Phenyl-containing heterocyclic derivative regulator as well as preparation method and application thereof

Abstract

The invention relates to a phenyl-containing heterocyclic derivative regulator as well as a preparation method and application thereof. In particular, the present invention relates to a compound represented by general formula (XVI), a preparation method thereof, a pharmaceutical composition containing the compound, and an application of the compound as a regulator in the preparation of drugs for treating metabolic diseases and related diseases, each substituent in the general formula (XVI) being as defined in the specification # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of drug synthesis, and in particular relates to a phenyl-containing heterocyclic derivative regulator, a preparation method and an application thereof. Background Art

[0002] Diabetes mellitus is a common endocrine and metabolic disease caused by a variety of metabolic disorders, leading to multi-system and multi-organ damage. It has a high incidence rate, with approximately 425 million people suffering from diabetes worldwide. In China, the incidence rate is approximately 10%, of which type 2 diabetes accounts for 90%. The prevalence is still increasing, and the age of onset is becoming younger.

[0003] Currently, there are many types of drugs on the market for the treatment of type 2 diabetes, including insulin, biguanides, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase (DPP-IV) inhibitors, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, α-glucosidase inhibitors, etc., among which GLP-1 receptor agonists are the most popular.

[0004] GLP-1 is a peptide hormone secreted by human intestinal L cells. Its receptors are distributed in pancreatic islet cells, various gastrointestinal cells, and neurons in the central and peripheral nervous systems. Activation of the GLP-1 receptor has physiological effects such as promoting insulin secretion, inhibiting glucagon secretion, suppressing appetite, and delaying gastric emptying. Clinical evidence shows that compared with other hypoglycemic drugs, GLP-1 receptor agonists have a better blood sugar-lowering effect and are less likely to cause side effects such as hypoglycemia. In addition, they have additional cardiovascular benefits, can reduce food intake and delay gastric emptying, and are beneficial for weight control.

[0005] Currently available GLP-1 receptor agonists are all peptide drugs, most of which require subcutaneous administration, resulting in poor patient compliance. Furthermore, oral peptides have very low bioavailability. Therefore, there is a significant clinical need for the development of oral small molecule GLP-1 receptor agonists.

[0006] While no small-molecule GLP-1 receptor agonists have been approved, three have entered clinical development, including PF-06882961 and PF-07081532 developed by Pifzer, and TTP273 developed by vTv. All are currently in Phase I / II clinical trials. PF-06882961 has demonstrated significant glucose-lowering and weight-reducing effects in early clinical trials, with a safety profile similar to that of peptide-based GLP-1 receptor agonists. It is expected to provide additional treatment options for patients with diabetes, obesity, and NASH.

[0007] There is a huge clinical need for GLP-1 receptor agonists. Oral small-molecule GLP-1 receptor agonists with lower costs and better compliance have the potential to treat a variety of metabolic diseases and have broad market prospects. Summary of the Invention

[0008] The object of the present invention is to provide a compound represented by general formula (XVI), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0009]

[0010] in,

[0011] Ring A is selected from C 3-18 Cycloalkyl, 3-18 membered heterocyclic group, C 6-18 Aryl or 5-18 membered heteroaryl;

[0012] Ring B is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, mercapto, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy or C 1-6 substituted by one or more substituents in a deuterated haloalkoxy group;

[0013] Ring C is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, mercapto, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy or C 1-6 substituted by one or more substituents in a deuterated haloalkoxy group;

[0014] Ring E is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-10 membered heteroaryl;

[0015] Alternatively, ring E is Optionally further substituted with one or more substituents selected from halogen, methoxy or deuterated methyl;

[0016] L1, L2 or L3 are each independently selected from a bond, a sub-C 2-4 Alkenyl, C 2-4 Alkynyl, -(CH2) n1 -or-(CH2) n5 NR b5 , the sub-C 2-4 Alkenyl, C 2-4 Alkynyl, -(CH2) n1 -or-(CH2) n5 NR b5 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0017] R 1 Each independently selected from Hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5C(O)NR a10 R b10 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further Halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0018] or,

[0019] R 1 Linked to the connected atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further Deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2)n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents in;

[0020] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0021] or,

[0022] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a6 and R b6 、R a8 and R b8 、R a9 and R b9 、R a10 and R b10 Linked to adjacent atoms to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0023] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0024] R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl or -(CH2) m1 OR c1 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl or -(CH2) m1 OR c1 , optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0025] R c1 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0026] Or, R7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0027] or,

[0028] R 10 and R 12 The atoms connected to it form a C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0029] n1-n5, m1 or x are each independently selected from 0, 1, 2, 3, 4 or 5.

[0030] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0031] Ring A is selected from C 3-12 Cycloalkyl, 3-14 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-14 Aryl or a 5-14 membered heteroaryl group containing 1-3 heteroatoms selected from N, O or S;

[0032] Preferably, ring A is selected from C 3-10 Cycloalkyl, 5-14 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or a 5-10 membered heteroaryl group containing 1-3 heteroatoms selected from N, O or S;

[0033] More preferably, ring A is selected from C 3-6 Bridged cycloalkyl, 8-14 membered tricyclic fused heterocyclic group containing 1-5 heteroatoms, 3-8 membered bridged heterocyclic group containing 1-3 heteroatoms, fused heterocyclic group containing 1-3 heteroatoms, bridged heterocyclic group containing 1-3 heteroatoms, C 6-10 Aryl or a 5-10 membered fused heteroaryl group containing 1-3 heteroatoms;

[0034] More preferably, ring A is selected from phenyl, pyridyl, pyrimidinyl, thiazolyl, pyridazinyl, oxazolyl, morpholinyl,

[0035]

[0036]

[0037] Note: Indicates connection with L1.

[0038] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0039] Ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms; optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, mercapto, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy or C 1-3 substituted by one or more substituents in a deuterated haloalkoxy group;

[0040] Preferably, ring B is selected from C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms or 5-8 membered heteroaryl containing 1-3 N, O or S atoms; optionally further substituted by halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents;

[0041] More preferably, ring B is selected from

[0042] Optionally further substituted by halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents.

[0043] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0044] Ring C is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 selected from N, O or S; optionally further substituted by halogen, amino, nitro, hydroxyl, cyano, oxo, mercapto, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy or C 1-3 substituted by one or more substituents in a deuterated haloalkoxy group;

[0045] Preferably, ring C is selected from C 3-8 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 selected from N, O or S or 5-6 membered heteroaryl containing 1-3 selected from N, O or S; optionally further substituted by hydroxyl, thioxo, oxo or C 1-6 substituted by one or more substituents in a haloalkoxy group;

[0046] More preferably, ring C is selected from Optionally further substituted with one or more substituents selected from the group consisting of hydroxy, thio or oxo.

[0047] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0048] Ring E is selected from C 3-10 Cycloalkyl, 3-12 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0049] Preferably, ring E is selected from C 3-6Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted with one or more substituents selected from halogen, methoxy or deuterated methyl;

[0050] More preferably, ring E is selected from Optionally further substituted with one or more substituents selected from halogen, methoxy or deuterated methyl.

[0051] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0052] Ring E is Optionally further substituted with one or more substituents selected from halogen, methoxy or deuterated methyl.

[0053] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0054] R 1 Each independently selected from Hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n1 S(O)2R b5 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 Rb9 or -(CH2) n1 S(O)2R b5 , optionally further Halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0055] Preferably, R 1 Each independently selected from Hydrogen, deuterium, amino, oxo, fluorine, chlorine, bromine, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spiroalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NRa8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spiroalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further Halogen, cyano or C 1-3 The alkyl group is substituted by one or more substituents.

[0056] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0057] More preferably, R 1 Each independently selected from Hydrogen, deuterium, amino, oxo, cyano, fluorine, chlorine, bromine, methyl, ethyl, cyclopropyl, -CD3, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino, methyl, ethyl, cyclopropyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2)n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further Halogen, cyano or C 1-3 The alkyl group is substituted by one or more substituents.

[0058] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0059] R 1 Linked to the connected atoms to form C 3-6 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 selected from N, O or S, optionally further Deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NRa4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents in;

[0060] Preferably, R 1 Linked to the connected atoms to form C 3-4 Cycloalkyl or 5-7 membered heterocyclic group containing 1-3 selected from N, O or S, optionally further Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl, amino, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents in;

[0061] More preferably, R 1 Respectively linked to the atoms to form a cyclopropyl group, optionally further Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl, amino, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents.

[0062] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0063] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、Rb7 、R a8 、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen or C 1-3 The alkyl group is substituted by one or more substituents;

[0064] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, methyl, ethyl, cyano, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, The methyl, ethyl, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, Optionally further substituted with one or more fluorines.

[0065] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0066] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a6 and R b6 、R a8 and R b8 、R a9 and R b9 、R a10 and R b10 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0067] Preferably, R a1 and Rb1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a6 and R b6 、R a8 and R b8 、R a9 and R b9 、R a10 and R b10 Linked to adjacent atoms to form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents.

[0068] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0069] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic or 5-8 membered heteroaryl, the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0070] Preferably, R 4 、R 5 or R 6 Each is independently selected from fluoro, cyano, cyclopropyl or methyl, and the cyclopropyl or methyl is optionally further substituted by one or more substituents selected from deuterium, deuterated methyl, methyl, cyclopropyl or oxo.

[0071] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0072] R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C6-10 Aryl, 5-8 membered heteroaryl or -(CH2) m1 OR c1 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl or -(CH2) m1 OR c1 , optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0073] Preferably, R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, cyano, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or -(CH2) m1 OR c1 , the C 2-4Alkynyl, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or -(CH2) m1 OR c1 , optionally further substituted with one or more substituents selected from deuterium, deuterated methyl, methyl, cyclopropyl or oxo;

[0074] More preferably, R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 Each is independently selected from cyano, methyl, fluoro, cyclopropyl, ethynyl or -(CH2) m1 OR c1 , the methyl, cyclopropyl, ethynyl or -(CH2) m1 OR c1 , optionally further substituted with one or more substituents selected from deuterium, deuterated methyl, methyl, cyclopropyl or oxo.

[0075] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0076] R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 Each is independently selected from cyano, methyl, fluoro, cyclopropyl, ethynyl or -(CH2) m1 OR c1 , the methyl, cyclopropyl, ethynyl or -(CH2) m1 OR c1 , optionally further substituted with one or more substituents selected from deuterium, hydroxy, deuterated methyl, methyl, cyclopropyl or oxo.

[0077] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0078] R c1 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic or 5-8 membered heteroaryl, the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0079] Preferably, R c1is selected from fluorine, methyl, cyano, difluoromethyl, trifluoromethyl, ethynyl, methylthio, amino, cyclopropyl or oxetane, wherein the methyl, difluoromethyl, trifluoromethyl, ethynyl, methylthio, amino, cyclopropyl or oxetane is optionally further substituted with one or more substituents selected from halogen, methoxy or deuterated methyl.

[0080] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0081] R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 The atoms connected to them form C 3-6 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 N, O or S atoms;

[0082] Preferably, R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 N, O or S atoms;

[0083] More preferably, R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 or R 15 The atoms to which they are connected form cyclopropyl or

[0084] In a further preferred embodiment of the present invention, the compound of formula (XVI):

[0085] R 10 and R 12 The atoms connected to it form a C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms;

[0086] Preferably, R 10 and R 12 The atoms connected to it form a C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 N, O or S atoms;

[0087] More preferably, R 10 and R 12 The atoms connected to it form a link

[0088] In a further preferred embodiment of the present invention, the compound of general formula (XVI) is further represented by general formula (XVI-1):

[0089]

[0090] In a further preferred embodiment of the present invention, the compound of general formula (XVI) is further represented by general formula (XVI-A):

[0091]

[0092] in,

[0093] R 1 and R 2 、R 1 and R 11 Linked to adjacent atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further Hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)Ra1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents in;

[0094] or,

[0095] R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 Ra5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0096] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0097] or,

[0098] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a6 and R b6 、R a8 and R b8 、R a9 and R b9 、R a10 and R b10 Linked to adjacent atoms to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0099] Ring B, Ring C, Ring E, L1, L2, L3, R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 、R 15, n1, n2, n3, n4, n5, m1, and x are defined as described in the general formula (XVI).

[0100] In a further preferred embodiment of the present invention, the compound of formula (XVI-A):

[0101] R 1 and R 2 、R 1 and R 11 Linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 selected from N, O or S, optionally further Deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents in;

[0102] Preferably, R 1 and R 2 、R 1 and R 11 Respectively linked with adjacent atoms to form a 5-7 membered heterocyclic group containing 1-3 selected from N, O or S, optionally further Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl, amino, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents in;

[0103] More preferably, R 1 and R 2 、R 1 and R 11 Linked with adjacent phenyl groups to form

[0104]

[0105]

[0106] Optionally further -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 、-(CH2) n5 C(O)NR a10 R b10 、 Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 The alkyl group is substituted by one or more substituents selected from cycloalkyl, amino or oxo.

[0107] Note: Indicates connection with L1.

[0108] In a further preferred embodiment of the present invention, the compound of formula (XVI-A):

[0109] R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0110] Preferably, R 1 、R 2 、R3 or R 11 are each independently selected from hydrogen, deuterium, amino, oxo, fluorine, chlorine, bromine, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spiroalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spiroalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)Ra3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further substituted by halogen, cyano or C 1-3 The alkyl group is substituted by one or more substituents.

[0111] In a further preferred embodiment of the present invention, the compound of formula (XVI-A):

[0112] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen or C 1-3 The alkyl group is substituted by one or more substituents;

[0113] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, methyl, ethyl, cyano, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, The methyl, ethyl, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, Optionally further substituted with one or more fluorines.

[0114] In a further preferred embodiment of the present invention, the compound of formula (XVI-A):

[0115] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a6 and R b6 、R a8 and R b8 、R a9 and R b9 、R a10 and R b10 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0116] Preferably, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a6 and R b6 、R a8 and R b8 、R a9 and R b9 、R a10and R b10 Linked to adjacent atoms to form C 3-6 Cycloalkyl or a 3-6 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S.

[0117] In a further preferred embodiment of the present invention, the compound of formula (XVI-A):

[0118] In the general formula (XVI-A) Further As shown, optionally further substituted by halogen, methoxy, C 1-3 Cycloalkyl, C 3-6 substituted by one or more substituents of cycloalkyl or deuterated methyl;

[0119] Ring M1, ring M2, ring M3, ring M4, ring M5, ring M6, ring M7 or ring M8 are each independently selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0120] In a further preferred embodiment of the present invention, the compound of formula (XVI-A):

[0121] In the general formula (XVI-A) Further As shown, optionally further substituted by halogen, methoxy, C 1-3 Cycloalkyl, C 3-6 substituted by one or more substituents of cycloalkyl or deuterated methyl;

[0122] Ring M1, ring M2, ring M3, ring M4, ring M5, ring M6, ring M7 or ring M8 are each independently selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0123] Preferably, ring M1, ring M2, ring M3, ring M4, ring M5, ring M6, ring M7 or ring M8 are each independently selected from C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted by halogen, methoxy, C 1-3 Cycloalkyl, C 3-6 The cycloalkyl group or the deuterated methyl group is substituted with one or more substituents.

[0124] In a further preferred embodiment of the present invention, the compound of formula (XVI-A) is further represented by formula (XVI-B):

[0125]

[0126] The object of the present invention is to provide a compound represented by general formula (I), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0127]

[0128] in:

[0129] R 1 、R 2 or R3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0130] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0131] Or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0132] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0133] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0134] Or, R 7 、R 8 、R 9 or R 10 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0135] n1 to n4 are integers from 0 to 5;

[0136] When R 4 、R 6 、R 9 、R 10 is methyl, R 7 、R 8 is hydrogen, R 5 is fluorine, R 1 is methoxy, R 2 When it is fluorine, R 3 It cannot be hydrogen;

[0137] When R 4 、R 6 、R 9 、R 10 is methyl, R 7 、R 8 is hydrogen, R 5 is fluorine, R 1 for R 2 When it is methyl, R 3 It cannot be hydrogen;

[0138] When R 4 、R 6 、R 9 、R 10 is methyl, R 7 、R 8 is hydrogen, R 5 is fluorine, R 1 for R 2 When it is methyl, R 3 It cannot be hydrogen;

[0139] When R 4 、R 6 、R 9 、R 10 is methyl, R 7 、R 8 is hydrogen, R 5 is fluorine, R 1 for When R 2 and R 3 It cannot be hydrogen at the same time.

[0140] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0141] R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10Aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0142] Preferably, R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclyl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 Rb1 、C 1-3 Alkyl or C 3-6 substituted by one or more substituents in the cycloalkyl group;

[0143] More preferably, R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spiroalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 Alkyl or C 3-6 The cycloalkyl group is substituted by one or more substituents.

[0144] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0145] R 1 、R 2 or R3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0146] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0147] R 1 、R 2 or R3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C6-10 aryl and 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0148] Preferably, R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, -NS(O)R a1 R b1、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 The alkyl group is substituted by one or more substituents.

[0149] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0150] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen or C 1-3 The alkyl group is substituted by one or more substituents;

[0151] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, methyl, cyclopropyl, Optionally, further substituted with fluorine.

[0152] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0153] R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0154] Preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 Linked to adjacent atoms to form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0155] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0156] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl; or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0157] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0158] R a1 、R b1 、R a2 、R b2 、R a3 、Rb3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 alkyl halide;

[0159] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 Each is independently selected from hydrogen, deuterium, halogen, and methyl.

[0160] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0161] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0162] Preferably, R a2 and R b2 、R a3 and R b3 Each independently links with adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0163] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0164] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 alkyl halide;

[0165] Preferably, R 4 、R 5 or R 6 Each independently selected from fluoro, methyl.

[0166] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0167] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 alkyl halide;

[0168] Preferably, R 7 、R 8 、R 9 or R 10 Selected from methyl.

[0169] In another embodiment of the present invention, the compound of formula (I):

[0170] R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 The amino group, C 1-6 Alkyl, C 1-6Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0171] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0172] R 1 and R 2 Linking with adjacent atoms to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 aryl or 5-12 membered heteroaryl.

[0173] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0174] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 or R b7 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0175] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0176] R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0177] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0178] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0179] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0180] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0181] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0182] R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 Rb3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 Rb6, -(CH2) n1 P(O)R a3 R b3 、 The amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0183] Preferably, R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclyl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NRa5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 The amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 3-6 substituted by one or more substituents in the cycloalkyl group;

[0184] More preferably, R 1 、R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spiroalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 The amino group, C 1-3 Alkyl, C 1-3Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 3-6 The cycloalkyl group is substituted by one or more substituents.

[0185] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0186] R 1 and R 2 Linked with adjacent atoms to form a 3-10 membered fused heterocyclic group containing 1-4 heteroatoms;

[0187] Preferably, R 1 and R 2 It is linked to adjacent atoms to form a 9-membered fused heterocyclic group containing 1-4 N atoms.

[0188] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0189] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 or R b7 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms, C 6-10 Aryl, 5-6 membered heteroaryl containing 1-3 heteroatoms, the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms, C 6-10 Aryl, 5-6 membered heteroaryl containing 1-3 heteroatoms, optionally further substituted with halogen, C 1-3 Alkyl substituted;

[0190] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 or R b7 are each independently selected from hydrogen, deuterium, halogen, methyl, cyclopropyl, Optionally, further substituted with fluorine.

[0191] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0192] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0193] Preferably, R a2 and R b2 、R a3 and R b3 Each independently links with adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0194] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0195] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 alkyl halide;

[0196] Preferably, R 4 、R 5 or R 6 Each independently selected from fluoro, methyl.

[0197] In another further preferred embodiment of the present invention, the compound of general formula (I):

[0198] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 alkyl halide;

[0199] Preferably, R 7 、R 8 、R 9 or R 10 are each independently selected from methyl.

[0200] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0201] R 7 、R 8 、R 9 or R 10 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0202] Preferably, R 7 、R 8 、R 9 or R 10 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0203] More preferably, R 7 、R 8 、R 9 or R 10 The atoms to which they are attached are linked to form a cyclopropyl group.

[0204] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0205] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0206] Preferably, R 4 、R 5 or R6 Each is independently selected from fluoro, cyano, cyclopropyl or methyl.

[0207] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0208] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, methyl, deuterated methyl, cyclopropyl, Optionally, further substituted with fluorine.

[0209] In a further preferred embodiment of the present invention, the compound of general formula (I):

[0210] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0211] Preferably, R 7 、R 8 、R 9 or R 10 Each is independently selected from methyl or cyclopropyl.

[0212] In a further preferred embodiment of the present invention, the compound of general formula (I) is further represented by general formula (I-1):

[0213]

[0214] The object of the present invention is to provide a compound represented by the general formula (XI), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0215]

[0216] in,

[0217] Ring E is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl;

[0218] L2 is selected from a bond, -(CH2) n4 -, C2-4 alkenylene, C2-4 alkynylene;

[0219] R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents in aryl or 5-10 membered heteroaryl; R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0220] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0221] Or, R 7 、R 8 、R 9 or R 10 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0222] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0223] Or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a7 and R b7 or R a8 and R b8 or R a9 and R b9 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0224] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0225] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0226] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0227] Or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a7 and R b7 or R a8 and R b8 or R a9 and R b9 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0228] n1~n4 are integers of 0~5.

[0229] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0230] Ring E is selected from C 3-8 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms;

[0231] Preferably, ring E is selected from

[0232] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0233] Ring E is selected from

[0234] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0235] Ring E is selected from

[0236] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0237] R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 The amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 In a further preferred embodiment of the present invention, the compound of formula (XI) is:

[0238] Preferably, R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0239] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0240] R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 The amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0241] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0242] R 1 and R 2 or R 1 and R 11 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 In a further preferred embodiment of the present invention, the compound of formula (XI):

[0243] Preferably, R 1 and R 2 or R 1 and R 11 Linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 is substituted by one or more substituents in;

[0244] More preferably, R 1 and R 2 or R 1 and R 11 Respectively linked to adjacent atoms to form a phenyl group, a 5-7 membered heterocyclic group containing 1-3 selected from N, O or S, optionally further substituted by an oxo group, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5、-(CH2) n1 O(CH2) n2 R b5 、 replaced.

[0245] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0246] R 1 and R 2 or R 1 and R 11 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents in;

[0247] Preferably, R 1 and R 2 or R 1 and R11 They are linked to adjacent atoms to form phenyl or a 5-7 membered heterocyclic group containing 1-3 groups selected from N, O or S, optionally further substituted by methyl, halogen, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents in;

[0248] More preferably, R 1 and R 2 or R 1 and R 11 Linked to adjacent atoms Optionally further substituted with methyl, halogen, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n P(O)R a7 R b7 or -(CR a8 R b8 )n4 C(O)NR a9 R b9 is substituted by one or more substituents.

[0249] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0250] R 1 and R 2 or R 1 and R 11 Linked to adjacent atoms

[0251] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0252] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl, C 1-3 alkyl halide;

[0253] Preferably, R 4 、R 5 or R 6 Each is independently selected from fluoro, methyl, and cyclopropyl.

[0254] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0255] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 alkyl halide;

[0256] Preferably, R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen or methyl.

[0257] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0258] R a1 、R b1 、R a2 、R b2 、R a3、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 or R b6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl; or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 In a further preferred embodiment of the present invention, the compound of formula (XI) is substituted by one or more substituents of aryl or 5-10 membered heteroaryl.

[0259] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0260] R a1 、R b1 、R a2 、R b2 、R a3 、R b3、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0261] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, cyano, cyclopropyl, cyclopentyl, methyl, ethyl, phenyl or

[0262] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0263] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 or R b6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 alkyl halide;

[0264] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 or R b6 Each is independently selected from hydrogen, deuterium, halogen, and methyl.

[0265] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0266] Ring E is

[0267] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0268] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl or C 1-3 alkyl halide;

[0269] Preferably, R 4 、R 5 or R 6 Each is independently selected from fluoro, methyl, cyano or cyclopropyl.

[0270] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0271] R 7 、R 8 、R 9 or R 10 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0272] Preferably, R 7 、R 8 、R 9 or R 10 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0273] More preferably, R 7 、R 8 、R 9 or R 10 The atoms to which they are attached are linked to form a cyclopropyl group.

[0274] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0275] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, cyano, cyclopropyl, cyclopentyl, methyl, ethyl, deuterated methyl, phenyl or

[0276] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0277] R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a7 and R b7 or R a8 and R b8 or R a9 and R b9 Linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, the C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0278] Preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a7 and R b7 or R a8 and R b8 or R a9 and R b9 They are linked to adjacent atoms to form cyclopropyl groups.

[0279] In a further preferred embodiment of the present invention, the compound of formula (XI):

[0280] R 1 and R 2 or R 1 and R 11 They are linked to adjacent atoms to form phenyl or a 5-7 membered heterocyclic group containing 1-3 groups selected from N, O or S, optionally further substituted by methyl, halogen, oxo, cyclopropyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents in;

[0281] Preferably, R 1 and R 2 or R 1 and R 11 Linked to adjacent atoms

[0282] Optionally further substituted with methyl, halogen, oxo, cyclopropyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 、 -(CH2) n1 P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents.

[0283] In a further preferred embodiment of the present invention, the compound of general formula (XI) is further represented by general formula (XI-1):

[0284]

[0285] The object of the present invention is to provide a compound represented by general formula (XV), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0286]

[0287] in,

[0288] R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0289] or,

[0290] R 1 and R 2 、R 1 and R 11 Linked to adjacent atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0291] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0292] Or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 or R a10 and R b10 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0293] Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, mercapto, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy or C 1-6 substituted by one or more substituents in a haloalkoxy group;

[0294] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0295] R 7 、R 8 、R 9 、R 10 、R 12 、R 13 or R 14 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0296] Or, R 7 、R 8 、R 9 、R 10 、R 12 、R 13 or R 14 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0297] n1-n5 are integers from 0 to 5;

[0298] x is an integer from 0 to 5.

[0299] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0300] R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0301] Preferably, R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclyl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2)n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 Alkyl or C 3-6 substituted by one or more substituents in the cycloalkyl group;

[0302] More preferably, R 1 、R 2 、R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spiroalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 Alkyl or C 3-6 The cycloalkyl group is substituted by one or more substituents.

[0303] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0304] R 1 and R 2 、R 1 and R 11 Linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, C 1-3 Alkyl, C 3-6 substituted by one or more substituents of cycloalkyl, amino or oxo;

[0305] Preferably, R 1 and R 2 、R 1 and R 11 are linked to adjacent atoms to form a 5-7 membered heterocyclic group containing 1-3 atoms selected from N, O or S, optionally further C 3-6 substituted by cycloalkyl or oxo;

[0306] More preferably, R 1 and R 2 or R 1 and R 11 Linked with adjacent phenyl groups to form

[0307] Optionally further halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 The alkyl group is substituted by one or more substituents selected from cycloalkyl, amino or oxo.

[0308] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0309] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、Rb6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen or C 1-3 The alkyl group is substituted by one or more substituents;

[0310] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, methyl, deuterated methyl, cyclopropyl, Optionally, further substituted with fluorine.

[0311] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0312] R a1 and R b1or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 or R a10 and R b10 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0313] Preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 or R a10 and R b10 Linked to adjacent atoms to form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0314] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0315] Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; optionally further substituted by halogen, amino, oxo, mercapto, thio or C 1-6 The alkyl group is substituted by one or more substituents;

[0316] Preferably, ring A is selected from C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms or 5-8 membered heteroaryl containing 1-3 N, O or S atoms; optionally further substituted by halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents;

[0317] More preferably, ring A is selected from

[0318] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0319] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0320] Preferably, R 4 、R 5 or R 6 Each is independently selected from fluoro, cyano, cyclopropyl or methyl.

[0321] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0322] R 7 、R 8 、R 9 、R 10 、R 12 、R 13 or R 14 are each independently selected from hydrogen, deuterium, halogen, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0323] Preferably, R 7 、R 8 、R 9 、R 10 、R 12 、R 13 or R 14 Each is independently selected from methyl or cyclopropyl.

[0324] In a further preferred embodiment of the present invention, the compound of formula (XV):

[0325] R 7 、R 8 、R 9 、R 10 、R 12 、R 13 or R 14 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0326] Preferably, R7 、R 8 、R 9 、R 10 、R 12 、R 13 or R 14 The atoms to which they are attached are linked to form a cyclopropyl group.

[0327] In a further preferred embodiment of the present invention, the compound of general formula (XV) is further represented by general formula (XV-1):

[0328]

[0329] The object of the present invention is to provide a compound represented by general formula (III), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0330]

[0331] in,

[0332] Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl;

[0333] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0334] Ring A cannot be

[0335] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0336] R a1 、R b1 、R a2 、R b2 、Ra3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0337] Or, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0338] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0339] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0340] n1 is an integer from 0 to 5.

[0341] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0342] Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms;

[0343] Preferably, ring A is selected from

[0344] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0345] Ring A is selected from

[0346] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0347] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0348] Preferably, R 12 Selected from C 1-3 alkyl;

[0349] More preferably, R 12 Selected from methyl.

[0350] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0351] Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl;

[0352] Preferably, ring A is selected from C 3-8 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms;

[0353] More preferably, ring A is selected from

[0354] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0355] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0356] Preferably, R 3 Selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl, optionally further substituted with halogen, -NS(O)R a1 R b1 or C 1-3 The alkyl group is substituted by one or more substituents.

[0357] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0358] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0359] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen or methyl;

[0360] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0361] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aryl or 5-8 membered heteroaryl.

[0362] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0363] R a2 and R b2 、R a3 and R b3 Linked to adjacent atoms to form C 3-8 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0364] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0365] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0366] Preferably, R 4 、R 5 or R 6 are each independently selected from fluoro or methyl.

[0367] In a further preferred embodiment of the present invention, the compound of general formula (III):

[0368] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0369] Preferably, R 7 、R 8 、R 9 or R 10 are each independently selected from methyl.

[0370] In a further preferred embodiment of the present invention, the compound of general formula (III) is further represented by general formula (III-1):

[0371]

[0372] The object of the present invention is to provide a compound represented by general formula (VIII), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0373]

[0374] in,

[0375] R 14 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0376] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0377] R a1 、R b1 、R a2 、R b2 、R a3 、Rb3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0378] Or, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0379] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0380] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0381] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0382] n1 is an integer from 0 to 5.

[0383] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0384] R 14 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-5 Alkenyl, C 2-5 Alkynyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0385] Preferably, R 14 is selected from thio or trifluoromethyl.

[0386] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0387] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0388] Preferably, R 3 Selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, optionally further substituted with halogen, -NS(O)R a1 R b1 or C 1-3 The alkyl group is substituted by one or more substituents.

[0389] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0390] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0391] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen or methyl.

[0392] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0393] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0394] Preferably, R a2 and R b2 or R a3 and R b3 Linked to adjacent atoms to form C 3-8 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0395] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0396] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0397] Preferably, R 4 、R 5 or R 6 are each independently selected from fluoro or methyl.

[0398] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0399] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0400] Preferably, R 7 、R 8 、R 9 or R 10 are each independently selected from methyl.

[0401] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0402] R 12 Selected from C 1-3 alkyl;

[0403] Preferably, R 12 Selected from methyl.

[0404] In a further preferred embodiment of the present invention, the compound of general formula (VIII):

[0405] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0406] Preferably, R 12 Selected from C 1-3 Alkyl or C 3-6 Cycloalkyl;

[0407] More preferably, R 12 is selected from methyl or cyclopropyl.

[0408] In a further preferred embodiment of the present invention, the compound of general formula (VIII) is further represented by general formula (VIII-1):

[0409]

[0410] The object of the present invention is to provide a compound represented by general formula (IX), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0411]

[0412] in,

[0413] M1 is S or N;

[0414] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0415] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0416] R a1 、Rb1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0417] Or, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0418] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0419] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0420] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0421] n1 is an integer from 0 to 5.

[0422] In a further preferred embodiment of the present invention, the compound of formula (IX):

[0423] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0424] Preferably, R 3 Selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 The alkyl group is substituted by one or more substituents.

[0425] In a further preferred embodiment of the present invention, the compound of formula (IX):

[0426] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0427] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen or methyl.

[0428] In a further preferred embodiment of the present invention, the compound of formula (IX):

[0429] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0430] Preferably, R a2 and R b2 、R a3 and R b3 Linked to adjacent atoms to form C 3-8 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0431] In a further preferred embodiment of the present invention, the compound of formula (IX):

[0432] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0433] Preferably, R 4 、R 5 or R 6 are each independently selected from fluoro or methyl.

[0434] In a further preferred embodiment of the present invention, the compound of formula (IX):

[0435] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0436] Preferably, R 7 、R 8 、R 9 or R 10 are each independently selected from methyl.

[0437] In a further preferred embodiment of the present invention, the compound of formula (IX):

[0438] R 12 Selected from C 1-3 alkyl;

[0439] Preferably, R 12 Selected from methyl.

[0440] In a further preferred embodiment of the present invention, the compound of formula (IX):

[0441] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0442] Preferably, R 12 Selected from C 1-3 Alkyl or C 3-6 Cycloalkyl;

[0443] More preferably, R 12 is selected from methyl or cyclopropyl.

[0444] In a further preferred embodiment of the present invention, the compound of general formula (IX) is further represented by general formula (IX-1):

[0445]

[0446] The object of the present invention is to provide a compound represented by general formula (X), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0447]

[0448] in,

[0449] L2 is selected from a bond, -(CH2) n4 -, Sub-C 2-4 Alkenyl, C 2-4 Alkynyl;

[0450] R 15 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0451] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0452] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0453] Or, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0454] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0455] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0456] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0457] n1 is an integer from 0 to 5;

[0458] n4 is an integer from 0 to 5.

[0459] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0460] R 15 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0461] Preferably, R 15 Selected from methyl.

[0462] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0463] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0464] Preferably, R 3 Selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 or -NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3 The alkyl group is substituted by one or more substituents.

[0465] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0466] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0467] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen or methyl.

[0468] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0469] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0470] Preferably, R a2 and R b2 、R a3 and R b3 Linked to adjacent atoms to form C 3-8 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0471] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0472] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0473] Preferably, R 4 、R 5 or R 6 are each independently selected from fluoro or methyl.

[0474] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0475] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0476] Preferably, R 7 、R 8 、R 9 or R 10 are each independently selected from methyl.

[0477] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0478] R 12 Selected from C 1-3 alkyl;

[0479] Preferably, R 12 Selected from methyl.

[0480] In a further preferred embodiment of the present invention, the compound of general formula (X):

[0481] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0482] Preferably, R 12 Selected from C 1-3 Alkyl or C 3-6 Cycloalkyl;

[0483] More preferably, R 12 is selected from methyl or cyclopropyl.

[0484] In a further preferred embodiment of the present invention, the compound of general formula (X) is further represented by general formula (X-1):

[0485]

[0486] The object of the present invention is to provide a compound represented by general formula (XIII), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0487]

[0488] in,

[0489] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0490] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0491] R a1 、R b1 、R a2、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl;

[0492] Or, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0493] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0494] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0495] R 13 Selected from deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0496] n1 is an integer from 0 to 5.

[0497] In a further preferred embodiment of the present invention, the compound of general formula (XIII):

[0498] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0499] Preferably, R 4 、R 5 or R 6 are each independently selected from fluoro or methyl.

[0500] In a further preferred embodiment of the present invention, the compound of general formula (XIII):

[0501] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0502] Preferably, R 3 Selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, optionally further substituted with halogen, -NS(O)R a1 R b1 、C 1-3The alkyl group is substituted by one or more substituents.

[0503] In a further preferred embodiment of the present invention, the compound of general formula (XIII):

[0504] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0505] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 or R b4 are each independently selected from hydrogen, deuterium, halogen or methyl.

[0506] In a further preferred embodiment of the present invention, the compound of general formula (XIII):

[0507] R a2 and R b2 、R a3 and R b3 Each independently links with adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0508] In a further preferred embodiment of the present invention, the compound of general formula (XIII):

[0509] R 7 、R 8 、R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0510] Preferably, R 7 、R 8 、R 9 or R 10 are each independently selected from methyl.

[0511] In a further preferred embodiment of the present invention, the compound of general formula (XIII):

[0512] R 12 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0513] Preferably, R 12 Selected from methyl.

[0514] In a further preferred embodiment of the present invention, the compound of general formula (XIII):

[0515] R 13 Selected from deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0516] Preferably, R 13 is selected from methoxy or cyclopropyl.

[0517] In a further preferred embodiment of the present invention, the compound of general formula (XIII) is further represented by general formula (XIII-1):

[0518]

[0519] The object of the present invention is to provide a compound represented by general formula (XIV), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0520]

[0521] in,

[0522] R 12 or R 13 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n2 R a5 R b5 、 or -(CH2) n4 (CR a7 Rb7 ) n5 C(O)NR a8 R b8 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0523] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n2 R a5 R b5 or The amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0524] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0525] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8 or R b8 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0526] Or, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a5 and R b5 、R a6 and R b6 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0527] R 7 、R 8 、R 9 、R 10 、R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0528] Or, R 7 、R 8 、R 9 、R 10 、R 14 or R 15 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl;

[0529] n1-n5 are integers ranging from 0 to 5.

[0530] In a further preferred embodiment of the present invention, the compound of general formula (XIV):

[0531] R 12or R 13 Each independently selected from C 1-3 Alkyl, C 3-6 Cycloalkyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n2 R a5 R b5 、 or -(CH2) n4 (CR a7 R b7 ) n5 C(O)NR a8 R b8 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0532] Preferably, R 12 or R 13 Each independently selected from methyl, cyclopropyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、 or -(CH2) n4 (CR a7 R b7 ) n5 C(O)NR a8 R b8, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl group or the 5-8 membered heteroaryl group is substituted by one or more substituents.

[0533] In a further preferred embodiment of the present invention, the compound of general formula (XIV):

[0534] R 3 Selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n2 R a5 R b5 or The amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, optionally further substituted by halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 、C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by one or more substituents selected from cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl;

[0535] Preferably, R 3 Selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n2 R a5 R b5 or The amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl, optionally further substituted with halogen, -NS(O)R a1 R b1 or C 1-3 The alkyl group is substituted by one or more substituents.

[0536] In a further preferred embodiment of the present invention, the compound of general formula (XIV):

[0537] R 4 、R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 1-3 Alkyl, C 1-3 Sulfanyl, C 2-4 Alkynyl, C 3-6Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 N, O or S atoms; optionally further substituted by halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 substituted by one or more substituents in the alkoxy group;

[0538] Preferably, R 4 、R 5 or R 6 Each is independently selected from fluoro, methyl, cyano, ethynyl, methylthio, amino, cyclopropyl or oxetane; optionally further substituted by halogen, methoxy or deuterated methyl.

[0539] In a further preferred embodiment of the present invention, the compound of general formula (XIV):

[0540] R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8 or R b8 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0541] Preferably, R a1 、R b1 、R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、Rb7 、R a8 or R b8 are each independently selected from hydrogen, deuterium, halogen or methyl.

[0542] In a further preferred embodiment of the present invention, the compound of general formula (XIV):

[0543] R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a5 and R b5 、R a6 and R b6 Linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0544] Preferably, R a1 and R b1 、R a2 and R b2 、R a3 and R b3 、R a4 and R b4 、R a5 and R b5 、R a6 and R b6 Linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 heteroatoms.

[0545] In a further preferred embodiment of the present invention, the compound of general formula (XIV):

[0546] R 7 、R 8 、R 9 、R 10 、R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl;

[0547] Preferably, R 7 、R 8 、R 9 、R 10 、R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, cyano, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 alkyl halide;

[0548] More preferably, R 7 、R 8 、R 9 、R 10 、R 14 or R 15 Each is independently selected from methyl, fluoro, cyclopropyl or ethynyl.

[0549] In a further preferred embodiment of the present invention, the compound of general formula (XIV):

[0550] R 7 、R 8 、R 9 、R 10 、R 14 or R 15 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl;

[0551] Preferably, R 7 、R 8 、R 9 、R 10 、R 14 or R 15The atoms to which they are attached are linked to form a cyclopropyl group.

[0552] In a further preferred embodiment of the present invention, the compound of general formula (XIV) is further represented by general formula (XIV-1):

[0553]

[0554] The object of the present invention is to provide a compound represented by general formula (XVI-X), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0555]

[0556] Among them, R 1 、R 2 、R 3 or R 11 are each independently selected from halogen, amino, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 、 -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group is optionally further C 1-6 Alkyl, C 1-6 substituted with one or more substituents of a deuterated alkyl group;

[0557] R4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 12 、R 13 、R 14 、R a1 、R b1 R a2 、R b2 、R a3 、R b3 、R a4 、R b4 、R a5 、R b5 、R a6 、R b6 、R a7 、R b7 、R a8 、R b8 、R a9 、R b9 、R a10 、R b10 , n1, n2, n3, n4, and n5 are defined as described in the general formula (XVI-A).

[0558] The present invention further relates to a pharmaceutical composition comprising a therapeutically effective dose of any compound of the general formula shown, its prodrug, its stereoisomer or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0559] In certain embodiments of the present invention, the pharmaceutical composition, calculated as the free base, the weight percentage of the compound, its prodrug, its stereoisomer or its pharmaceutically acceptable salt is 0.1% to 95%, preferably 5-70%, for example 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10% or 5%.

[0560] In certain embodiments of the present invention, the pharmaceutical composition is selected from tablets, capsules, liquid preparations or injections, and preferably further comprises a filler, optionally a disintegrant, or further comprises one or more of a glidant or a lubricant.

[0561] In certain embodiments of the present invention, the pharmaceutical composition is a rapid-release formulation or a sustained-release formulation.

[0562] In certain embodiments of the present invention, the pharmaceutical composition, calculated as the free base, the unit dose of the compound, its prodrug, its stereoisomer or its pharmaceutically acceptable salt 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.

[0563] In certain embodiments of the present invention, the compound, its prodrug, its stereoisomer or a pharmaceutically acceptable salt thereof, can be administered by any convenient method, for example, by oral, parenteral, buccal, sublingual, nasal, rectal, intrathecal or transdermal administration, and the pharmaceutical composition adjusted accordingly.

[0564] In certain embodiments of the present invention, the compound, its prodrug, its stereoisomer or a pharmaceutically acceptable salt thereof can be formulated into liquid or solid preparations, such as syrups, suspensions, emulsions, tablets, capsules, powders, granules, or lozenges.

[0565] The present invention further relates to the use of any compound of the general formula shown, its prodrug, its stereoisomer or pharmaceutically acceptable salt, or the pharmaceutical composition in the preparation of GLP-1 receptor agonist drugs.

[0566] The present invention further relates to the use of a compound represented by the general formula, a prodrug thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the preparation of a medicament for treating metabolic-related diseases, wherein the disease is selected from diabetes, obesity, or non-alcoholic steatohepatitis-related diseases or other related diseases caused by diabetes, obesity, or non-alcoholic steatohepatitis.

[0567] The present invention further relates to a method for using the compound represented by the general formula, its prodrug, its stereoisomer or pharmaceutically acceptable salt, or its pharmaceutical composition in the preparation of drugs for treating metabolic diseases and related diseases.

[0568] The present invention also relates to a method for treating, preventing and / or treating metabolic-related diseases, which comprises administering to a patient a therapeutically effective dose of a compound represented by the general formula, a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0569] The present invention also provides methods of using the compounds or pharmaceutical compositions of the present invention to treat disease conditions, including but not limited to conditions associated with GLP-1 receptor modulators.

[0570] The present invention also relates to a method for treating metabolic disease-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.

[0571] Detailed Description of the Invention

[0572] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0573] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight or branched chain 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 various branched-chain isomers thereof. More preferred are lower alkyl groups containing 1 to 6 carbon atoms, non-limiting examples of which 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, and the like. The alkyl group may be substituted or unsubstituted. When substituted, the substituent may be substituted at any available point of attachment. The substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate groups. Methyl, ethyl, isopropyl, tert-butyl, haloalkyl, deuterated alkyl, alkoxy-substituted alkyl and hydroxy-substituted alkyl are preferred.

[0574] The term "alkylene" means that one hydrogen atom of an alkyl group 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.

[0575] 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, for example, ethenyl, 1-propenyl, 2-propenyl, 1-, 2- or 3-butenyl, etc. The alkenyl group may be 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, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio.

[0576] The term "alkenylene" refers to an alkenyl group with one hydrogen atom further substituted, for example, "vinylene" refers to -CH2=CH2-, "propenylene" refers to -CH2-=CH2-CH2-, etc. Alkenylene 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, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio. The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent, the cycloalkyl ring containing 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 8 carbon atoms, and even more preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like; polycyclic cycloalkyl groups include spiro, fused, and bridged cycloalkyl groups, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.

[0577] The term "spiroalkyl" refers to a polycyclic group having a carbon atom (called a spiro atom) shared between 5 to 20 monocyclic rings, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. Preferably, it is 6 to 14 yuan, more preferably 7 to 10 yuan. According to the number of spiro atoms shared between the rings, the spiroalkyl group is divided into a single spiroalkyl group, a double spiroalkyl group or a multi-spiroalkyl group, preferably a single spiroalkyl group and a double spiroalkyl group. More preferably, it is a 4 yuan / 4 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 5 yuan or 5 yuan / 6 yuan single spiroalkyl group. Non-limiting examples of spiroalkyl groups include:

[0578]

[0579] It also includes spirocycloalkyl groups that share a spiro atom with a heterocycloalkyl group. Non-limiting examples include:

[0580]

[0581] The term "fused cycloalkyl" refers to a 5 to 20-membered, all-carbon polycyclic group in which each ring in the system shares a pair of adjacent carbon atoms with the other rings in the system, wherein one or more rings may contain one or more double bonds, but no ring has a completely conjugated π electron system. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. Depending on the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused cycloalkyl groups, preferably bicyclic or tricyclic, more preferably 5-membered / 5-membered or 5-membered / 6-membered bicyclic alkyl groups. Non-limiting examples of fused cycloalkyl groups include:

[0582]

[0583] The term "bridged cycloalkyl" refers to a 5-20 membered, all-carbon polycyclic group in which any two rings share two carbon atoms that are not directly connected, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. Preferably, it is 6-14 members, more preferably 7-10 members. Depending on the number of constituent rings, it can be classified as a bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl group, preferably a bicyclic, tricyclic or tetracyclic group, more preferably a bicyclic or tricyclic group. Non-limiting examples of bridged cycloalkyl groups include:

[0584]

[0585] The cycloalkyl ring may be fused to an aryl, heteroaryl or heterocycloalkyl ring, wherein the ring attached to the parent structure is a cycloalkyl, non-limiting examples of which include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc. The cycloalkyl group may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0586] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, one or more of which is selected from nitrogen, oxygen or S(O) m(wherein m is an integer from 0 to 2) heteroatoms, but excluding the ring portion of -OO-, -OS- or -SS-, the remaining ring atoms are carbon. Preferably, it contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms; more preferably, it contains 3 to 10 ring atoms; further preferably, it contains 3 to 8 ring atoms. Non-limiting examples of monocyclic heterocyclic groups include pyrrolidinyl, azetidinyl, oxetanyl, oxetanyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl and pyranyl; preferably, pyrrolidinyl, azetidinyl, oxetanyl, tetrahydrofuranyl, pyrazolidinyl, morpholinyl, Piperazinyl and pyranyl; more preferably pyrrolidinyl, azetidinyl, oxetanyl, oxahenyl, piperidinyl, Piperazinyl and pyranyl. Polycyclic heterocyclic groups include spirocyclic, fused-ring and bridged heterocyclic groups; wherein the spirocyclic, fused-ring and bridged heterocyclic groups are optionally connected to other groups through single bonds, or further connected to other cycloalkyl, heterocyclic, aryl and heteroaryl groups through any two or more atoms on the ring.

[0587] The term "spiroheterocyclyl" refers to a polycyclic heterocyclic group in which the monocyclic rings of 5 to 20 members share one atom (called a spiro atom), wherein one or more ring atoms are selected from nitrogen, oxygen or S(O) m (wherein m is an integer 0 to 2) heteroatom, and the remaining ring atoms are carbon. It may contain one or more double bonds, but no ring has a completely conjugated π electron system. It is preferably 6 to 14 members, more preferably 7 to 10 members. According to the number of shared spiral atoms between the rings, the spiro heterocyclic group is divided into a monospiro heterocyclic group, a dispiro heterocyclic group or a polyspiro heterocyclic group, preferably a monospiro heterocyclic group and a dispiro heterocyclic group. It is more preferably 4 yuan / 4 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 5 yuan or 5 yuan / 6 yuan monospiro heterocyclic group. Non-limiting examples of spiro heterocyclic groups include:

[0588]

[0589] The term "fused heterocyclyl" refers to a polycyclic heterocyclic group of 5 to 20 members, wherein each ring in the system shares a pair of adjacent atoms with other rings in the system, one or more rings may contain one or more double bonds, but no ring has a completely conjugated π electron system, wherein one or more ring atoms are selected from nitrogen, oxygen or S(O) m (wherein m is an integer from 0 to 2) heteroatoms, the remaining ring atoms being carbon. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. According to the number of constituent rings, it can be divided into 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:

[0590]

[0591] The term "bridged heterocyclyl" refers to a 5- to 14-membered polycyclic heterocyclic group in which any two rings share two atoms that are not directly connected, which may contain one or more double bonds but no ring has a completely conjugated π electron system, wherein one or more ring atoms are selected from nitrogen, oxygen or S(O) m (wherein m is an integer from 0 to 2) heteroatoms, the remaining ring atoms being carbon. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. Depending on the number of constituent rings, it can be classified as a bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclic group, preferably a bicyclic, tricyclic or tetracyclic group, more preferably a bicyclic or tricyclic group. Non-limiting examples of bridged heterocyclic groups include:

[0592]

[0593] The heterocyclyl ring may be fused to an aryl, heteroaryl or cycloalkyl ring, wherein the ring attached to the parent structure is a heterocyclyl, non-limiting examples of which include:

[0594]

[0595] The heterocyclyl group may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0596] The term "aryl" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably 6- to 10-membered, more preferably 6- to 8-membered, such as phenyl and naphthyl. Phenyl is more preferred. The aryl ring may be fused to a heteroaryl, heterocyclyl, or cycloalkyl ring, wherein the ring attached to the parent structure is the aryl ring, non-limiting examples of which include:

[0597]

[0598] The aryl group may be substituted or unsubstituted. When substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0599] The term "heteroaryl" refers to a heteroaromatic system containing 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 10-membered, more preferably 5 to 8-membered, and most preferably 5-membered or 6-membered, such as imidazolyl, furyl, thienyl, thiazolyl, pyrazolyl, oxazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, thiadiazole, pyrazinyl, etc., preferably triazolyl, thienyl, imidazolyl, pyrazolyl or pyrimidinyl, thiazolyl; more preferably triazolyl, pyrrolyl, thienyl, thiazolyl and pyrimidinyl. The heteroaryl ring can be fused to an aryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaryl ring, non-limiting examples of which include:

[0600]

[0601] The heteroaryl group may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0602] The term "alkoxy" refers to -O-(alkyl) and -O-(unsubstituted cycloalkyl), wherein alkyl is as defined above, preferably containing an alkyl group of 1 to 8 carbon atoms, more preferably an alkyl group of 1 to 6 carbon atoms, and most preferably an alkyl group of 1 to 3 carbon atoms. Non-limiting examples of alkoxy include: methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy. Alkoxy 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, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0603] "Haloalkyl" refers to an alkyl group substituted with one or more halogens, wherein alkyl is as defined above.

[0604] "Haloalkoxy" refers to an alkoxy group substituted with one or more halogens, wherein alkoxy is as defined above.

[0605] "Hydroxyalkyl" refers to an alkyl group substituted with a hydroxy group, wherein alkyl is as defined above.

[0606] "Alkenyl" refers to a chain alkenyl group, also known as an alkene group, preferably an alkyl group containing 2 to 8 carbon atoms, more preferably an alkyl group containing 2 to 6 carbon atoms, and most preferably an alkyl group containing 2 to 3 carbon atoms. The alkenyl group may be further substituted with other related groups, such as alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate groups.

[0607] "Alkynyl" refers to (CH≡C-), preferably an alkyl group containing 2 to 8 carbon atoms, more preferably an alkyl group containing 2 to 6 carbon atoms, and most preferably an alkyl group containing 2 to 3 carbon atoms. The alkynyl group may be further substituted with other related groups, such as alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0608] The term "alkynylene" refers to an alkynyl group with one hydrogen atom further substituted, for example, "ethynylene" refers to -C≡C-, "propenylene" refers to -C≡C-CH2-, etc. Alkynylenes (containing three or more carbon atoms) may be substituted or unsubstituted. When substituted, the substituents are preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, and heterocycloalkylthio.

[0609] "Fused cyclic group" refers to a polycyclic group formed by two or more carbon rings or heterocyclic rings with a common ring edge. The fused cyclic group includes fused cycloalkyl, fused heteroaryl, fused aryl and fused heteroaryl. The fused cycloalkyl refers to a polycyclic group formed by a cycloalkyl and a heterocyclic group, an aryl, or a heteroaryl with a common ring edge; the fused heterocyclic group refers to a polycyclic group formed by a heterocyclic group and a cycloalkyl, an aryl, or a heteroaryl with a common ring edge; the fused aryl refers to a polycyclic group formed by an aryl and a cycloalkyl, a heterocyclic group, or a heteroaryl with a common ring edge; the fused heteroaryl refers to a polycyclic group formed by a heteroaryl and a cycloalkyl, a heterocyclic group, or a heteroalkyl with a common ring edge; for example:

[0610]

[0611] "Haloalkyl" refers to an alkyl group substituted with one or more halogens, wherein alkyl is as defined above.

[0612] "Haloalkoxy" refers to an alkoxy group substituted with one or more halogens, wherein alkoxy is as defined above.

[0613] "Hydroxyalkyl" refers to an alkyl group substituted with a hydroxy group, wherein alkyl is as defined above.

[0614] "Hydroxy" refers to an -OH group.

[0615] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[0616] "Amino" refers to -NH2.

[0617] "Cyano" refers to -CN.

[0618] "Nitro" refers to -NO2.

[0619] "Carboxyl" refers to -C(O)OH.

[0620] "THF" refers to tetrahydrofuran.

[0621] "EtOAc" refers to ethyl acetate.

[0622] "MeOH" refers to methanol.

[0623] "DMF" refers to N,N-dimethylformamide.

[0624] "DIPEA" refers to diisopropylethylamine.

[0625] "TFA" refers to trifluoroacetic acid.

[0626] "MeCN" refers to acetylene glycol.

[0627] "DMA" refers to N,N-dimethylacetamide.

[0628] "Et2O" refers to diethyl ether.

[0629] "DCE" refers to 1,2-dichloroethane.

[0630] "DIPEA" refers to N,N-diisopropylethylamine.

[0631] "NBS" refers to N-bromosuccinimide.

[0632] "NIS" refers to N-iodosuccinimide.

[0633] "Cbz-Cl" refers to benzyl chloroformate.

[0634] "Pd2(dba)3" refers to tris(dibenzylideneacetone)dipalladium.

[0635] "Dppf" refers to 1,1'-bisdiphenylphosphinoferrocene.

[0636] "HATU" refers to 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0637] "KHMDS" refers to potassium hexamethyldisilazide.

[0638] "LiHMDS" refers to lithium bistrimethylsilylamide.

[0639] "MeLi" refers to methyllithium.

[0640] "n-BuLi" refers to n-butyllithium.

[0641] "NaBH(OAc)3" refers to sodium triacetoxyborohydride.

[0642] Different expressions 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.

[0643] The hydrogen atoms described in the present invention can all be replaced by their isotope deuterium, and any hydrogen atom in the example compounds of the present invention can also be replaced by a deuterium atom.

[0644] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, "a heterocyclic group optionally substituted with an alkyl group" means that the alkyl group may but need not be present, and that the description includes instances where the heterocyclic group is substituted with an alkyl group and instances where the heterocyclic group is not substituted with an alkyl group.

[0645] "Substituted" means that one or more hydrogen atoms, preferably up to 5, more preferably 1 to 3 hydrogen atoms, in a group are replaced independently of one another by a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and a person skilled in the art can determine (by experiment or theory) which substitutions are possible or impossible without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (e.g., olefinic) bond.

[0646] A "pharmaceutical composition" refers to a mixture containing one or more compounds described herein, or their physiologically / pharmaceutically acceptable salts or prodrugs, together with other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitating absorption of the active ingredient and thereby exerting its biological activity.

[0647] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention that are safe and effective when used in mammals and have the desired biological activity. DETAILED DESCRIPTION

[0648] The present invention is further described below with reference to the following examples, but these examples are not intended to limit the scope of the present invention.

[0649] Example

[0650] The structures of the compounds of the present invention are determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer, using deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3) as the solvents, with tetramethylsilane (TMS) as the internal standard.

[0651] Liquid chromatography-mass spectrometry (LC-MS) was performed using an Agilent 1200 Infinity Series mass spectrometer. HPLC was performed using an Agilent 1200DAD high-pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-pressure liquid chromatograph (Gimini C18 150×4.6 mm column).

[0652] Thin layer chromatography silica gel plates use Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications used for TLC are 0.15mm-0.20mm, and the specifications used for thin layer chromatography separation and purification products are 0.4mm-0.5mm. Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[0653] The starting materials in the examples of the present invention are known and can be purchased commercially, or can be synthesized using or according to methods known in the art.

[0654] Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, with dry solvents and reaction temperatures in degrees Celsius.

[0655] Intermediate A

[0656]

[0657] The first step: zinc powder (4.88g, 74.6mmol) is suspended in DMF (20mL), and suspension is carried out nitrogen replacement protection.Add chlorotrimethylsilane (1.01g, 9.32mmol) and 1,2-ethylene dibromide (1.75g, 9.32mmol), and the mixture produced is stirred at room temperature 5 minutes.In mixture, drip DMF (25mL) solution of 4-iodo-2,2-dimethyltetrahydropyran (13.43g, 55.95mmol), and mixture is stirred at room temperature 20 minutes.In above-mentioned solution, add palladium acetate (209mg, 0.93mmol) and 4-(N, N-dimethylamino) phenyl] di-tert-butyl phosphine (494mg, 1.86mmol), 5-bromoindole-2-ethyl formate (5.0g, 18.65mmol), and nitrogen is introduced in container. The mixture was stirred at an external temperature of 50°C for 1 hour, then the external temperature was cooled to 0°C and 5N hydrochloric acid (6 mL) was added for neutralization. 30% aqueous sodium chloride solution (50 mL) and ethyl acetate (300 mL) were added, and insoluble matter was removed with celite. The filtrate was extracted with ethyl acetate, and the organic layer was washed with a 30% aqueous sodium chloride solution. It was then dried over magnesium sulfate and passed through a filter, and the solvent was removed by evaporation under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate: hexane = 1: 1) to obtain the product, which was subjected to chiral separation to obtain the product compound (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid ethyl ester (1.96 g, 35% yield).

[0658] MS m / z(ESI):302.2[M+1].

[0659] Step 2: (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid ethyl ester (1.96 g, 6.5 mmol) was dissolved in acetonitrile (30 mL) at room temperature, and potassium carbonate (2.70 g, 19.51 mmol) was added to the solution. 2-Chloroacetonitrile (736 mg, 9.75 mmol) was added to the resulting solution at an external temperature of 10°C, and the solution was stirred for 12 hours. Saturated brine (50 mL) and ethyl acetate (100 mL) were added to the reaction solution for extraction, and the aqueous layer was extracted a second time with ethyl acetate (20 mL). The combined organic layers were washed with a saturated aqueous solution of common salt (50 mL), and then concentrated under reduced pressure at an external temperature of 40° C. to give (S)-1-(cyanomethyl)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid ethyl ester (2 g), which was used in the subsequent step without purification.

[0660] MS m / z(ESI):341.2[M+1].

[0661] The third step: (S) -1- (cyanomethyl) -5- (2,2- dimethyltetrahydro -2H- pyran -4- bases) -1H- indole -2- carboxylic acid ethyl ester (2g, 5.88mmol) and (4R) -4- methyl -1,3,2- dioxathiolane 2,2- dioxide (2.43g, 17.6mmol) were dissolved in tetrahydrofuran (15mL), and the mixture was cooled to 0 ° C. Under a nitrogen atmosphere, a THF solution of potassium bis (trimethylsilyl) amide (23.5mL, 23.5mmol, 1M) was slowly added dropwise. The reaction mixture was stirred at 0 ° C for 2.5 hours, then formic acid (3mL) was added, and extracted with a mixture of ethyl acetate (40mL). The organic layer was washed three times with water, twice with a saturated aqueous solution of sodium bicarbonate, and once with brine, and then dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4) to give 1-((1S,2S)-1-cyano-2-methylcyclopropyl)-5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid ethyl ester (1.20 g, yield 54%).

[0662] MS m / z(ESI):381.2[M+1].

[0663] Step 4: To a solution of ethyl 1-((1S,2S)-1-cyano-2-methylcyclopropyl)-5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylate (1.20 g, 3.15 mmol) in dimethyl sulfoxide (DMSO) (10 mL) was added 50% aqueous hydroxylamine solution (2.08 g, 31.5 mmol), and the mixture was stirred at room temperature for 17 hours. Ethyl acetate (50 mL) was added, and the mixture was washed with water (50 mL) and brine (50 mL), and then dried over magnesium sulfate. After the mixture was filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was dissolved in DMSO (10 mL). Then, carbonyldiimidazole (1.02 g, 6.31 mmol) and 1,8-diazabicycloundec-7-ene (1.20, 7.88 mmol) were added, and the resulting mixture was stirred at room temperature for 0.5 hours. To the mixture was added formic acid, which was then purified by reverse phase chromatography (acetonitrile / water, 0.1% formic acid) to give ethyl 5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1-((1S,2S)-2-methyl-1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-1H-indole-2-carboxylate (0.96 g, 69% yield).

[0664] MS m / z(ESI):440.2[M+1].

[0665] Step 5: To a solution of ethyl 5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1-((1S,2S)-2-methyl-1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-1H-indole-2-carboxylate (0.96 g, 2.18 mmol) in DMSO (8 mL) was added 2 M aqueous sodium hydroxide solution (3.28 mL, 6.55 mmol), and the mixture was stirred at room temperature for 1.5 hours. To the mixture was added formic acid, followed by purification by reverse phase chromatography (acetonitrile / water, 0.1% formic acid) to afford 5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1-((1S,2S)-2-methyl-1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-1H-indole-2-carboxylic acid (0.65 g, 72% yield).

[0666] MS m / z(ESI):412.2[M+1].

[0667] Intermediate B

[0668]

[0669] The first step: To a solution of (S)-3-((2-cyanoethyl)amino)butyronitrile (2.4 g, 17.9 mmol) in tetrahydrofuran (THF) (20 mL) was added a 1 M solution of potassium tert-butoxide in THF (17.9 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered, washed with THF (50 mL), and the filtrate was dried under reduced pressure to give potassium (S)-(5-cyano-6-methyl-1,2,3,6-tetrahydropyridin-4-yl)amide (2.7 g, 88% yield).

[0670] MS m / z(ESI):138.1[M+1].

[0671] Second step: To a solution of hydrazine hydrochloride (1.06 g, 15.4 mmol) and (S)-(5-cyano-6-methyl-1,2,3,6-tetrahydropyridin-4-yl)amide potassium (2.7 g, 15.4 mmol) in ethanol (30 mL) was added 2N hydrochloric acid (11.5 mL, 23.1 mmol), and the mixture was stirred at 50°C for 1 hour. After the reaction mixture was cooled to 0°C, 5M aqueous sodium hydroxide solution (4.62 mL, 23.1 mmol) and di-tert-butyl dicarbonate (3.36 g, 15.4 mmol) were added, and the mixture was stirred at 0°C for 1 hour. Water was added to the reaction mixture, and extraction was performed with ethyl acetate, and the organic layer was then washed with brine and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=20:1) to give (S)-3-amino-4-methyl-6,7-dihydro-2l2-pyrazolo[4,3-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (2.5 g, yield 65%).

[0672] MS m / z(ESI):253.1[M+1].

[0673] Step 3: Dissolve (S)-tert-butyl 3-amino-4-methyl-6,7-dihydro-2l2-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate (2.5 g, 9.91 mmol), 2-fluoro-5-iodo-1,3-dimethylbenzene (2.48 g, 9.91 mmol), and L-proline (342.23 mg, 2.97 mmol) in dimethyl sulfoxide (30 mL). Under nitrogen, add cuprous iodide (754.82 mg, 3.96 mmol) and potassium carbonate (1.10 g, 7.93 mmol). The mixture was stirred at 120°C for 19 hours. The reaction was quenched by adding saturated brine (150 mL) to the mixture, which was then extracted with ethyl acetate (50 mL × 3). The organic phases were combined, washed with saturated brine (50 mL × 5), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (petroleum ether: ethyl acetate = 100:0 to 50:50) to give the target product (S)-3-amino-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (2.9 g, yield 78%).

[0674] MS m / z(ESI):375.2[M+1].

[0675] The 4th step: to (S) -3- amino -2- (4- fluoro -3,5- dimethylphenyl) -4- methyl -2,4,6,7- tetrahydro -5H- pyrazolo [4,3-c] pyridine -5- carboxylic acid tert-butyl ester (2.9g, 7.4mmol) pyridine (10mL) solution, add 2- isocyanate -1,1- dimethoxyethane (2.03g, 15.49mmol), and the mixture is stirred at room temperature. After 3 hours, diethylamine (1.13g, 15.49mmol) is added, and the mixture is stirred at room temperature for 5 minutes, then water (50mL) is added, and the mixture obtained is stirred at room temperature for 20 minutes. The reaction mixture, which had become a suspension, was filtered, and the obtained solid was washed with water (20 mL) and then dried under reduced pressure to give (S)-3-(3-(2,2-dimethoxyethyl)ureido)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (3.6 g, yield 92%).

[0676] MS m / z(ESI):506.3[M+1].

[0677] The 5th step: to (S) -3- (3- (2,2- dimethoxyethyl) urea groups) -2- (4- fluoro- 3,5- dimethylphenyl) -4- methyl -2,4,6,7- tetrahydro -5H- pyrazolo [4,3-c] pyridine -5- carboxylic acid tert-butyl ester (3.6g, 7.12mmol) add formic acid (40mL), and the mixture is stirred at room temperature for 21 hours. The reaction mixture is concentrated under reduced pressure, and toluene is added, and solvent is removed by evaporation under reduced pressure. Dichloromethane (10mL) is added to the residue, to dissolve the residue, then hydrogen chloride (4M dioxane solution, 10mL) is added at room temperature, stirred at room temperature for 2 hours. The reaction mixture is concentrated under reduced pressure. Toluene was added and the solvent was evaporated under reduced pressure to give a crude product of (S)-1-(2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-3-yl)-1,3-dihydro-2H-imidazol-2-one (3.6 g).

[0678] MS m / z(ESI):342.2[M+1].

[0679] Intermediate C and Intermediate D

[0680]

[0681] Step 1: Dissolve (S)-tert-butyl 3-amino-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate (2.5 g, 6.68 mmol) in bromoform (8 mL). Under nitrogen, add isoamyl nitrite (2.07 g, 20.03 mmol). The mixture is stirred at 60°C for 2 hours. The mixture is concentrated under reduced pressure, quenched by the addition of saturated brine (30 mL), extracted with ethyl acetate (50 mL), washed with saturated brine (50 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (petroleum ether:ethyl acetate = 100:0 to 50:50) to give the target product (S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (2.1 g, yield 72%).

[0682] MS m / z(ESI):438.1, 440.1[M+1].

[0683] Step 2: (S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (2.1 g, 4.79 mmol) was added to hydrogen chloride (4 M dioxane solution, 20 mL) at room temperature and stirred at room temperature for 2 hours. The crude product (S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine (1.7 g) was obtained by concentration under reduced pressure and used directly in the next step.

[0684] MS m / z(ESI):338.0, 340.0[M+1].

[0685] Step 3: (S)-3-Bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine hydrochloride (1.7 g, 4.54 mmol), Intermediate A (526.84 mg, 4.54 mmol), and diisopropylethylamine (1.76 g, 13.61 mmol, 2.37 mL) were dissolved in N,N'-dimethylformamide (15 mL). 2-(7-Azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (2.59 g, 6.81 mmol) was added under nitrogen. The mixture was stirred at 25°C for 12 hours. The crude reaction solution was separated by preparative high performance liquid chromatography to give the product 3-((1S,2S)-1-(2-((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazol-5(4H)-one (2 g, yield 60%).

[0686] MS m / z(ESI):731.2,733.2[M+1].

[0687] Step 4: 3-((1S,2S)-1-(5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-1H-indol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[0688] 3-((1S,2S)-1-(2-((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazole Oxazol-5(4H)-one (1 g, 1.37 mmol), bis(pinacolato) boronate (0.52 g, 2.05 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (100 mg, 137 μmol) were dissolved in 1'4-dioxane (30 mL). Potassium acetate (335 mg, 3.42 mmol) was added under nitrogen. The mixture was stirred at 90°C for 12 hours. The mixture was concentrated under reduced pressure. The crude product was quenched with saturated brine (50 mL) and extracted with ethyl acetate (50 mL x 2). The organic phases were combined, washed sequentially with saturated brine (50 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was separated by preparative high-performance liquid chromatography to obtain the product (0.6 g, 56% yield).

[0689] MS m / z(ESI):779.4[M+1].

[0690] Intermediate E

[0691]

[0692] Step 1: 3-((1S,2S)-1-(5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-(2-carbonyl-2,3-dihydro-1H-imidazol-1-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-1H-indol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[0693] The product was obtained by referring to Intermediate C and Intermediate D in the third step.

[0694] MS m / z(ESI):735.3[M+1].

[0695] Intermediate F

[0696]

[0697] first step

[0698] 5-(2,2-Dimethyl-3,6-dihydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester

[0699] Ethyl 5-bromo-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (5.0 g, 18.58 mmol, 1.0 eq.), 2-(6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8.6 g, 22.30 mmol, 1.2 eq.), K3PO4 (11.8 g, 55.75 mmol, 3.0 eq.), and Pd(dppf)Cl2 (1.52 g, 1.86 mmol, 0.1 eq.) were added sequentially into a 500 ml three-necked flask, followed by dioxane (100 mL) and H2O (20 mL). The atmosphere was replaced with nitrogen three times and the mixture was refluxed for 12 h. After LCMS confirmed complete reaction of the starting materials, the reaction solution was cooled to room temperature and 100 mL of H₂O was added for separation. The aqueous phase was extracted with ethyl acetate (100 mL × 3). The combined organic phases were washed with saturated brine (100 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by silica gel column chromatography afforded product 2 (4.18 g, 74.90% yield) as a yellow oil.

[0700] MS m / z(ESI):301.1[M+1].

[0701] Step 2

[0702] 5-(2,2-Dimethyltetrahydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester

[0703] Product 2 (4.0 g, 13.32 mmol, 1.0 eq.) was dissolved in a mixture of anhydrous methanol (20 mL) and THF (20 mL). Pd / C (0.4 g, 10% w / w) was added to the system. The atmosphere was purged with nitrogen three times and then with hydrogen three times. Catalytic hydrogenation was carried out using a hydrogen balloon at 30°C for 10 hours. LCMS indicated that the reaction was complete. The Pd / C was removed by filtration through celite, and the filtrate was concentrated to dryness at 45°C to afford product 3 (4 g, 99.32% yield) as a light yellow oil.

[0704] MS m / z(ESI):303.1[M+1].

[0705] Step 3

[0706] 5-(2,2-Dimethyltetrahydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

[0707] Product 3 (4.0 g, 13.23 mmol, 1.0 eq.) and sodium hydroxide solution (14.6 ml, 29.11 mmol, 2 N, 2.2 eq.) were dissolved in methanol (40 mL) and reacted at 70°C for 3 hours. The reaction mixture was cooled to room temperature, and the aqueous phase was washed with ethyl acetate (50 mL x 3). The pH was adjusted to 5 with hydrochloric acid (3 N), and then extracted with ethyl acetate (50 mL x 3). The mixture was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Product 4 (2.72 g, 74.98% yield) was obtained as an off-white solid. MS m / z (ESI): 275.1 [M+1].

[0708] Step 4

[0709] 5-(2,2-Dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0710] Product 4 (2.0 g, 7.29 mmol) was added to a 100 mL single-necked flask, followed by 20 mL of toluene. Under nitrogen, oxalyl chloride (1.85 g, 14.58 mmol, 2.0 eq.) and 2 drops of dry DMF were slowly added at room temperature. The reaction mixture was allowed to react at 100°C for 2 hours. The reaction solution was concentrated to dryness, and dry dichloromethane (100 mL) was added. N-methylaniline (1.56 g, 14.58 mmol, 2.0 eq.) was slowly added to the reaction system. After the addition was complete, triethylamine (1.48 g, 14.58 mmol, 2.0 eq.) was slowly added dropwise. After the addition was complete, the reaction mixture was allowed to react at 30°C for 8 hours. After completion of the reaction as monitored by LCMS, H2O (50 mL) was added to the reaction system, and the mixture was extracted with dichloromethane (100 mL x 3). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography to give the desired product (1.58 g, 59.63% yield) as a yellow oil.

[0711] MS m / z(ESI):364.2[M+1].

[0712] Step 5

[0713] 1-(Cyanomethyl)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0714] Product 5 (1.5 g, 4.13 mmol, 1.0 eq.) was dissolved in 15 ml of dry DMF and cooled to 0°C in an ice bath under nitrogen. NaH (495 mg, 12.38 mmol, 3.0 eq.) was slowly added. After addition, the mixture was stirred at 0°C for 0.5 hours. Bromoacetonitrile (2.48 g, 20.65 mmol, 5.0 eq.) was slowly added. After addition, the mixture was allowed to react at 30°C for 8 hours. Ethyl acetate and water were added to the reaction system, and the mixture was extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography to obtain the desired product (997 mg, 60% yield) as a yellow foamy solid.

[0715] MS m / z(ESI):403.2[M+1].

[0716] Step 6

[0717] 1-((1S,2S)-1-cyano-2-methylcyclopropyl)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0718] Product 6 (900 mg, 2.24 mmol, 1.0 eq.) and (R)-4-methyl-1,3,2-dioxathiane 2,2-dioxide (1.08 g, 7.84 mmol, 3.5 eq.) were dissolved in DMPU (20 mL). After cooling to 0°C in an ice bath, KHMDS (22.4 mmol, 10.0 eq., 1 M in THF) was slowly added dropwise. The reaction was incubated for 5 hours. Ethyl acetate and water were added to the reaction system, and the mixture was extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography to obtain the desired product (496 mg, 50% yield) as a yellow foamy solid.

[0719] MS m / z(ESI):443.2[M+1].

[0720] Chiral separation of 7 afforded 7A and 7B.

[0721] MS m / z(ESI):443.2[M+1].

[0722] Step 7

[0723] 5-((S)-2,2-Dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-1-((1S,2S)-2-methyl-1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-N-phenyl-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

[0724] Product 7A (450 mg, 1.02 mmol, 1.0 eq.), hydroxylamine hydrochloride (354 mg, 5.10 mmol, 5.0 eq.), K2CO3 (775 mg, 5.61 mmol, 5.5 eq.), and anhydrous ethanol (25 mL) were added sequentially to a 100 mL single-necked flask and reacted at 95°C for 5 hours. The reaction solution was concentrated to dryness, and dry THF (30 mL) was added. After stirring until clear, the insoluble matter was filtered off. N,N'-carbonyldiimidazole (364 mg, 2.24 mmol, 2.2 eq.) and 1,8-diazabicyclo[5.4.0]undec-7-ene (466 mg, 3.06 mmol, 3.0 eq.) were added to the filtrate. The reaction mixture was stirred at 50°C for three hours. The reaction solution was concentrated to dryness, and the resulting residue was purified by silica gel column chromatography to obtain product 8 (417 mg, 81.6% yield) as a light yellow solid.

[0725] MS m / z(ESI):502.2[M+1].

[0726] Step 8

[0727] 5-((S)-2,2-Dimethyltetrahydro-2H-pyran-4-yl)-1-((1S,2S)-2-methyl-1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

[0728] Product 8 (400 mg, 0.80 mmol, 1.0 eq.) was dissolved in ethylene glycol dimethyl ether (20 mL), and KOH (404 mg, 7.2 mmol, 9.0 eq.) was added and the mixture was reacted at 100°C for 5 hours. The reaction solution was concentrated to dryness. The resulting residue was purified by silica gel column chromatography to obtain the desired product (200 mg, 60.60% yield) as a yellow solid.

[0729] MS m / z(ESI):413.2[M+1].

[0730] Intermediate G

[0731]

[0732] Step 1: tert-Butyl (S)-3-amino-2-(4-cyano-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

[0733] To a vial, add tert-butyl (2S)-3-cyano-2-methyl-4-carbonylpiperidine-1-carboxylate (2g, 8.4mmol), toluene (20mL, 10v), 4-hydrazino-2,6-dimethylbenzonitrile hydrochloride (1.65g, 8.4mmol), and pyridine hydrochloride (485mg, 4.2mmol). After addition, raise the temperature to 96°C under nitrogen and stir overnight. After completion of the reaction, add water and extract with ethyl acetate (50mL*3). The organic phase is dried over Na2SO4, and the residue is purified by silica gel column chromatography (PE:EA = 1:1) to obtain the product (1.32g, 41.3% yield).

[0734] MS m / z(ESI):382.2[M+1].

[0735] Step 2: tert-Butyl (S)-2-(4-cyano-3,5-dimethylphenyl)-3-(3-(2,2-dimethoxyethyl)ureido)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

[0736] Compound 2 (1.22 g, 3.2 mmol), dimethyl sulfoxide (30 ml, 15 v), N-(2,2-dimethoxyethyl)-1H-imidazole-1-carboxamide (766 mg, 3.8 mmol), and potassium tert-butoxide (1.29 g, 11.6 mmol) were added to a vial. After nitrogen replacement, the mixture was stirred at room temperature overnight. LC-MS confirmed the completion of the reaction. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate (80 mL*3). The organic phase was dried over Na2SO4, and the residue was purified by silica gel column chromatography (PE:EA = 3:1) to obtain the product (1.08 g, 65.8% yield).

[0737] MS m / z(ESI):513.2[M+1].

[0738] Step 3: tert-Butyl (S)-2-(4-cyano-3,5-dimethylphenyl)-4-methyl-3-(2-carbonyl-2,3-dihydro-1H-imidazol-1-yl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

[0739] Compound 3 (500 mg, 0.98 mmol), tetrahydrofuran (15 ml, 30 v), and MsOH (470.4 mg, 4.90 mmol) were added to a vial. The atmosphere was replaced with nitrogen and the reaction temperature was raised to 60°C for 6 hours. LC-MS analysis revealed no compound 3. The reaction mixture was cooled to room temperature and potassium phosphate (1.67 g, 7.84 mmol) was added. After the reaction system was alkaline, Boc anhydride (320 mg, 1.47 mmol) was added. The mixture was stirred at room temperature for 2 hours. Water was added and the mixture was extracted with ethyl acetate (80 mL x 3). The organic phase was dried over Na2SO4. The residue was purified by silica gel column chromatography (PE:EA = 3:1) to obtain the product (380 mg, 86.5% yield).

[0740] MS m / z(ESI):449.2[M+1].

[0741] Example 1

[0742]

[0743] Step 1: 3-((1S,2S)-1-(2-((S)-3-(3-(4-((dimethyl(carbonyl)-16-sulfaneylidene)amino)-2-fluorophenyl)-2-carbonyl-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[0744] To a suspension of Intermediate E (20 mg, 0.027 mmol), ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione (14.5 mg, 0.054 mmol), (1S,2S)-1-N,2-N-dimethylcyclohexane-1,2-diamine (1.9 mg, 0.013 mmol) and potassium carbonate (11.3 mg, 0.082 mmol) in N-methylpyrrolidone (0.5 mL) was added copper (I) iodide (1.0 mg, 0.0054 mmol) at room temperature, and the mixture was stirred at 130° C. under a nitrogen atmosphere for 3 hours. The reaction mixture was purified by reverse phase silica gel chromatography (acetonitrile / water, 0.1% formic acid) to obtain the target compound (10 mg, 40% yield).

[0745] MS m / z(ESI):920.3[M+1].

[0746] Example 3

[0747]

[0748] Step 1: (4-bromo-3-fluorophenyl)(imino)(methyl)-16-aminosulfonone

[0749] The target product was obtained using 1-thiomethyl-4-bromo-3-fluorobenzene as starting material, with reference to European Journal of Organic Chemistry, 2017, vol. 2017, #44, p. 6486-6490.

[0750] MS m / z(ESI):251.9, 253.9[M+1].

[0751] Step 2: 3-((1S,2S)-1-(5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-(2-(2-fluoro-4-(S-methylsulfonylimino)phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3]pyridine-5-carbonyl)-1H-indol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[0752] The target product was obtained by referring to Example 1.

[0753] MS m / z(ESI):906.4[M+1].

[0754] Example 5

[0755]

[0756] Step 1: 1-(4-bromo-3-fluorophenyl)-4,5-dihydro-3H-isothiazole 1-oxide

[0757] The target product was obtained using 4-bromo-3-fluorobenzenethiol as the starting material, with reference to Angewandte Chemie-International Edition, 2018, vol. 57, #37, p. 12053-12056.

[0758] MS m / z(ESI):278.0, 280.0[M+1].

[0759] Step 2: 3-((1S,2S)-1-(5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-(3-(2-fluoro-4-(1-oxido-4,5-dihydro-3H-116-isothiazol-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3]pyridine-5-carbonyl)-1H-indol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[0760] The target product was obtained by referring to Example 1.

[0761] MS m / z(ESI):932.4[M+1].

[0762] Example 6

[0763]

[0764] Step 1: (4-bromo-2-(methylamino)phenyl)diethylphosphine oxide

[0765] Using 4-bromo-2-fluoro-1-iodobenzene as raw material, refer to WO2023 / 16546,2023,A1 Page / Page column160-162 to obtain the target product.

[0766] MS m / z(ESI):290.0, 292.0[M+1].

[0767] Step 2: Obtain the target product by referring to Example 1.

[0768] MS m / z(ESI):944.4[M+1].

[0769] 903.4[M+1]

[0770] Example 9

[0771]

[0772] Step 1: 2-Bromo-5-methyl-5,6,7,8-tetrahydroimidazo[1,2-c]pyrimidin-3-amine

[0773] 2-(2-Aminoethyl)-4-bromo-1H-imidazol-5-amine (0.2 g, 0.97 mmol) was dissolved in 1,2-dichloroethane (10 mL), followed by the addition of aqueous acetaldehyde (859 mg, 4.88 mmol, 25% aqueous solution). The reaction mixture was stirred at room temperature for 1 hour and then heated to reflux for 5 hours. The reaction mixture was evaporated to dryness, washed with water, and dried to obtain a crude product (0.2 g), which was used directly in the next step.

[0774] MS m / z(ESI):231.0,233.0[M+1].

[0775] Step 2: (R)-2-(4-fluoro-3,5-dimethylphenyl)-5-methyl-5,6,7,8-tetrahydroimidazo[1,2-c]pyrimidin-3-amine

[0776] 2-Bromo-5-methyl-5,6,7,8-tetrahydroimidazo[1,2-c]pyrimidin-3-amine (0.2 g, 0.87 mmol), 2-(4-fluoro-3,5-dimethylphenyl)-4,4,5-5-tetramethyl-1,3,2-dioxaborolane (216 mg, 0.87 mmol), and sodium carbonate (273.77 mg, 2.58 mmol) were dissolved in 1'4-dioxane (8 mL) and water (2 mL). Under nitrogen, ditriphenylpalladium dichloride (30.22 mg, 43.05 μmol) was added. The mixture was stirred at 90°C for 5 hours. After the reaction solution was cooled, saturated brine (5 mL) was added to quench the reaction and extracted with ethyl acetate (30 mL × 2). The mixture was separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The crude product was separated by preparative HPLC and chiral resolution to give the product (45 mg, yield 19%).

[0777] MS m / z(ESI):275.2[M+1].

[0778] Step 3: Refer to the fourth and fifth steps of Intermediate B, the first step of Intermediate E, and Example 1 (using 5-bromo-4-fluoro-1-methyl-1H-indazole instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0779] MS m / z(ESI):883.4[M+1].

[0780] Example 10

[0781]

[0782] Step 1: Ethyl 3-(4-fluoro-1-methyl-1H-indazol-5-yl)propionate

[0783] The target product was obtained using 4-fluoro-5-iodo-1-methyl-1H-indazole as starting material according to Organic and Biomolecular Chemistry, 2018, vol. 16, #34, p. 6341–6349.

[0784] MS m / z(ESI):247.1[M+1].

[0785] Step 2: 5-(4-Fluoro-1-methyl-1H-indazol-5-yl)isoxazol-3(2H)-one

[0786] Dissolve ethyl 3-(4-fluoro-1-methyl-1H-indazol-5-yl)propanoate (1.43 g, 5.8 mmol) in ethanol (15 mL), then add dropwise 10% sodium hydroxide solution (17 mL) of hydroxylamine hydrochloride (1.2 g, 17.5 mmol). Stir the reaction mixture overnight at room temperature. Adjust the pH of the reaction mixture to 2 with concentrated hydrochloric acid, stir for 30 minutes, filter, and wash with water to obtain a solid product (0.6 g, 44% yield).

[0787] MS m / z(ESI):234.1[M+1].

[0788] Step 3: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0789] MS m / z(ESI):884.4[M+1].

[0790] Example 11

[0791]

[0792] Step 1: 4-Fluoro-1-methyl-5-(piperazin-1-yl)-1H-indazole

[0793] The target product was obtained using 5-bromo-4-fluoro-1-methyl-1H-indazole as the starting material according to Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, #13, p. 3941–3945.

[0794] MS m / z(ESI):235.1[M+1].

[0795] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0796] MS m / z(ESI):885.4[M+1].

[0797] Example 12

[0798]

[0799] Step 1: 4-Fluoro-1-methyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl)-1H-indazole

[0800] Using 5-bromo-4-fluoro-1-methyl-1H-indazole as the starting material, the target product was obtained according to ACS Medicinal Chemistry Letters, 2021, vol. 12, #7, p. 1108–1115.

[0801] MS m / z(ESI):358.2[M+1].

[0802] Step 2: Using intermediate C as raw material, refer to the second step of Example 9 to obtain the target product.

[0803] MS m / z(ESI):882.4[M+1].

[0804] Example 13

[0805]

[0806] Step 1: 1-(4-Fluoro-1-methyl-1H-indazol-5-yl)piperazin-2-one

[0807] The target product was obtained using 5-bromo-4-fluoro-1-methyl-1H-indazole as the starting material according to Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, #13, p. 3941-3945.

[0808] MS m / z(ESI):249.1[M+1].

[0809] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0810] MS m / z(ESI):899.4[M+1].

[0811] Example 14

[0812]

[0813] Step 1: 3-(4-Fluoro-1-methyl-1H-indazol-5-yl)-1,3-oxazin-2-one

[0814] Using 5-bromo-4-fluoro-1-methyl-1H-indazole as raw material, the target product was obtained by referring to Example 1.

[0815] MS m / z(ESI):250.1[M+1].

[0816] Step 2: 6-Bromo-3-(4-fluoro-1-methyl-1H-indazol-5-yl)-1,3-oxazin-2-one

[0817] 3-(4-Fluoro-1-methyl-1H-indazol-5-yl)-1,3-oxazin-2-one (50 mg, 0.20 mmol) was dissolved in dichloromethane (4 mL), followed by the addition of N-bromosuccinimide (NBS) (35 mg, 0.20 mmol). The reaction mixture was stirred at room temperature for 1 hour. The residue was then separated by TLC (petroleum ether:ethyl acetate = 1:1) to afford the desired product (10 mg, 15% yield).

[0818] MS m / z(ESI):328.0, 330.0[M+1].

[0819] Step 3: Using intermediate D as raw material, refer to the second step of Example 9 to obtain the target product.

[0820] MS m / z(ESI):900.4[M+1].

[0821] Example 15

[0822]

[0823] Step 1: 2-(4-fluoro-1-methyl-1H-indazol-5-yl)-1,2,5-thiadiazolidine 1,1-dioxide

[0824] Using 5-bromo-4-fluoro-1-methyl-1H-indazole and 1,2,5-thiadiazolidine 1,1-dioxide as raw materials, the target product was obtained by referring to Example 1.

[0825] MS m / z(ESI):271.1[M+1].

[0826] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0827] MS m / z(ESI):919.3[M+1].

[0828] Example 16

[0829]

[0830] Step 1: 1-(4-fluoro-1-methyl-1H-indazol-5-yl)tetrahydropyrimidin-2(1H)-one

[0831] Using 5-bromo-4-fluoro-1-methyl-1H-indazole and tetrahydropyrimidin-2(1H)-one as raw materials, the target product was obtained by referring to Example 1.

[0832] MS m / z(ESI):249.1[M+1].

[0833] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0834] MS m / z(ESI):880.4[M+1].

[0835] Example 17

[0836]

[0837] Step 1: 4-(4-Fluoro-1-methyl-1H-indazol-5-yl)-1,2,4-oxadiazolidine-3,5-dione

[0838] The target product was obtained using 4-fluoro-1-methyl-1H-indazol-5-amine as starting material according to the method described in Archive der Pharmazie, 1981, vol. 314, #4, p. 294-302.

[0839] MS m / z(ESI):251.1[M+1].

[0840] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0841] MS m / z(ESI):901.4[M+1].

[0842] Example 18

[0843]

[0844] Step 1: 3-(4-fluoro-1-methyl-1H-indazol-5-yl)oxazol-2(3H)-one

[0845] The target product was obtained using 4-fluoro-1-methyl-1H-indazol-5-amine as starting material according to Organic Letters, 2008, vol. 10, #5, p. 925–928.

[0846] MS m / z(ESI):234.1[M+1].

[0847] Step 2: 5-bromo-3-(4-fluoro-1-methyl-1H-indazol-5-yl)oxazol-2(3H)-one

[0848] The target product was obtained by referring to the second step of Example 14.

[0849] MS m / z(ESI):312.0, 314.0[M+1].

[0850] Step 3: Using intermediate D as raw material, refer to the second step of Example 9 to obtain the target product.

[0851] MS m / z(ESI):884.4[M+1].

[0852] Example 19

[0853]

[0854] Step 1: 3-Ethoxy-4-((4-fluoro-1-methyl-1H-indazol-5-yl)amino)cyclobut-3-ene-1,2-dione

[0855] The target product was obtained using 4-fluoro-1-methyl-1H-indazol-5-amine as starting material according to the method of Journal of Organic Chemistry, 2010, vol. 75, #12, p. 3983–3992.

[0856] MS m / z(ESI):261.0[M+1].

[0857] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0858] MS m / z(ESI):911.4[M+1].

[0859] Example 20

[0860]

[0861] Step 1: 3-(4-fluoro-1-methyl-1H-indazol-5-yl)imidazolidine-2,4-dione

[0862] The target product was obtained using 5-bromo-4-fluoro-1-methyl-1H-indazole as the starting material, according to Journal of Medicinal Chemistry, 2012, vol. 55, #7, p. 2945–2959.

[0863] MS m / z(ESI):249.1[M+1].

[0864] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0865] MS m / z(ESI):899.4[M+1].

[0866] Example 21

[0867]

[0868] Step 1: 2-(4-fluoro-1-methyl-1H-indazol-5-yl)-2,4-diazabicyclo[3.1.0]hexan-3-one

[0869] Using 5-bromo-4-fluoro-1-methyl-1H-indazole as raw material, the target product was obtained by referring to Example 1.

[0870] MS m / z(ESI):247.1[M+1].

[0871] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0872] MS m / z(ESI):897.4[M+1].

[0873] Example 22

[0874]

[0875] Step 1: 1-(4-fluoro-1-methyl-1H-indazol-5-yl)-1,3-dihydro-2H-imidazole-2-thione

[0876] The target product was obtained using 4-fluoro-1-methyl-1H-indazol-5-amine as starting material according to New Journal of Chemistry, 2014, vol. 38, #9, p. 4071–4082.

[0877] MS m / z(ESI):249.1[M+1].

[0878] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0879] MS m / z(ESI):899.4[M+1].

[0880] Example 23

[0881]

[0882] Step 1: 4-Fluoro-5-(1H-imidazol-4-yl)-1-methyl-1H-indazole

[0883] The target product was obtained using 5-bromo-4-fluoro-1-methyl-1H-indazole as starting material according to Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, #16, p. 2061–2065.

[0884] MS m / z(ESI):217.1[M+1].

[0885] Step 2: Using intermediate C as raw material, refer to Example 1 to obtain the target product.

[0886] MS m / z(ESI):867.4[M+1].

[0887] Example 24

[0888]

[0889] Step 1: Referring to the third step of Intermediate B, 4-iodo-2,6-dimethylbenzonitrile was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0890] MS m / z(ESI):890.4[M+1].

[0891] Example 25

[0892]

[0893] Step 1: Referring to the third step of Intermediate B, 5-bromo-1-cyclopropyl-2-fluoro-3-toluene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0894] MS m / z(ESI):909.4[M+1].

[0895] Example 26

[0896]

[0897] Step 1: Referring to the third step of Intermediate B, 5-bromo-2-cyclopropyl-1,3-dimethylbenzene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0898] MS m / z(ESI):905.4[M+1].

[0899] Example 27

[0900]

[0901] Step 1: 5-iodo-2-(1-methoxycyclopropyl)-1,3-dimethylbenzene

[0902] The target product was synthesized using 4-iodo-2,6-dimethylbenzaldehyde as raw material and referring to WO2020 / 201079.

[0903] MS m / z(ESI):303.0[M+1].

[0904] Step 2: Referring to the third step of intermediate B, 5-iodo-2-(1-methoxycyclopropyl)-1,3-dimethylbenzene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0905] MS m / z(ESI):935.4[M+1].

[0906] Example 28

[0907]

[0908] Step 1: 2-(1-fluorocyclopropyl)-5-iodo-1,3-dimethylbenzene

[0909] The target product was obtained using 1-(4-iodo-2,6-dimethylphenyl)ethan-1-one as starting material according to Chemical Communications, 1996, #10, p.1103–1104.

[0910] MS m / z(ESI):291.0[M+1].

[0911] Step 2: Referring to the third step of intermediate B, 2-(1-fluorocyclopropyl)-5-iodo-1,3-dimethylbenzene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then the target product was synthesized by referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione).

[0912] MS m / z(ESI):923.4[M+1].

[0913] Example 29

[0914]

[0915] Step 1: 3-(4-bromo-2,6-dimethylphenyl)oxetane

[0916] Using 5-bromo-2-iodo-1,3-dimethylbenzene as raw material, refer to WO2021 / 155320,2021,A1 Page / Pagecolumn 71; 115-116 to obtain the target product.

[0917] MS m / z(ESI):241.0[M+1].

[0918] Step 2: Referring to the third step of intermediate B, 3-(4-bromo-2,6-dimethylphenyl)oxetane was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then the target product was synthesized by referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione).

[0919] MS m / z(ESI):921.4[M+1].

[0920] Example 30

[0921]

[0922] Step 1: Referring to the third step of intermediate B, 6-bromo-8-methyl-romene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0923] MS m / z(ESI):907.4[M+1].

[0924] Example 31

[0925]

[0926] Step 1: Referring to the third step of Intermediate B, 6-bromo-8-methyl-2H-chromene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0927] MS m / z(ESI):905.4[M+1].

[0928] Example 32

[0929]

[0930] Step 1: Referring to the third step of intermediate B, 7-bromo-5-methyl-2,3-dihydrobenzo[b][1,4]dioxazine was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0931] MS m / z(ESI):909.4[M+1].

[0932] Example 33

[0933]

[0934] Step 1: Referring to the third step of Intermediate B, 5-bromo-1-ethynyl-2-fluoro-3-toluene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0935] MS m / z(ESI):893.4[M+1].

[0936] Example 34

[0937]

[0938] Step 1: Referring to the third step of intermediate B, 4-iodo-2,6-dimethyl-N-(methyl-d3)aniline was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0939] MS m / z(ESI):897.4[M+1].

[0940] Example 35

[0941]

[0942] Step 1: Referring to the third step of Intermediate B, 2-fluoro-5-iodo-3-methyl(thiomethyl)benzene was used instead of 2-fluoro-5-iodo-1,3-dimethylbenzene to synthesize the intermediate, and then the target product was synthesized by referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione).

[0943] MS m / z(ESI):915.4[M+1].

[0944] Example 36

[0945]

[0946] Step 1: Referring to the second step of intermediate A, 4-(chloromethyl)cyclopentane-1,3-dione was used instead of 2-chloroacetonitrile to synthesize the intermediate, and then the target product was synthesized by referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione).

[0947] MS m / z(ESI):895.4[M+1].

[0948] Example 37

[0949]

[0950] Step 1: Referring to the second step of intermediate A, 4-(chloromethyl)-1,2,5-thiadiazole-3-ol was used instead of 2-chloroacetonitrile to synthesize the intermediate, and then referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0951] MS m / z(ESI):899.4[M+1].

[0952] Example 38

[0953]

[0954] Step 1: Referring to the second step of intermediate A, 3-(chloromethyl)-4-hydroxycyclobut-3-ene-1,2-dione was used instead of 2-chloroacetonitrile to synthesize the intermediate, and then the target product was synthesized by referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione).

[0955] MS m / z(ESI):895.4[M+1].

[0956] Example 39

[0957]

[0958] Step 1: Referring to the second step of intermediate A, N-(5-(chloromethyl)-1H-1,2,4-triazol-3-yl)methanesulfonamide was used instead of 2-chloroacetonitrile to synthesize the intermediate, and then the target product was synthesized by referring to intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione).

[0959] MS m / z(ESI):959.4[M+1].

[0960] Example 40

[0961]

[0962] Step 1: Refer to the synthesis conditions of the second step of intermediate A to obtain the title product 1-(cyanomethyl)-5-formyl-1H-indole-2-carboxylic acid ethyl ester 40-2,

[0963] MS m / z(ESI):257.1[M+1].

[0964] Step 2: A mixture of 1-(cyanomethyl)-5-formyl-1H-indole-2-carboxylic acid ethyl ester 40-2 (3.2 g, 12.5 mmol), 4-methylbenzenesulfonylhydrazide (2.33 g, 12.5 mmol) and tetrahydrofuran (50 mL) was stirred at room temperature for 12 hours. After the reaction was completed, the mixture was concentrated under reduced pressure and the crude product was used directly in the next step to obtain the title product (E)-1-(cyanomethyl)-5-((2-toluenesulfonylhydrazide)methyl)-1H-indole-2-carboxylic acid ethyl ester 40-3 (5.7 g, crude product)

[0965] MS m / z(ESI):425.1[M+1].

[0966] Step 3: To a solution of ethyl (E)-1-(cyanomethyl)-5-((2-toluenesulfonylhydrazide)methyl)-1H-indole-2-carboxylate 40-3 (5.7 g, 13.44 mmol) in tetrahydrofuran (50 mL) was added sodium hydrogen hydride (60%, 538 mg, 13.44 mmol), stirred at 60 ° C for 1 hour, cooled, filtered, and the filtrate was concentrated under reduced pressure to dryness to obtain a residue. The residue was dissolved in dichloromethane (20 mL) and then added dropwise to a solution of 2,5-dihydro-2,2-dimethylfuran (1.32 g, 13.44 mmol) and zinc iodide (41 mg, 0.13 mmol) in dichloromethane (15 mL). The mixture was stirred at room temperature for 1 hour, water was added, and the mixture was extracted with dichloromethane (50 mL*3). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and dried by spin drying. The title product, 1-(cyanomethyl)-5-(2,2-dimethyl-3-oxabicyclo[3.1.0]hexane-6-yl)-1H-indole-2-carboxylic acid, ethyl ester 40-4 (900 mg), was obtained in a yield of 19.8%.

[0967] MS m / z(ESI):339.2[M+1].

[0968] Step 4: Referring to the synthesis conditions of intermediate A, the title product 5-(2,2-dimethyl-3-oxabicyclo[3.1.0]hexane-6-yl)-1-((2S)-2-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-1H-indole-2-carboxylic acid 40-5 was obtained.

[0969] MS m / z(ESI):410.1[M+1].

[0970] Step 5: Refer to the synthesis conditions of intermediate E to obtain the title product 40-6.

[0971] MS m / z(ESI):733.3[M+1].

[0972] Step 6: Refer to the synthesis conditions of Example 1, and then chiral separation to obtain the title product 40

[0973] MS m / z(ESI):881.4[M+1].

[0974] Example 41

[0975]

[0976] Step 1: Referring to the first step of Intermediate A, 6-iodo-2-oxaspiro[3.3]heptane was used instead of 4-iodo-2,2-dimethyltetrahydropyran to synthesize the intermediate, and then referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0977] MS m / z(ESI):867.4[M+1].

[0978] Example 42

[0979]

[0980] Step 1: Dissolve ethyl 5-bromo-1H-indole-2-carboxylate (0.3 g, 1.12 mmol), 2-(2,2-dimethyl-3,6-dihydro-2H-pyran-4-yl)-4,4,5-tetramethyl-1,3,2-dioxaborolane (266.46 mg, 1.12 mmol), and sodium carbonate (355.79 mg, 3.36 mmol) in 1'4-dioxane (12 mL) and water (4 mL). Under nitrogen, ditriphenylpalladium dichloride (39.27 mg, 55.95 μmol) was added. The mixture was stirred at 90°C for 5 hours. The reaction was quenched by adding saturated brine (50 mL) and extracted with ethyl acetate (30 mL x 2). The organic phases were combined, washed with saturated brine (30 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (eluted with petroleum ether:ethyl acetate = 100:0 to 50:50) to give the desired product (0.28 g, 84% yield).

[0981] MS m / z(ESI):300.2[M+1].

[0982] Step 2: Dissolve trimethylsulfoxide iodide (617.51 ​​mg, 2.81 mmol) in dimethylsulfoxide (10 mL). Add sodium hydroxide (112.23 mg, 2.81 mmol, 60% w / w) under nitrogen. The mixture is stirred at 25°C for 1 hour. Ethyl 5-(2,2-dimethyl-3,6-dihydro-2H-pyran-4-yl)-1H-indole-2-carboxylate (0.28 g, 935.32 μmol) is then added at 0°C. The mixture is stirred at 25°C for 12 hours. The reaction is quenched by adding saturated brine (50 mL) and extracted with ethyl acetate (30 mL x 2). The organic phases are combined, washed sequentially with saturated brine (30 mL x 5), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (petroleum ether:ethyl acetate = 100:0 to 50:50) to give the desired product (0.13 g, 44% yield). The product was chirally separated to give ethyl 5-((6S)-4,4-dimethyl-3-oxabicyclo[4.1.0]heptane-6-yl)-1H-indole-2-carboxylate (46 mg).

[0983] MS m / z(ESI):314.2[M+1].

[0984] Step 3: Referring to the second step of Intermediate A, 5-((6S)-4,4-dimethyl-3-oxabicyclo[4.1.0]heptane-6-yl)-1H-indole-2-carboxylic acid ethyl ester was used instead of (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid ethyl ester to synthesize the intermediate, and then referring to Intermediate E and Example 1 (using 5-bromo-4-fluoro-1-methyl-1H-indazole instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[0985] MS m / z(ESI):895.4[M+1].

[0986] Example 43

[0987]

[0988] Step 1: Referring to the first step of Intermediate A, 4-iodo-2,2-dimethyltetrahydropyran was used instead of 4-iodo-2,2-dimethyltetrahydropyran to synthesize the intermediate, and then the target product was synthesized by referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione).

[0989] MS m / z(ESI):857.4[M+1].

[0990] Example 44

[0991]

[0992] Step 1: 5-bromo-4-fluoro-1-methyl-1H-indazole (2.29 g, 10 mmol), 1,3-dihydro-2H-imidazol-2-one (0.84 g, 10 mmol), cuprous iodide (1.91 g, 10 mmol), potassium phosphate (3.92 g, 20 mmol) and N,N,N',N'-tetramethylethylenediamine (1.16 g, 10 mmol) were dissolved in toluene (30 mL) at room temperature to replace nitrogen. The mixture was heated to reflux for 24 hours, cooled to room temperature, filtered, and the filter residue was washed with ethyl acetate (30 mL). The organic phase was washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, filtered, and dried. The residue was purified by Flash column (dichloromethane: methanol = 20: 1) to give 1-(4-fluoro-1-methyl-1H-indazol-5-yl)-1,3-dihydro-2H-imidazol-2-one (1.28 g, yield: 55%).

[0993] MS m / z(ESI):233.1[M+H]+.

[0994] Step 2: At room temperature, 1-(4-fluoro-1-methyl-1H-indazol-5-yl)-1,3-dihydro-2H-imidazol-2-one (1.28 g, 5.5 mmol), (S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (2.41 g, 5.5 mmol), and cuprous iodide (1.05 g, 5.5 mmol) were added. Potassium phosphate (2.16 g, 11 mmol) and N,N,N',N'-tetramethylethylenediamine (0.64 g, 5.5 mmol) were dissolved in toluene (30 mL), nitrogen was replaced, heated under reflux for 24 hours, cooled to room temperature, filtered, and the filter residue was washed with ethyl acetate (20 mL). The organic phase was washed with saturated brine (20 mL × 2), and the organic phase was dried over anhydrous sodium sulfate, filtered, and dried. The residue was purified by Flash column (dichloromethane: methanol = 20:

[0995] 1) Obtain (S)-3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (1.26 g, yield: 39%)

[0996] MS m / z(ESI):590.2[M+H]+.

[0997] Step 3: At room temperature, S)-3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (1.26 g, 2.15 mmol) was dissolved in dichloromethane (25 mL), and trifluoroacetic acid (6 mL) was added. The mixture was stirred at room temperature for 2 hours. LCMS indicated that the reaction was complete. The mixture was dried and the residue was The product was dissolved in ethyl acetate (30 mL), then washed with saturated sodium bicarbonate solution (15 mL × 2) and saturated brine (20 mL × 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and dried to give (S)-1-(4-fluoro-1-methyl-1H-indazol-5-yl)-3-(2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-3-yl)-1,3-dihydro-2H-imidazole-2-one (1.0 g, yield: 95%).

[0998] MS m / z(ESI):490.2[M+H]+.

[0999] Step 4: Under ice bath, (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid ethyl ester (3.01 g, 10 mmol) was dissolved in tetrahydrofuran (30 mL), the nitrogen atmosphere was replaced, and then lithium aluminum tetrahydride (0.76 g, 20 mmol) was slowly added. The mixture was stirred under ice bath for 2 hours. LCMS indicated that the reaction was complete. The reaction solution was quenched with ethyl acetate (50 mL), then washed with saturated brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and dried. The residue was purified by Flash column (petroleum ether:ethyl acetate = 10:1-3:1 for elution) to obtain (S)-(5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)methanol (2.07 g, yield: 80%).

[1000] MS m / z(ESI):260.2[M+H]+.

[1001] Step 5: (S)-(5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)methanol (2.07 g, 8 mmol) was dissolved in dichloromethane (30 mL) at room temperature, and then Dess-Martin (6.78 g, 16 mmol) was added. The mixture was stirred at room temperature for 2 hours. LCMS indicated that the reaction was complete. The reaction solution was quenched with saturated sodium bicarbonate solution (30 mL) and then extracted with dichloromethane (25 mL×3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and dried by rotary evaporation. The residue was purified by Flash column (petroleum ether:ethyl acetate = 10:1-5:1) to obtain (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carbaldehyde (1.64 g, yield: 80%).

[1002] MS m / z(ESI):258.2[M+H]+.

[1003] Step 6: At room temperature, (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carbaldehyde (1.64 g, 6.4 mmol) was dissolved in N,N-dimethylformamide (20 mL), and potassium carbonate (1.77 g, 12.8 mmol) and trifluoromethyltrimethylsilane (1.82 g, 12.8 mmol) were added. The mixture was stirred at room temperature overnight. LCMS indicated that the reaction was complete. The reaction solution was quenched with water (20 mL) and then extracted with ethyl acetate (15 mL×3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and dried to give 1-(5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)-2,2,2-trifluoroethane-1-ol (1.51 g, yield: 72%).

[1004] MS m / z(ESI):328.1[M+H]+.

[1005] Step 7: 1-(5-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)-2,2,2-trifluoroethane-1-ol (1.51 g, 4.61 mmol) was dissolved in dichloromethane (30 mL) at room temperature, and then Dess-Martin (2.93 g, 6.92 mmol) was added and stirred at room temperature for 3 hours. LCMS indicated that the reaction was complete. The reaction solution was washed with saturated sodium bicarbonate solution ( The product was quenched with the mixture of 5-nitropropane-2-yl and 1-nitropropane-3-yl (30 mL), then extracted with dichloromethane (25 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and spin-dried. The residue was purified by Flash column (eluted with petroleum ether: ethyl acetate = 10:1-5:1) to give (S)-1-(5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)-2,2,2-trifluoroethane-1-one (1.23 g, yield: 82%).

[1006] MS m / z(ESI):326.1[M+H]+.

[1007] Step 8: (S)-1-(5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)-2,2,2-trifluoroethane-1-one (1.23 g, 3.78 mmol) and (S)-1-(4-fluoro-1-methyl-1H-indazol-5-yl)-3-(2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro- Hydrogen-2H-pyrazolo[4,3-c]pyridin-3-yl)-1,3-dihydro-2H-imidazol-2-one (2.03 g, 4.16 mmol) was dissolved in tetrahydrofuran (20 mL), and then tetraisopropyl titanate (2.15 g, 7.56 mmol) was added. The mixture was heated to 60°C for 2 hours, cooled to 0°C, and then sodium borohydride (0.29 g, 7.56 mmol) was added. The mixture was stirred at room temperature for 2 hours. The reaction solution was then poured into aqueous ammonia. Solids precipitated and the residue was filtered. The filter residue was washed with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution and saturated brine in sequence. The organic phase was dried over anhydrous sodium sulfate, filtered, and dried. The residue was purified by Flash column (petroleum ether: ethyl acetate = 10:1-1:1) to obtain 1-((4S)-5-(1-(5-(5-(((S) 1-dihydro-2-pyrazol-4-yl)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5-5,6,6,7-tetrahydro-2-dihydro-4-pyrazol-4,3-c]pyridin-3-yl-3-yl-3-(4-fluoro-1-methyl-1-dihydro-3-dihydro-1-4-dihydro-3-dihydro-1-2H-imidazol-2-one) (1.27 g, yield: 42%).

[1008] MS m / z(ESI):799.3[M+H]+.

[1009] Step 9: Using 1-((4S)-5-(1-(5-(5-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl-2-2-2-2-2-2-fluorofluoroethyl)-2-(4-fluoro-3,5-3-dimethylphenyl)-4-methyl-4,5-5,6,6,7-tetrahydro-2-dihydro-4-pyrazol-4,3-c]pyridin-3-yl-3-yl-3-(4-fluoro-1-methyl-1-1-dihydro-3-dihydro-1-11 1 1 1-4-dihydro-3-dihydro-1 1 1 1 2H-imidazole-2-one as raw material, refer to the second, third and fourth steps of intermediate A to obtain the target product.

[1010] MS m / z(ESI):937.4[M+H]+.

[1011] Example 45

[1012]

[1013] Step 1: Using (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid ethyl ester as starting material, refer to the fifth step of intermediate A in the example to obtain (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid.

[1014] MS m / z(ESI):274.1[M+H]+.

[1015] The second step: using (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indole-2-carboxylic acid and (S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine as raw materials, with reference to the third step of intermediate D in the example, ((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl(5-(S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)methanone was obtained.

[1016] MS m / z(ESI):593.2[M+H]+.

[1017] Step 3: At room temperature, ((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl(5-(S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)methanone (2.97 g, 5 mmol) was dissolved in toluene (30 mL), and then Lawesson's reagent (1.01 g, 2.5 mmol) was added. The mixture was heated under reflux for 14 hours, cooled to room temperature, filtered, and the filter residue was washed with ethyl acetate. The organic phase was washed successively with saturated sodium bicarbonate solution and saturated brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried. The residue was separated by Flash column chromatography (PE:EA=2:1) ​​to give ((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl(5-(S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)methanthione (1.52 g, yield: 42%).

[1018] MS m / z(ESI):609.2[M+H]+.

[1019] In the fourth step, ((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl(5-(S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-2-yl)methanthione was used as a starting material. Referring to the second step of intermediate A in the example, 2-(2-(((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonylthio)-5-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-1-yl)acetonitrile was obtained.

[1020] MS m / z(ESI):648.2[M+H]+.

[1021] Step 5: Using 1-(4-fluoro-1-methyl-1H-indazol-5-yl)-1,3-dihydro-2H-imidazol-2-one and 2-(2-(((S)-3-bromo-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonylthio)-5-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-1H-indol-1-yl)acetonitrile as raw materials, refer to Example 45: In the first step, 2-(5-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(((S)-3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3]pyridine-5-carbonyl)-1H-indol-1-yl)acetonitrile was obtained.

[1022] MS m / z(ESI):800.3[M+H]+.

[1023] Step 6: Using 2-(5-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-(((S)-3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3]pyridine-5-carbonyl)-1H-indol-1-yl)acetonitrile as raw material, refer to the third step of intermediate A, and obtain the target product in the fourth step.

[1024] MS m / z(ESI):899.4[M+H]+.

[1025] Example 46

[1026]

[1027] Step 1: In a 250 mL reaction flask, (R)-3-amino-3-cyclopropylpropionitrile (10.0 g, 90.78 mmol) was dissolved in ethanol (50.0 mL), and triethylamine (11.02 g, 108.93 mmol) and acrylonitrile (5.78 g, 108.93 mmol) were added. The reaction solution was stirred at 70° C. for 3 hours. The reaction was stopped, cooled to room temperature, and concentrated to give the product (R)-3-((2-cyanoethyl)amino)-3-cyclopropylpropionitrile (21.0 g) in a yield of 87.8%.

[1028] MS m / z(ESI):164.1[M+1].

[1029] In the second step, (R)-3-((2-cyanoethyl)amino)-3-cyclopropylpropionitrile was used as a raw material to obtain the product with reference to Example 1.

[1030] MS m / z(ESI):909.3[M+1].

[1031] Example 47

[1032]

[1033] Step 1: Referring to the first step of Intermediate A, 5-bromo-1H-benzo[d]imidazole-2-carboxylic acid ethyl ester was used instead of 5-bromoindole-2-carboxylic acid ethyl ester to synthesize the intermediate, and then referring to Intermediate E and Example 1 (using 5-bromo-4-fluoro-1-methyl-1H-indazole instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[1034] MS m / z(ESI):884.4[M+1].

[1035] Example 48

[1036]

[1037] Step 1: To a solution of methyltriphenylphosphonium bromide (27.9 g, 78.13 mmol) in dimethyl sulfoxide (300 mL) was added potassium tert-butoxide (8.75 g, 78.13 mmol), stirred at room temperature for 1 hour, then added 2,2-dimethyltetrahydro-4H-pyran-4-one 48-1 (5 g, 39.06 mmol) and stirred at 80 degrees Celsius for 12 hours. Water was added and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and dried by spin drying. Then, column chromatography was performed to obtain the product 2,2-dimethyl-4-methylenetetrahydro-2H-pyran 48-2 (3.5 g). Yield: 71%

[1038] MS m / z(ESI):127.1[M+1].

[1039] Step 2: Borane-tetrahydrofuran solution (55.6 mL, 55.6 mmol, 1 M) was added dropwise to a solution of 2,2-dimethyl-4-methylenetetrahydro-2H-pyran 48-2 (3.5 g, 27.78 mmol) in tetrahydrofuran (50 mL), and then stirred at 70 degrees Celsius for 1 hour, cooled, quenched with methanol, and then sodium hydroxide aqueous solution (2N, 27.8 mL) and hydrogen peroxide (30%, 12 mL) were added dropwise and stirred at room temperature for 2 hours. Water was added and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and dried, and then separated by column chromatography to obtain the product (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol 48-3 (2.7 g), with a yield of 67%.

[1040] MS m / z(ESI):145.1[M+1].

[1041] Step 3: In a 25 mL reaction flask, (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol 48-3 (2.7 g, 18.75 mmol) and triethylamine (3.8 g, 37.5 mmol) were dissolved in dichloromethane (50 mL). Methanesulfonyl chloride (3.2 g, 28.13 mmol) was then added dropwise. The reaction mixture was stirred at room temperature for 3 hours. The reaction was stopped and quenched with water (50 mL). The mixture was extracted with dichloromethane (50 mL × 3). The combined organic phases were washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to dryness to obtain the product (2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl methanesulfonate 48-4 (3 g, crude product).

[1042] MS m / z(ESI):223.1[M+1].

[1043] Step 4: A mixture of 2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl methanesulfonate 48-4 (3 g, 13.51 mmol), sodium mercaptobenzothiazole (5.1 g, 27.02 mmol), toluene (50 mL), and water (20 mL) was stirred at 80 degrees Celsius for 12 hours, cooled, added with water, extracted with dichloromethane, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and dried by spin drying. The product 2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)thio)benzo[d]thiazole 48-5 (1.4 g) was obtained in a yield of 35%.

[1044] MS m / z(ESI):294.1[M+1].

[1045] Step 5: To a solution of 2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)thio)benzo[d]thiazole 48-5 (1.4 g, 4.77 mmol) in dichloromethane (15 mL) was added m-chloroperbenzoic acid (1.6 g, 9.56 mmol), then stirred at room temperature overnight, added saturated sodium bicarbonate aqueous solution, extracted with dichloromethane, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and dried by spin drying. Then, column chromatography was performed to obtain the product 2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)sulfonyl)benzo[d]thiazole 48-6 (1.1 g), yield: 71%

[1046] MS m / z(ESI):326.1[M+1].

[1047] Step 6: To a solution of 2-(((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)sulfonyl)benzo[d]thiazole 48-6 (1.1 g, 3.38 mmol) in tetrahydrofuran (15 mL) at -40 °C, lithium bis(trimethylsilyl)amide (6.8 mL, 6.8 mmol, 1 M) was added dropwise. After stirring for 0.5 h, ethyl 4-formyl-5-methyl-1H-pyrrole-2-carboxylate (612 mg, 3.38 mmol), stirring was continued for 2 hours, then saturated aqueous ammonium chloride solution was added to quench, extracted with dichloromethane, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, spin-dried, and then separated by column chromatography to obtain the product (E)-4-(2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)vinyl)-5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester 48-7 (400 mg), yield: 41%

[1048] MS m / z(ESI):292.2[M+1].

[1049] Step 7: Referring to the synthesis conditions of intermediate A, the product 4-((E)-2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)vinyl)-5-methyl-1-((1S,2S)-2-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)-1H-pyrrole-2-carboxylic acid 48-8 was obtained.

[1050] MS m / z(ESI):402.2[M+1].

[1051] Step 8: Referring to the synthesis conditions of intermediate E, the product 3-((1S,2S)-1-(3-((E)-2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)vinyl)-5-((S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-(2-oxo-2,3-dihydro-1H-imidazol-1-yl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-2-methyl-1H-pyrrol-1-yl)-2-methylcyclopropyl)-1,2,4-oxadiazol-5(4H)-one 48-10 was obtained.

[1052] MS m / z(ESI):725.3[M+1].

[1053] Step 9: Refer to the synthesis conditions of Example 1, and then chiral separation to obtain product 48

[1054] MS m / z(ESI):873.4[M+1].

[1055] Example 49

[1056]

[1057] The first step: using 3,3'-nitrogendiyldipropionitrile as a raw material, refer to Example 1 to obtain the product 3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

[1058] MS m / z(ESI):576.2[M+1].

[1059] Step 2: In a 50 mL reaction bottle, tert-butyl 3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate (100 mg, 173.73 μmol) was added. MS (molecular sieves, 120 mg) was dissolved in dichloromethane (2 mL), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (43.38 mg, 191.10 μmol) was added portionwise. The reaction solution was stirred at 25°C for 1 hour. Tributyltin cyanide ((n-Bu)3SnCN) (137.28 mg, 434.31 μmol) was then added dropwise, and the reaction solution was stirred at 25°C for 1 hour. The reaction was stopped and quenched by adding aqueous sodium bicarbonate solution (2 mL). The mixture was extracted with dichloromethane (2 mL×2). The combined organic phases were washed with saturated sodium chloride (2 mL), dried over anhydrous sodium sulfate, filtered, and the residue was purified by silica gel column chromatography with an eluent system of petroleum ether and ethyl acetate. The product was then separated to give tert-butyl 4-cyano-3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate (60 mg) in a yield of 57.5%.

[1060] MS m / z(ESI):601.2[M+1].

[1061] Step 3: Using 4-cyano-3-(3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-2-(4-fluoro-3,5-dimethylphenyl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester as raw material, the product was obtained by reference to Example 1.

[1062] MS m / z(ESI):894.3[M+1].

[1063] Example 50

[1064]

[1065] Step 1: Referring to the third step of Intermediate A, 4,6-dioxa-5-thiospiro[2.4]heptane 5,5-dioxide was used instead of (4R)-4-methyl-1,3,2-dioxathiolane 2,2-dioxide to synthesize the intermediate, and then referring to Intermediate E and Example 1 (5-bromo-4-fluoro-1-methyl-1H-indazole was used instead of ((4-bromo-3-fluorophenyl)imino)dimethyl-6-thione) to synthesize the target product.

[1066] MS m / z(ESI):895.4[M+1].

[1067] Example 51

[1068]

[1069] Step 1: 3-(1-(7-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-(2-carbonyl-2,3-dihydro-1H-imidazol-1-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)indolizin-3-yl)cyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[1070] Using (S)-7-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-3-(1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)indolizine-2-carboxylic acid as the starting material, the product was obtained by referring to the third step of intermediate C and intermediate D.

[1071] MS m / z(ESI):721.3[M+1].

[1072] Step 2: Using (4-bromo-2-(methylamino)phenyl)dimethylphosphine oxide, refer to Example 1 to obtain the target product.

[1073] MS m / z(ESI):902.4[M+1].

[1074] Example 53

[1075]

[1076] Step 1: 3-(1-(6-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-(2-carbonyl-2,3-dihydro-1H-imidazol-1-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-5-carbonyl)indolizin-1-yl)cyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[1077] Using (S)-6-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-1-(1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)indolizine-2-carboxylic acid as the starting material, the product was obtained by referring to the third step of intermediate C and intermediate D.

[1078] MS m / z(ESI):721.3[M+1].

[1079] Step 2: Obtain the target product with reference to Example 1

[1080] MS m / z(ESI):902.3[M+1].

[1081] Example 54

[1082]

[1083] Step 1: (S)-1-(2-(3-cyclopropyl-4-fluorophenyl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-3-yl)-1,3-dihydro-2H-imidazol-2-one

[1084] The product was obtained by referring to intermediate B using (S)-3-amino-4-methyl-6,7-dihydro-2l2-pyrazolo[4,3-c]pyridine-5(4H)-carboxylic acid tert-butyl ester and 2-cyclopropyl-1-fluoro-4-iodobenzene as raw materials.

[1085] MS m / z(ESI):354.2[M+1].

[1086] Step 2: 3-(1-(2-((S)-2-(3-cyclopropyl-4-fluorophenyl)-4-methyl-3-(2-carbonyl-2,3-dihydro-1H-imidazol-1-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-7-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)indolizin-3-yl)cyclopropyl)-1,2,4-oxadiazol-5(4H)-one

[1087] The product was obtained by referring to Intermediate C and Intermediate D in the third step.

[1088] MS m / z(ESI):733.3[M+1].

[1089] Step 3: Using (4-bromo-3-fluorobenzyl)(imino)(methyl)-16-aminosulfonone as raw material, refer to Example 1 to obtain the target product.

[1090] MS m / z(ESI):918.4[M+1].

[1092] Example 56

[1093]

[1094] Step 1: Using (S)-2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-5-(1-(5-carbonyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl)pyrrolo[1,2-b]pyridazine-6-carboxylic acid as raw material, refer to the third step of intermediate C and intermediate D to obtain the product.

[1095] MS m / z(ESI):722.3[M+1].

[1096] Step 2: Using 4-bromo-3-fluorophenyl)(imino)(methyl)-16-aminosulfonone as raw material, refer to Example 3 to obtain the target product.

[1097] MS m / z(ESI):893.3[M+1].

[1098] Example 59

[1099]

[1100] Step 1: 3-(4-bromo-3-fluorophenoxy)tetrahydrofuran

[1101] At room temperature, 4-bromo-3-fluorophenol (1.91 g, 10 mmol) was dissolved in acetonitrile (30 mL), and then potassium carbonate (4.15 g, 30 mmol) and 3-bromotetrahydrofuran (3.02 g, 20 mmol) were added. The mixture was heated to 85°C and reacted for 24 hours. The mixture was cooled to room temperature, and the reaction solution was diluted with ethyl acetate (30 mL), and then washed with saturated brine (25 mL × 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and dried. The residue was separated by Flash column chromatography (PE: EA = 2: 1) to obtain the target product as a yellow oil (2.09 g, yield 80%).

[1102] Step 2: Using 3-(4-bromo-3-fluorophenoxy)tetrahydrofuran and intermediate E as raw materials, refer to Example 1 to obtain the target product.

[1103] MS m / z(ESI):915.4[M+H]+.

[1104] Example 60

[1105]

[1106] Step 1: 4-((4-bromo-3-fluorophenoxy)methyl)pyridine

[1107] At room temperature, 4-bromo-3-fluorophenol (1.91 g, 10 mmol) was dissolved in N,N-dimethylformamide (30 mL), and then potassium carbonate (2.76 g, 20 mmol) and 4-bromomethylpyridine (2.06 g, 12 mmol) were added. The reaction was allowed to react at room temperature for 12 hours. LCMS indicated that the reaction was complete. The reaction solution was diluted with ethyl acetate (60 mL) and then washed with saturated brine (25 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and dried. The residue was separated by Flash column chromatography (PE:EA=2:1) ​​to obtain the target product as a yellow solid (0.28 g, yield 10%).

[1108] MS m / z(ESI):282.1,284.1[M+H]+.

[1109] Step 2: Using 4-((4-bromo-3-fluorophenoxy)methyl)pyridine and intermediate E as raw materials, refer to Example 1 to obtain the target product.

[1110] MS m / z(ESI):936.4[M+H]+.

[1111] Example 61

[1112]

[1113] Step 1: 1-(4-bromo-3-fluorophenoxy)-3-fluorobicyclo[1.1.1]pentane

[1114] At room temperature, 4-bromo-3-fluorophenol (1.91 g, 10 mmol) was dissolved in acetonitrile (30 mL), and then potassium carbonate (4.15 g, 30 mmol) and 1-bromo-3-fluorobicyclo[1.1.1]pentane (3.3 g, 20 mmol) were added. The mixture was heated to 85°C and reacted for 24 hours. The mixture was cooled to room temperature, and the reaction solution was diluted with ethyl acetate (30 mL), then washed with saturated brine (25 mL × 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and dried. The residue was separated by Flash column chromatography (PE:EA=3:1) to obtain the target product as a yellow oil (1.93 g, yield 70%).

[1115] Step 2: Using 1-(4-bromo-3-fluorophenoxy)-3-fluorobicyclo[1.1.1]pentane and intermediate E as raw materials, refer to Example 1 to obtain the target product.

[1116] MS m / z(ESI):929.4[M+H]+.

[1117] Example 62

[1118]

[1119] Step 1: 1-((4-bromo-3-fluorophenoxy)methyl)spiro[2.2]pentane ...

Claims

1. A compound represented by general formula (XVI), a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in, Ring A is selected from C 3-18 Cycloalkyl, 3-18 membered heterocyclic group, C 6-18 Aryl or 5-18 membered heteroaryl; Preferably, ring A is selected from C 3-12 Cycloalkyl, 3-14 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-14 Aryl or 5-14 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S; More preferably, ring A is selected from C 3-10 Cycloalkyl, 5-14 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or a 5-10 membered heteroaryl group containing 1-3 heteroatoms selected from N, O or S; More preferably, ring A is selected from C 3-6 bridged cycloalkyl, 8-14 membered tricyclic fused heterocyclic group containing 1-5 heteroatoms, 3-8 membered bridged heterocyclic group containing 1-3 heteroatoms, fused heterocyclic group containing 1-3 heteroatoms, bridged heterocyclic group containing 1-3 heteroatoms, C 6-10 Aryl or 5-10 membered fused heteroaryl containing 1-3 heteroatoms; More preferably, ring A is selected from phenyl, pyridyl, pyrimidinyl, thiazolyl, pyridazinyl, oxazolyl, morpholinyl, Ring B is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; optionally further substituted with halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy or C 1-6 is substituted by one or more substituents in a deuterated haloalkoxy group; Preferably, ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms; optionally further substituted by halogen, amino, nitro, hydroxyl, cyano, oxo, mercapto, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy or C 1-3 is substituted by one or more substituents in a deuterated haloalkoxy group; More preferably, ring B is selected from C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms, or 5-8 membered heteroaryl containing 1-3 N, O or S atoms; optionally further substituted by halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents; More preferably, ring B is selected from Optionally further substituted with halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents; Ring C is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; optionally further substituted with halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy or C 1-6 is substituted by one or more substituents in a deuterated haloalkoxy group; Preferably, ring C is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 selected from N, O or S, C 6-10 aryl or 5-8 membered heteroaryl containing 1-3 selected from N, O or S; optionally further substituted with halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy or C 1-3 is substituted by one or more substituents in a deuterated haloalkoxy group; More preferably, ring C is selected from C 3-8 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 selected from N, O or S, or 5-6 membered heteroaryl containing 1-3 selected from N, O or S; optionally further substituted by hydroxyl, thioxo, oxo or C 1-6 is substituted by one or more substituents in a haloalkoxy group; More preferably, ring C is selected from Optionally further substituted with one or more substituents selected from hydroxy, thio or oxo; Ring E is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-10 membered heteroaryl; Preferably, ring E is selected from C 3-10 Cycloalkyl, 3-12 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-12 Aryl or 5-12 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 substituted by one or more substituents in aryl or 5-8 membered heteroaryl; More preferably, ring E is selected from C 3-6 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms, optionally further substituted by one or more substituents selected from halogen, methoxy or deuterated methyl; More preferably, ring E is selected from Optionally further substituted with one or more substituents selected from halogen, methoxy or deuterated methyl; Alternatively, ring E is Optionally further substituted with one or more substituents selected from halogen, methoxy or deuterated methyl; L1, L2 or L3 are each independently selected from a bond, a sub-C 2-4 Alkenyl, C 2-4 Alkynyl, -(CH2) n1 -or-(CH2) n5 NR b5 , the sub-C 2-4 Alkenyl, C 2-4 Alkynyl, -(CH2) n1 -or-(CH2) n5 NR b5 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; R 1 Each independently selected from Hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further Halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 1 Each independently selected from Hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n1 S(O)2R b5 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n1 S(O)2R b5 , optionally further Halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R 1 Each independently selected from Hydrogen, deuterium, amino, oxo, fluorine, chlorine, bromine, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spirocycloalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spirocycloalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further Halogen, cyano or C 1-3 The alkyl group is substituted by one or more substituents; More preferably, R 1 Each independently selected from Hydrogen, deuterium, amino, oxo, cyano, fluorine, chlorine, bromine, methyl, ethyl, cyclopropyl, -CD3, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino, methyl, ethyl, cyclopropyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further Halogen, cyano or C 1-3 The alkyl group is substituted by one or more substituents; or, R 1 Link to the connected atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further Deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents; Preferably, R 1 Link to the connected atoms to form C 3-6 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 selected from N, O or S, optionally further Deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents; More preferably, R 1 Link to the connected atoms to form C 3-4 Cycloalkyl or a 5-7 membered heterocyclic group containing 1-3 groups selected from N, O or S, optionally further Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl, amino, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents; More preferably, R 1 are linked to the atoms to form a cyclopropyl group, which may be further Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl, amino, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents; R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spiroalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 aryl or a 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spirocycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted with halogen or C 1-3 The alkyl group is substituted by one or more substituents; More preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, methyl, ethyl, cyano, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, The methyl, ethyl, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, Optionally, further substituted with one or more fluorine; or, R a1 and R b1 , R a2 and R b2 , R a3 and R b3 , R a4 and R b4 , R a6 and R b6 , R a8 and R b8 , R a9 and R b9 , R a10 and R b10 They are linked to adjacent atoms to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 and R b1 , R a2 and R b2 , R a3 and R b3 , R a4 and R b4 , R a6 and R b6 , R a8 and R b8 , R a9 and R b9 , R a10 and R b10 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R a1 and R b1 , R a2 and R b2 , R a3 and R b3 , R a4 and R b4 , R a6 and R b6 , R a8 and R b8 , R a9 and R b9 , R a10 and R b10 They are linked to adjacent atoms to form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, optionally further substituted by halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents; R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic or 5-8 membered heteroaryl, the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R 4 , R 5 or R 6 Each is independently selected from fluorine, cyano, cyclopropyl or methyl, wherein the cyclopropyl or methyl is optionally further substituted with one or more substituents selected from deuterium, deuterated methyl, methyl, cyclopropyl or oxo; R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl or -(CH2) m1 OR c1 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl or -(CH2) m1 OR c1 , optionally further substituted with deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic, 5-8 membered heteroaryl or -(CH2) m1 OR c1 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic, 5-8 membered heteroaryl or -(CH2) m1 OR c1 , optionally further substituted with deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 are each independently selected from hydrogen, deuterium, halogen, cyano, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or -(CH2) m1 OR c1 , the C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or -(CH2) m1 OR c1 , optionally further substituted with one or more substituents selected from deuterium, deuterated methyl, methyl, cyclopropyl or oxo; More preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 Each is independently selected from cyano, methyl, fluoro, cyclopropyl, ethynyl or -(CH2) m1 OR c1 , the methyl, cyclopropyl, ethynyl or -(CH2) m1 OR c1 , optionally further substituted with one or more substituents selected from deuterium, hydroxyl, deuterated methyl, methyl, cyclopropyl or oxo; R c1 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R c1 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic or 5-8 membered heteroaryl, the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aromatic or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R c1 is selected from fluorine, methyl, cyano, difluoromethyl, trifluoromethyl, ethynyl, methylthio, amino, cyclopropyl or oxetane; the methyl, difluoromethyl, trifluoromethyl, ethynyl, methylthio, amino, cyclopropyl or oxetane is optionally further substituted by one or more substituents selected from halogen, methoxy or deuterated methyl; Or, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl; Preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 The atoms connected to them form C 3-6 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 N, O or S atoms; More preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 N, O or S atoms; More preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 or R 15 The atoms connected to them form cyclopropyl or or, R 10 and R 12 The atoms connected to it form a C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl; Preferably, R 10 and R 12 The atoms connected to it form a C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms; More preferably, R 10 and R 12 The atoms connected to it form a C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 N, O or S atoms; More preferably, R 10 and R 12 The atoms connected to it form a link n1-n5, m1 or x are each independently selected from 0, 1, 2, 3, 4 or 5.

2. The compound, prodrug, stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The general formula (XVI) is further shown in the general formula (XVI-A): in, R 1 and R 2 , R 1 and R 11 They are linked to adjacent atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further Hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents; Preferably, R 1 and R 2 , R 1 and R 11 They are linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 selected from N, O or S, optionally further Deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thio, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents; More preferably, R 1 and R 2 , R 1 and R 11 are linked to adjacent atoms to form a 5-7 membered heterocyclic group containing 1-3 atoms selected from N, O or S, optionally further Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl, amino, oxo, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 is substituted by one or more substituents; More preferably, R 1 and R 2 , R 1 and R 11 Linked with adjacent phenyl groups to form Optionally further -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 、-(CH2) n5 C(O)NR a10 R b10 , Deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 is substituted by one or more substituents of cycloalkyl, amino or oxo; or, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, amino, oxo, fluorine, chlorine, bromine, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spirocycloalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spirocycloalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , optionally further substituted with halogen, cyano or C 1-3 The alkyl group is substituted by one or more substituents; R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spirocycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 aryl or a 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 3-6 Bridged cycloalkyl, C 3-6 Spirocycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted with halogen or C 1-3 The alkyl group is substituted by one or more substituents; More preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, methyl, ethyl, cyano, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, The methyl, ethyl, deuterated methyl, cyclopropyl, cyclopentyl, phenyl, Optionally, further substituted with one and or more fluorine; or, R a1 and R b1 , R a2 and R b2 , R a3 and R b3 , R a4 and R b4 , R a6 and R b6 , R a8 and R b8 , R a9 and R b9 , R a10 and R b10 They are linked to adjacent atoms to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Deuterated hydroxyalkyl, C 1-6 Sulfanyl, C 1-6 Deuterated sulfanyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Deuterated haloalkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 and R b1 , R a2 and R b2 , R a3 and R b3 , R a4 and R b4 , R a6 and R b6 , R a8 and R b8 , R a9 and R b9 , R a10 and R b10 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-8 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Deuterated haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Deuterated hydroxyalkyl, C 1-3 Sulfanyl, C 1-3 Deuterated sulfanyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Deuterated haloalkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R a1 and R b1 , R a2 and R b2 , R a3 and R b3 , R a4 and R b4 , R a6 and R b6 , R a8 and R b8 , R a9 and R b9 , R a10 and R b10 They are linked to adjacent atoms to form C 3-6 Cycloalkyl or a 3-6 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S; Ring B, Ring C, Ring E, L1, L2, L3, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 , n1, n2, n3, n4, n5, m1, and x are defined as described in claim 1.

3. The compound according to claim 1, its prodrug, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The general formula (XVI) is further shown in the general formula (I): in: R 1 , R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 1 , R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R 1 , R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclyl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 , C 1-3 Alkyl or C 3-6 The cycloalkyl group is substituted by one or more substituents; More preferably, R 1 , R 2 or R 3 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spirocycloalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 , C 1-3 Alkyl or C 3-6 The cycloalkyl group is substituted by one or more substituents; or, R 1 and R 2 They are linked to adjacent atoms to form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl; Preferably, R 1 and R 2 Linked with adjacent atoms to form a 3-10 membered fused heterocyclic group containing 1-4 heteroatoms; More preferably, R 1 and R 2 Linked with adjacent atoms to form a 9-membered fused heterocyclic group containing 1-4 N atoms; R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spirocycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 aryl or a 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spirocycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted with halogen or C 1-3 The alkyl group is substituted by one or more substituents; More preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, methyl, deuterated methyl, cyclopropyl, Optionally, further substituted with fluorine; Or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl; More preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 They are linked to adjacent atoms to form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms; R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl; More preferably, R 4 , R 5 or R 6 are each independently selected from fluoro, cyano, cyclopropyl or methyl; R 7 , R 8 , R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 7 , R 8 , R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl; More preferably, R 7 , R 8 , R 9 or R 10 Each is independently selected from methyl or cyclopropyl; Or, R 7 , R 8 , R 9 or R 10 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl; Preferably, R 7 , R 8 , R 9 or R 10 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl; More preferably, R 7 , R 8 , R 9 or R 10 The atoms connected to them are linked to form a cyclopropyl group; n1-n4 are integers ranging from 0 to 5; When R 4 , R 6 , R 9 , R 10 is methyl, R 7 , R 8 is hydrogen, R 5 is fluorine, R 1 is methoxy, R 2 When it is fluorine, R 3 It cannot be hydrogen; When R 4 , R 6 , R 9 , R 10 is methyl, R 7 , R 8 is hydrogen, R 5 is fluorine, R 1 for R 2 When it is methyl, R 3 It cannot be hydrogen; When R 4 , R 6 , R 9 , R 10 is methyl, R 7 , R 8 is hydrogen, R 5 is fluorine, R 1 for R 2 When it is methyl, R 3 It cannot be hydrogen; When R 4 , R 6 , R 9 , R 10 is methyl, R 7 , R 8 is hydrogen, R 5 is fluorine, R 1 for When R 2 and R 3 It cannot be hydrogen at the same time.

4. The compound according to claim 1, its prodrug, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The general formula (XVI) is further shown in the general formula (XI): in, Ring E is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; Preferably, ring E is selected from C 3-8 Cycloalkyl, 3-10 membered heterocyclic group containing 1-3 N, O or S atoms, C 6-10 Aryl or 5-10 membered heteroaryl containing 1-3 N, O or S atoms; More preferably, ring E is selected from Alternatively, ring E is L2 is selected from a bond, -(CH2) n4 -, Sub-C 2-4 Alkenyl or C 2-4 Alkynyl; R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n4 P(O)R a7 R b7 or -(CR a8 R b8 ) n5 C(O)NR a9 R b9 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Or, R 1 and R 2 or R 1 and R 11 They are linked to adjacent atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents; Preferably, R 1 and R 2 or R 1 and R 11 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents; More preferably, R 1 and R 2 or R 1 and R 11 are linked to adjacent atoms to form a phenyl group or a 5-7 membered heterocyclic group containing 1-3 groups selected from N, O or S, optionally further substituted by methyl, halogen, oxo, cyclopropyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents; More preferably, R 1 and R 2 or R 1 and R 11 Linked to adjacent atoms Optionally further substituted with methyl, halogen, oxo, cyclopropyl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 S(O)2R a5 、-(CH2) n1 O(CH2) n2 R b5 , -(CH2) n1 P(O)R a7 R b7 or -(CR a8 R b8 ) n4 C(O)NR a9 R b9 is substituted by one or more substituents; R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 Cycloalkyl or C 1-3 Haloalkyl; More preferably, R 4 , R 5 or R 6 are each independently selected from fluoro, methyl, cyano or cyclopropyl; R 7 , R 8 , R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 7 , R 8 , R 9 or R 10 are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl; More preferably, R 7 , R 8 , R 9 or R 10 are each independently selected from hydrogen or methyl; Or, R 7 , R 8 , R 9 or R 10 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl; Preferably, R 7 , R 8 , R 9 or R 10 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl; More preferably, R 7 , R 8 , R 9 or R 10 The atoms connected to them are linked to form a cyclopropyl group; R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R b5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; Preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R b5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl; More preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R b5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 or R b9 are each independently selected from hydrogen, deuterium, halogen, cyano, cyclopropyl, cyclopentyl, methyl, ethyl, deuterated methyl, phenyl or Or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a7 and R b7 or R a8 and R b8 or R a9 and R b9 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a7 and R b7 or R a8 and R b8 or R a9 and R b9 They are linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, the C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a7 and R b7 or R a8 and R b8 or R a9 and R b9 They are linked to adjacent atoms to form cyclopropyl groups; n1~n4 are integers of 0~5.

5. The compound, prodrug, stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The general formula (XVI) is further shown in the general formula (XV): in, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-8 membered heteroaryl; More preferably, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclyl, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 , C 1-3 Alkyl or C 3-6 The cycloalkyl group is substituted by one or more substituents; More preferably, R 1 , R 2 , R 3 or R 11 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 2-4 Alkynyl, C 3-8 Bridged cycloalkyl, C 3-8 Spirocycloalkyl, 3-8 membered spiro heterocyclic group containing 1-3 heteroatoms, 5-8 membered heteroaryl, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CR a8 R b8 ) n4 C(O)NR a9 R b9 or -(CH2) n5 C(O)NR a10 R b10 , the amino group, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl or C 2-4 Alkynyl, optionally further substituted with halogen, -NS(O)R a1 R b1 , C 1-3 Alkyl or C 3-6 The cycloalkyl group is substituted by one or more substituents; or, R 1 and R 2 , R 1 and R 11 They are linked to adjacent atoms to form C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, the C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 1 and R 2 , R 1 and R 11 They are linked to adjacent atoms to form C 3-6 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl, optionally further substituted with halogen, C 1-3 Alkyl, C 3-6 is substituted by one or more substituents of cycloalkyl, amino or oxo; More preferably, R 1 and R 2 , R 1 and R 11 are linked to adjacent atoms to form a 5-7 membered heterocyclic group containing 1-3 atoms selected from N, O or S, optionally further C 3-6 Substituted by cycloalkyl or oxo; More preferably, R 1 and R 2 or R 1 and R 11 Linked with adjacent phenyl groups to form Optionally further halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 3-6 is substituted by one or more substituents of cycloalkyl, amino or oxo; R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the amino C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, -NS(O)R a1 R b1 , C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spirocycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 aryl or a 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, wherein the amino, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 3-6 Bridged cycloalkyl, C 3-6 Spirocycloalkyl, 3-8 membered heterocyclic group containing 1-3 heteroatoms selected from N, O or S, C 6-10 Aryl or 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, optionally further substituted with halogen or C 1-3 The alkyl group is substituted by one or more substituents; More preferably, R a1 , R b1 , R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 or R b10 are each independently selected from hydrogen, deuterium, halogen, methyl, deuterated methyl, cyclopropyl, Optionally, further substituted with fluorine; Or, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 or R a10 and R b10 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, the C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 or R a10 and R b10 They are linked to adjacent atoms to form C 3-8 Cycloalkyl, 3-6 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl; More preferably, R a1 and R b1 or R a2 and R b2 or R a3 and R b3 or R a4 and R b4 or R a6 and R b6 or R a8 and R b8 or R a9 and R b9 or R a10 and R b10 They are linked to adjacent atoms to form C 3-6 Cycloalkyl or 3-6 membered heterocyclic group containing 1-3 heteroatoms; Ring A is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-14 membered heteroaryl; optionally further substituted with halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy or C 1-6 is substituted by one or more substituents in a haloalkoxy group; Preferably, ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; optionally further substituted by halogen, amino, oxo, thiol, thio or C 1-6 The alkyl group is substituted by one or more substituents; More preferably, ring A is selected from C 3-6 Cycloalkyl, 3-6 membered heterocyclic group containing 1-3 N, O or S atoms, or 5-8 membered heteroaryl containing 1-3 N, O or S atoms; optionally further substituted by halogen, amino, oxo, thio or C 1-3 The alkyl group is substituted by one or more substituents; More preferably, ring A is selected from R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aromatic or 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 4 , R 5 or R 6 are each independently selected from hydrogen, deuterium, halogen, amino, cyano, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl; More preferably, R 4 , R 5 or R 6 are each independently selected from fluoro, cyano, cyclopropyl or methyl; R 7 , R 8 , R 9 , R 10 , R 12 , R 13 or R 14 are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl, optionally further substituted with halogen, amino, nitro, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 is substituted by one or more substituents of aryl or 5-10 membered heteroaryl; Preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 or R 14 are each independently selected from hydrogen, deuterium, halogen, C 3-6 Cycloalkyl, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl; More preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 or R 14 Each is independently selected from methyl or cyclopropyl; Or, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 or R 14 The atoms connected to them form C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl or 5-12 membered heteroaryl; Preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 or R 14 The atoms connected to them form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl or 5-8 membered heteroaryl; More preferably, R 7 , R 8 , R 9 , R 10 , R 12 , R 13 or R 14 The atoms connected to them are linked to form a cyclopropyl group; n1-n5 are integers from 0 to 5; x is an integer from 0 to 5.

6. The compound, prodrug, stereoisomer or pharmaceutically acceptable salt thereof according to claim 2, characterized in that: The general formula (XVI-A) is further represented by the general formula (XVI-X): Among them, R 1 , R 2 , R 3 or R 11 are each independently selected from halogen, amino, -NS(O)R a1 R b1 、-(CH2) n1 S(O)NR a2 R b2 、-P(O)R a3 R b3 、-NR a5 S(O)NR a4 R b4 、-(CH2) n1 O(CH2) n2 R a5 、-(CH2) n1 C(O)NR a6 R b6 、-(CH2) n1 P(O)R a3 R b3 , -(CH2) n1 NR a8 C(O)R b8 、-(CR a8 R b8 ) n4 C(O)NR a9 R b9 、-(CH2) n1 S(O)2R b5 or -(CH2) n5 C(O)NR a10 R b10 , the amino group is optionally further C 1-6 Alkyl, C 1-6 is substituted with one or more substituents of a deuterated alkyl group; R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R a1 , R b1 R a2 , R b2 , R a3 , R b3 , R a4 , R b4 , R a5 , R b5 , R a6 , R b6 , R a7 , R b7 , R a8 , R b8 , R a9 , R b9 , R a10 , R b10 , n1, n2, n3, n4, n5 are defined as described in claim 2.

7. The compound, prodrug, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein: The compound structure is as follows:

8. A pharmaceutical composition comprising a therapeutically effective dose of a compound as claimed in any one of claims 1 to 7, a prodrug thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.

9. Use of the compound according to any one of claims 1 to 7, its prodrug, its stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 8 in the preparation of a GLP-1 receptor agonist drug.

10. Use of the compound according to any one of claims 1 to 7, its prodrug, its stereoisomer or its pharmaceutically acceptable salt, or the pharmaceutical composition according to claim 8 in the preparation of a medicament for treating metabolic-related diseases; the disease is selected from diabetes, obesity or non-alcoholic fatty liver disease-related diseases or other related diseases caused by diabetes, obesity or non-alcoholic fatty liver disease.

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