(4-aminophenyl)-2,3-dihydrobenzofuran-7-carboxylate (0.82 g, 2.55 mmol), yield: 76.4%. MS m / z (ESI): 312.2 [M+H] +

[0696] Step 3

[0697] 4-(4-aminophenyl)-2,3-dihydrobenzofuran-7-carboxylate tert-butyl ester (200 mg, 0.64 mmol), ((3-fluoro-4-isopropylphenyl)carbamoyl)-D-proline (189 mg, 0.64 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (135 mg, 0.71 mmol) were dissolved in dichloromethane (10 mL) and stirred at 20 °C for 6 hours. The reaction solution was concentrated and purified by silica gel column chromatography to give (R)-4-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)-2,3-dihydrobenzofuran-7-carboxylate tert-butyl ester (150 mg, 47% purity, 0.076 mmol), yield: 11.9%. MS m / z (ESI): 588.3 [M+H] + .

[0698] Step 4

[0699] At room temperature, trifluoroacetic acid (5 mL) was added to a solution of (R)-4-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)-2,3-dihydrobenzofuran-7-carboxylic acid tert-butyl ester (150 mg, 47% purity, 0.12 mmol) in dichloromethane (5 mL), and the reaction was stirred at room temperature for 1 hour. The residue obtained by concentration of the reaction solution was purified by preparative HPLC to (R)-4-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)-2,3-dihydrobenzofuran-7-carboxylic acid (37.7 mg, 0.07 mmol), yield: 59.3%. MS m / z (ESI): 532.2 [M+H] + . 1 H NMR (400MHz, DMSO) δ10.16(s,1H),8.41(s,1H),7.76–7.69(m,2H),7.65(d,J=8.2Hz,1H),7.54–7.48(m,2 H),7.41(dd,J=13.7,2.1Hz,1H),7.24(dd,J=8.5,2.1Hz,1H),7.16(t,J=8.7Hz,1H),6.96(d,J=8.2Hz,1H) ,4.60(t,J=8.7Hz,2H),4.47(dd,J=8.3,3.7Hz,1H),3.70–3.60(m,1H),3.52(q,J=7.3Hz,1H),3.28(t,J= 8.7Hz,2H),3.06(p,J=6.9Hz,1H),2.20(dq,J=11.4,7.9Hz,1H),2.10–1.83(m,3H),1.17(d,J=6.9Hz,6H).

[0700] Example G

[0701] (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)-3,3-dimethylazacyclobutane-2-carbamoyl)phenyl)-6-methylpyridinecarboxylic acid

[0702] first step

[0703] At room temperature, 3-fluoro-4-isopropylaniline (24 mg, 0.15 mmol) was dissolved in acetonitrile (1 mL), and N,N'-carbonyldiimidazole (27 mg, 0.17 mmol) was added with stirring. The mixture was stirred at room temperature for half an hour, and the reaction solution was concentrated. The residue was dissolved in acetonitrile (1 mL). This solution was added dropwise to (R)-3,3-dimethylazacyclobutane-2-2-carboxylic acid (20 mg, 0.15 mmol) and N-methylmorpholine (31 mg, 0.31 mmol) in acetonitrile (1 mL). The reaction was continued with stirring at room temperature for 16 hours. Water (10 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (2 x 10 mL). The organic phase was dried and concentrated under reduced pressure to obtain a colorless oil. The crude product was used directly in the next reaction. MS m / z (ESI): 309.1 [M+H]+.

[0704] Step 2

[0705] (R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)-3,3-dimethylazacyclobutane-2-carboxylic acid (40 mg, 0.13 mmol), tert-butyl 5-(4-aminophenyl)-6-methylpyridinecarboxylate (37 mg, 0.13 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (30 mg, 0.16 mmol) were dissolved in dichloromethane (3 mL) and stirred at room temperature for 16 hours. Water (10 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (2 x 10 mL). The organic phase was dried, and the residue was purified by silica gel column chromatography (elution system A) to give (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)-3,3-dimethylazacyclobutane-2-carbamate)phenyl)-6-methylpyridinecarboxylate tert-butyl ester (22 mg), yield: 29.5%. MS m / z (ESI): 575.4 [M+H]+.

[0706] Step 3

[0707] At room temperature, tert-butyl (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)-3,3-dimethylazacyclobutane-2-carbamoyl)phenyl)-6-methylpyridinecarboxylic acid (22 mg, 0.038 mmol) was dissolved in dichloromethane (2 mL), followed by the addition of trifluoroacetic acid (2 mL). The mixture was stirred at room temperature for 3 hours, concentrated, and the residue was purified by preparative HPLC (formic acid system) to obtain (R)-5-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)-3,3-dimethylazacyclobutane-2-carbamoyl)phenyl)-6-methylpyridinecarboxylic acid (12 mg), yield: 59.4%. MS m / z (ESI): 519.4 [M+H]+;1H NMR (400MHz, MeOD) δ8.06(d,J=8.0Hz,1H),7.86(d,J=7.7Hz,1H),7.77(d,J=8.3Hz,2H),7.39(d,J=8.5Hz,2H),7.34–7.27(m,1H),7.16(dd,J=4.3,2. 2Hz,2H),4.50(s,1H),3.86(d,J=7.4Hz,1H),3.79(d,J=7.4Hz,1H),3.18– 3.12(m,1H),2.58(s,3H),1.48(s,3H),1.27(s,3H),1.23(d,J=6.9Hz,6H).

[0708] Example H

[0709] (S)-4'-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid

[0710] first step

[0711] Under nitrogen protection, tert-butyl carbamate (500 mg, 1.55 mmol), methyl 4-bromobenzoate (399.17 mg, 1.86 mmol), 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (113.18 mg, 0.15 mmol), and potassium phosphate (985.04 mg, 4.64 mmol) were dissolved in 1,4-dioxane (8 mL) and water (2 mL), and the mixture was heated to 90 °C and stirred for 12 hours. The reaction mixture was cooled to room temperature, and water (15 mL) was added to the reaction solution. Extraction was performed with ethyl acetate (2 x 30 mL), the organic phase was dried, and the mixture was concentrated. The residue was purified by silica gel column chromatography (elution system A) to give methyl 4'-((tert-butoxycarbonyl)amino)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (450 mg), yield: 86.5%. MS m / z (ESI): 276.1 [M-(t-Bu)+H] + .

[0712] Step 2

[0713] Methyl 4'-((tert-Butoxycarbonyl)amino)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (250 mg, 0.74 mmol) was dissolved in dichloromethane (3.0 mL) under ice bath conditions. Trifluoroacetic acid (1.0 mL, 12.87 mmol) was slowly added dropwise with stirring, and the mixture was brought to room temperature and stirred for 16 hours. The pH of the reaction mixture was adjusted to approximately 8 by adding saturated sodium bicarbonate solution. Extraction was performed with dichloromethane (2 x 30 mL), the organic phase was dried, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give methyl 4'-amino-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (140 mg), yield: 80.6%. MS m / z (ESI): 232.3 [M+H] + .

[0714] Step 3

[0715] Under nitrogen protection, methyl 4'-amino-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (70 mg, 0.30 mmol), ((3-fluoro-4-isopropylphenyl)carbamoyl)-D-proline (88.12 mg, 0.30 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (68.88 mg, 0.36 mmol) were dissolved in dichloromethane (3 mL) and stirred at room temperature for 16 hours. Water (10 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (2 x 30 mL). The organic phase was dried, and the residue was purified by silica gel column chromatography (elution system A) to give methyl 4'-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (120 mg), yield: 68.2%. MS m / z (ESI): 508.4 [M+H] + .

[0716] Step 4

[0717] At room temperature, methyl 4'-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (120 mg, 0.20 mmol) was dissolved in tetrahydrofuran (3 mL), methanol (1 mL), and water (1 mL). Lithium hydroxide (19.55 mg, 0.82 mmol) was added with stirring, and the reaction was stirred at room temperature for 6 hours. The reaction solution was concentrated, and the residue was dissolved in water (5 mL). The pH was adjusted to 3 with citric acid aqueous solution, and the aqueous phase was extracted with ethyl acetate (30 mL). The organic phase was dried and concentrated, and the residue was purified by preparative HPLC (formic acid system) to obtain (S)-4'-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (13.2 mg), yield: 13.1%. MS m / z (ESI): 494.2 [M+H] + . 1H NMR(400MHz,DMSO-d6)δ12.84(br s,1H),8.28(s,1H),7.89-7.83(m,2H),7.52(d,2H,J=8.4Hz),7.41(d,1H,J=1.8Hz) ,7.38(d,1H,J=1.8Hz),7.22(dd,1H,J=1.8,8.4Hz),7.14(t,1H,J=8.6Hz),6.24(br s,1H),4.30(dd,1H,J=3.2,8.2Hz),3.85(br s,1H),3.62-3.54(m,1H),3.47-3.39(m,1H),3.07(q,1H,J=7.0Hz),2.46-2.39(m,2 H),2.16-2.00(m,2H),1.99-1.80(m,5H),1.74-1.62(m,1H),1.18(d,6H,J=6.8Hz).

[0718] Example I

[0719] (R)-4-(3-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carbamoyl)bicyclo[1.1.1]pentan-1-yl)benzoic acid

[0720] first step

[0721] 3-Fluoro-4-isopropylaniline (200 mg, 1.31 mmol), tert-butyloxycarbonyl-D-proline (281 mg, 1.31 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbamoyldiimide hydrochloride (251 mg, 1.31 mmol) were dissolved in dichloromethane (10 mL) and stirred at 20 °C for 6 hours. The reaction mixture was quenched with water (100 mL), extracted with dichloromethane (30 mL x 3), dried over the organic phase, and concentrated to give crude (R)-2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carboxylic acid tert-butyl ester (500 mg). MS m / z (ESI): 351 [M+H] +

[0722] Step 2

[0723] To a solution of (R)-2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carboxylic acid tert-butyl ester (500 mg) in dichloromethane (10 mL), trifluoroacetic acid (2 mL) was added, and the mixture was stirred at 20 °C for 1 hour. The reaction solution was concentrated under reduced pressure to give the crude product (R)-N-(3-fluoro-4-isopropylphenyl)pyrrole-2-carboxamide (830 mg). MS m / z (ESI): 251 [M+H] +

[0724] Step 3

[0725] A solution of methyl 3-(3-aminobicyclo[1.1.1]pentan-1-yl)benzoate (40 mg, 0.18 mmol) and N,N'-carbodiimidazole (35.82 mg, 0.22 mmol) in acetonitrile (5 mL) was stirred at 20 °C for 1 hour, and the solvent was removed by concentration under reduced pressure. Crude (R)-N-(3-fluoro-4-isopropylphenyl)pyrrole-2-carboxamide (150 mg) and a solution of N-methylmorpholine (223 mg, 2.21 mmol) in tetrahydrofuran (5 mL) were added, and the mixture was stirred at 20 °C for 6 hours. The reaction solution was quenched with sodium bicarbonate solution (10 mL), extracted with ethyl acetate (10 mL x 3), the organic phase was dried, and concentrated to obtain crude tert-butyl 5-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carboxamido)phenyl)-6-methylpyridine-2-carboxylic acid (100 mg). MS m / z (ESI): 494 [M+H] +

[0726] Step 4

[0727] Crude tert-butyl 5-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carbamoyl)phenyl)-6-methylpyridine-2-carboxylic acid (100 mg) was dissolved in tetrahydrofuran (2 mL), methanol (2 mL), and water (2 mL). Lithium hydroxide (48.52 mg, 2.03 mmol) was added, and the reaction was stirred at 20 °C for 4 hours until complete. The organic solvent was removed by vacuum concentration, neutralized with 2N hydrochloric acid, and the pH was adjusted to 3-4. The crude product was obtained by filtration and purified by preparative HPLC to obtain product (R)-4-(3-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carbamoyl)bicyclo[1.1.1]pentan-1-yl)benzoic acid (38.7 mg, 76.67 mmol), yield: 37.8%. MS m / z (ESI): 480 [M+H] + . 1H NMR (400MHz, DMSO-d6) δppm 1.12 (d, J=6.88Hz, 6H) 1.74-2.06 (m, 4H) 2.17 (s, 4H) 3.02 (dquin, J=13.84, 6.92, 6.92, 6.92, 6.92Hz, 1H) 3.22 (br dd,J=16.45,7.19Hz,2H)3.34(td,J=8.25,4.13Hz,2H)4.26(dd,J=8.32,3.06Hz,1H)6.96(s,1H)7.0 5-7.22(m,2H)7.26(m,J=8.25Hz,2H)7.44-7.52(m,1H)7.80(m,J=8.25Hz,2H)10.01(s,1H)12.80(br s,1H).

[0728] Example J

[0729] (1R,4r)-4-(4-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)cyclohexane-1-carboxylic acid

[0730] first step

[0731] Ethyl 4'-amino-2,3,4,5-tetrahydro-[1,1'-biphenyl]-4-carboxylate (70 mg, 0.27 mmol) was dissolved in tetrahydrofuran (4 mL) at room temperature. 10% palladium on carbon (72.94 mg, 0.69 mmol) was added with stirring, followed by hydrogen purging. The reaction was stirred at room temperature for 16 hours. The mixture was filtered through diatomaceous earth, extracted with dichloromethane (3 x 20 mL), dried over the organic phase, concentrated, and purified by silica gel column chromatography (elution system A) to give ethyl 4-(4-aminophenyl)cyclohexane-1-carboxylate (65 mg), yield: 92.1%. MS m / z (ESI): 248.4 [M+H] + .

[0732] Step 2

[0733] Under nitrogen protection, ethyl 4-(4-aminophenyl)cyclohexane-1-carboxylate (65 mg, 0.26 mmol), ((3-fluoro-4-isopropylphenyl)carbamoyl)-D-proline (77.35 mg, 0.26 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (61.34 mg, 0.32 mmol) were dissolved in dichloromethane (3 mL) and stirred at room temperature for 16 hours. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2 x 30 mL). The organic phase was dried, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give (R)-4-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)cyclohexane-1-carboxylate (115 mg), yield: 75.8%. MS m / z (ESI): 524.3 [M+H] + .

[0734] Step 3

[0735] Ethyl (R)-4-(4-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)cyclohexane-1-carboxylic acid (105 mg, 0.20 mmol) was dissolved in tetrahydrofuran (3 mL), methanol (1 mL), and water (1 mL) under ice bath conditions. Lithium hydroxide (18.94 mg, 0.79 mmol) was added with stirring, and the mixture was heated to room temperature and stirred for 5 hours. The reaction solution was concentrated, and the residue was dissolved in water (5 mL). The pH was adjusted to 3 with citric acid aqueous solution, and the aqueous phase was extracted with ethyl acetate (30 mL). The organic phase was dried and concentrated, and the residue was purified by preparative HPLC (formic acid system) to obtain (1R,4r)-4-(4-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)phenyl)cyclohexane-1-carboxylic acid (43.9 mg), yield: 44.8%. MS m / z(ESI): 496.4 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ12.14(br s,1H),9.90(s,1H),8.37(s,1H),7.54-7.46(m,2H),7.40(br d,1H,J=13.6Hz),7.23(br d,1H,J=7.8Hz),7.19-7.12(m,1H),7.12-7.05(m,2H),4.43(br d,1H,J=5.4Hz),3.67-3.56(m,1H),3.54-3.43(m,1H),3.11-3.00(m,1H),2.61(br s,1H),2.23-2.03(m,3H),2.03-1.83(m,3H),1.70-1.59(m,2H),1.59-1.44(m,4H),1.17(br d,6H,J=6.8Hz).

[0736] Example K

[0737] 4-((1R,4r)-4-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carbamoyl)cyclohexyl)benzoic acid

[0738] first step

[0739] Methyl 4'-amino-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid (70 mg, 0.30 mmol) was dissolved in methanol (3 mL) at room temperature. 10% palladium on carbon (63.73 mg, 0.60 mmol) was added with stirring, followed by hydrogen purging. The reaction was stirred at room temperature for 16 hours. The mixture was filtered through diatomaceous earth, extracted with dichloromethane (3 x 20 mL), dried over the organic phase, concentrated, and purified by silica gel column chromatography (elution system A) to give methyl 4-(4-aminocyclohexyl)benzoate (62 mg), yield: 87.1%. MS m / z (ESI): 234.2 [M+H] + .

[0740] Step 2

[0741] Under nitrogen protection, methyl 1-(4-aminophenyl)piperidin-4-carboxylic acid (62 mg, 0.26 mmol), ((3-fluoro-4-isopropylphenyl)carbamoyl)-D-proline (76.78 mg, 0.26 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (60.01 mg, 0.31 mmol) were dissolved in N,N-dimethylformamide (3 mL) and stirred at room temperature for 16 hours. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2 x 30 mL). The organic phase was dried, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give methyl 4-((1R,4r)-4-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carbamoyl)cyclohexyl)benzoate (30 mg), yield: 21.2%. MS m / z (ESI): 510.4 [M+H] + .

[0742] Step 3

[0743] Methyl 4-((1R,4r)-4-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carbamoyl)cyclohexyl)benzoate (30 mg, 0.05 mmol) was dissolved in tetrahydrofuran (3 mL), methanol (1 mL), and water (1 mL) under ice bath conditions. Lithium hydroxide (4.87 mg, 0.20 mmol) was added with stirring, and the mixture was brought to room temperature and stirred for 6 hours. The reaction solution was concentrated, and the residue was dissolved in water (5 mL). The pH was adjusted to 3 with citric acid aqueous solution, and the aqueous phase was extracted with ethyl acetate (30 mL). The organic phase was dried and concentrated, and the residue was purified by preparative HPLC (formic acid system) to obtain 4-((1R,4r)-4-((R)-1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)cyclohexyl)benzoic acid (11.9 mg), yield: 47.2%. MS m / z (ESI): 496.2 [M+H] + . 1H NMR(400MHz,DMSO-d6)δ12.70(br s,1H),8.35(s,1H),7.87(d,1H,J=7.8Hz),7.78(d,2H,J=8.4Hz),7.4-7.5(m,1H),7.42(d,1H,J= 2.0Hz),7.34(d,2H,J=8.4Hz),7.29-7.23(m,1H),7.19-7.12(m,1H),4.47-4.42(m,1H),3.94(br s,1H),3.63-3.55(m,1H),3.48-3.40(m,1H),3.12-3.03(m,1H),2.65-2.54(m,1H),2.08-1.86(m,4H),1.75(br d,4H,J=12.4Hz),1.65-1.51(m,4H),1.18(d,6H,J=6.8Hz).

[0744] Example L

[0745] (R)-5-(6-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)pyridin-3-yl)bicyclo[4.2.0]octyl-1(6),2,4-trien-2-carboxylic acid

[0746] first step

[0747] Under nitrogen protection, 2,5-dibromobicyclo[4.2.0]oct-1(6),2,4-triene (4.76 g, 18.18 mmol), pinacol ester of 2-aminopyridine-5-boronic acid (2.00 g, 9.09 mmol), potassium carbonate (3.77 g, 27.26 mmol) and bis(diphenylphosphine)ferrocene palladium dichloride (665 mg, 0.91 mmol) were dissolved in 1,4-dioxane (20 mL) and water (2 mL), and the reaction was heated to 90 °C and stirred for 6 hours. The reaction mixture was cooled to room temperature, and water (50 mL) was added to the reaction solution. Extraction was performed with ethyl acetate (3 x 100 mL), followed by drying and concentration. The residue was purified by silica gel column chromatography to obtain 1.38 g of 5-(5-bromobicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridine-2-amine, yield: 53.5%. MS m / z (ESI): 275.2 [M+H]+.

[0748] Step 2

[0749] Under nitrogen protection, 5-(5-bromobicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridine-2-amine (500 mg, 1.82 mmol), potassium ethylenetrifluoroborate (487 mg, 3.63 mmol), potassium carbonate (753 mg, 5.45 mmol), and palladium dichloride bis(triphenylphosphine) (128 mg, 0.18 mmol) were dissolved in 1,4-dioxane (18 mL) and water (2 mL). The reaction mixture was heated to 90 °C and stirred for 16 hours. After cooling to room temperature, water (50 mL) and ethyl acetate (2 x 100 mL) were added to the reaction mixture for extraction. The mixture was dried, concentrated, and the residue was purified by silica gel column chromatography to obtain 5-(5-vinylbicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridine-2-amine (410 mg), yield: 85.2%. MS m / z(ESI): 223.1[M+H]+.

[0750] Step 3

[0751] At room temperature, 5-(5-vinylbicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridine-2-amine (150 mg, 0.67 mmol), ((3-fluoro-4-isopropylphenyl)carbamoyl)-D-proline (298 mg, 1.01 mmol), 2-chloro-1-methyliodopyridine (345 mg, 1.35 mmol), and N,N-diisopropylethylamine (0.94 mL, 5.40 mmol) were dissolved in tetrahydrofuran (5 mL). The reaction was stirred at 50 °C for 16 hours. The reaction solution was concentrated, and the residue was purified by silica gel column chromatography to obtain (R)-N 1 -(3-Fluoro-4-isopropylphenyl)-N 2 -(5-(5-vinylbicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridin-2-yl)pyrrolidine-1,2-dicarboxamide (30 mg), yield: 8.83%. MS m / z (ESI): 499.2 [M+H]+.

[0752] Step 4

[0753] At room temperature, towards (R)-N 1 -(3-Fluoro-4-isopropylphenyl)-N 2In a solution of 30 mg (60.2 μmol) of 5-(5-vinylbicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridin-2-yl)pyrrolidine-1,2-dicarboxamide in acetone (3 mL) and water (3 mL), sodium periodate (64 mg, 0.30 mmol) and potassium osmium tetroxide dihydrate (2 mg, 6.0 μmol) were added. The reaction was stirred at room temperature for 1 hour, quenched with sodium sulfite solution (10 mL), extracted with ethyl acetate (10 mL x 3), dried, and concentrated to obtain crude product (R)-N. 1 -(3-Fluoro-4-isopropylphenyl)-N 2 -(5-(5-formylbicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridin-2-yl)pyrrolidine-1,2-dicarboxamide (30 mg). MS m / z (ESI): 501.2 [M+H]+.

[0754] Step 5

[0755] At room temperature, towards (R)-N 1 -(3-Fluoro-4-isopropylphenyl)-N 2 In a solution of 30 mg (60.0 μmol) of 5-(5-formylbicyclo[4.2.0]oct-1(6),2,4-trien-2-yl)pyridin-2-yl)pyrrolidine-1,2-dicarboxamide in tert-butanol (3 mL) and water (3 mL), sodium dihydrogen phosphate (36 mg, 0.30 mmol), 2-methyl-2-butene (34 mg, 0.48 mmol) and sodium chlorite (11 mg, 0.12 mmol) were added. The reaction was stirred at room temperature for 16 hours, and the crude product was concentrated. The crude product was then purified by preparative HPLC to obtain product (R)-5-(6-(1-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolidine-2-carboxamido)pyridin-3-yl)bicyclo[4.2.0]oct-1(6),2,4-trien-2-carboxylic acid (4.1 mg), yield: 10.9%. MS m / z(ESI): 517.2[M+H]+. 1H NMR (400MHz, DMSO) δ10.68(s,1H),8.72(d,J=1.7Hz,1H),8.42(s,1H),8.17(d,J =2.0Hz,2H),7.78–7.67(m,2H),7.40(dd,J=13.6,2.1Hz,1H),7.28–7.12(m,2H) ,4.63(d,J=6.8Hz,1H),3.67–3.59(m,1H),3.56–3.48(m,1H),3.47–3.41(m,2H) ,3.39–3.34(m,2H),3.06(p,J=6.9Hz,1H),2.23–2.12(m,1H),2.05–1.90(m,3H).

[0756] Example M

[0757] (R)-4-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carbamoyl)bicyclo[2.2.2]octane-1-yl)-2-methoxybenzoic acid

[0758] first step

[0759] At room temperature, 25.0 g (92.82 mmol) of 4-((tert-butyloxycarbonyl)amino)bicyclo[2.2.2]octane-1-carboxylic acid, 16.66 g (102.10 mmol) of N-hydroxyphthalimide, and 567 mg (4.64 mmol) of 4-dimethylaminopyridine were dissolved in 200 mL of dichloromethane. N,N'-diisopropylcarbodiimide (21.56 mL, 139.23 mmol) was added, and the reaction was stirred at room temperature for 2 hours. The reaction solution changed from orange to pale yellow. The solution was filtered through 2-3 cm silica gel, washed with 500 mL of dichloromethane, and the filtrate was concentrated to give 38.47 g (38.47 g) of 1,3-dioxoisoindoline-2-yl 4-((tert-butyloxycarbonyl)amino)bicyclo[2.2.2]octane-1-carboxylic acid ester, with a yield of 98.9%. 1 H NMR (400MHz, CHLOROFORM-d) δ7.89-7.86(m,2H),7.79-7.64(m,2H),2.15-2.09(m,6H),1.97-1.91(m,6H),1.46-1.40(m,9H).

[0760] Step 2

[0761] 1,3-dioxoisoindoline-2-yl 4-((tert-butoxycarbonyl)amino)bicyclo[2.2.2]octane-1-carboxylate (20.00 g, 48.26 mmol), methyl 4-iodo-2-methoxybenzoate (14.09 g, 48.26 mmol), nickel dimethyl ethylene glycol bromide (5.96 g, 19.30 mmol), pyridine-2,6-bis(formamidinium) dihydrochloride (4.56 g, 19.30 mmol), and zinc powder (15.78 g, 241.28 mmol) were placed in a two-necked flask, purged with argon three times, and dissolved in N,N-dimethylacetamide (140 mL). The mixture was stirred rapidly at room temperature for 2 hours. An aqueous solution of ammonium chloride (300 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (200 mL x 2). The mixture was washed with sodium chloride solution, dried over the organic phase, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give methyl 4-(4-((tert-butoxycarbonyl)amino)bicyclo[2.2.2]octane-1-yl)-2-methoxybenzoate (8.50 g), yield: 45.2%. MS m / z (ESI): 390.3 [M+H] + .

[0762] Step 3

[0763] Methyl 4-(4-((tert-Butoxycarbonyl)amino)bicyclo[2.2.2]octan-1-yl)-2-methoxybenzoate (8.50 g, 21.82 mmol) was dissolved in trifluoroacetic acid (20 mL) and dichloromethane (100 mL) at room temperature, and the reaction was continued with stirring at room temperature for 2 hours. The reaction solution was concentrated, the residue was quenched with saturated sodium bicarbonate solution, extracted with dichloromethane (3 x 200 mL), and purified by silica gel column chromatography (elution system A) to give methyl 4-(4-aminobicyclo[2.2.2]octan-1-yl)-2-methoxybenzoate (3.05 g), yield: 45.2%. MS m / z (ESI): 290.3 [M+H] + .

[0764] Step 4

[0765] At room temperature, methyl 4-(4-aminobicyclo[2.2.2]octane-1-yl)-2-methoxybenzoate (1.40 g, 4.79 mmol) and N,N'-carbonyldiimidazole (933 mg, 5.75 mmol) were dissolved in acetonitrile (100 mL), and 1,8-diazabicyclo[5.4.0]undecene (1.46 g, 9.59 mmol) was added with stirring. The reaction was stirred at room temperature for 1 hour. The reaction solution was concentrated, and the residue was dissolved in tetrahydrofuran (2 mL). (R)-N-(3-fluoro-4-isopropylphenyl)pyrrole-2-carboxamide (1.20 g, 4.79 mmol) was added, and the reaction was stirred at room temperature for another 3 hours. After the reaction was complete, the reaction solution was concentrated to obtain crude (R)-4-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrolo-1-carboxamido)bicyclo[2.2.2]octane-1-yl)-2-methoxybenzoate (5.60 g). MS m / z (ESI): 565.3 [M+H] + .

[0766] Step 5

[0767] At room temperature, crude (R)-4-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carbamoyl)bicyclo[2.2.2]octane-1-yl)-2-methoxybenzoate (5.60 g) was dissolved in methanol (20 mL), tetrahydrofuran (10 mL) and water (10 mL), and lithium hydroxide (150 mg, 0.166 mmol) was added. The reaction was stirred at room temperature for 3 hours. The pH was adjusted to 3 with 6N hydrochloric acid, and the aqueous phase was extracted with dichloromethane (30 mL). The organic phase was dried and concentrated, and the residue was purified by preparative HPLC (formic acid system) to obtain (R)-4-(4-(2-((3-fluoro-4-isopropylphenyl)carbamoyl)pyrrole-1-carboxamido)bicyclo[2.2.2]octane-1-yl)-2-methoxybenzoic acid (1.40 g), yield: 52.4%. MS m / z (ESI): 552.3 [M+H] + . 1H NMR(400MHz,DMSO)δ12.37(s,1H),10.07(s,1H),7.59–7.49(m,2H),7.30–7.19(m,2H),7 .00(d,J=1.6Hz,1H),6.94(dd,J=8.1,1.6Hz,1H),5.33(s,1H),4.31(dd,J=8.3,3.1Hz,1H ),3.81(s,3H),3.44(td,J=8.6,4.1Hz,1H),3.27(dt,J=8.8,6.7Hz,1H),3.10(hept,J=6 .9Hz,1H),2.05(ddt,J=14.1,9.4,4.0Hz,1H),1.98–1.80(m,15H),1.19(d,J=6.9Hz,6H).

[0768] Example N

[0769] (R)-4-(4-(1-((3-(trifluoromethylthio)phenyl)carbamoyl)pyrrole-2-carboxamido)phenyl)bicyclo[2.2.2]octane-1-carboxylic acid

[0770] first step

[0771] At room temperature, 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (5.00 g, 23.56 mmol), N-hydroxyphthalimide (4.23 g, 25.91 mmol), and 4-dimethylaminopyridine (143 mg, 1.18 mmol) were dissolved in dichloromethane (25 mL), and N,N'-diisopropylcarbodiimide (5.31 mL, 35.34 mmol) was added. The reaction was stirred at room temperature for 2 hours, and the reaction solution changed from orange to pale yellow. The solution was filtered through 2-3 cm silica gel, washed with dichloromethane (100 mL), and the filtrate was concentrated to give 1,3-dioxoisoindoline-2-yl-4-methylbicyclo[2.2.2]octane-1,4-dicarboxylic acid ester (8.20 g), yield: 97.4%. 1 H NMR (400MHz, CDCl3) δ7.88 (dt, J=5.4, 2.6Hz, 2H), 7.78 (dt, J=5.3, 2.4Hz, 2H), 3.68 (d, J= 1.8Hz, 3H), 2.11–2.02 (m, 6H), 1.90 (dd, J=10.3, 5.8Hz, 6H), 1.23 (dd, J=6.3, 1.6Hz, 3H).

[0772] Step 2

[0773] 1,3-Dioxoisoindoline-2-yl-4-methylbicyclo[2.2.2]octane-1,4-dicarboxylate (4.00 g, 11.19 mmol), tert-butyl (4-iodophenyl)carbamate (3.57 g, 11.19 mmol), ethylene glycol dimethyl ether nickel chloride (983 mg, 4.48 mmol), 6-methoxypyridine-3-carbamate hydrochloride (840 mg, 4.48 mmol), tetrabutylammonium iodide (4.13 g, 11.19 mmol), and zinc powder (7.32 g, 111.93 mmol) were placed in a two-necked flask, purged with nitrogen three times, dissolved in N,N-dimethylacetamide (20 mL), and then trifluoroacetic acid (0.34 mL, 4.48 mmol) was added. The mixture was stirred rapidly at room temperature for 2 hours. An aqueous solution of ammonium chloride (300 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (2 x 200 mL). The mixture was washed with sodium chloride solution, dried over the organic phase, concentrated, and the residue was purified by silica gel column chromatography (elution system A) to obtain crude methyl 4-(4-((tert-butoxycarbonyl)amino)phenyl)bicyclo[2.2.2]octane-1-carboxylate (10.05 g). MS m / z (ESI): 360.1 [M+H] +

[0774] Step 3

[0775] 10.05 g of methyl 4-(4-((tert-butoxycarbonyl)amino)phenyl)bicyclo[2.2.2]octane-1-carboxylate was dissolved in 20 mL of trifluoroacetic acid and 100 mL of dichloromethane at room temperature, and the reaction was continued with stirring at room temperature for 2 hours. The reaction solution was concentrated, the residue was quenched with saturated sodium bicarbonate solution, extracted with dichloromethane (3 x 200 mL), concentrated, and the residue was purified by silica gel column chromatography (elution system A) to give methyl 4-(4-aminophenyl)bicyclo[2.2.2]octane-1-carboxylate (700 mg, purity 70%), yield: 16.9%. MS m / z (ESI): 260.1 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ6.95(d,J=8.5Hz,2H),6.47(d,J=8.4Hz,2H),4.81(br s,2H),3.58(s,3H),1.82-1.75(m,6H),1.74-1.65(m,6H)

[0776] Step 4

[0777] A solution of 3-(trifluoromethylthio)aniline (500 mg, 2.59 mmol) and N,N'-carbamodiimidazole (420 mg, 2.59 mmol) in acetonitrile (10 mL) was stirred at 20 °C for 1 hour, and the solvent was removed by concentration under reduced pressure. The solution was dissolved in tetrahydrofuran (10 mL), followed by the sequential addition of N-methylmorpholine (785 mg, 7.76 mmol) and D-proline (298 mg, 2.59 mmol), and stirred at 20 °C for 6 hours. After the reaction was complete, the reaction solution was quenched with sodium bicarbonate solution (50 mL), washed with diethyl ether (30 mL), and the aqueous phase was acidified with hydrochloric acid to pH 3. The solution was extracted with ethyl acetate (50 mL x 3), dried over sodium sulfate, filtered, and concentrated to give ((3-(trifluoromethylthio)phenyl)carbamoyl)-D-proline (690 mg), yield 78.9%. MS m / z(ESI): 335.0 [M+H] +

[0778] Step 5

[0779] ((3-(trifluoromethylthio)phenyl)carbamoyl)-D-proline (150 mg, 0.45 mmol), methyl 4-(4-aminophenyl)bicyclo[2.2.2]octane-1-carboxylate (116 mg, 0.45 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) were dissolved in dichloromethane (5 mL) and stirred at 20 °C for 6 hours. After the reaction was complete, the solution was concentrated under reduced pressure to obtain crude (R)-4-(4-(1-((3-(trifluoromethylthio)phenyl)carbamoyl)pyrrole-2-carboxamido)phenyl)bicyclo[2.2.2]octane-1-carboxylate (400 mg). MS m / z (ESI): 576.2 [M+H] + .

[0780] Step 6

[0781] At room temperature, crude (R)-4-(4-(1-((3-(trifluoromethylthio)phenyl)carbamoyl)pyrrole-2-carbamate)phenyl)bicyclo[2.2.2]octane-1-carboxylic acid methyl ester (400 mg) was dissolved in methanol (6 mL), tetrahydrofuran (3 mL), and water (3 mL). Lithium hydroxide (107 mg, 4.48 mmol) was added, and the reaction was stirred at room temperature for 3 hours. The pH was adjusted to 3 with 6N hydrochloric acid, and the mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC (formic acid system) to obtain (R)-4-(4-(1-((3-(trifluoromethylthio)phenyl)carbamoyl)pyrrole-2-carbamate)phenyl)bicyclo[2.2.2]octane-1-carboxylic acid (68.4 mg), yield: 26.9%. MS m / z (ESI): 562.2 [M+H] + . 1H NMR(400MHz,DMSO-d6)δ12.02(br s,1H),9.90(s,1H),8.57(s,1H),7.99(s,1H),7.73(d,J=7.9Hz,1H),7.50(d,J=8.6Hz,2H),7.39(t,J=8.0Hz,1H),7.29-7.20(m, 3H), 4.45 (dd, J = 3.7, 8.2Hz, 1H), 3.69-3.60 (m, 1H), 3.57-3.49 (m, 1H), 2.24-2.11 (m, 1H), 2.06-1.84 (m, 3H), 1.83-1.71 (m, 12H).

[0782] Example O

[0783] (R)-2-methoxy-4-(4-(1-((3-(trifluoromethylthio)phenyl)carbamoyl)pyrrole-2-carboxamido)bicyclo[2.2.2]octane-1-yl)benzoic acid

[0784] first step

[0785] ((3-(trifluoromethylthio)phenyl)carbamoyl)-D-proline (150 mg, 0.45 mmol), methyl 4-(4-aminobicyclo[2.2.2]octane-1-yl)-2-methoxybenzoate (129 mg, 0.45 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) were dissolved in dichloromethane (5 mL) and stirred at 20 °C for 6 hours. After the reaction was complete, the solution was concentrated under reduced pressure to obtain crude (R)-2-methoxy-4-(4-(1-((3-(trifluoromethylthio)phenyl)carbamoyl)pyrrole-2-carbamate)bicyclo[2.2.2]octane-1-yl)benzoate (400 mg). MS m / z (ESI): 606.2 [M+H] + .

[0786] Step 2

[0787] At room temperature, crude methyl benzoate (R)-2-methoxy-4-(4-(1-((3-(trifluoromethylthio)phenyl)carbamoyl)pyrrole-2-carbamoyl)bicyclo[2.2.2]octane-1-yl)benzoate (400 mg) was dissolved in methanol (6 mL), tetrahydrofuran (3 mL), and water (3 mL). Lithium hydroxide (107 mg, 4.48 mmol) was added, and the reaction was stirred at room temperature for 3 hours. The pH was adjusted to 3 with 6N hydrochloric acid, and the mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC (formic acid syste...

Claims

1. A compound of general formula (I) or a pharmaceutically acceptable salt thereof: in: M1 or M2 are each independently selected from CH or N; L1, L2, or L3 is independently selected from a bond, -C(O)-, -NR 11 C(O)-, -C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)NR 11 -, -NR 11 C(O)(CR 22 R 33 ) n3 -, -NR 11 C(O)NR 22 -, -C(S)-, -NR 11 C(S)-, -C(S)NR 11 -, -(CR 22 R 33 ) n3 C(S)NR 11 -, -NR 11 C(S)NR 22 -, -(CR 22 R 33 ) n3 -, -NR 11 -, -(CR 22 R 33 ) n3 NR 11 -, -NR 11 (CR 22 R 33 ) n3 -, -S(O) n4 -, -NR 11 S(O) n4 -, -S(O) n4 NR 11 -, -NR 11 C=NR 22 -, -NR 11 C=CR 22 R 33 -, -R 11 C=CR 22 -, -NR 11 C(O)C(O)-, -C(O)C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)-, -C(O)(CR 22 R 33 ) n3 -, -NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally substituted with one or more of the following substituents: halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl. Alternatively, L1 and L2 may form heterocyclic groups with the atoms they are attached to; Ring A, ring B, or ring D are each independently selected from cycloalkyl, heterocyclic, aryl, or heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, alkenylcarboxyl, or alkynylcarboxyl groups. R 11 R 22 or R 33 Each of the following groups is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, is optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl; R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 -C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH、 -(CR aa R bb ) m1 C(O)C(O)R 31 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl groups are optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl or carboxyl groups. Alternatively, any two atoms connected to R1, R2, R3, and R4 may form a cycloalkyl, heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups. Alternatively, when y is 2, 3, or 4, the two R2 atoms connected to them form a cycloalkyl, heterocyclic, or aryl group, wherein the cycloalkyl, heterocyclic, or aryl group is optionally substituted by one or more substituents selected from hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or carboxyl groups. R 31 R 32 R 33 R aa R bb or R cc Each of the following is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl, optionally substituted by one or more substituents selected from halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl; Or, R aa R bb It forms cycloalkyl or heterocyclic groups with the atoms attached to it; x, y, z and t are each independently 0, 1, 2, 3 or 4; n1 or n2 can be 0, 1, 2 or 3 independently; n3 can be 0, 1, 2 or 3 independently; n4 or m2 are each independently 0, 1, or 2; and m1 can be 0, 1, 2 or 3 independently; The conditions are: When M1 is N, M2 is CH, and ring A is pyridyl, pyrazolyl, phenyl, or... Ring B is pyridyl, phenyl, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, acetamido, and when R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not phenyl or pyridyl.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, The compound is further represented by general formula (II-1), (II-2), (II-3), or (II-4): in: X5, X6, X7, X8, or X9 are each independently selected from CH or N; The definitions of L1, L2, L3, ring A, ring B, ring D, R1, R2, R3, R4, n1, n2, x, y, and z are as described in claim 1; And at least one R4 is selected from a carboxyl group; t is 1, 2, 3, or 4; The conditions are: (1) In general formula (II-1), X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, phenyl, When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, acetamiprid, and when R4 is selected from 1, 2 or 3 substituents from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not phenyl or pyridyl. (2) In general formula (II-2), X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is phenyl or pyridine, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, then ring A is not pyridyl, pyrazolyl, phenyl, or 3. A compound of general formula (III-1) or a pharmaceutically acceptable salt thereof: in: Ring D is selected from C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; Preferably, ring D is selected from C. 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1- 3-Hydroalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; X5, X6, X7, X8, or X9 are each independently selected from C or N; L1 or L2 are each independently selected from bonds, C(O), and NR. 11 C(O), C(O)NR 11 、(CR 22 R 33 ) n3 C(O)NR 11 NR 11 C(O)NR 22 、(CR 22 R 33 ) n3 NR 11 、(CR 22 R 33 ) n3 NR 11 NR 11 (CR 22 R 33 ) n3 S(O) n4 NR 11 S(O) n4 S(O) n4 NR 11 Or O; R 11 R 22 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Preferably, R 11 R 22 or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1- 3-alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-3 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -N(CR) aa R bb ) m1 R 31 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH or The amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. R 31 R 32 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Preferably, R 31 R 32 or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, or propoxy groups are optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Preferably, R aa R bb or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy. Ring B is selected from C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-14 Aryl or 5-14 membered heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-14 A aryl group or a 5-14 membered heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH or One or more substituents are substituted in the sample; Preferably, ring B is selected from C. 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, 8-14 member fused heteroaryl containing 1-3 N, O or S atoms, carboxyl, -(CR aa =CR bb ) m1 COOH or The C mentioned 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5- 10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-14 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring B is selected from C. 3-6 Monocycloalkyl, C 6-14 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-14 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-14 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-14 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-14 aryl, 5-6 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-14 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1- 3-Hydroalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Substitution with one or more substituents, such as alkyl, carboxyl, or (CH=CH)COOH; More preferably, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ... Phenyl, It may be optionally substituted with one or more of the following substituents: hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, carboxyl, or (CH=CH)COOH; x, y, z and t are each independently 0, 1, 2, 3 or 4; n1 or n2 are each independently 0, 1 or 2; n3 can be 0, 1, 2 or 3 independently; n4 or m2 are each independently 0, 1, or 2; and m1 can be 0, 1, 2 or 3 independently; The conditions are: When X5, X6, X7, X8, and X9 are each independently selected from C or N, L1 is NHC(O), L2 is C(O)NH, and ring B is pyridine, benzene ring, or... When both n1 and n2 are 1, ring D is neither a benzene ring nor a pyridine ring.

4. A compound of general formula (II-1) or a pharmaceutically acceptable salt thereof: in: X5, X6, X7, X8, or X9 are each independently selected from CH or N; Ring D is selected from C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents in the alkyl group, -SF5 or -SCF3 are substituted; Preferably, ring D is selected from C. 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution; More preferably, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1- 3-Hydroalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution; L1, L2, or L3 is independently selected from a bond, -C(O)-, -NR 11 C(O)-, -C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)NR 11 -, -NR 11 C(O)(CR 22 R 33 ) n3 -, -NR 11 C(O)NR 22 -, -C(S)-, -NR 11 C(S)-, -C(S)NR 11 -, -(CR 22 R 33 ) n3 C(S)NR 11 -, -NR 11 C(S)NR 22 -, -(CR 22 R 33 ) n3 -, -NR 11 -, -(CR 22 R 33 ) n3 NR 11 -, -NR 11 (CR 22 R 33 ) n3 -, -S(O) n4 -, -NR 11 S(O) n4 -, -S(O) n4 NR 11 -, -NR 11 C=NR 22 -, -NR 11 C=CR 22 R 33 -, -R 11 C=CR 22 -, -NR 11 C(O)C(O)-, -C(O)C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)-, -C(O)(CR 22 R 33 ) n3 -, -NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 3-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted; R 11 R 22 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Preferably, R 11 R 22 or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1- 3-alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; More preferably, L1, L2, or L3 are each independently selected from the following: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-, More preferably, L1 or L2 is independently selected from -NHC(O)-, -C(O)NH-, -NHC(S)- or -C(S)NH-; R1, R2, R3, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH、 -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. R 31 R 32 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Or, R aa R bb Forming C with the attached atoms 3-10 Cycloalkyl or containing 1-4 3-10 membered heterocyclic groups selected from N, O or S heteroatoms; Preferably, R 31 R 32 or R 33 Each group is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl group is optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy. Or, R aa R bb Forming C with the attached atoms 3-6 Cycloalkyl or containing 1-4 4-6 membered heterocyclic groups selected from N, O or S heteroatoms. More preferably, R1, R2, R3, R4, or R5 are each independently selected from hydrogen, fluorine, chlorine, bromine, amino, oxo, methylamino, dimethylamino, hydroxyl, cyano, nitro, carboxyl, methyl, ethyl, isopropyl, tert-butyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, difluorovinyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, cyclopropoxy, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SF5, -B(OH)2, -SCF3, -CH2COOH, -S(O)OH, More preferably, R1, R2, R3, R4, or R5 are each independently selected from hydrogen, fluorine, carboxyl, methyl, isopropyl, methoxy, trifluoromethyl, -SF5, -B(OH)2, Ring B is selected from C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, 5-8 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 A aryl group, a 5-8 membered mono-heteroaryl group containing 1-4 N, O, S, P, or B atoms, or an 8-14 membered fused heteroaryl group containing 1-4 N, O, S, P, or B atoms, optionally prefixed with an oxo group, a thio group, a halogen, an amino group, a hydroxyl group, a cyano group, a nitro group, or a C group. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1- 3-alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R3, -(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample; More preferably, ring B is selected from C. 3-6 Monocycloalkyl, C 6-14 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-8 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, 5-6 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-6 Monocycloalkyl, C 6-14 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-8 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 A aryl group, a 5-6 member mono-heteroaryl group containing 1-4 N, O, S, P, or B atoms, or an 8-14 member fused heteroaryl group containing 1-4 N, O, S, P, or B atoms, optionally prefixed with an oxo group, a thio group, a halogen, an amino group, a hydroxyl group, a cyano group, a nitro group, or a C group. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb COOH, -S(O) m2 R 32 -S(O)(=NR) cc )R 32 -BR 31 R 32 、-(NR 31 )C(O)R 32 -C(O)C(O)R 31 -C(O)NR 31 R 32 or -S(O) m2 NR 31 R 32 One or more substituents are substituted in the sample; More preferably, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, Optional radicals include hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -(CH=CH)COOH, -B(OH)2, -CH2COOH, and -S(O)OH. One or more substituents are substituted in the sample; More preferably, ring B is selected from phenyl, Optional radicals include hydrogen, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -B(OH)2, or... One or more substituents are substituted in the sample; x, y, z and t are each independently 0, 1, 2, 3 or 4; n1 or n2 are each independently 0, 1 or 2; n3 can be 0, 1, 2 or 3 independently; n4 or m2 are each independently 0, 1, or 2; and m1 can be 0, 1, 2 or 3 independently; The conditions are: When X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, and L1 and L2 do not form heterocyclic groups with the atoms they are attached to. Ring B is pyridine, benzene ring, etc. When n1 is 2, n2 is 0, R1 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano or acetamido, and R4 is selected from 1, 2 or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano or -C(O)NH2, ring D is not a benzene ring or a pyridine ring.

5. A compound of general formula (II-2) or a pharmaceutically acceptable salt thereof: in: X5, X6, X7, X8, or X9 are each independently selected from CH or N; Ring D is selected from C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally surrounded by an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents in the alkyl group, -SF5 or -SCF3 are substituted; Preferably, ring D is selected from C. 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution; More preferably, ring D is selected from C. 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1- 3-Hydroalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 One or more substituents from alkyl, -SF5, or -SCF3 are used for substitution; L1, L2, or L3 is independently selected from a bond, -C(O)-, -NR 11 C(O)-, -C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)NR 11 -, -NR 11 C(O)(CR 22 R 33 ) n3 -, -NR 11 C(O)NR 22 -, -C(S)-, -NR 11 C(S)-, -C(S)NR 11 -, -(CR 22 R 33 ) n3 C(S)NR 11 -, -NR 11 C(S)NR 22 -, -(CR 22 R 33 ) n3 -, -NR 11 -, -(CR 22 R 33 ) n3 NR 11 -, -NR 11 (CR 22 R 33 ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 3-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted; R 11 R 22 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Preferably, R 11 R 22 or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1- 3-alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; More preferably, L1, L2, or L3 are each independently selected from the following: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-, More preferably, L1 or L2 is independently selected from -NHC(O)-, -C(O)NH-, -NHC(S)- or -C(S)NH-; R1, R2, R3, or R4 are each independently selected from halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2- 4-Alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH、 -(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. Alternatively, R3, R4, and the atoms attached to them form a 3-10 membered heterocyclic group containing 1-4 N, O, or S atoms, optionally surrounded by a halogen, amino, hydroxyl, oxo, cyano, nitro, or C atom. 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. Alternatively, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, or C 6-10 Aryl, the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, or C 6-10 aryl, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. R 31 R 32 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Or, R aa R bb Forming C with the attached atoms 3-10 Cycloalkyl or containing 1-4 3-10 membered heterocyclic groups selected from N, O or S heteroatoms; Preferably, R 31 R 32 or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxy, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazole. The group consisting of amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl, optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy. Or, R aa R bb Forming C with the attached atoms 3-6 Cycloalkyl or containing 1-4 4-6 membered heterocyclic groups selected from N, O or S heteroatoms; More preferably, R1, R2, R3, R4, or R5 are each independently selected from fluorine, chlorine, bromine, amino, oxo, methylamino, dimethylamino, hydroxyl, cyano, nitro, carboxyl, methyl, ethyl, isopropyl, tert-butyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, difluorovinyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, cyclopropoxy, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SF5, -B(OH)2, -SCF3, -CH2COOH, -S(O)OH, Alternatively, R3, R4 and the atoms they are bonded to form Alternatively, when y is 2, 3 or 4, the two R2 atoms connected to them form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl groups; More preferably, R1, R2, R3, R4, or R5 are each independently selected from fluorine, carboxyl, methyl, isopropyl, methoxy, trifluoromethyl, -SF5, -B(OH)2, Ring A is selected from C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; Preferably, ring A is selected from C. 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, a 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or an 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with an oxo group, thio group, halogen, amino group, hydroxyl group, cyano group, nitro group, C group, etc. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ... Optionally substituted with one or more substituents selected from fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl; More preferably, ring A is selected from... Optionally substituted with one or more substituents selected from fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl; x, y, z and t are each independently 0, 1, 2, 3 or 4; n1 or n2 are each independently 0, 1 or 2; n3 can be 0, 1, 2 or 3 independently; n4 or m2 are each independently 0, 1, or 2; and m1 can be 0, 1, 2 or 3 independently; The conditions are: In general formula (III-5), X5, X6, X7, X8, and X9 are each independently selected from CH or N, L1 is -NHC(O)-, L2 is -C(O)NH-, L3 is a bond, L1 and L2 do not form heterocyclic groups with the atoms they are attached to, ring D is a benzene ring or a pyridine ring, n1 is 2, n2 is 0, R1 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, tert-butyl, 3-6 membered cycloalkyl, trifluoromethyl, propenyl, or methoxy, R2 is selected from one or more substituents selected from hydrogen, fluorine, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, cyano, or acetamido, and R4 is selected from 1, 2, or 3 substituents selected from halogen, methyl, isopropyl, hydroxy, trifluoromethyl, methoxy, carboxyl, cyano, or -C(O)NH2, then ring A is not a pyridine ring, benzene ring, or 6. The compound according to any one of claims 1-5, or a pharmaceutically acceptable salt thereof, characterized in that, Ring D is selected from C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O or S atoms, or 6-10 membered bridged heterocyclic groups containing 1-3 N, O or S atoms.

7. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-6, characterized in that, Cyclode D is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, The compound is further shown in general formula (II-5): in: n5 or n6 are each independently 1, 2 or 3; and n7 can be 0, 1, 2, or 3; The definitions of L1, L2, L3, ring A, ring B, R1, R2, R3, R4, n1, n2, x, y, z, and t are as described in claim 1.

9. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, The compound is further represented by general formula (III-2) or (III-3): in: n1 or n2 are each independently 0, 1 or 2; The definitions of L1, L2, ring A, ring B, R1, R2, R3, R4, n1, n2, x, y, z, and t are as described in claim 1.

10. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that, The compound is further represented by general formula (IV-1), (IV-2), (IV-3), (IV-4), or (IV-5): The definitions of L1, L2, ring A, ring B, R1, R2, R3, R4, n1, n2, x, y, z, and t are as described in claim 1; the definitions of X5, X6, X7, X8, or X9 are as described in claim 2.

11. The compound according to claim 10 or a pharmaceutically acceptable salt thereof, characterized in that, The compound is further represented by the general formula (V-1), (V-2), (V-3), (V-4), (V-5), (V-6), (V-7), (V-8), (V-9), (V-10), or (V-11): in: X0, X1, X2, X3, or X4 are each independently selected from CH or N; The definitions of L1, L2, ring A, ring B, R1, R2, R3, R4, n1, n2, x, y, z, and t are as described in claim 1; the definitions of X5, X6, X7, X8, or X9 are as described in claim 2; Preferably, the compound further comprises the general formula (V-1A), (V-2A), (V-3A), (V-4A), (V-5A), (V-6A), (V-7A), (V-8A), (V-9A), (V-10A), or (V-11A): in: X0, X1, X2, X3, or X4 are each independently selected from CH or N; The definitions of L1, L2, ring A, ring B, R1, R2, R3, R4, n1, n2, x, y, z, and t are as described in claim 1; the definitions of X5, X6, X7, X8, or X9 are as described in claim 2.

12. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-11, characterized in that, L1 or L2 is independently selected from a bond, -C(O)-, -NR 11 C(O)-, -C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)NR 11 -, -NR 11 C(O)(CR 22 R 33 ) n3 -, -NR 11 C(O)NR 22 -, -C(S)-, -NR 11 C(S)-, -C(S)NR 11 -, -(CR 22 R 33 ) n3 C(S)NR 11 -, -NR 11 C(S)NR 22 -, -(CR 22 R 33 ) n3 -, -NR 11 ) -, -(CR 22 R 33 ) n3 NR 11 -, -NR 11 (CR 22 R 33 ) n3 -, -S(O) n4 -, -NR 11 S(O) n4 -, -S(O) n4 NR 11 -, -NR 11 C=NR 22 -, -NR 11 C=CR 22 R 33 -, -R 11 C=CR 22 -, -NR 11 C(O)C(O)-, -C(O)C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)-, -C(O)(CR 22 R 33 ) n3 -, -NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally converted by a halogen, amino, hydroxyl, oxo, cyano, nitro, or C group. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1- 6-alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; Alternatively, L1, L2, and the atoms attached to them form 3-12 membered heterocyclic groups, optionally surrounded by halogen, amino, hydroxyl, oxo, cyano, nitro, or C groups. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; R 11 R 22 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1- 6-alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally surrounded by hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 The alkyl halogroup is substituted by one or more substituents; Preferably, each of L1 and L2 is independently selected from a bond, -C(O)-, -NR 11 C(O)-, -C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)NR 11 -, -NR 11 C(O)(CR 22 R 33 ) n3 -, -NR 11 C(O)NR 22 -, -C(S)-, -NR 11 C(S)-, -C(S)NR 11 -, -(CR 22 R 33 ) n3 C(S)NR 11 -, -NR 11 C(S)NR 22 -, -(CR 22 R 33 ) n3 -, -NR 11 -, -(CR 22 R 33 ) n3 NR 11 -, -NR 11 (CR 22 R 33 ) n3 -, -S(O) n4 -, -NR 11 S(O) n4 -, -S(O) n4 NR 11 -, -NR 11 C=NR 22 -, -NR 11 C=CR 22 R 33 -, -R 11 C=CR 22 -, -NR 11 C(O)C(O)-, -C(O)C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)-, -C(O)(CR 22 R 33 ) n3 -, -NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 3-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted; Alternatively, L1, L2, and the atoms attached to them form a 5-12 membered heterocyclic group containing 1-6 N, O, or S atoms, optionally coated with a halogen, hydroxyl group, oxo group, or C group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted; R 11 R 22 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; More preferably, R 11 R 22 or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; More preferably, L1 or L2 is independently selected from the following: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-, -NHC(O)CH2-, -CH2NHC(O)NH-, Alternatively, L1, L2 and the atoms connected to them form Optionally substituted with one or more of the following: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl. More preferably, L1 or L2 is independently selected from -NHC(O)-, -C(O)NH-, -NHC(S)-, -C(S)NH-, -CH2C(O)NH-, -CH2NHC(O)- or 13. The compound or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that, L3 is selected from a bond, -C(O)-, -NR 11 C(O)-, -C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)NR 11 -, -NR 11 C(O)(CR 22 R 33 ) n3 -, -NR 11 C(O)NR 22 -, -C(S)-, -NR 11 C(S)-, -C(S)NR 11 -, -(CR 22 R 33 ) n3 C(S)NR 11 -, -NR 11 C(S)NR 22 -, -(CR 22 R 33 ) n3 -, -NR 11 -, -(CR 22 R 33 ) n3 NR 11 -, -NR 11 (CR 22 R 33 ) n3 -, -S(O) n4 -, -NR 11 S(O) n4 -, -S(O) n4 NR 11 -, -NR 11 C=NR 22 -, -NR 11 C=CR 22 R 33 -, -R 11 C=CR 22 -, -NR 11 C(O)C(O)-, -C(O)C(O)NR 11 -, -(CR 22 R<00多1662>) n3 C(O)-, -C(O)(CR 22 R 33 ) n3 -, -NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-10 cycloalkylene group-, -3-10 cycloalkylene group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )3-10 cycloalkylene group -, -3-10 cycloalkylene group (NR 11 (CR 22 R 33 ) n3 )-、-(NR 11 C(O))4-10 heterocyclic group-,-4-10 heterocyclic group (NR) 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 )4-10-membered heterocyclic group- or -4-10-membered heterocyclic group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic, cycloalkyl, or heteroaryl group is optionally converted by a halogen, amino, hydroxyl, oxo, cyano, nitro, or C group. 1- 6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; R 11 R 22 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1- 6-alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally surrounded by hydroxyl, halogen, cyano, amino, C 1-6 Alkyl, C 1-6 The alkyl halogroup is substituted by one or more substituents; Preferably, L3 is selected from a bond, -C(O)-, -NR 11 C(O)-, -C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)NR 11 -, -NR 11 C(O)(CR 22 R 33 ) n3 -, -NR 11 C(O)NR 22 -, -C(S)-, -NR 11 C(S)-, -C(S)NR 11 -, -(CR 22 R 33 ) n3 C(S)NR 11 -, -NR 11 C(S)NR 22 -, -(CR 22 R 33 ) n3 -, -NR 11 -, -(CR 22 R 33 ) n3 NR 11 -, -NR 11 (CR 22 R 33 ) n3 -, -S(O) n4 -, -NR 11 S(O) n4 -, -S(O) n4 NR 11 -, -NR 11 C=NR 22 -, -NR 11 C=CR 22 R 33 -, -R 11 C=CR 22 -, -NR 11 C(O)C(O)-, -C(O)C(O)NR 11 -, -(CR 22 R 33 ) n3 C(O)-, -C(O)(CR 22 R 33 ) n3 -, -NR 11 (CR 22 R 33 ) n3 C(O)-、-C(O)(CR 22 R 33 ) n3 NR 11 -、-C(O)NR 11 (CR 22 R 33 ) n3 -、-(CR 22 R 33 ) n3 NR 11 C(O)-、-(CR 22 R 33 ) n3 NR 11 C(O)NR 22 -、-NR 11 C(O)NR 22 (CR 22 R 33 ) n3 -、-(NR 11 )3-10-membered heterocyclic group-, -3-10-membered heterocyclic group (NR 11 )-、-(NR 11 )3-8 cycloalkylene group -, -3-8 cycloalkylene group (NR 11 )-、-(NR 11 5-10-membered heteroaryl-, -5-10-membered heteroaryl (NR) 11 )-、-O-、-(NR 11 C(O))3-8 membered cycloalkylene group-,-3-8 membered cycloalkylene group (NR 11 C(O))-、-(NR 11 (CR 22 R 33 ) n3 3-8 cyclic alkylene group - or -3-8 cyclic alkylene group (NR) 11 (CR 22 R 33 ) n3 The heterocyclic group, cycloalkyl group, or heteroaryl group is optionally converted by a halogen, hydroxyl group, oxo group, or C- group. 1-3 Alkyl, C 2-3 alkenyl, C 1-3 One or more substituents in the haloalkyl group are substituted; R 11 R 22 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl or containing 1-3 5-10 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; More preferably, R 11 R 22 or R 33 Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, wherein the amino, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, epoxyethyl, epoxypropyl, or epoxybutyl, optionally by a hydroxyl, halogen, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; More preferably, L3 is selected from the following: -C(O)-, -NHC(O)-, -C(O)NH-, -NH-, -C(S)-, -NHC(S)-, -C(S)NH-, -NHC(O)NH-, -NHS(O)2-, -CH2-, -NHCH2-, -CH2NH-, -C(O)C(O)-, -CH2C(O)-, -C(O)CH2-, -C(O)N(CH3)-, -N(CH3)C(O)-, -CH2C(O)NH-, -O-, -NHCH2C(O)-, -CH2C(O)NH-, -C(O)NHCH2-, -CH2NHC(O)-, -NHC(O)CH2- or -CH2NHC(O)NH-.

14. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-11, characterized in that, R1, R2, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH、-CR aa =CR aa R bb 、 -(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally further converted by halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; Alternatively, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, optionally further bonded by hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; R 31 R 32 R 33 R aa R bb or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1- 6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally halogenated, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; Or, R aa R bb Forming C with the attached atoms 3-15 Cycloalkyl or containing 1-5 3-15 membered heterocyclic groups selected from N, O or S heteroatoms; Preferably, R1, R2, or R4 are each independently selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH、 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. Alternatively, when y is 2, 3, or 4, the two R2 atoms and their connected atoms form C. 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally coated with hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, or C. 1-3 Alkyl, C 2- 4-Alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1- 3-alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. R 31 R 32 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Or, R aa R bb Forming C with the attached atoms 3-10 Cycloalkyl or containing 1-4 3-10 membered heterocyclic groups selected from N, O or S heteroatoms; More preferably, R 31 R 32 or R 33 Each group is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl group is optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy. Or, R aa R bb Forming C with the attached atoms 3-6 Cycloalkyl or containing 1-4 4-6 membered heterocyclic groups selected from N, O or S heteroatoms. More preferably, R aa R bb It forms pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups with the attached atoms. Optionally substituted with one or more of the following: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl. More preferably, R1, R2, or R4 are each independently selected from hydrogen, fluorine, chlorine, bromine, amino, oxo, methylamino, dimethylamino, hydroxy, cyano, nitro, carboxyl, methyl, ethyl, isopropyl, tert-butyl, n-butyl, fluoromethyl, chloromethyl, fluoroethyl, chloroethyl, difluoromethyl, difluoroethyl, difluorovinyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, cyclopropoxy, hydroxymethyl, hydroxyethyl, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SF5, -B(OH)2, -SCF3, -CH2COOH, -S(O)OH, -C(O)NH2, Alternatively, when y is 2, 3 or 4, the two R2 atoms connected to them form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl groups; More preferably, R1, R2, or R4 are each independently selected from hydrogen, fluorine, carboxyl, methyl, isopropyl, methoxy, trifluoromethyl, -SF5, -B(OH)2, 15. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-10, characterized in that, R3 is selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH、-CR aa =CR aa R bb 、 -(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally further converted by halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; Alternatively, R3, R4, and the atoms they are bonded to form C. 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3- 14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, optionally further bonded by hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; R 31 R 32 R 33 R aa R bb or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1- 6-alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl, wherein the amino group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl or 5-12 heteroaryl groups, optionally halogenated, amino, hydroxyl, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 One or more substituents in the aryl or 5-12 heteroaryl groups are used for substitution; Or, R aa R bb Forming C with the attached atoms 3-15 Cycloalkyl or containing 1-5 3-15 membered heterocyclic groups selected from N, O or S heteroatoms; Preferably, R3 is selected from hydrogen, halogen, amino, hydroxyl, mercapto, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3- 10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 aryl, 5-10 heteroaryl groups containing 1-4 N, O or S atoms, carboxyl, -O(CR) aa R bb ) m1 R 31 -NR 31 (CR aa R bb ) m1 R 32 -S(CR) aa R bb ) m1 R 31 -OCR 31 R 32 R 33 、-(CR aa R bb ) m1 C(O)R 31 N = S = OR 31 R 32 、N(R 31 ) = S = OR 32 -、-(CH2) m1 C(O)NR 31 R 32 -(CH2) m1 P(O)R 31 R 32 -(CH2) m1 P(O)2R 31 R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)NR 31 R 32 、-(CR aa R bb ) m1 (NR 31 )S(O) m2 R 32 、-C(O)NR 31 S(O) m1 R 32 、-(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa =CR bb ) m1 COOH、 -CR aa =CR aa R bb 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(=NR 31 )R 32 The amino, hydroxyl, thiol, and C groups mentioned above 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1- 3-alkoxy group, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-4 N, O, or S atoms, C 6-10 Aryl or containing 1-4 5-10 heteroaryl groups selected from N, O, or S atoms, optionally coated with halogen, amino, hydroxyl, oxo, cyano, nitro, C 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. Alternatively, R3, R4, and the atoms they are bonded to form C. 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally coated with hydrogen, halogen, amino, hydroxyl, oxo, cyano, nitro, or C. 1-3 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 The aryl group or one or more substituents selected from 1-3 5-10 heteroaryl groups chosen from N, O or S atoms are used for substitution. R 31 R 32 or R 33 Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 The aryl group or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, wherein the amino group, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-10 Aryl or containing 1-3 5-8 heteroaryl groups selected from N, O, or S atoms, optionally surrounded by hydroxyl, halogen, cyano, amino, or C atoms. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, the amino groups, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 Alkyl groups, optionally replaced by hydroxyl, halogen, cyano, amino, or C groups. 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; Or, R aa R bb Forming C with the attached atoms 3-10 Cycloalkyl or containing 1-4 3-10 membered heterocyclic groups selected from N, O or S heteroatoms; More preferably, R 31 R 32 or R 33 Each group is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl, wherein the amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, aminomethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, or oxazolyl group is optionally replaced by hydroxyl, fluorine, chlorine, bromine, cyano, amino, C 1-3 Alkyl, C 1-3 The alkyl halogroup is substituted by one or more substituents; R aa R bb or R cc Each is independently selected from hydrogen, fluorine, chlorine, bromine, amino, methylamino, dimethylamino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, aminomethyl, methoxy, ethoxy, or propoxy. Or, R aa R bb Forming C with the attached atoms 3-6 Cycloalkyl or containing 1-4 4-6 membered heterocyclic groups selected from N, O or S heteroatoms. More preferably, R aa R bb It forms pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups with the attached atoms. Optionally substituted with one or more of the following: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl. More preferably, R3 is selected from hydrogen, fluorine, chlorine, bromine, amino, oxo, methylamino, dimethylamino, hydroxy, cyano, nitro, carboxyl, methyl, ethyl, isopropyl, tert-butyl, n-butyl, fluoromethyl, chloromethyl, fluoroethyl, chloroethyl, difluoromethyl, difluoroethyl, difluorovinyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, cyclopropoxy, hydroxymethyl, hydroxyethyl, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SF5, -B(OH)2, -SCF3, -CH2COOH, -S(O)OH, -C(O)NH2, Alternatively, R3, R4 and the atoms they are bonded to form It may optionally be substituted with one or more of the following substituents: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl.

16. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-2 or 5-10, characterized in that, Ring A is selected from C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 Aryl or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P or B atoms, optionally surrounded by hydrogen, halogen, amino, hydroxyl, mercapto, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, carboxyl, -S(CR) aa R bb ) m1 R 31 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 One or more substituents are substituted in the sample; Preferably, ring A is selected from C. 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-10 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, or C. 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring A is selected from C. 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-10 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally surrounded by hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring A is selected from C. 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-8 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-10 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl or cyano-substituted C 1-3 One or more substituents in the alkyl group are substituted; More preferably, ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ... The radical can be optionally covered by hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl. One or more substituents are substituted in the sample; More preferably, ring A is selected from... Optionally substituted with one or more of the following substituents: hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl; More preferably, ring A is selected from 17. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 or 6-10, characterized in that, Ring B is selected from C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 Aryl or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P or B atoms, optionally surrounded by hydrogen, halogen, amino, hydroxyl, mercapto, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, carboxyl, -S(CR) aa R bb ) m1 R 31 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample; Preferably, ring B is selected from C. 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6- 14 Aryl or 5-14 membered heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 A aryl group or a 5-14 membered heteroaryl group containing 1-4 N, O, S, P or B atoms, optionally surrounded by hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R 32 、-(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample; More preferably, ring B is selected from C. 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-4 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, 5-8 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5- 10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-4 N, O, S, P or B atoms, 4-14 membered fused heterocyclic groups containing 1-3 N, O, S, P or B atoms, 5-10 membered spirocyclic groups containing 1-4 N, O, S, P or B atoms, 4-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P or B atoms, C 6-14 Aryl, a 5-8 membered mono-heteroaryl containing 1-4 N, O, S, P or B atoms, or an 8-14 membered fused heteroaryl containing 1-4 N, O, S, P or B atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1- 3-Hydroalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 S(O) m2 NR 31 R 32 、-(CR aa R bb ) m1 S(O) m2 R3, -(CR aa R bb ) m1 S(O)(=NR cc )R 32 、-(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 、-(CR aa R bb ) m1 BR 31 R 32 or -(CR) aa R bb ) m1 C(O)NR 31 R 32 One or more substituents are substituted in the sample; More preferably, ring B is selected from C. 3-6 Monocycloalkyl, C 6-14 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P, or B atoms, 5-9 membered spirocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P, or B atoms, C 6-14 Aryl, 5-6 member monoheteroaryl containing 1-4 N, O, S, P or B atoms, 8-14 member fused heteroaryl containing 1-4 N, O, S, P or B atoms, wherein the C 3-6 Monocycloalkyl, C 6-14 fused cycloalkyl, C 5-8 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-14 membered fused heterocyclic groups containing 1-4 N, O, S, P, or B atoms, 5-9 membered spirocyclic groups containing 1-4 N, O, S, P, or B atoms, 6-10 membered bridged heterocyclic groups containing 1-4 N, O, S, P, or B atoms, C 6-14 Aryl, a 5-6 membered mono-heteroaryl containing 1-4 N, O, S, P or B atoms, or an 8-14 membered fused heteroaryl containing 1-4 N, O, S, P or B atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, carboxyl, -(CR) aa =CR bb COOH, -S(O) m2 R 32 -S(O)(=NR) cc )R 32 -BR 31 R 32 、-(NR 31 )C(O)R 32 -C(O)C(O)R 31 -C(O)NR 31 R 32 or -S(O) m2 NR 31 R 32 One or more substituents are substituted in the sample; More preferably, ring B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, The following groups are optionally covered: hydrogen, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -(CH=CH)COOH, -B(OH)2, -CH2COOH, -S(O)OH, -C(O)NH2. One or more substituents are substituted in the sample; More preferably, ring B is selected from cyclohexyl, phenyl, Optional radicals include hydrogen, methyl, ethyl, isopropyl, methoxy, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, oxo, carboxyl, -B(OH)2, or... One or more substituents are substituted in the sample; More preferably, ring B is selected from cyclohexyl, phenyl, 18. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, Selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally substituted with one or more of the following: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl or -SCF3; Preferably, Selected from Optionally substituted with one or more of the following: hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl. More preferably, Selected from Optionally substituted with one or more substituents selected from hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, or trifluoroethyl, wherein This indicates that it is connected to L1. This indicates that it is connected to L2.

19. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that, Ring D is selected from C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 The aryl group or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P, or B atoms, wherein the C 3-14 Cycloalkyl groups, 3-14 membered heterocyclic groups containing 1-5 atoms selected from N, O, S, P or B, C 6-14 Aryl or containing 1-5 5-14 heteroaryl groups selected from N, O, S, P or B atoms, optionally surrounded by hydrogen, halogen, amino, hydroxyl, mercapto, oxo, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 Alkyl, C 3-14 Cycloalkyl, 3-14 membered heterocyclic groups, C 6-14 Aryl, 5-14 heteroaryl, carboxyl, -S(CR) aa R bb ) m1 R 31 、-(CR aa =CR bb ) m1 COOH, -(CR aa R bb ) m1 (NR 31 )C(O)R 32 、-(CR aa R bb ) m1 C(O)C(O)R 31 or -(CR) aa R bb ) m1 BR 31 R 32 One or more substituents are substituted in the sample; Preferably, ring D is selected from C. 3-10 Cycloalkyl groups, 3-12 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 heteroaryl groups containing 1-3 N, O, or S atoms, wherein the C 3-10 Cycloalkyl groups, 3-12 membered heterocyclic groups containing 1-3 N, O or S atoms, C 6-12 A aryl group or a 5-12 heteroaryl group containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, or C. 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-10 One or more substituents from cycloalkyl, -SF5, or -SCF3 are used for substitution; More preferably, ring D is selected from C. 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-12 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-12 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-8 Monocycloalkyl, C 4-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 4-10 Bridged cycloalkyl groups, 3-8 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-12 membered spirocyclic groups containing 1-3 N, O, or S atoms, 4-12 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-8 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-12 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally surrounded by hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3-8 One or more substituents from cycloalkyl, -SF5, or -SCF3 are used for substitution; More preferably, ring D is selected from C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-11 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 member monoheteroaryl containing 1-3 N, O or S atoms, or 8-10 member fused heteroaryl containing 1-3 N, O or S atoms, wherein the C 3-6 Monocycloalkyl, C 6-10 fused cycloalkyl, C 5-9 Spirocycloalkyl, C 6-10 Bridged cycloalkyl groups, 3-6 membered monoheterocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered fused heterocyclic groups containing 1-3 N, O, or S atoms, 5-11 membered spirocyclic groups containing 1-3 N, O, or S atoms, 6-11 membered bridged heterocyclic groups containing 1-3 N, O, or S atoms, C 6-10 Aryl, 5-6 membered mono-heteroaryl containing 1-3 N, O, or S atoms, or 8-10 membered fused heteroaryl containing 1-3 N, O, or S atoms, optionally prefixed with hydrogen, oxo, thio, halogen, amino, hydroxyl, cyano, nitro, C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 1-3 Haloalkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 Alkyl, C 3- One or more substituents selected from 6-cycloalkyl, -SF5, or -SCF3; More preferably, ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyridine, pyrimidine, pyridazine, etc. Optional radicals include hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, tert-butyl, n-butyl, cyclopropyl, propynyl, methoxy, ethoxy, fluoromethyl, chloromethyl, fluoroethyl, chloroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, -SF5, -SCF3. One or more substituents are substituted in the sample; More preferably, ring D is selected from cyclobutyl, cyclohexyl, phenyl, Optional radicals include hydrogen, oxo, fluorine, chlorine, bromine, amino, hydroxyl, cyano, nitro, methyl, ethyl, isopropyl, propynyl, fluoromethyl, fluoroethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyclopropyl, -SF5, or One or more substituents are substituted in the sample.

20. The following compounds, or their pharmaceutically acceptable salts, have the following specific structures:

21. A method for preparing the compounds as described in claims 1-20 or pharmaceutically acceptable salts thereof, characterized in that, It includes the following steps: in: The definitions of ring B, ring D, R1, R2, R3, R4, L1, X5, X6, X7, X8, X9, x, y, z, and t are as described in claim 1; L2 is -C(O)NH-; General formulas (M-1A) and (M-1B) react under the action of a condensing agent and a base to obtain general formula (III-1); Preferably, the condensing agent is selected from EDCI, DIC, DCC, TBTU, HATU, HBTU, HCTU, DEPBT, PyBOP or PyAOP, more preferably EDCI or HATU; Preferably, the alkali is selected from DIEA, TEA, NMP, DBU or DABCO, more preferably DIEA; When at least one R4 is selected from C(O)O-PG1, the process also includes the step of removing the protecting group PG1 under the action of acid or base. Preferably, PG1 is selected from methyl, ethyl, isopropyl, tert-butyl, or benzyl, with methyl or tert-butyl being more preferred; Preferably, the alkali is selected from LiOH, NaOH, KOH or Cs2CO3, and more preferably LiOH; Preferably, the acid is selected from hydrochloric acid, formic acid, acetic acid, MSA, or TFA, more preferably MSA or TFA; Alternatively, it may include the following steps: in: The definitions of ring B, ring D, R1, R2, R3, R4, L2, X5, X6, X7, X8, X9, x, y, z, and t are as described in claim 1; L1 is -NHC(O)-; General formulas (M-2A) and (M-2B) react in the presence of a carbonylating agent and a base to give general formula (III-1); Preferably, the carbonylating agent is selected from CDI, triphosgene, diester carbonate or isocyanate, more preferably CDI or triphosgene; Preferably, the alkali is selected from DIEA, TEA, NMP, DBU, DABCO or NMM, more preferably TEA, DBU or NMM; When at least one R4 is selected from C(O)O-PG1, the process also includes the step of removing the protecting group PG1 under the action of acid or base. Preferably, PG1 is selected from methyl, ethyl, isopropyl, tert-butyl, or benzyl, more preferably methyl or tert-butyl; Preferably, the alkali is selected from LiOH, NaOH, KOH or Cs2CO3, and more preferably LiOH; Preferably, the acid is selected from hydrochloric acid, formic acid, acetic acid, MSA or TFA, more preferably MSA or TFA.

22. A pharmaceutical composition comprising a therapeutically effective dose of any of the compounds shown in claims 1-20 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients.

23. The use of any compound shown in claims 1-20 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition of claim 22 in the preparation of a medicament for treating GIPR-related diseases, preferably, GIPR-related diseases are selected from diabetes, obesity, NASH, kidney disease and related conditions, more preferably type I diabetes, type II diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease, renal tubular dysfunction, proximal tubular pro-inflammatory changes, chronic kidney disease, diabetic retinopathy, obesity, glomerulosclerosis, chronic renal failure, metabolic syndrome, obesity or NASH.

Images