Pyrazole derivative inhibitor as well as preparation method and application thereof

Abstract

The invention relates to a pyrazole derivative inhibitor as well as a preparation method and application thereof. In particular, the present invention relates to a compound, a preparation method thereof, a pharmaceutical composition containing the compound, and a use thereof as an inhibitor in the treatment of autoimmune diseases.

Description

[0001] This application claims the priority of Chinese patent application No. 202310779925X with a filing date of 2023 / 06 / 28, Chinese patent application No. 2023108046676 with a filing date of 2023 / 06 / 30, Chinese patent application No. 2023108637341 with a filing date of 2023 / 07 / 13, Chinese patent application No. 202310937216X with a filing date of 2023 / 07 / 27, and Chinese patent application No. 2023110710985 with a filing date of 2023 / 08 / 23. This application cites the full text of the above Chinese patent application. Technical Field

[0002] The present invention belongs to the field of biomedicine, and specifically relates to a pyrazole derivative inhibitor and a preparation method and application thereof. Background Art

[0003] Human IL-17 (interleukin 17) is a large class of proinflammatory cytokines. Human IL-17 contains 6 family members: IL-17A (also known as CTLA-8), IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25) and IL-17F. The human IL-17 receptor family contains 5 family members: IL-17RA, IL-17RB, IL-17RC, IL-17RD, IL-17RE. Human IL-17 activates downstream signaling pathways by binding to the heterodimeric IL-17 receptor.

[0004] IL-17A is the most studied cytokine. IL-17A is produced by a variety of cells, such as Th17 (helper T cell 17), Tc17 (killer T cell 17), NKT (natural killer T cell), γδT (γδT cell), epithelial cell, etc. IL-17 binds to the IL-17 receptor of skin cells, activates the Act1 (TRAF3 interacting protein 2)-dependent MAPK and NF-κb signaling pathways, and increases the expression levels of a variety of cytokines (such as IL-6, TNF-α, G-CSF, GM-CSF, etc.), chemokines (such as CXCL1, CXCL2, CXCL5, CXCL8, CXCL10, etc.), antimicrobial peptides (such as Defensin, MUCSAC, S100A7, etc.) and matrix metalloproteinases (such as MMP1, etc.) at the transcriptional level. IL-17A participates in the regulation of a variety of important biological processes, such as bacterial and fungal infections, wound repair, and the promotion of inflammation.

[0005] The IL-17A pathway also plays an important role in autoimmune / inflammatory diseases. Preclinical studies have shown that IL-23 or IL-17RA knockout mice are resistant to imiquimod (IMQ)-induced psoriasis; IL-17 monoclonal antibodies can effectively inhibit IMQ- or IL-23-induced psoriasis-related scores. IL-17-related therapeutic antibodies (Secukinumab, Ixekizumab, Brodalumab, Bimekizumab, etc.) have also been approved for the treatment of psoriasis, ankylosing spondylitis and other diseases, with excellent clinical efficacy and mild and controllable toxic side effects.

[0006] Despite this, IL-17-related therapeutic antibodies are expensive and require subcutaneous or intravenous injections, which are less accessible and convenient for patients with autoimmune / inflammatory diseases who require long-term medication. The development of highly active oral IL-17 small molecule inhibitors can greatly improve the accessibility and convenience of medication for patients, and has extremely high clinical and commercial value. Summary of the invention

[0007] The object of the present invention is to provide a compound as shown in formula (I), its stereoisomers or pharmaceutically acceptable salts thereof:

[0008]

[0009] wherein M1 is selected from N or CH; M2 is selected from N or CH; M3 is selected from N or CH;

[0010] Ring A is selected from C 6-10 Aryl or 5-10 membered heteroaryl;

[0011] Ring B is present or absent. When ring B is present, ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, benzene ring or 5-6 membered heteroaryl;

[0012] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0013] R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0014] Preferably, R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2)m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0015] R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0016] R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHRd4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0017] Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0018] R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0019] R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0020] R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0021] x is 0, 1, 2, 3, 4, or 5; y is 0, 1, 2, 3, 4, or 5;

[0022] m1, m2, m3, m4, m5, m6, m8, m9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6;

[0023] p1, p2, p3, p4, p5, p6, p8, p9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6;

[0024] m7 and p7 are each independently selected from 0, 1, 2 or 3.

[0025] The present invention also provides a compound represented by formula (IX), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0026]

[0027] wherein M1 is selected from N or CH; M2 is selected from N or CH; M3 is selected from N or CH;

[0028] L1 is selected from O, S, CH2 or NH, wherein CH2 and NH can be further substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0029] Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0030] Ring B is present or absent. When ring B is present, ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, benzene ring or 5-6 membered heteroaryl;

[0031] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0032] R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0033] R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0034] R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CHR d10 ) p1 OR d1、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0035] Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0036] R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0037] R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0038] R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0039] x is 0, 1, 2, 3, 4, or 5; y is 0, 1, 2, 3, 4, or 5;

[0040] m1, m2, m3, m4, m5, m6, m8, m9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6;

[0041] p1, p2, p3, p4, p5, p6, p8, p9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6;

[0042] m7 and p7 are each independently selected from 0, 1, 2 or 3.

[0043] The present invention also provides a compound represented by formula (X), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0044]

[0045] Wherein: L2 is selected from a bond, -O-, -NH-, -CO-, -CONH-, C 1-3 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -OC 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-, -C 1-3 Alkylene -C(O)NH-, -C 1-3 Alkylene-NHC(O)-, -C 1-3 Alkylene-S(O) r4 -、-C 1-3 Alkylene-NHS(O) r5 -or-C 1-3 Alkylene-S(O) r6 NH-; the -NH-, -CONH-, C 1-3 Alkylene, C2-4 Alkenylene, C 2-4 Alkynylidene, -OC 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-, -C 1-3 Alkylene -C(O)NH-, -C 1-3 Alkylene-NHC(O)-, -C 1-3 Alkylene-S(O) r4 -、-C 1-3 Alkylene-NHS(O) r5 -or-C 1-3 Alkylene-S(O) r6 NH- is optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted;

[0046] Ring E is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, preferably 3-12 membered heterocyclic group;

[0047] R 2-1-1 Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, =CF2, =CHF, =NOC 1-6 Alkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Heteroalkyl, C 1-6 Deuterated heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10Aryl or 5-10 membered heteroaryl, wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Heteroalkyl, C 1-6 Deuterated heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl and 5-10 membered heteroaryl groups are optionally further substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, carboxyl, oxo, thio, =CF2, =CHF, =NOC 1-6 Alkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Heteroalkyl, C 1-6 Deuterated heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted, R 2-1-1 Preferred are methyl, ethyl, methoxy, F, =CF2, -CHF2, -CH2F, -CF3, -CH2CHF2, -CHF2CH3, -CH2CF3, -CH2OCH3, -CH2OCD3, -CH2OCF3, -CH2Ocyclopropyl, -CH2SCF3, cyclopropyl, cyclobutyl, OCD3 or OCF3;

[0048] j is 0, 1, 2, 3, 4 or 5; r4, r5, r6 are each independently selected from 0, 1 or 2;

[0049] M1 is selected from N or CH; M2 is selected from N or CH; M3 is selected from N or CH;

[0050] L1 is selected from O, S, CH2 or NH, wherein CH2 and NH can be further substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0051] Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0052] Ring B is present or absent. When ring B is present, ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, benzene ring or 5-6 membered heteroaryl;

[0053] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0054] R 2-2 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0055] R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0056] R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0057] Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0058] R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0059] R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and Ra9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0060] R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0061] x is 0, 1, 2, 3, 4, or 5; y is 0, 1, 2, 3, 4, or 5;

[0062] m1, m2, m3, m4, m5, m6, m8, m9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6;

[0063] p1, p2, p3, p4, p5, p6, p8, p9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6;

[0064] m7 and p7 are each independently selected from 0, 1, 2 or 3.

[0065] In certain embodiments of the present invention, the compound has a structure shown in formula (X-1), (X-2) or (X-3)

[0066]

[0067] In certain embodiments of the present invention, the compound has a structure shown in formula (X-1-1), (X-2-1) or (X-3-1):

[0068]

[0069]

[0070] In certain embodiments of the present invention, Ring A is selected from C 3-8 Cycloalkyl or 5-10 membered heteroaryl, preferably C 3-6 Cycloalkyl or 5-6 membered heteroaryl, more preferably cyclopropyl or 5 membered heteroaryl, further preferably cyclopropyl,

[0071] In certain embodiments of the present invention, Ring A is selected from 5-10 membered heteroaryl, preferably 5-6 membered heteroaryl, more preferably 5 membered heteroaryl, and further preferably

[0072] In certain embodiments of the invention, Ring B is absent.

[0073] In certain embodiments of the present invention, ring B is present, and ring B is selected from a benzene ring or a 5-6 membered heteroaryl group, preferably, ring B is selected from a pyridinyl group;

[0074] Preferably, Selected from

[0075] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (II-1) or formula (II-2):

[0076]

[0077] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (II-1-1) or formula (II-2-1):

[0078]

[0079] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (III-1) or formula (III-2):

[0080]

[0081] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (III-1-1) or formula (III-2-1):

[0082]

[0083] In certain embodiments of the present invention, the compound represented by formula (III-2-1) is further represented by formula (III-2-1-1):

[0084]

[0085] Among them, R 4-1-1 are independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl or 3-6 membered heterocyclic group;

[0086] u is 0, 1, 2, 3, 4, 5, or 6.

[0087] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (IV-1) or formula (IV-2):

[0088]

[0089] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (IV-1-1) or formula (IV-2-1):

[0090]

[0091] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (V-1) or formula (V-2):

[0092]

[0093] In certain embodiments of the present invention, the compound represented by formula (I) is represented by formula (V-1-1) or formula (V-2-1):

[0094]

[0095] The present invention also provides a compound represented by formula (VI), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0096]

[0097] Wherein, ring A is selected from C6-10 Aryl or 5-10 membered heteroaryl;

[0098] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0099] R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0100] R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 )p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0101] Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0102] R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0103] R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0104] x is 0, 1, 2, 3, 4 or 5; y is 0, 1, 2, 3, 4 or 5; z is 0, 1, 2, 3, 4 or 5; p1, p2, p3, p4, p5, p6, p8, p9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6;

[0105] p7 is selected from 0, 1, 2 or 3.

[0106] In certain embodiments of the present invention, Ring A is selected from 5-10 membered heteroaryl, preferably 5-6 membered heteroaryl, more preferably 5 membered heteroaryl, and further preferably

[0107] In certain embodiments of the present invention, the compound represented by formula (VI) is represented by formula (VII-1) or formula (VII-2):

[0108]

[0109] In certain embodiments of the present invention, the compound represented by formula (VI) is represented by formula (VII-1-1) or formula (VII-2-1):

[0110]

[0111] The present invention also provides a compound represented by formula (VIII), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0112]

[0113] Wherein, ring A is selected from C 6-10 Aryl or 5-10 membered heteroaryl;

[0114] Ring C is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[0115] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0116] R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0117] Preferably, R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0118] R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0119] R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0120] R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0121] R 6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0122] R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted;

[0123] x is 0, 1, 2, 3, 4 or 5; y is 0, 1, 2, 3, 4 or 5; w is 0, 1, 2, 3, 4 or 5; m1, m2, m3, m4, m5, m6, m8, m9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6; m7 is selected from 0, 1, 2 or 3.

[0124] In certain embodiments of the present invention, Ring A is selected from 5-10 membered heteroaryl, preferably 5-6 membered heteroaryl, more preferably 5 membered heteroaryl, and further preferably

[0125] In certain embodiments of the present invention, ring C is selected from 5-6 membered heterocyclyl or 5-6 membered heteroaryl; preferably

[0126] In certain embodiments of the present invention, the compound represented by formula (VIII) is represented by formula (VIII-1): wherein M4 is N or CH; in certain embodiments of the present invention, the compound represented by formula (VIII-1) is represented by formula (VIII-1-1):

[0127]

[0128] In certain embodiments of the present invention, R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted.

[0129] In certain embodiments of the present invention, R1 is hydrogen, chlorine, fluorine, bromine, cyano, -CH2CF3, -CH2-cyclopropyl, -CH=CF2, -CH2CHF2. In certain embodiments of the present invention, R1 is hydrogen, chlorine, fluorine, cyano, -CH2CF3, -CH2-cyclopropyl, -CH=CF2, -CH2CHF2. In certain embodiments of the present invention, R1 is hydrogen, cyano, -CH2CF3, -CH2-cyclopropyl, -CH=CF2, -CH2CHF2.

[0130] In certain embodiments of the present invention, R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2)m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl;

[0131] Preferably, R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2)m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl;

[0132] R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted.

[0133] In certain embodiments of the present invention, R 2-1 Selected from -CH2-cyclopropyl, -CH2OCHF2, -CH2COOH, In certain embodiments of the present invention, R 2-1 Selected from -CH2-cyclopropyl, -CH2OCHF2.

[0134] In certain embodiments of the present invention, R 2-2 Selected from hydrogen.

[0135] In certain embodiments of the present invention, R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted.

[0136] In certain embodiments of the present invention, R 3-1 are independently hydrogen. In certain embodiments of the present invention, R 3-2 are independently hydrogen or fluorine.

[0137] In certain embodiments of the present invention, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl;

[0138] R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted.

[0139] In certain embodiments of the present invention, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted.

[0140] In certain embodiments of the present invention, R 4-1 Selected from

[0141] In certain embodiments of the present invention, R 4-1 Selected from Preferably, R 4-1 Selected from

[0142] In certain embodiments of the present invention, R 4-1 Selected from In certain embodiments of the present invention, R 4-1 Selected from In certain embodiments of the present invention, R 4-1 Selected from

[0143] In certain embodiments of the present invention, R 4-2 Selected from hydrogen.

[0144] In certain embodiments of the present invention, R5 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted.

[0145] In certain embodiments of the present invention, R5 is selected from hydrogen, methyl, ethyl or isopropyl.

[0146] In certain embodiments of the present invention, R5 is selected from hydrogen, methyl or isopropyl.

[0147] In certain embodiments of the present invention, R 6-1 and R6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl;

[0148] Preferably, R 6-1 are independently selected from hydrogen or methyl;

[0149] Preferably, R 6-2 Independently selected from

[0150] In certain embodiments of the present invention, Ring E is C 3-6 Cycloalkyl or Wherein, ring E' is selected from 3-12 membered heterocyclic groups, preferably 3-8 membered monocyclic heterocyclic groups, 3-8 membered fused ring heterocyclic groups, 3-8 membered bridged ring heterocyclic groups or 3-8 membered spiro heterocyclic groups, more preferably 3-8 membered monocyclic heterocyclic groups, 3-8 membered fused ring heterocyclic groups or 3-8 membered spiro heterocyclic groups, more preferably 5-9 membered heterocyclic groups, more preferably 5-6 membered heterocyclic groups; preferably, ring E' is selected from

[0151] In certain embodiments of the present invention, L2 is CH2.

[0152] The present invention also provides a compound represented by the general formula (INT), its stereoisomers or pharmaceutically acceptable salts thereof

[0153]

[0154] Wherein, R7 is selected from hydrogen or an amino protecting group, preferably H or Boc;

[0155] Ring B, Ring E, R1, R 2-1-1 , R 2-2 , R 3-1 , R 3-2 , R 4-1 , R 4-2 , L2, M1, M2, M3, z and j are defined as above.

[0156] The present invention also provides a method for preparing a compound represented by general formula (X), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (INT-1) and the compound represented by formula (INT) are reacted to obtain a compound represented by formula (X):

[0157]

[0158] Wherein, R8 is selected from halogen or OH;

[0159] Preferably, the reaction is carried out in the presence of a base and a catalyst, the base is an organic base, preferably DIPEA, and the catalyst is an amide condensation agent, preferably HATU;

[0160] Ring A, Ring B, Ring E, R1, R 2-1-1 , R 2-2 , R 3-1 , R 3-2 , R 4-1 , R 4-2 , R5, L1, L2, M1, M2, M3, y, z and j are defined as above.

[0161] The present invention also provides a pharmaceutical composition, which comprises a therapeutically effective dose of the above compound, its stereoisomer or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0162] In certain embodiments of the present invention, the weight percentage of the compound, its stereoisomer or pharmaceutically acceptable salt thereof in the composition is 0.1% to 95%, preferably 0.5% to 85%, more preferably 1% to 60%, further preferably 10% to 50%, further preferably 15-40%, further preferably 20-30%, further preferably 20-25% (based on the total weight of the pharmaceutical composition).

[0163] The present invention further relates to the use of the above-mentioned compound, its stereoisomer or its pharmaceutically acceptable salt, or the pharmaceutical composition in the preparation of IL-17 inhibitor drugs. The IL-17 is preferably IL-17A.

[0164] The present invention further relates to the use of the compound, its stereoisomer or pharmaceutically acceptable salt, or its pharmaceutical composition in the preparation of a drug for treating an autoimmune disease, wherein the autoimmune disease is preferably selected from psoriasis, plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, suppurative hidradenitis, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis and non-infectious uveitis.

[0165] The present invention also relates to a method for preventing and / or treating autoimmune diseases, which comprises administering a therapeutically effective dose of the compound, its stereoisomer or its pharmaceutically acceptable salt, or its pharmaceutical composition to a patient.

[0166] In certain embodiments of the invention, the autoimmune disease is selected from psoriasis, plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis and non-infectious uveitis.

[0167] Detailed description of the invention

[0168] Unless otherwise stated, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art. Specifically, the terms used in the specification and claims have the following meanings.

[0169] The term "alkyl" refers to a straight or branched saturated aliphatic hydrocarbon group, which may be optionally substituted with one or more substituents. In a specific embodiment, an alkyl group refers to a saturated aliphatic hydrocarbon group having 1 to 20 (C1-20 ), 1 to 15 (C 1-15 ), 1 to 12 (C 1-12 ), 1 to 10 (C 1-10 ), 1 to 8 (C 1-8 ), 1 to 6 (C 1-6 ) or 1 to 3 (C 1-3 ) carbon atoms, or a straight-chain saturated hydrocarbon group having 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms. The straight chain C 1-6 Alkyl and branched C 3-6 Alkyl groups are also called "lower alkyl". 1-6 Alkyl refers to a linear saturated monovalent hydrocarbon group having 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon group having 3 to 6 carbon atoms. 1-6 The alkyl group contains 1 to 6 (e.g., 1, 2, 3, 4, 5, 6) 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-ethylpentyl, 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, and the like. In one embodiment, the alkyl group is an optionally substituted alkyl group described elsewhere herein.

[0170] The term "alkylene" refers to a further substitution of a hydrogen atom of an alkyl group, wherein "alkyl" is as defined above. Non-limiting examples of "alkylene" include: methylene (-CH2-), ethylene (-(CH2)2-), propylene (-(CH2)3-) or butylene (-(CH2)4-). In one embodiment, the alkylene group is an optionally substituted alkyl group described elsewhere herein.

[0171] The term "alkenyl" refers to a straight or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon double bond and the carbon-carbon double bond can be located at any position within the alkenyl group, and the alkenyl group can be optionally substituted with one or more substituents. In a specific embodiment, the alkenyl group is a group having 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12 ), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ) or 2 to 4 (C 2-4 ) carbon atoms, or a straight-chain unsaturated hydrocarbon group having 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms. Unless otherwise specified, the term "alkenyl" as used herein includes both straight-chain and branched alkenyl groups. For example, C 2-6 Alkenyl refers to a straight chain unsaturated hydrocarbon group having 2 to 6 carbon atoms or a branched unsaturated hydrocarbon group having 3 to 6 carbon atoms. 2-6 The alkenyl group contains 2 to 6 (e.g., 2, 3, 4, 5, 6) carbon atoms. Non-limiting examples of alkenyl groups include: One of ordinary skill in the art will appreciate that the term "alkenyl" may also include groups having "cis" and "trans" configurations, or alternatively, groups having "E" and "Z" configurations. In one embodiment, the alkenyl is an optionally substituted alkenyl described elsewhere herein.

[0172] The term "alkynyl" refers to a straight or branched unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon triple bond and the carbon-carbon triple bond can be located at any position within the alkynyl group, and the alkynyl group can be optionally substituted with one or more substituents. In a specific embodiment, the alkynyl group is a 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 12 (C 2-12), 2 to 10 (C 2-10 ), 2 to 8 (C 2-8 ), 2 to 6 (C 2-6 ) or 2 to 4 (C 2-4 ) carbon atoms, or a straight-chain unsaturated hydrocarbon group having 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 12 (C 3-12 ), 3 to 10 (C 3-10 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms. Unless otherwise indicated, the term "alkynyl" as used herein includes both straight-chain and branched alkynyl groups. For example, C 2-6 Alkynyl refers to a straight chain unsaturated hydrocarbon group having 2 to 6 carbon atoms or a branched unsaturated hydrocarbon group having 3 to 6 carbon atoms. 2-6 Alkynyl groups contain 2 to 6 (e.g., 2, 3, 4, 5, 6) carbon atoms. Non-limiting examples of alkynyl groups include: In one embodiment, the alkynyl group is an optionally substituted alkynyl group described elsewhere herein.

[0173] The term "cycloalkyl" refers to a saturated or partially unsaturated aliphatic hydrocarbon monocyclic, polycyclic (two or more) cyclic group, which may be optionally substituted with one or more substituents. In a specific embodiment, the cycloalkyl ring contains 3 to 20 (C 3-20 ), 3 to 12 (C 3-12 ), 3 to 8 (C 3-8 ) or 3 to 6 (C 3-6 ) carbon atoms; in one embodiment, the cycloalkyl ring contains 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) carbon atoms; it may contain one or more double bonds, but does not have a completely conjugated π electron system. Non-limiting examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl or cyclooctyl, etc.; polycyclic cycloalkyls include spirocycloalkyls, fused cycloalkyls and bridged cycloalkyls in one embodiment. In one embodiment, the cycloalkyl is an optionally substituted cycloalkyl described elsewhere herein or a cycloalkyl optionally fused to a heterocyclyl, aryl or heteroaryl, non-limiting examples include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc.

[0174] The term "spirocycloalkyl" refers to an aliphatic polycyclic group in which the single rings share a carbon atom (called a spiro atom), which may contain one or more double bonds, but none of the rings has a completely conjugated π electron system. In a specific embodiment, the spirocycloalkyl contains 5 to 20 (C 5-20), 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) (e.g., 7, 8, 9, 10) carbon atoms. According to the number of shared spiro atoms between rings, spirocycloalkyl is divided into single spirocycloalkyl, double spirocycloalkyl or multi-spirocycloalkyl, and in one embodiment is single spirocycloalkyl and double spirocycloalkyl. In one embodiment, it is 4 yuan / 4 yuan, 3 yuan / 5 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 5 yuan or 5 yuan / 6 yuan single spirocycloalkyl. In one embodiment, the spirocycloalkyl is an optionally substituted spirocycloalkyl described elsewhere herein. Non-limiting examples of spirocycloalkyl include:

[0175]

[0176] The term "fused cycloalkyl" refers to an all-carbon polycyclic group in which each ring in the system shares a pair of adjacent carbon atoms with other rings in the system, wherein one or more rings may contain one or more double bonds, but no ring has a completely conjugated π-electron system. In a specific embodiment, the fused cycloalkyl contains 5 to 20 (C 5-20 ), 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) (e.g., 7, 8, 9, 10) carbon atoms. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic condensed cycloalkyl, in one embodiment, bicyclic or tricyclic, and further in one embodiment, 3-membered / 5-membered, 4-membered / 5-membered, 5-membered / 5-membered or 5-membered / 6-membered bicyclic alkyl. In one embodiment, the condensed cycloalkyl is an optionally substituted condensed cycloalkyl described elsewhere herein or a condensed cycloalkyl optionally fused to a heterocyclic group, an aryl group or a heteroaryl group. Non-limiting examples of condensed cycloalkyls include:

[0177]

[0178] The term "bridged cycloalkyl" refers to a full-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. In a specific embodiment, the bridged cycloalkyl contains 5 to 20 (C 5-20 ), 6 to 14 (C 6-14 ) or 7 to 10 (C 7-10 ) (e.g., 7, 8, 9, 10) carbon atoms. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl, preferably bicyclic or tricyclic. In one embodiment, the bridged cycloalkyl is an optionally substituted bridged cycloalkyl described elsewhere herein. Non-limiting examples of bridged cycloalkyl include:

[0179]

[0180] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon group, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, wherein the nitrogen, phosphorus or sulfur atom may be optionally oxidized, the nitrogen atom may be optionally quaternized, the ring carbon atom may be optionally substituted by oxygen, but does not include the ring part of -OO-, -OS-, and the remaining ring atoms are carbon, which may contain one or more double bonds, but does not have a completely conjugated π electron system. In a specific embodiment, the heterocyclyl contains 3 to 20, 3 to 12, 3 to 8 or 3 to 6 ring atoms, of which 1 to 4 are heteroatoms; in one embodiment, the heterocyclyl contains 3 to 6, 4 to 6, 3 to 8, 3 to 10, 6 to 10 or 7 to 11 ring atoms; in one embodiment, the heterocyclyl contains 3 to 8 (e.g., 3, 4, 5, 6, 7, 8) ring atoms. The limiting examples of monocyclic heterocyclic radical include tetrahydropyrrolyl, azetidinyl, oxetanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl and pyranyl etc..Polycyclic heterocyclic radical includes spiro heterocyclic radical, condensed heterocyclic radical and bridge heterocyclic radical.In one embodiment, the heterocyclic radical is the optionally substituted described elsewhere herein, or the heterocyclic radical further and ring-connected with other cycloalkyl, heterocyclic radical, aryl and heteroaryl by any two or more atoms on the ring.

[0181] The term "spiroheterocyclyl" refers to a polycyclic heterocyclic group in which one atom (called a spiro atom) is shared between the rings, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, and the remaining ring atoms are carbon, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. In a specific embodiment, the spiroheterocyclyl contains 5 to 20 or 6 to 14 ring atoms; in one embodiment, it contains 7 to 11 (e.g., 7, 8, 9, 10, 11) ring atoms; according to the number of spiro atoms shared between the rings, the spiroheterocyclyl is divided into a monospiroheterocyclyl, a bispiroheterocyclyl or a polyspiroheterocyclyl; preferably a monospiroheterocyclyl and a bispiroheterocyclyl; in one embodiment, the spiroheterocyclyl is a 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered or 5-membered / 6-membered monospiroheterocyclyl; in one embodiment, the spiroheterocyclyl is an optionally substituted spiroheterocyclyl described elsewhere herein; non-limiting examples of spiroheterocyclyls include:

[0182]

[0183] The term "fused heterocyclic group" refers to a polycyclic heterocyclic group in which 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 heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, and the remaining ring atoms are carbon. In a specific embodiment, the fused heterocyclic group is a heterocyclic group containing 5 to 20 or 6 to 14 ring atoms, and in one embodiment contains 7 to 10 (e.g., 7, 8, 9, 10) ring atoms; according to the number of constituent rings, it can be divided into a bicyclic, tricyclic, tetracyclic or polycyclic fused heterocyclic group; preferably a bicyclic or tricyclic group; in one embodiment, it is a 5-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclic group; in one embodiment, the fused heterocyclic group is a fused heterocyclic group described elsewhere herein that is optionally substituted or fused with a cycloalkyl, heterocyclic, aryl or heteroaryl group; non-limiting examples of fused heterocyclic groups include:

[0184]

[0185]

[0186] The term "bridged heterocyclic group" refers to a 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 none of the rings has a completely conjugated π electron system, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, boron, phosphorus or sulfur, and the remaining ring atoms are carbon. In a specific embodiment, the bridged heterocyclic group contains 5 to 20 or 6 to 14 ring atoms; in one embodiment, it contains 7 to 10 (e.g., 7, 8, 9, 10) ring atoms; according to the number of constituent rings, it can be divided into a bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclic group; preferably a bicyclic, tricyclic or tetracyclic group; in one embodiment, it is a bicyclic or tricyclic group; in one embodiment, the bridged heterocyclic group is an optionally substituted bridged heterocyclic group described elsewhere herein; non-limiting examples of bridged heterocyclic groups include:

[0187]

[0188] The term "aryl" refers to an all-carbon monocyclic or fused polycyclic (i.e., rings that share adjacent pairs of carbon atoms) group containing at least one conjugated π electron system, which may be optionally substituted by one or more substituents. In specific embodiments, the aryl group contains 6 to 20, 6 to 14, or 6 to 10 ring atoms; in one embodiment, the aryl group may further refer to a bicyclic, tricyclic, or tetracyclic ring system, wherein at least one ring is an aromatic ring, and the other rings may be saturated, partially unsaturated carbon rings, or rings containing one or more heteroatoms independently selected from O, S, and N; in one embodiment, the aryl group is selected from a benzo 5-10 membered heteroaryl, a benzo 3-10 membered cycloalkyl, or a benzo 3-10 membered heterocyclyl. In one embodiment, the aryl group is selected from a benzo 5-6 membered heteroaryl, a benzo 3-6 membered cycloalkyl, or a benzo 3-6 membered heterocyclyl, wherein the heterocyclyl group is a heterocyclyl group containing 1-3 nitrogen atoms, oxygen atoms, or sulfur atoms. Non-limiting examples include phenyl, naphthyl, fluorenyl, azulenyl, anthracenyl, phenanthrenyl, pyrenyl, biphenyl, terphenyl, dihydronaphthyl, indenyl, tetrahydronaphthyl (tetralinyl),

[0189]

[0190] The term "arylene group" refers to a divalent aromatic group formed by further replacing one hydrogen atom of an aryl group, wherein the arylene group is optionally substituted or unsubstituted, and the aryl group is as defined above.

[0191] The term "heteroaryl" refers to an optionally substituted monocyclic, polycyclic group or ring system containing at least one aromatic ring, wherein the aromatic ring has one or more heteroatoms independently selected from O, S and N. In specific embodiments, the heteroaryl group contains 5 to 20, 5 to 15 or 5 to 10 ring atoms, of which 1 to 4 are heteroatoms; in one embodiment, the heteroaryl group contains 5 or 6 ring atoms; in specific embodiments, the heteroaryl group may further refer to a bicyclic, tricyclic or tetracyclic ring, wherein at least one ring is an aromatic ring having one or more heteroatoms independently selected from O, S and N, and the other rings may be saturated, partially unsaturated carbocyclic rings or rings containing one or more heteroatoms independently selected from O, S and N. In one embodiment, the heteroaryl group is selected from heteroaryl and 6-10 membered aryl, heteroaryl and 3-10 membered cycloalkyl or heteroaryl and 3-10 membered heterocyclyl; further in one embodiment, the heteroaryl group is selected from 5- or 6-membered heteroaryl and 6-10 membered aryl, 5- or 6-membered heteroaryl and 3-6 membered cycloalkyl, 5- or 6-membered heteroaryl and 3-6 membered heterocyclyl, wherein the heterocyclyl group is a heterocyclyl group containing 1-3 nitrogen atoms, oxygen atoms or sulfur atoms. Non-limiting examples include furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, triazolyl, benzofuranyl, benzimidazolyl, benzisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiophenyl, benzothiophenyl, benzotriazolyl, imidazopyridinyl, imidazothiazolyl , indolizinyl, indolyl, indazolyl, isobenzofuranyl, isobenzothiophenyl, isoindolyl, isoquinolyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl, pteridinyl, purinyl, pyridopyridinyl, pyrrolopyridinyl, quinolyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidinyl, thienopyridinyl, acridinyl, benzindolyl, carbazolyl, bibenzofuranyl, phenanthrolinyl, phenanthridinyl, phenpyrazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl,

[0192] The term "heteroarylene" refers to a divalent heteroaryl group formed by further replacing one hydrogen atom of a cycloalkyl group, wherein the heteroarylene group is optionally substituted or unsubstituted, and the heteroaryl group is as defined above.

[0193] The term "heteroalkyl" refers to a stable straight or branched chain, or cyclic hydrocarbon group, or a combination thereof, consisting of the indicated number of carbon atoms and one or more (in one embodiment, one to three) heteroatoms selected from O, N, Si, and S, and wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. In one embodiment, the heteroatoms O, N, and S may be placed at any interior position of the heteroalkyl group. In one embodiment, the heteroatom Si may be placed at any position (e.g., interior or terminal position) of the heteroalkyl group, including the position where the alkyl group is attached to the remainder of the molecule. Non-limiting examples thereof include: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2-S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, and -CH=CH-N(CH3)-CH3. Up to two heteroatoms may be consecutive, for example, -CH2-NH-O-CH3 and -CH2-O-Si(CH3)3. In a particular embodiment, the heteroalkyl group is an optionally substituted heteroalkyl group described elsewhere herein.

[0194] The term "alkoxy" refers to -O-(alkyl) and -O-(unsubstituted cycloalkyl), wherein alkyl or cycloalkyl are as defined above. Non-limiting examples of alkoxy include: methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or cyclohexyloxy. In one embodiment, the alkoxy is an optionally substituted alkoxy described elsewhere herein.

[0195] The term "alkylacyl" refers to a -C(O)-alkyl group, wherein alkyl is as previously defined.

[0196] The term "haloalkyl" refers to an alkyl group substituted by one or more halogens, wherein the definition of alkyl is the same as above. Non-limiting examples of the haloalkyl group include: trifluoromethyl, -CH2CF3,

[0197] The term "haloalkoxy" refers to an alkoxy group substituted with one or more halogen groups, wherein alkoxy is as defined above.

[0198] The term "hydroxyalkyl" refers to an alkyl group substituted with a hydroxy group, wherein alkyl is as defined above.

[0199] The term "alkylthio" refers to -S-(alkyl) and -S-(unsubstituted cycloalkyl), wherein alkyl or cycloalkyl are as defined above. Non-limiting examples of alkylthio include: methylthio, ethylthio, propylthio, butylthio, cyclopropylthio, cyclobutylthio, cyclopentylthio or cyclohexylthio. In one embodiment, the alkylthio is an optionally substituted alkylthio described elsewhere herein.

[0200] The term "haloalkylthio" refers to an alkylthio group substituted with one or more halogens, wherein alkylthio is as defined above.

[0201] The term "alkenylcarbonyl" refers to -C(O)-(alkenyl), wherein alkenyl is as defined above. Non-limiting examples of alkenylcarbonyl include: vinylcarbonyl, propenylcarbonyl, or butenylcarbonyl. In one embodiment, the alkenylcarbonyl is an optionally substituted alkenylcarbonyl described elsewhere herein.

[0202] The term "aminocarbonyl" refers to NH2-C(O)-.

[0203] The term "alkylaminocarbonyl" refers to an aminocarbonyl (NH2-C(O)-) group in which one or both of the two hydrogen atoms are replaced by alkyl groups, wherein the alkyl group has the same definition as above.

[0204] The term "alkylamino" refers to an amino group in which one or both of the two hydrogen atoms are replaced by an alkyl group, wherein the alkyl group has the same definition as above.

[0205] The term "carbonyl" refers to a -C(O)-, -(CO)-, or -C(=O)- group. All notations are used interchangeably in the specification.

[0206] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0207] The term "hydrogen" includes protons ( 1 H), deuterium ( 2 H), tritium ( 3 H) and / or mixtures thereof. In a particular embodiment, one or more positions occupied by hydrogen in the compound may be enriched with deuterium and / or tritium. Such isotopically enriched analogs may be prepared from suitable isotopically labeled starting materials obtained from commercial sources or prepared by known literature procedures.

[0208] The alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylene, heteroaryl, heteroarylene, heteroalkyl, alkoxy, alkylthio, hydroxyalkyl, alkenylcarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylamino, and alkylacyl may be substituted or unsubstituted. In one embodiment, the substituent is selected from one or more of the following groups: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, alkylacyl, halogen, sulfhydryl, hydroxyl, nitro, cyano, azido, oxime, phosphate, oxo, thio, carboxyl, carboxylate, cycloalkyl, heterocyclyl, aryl, heteroaryl, heterocycloalkyloxy, cycloalkylthio, or heterocycloalkylthio.

[0209] 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”, “X is A, B and C” all express the same meaning, that is, X can be any one or more of A, B, C.

[0210] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs or does not occur. For example, "a heterocyclic group optionally substituted with an alkyl group" means that an alkyl group may but need not be present, and 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.

[0211] In various parts of the present invention, linking substituents are described. When the structure clearly requires a linking group, the Markush variable listed for that group should be understood as a linking group. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl" or "aryl", it should be understood that the "alkyl" or "aryl" represents an alkylene group or an arylene group, respectively, that is linked.

[0212] "Substituted" means that any one or more hydrogen atoms on a particular atom are replaced by a substituent, as long as the valence state of the particular atom is normal and the substituted compound is stable in one embodiment. In one embodiment. When the substituent is oxo (i.e., =O), it means that two hydrogen atoms are replaced. The term "optionally substituted" means that it may be substituted or not substituted, and unless otherwise specified, the type and number of the substituent may be arbitrary on the basis of chemical realization. It goes without saying that the substituent is only in their possible chemical position, and those skilled in the art can determine (by experiment or theory) possible or impossible substitution without paying too much effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (such as olefinic) bond.

[0213] In this specification and the claims, the indefinite articles "a" and "an" and the definite article "the" include plural as well as singular, unless stated to the contrary.

[0214] "Pharmaceutical composition" means a mixture containing one or more compounds described herein or their physiologically / pharmaceutically acceptable salts or prodrugs and 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, facilitate the absorption of the active ingredient, and thus exert biological activity.

[0215] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention, which are safe and effective when used in mammals and have the desired biological activity.

[0216] "Stereoisomers" encompass all enantiomerically / diastereomerically / stereomerically pure and enantiomerically / diastereomerically / stereomerically enriched forms of the compounds of the invention.

[0217] "Stereomerically pure" refers to a composition comprising one stereoisomer of a compound and being substantially free of another stereoisomer of the compound. For example, a stereomerically pure composition of a compound having one chiral center will be substantially free of the opposite enantiomer of the compound. A stereomerically pure composition of a compound having two chiral centers will be substantially free of other diastereomers of the compound. A typical stereoisomerically pure compound contains greater than about 80% by weight of one stereoisomer of the compound and less than about 20% by weight of another stereoisomer of the compound, greater than about 90% by weight of one stereoisomer of the compound and less than about 10% by weight of another stereoisomer of the compound, greater than about 95% by weight of one stereoisomer of the compound and less than about 5% by weight of another stereoisomer of the compound, greater than about 97% by weight of one stereoisomer of the compound and less than about 3% by weight of another stereoisomer of the compound, or greater than about 99% by weight of one stereoisomer of the compound and less than about 1% by weight of another stereoisomer of the compound.

[0218] "Stereoisomerically enriched" refers to a composition comprising greater than about 55% by weight, greater than about 60% by weight, greater than about 70% by weight, or greater than about 80% by weight of one stereoisomer of a compound.

[0219] "Enantiomerically pure" refers to a stereomerically pure composition of a compound having one chiral center. Similarly, the term "enantiomerically enriched" refers to a stereomerically enriched composition of a compound having one chiral center.

[0220] "Optically active" and "enantiomeric activity" refer to a combination of molecules having an enantiomeric or diastereomeric excess of not less than about 50%, not less than about 70%, not less than about 80%, not less than about 90%, not less than about 91%, not less than about 92%, not less than about 93%, not less than about 94%, not less than about 95%, not less than about 96%, not less than about 97%, not less than about 98%, not less than about 99%, not less than about 99.5%, or not less than about 99.8%. In certain embodiments, the compound comprises about 95% or more of the desired enantiomer or diastereomer and about 5% or less of the less preferred enantiomer or diastereomer, based on the total weight of the racemate.

[0221] When describing an optically active compound, the prefixes R and S are used to denote the absolute configuration of the molecule with respect to its chiral center. (+) and (-) are used to denote the optical rotation of the compound, i.e., the direction of the plane of polarized light rotated by the optically active compound. The prefix (-) indicates that the compound is levorotatory, i.e., the compound rotates the plane of polarized light to the left or counterclockwise. The prefix (+) indicates that the compound is dextrorotatory, i.e., the compound rotates the plane of polarized light to the right or clockwise. However, the signs (+) and (-) of the optical rotation have nothing to do with the absolute configuration, R and S, of the molecule. DETAILED DESCRIPTION

[0222] The present invention is further described below in conjunction with examples, but these examples are not intended to limit the scope of the present invention.

[0223] Example

[0224] The structure of the compound of the present invention is determined by nuclear magnetic resonance (NMR) or / and liquid chromatography-mass spectrometry (LC-MS). The NMR chemical shift (δ) is given in parts per million (ppm). The NMR is measured using a Bruker AVANCE-400 nuclear magnetic spectrometer, and the measurement solvents are deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD) and deuterated chloroform (CDCl3), and the internal standard is tetramethylsilane (TMS).

[0225] 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 C 18 150×4.6mm chromatographic column).

[0226] 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.

[0227] The starting materials in the examples of the present invention are known and can be purchased on the market, or can be synthesized by or according to methods known in the art.

[0228] Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, the solvent is a dry solvent, and the reaction temperature is in degrees Celsius.

[0229] Synthetic route

[0230]

[0231]

[0232] The following examples were prepared according to the above synthetic route

[0233]

[0234]

[0235]

[0236]

[0237]

[0238]

[0239]

[0240]

[0241]

[0242] Example 112 can also be synthesized according to the following steps

[0243]

[0244] Step 1: Preparation of 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)but-3-en-1-ol

[0245]

[0246] Dissolve 6-bromoimidazo[1,2-a]pyridine-3-carboxaldehyde (10 g, 44.4 mmol) in tetrahydrofuran (200 mL), cool to 0°C in an ice-water bath, add allylmagnesium bromide (49 mL, 1 M, 49 mmol) dropwise under stirring, and after the addition is complete, warm the reaction solution to room temperature and stir for 2 hours. Add saturated aqueous ammonium chloride solution (25 mL) to quench the reaction, extract the reaction solution three times with ethyl acetate, combine the organic phases and wash with saturated aqueous sodium chloride solution, separate the organic phase, dry it with anhydrous sodium sulfate, filter and concentrate the organic solvent under reduced pressure, and separate the residue by column chromatography to obtain the title compound (9.7 g, 82%). MS m / z(ESI):267.0[M+H] + .

[0247] Step 2: Preparation of 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethane-1-ol

[0248]

[0249] Dissolve 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)but-3-en-1-ol (2 g, 7.49 mmol) and diiodomethane (6 g, 22.46 mmol) in toluene (20 mL), cool to 0°C in an ice-water bath, and add diethylzinc solution (23 mL, 1 M toluene solution, 23 mmol) under stirring. The reaction solution was stirred at room temperature for 12 hours, and saturated ammonium chloride aqueous solution was added to quench the reaction. The reaction solution was extracted with ethyl acetate three times, the organic phases were combined and washed with saturated sodium chloride aqueous solution, the separated organic phases were dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (1.8 g, 86%). MSm / z(ESI):281.0[M+H] +

[0250] Step 3: Preparation of 6-bromo-3-(2-cyclopropyl-1-(4-nitro-1H-pyrazol-1-yl)ethyl)imidazo[1,2-a]pyridine

[0251]

[0252] 4-Nitropyrazole (1 g, 8.84 mmol), 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethane-1-ol (2.25 g, 8.04 mmol) and triphenylphosphine (3.48 g, 13.27 mmol) were dissolved in dry tetrahydrofuran (20 mL). The reaction solution was protected with nitrogen and cooled to 0°C in an ice-water bath. Diisopropyl azodicarboxylate (2.68 g, 13.27 mmol) was slowly added dropwise to the reaction solution. The reaction solution was stirred at 0°C for 0.5 hours, and then heated to room temperature and stirred for 1 hour. Saturated aqueous ammonium chloride was added to quench the reaction, and the reaction solution was extracted with ethyl acetate three times. The organic phases were combined and washed with saturated aqueous sodium chloride solution. The organic phase was separated and dried over anhydrous sodium sulfate. After filtration, the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (2.32 g, 75%).

[0253] MS m / z(ESI):376.0[M+H] + .

[0254] Step 4: Preparation of 1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-amine

[0255]

[0256] Under stirring conditions, ammonium chloride (0.428 g, 8 mmol) was added to a mixed solution of 6-bromo-3-(2-cyclopropyl-1-(4-nitro-1H-pyrazol-1-yl)ethyl)imidazo[1,2-a]pyridine (300 mg, 0.8 mmol) and iron powder (448 mg, 8 mmol) in ethanol (10 mL)-water (2 mL), and the mixture was heated to 80°C and stirred for 2 h. After cooling to room temperature, the reaction solution was filtered through diatomaceous earth, and the filtrate was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated sodium chloride solution, separated and dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to remove the organic solvent, and the residue was separated by column chromatography to obtain the title compound (234 mg, 85%). MS m / z(ESI):346.1[M+H] + .

[0257] Step 5: Preparation of tert-butyl ((1S)-2-((1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-1-((trans)-4-methylcyclohexyl)-2-carbonylethyl)carbamate

[0258]

[0259] (S)-2-((tert-butoxycarbonyl)amino)-2-((trans)-4-methylcyclohexyl)acetic acid (172 mg, 0.64 mmol) and 1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-amine (110 mg, 0.32 mmol) were dissolved in DMF (10 mL), and DIPEA (123 mg, 0.95 mmol, 166 μL) and HATU (288 mg, 0.76 mmol) were added in sequence. The resulting reaction solution was stirred at room temperature for 12 hours. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction solution was extracted three times with ethyl acetate. The organic phases were combined and washed with saturated aqueous sodium chloride solution. The separated organic phase was dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (160 mg, 84%). MS m / z(ESI):599.2[M+H] + .

[0260] Step 6: Preparation of tert-butyl ((1S)-2-((1-(1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-1-((trans)-4-methylcyclohexyl)-2-carbonylethyl)carbamate

[0261]

[0262] N-((1S)-2-((1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-1-((trans)-4-methylcyclohexyl)-2-carbonylethyl)-4-ethyl-1,2,5-oxadiazole-3-carboxamide (160 mg, 0.27 mmol) was dissolved in DMF (3 mL), tetrakis(triphenylphosphine)palladium (46 mg, 0.04 mmol) and zinc cyanide (94 mg, 0.80 mmol) were added in sequence, the reaction solution was sealed and replaced with nitrogen three times, and microwave heating was performed at 110°C with stirring for 1 hour. The reaction was then cooled to room temperature, the reaction solution was diluted with ethyl acetate, washed with saturated ammonium chloride solution and saturated brine, the separated organic phase was dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (110 mg, 76%).

[0263] MS m / z(ESI):546.3[M+H] + .

[0264] Step 7: Preparation of N-((S)-2-((1-((R)-1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-1-((trans)-4-methylcyclohexyl)-2-carbonylethyl)-4-ethyl-1,2,5-oxadiazole-3-carboxamide

[0265]

[0266] Tert-butyl ((1S)-2-((1-(1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-1-((trans)-4-methylcyclohexyl)-2-carbonylethyl)carbamate (120 mg, 0.22 mmol) was dissolved in dichloromethane (5 mL), trifluoroacetic acid (5 mL) was added, and the reaction solution was stirred at room temperature for 1 hour. The solvent was removed by concentration under reduced pressure, and the residue was adjusted to pH 7-8 with saturated sodium bicarbonate solution, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. The obtained residue was dissolved in DMF (5 mL), and DIPEA (284 mg, 2.19 mmol, 0.38 mL), 4-ethyl-1,2,5-oxadiazole-3-carboxylic acid (32 mg, 0.22 mmol) and HATU (100 mg, 0.26 mmol) were added in sequence, and the reaction solution was stirred at room temperature for 12 hours. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction solution was extracted three times with ethyl acetate, the organic phases were combined and washed with saturated aqueous sodium chloride solution, the organic phase was separated and dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography and chiral HPLC to obtain the title compound (40 mg, 32%).

[0267] 1H NMR (400MHz, DMSO-d6) δ10.27(s,1H),9.22(s,1H),9.09(d,J=8.3Hz,1H),8.17(s,1H),7.93(s,1H),7.73(d ,J=9.4Hz,1H),7.50(dd,J=9.4,1.4Hz,1H),7.47(s,1H),6.07(dd,J=9.3,5.8Hz,1H),4.31(t,J=8.2Hz,1H) ,2.85(q,J=7.5Hz,2H),2.44-2.34(m,1H),2.19-2.07(m,1H),1.80-1.58(m,4H),1.53-1.46(m,1H),1.35-1 .16(m,9H),1.14-0.92(m,2H),0.54-0.43(m,1H),0.40-0.24(m,2H),0.17-0.11(m,1H),0.06-0.02(m,1H).

[0268] MS m / z(ESI):570.3[M+H] + .

[0269] Embodiment 118

[0270]

[0271] Example 118 can also be prepared by referring to Example 112.

[0272] 1 H NMR (400MHz, DMSO-d6) δ10.08(s,1H),9.24(s,1H),8.16(s,1H),7.95(s,1H),7.75(d,J=9.4Hz,1H), 7.53-7.49(m,1H),7.48(s,1H),7.29-7.25(m,1H),6.10-6.05(m,1H),3.93-3.88(m,1H),3.83(t,J=8 .2Hz,1H),2.46-2.33(m,1H),2.18-2.09(m,1H),1.72-1.57(m,3H),1.55-1.38(m,1H),1.11-0.91(m ,2H),0.87-0.74(m,6H),0.65-0.47(m,5H),0.42-0.28(m,2H),0.20-0.13(m,1H),0.07-0.01(m,2H).

[0273] MS m / z(ESI):530.3[M+H] + .

[0274] Embodiment 119

[0275]

[0276] Example 119 can also be prepared by referring to Example 112.

[0277] 1 H NMR (400MHz, DMSO-d6) δ9.89 (s, 1H), 9.31 (s, 1H), 8.29 (d, J = 2.0Hz, 1H), 7.97 (s, 1H), 7.77 (d ,J=9.4Hz,1H),7.53(dd,J=9.3,1.6Hz,1H),7.28(d,J=8.6Hz,1H),5.89-5.80(m,2H),5.08-4 .95(m,3H),4.01-3.86(m,2H),2.35-2.24(m,1H),2.02-1.86(m,2H),1.71-1.60(m,2H),1.56 -1.41(m,2H),1.27-1.22(m,4H),1.12-0.93(m,2H),0.82(d,J=6.6Hz,3H),0.63-0.52(m,4H).

[0278] MS m / z(ESI):548.3[M+H] +

[0279] Example 129 can also be synthesized according to the following steps

[0280]

[0281] Step 1: Preparation of tert-butyl ((2S,3R)-1-((1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-3-(1-methylcyclopropyloxy)-1-carbonylbutane-2-yl)carbamate

[0282]

[0283] N-(tert-Butoxycarbonyl)-O-(1-methylcyclopropyl)-L-threonine (126 mg, 0.46 mmol) and 1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-amine (80 mg, 0.23 mmol) were dissolved in DMF (10 mL), and DIPEA (90 mg, 0.69 mmol, 121 μL) and HATU (174 mg, 0.46 mmol) were added in sequence. The reaction solution was stirred at room temperature for 12 hours. The reaction solution was diluted with ethyl acetate, washed with saturated ammonium chloride solution and saturated brine in sequence, the organic phase was separated, dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (120 mg, 86%).

[0284] MS m / z(ESI):601.2[M+H] + .

[0285] Step 2: Preparation of tert-butyl ((2S,3R)-1-((1-(1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-3-(1-methylcyclopropyloxy)-1-carbonylbutane-2-yl)carbamate

[0286]

[0287] Tert-butyl ((2S,3R)-1-((1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-3-(1-methylcyclopropyloxy)-1-carbonylbutane-2-yl)carbamate (120 mg, 0.20 mmol) was dissolved in DMF (3 mL) solution, tetrakis(triphenylphosphine)palladium (35 mg, 0.03 mmol) and zinc cyanide (70 mg, 0.60 mmol) were added in sequence, the reaction solution was sealed and replaced with nitrogen three times, and microwave heated to 110°C and stirred for 1 hour. After cooling to room temperature, the reaction solution was diluted with ethyl acetate, saturated aqueous ammonium chloride solution was added to quench the reaction, the reaction solution was extracted with ethyl acetate three times, the organic phases were combined and washed with saturated aqueous sodium chloride solution, the separated organic phase was dried over anhydrous sodium sulfate, filtered and the organic solvent was concentrated under reduced pressure, and the residue was separated by column chromatography to obtain the title compound (88 mg, 81%). MS m / z(ESI):548.3[M+H] + .

[0288] Step 3: Preparation of N-((2S,3R)-1-((1-((R)-1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-3-(1-methylcyclopropyloxy)-1-carbonylbutane-2-yl)-4-ethyl-1,2,5-oxadiazole-3-carboxamide

[0289]

[0290] Tert-butyl ((2S,3R)-1-((1-(1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-cyclopropylethyl)-1H-pyrazol-4-yl)amino)-3-(1-methylcyclopropyloxy)-1-carbonylbutan-2-yl)carbamate (88 mg, 0.16 mmol) was dissolved in dichloromethane (5 mL), trifluoroacetic acid (5 mL) was added, and the reaction solution was stirred at room temperature for 1 hour. The organic solvent was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate, washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, and the organic phase was dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was dissolved in DMF (5 mL), and DIPEA (208 mg, 1.61 mmol, 280 μL), 4-ethyl-1,2,5-oxadiazole-3-carboxylic acid (46 mg, 0.32 mmol) and HATU (121 mg, 0.32 mmol) were added in sequence. The reaction solution was stirred at room temperature for 12 hours, then diluted with ethyl acetate, quenched by adding saturated ammonium chloride aqueous solution, extracted with ethyl acetate three times, the organic phases were combined and washed with saturated sodium chloride aqueous solution, the organic phase was separated and dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (30 mg, 33%).

[0291] 1H NMR (400MHz, DMSO-d6) δ10.14(s,1H),9.15(s,1H),8.48(d,J=8.9Hz,1H),8.24(s,1H),7.95(s,1H),7.7 5(d,J=9.4Hz,1H),7.57-7.47(m,2H),6.09(dd,J=9.6,5.3Hz,1H),4.51(dd,J=8.9,3.7Hz,1H),4.29-4. 12(m,1H),2.91(q,J=7.4Hz,2H),2.42-2.31(m,1H),2.24-2.09(m,1H),1.24-1.21(m,6H),1.18(d,J=6. 3Hz,3H),0.69-0.54(m,2H),0.53-0.45(m,1H),0.41-0.22(m,4H),0.18-0.12(m,1H),0.08-0.01(m,1H).

[0292] MS m / z(ESI):572.3[M+H] + .

[0293] Example 130-1

[0294]

[0295] Example 130-1 can also be prepared by referring to Example 112.

[0296] 1 H NMR (400MHz, DMSO-d6) δ10.29(d,J=6.2Hz,1H),9.11(d,J=8.2Hz,1H),8.71-8.60(m,1H),8.13(d,J=5.0Hz,1H),7. 85(d,J=2.2Hz,1H),7.60(d,J=9.5Hz,1H),7.48(s,1H),7.40-7.37(m,1H),6.10-6.05(m,1H),4.33(t,J=8.2Hz,1H) ,2.90-2.83(m,2H),2.41-2.31(m,1H),2.18-2.10(m,1H),1.84-1.59(m,4H),1.55-1.47(m,1H),1.29-1.18(m,4H) ,1.13-1.10(m,2H),0.88-0.78(m,5H),0.54-0.46(s,1H),0.41-0.28(m,2H),0.21-0.13(m,1H),0.04-0.01(m,1H).

[0297] MS m / z(ESI):623.2[M+H] + .

[0298] Embodiment 136

[0299] Cyclopropyl ((S)-2-((1-((R)-1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-yl)amino)-1-((1r,4S)-4-methylcyclohexyl)-2-carbonylethyl)carbamate

[0300]

[0301] Step 1: Preparation of 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-chloroethane-1-one

[0302]

[0303] Dissolve 2-amino-5-bromopyridine (5 g, 28.90 mmol) and N,N-dimethylformamide dimethyl acetal (3.44 g, 28.90 mmol) in isopropanol (40 mL), heat to 80 ° C and stir for 30 minutes. Concentrate under reduced pressure to remove the solvent, dissolve the residue in acetonitrile (40 mL), slowly drip it into 1,3-dichloroacetone (3.67 g, 28.90 mmol) in acetonitrile (40 mL), stir at room temperature for 12 hours, remove the solvent under reduced pressure to obtain the crude title compound, which is used directly in the next step. MS m / z (ESI): 274.9 [M+H] + .

[0304] Step 2: Preparation of 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethane-1-one

[0305]

[0306] Dissolve the crude 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-chloroethane-1-one in acetonitrile (40 mL), add diisopropylethylamine (4.13 g, 31.99 mmol) and morpholine (1.67 g, 19.19 mmol), and heat the reaction solution to 60°C and stir for 3 hours. Cool to room temperature, dilute the reaction solution with ethyl acetate, wash with saturated sodium carbonate solution and saturated brine in sequence, dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure. The residue is separated by column chromatography to obtain the title compound (1.1 g, total yield of two steps 12%). MS m / z(ESI):324.0[M+H] +

[0307] Step 3: Preparation of 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethane-1-ol

[0308]

[0309] Under ice bath, 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethane-1-one (1.1 g, 3.39 mmol) was dissolved in a mixture of tetrahydrofuran (20 mL) / methanol (20 mL), sodium borohydride (385 mg, 10.18 mmol) was slowly added, and the mixture was reacted at room temperature for 2 h. The reaction solution was diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. The residue was separated by column chromatography to obtain the title compound (980 mg, 89%). MS m / z(ESI):326.0[M+H] +

[0310] Step 4: Preparation of 4-(2-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-(3-fluoro-4-nitro-1H-pyrazol-1-yl)ethyl)morpholine

[0311]

[0312] Under ice bath, 1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethane-1-ol (300 mg, 919.71 μmol), 3-fluoro-4-nitropyrazole (121 mg, 919.71 μmol) and triphenylphosphine (362 mg, 1.38 mmol) were dissolved in tetrahydrofuran (40 mL) solution, DIAD (279 mg, 1.38 mmol) was slowly added, and the mixture was reacted at room temperature for 2 h. The reaction solution was diluted with ethyl acetate, washed with saturated brine, the organic phase was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. The residue was separated by column chromatography to obtain the title compound (266 mg, 66%). MS m / z(ESI):439.0[M+H] +

[0313] Step 5: Preparation of 1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-amine

[0314]

[0315] 4-(2-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-(3-fluoro-4-nitro-1H-pyrazol-1-yl)ethyl)morpholine (266 mg, 605.59 μmol) was dissolved in a mixed solution of ethanol (20 mL) / water (5 mL), iron powder (483 mg, 8.65 mmol) and ammonium chloride (463 mg, 8.65 mmol) were added, and the reaction solution was heated to 80°C and stirred for 30 minutes. The mixture was cooled to room temperature, filtered through diatomaceous earth to remove insoluble solids, the filtrate was adjusted to pH=8 with saturated sodium bicarbonate solution, extracted twice with ethyl acetate, the ethyl acetate extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. The residue was separated by column chromatography to obtain the title compound (210 mg, 85%).

[0316] MS m / z(ESI):409.1[M+H] +

[0317] Step 6: Preparation of tert-butyl ((1S)-2-((1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-yl)amino)-1-((1r,4S)-4-methylcyclohexyl)-2-carbonylethyl)carbamate

[0318]

[0319] 1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-amine (210 mg, 513.13 μmol) and (S)-2-((tert-butoxycarbonyl)amino)-2-((1r,4S)-4-methylcyclohexyl)acetic acid (167 mg, 615.75 μmol) were dissolved in DMF (10 mL) solution, and diisopropylethylamine (199 mg, 1.54 mmol, 268.13 μL) and HATU (290 mg, 769.69 μmol) were added in sequence, and the mixture was reacted at room temperature for 12 hours. The reaction solution was diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (215 mg, 63%). MS m / z(ESI):664.2[M+H] +

[0320] Step 7: Preparation of tert-butyl ((1S)-2-((1-(1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-yl)amino)-1-((1r,4S)-4-methylcyclohexyl)-2-carbonylethyl)carbamate

[0321]

[0322] Under the protection of dry nitrogen, tert-butyl ((1S)-2-((1-(1-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-yl)amino)-1-((1r,4S)-4-methylcyclohexyl)-2-carbonylethyl)carbamate (215 mg, 324.48 μmol), zinc cyanide (60 mg, 512.68 μmol) and tetrakistriphenylphosphine palladium (56 mg, 48.67 μmol) were added to a DMF (10 mL) solution, transferred to a microwave synthesizer, heated to 110°C and stirred for 1 hour. After cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was separated by column chromatography to obtain the title compound (160 mg, 81%). MS m / z(ESI):609.3[M+H] + .

[0323] Step 8: Preparation of cyclopropyl ((S)-2-((1-((R)-1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-yl)amino)-1-((1r,4S)-4-methylcyclohexyl)-2-carbonylethyl)carbamate

[0324]

[0325] Tert-butyl ((1S)-2-((1-(1-(6-cyanoimidazolo[1,2-a]pyridin-3-yl)-2-morpholinoethyl)-3-fluoro-1H-pyrazol-4-yl)amino)-1-((1r,4S)-4-methylcyclohexyl)-2-carbonylethyl)carbamate (160 mg, 262.85 μmol) was dissolved in a mixed solvent of dichloromethane (5 mL) and trifluoroacetic acid (5 mL) and stirred at room temperature for 1 hour. The solvent was removed by concentration under reduced pressure, and the residue was dissolved in ethyl acetate, washed with saturated sodium bicarbonate solution and saturated brine in sequence, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. The residue was dissolved in dichloromethane (5 mL), cooled to 0°C in an ice-water bath, and diisopropylethylamine (102 mg, 788.56 μmol) and cyclopropyl chloroformate (41 mg, 341 μmol) were added in sequence, and stirring continued at 0°C for 30 minutes. The residue was concentrated under reduced pressure, and the title compound (55 mg, 35%) was obtained by separation of the residue by chiral preparative column.

[0326] 1H NMR (400 MHz, DMSO-d6) δ9.90(s,1H),9.33(s,1H),8.27(d,J=1.9 Hz,1H),7.97(s,1H),7.77(d,J=9.4 Hz,1H),7.54(dd,J=9.4,1.6 Hz,1H),7.29(d,J=8.5 Hz,1H),6.12(t,J=7.3 Hz,1H),4.05-3.87(m,2H),3.50-3.44(m,4H),3.30-3.24(m,1H),3.09(dd,J=13.1,5.6 Hz,1H),2.65-2.55(m,2H),2.39-2.30(m,2H),1.76-1.40(m,6H),1.17-0.89(m,4H),0.83(d,J=6.5Hz,3H),0.64-0.52(m,4H).

[0327] MS m / z(ESI):593.3[M+H] + .

[0328] Embodiment 137

[0329]

[0330] Example 137 can also be prepared by referring to Example 112.

[0331] 1 H NMR (400MHz, DMSO-d6) δ10.32(d,J=8.0Hz,1H),9.23(d,J=8.0Hz,1H),8.58(d,J=8.1Hz,1H),8.19 (d,J=3.6Hz,1H),7.95(d,J=2.0Hz,1H),7.75(d,J=9.4Hz,1H),7.54-7.46(m,3H),6.93(s,1H),6. 10-6.07(m,1H),5.40-5.33(m,1H),4.37(t,J=8.6Hz,1H),2.46-2.37(m,1H),2.16-2.08(m,1H),2 .07-1.93(m,3H),1.88-1.56(m,2H),1.37-1.21(m,9H),0.55-0.46(s,1H),0.40-0.29(m,2H),0.20 -0.13(m,1H),0.07-0.01(m,2H).

[0332] MS m / z(ESI):604.3[M+H] + .

[0333] Embodiment 138

[0334]

[0335] Example 138 can also be prepared by referring to Example 136.

[0336] 1 H NMR (400MHz, DMSO-d6) δ10.08(s,1H),9.24(s,1H),8.15(s,1H),7.96(s,1H),7.76(d,J=9.4Hz,1H),7.52-7.50(m, 1H),7.44(s,1H),7.30-7.26(m,1H),6.27(t,J=7.2Hz,1H),3.96-3.87(m,1H),3.83(t,J=8.2Hz,1H),3.67(d,J=10 .9Hz,1H),3.40-3.25(m,3H),3.20-3.15(m,1H),2.94(d,J=11.0Hz,1H),2.60-2.53(m,1H),2.24-2.12(m,1H),1.8 1(t,J=10.5Hz,1H),1.72-1.58(m,3H),1.55-1.38(m,2H),1.07-0.91(m,5H),0.88-0.74(m,6H),0.64-0.48(m,4H).

[0337] MS m / z(ESI):589.3[M+H] + .

[0338] Embodiment 139

[0339]

[0340] Example 139 can also be prepared by referring to Example 136.

[0341] 1H NMR (400MHz, DMSO-d6) δ10.22(s,1H),9.24(t,J=1.3Hz,1H),8.16(s,1H),8.11-8.02(m,1H),7.97( s,1H),7.77-7.74(m,1H),7.53-7.50(m,1H),7.46(s,1H),6.27(t,J=7.2Hz,1H),4.20(t,J=8.4Hz, 1H),3.48(t,J=4.6Hz,4H),3.30-3.19(m,2H),2.60-2.54(m,2H),2.41-2.34(m,2H),1.78-1.70(m, 2H),1.68-1.60(m,2H),1.51-1.43(m,1H),1.30-1.21(m,4H),1.19-1.12(m,2H),0.89-0.78(m,6H).

[0342] MS m / z(ESI):577.3[M+H] + .

[0343] Biological test evaluation

[0344] The present invention is further described and explained in conjunction with the following test examples, but these examples are not intended to limit the scope of the present invention. Test Example 1: Determination of the competitive binding effect of the compound of the present invention on the ligand of human IL-17 receptor

[0345] 1. Experimental purpose: To quantitatively detect the blocking effect of compounds on the binding of human IL-17RA to IL-17A protein by competitive ELISA under in vitro conditions.

[0346] 2. Experimental instruments and reagents:

[0347] 2.1 Instruments:

[0348]

[0349] 2.2 Reagents:

[0350]

[0351]

[0352] 3. Experimental method: 0.0625 μg / mL IL-17A was coated in 96-well plates at 4°C overnight with 100 μL per well. After washing the plate 4 times with 300 μL of PBST per well each time, 300 μL of ELISABlocker blocking buffer was added to each well, blocked at 24°C for 2 hours, and the plate was washed again under the same conditions. 80 μL of PBS solution containing 1% BSA and 10 μL of 10× test compound solution were added to each well, mixed and incubated at room temperature for 1 hour, and then 10 μL of IL-17RA solution was added to make the final concentration 5 nM, mixed and incubated at 24°C for 1 hour. The corresponding concentration and volume of DMSO solution without compound was added to the positive control well, and 1% BSA solution without IL-17RA was added to the negative control well. After washing the plate 4 times, 100 μL of anti-Fc tag HRP-conjugated antibody was added and incubated at 37°C for 1 hour. After washing the plate 4 times, 100 μL of TMB substrate was added to each well and incubated at 37°C in the dark. After color development, 100 μL of stop solution was added to each well to terminate the reaction, and the absorbance was detected at 450 nm and 570 nm using an ELISA reader.

[0353] 4. Experimental data processing method:

[0354] 1) Inhibition rate (%): The original data (OD450-OD570) was calculated according to the following formula to obtain the inhibition rate.

[0355] Inhibition rate % = [(average value of positive control wells - value of sample wells) / (average value of positive control wells - average value of negative control wells)] × 100, where the positive control wells are wells without compound, and the negative control wells are wells without IL-17RA protein solution.

[0356] 2) Curve fitting: Use log(inhibitor) vs.respon---Variableslope(four parameters) in GraphPad Prism 8 to fit the compound concentration and the corresponding inhibition rate, fit the curve and obtain the compound IC 50 value.

[0357] The fitting calculation equation is Y = Bottom + (Top-Bottom) / (1 + 10^((LogIC 50 -X)*HillSlope))

[0358] 5. Experimental results:

[0359] Table 1

[0360] Example <![CDATA[IC 50 (nM)]]> 112 3.6 118 7.2 129 6.7 130-1 9.7

[0361] 6. Experimental conclusion: The compounds of the present invention show excellent inhibitory effects.

[0362] Test Example 2: Determination of the inhibitory effect of the compounds of the present invention on the secretion of Groα by HT-29 cells

[0363] Purpose of the experiment: The purpose of this test case is to measure the inhibitory ability of the compound on the secretion of Groα by HT-29 cells to evaluate the inhibition of the compound on the IL-17A pathway.

[0364] Experimental instruments and reagents:

[0365] instrument:

[0366]

[0367] Reagents:

[0368]

[0369] Experimental methods:

[0370] Prepare a cell suspension of 50,000 cells / ml, add 200 μl of cell suspension to each well of a 96-well plate, i.e., 10,000 cells / well, and culture overnight. In a 96-well V-bottom plate, dilute the 5 mM compound 3-fold with DMSO; dilute the compound 100-fold in each well with complete medium. The storage concentration of IL-17A protein (R&D, #BT7955-025 / CF) is 100 μg / ml, and it is diluted 333.33 times with complete medium. Mix the compound and IL-17A at a volume ratio of 1:1, and incubate at 37 degrees for 30 minutes. Add 50 μl of the compound and IL-17A mixture to the cell wells, and the final concentration of IL-17A protein is 30 ng / ml. Incubate in a cell culture incubator at 37°C, 5% CO2 for 48 hours. The concentration of Groα in the supernatant was determined by ELISA method Human Groα Valukin Elisa kit (Biotechne, #VAL139), and the absorbance at 450 nm was measured by microplate reader (PE, EnVision 2105). The data were analyzed by GraphPad Prism 8.3.0.

[0371] Experimental data processing method: GraphPad Prism 8.3.0 was used to analyze the data.

[0372] Inhibition rate % = [(average value of positive control wells - value of sample wells) / (average value of positive control wells - average value of negative control wells)] × 100%, where the sample wells are cells plus different concentration gradient compound wells, the positive control wells are cells plus IL-17A, and the negative control wells are culture medium plus IL-17A.

[0373] Curve fitting: According to the inhibition rate (%) of each concentration, the IC was obtained by curve fitting using log (inhibitor) vs. response--Variable slope (four parameters) in GraphPad Prism 6.0. 50 The calculation equation is Y = Bottom + (Top-Bottom) / (1 + 10^((LogIC 50 -X)*HillSlope)).

[0374] Experimental results:

[0375] Table 2

[0376]

[0377]

[0378] Experimental conclusion: The compounds of the present invention show excellent inhibitory effects.

Claims

1. A compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in, M1 is selected from N or CH; M2 is selected from N or CH; M3 is selected from N or CH; Ring A is selected from C 6-10 Aryl or 5-10 membered heteroaryl; Ring B is present or absent. When ring B is present, ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, benzene ring or 5-6 membered heteroaryl; R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; Preferably, R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; x is 0, 1, 2, 3, 4, or 5; y is 0, 1, 2, 3, 4, or 5; m1, m2, m3, m4, m5, m6, m8, m9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6; p1, p2, p3, p4, p5, p6, p8, p9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6; m7 and p7 are each independently selected from 0, 1, 2 or 3.

2. A compound represented by formula (IX), a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in, M1 is selected from N or CH; M2 is selected from N or CH; M3 is selected from N or CH; L1 is selected from O, S, CH2 or NH, wherein CH2 and NH can be further substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; Ring B is present or absent. When ring B is present, ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, benzene ring or 5-6 membered heteroaryl; R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; x is 0, 1, 2, 3, 4, or 5; y is 0, 1, 2, 3, 4, or 5; m1, m2, m3, m4, m5, m6, m8, m9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6; p1, p2, p3, p4, p5, p6, p8, p9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6; m7 and p7 are each independently selected from 0, 1, 2 or 3.

3. A compound represented by formula (X), a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in: L2 is selected from a bond, -O-, -NH-, -CO-, -CONH-, C 1-3 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -OC 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-, -C 1-3 Alkylene -C(O)NH-, -C 1-3 Alkylene-NHC(O)-, -C 1-3 Alkylene-S(O) r4 -、-C 1-3 Alkylene-NHS(O) r5 -or-C 1-3 Alkylene-S(O) r6 NH-; the -NH-, -CONH-, C 1-3 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylidene, -OC 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-, -C 1-3 Alkylene -C(O)NH-, -C 1-3 Alkylene-NHC(O)-, -C 1-3 Alkylene-S(O) r4 -、-C 1-3 Alkylene-NHS(O) r5 -or-C 1-3 Alkylene-S(O) r6 NH- is optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more of aryl and 5-6 membered heteroaryl are substituted; Ring E is selected from C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, preferably 3-12 membered heterocyclic group; R 2-1-1 Each is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, =CF2, =CHF, =NOC 1-6 Alkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Heteroalkyl, C 1-6 Deuterated heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Heteroalkyl, C 1-6 Deuterated heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl and 5-10 membered heteroaryl groups are optionally further substituted with hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, carboxyl, oxo, thio, =CF2, =CHF, =NOC 1-6 Alkyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Heteroalkyl, C 1-6 Deuterated heteroalkyl, C 1-6 Halogenated heteroalkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted, R 2-1-1 Preferred are methyl, ethyl, methoxy, F, =CF2, -CHF2, -CH2F, -CF3, -CH2CHF2, -CHF2CH3, -CH2CF3, -CH2OCH3, -CH2OCD3, -CH2OCF3, -CH2Ocyclopropyl, -CH2SCF3, cyclopropyl, cyclobutyl, OCD3 or OCF3; j is 0, 1, 2, 3, 4, or 5; r4, r5, r6 are each independently selected from 0, 1 or 2; M1 is selected from N or CH; M2 is selected from N or CH; M3 is selected from N or CH; L1 is selected from O, S, CH2 or NH, wherein CH2 and NH can be further substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; Ring A is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; Ring B is present or absent. When ring B is present, ring B is selected from C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, benzene ring or 5-6 membered heteroaryl; R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 2-2 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 The aryl or 5-10 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Deuterated alkoxy, C 1-6 Haloalkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, C 6-10 One or more of aryl and 5-10 membered heteroaryl are substituted; x is 0, 1, 2, 3, 4, or 5; y is 0, 1, 2, 3, 4, or 5; m1, m2, m3, m4, m5, m6, m8, m9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6; p1, p2, p3, p4, p5, p6, p8, p9 are each independently selected from 0, 1, 2, 3, 4, 5 or 6; m7 and p7 are each independently selected from 0, 1, 2 or 3.

4. The compound according to any one of claims 1 to 3, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Ring A is selected from C 3-8 Cycloalkyl or 5-10 membered heteroaryl, preferably C 3-6 Cycloalkyl or 5-6 membered heteroaryl, more preferably cyclopropyl or 5 membered heteroaryl, further preferably cyclopropyl, Preferably, ring A is selected from 5-10 membered heteroaryl, preferably 5-6 membered heteroaryl, more preferably 5 membered heteroaryl, and further preferably and / or Ring B is absent; Alternatively, ring B is present, and ring B is selected from a benzene ring or a 5-6-membered heteroaryl group, preferably, ring B is selected from a pyridyl group; Preferably, Selected from 5. The compound according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is represented by formula (II-1), formula (II-2), formula (III-1), formula (III-2), formula (IV-1) or formula (IV-2): Preferably, the compound is as shown in formula (II-1-1), formula (II-2-1), formula (III-1-1), formula (III-2-1), formula (IV-1-1) or formula (IV-2-1): The compound represented by formula (III-2-1) is further represented by formula (III-2-1-1): Among them, R 4-1-1 are independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl or 3-6 membered heterocyclic group; u is 0, 1, 2, 3, 4, 5, or 6.

6. The compound according to any one of claims 1 to 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; Preferably, R1 is hydrogen, chlorine, fluorine, bromine, cyano, -CH2CF3, -CH2-cyclopropyl, -CH=CF2, -CH2CHF2; Further preferably, R1 is hydrogen, chlorine, fluorine, cyano, -CH2CF3, -CH2-cyclopropyl, -CH=CF2, -CH2CHF2; More preferably, R1 is hydrogen, cyano, -CH2CF3, -CH2-cyclopropyl, -CH=CF2, -CH2CHF2; and / or R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, carboxyl, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 aryl and 5-6 membered heteroaryl; preferably, R 2-1 and R 2-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, -(CH2) m1 OR a1 、-(CH2) m2 C(O)R a2 、-(CH2) m3 NHC(O)R a3 、-(CH2) m4 C(O)NHR a4 、-(CH2) m5 NR a5 R a6 、-(CH2) m6 S(O) m7 R a7 、-(CH2) m8 S(O)2NHR a8 、-(CH2) m9 NHS(O)2R a9 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; R a1 , R a2 , R a3 , R a4 , R a5 , R a6 , R a7 , R a8 and R a9 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; Preferably, R 2-1 Selected from -CH2-cyclopropyl, -CH2OCHF2, -CH2COOH, More preferably, R 2-1 Selected from -CH2-cyclopropyl, -CH2OCHF2; Preferably, R 2-2 Selected from hydrogen; and / or R 3-1 and R 3-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; Preferably, R 3-1 are independently hydrogen; Preferably, R 3-2 are independently hydrogen or fluorine; and / or R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, -(CHR d10 ) p1 OR d1 、-(CHR d10 ) p2 C(O)R d2 、-(CHR d10 ) p3 NHC(O)R d3 、-(CHR d10 ) p4 C(O)NHR d4 、-(CHR d10 ) p5 NR d5 R d6 、-(CHR d10 ) p6 S(O) p7 R d7 、-(CHR d10 ) p8 S(O)2NHR d8 、-(CHR d10 ) p9 NHS(O)2R d9 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; Preferably, R 4-1 and R 4-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , R d7 , R d8 , R d9 and R d10 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; Preferably, R 4-1 Selected from More preferably, R 4-1 Selected from Preferably, R 4-1 Selected from More preferably, R 4-1 Selected from More preferably, R 4-1 Selected from More preferably, R 4-1 Selected from More preferably, R 4-2 Selected from hydrogen; and / or R5 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; Preferably, R5 is selected from hydrogen, methyl, ethyl or isopropyl; More preferably, R5 is selected from hydrogen, methyl or isopropyl; and / or R 6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 Aryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 The aryl or 5-6 membered heteroaryl group may be further optionally substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, oxo, thio, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Deuterated alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-10 One or more substitutions of aryl and 5-6 membered heteroaryl; Preferably, R 6-1 are independently selected from hydrogen or methyl; Preferably, R 6-2 Independently selected from and / or Ring E is C 3-6 Cycloalkyl or Wherein, ring E' is selected from 3-12 membered heterocyclic groups, preferably 3-8 membered monocyclic heterocyclic groups, 3-8 membered fused ring heterocyclic groups, 3-8 membered bridged ring heterocyclic groups or 3-8 membered spiro heterocyclic groups, more preferably 3-8 membered monocyclic heterocyclic groups, 3-8 membered fused ring heterocyclic groups or 3-8 membered spiro heterocyclic groups, more preferably 5-9 membered heterocyclic groups, more preferably 5-6 membered heterocyclic groups; preferably, ring E' is selected from and / or L2 is CH2.

7. The compound according to any one of claims 1 to 6, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is shown below:

8. A compound represented by the general formula (INT), its stereoisomer or a pharmaceutically acceptable salt thereof in, R7 is selected from hydrogen or an amino protecting group, preferably H or Boc; Ring B, Ring E, R1, R 2-1-1 , R 2-2 , R 3-1 , R 3-2 , R 4-1 , R 4-2 , L2, M1, M2, M3, z and j are defined as described in claim 3.

9. The compound according to claim 8, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound is selected from 10. A method for preparing a compound represented by general formula (X), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, comprising reacting a compound represented by formula (INT-1) and a compound represented by formula (INT) to obtain a compound represented by formula (X) in, R8 is selected from halogen or OH; Preferably, the reaction is carried out in the presence of a base and a catalyst, the base is an organic base, and the catalyst is an amide condensation agent; Ring A, Ring B, Ring E, R1, R 2-1-1 , R 2-2 , R 3-1 , R 3-2 , R 4-1 , R 4-2 , R5, L1, L2, M1, M2, M3, y, z and j are defined as described in claim 3.

11. A pharmaceutical composition comprising a therapeutically effective dose of the compound according to any one of claims 1 to 7, its stereoisomers or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

12. Use of the compound according to any one of claims 1 to 7, its stereoisomer or pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 11 in the preparation of an IL-17 inhibitor drug.

13. Use of the compound according to any one of claims 1 to 7, its stereoisomer or pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 11 in the preparation of a medicament for treating an autoimmune disease; wherein the autoimmune disease is preferably selected from psoriasis, plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, suppurative hidradenitis, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis and non-infectious uveitis.

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