KRAS G12D inhibitor and application thereof

Abstract

The invention relates to a KRAS G12D inhibitor and application thereof. In particular, the present invention relates to a KRAS G12D inhibitor having a structure represented by formula (I), a preparation method thereof, a pharmaceutical composition containing the KRAS G12D inhibitor, a use of the KRAS G12D inhibitor as the KRAS G12D inhibitor, and a use of the KRAS G12D inhibitor in treatment and / or prevention of KRAS G12D-related cancers or tumors. Wherein each substituent in the formula (I) is as defined in the specification. # imgabs0 #

Description

A KRAS G12D inhibitor and its application Technical Field

[0001] The present invention belongs to the field of drug synthesis, and in particular relates to a KRAS inhibitor, a preparation thereof, and a pharmaceutical application thereof. Background Art

[0002] The RAS gene family, comprising HRAS, KRAS, and NRAS, is a family of oncogenes that are frequently mutated in cancer. Mutated RAS proteins are found in 20-30% of human tumors. Activated RAS proteins contribute to the malignant phenotypes of cancer cells, including dysregulated cell growth and programmed cell death, increased invasiveness, and neoangiogenesis. However, the development of drugs targeting RAS proteins has been slow due to their high affinity for GTP / GDP and the lack of a well-defined binding pocket.

[0003] Under normal circumstances, RAS proteins function as molecular switches, alternating between an inactive, GDP-bound state and an activated, GTP-bound state. Following stimulation by exogenous growth factors, guanine nucleotide exchange factors (GEFs) facilitate the conversion of RAS proteins from the inactive, GDP-bound form to the activated, GTP-bound form, enabling them to bind and activate downstream signaling pathways. Subsequently, RAS reverts to its inactive, GDP-bound form, aided by its intrinsic GTPase activity and the assistance of GTPase activating / accelerating proteins (GAPs).

[0004] Missense mutations at codons 12, 13, or 61 lead to abnormal activation of RAS. These mutations prolong the time that the RAS protein remains in the GTP-bound state, leading to persistent activation of downstream signaling pathways. K-RAS is the most common mutation subtype in the RAS family in human cancers, including pancreatic cancer (71%), small intestine cancer (35%), colon cancer (35%), biliary tract cancer (26%), endometrial cancer (17%), and lung cancer (19%). In terms of mutation sites, G12D / G12V / G12C / G13D is the most common mutation type of K-RAS in pancreatic cancer, lung cancer, and colorectal cancer.

[0005] The development of KRAS inhibitors is challenging due to the protein's lack of a distinct pocket. Recent studies have revealed a previously undiscovered pocket in the GDP-bound state of KRAS. Based on these new findings, covalently bound inhibitors targeting the cysteine ​​mutated at codon 12 have become a hot topic in the development of KRAS inhibitors and have made some progress. However, in addition to the G12C mutation, targeting other activating mutations of KRAS remains an urgent task, particularly the KRAS G12D mutation. Therefore, it is necessary to develop safe and effective KRAS G12D inhibitors for the treatment of KRAS-G12D-mediated cancers.

[0006] Summary of the Invention

[0007] The present invention aims to provide a KRAS G12D inhibitor and its use. The compounds of the present invention have a strong inhibitory effect on KRAS G12D and can be widely used to prepare drugs for treating and / or preventing KRAS G12D-related cancers or tumors, thus potentially leading to the development of a new generation of KRAS G12D inhibitors.

[0008] The first aspect of the present invention provides a compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

[0009] Wherein, X is CR9 or N;

[0010] Ring A is C 6-10 Aryl or 5-10 membered heteroaryl, preferably, the C 6-10 aryl or 5-10 membered heteroaryl is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, indole, benzothiophene, benzimidazole, benzopyrazole, benzoxazole and benzothiazole;

[0011] R1 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 ;

[0012] R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 ;

[0013] R3 is selected from hydrogen, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, -C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0014] R4 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0015] R 5a Selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 2-10 Alkenyl, C2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-S(O) r NR 16 R 17 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C0-8 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0016] R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-S(O) r NR 16 R 17 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted with a substituent, provided that R 5a 、R 5b and R 5c Not simultaneously hydrogen;

[0017] Or, R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-10 Cycloalkyl or 3-10 membered heterocyclic group, each of which is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Substituents, R 5a The definitions are as above;

[0018] Or, R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5a The definitions are as above;

[0019] Or, R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached,

[0020] R 5d 、R 5e and R 5f are independently selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-8 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 substituted by aryl and 5-10 membered heteroaryl substituents;

[0021] Each R6 and R7 are independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkylene, halogen substituted C 1-10 Alkylene, deuterium substituted C 1-10 Alkylene, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, halogen-substituted C 3-12 Cycloalkylene, deuterium substituted C 3-12 Cycloalkylene, 3-12 membered heterocyclic group, C 3-12 Heterocycloalkylene, halogen-substituted C 3-12 Heterocycloalkylene, deuterium substituted C 3-12 Heterocycloalkylene, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 , provided that at least one of R6 or R7 is C 1-10 Alkylene, halogen substituted C 1-10 Alkylene, deuterium substituted C 1-10 Alkylene, C 1-10 Cycloalkylene, halogen-substituted C 1-10 Cycloalkylene, deuterium substituted C 1-10 Cycloalkylene, C 1-10 Heterocycloalkylene, halogen-substituted C 1-10 Heterocycloalkylene or deuterium substituted C 1-10 heterocycloalkylene;

[0022] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 , or, when p≥2, two adjacent R8 and their directly connected parts together form C 5-12 Cycloalkyl or 5-12 membered heterocyclic group, each of which is independently optionally further substituted by one or more groups selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0023] R9 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、 -C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 ;

[0024] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-10 Cycloalkyl or 3-10 membered heterocyclic group, the above C 3-10 Cycloalkyl or 3-10 membered heterocyclic groups are independently optionally further substituted with one or more radicals selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0025] Each R 10 are each independently selected from hydrogen, deuterium, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)R 15 and -C 0-8 Alkyl-C(O)NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0026] Each R 11 and R 12 are independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, or R 11 and R 12 Together with the sulfur atom directly connected thereto, a 3-10 membered heterocyclic group is formed, wherein each of the above groups is independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 13、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0027] Each R 13 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent;

[0028] Each R 14 independently selected from hydrogen, deuterium, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, each of which is independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent;

[0029] Each R 15 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent;

[0030] Each R 16 and R 17 are independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-10 Alkanoyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10 Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent;

[0031] Or, R 16 and R 17 Together with the nitrogen atom directly connected thereto, a 4-10 membered heterocyclic group or a 5-10 membered heteroaryl group is formed, wherein the 4-10 membered heterocyclic group or the 5-10 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, ═O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10 Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent;

[0032] m is 0, 1 or 2; n is 0, 1 or 2;

[0033] p is 0, 1, 2, 3, 4, 5 or 6; and

[0034] Each r is independently 0, 1 or 2.

[0035] As a preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, X is CR9 or N;

[0036] R1 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 ;

[0037] R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 ;

[0038] R3 is selected from hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -C 0-4 Alkyl-S(O) r R13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0039] R4 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0040] R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-S(O) r NR 16 R 17 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0041] R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-4 Alkyl-S(O) r R 13、-C 0-4 Alkyl-S(O) r NR 16 R 17 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted with a substituent, provided that R 5a 、R 5b and R 5c Not simultaneously hydrogen;

[0042] Or, R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituents, R 5a The definitions are as above;

[0043] Or, R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5a The definitions are as above;

[0044] Or, R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached,

[0045] R 5d 、R 5e and R 5f are independently selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl and 5-8 membered heteroaryl substituents;

[0046] Each R6 and R7 are independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkylene, halogen substituted C 1-4 Alkylene, deuterium substituted C 1-4 Alkylene, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkylene, halogen-substituted C 3-6 Cycloalkylene, deuterium substituted C 3-6 Cycloalkylene, 3-6 membered heterocyclic group, C 3-6 Heterocycloalkylene, halogen-substituted C 3-6 Heterocycloalkylene, deuterium substituted C 3-6 Heterocycloalkylene, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O)r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , provided that at least one of R6 or R7 is C 1-4 Alkylene, halogen substituted C 1-4 Alkylene, deuterium substituted C 1-4 Alkylene, C 3-6 Cycloalkylene, halogen-substituted C 3-6 Cycloalkylene, deuterium substituted C 3-6 Cycloalkylene, C 3-6 Heterocycloalkylene, halogen-substituted C 3-6 Heterocycloalkylene or deuterium substituted C 3-6 heterocycloalkylene;

[0047] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , or, when p≥2, two adjacent R8 and their directly connected parts together form C 5-10 Cycloalkyl or 5-10 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0048] R9 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 ;

[0049] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more radicals selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0050] Among them, R 10 、R 11 、R 12、R 13 、R 14 、R 15 、R 16 、R 17 and r are as defined for the compound of formula (I).

[0051] As a preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts, each R 10 are each independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)R 15 and -C 0-4 Alkyl-C(O)NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent;

[0052] Each R 11 and R 12 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl and 5-8 membered heteroaryl, or R 11 and R 12 Together with the sulfur atom directly connected thereto, a 3-6 membered heterocyclic group is formed, wherein each of the above groups is independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R15 substituted by a substituent;

[0053] Each R 13 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent;

[0054] Each R 14 independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl and 5-8 membered heteroaryl, each of which is independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent;

[0055] Each R 15 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent;

[0056] Each R 16 and R 17 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-4 Alkanoyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent;

[0057] Or, R 16 and R 17 Together with the nitrogen atom directly connected thereto, a 4-8 membered heterocyclic group or a 5-8 membered heteroaryl group is formed, wherein the 4-8 membered heterocyclic group or the 5-8 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent,

[0058] Each r is independently 0, 1 or 2.

[0059] As a preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R2 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ;

[0060] R3 is selected from hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-C(O)R 15 、-OC(O)R 15 、-NR 16 R 17 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0061] R4 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0062] Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r are as defined for the compound of formula (I).

[0063] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R2 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups;

[0064] R3 is selected from hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-C(O)R 15 、-OC(O)R 15 、-NR 16 R 17 、-C(O)NR 16 R 17and -N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by a cycloalkyl group or a 3-6 membered heterocyclic group;

[0065] R4 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, each of which is independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl, 5-8 membered heteroaryl, =O and =S;

[0066] Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r are as defined for the compound of formula (I).

[0067] As a preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIa) or (IIb):

[0068] wherein each X is independently CR9 or N;

[0069] Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole;

[0070] Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ;

[0071] Each R2 is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups;

[0072] Each R 5a are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0073] Each R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16)-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted with a substituent, provided that R 5a 、R 5b and R 5c Not simultaneously hydrogen;

[0074] Or, R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituents, R 5a The definitions are as above;

[0075] Or, R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5a The definitions are as above;

[0076] Or, R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached,

[0077] Each R 5d and R 5e are independently selected from hydrogen, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 aryl and 5-8 membered heteroaryl substituents, provided that R 5d and R 5e Not simultaneously hydrogen;

[0078] Each R 5f are independently selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl and 5-8 membered heteroaryl substituents;

[0079] In the compound of formula (IIb), R 6a and R 6b are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 Alkyl, or R 6a and R 6b Together with the carbon atom to which it is directly attached, it forms a C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 Cycloalkyl or 3-6 membered heterocyclyl are independently optionally further substituted with one or more substituents selected from deuterium or halogen;

[0080] Each R 7a and R 7b are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0081] Or, R 7a and R 7b Together with the carbon atom to which it is directly attached, it forms a C3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 The cycloalkyl or 3-6 membered heterocyclyl is independently optionally further substituted with one or more substituents which are deuterium or halogen;

[0082] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , or, when p≥2, two adjacent R8 and their directly connected parts together form C 5-6 Cycloalkyl or 5-6 membered heterocyclic group, each of which is independently optionally further substituted by one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0083] Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ;

[0084] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、 -N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0085] Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 , p and r are as defined for the compound of formula (I).

[0086] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl;

[0087] Or, R 7a and R 7b Together with the carbon atom to which it is directly attached, it forms a C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 The cycloalkyl or 3-6 membered heterocyclyl groups are independently optionally further substituted with one or more substituents selected from deuterium, fluorine, chlorine and bromine.

[0088] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, in the compound of formula (IIb), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl, or, R 6a and R 6b Together with the carbon atom to which it is directly attached, it forms a C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 The cycloalkyl or 3-6 membered heterocyclyl groups are independently optionally further substituted with one or more substituents selected from deuterium, fluorine, chlorine and bromine.

[0089] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, X is CR9 or N;

[0090] R1 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17;

[0091] R9 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 ;

[0092] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0093] Among them, R 14 、R 16 and R 17 As defined for the compounds of formula (I).

[0094] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, X is CR9 or N;

[0095] R is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, azirane, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, trideuteriomethoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino, and amino;

[0096] R is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, aziridine, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino, and amino;

[0097] Alternatively, R9 and R1 together with the portion to which they are directly attached form an oxetane group, which is optionally further substituted with one or more substituents selected from the group consisting of deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, azirane, oxetanyl, azetidinyl, =O, =S, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino.

[0098] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16)-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0099] Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r are as defined for the compound of formula (I).

[0100] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0101] Among them, R 14 、R 16 and R 17 As defined for the compounds of formula (I).

[0102] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R8 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, aziridine, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino, and each of the above groups is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, aziridine, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino. and optionally further substituted with one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, cyano, hydroxy, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, azirane, oxetanyl, azetidinyl, =0, =S, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino, and amino.

[0103] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a Selected from deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0104] R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O)r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0105] Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r are as defined for the compound of formula (I).

[0106] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a Selected from deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -C(O)NR 16 R 17 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by cycloalkyl, 3-6 membered heterocyclyl, =O and =S;

[0107] R 5b and R 5c are each independently hydrogen, deuterium, halogen or C 1-4Alkyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, =O, =S and -OR 14 substituted by a substituent;

[0108] Among them, R 14 、R 16 and R 17 As defined for the compounds of formula (I).

[0109] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0110] R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0111] Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r are as defined for the compound of formula (I).

[0112] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl and -OR 14 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, =O, =S and -OR14 substituted by a substituent;

[0113] R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 Substituents of

[0114] Among them, R 14 、R 16 and R 17 As defined for the compounds of formula (I).

[0115] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent;

[0116] R 5b and R 5c Together with the carbon atom to which it is directly attached,

[0117] R 5d and R 5e are independently selected from hydrogen, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 aryl and 5-8 membered heteroaryl substituents, provided that R 5d and R 5e Not simultaneously hydrogen;

[0118] Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r are as defined for the compound of formula (I).

[0119] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a Selected from hydrogen, deuterium, halogen and C 1-4 Alkyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, =O, =S and -OR 14 substituted by a substituent;

[0120] R 5b and R 5c Together with the carbon atom to which it is directly attached,

[0121] R 5d and R 5e are independently selected from hydrogen, halogen, cyano, C 1-4Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 aryl and 5-8 membered heteroaryl substituents, provided that R 5d and R 5e Not simultaneously hydrogen;

[0122] Among them, R 14 、R 16 and R 17 As defined for the compounds of formula (I).

[0123] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached,

[0124] R 5f Selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl and 5-8 membered heteroaryl substituents;

[0125] Among them, R 16 and R 17 As defined for the compounds of formula (I).

[0126] As a preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIIa1) or compound of formula (IIIb1):

[0127] wherein each X is independently CR9 or N;

[0128] Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole;

[0129] Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0130] Each each independently selected from deuterium-substituted methyl, ethyl, isopropyl, methoxymethyl, cyclopropyloxymethyl and 1-hydroxy-1-methyl-ethyl, wherein the ethyl, isopropyl, methoxymethyl, cyclopropyloxymethyl or 1-hydroxy-1-methyl-ethyl is each independently optionally further substituted with one or more deuteriums;

[0131] In the compound of formula (IIIb1), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0132] Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0133] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0134] Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0135] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0136] Among them, R 14 、R 16 、R 17 and p are as defined for the compound of formula (I).

[0137] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each Each is independently selected from deuterium-substituted methyl, ethyl, isopropyl, cyclopropyloxymethyl and 1-hydroxy-1-methyl-ethyl, and the ethyl, isopropyl, cyclopropyloxymethyl or 1-hydroxy-1-methyl-ethyl is each independently further substituted by at least 1, 2, 3, 4, 5, 6 or 7 deuterium.

[0138] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each Each independently selected from -CH2D, -CHD2, -CD3,

[0139] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each Each independently selected from -CH2D, -CHD2, -CD3,

[0140] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each are each independently ethyl or isopropyl.

[0141] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each are each independently a methoxymethyl group, which is optionally further substituted with one or more deuterium groups; provided that the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are not the following compounds:

[0142] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each Each is independently a methoxymethyl group, which is optionally further substituted with at least 1, 2, 3, 4 or 5 deuterium groups.

[0143] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each Each independently selected from

[0144] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each Each independently

[0145] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each X is independently CR9 or N;

[0146] Each R1 is independently selected from methoxy, ethoxy, isopropoxy, cyclopropyloxy, trideuteriomethoxy, monomethylamino, dimethylamino and amino;

[0147] Each R9 is independently selected from hydrogen, fluorine, chlorine, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

[0148] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each X is independently CR9, and R9 and R1 together with the part directly connected thereto form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0149] Among them, R 14 、R 16 and R 17 As defined for the compounds of formula (I).

[0150] As a preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIIa2) or compound of formula (IIIb2):

[0151] wherein each X is independently CR9 or N;

[0152] Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole;

[0153] Each ring B is independently selected from oxetanyl, oxolanyl and oxhexyl;

[0154] Each R a are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 ;

[0155] Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0156] In the compound of formula (IIIb2), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0157] Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0158] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0159] Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0160] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0161] q is 0, 1, 2, or 3;

[0162] Among them, R 14 、R 16 、R 17 and p are as defined for the compound of formula (I).

[0163] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each ring B is independently oxetane or oxhexyl;

[0164] Each R a Each is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

[0165] As a preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIIa3) or (IIIb3):

[0166] wherein each X is independently CR9 or N;

[0167] Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole;

[0168] Each ring C is independently selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;

[0169] Each R b are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 ;

[0170] Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0171] In the compound of formula (IIIb3), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0172] Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0173] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0174] Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0175] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0176] q is 0, 1, 2, or 3;

[0177] Among them, R 14 、R 16 、R 17 and p are as defined for the compound of formula (I).

[0178] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each ring C is independently a cyclopropyl group;

[0179] Each R b Each is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

[0180] As a preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIIa4) or formula (IIIb4):

[0181] wherein each X is independently CR9 or N;

[0182] Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole;

[0183] Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0184] R 5a is selected from hydrogen, fluorine and methyl;

[0185] R 5d is selected from hydrogen, fluorine and methyl;

[0186] R 5e is selected from hydrogen, fluorine and methyl;

[0187] In the compound of formula (IIIb4), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0188] Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0189] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0190] Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0191] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0192] Among them, R 14 、R 16 、R 17 and p are as defined for the compound of formula (I).

[0193] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5a is hydrogen; R 5d is fluorine; R 5e is hydrogen or fluorine.

[0194] As a preferred embodiment, among the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, the compound of formula (I) is the following compound of formula (IIIa5) or (IIIb5):

[0195] wherein each X is independently CR9 or N;

[0196] Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole;

[0197] Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ;

[0198] R 5f is selected from hydrogen, fluorine and methyl;

[0199] In the compound of formula (IIIb5), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0200] Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl;

[0201] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0202] Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14and -NR 16 R 17 ;

[0203] Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent;

[0204] Among them, R 14 、R 16 、R 17 and p are as defined for the compound of formula (I).

[0205] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 5f It is a methyl group.

[0206] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each X is independently CR9 or N;

[0207] Each R1 is independently selected from hydrogen, halogen, -OR 14 and -NR 16 R 17 ;

[0208] Each R9 is independently selected from hydrogen, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl and deuterium substituted C 1-4 alkyl;

[0209] Alternatively, R9 and R1 together with the part to which they are directly attached form a 3-8 membered heterocyclic group containing N or O;

[0210] Among them, R 14 、R 16 and R 17 As defined for the compounds of formula (I).

[0211] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each X is independently CR9 or N;

[0212] Each R1 is independently selected from hydrogen, fluorine, chlorine, hydroxy, methoxy, ethoxy, isopropoxy, cyclopropyloxy, trideuteriomethoxy, monomethylamino, dimethylamino and amino;

[0213] Each R9 is independently selected from hydrogen, fluorine, chlorine, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl;

[0214] Alternatively, R9 and R1 together with the moiety to which they are directly attached form an oxacyclohexyl group.

[0215] As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, is characterized in that each ring A is independently selected from phenyl, naphthyl, pyridyl, pyrimidinyl, benzothiophene and benzothiazole;

[0216] Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -OR 14 and -NH2, each of the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NH2 substituents;

[0217] Among them, R 14 As defined for the compounds of formula (I).

[0218] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each Each is independently selected from the following structures:

[0219] Each R 8a 、R 8b 、R 8c and R 8dEach of the above groups is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxy, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, aziridine, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino, each of the above groups is independently selected from deuterium, fluorine, The alkylene group may be substituted with chloro, bromo, cyano, hydroxy, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, azirane, oxetanyl, azetidinyl, =0, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino substituents.

[0220] As a further preferred embodiment, the compound of formula (I), its stereoisomer or pharmaceutically acceptable salt thereof is characterized in that R 6a and R 6b Each is independently selected from hydrogen, deuterium, fluorine, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

[0221] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R 6a and R 6b are each independently hydrogen, deuterium or fluorine.

[0222] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R 7a and R 7b Each is independently selected from hydrogen, deuterium, fluorine, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

[0223] As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, each R 7a and R 7b are each independently hydrogen, deuterium or fluorine.

[0224] As the most preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof include but are not limited to the following compounds:

[0225] The second aspect of the present invention provides a method for preparing a compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, comprising the following steps:

[0226] The compound of formula (Ia) or its acid salt reacts with the compound of formula (Ib) or its acid salt to produce the compound of formula (I) or its acid salt; or

[0227] The compound of formula (Ic) or its acid salt reacts with the compound of formula (Id) or its acid salt to produce the compound of formula (I) or its acid salt; wherein X1 and X2 are each independently fluorine, chlorine or bromine, and X, R1, R2, R3, R4, R 5a 、R 5b 、 R 5c , R6, R7, R8, p, m and n are as defined for the compound of formula (I).

[0228] The third aspect of the present invention provides a pharmaceutical composition comprising a compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0229] The present invention also relates to the use of the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof in the preparation of drugs for treating and / or preventing cancers or tumors associated with KRAS G12D.

[0230] The present invention also relates to the use of the aforementioned compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof in the preparation of a method for preventing and / or treating sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, teratoma, bronchial cancer (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar carcinoma) cancer, bronchial adenoma, lymphoma, chondromatous hamartoma, mesothelioma, esophageal cancer (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), gastric cancer (lymphoma, leiomyosarcoma), pancreatic cancer (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestinal cancer (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyomas, hemangiomas, lipomas, neuroendocrine tumors). fibroma, fibroma), colorectal cancer (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); kidney cancer (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra cancer (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate cancer (adenocarcinoma, sarcoma), testicular cancer (seminoma, teratoma, embryonal carcinoma, teratothelioma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); liver cancer (hepatocellular carcinoma), bile duct cancer, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; gallbladder cancer, ampullary cancer, bile duct cancer; osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous group fibroblastoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondroma (osteocartilaginous exostosis), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; skull cancer (osteomas, hemangiomas, granulomas, xanthomas, osteitis deformans), meningeal cancer (meningioma, meningeal sarcoma, glioma), brain cancer (astrocytoma, medulloblastoma, glioma, ependymoma, blastoma (pinealoma), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors, spinal neurofibroma, meningioma, neuro Glioma, sarcoma); Uterine cancer (endometrial cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa theca cell tumor, Settley-Redig cell tumor, dysgerminoma, malignant teratoma; vulvar cancer (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma); vaginal cancer (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonic rhabdomyosarcoma)); fallopian tube (carcinoma); Hematological cancer (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndrome); Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma);Use in medicine for malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevus dysplasia, lipoma, hemangioma, dermatofibroma, keloid, psoriasis, adrenal tumor or neuroblastoma.

[0231] The present invention also relates to the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof for use as a medicament.

[0232] The present invention also relates to the use of the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof for treating and / or preventing cancers or tumors associated with KRAS G12D.

[0233] The present invention also relates to the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, for use in treating and / or preventing sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, teratoma associated with KRAS G12D; bronchial cancer (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar carcinoma) cancer, bronchial adenoma, lymphoma, chondromatous hamartoma, mesothelioma; esophageal cancer (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), gastric cancer (lymphoma, leiomyosarcoma), pancreatic cancer (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestinal cancer (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyomas, hemangiomas, lipomas, neuroendocrine tumors). fibroma, fibroma), colorectal cancer (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); kidney cancer (adenocarcinoma, Wilms' tumor (Nephroblastoma), lymphoma, leukemia), bladder and urethra cancer (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate cancer (adenocarcinoma, sarcoma), testicular cancer (seminoma, teratoma, embryonal carcinoma, teratothelioma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); liver cancer (hepatocellular carcinoma), bile duct cancer, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; gallbladder cancer, ampullary carcinoma, bile duct cancer; osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous tissue Cell tumor, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondroma (osteocartilaginous exostosis), benign enchondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; skull cancer (osteomas, hemangiomas, granulomas, xanthomas, osteitis deformans), meningeal cancer (meningioma, meningiosarcoma, glioma), brain cancer (astrocytoma, medulloblastoma, glioma, ependymoma, blastoma (pinealoma), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors, spinal neurofibroma, meningioma, glioma Cancers of the uterus (endometrial cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa theca cell tumor, Settley-Redig cell tumor, dysgerminoma, malignant teratoma), vulvar cancer (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vaginal cancer (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma)), fallopian tube (carcinoma); blood cancers (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma);malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus, lipoma, hemangioma, dermatofibroma, keloid, psoriasis, adrenal tumor or neuroblastoma.

[0234] The present invention also relates to a method for treating and / or preventing cancer or tumor associated with KRAS G12D, comprising administering a therapeutically effective amount of the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof to a patient in need thereof.

[0235] The present invention also relates to a method for treating and / or preventing sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, teratoma associated with KRAS G12D; bronchial cancer (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) cancer, bronchial adenoma, lymphoma, chondromatous hamartoma, mesothelioma; esophageal cancer (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), gastric cancer (lymphoma, leiomyosarcoma), pancreatic cancer (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestinal cancer (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyomas, hemangiomas, lipomas, neuroendocrine tumors). fibroma, fibroma), colorectal cancer (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); kidney cancer (adenocarcinoma, Wilms' tumor (Nephroblastoma), lymphoma, leukemia), bladder and urethra cancer (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate cancer (adenocarcinoma, sarcoma), testicular cancer (seminoma, teratoma, embryonal carcinoma, teratothelioma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); liver cancer (hepatocellular carcinoma), bile duct cancer, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; gallbladder cancer, ampullary carcinoma, bile duct cancer; osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous tissue Cell tumor, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondroma (osteocartilaginous exostosis), benign enchondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; skull cancer (osteomas, hemangiomas, granulomas, xanthomas, osteitis deformans), meningeal cancer (meningioma, meningiosarcoma, glioma), brain cancer (astrocytoma, medulloblastoma, glioma, ependymoma, blastoma (pinealoma), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors, spinal neurofibroma, meningioma, glioma Cancers of the uterus (endometrial cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa theca cell tumor, Settley-Redig cell tumor, dysgerminoma, malignant teratoma), vulvar cancer (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vaginal cancer (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma)), fallopian tube (carcinoma); blood cancers (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma);A method for treating malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevus dysplasia, lipoma, hemangioma, dermatofibroma, keloid, psoriasis, adrenal tumor or neuroblastoma, comprising administering a therapeutically effective amount of the compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof to a patient in need thereof. DETAILED DESCRIPTION

[0236] After extensive and in-depth research, the inventors of this application have developed, for the first time, a KRAS G12D inhibitor having the structure of Formula (I) below. This series of compounds can be widely used in the preparation of drugs for treating and / or preventing KRAS G12D-related cancers or tumors, and is expected to be developed into a new generation of KRAS G12D inhibitors. This has led to the completion of the present invention.

[0237] Detailed Description: Unless otherwise stated or specifically indicated, the following terms used in the specification and claims have the following meanings.

[0238] "Alkyl" refers to a straight chain or branched saturated aliphatic hydrocarbon group, preferably a straight chain alkyl group and a branched alkyl group having 1 to 10, 1 to 6 or 1 to 4 carbon atoms, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2- Dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl , 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl or various branched chain isomers thereof. “C 1-10 "Alkyl" refers to a straight chain alkyl group or a branched chain alkyl group containing 1 to 10 carbon atoms. 1-4 "Alkyl" refers to straight chain alkyl and branched chain alkyl groups including 1 to 4 carbon atoms. 1-3 "Alkyl" refers to straight chain alkyl and branched chain alkyl groups containing 1 to 3 carbon atoms, "C 0-8"Alkyl" refers to straight chain alkyl and branched chain alkyl groups including 0 to 8 carbon atoms, "C 0-4 The term "alkyl" refers to straight-chain and branched-chain alkyl groups having 0 to 4 carbon atoms.

[0239] Alkyl groups may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0240] "Alkylene" refers to a group of the formula "=R", where "R" is an "alkyl" as defined above with two hydrogen atoms removed. Preferably, it includes a straight-chain alkyl group of 1 to 10, 1 to 6, or 1 to 4 carbon atoms and a branched alkyl group with two hydrogen atoms removed, including but not limited to methylene (=CH2), ethylene (=CHCH3), hexylene (=CH(CH2)4CH3), etc. For example, in the following compound: The arrow indicates the methylene group.

[0241] Alkylene may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0242] "Cycloalkyl" or "carbocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent. The partially unsaturated cyclic hydrocarbon refers to a cyclic hydrocarbon that may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system. Cycloalkyl is divided into monocyclic cycloalkyl and polycyclic cycloalkyl, preferably a cycloalkyl containing 3 to 12, 3 to 8 or 3 to 6 carbon atoms, for example, "C 3-12 "Cycloalkyl" refers to a cycloalkyl group comprising 3 to 12 carbon atoms, "C 3-10 "Cycloalkyl" refers to a cycloalkyl group comprising 3 to 10 carbon atoms, "C 3-8 "Cycloalkyl" refers to a cycloalkyl group comprising 3 to 8 carbon atoms, "C 3-6 "Cycloalkyl" refers to a cycloalkyl group comprising 3 to 6 carbon atoms, wherein:

[0243] Monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like.

[0244] Polycyclic cycloalkyl groups include spiro, fused, and bridged cycloalkyl groups. "Spiroalkyl" refers to a polycyclic group in which the rings share a carbon atom (called a spiro atom). These may contain one or more (preferably 1, 2, or 3) double bonds, but no ring has a completely conjugated π electron system. Spiroalkyl groups are classified as monospiroalkyl, bispiroalkyl, or polyspiroalkyl groups based on the number of spiro atoms shared between the rings. Spiroalkyl groups include, but are not limited to:

[0245] "Fused cycloalkyl" refers to an all-carbon polycyclic group in which each ring shares a pair of adjacent carbon atoms with other rings in the system, wherein one or more rings may contain one or more (preferably 1, 2, or 3) double bonds, but no ring has a completely conjugated π electron system. Depending on the number of constituent rings, fused cycloalkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Fused cycloalkyl groups include, but are not limited to:

[0246] "Bridged cycloalkyl" refers to an all-carbon polycyclic group in which any two rings share two carbon atoms that are not directly connected. These may contain one or more (preferably 1, 2, or 3) double bonds, but no ring has a completely conjugated π electron system. Depending on the number of constituent rings, bridged cycloalkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Bridged cycloalkyl groups include, but are not limited to:

[0247] The cycloalkyl ring may be fused to an aryl, heteroaryl or heterocycloalkyl ring, wherein the ring connected to the parent structure is a cycloalkyl, including but not limited to indanyl, tetrahydronaphthyl, benzocycloheptanyl and the like.

[0248] Cycloalkyl may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0249] "Cycloalkylene" refers to a group of the formula "=R a " group, wherein "R a " is a group after removing two hydrogen atoms from a "cycloalkyl" as defined above. Preferably, it includes a group after removing two hydrogen atoms from a cycloalkyl of 3 to 12, 3 to 8, or 3 to 6 carbon atoms, including but not limited to cyclopropylene Cyclobutylene Cyclopentylene etc. For example, in the following compound: The arrow indicates the cyclopropylene group.

[0250] Cycloalkylene may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0251] "Heterocyclyl" or "heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent, wherein the partially unsaturated cyclic hydrocarbon refers to a cyclic hydrocarbon that may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system, and one or more (preferably 1, 2, 3 or 4) ring atoms in the heterocyclyl are selected from N, O, N·O or S(O) r(wherein r is an integer of 0, 1, or 2), but excluding the ring portion of -OO-, -OS-, or -SS-, the remaining ring atoms are carbon. Preferably, the heterocyclyl group comprises 3 to 12, 3 to 10, 3 to 8, or 3 to 6 ring atoms, for example, "3-6 membered heterocyclyl" refers to a heterocyclyl group comprising 3 to 6 ring atoms, "3-8 membered heterocyclyl" refers to a heterocyclyl group comprising 3 to 8 ring atoms, "3-10 membered heterocyclyl" refers to a heterocyclyl group comprising 3 to 10 ring atoms, "4-8 membered heterocyclyl" refers to a heterocyclyl group comprising 4 to 8 ring atoms, "4-10 membered heterocyclyl" refers to a heterocyclyl group comprising 4 to 10 ring atoms, "5-8 membered heterocyclyl" refers to a heterocyclyl group comprising 5 to 8 ring atoms, and "3-12 membered heterocyclyl" refers to a heterocyclyl group comprising 3 to 12 ring atoms.

[0252] Monocyclic heterocyclyl groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, oxetanyl, tetrahydrofuranyl, and the like.

[0253] Polycyclic heterocyclic groups include spiro, fused and bridged heterocyclic groups. "Spiro heterocyclic group" refers to a polycyclic heterocyclic group in which the single rings share an atom (called a spiro atom), wherein one or more (preferably 1, 2, 3 or 4) ring atoms are selected from N, O, N·O or S(O). r (where r is an integer 0, 1, or 2) with the remaining ring atoms being carbon. These may contain one or more double bonds (preferably 1, 2, or 3), but no ring has a completely conjugated π electron system. Spiro heterocyclic groups are classified as monospiro heterocyclic groups, dispiro heterocyclic groups, or polyspiro heterocyclic groups based on the number of spiro atoms shared between the rings. Spiro heterocyclic groups include, but are not limited to:

[0254] "Fused heterocyclyl" refers to a polycyclic heterocyclic group in which each ring in the system shares a pair of adjacent atoms with the other rings in the system, one or more (preferably 1, 2, 3 or 4) rings may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system, wherein one or more (preferably 1, 2, 3 or 4) ring atoms are selected from N, O, N·O or S(O) r (where r is an integer of 0, 1, or 2) and the remaining ring atoms are carbon. Depending on the number of rings, fused heterocyclic alkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Fused heterocyclic groups include, but are not limited to:

[0255] "Bridged heterocyclic group" refers to a polycyclic heterocyclic group in which any two rings share two atoms that are not directly connected, these may contain one or more (preferably 1, 2 or 3) double bonds, but no ring has a completely conjugated π electron system, wherein one or more (preferably 1, 2, 3 or 4) ring atoms are selected from N, O, N atoms or S(O)r (where r is an integer of 0, 1, or 2) and the remaining ring atoms are carbon. Depending on the number of rings, bridged heterocyclic groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Bridged heterocyclic groups include, but are not limited to:

[0256] The heterocyclyl ring may be fused to an aryl, heteroaryl or cycloalkyl ring, wherein the ring connected to the parent structure is a heterocyclyl, including but not limited to:

[0257] The heterocyclic group may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0258] "Heterocycloalkylene" refers to a group of the formula "=R b " group, wherein "R b " is a group after removing two hydrogen atoms from a "heterocycloalkyl" as defined above. Preferably, it includes a group after removing two hydrogen atoms from a heterocycloalkyl of 3 to 12, 3 to 8, or 3 to 6 carbon atoms, including but not limited to oxyheterocyclopropyl Aziridinyl etc. For example, in the following compound:

[0259] The arrow indicates the box containing the oxacyclopropylidene group.

[0260] Heterocycloalkylene may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O)r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0261] "Aryl" or "aromatic ring" refers to an all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group, a polycyclic (i.e., rings with adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably an all-carbon aromatic group containing 6-10 or 6-8 carbon atoms, for example, "C 6-10 "Aryl" refers to an all-carbon aromatic group containing 6-10 carbon atoms, including but not limited to phenyl and naphthyl. 6-8 "Aryl" refers to an all-carbon aromatic group containing 6-8 carbon atoms. The aromatic ring may be fused to a heteroaryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is an aromatic ring, including but not limited to:

[0262] "Aryl" may be substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0263] "Heteroaryl" refers to a heteroaromatic system containing one or more (preferably 1, 2, 3 or 4) heteroatoms, including N, O, N series, and S(O)r (wherein r is an integer of 0, 1 or 2), preferably a heteroaromatic system containing 5-10, 5-8 or 5-6 ring atoms, for example, "5-8 membered heteroaryl" refers to a heteroaromatic system containing 5-8 ring atoms, and "5-10 membered heteroaryl" refers to a heteroaromatic system containing 5-10 ring atoms, including but not limited to furanyl, thienyl, pyridyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, imidazolyl, tetrazolyl, etc. The heteroaryl ring can be fused to an aryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaryl ring, including but not limited to:

[0264] "Heteroaryl" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0265] "Alkenyl" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon double bond, preferably a straight or branched alkenyl group containing 2-10 or 2-4 carbon atoms, for example, "C 2-10 "Alkenyl" refers to a straight or branched chain alkenyl containing 2 to 10 carbon atoms. 2-4 "Alkenyl" refers to a straight or branched chain alkenyl group containing 2 to 4 carbon atoms, including but not limited to ethenyl, 1-propenyl, 2-propenyl, 1-, 2- or 3-butenyl, etc.

[0266] "Alkenyl" may be substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0267] "Alkynyl" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon triple bond, preferably a straight or branched chain alkynyl group containing 2-10 or 2-4 carbon atoms, for example, "C 2-10 "Alkynyl" refers to a straight or branched chain alkynyl containing 2 to 10 carbon atoms. 2-4 "Alkynyl" refers to a straight or branched chain alkynyl containing 2-4 carbon atoms, including but not limited to ethynyl, 1-propynyl, 2-propynyl, 1-, 2- or 3-butynyl, etc.

[0268] "Alkynyl" may be substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0269] "Alkoxy" refers to an -O-alkyl group, wherein alkyl is as defined above, for example, "C 1-10 "Alkoxy" refers to an alkyloxy group containing 1 to 10 carbon atoms. 1-4"Alkoxy" refers to an alkyloxy group containing 1 to 4 carbon atoms. 1-2 The term "alkoxy" refers to an alkyloxy group containing 1 to 2 carbon atoms, including but not limited to methoxy, ethoxy, propoxy, butoxy, etc.

[0270] "Alkoxy" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16)-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0271] "Cycloalkoxy" or "cycloalkyloxy" refers to an -O-cycloalkyl group, wherein cycloalkyl is as defined above, for example, "C 3-12 "Cycloalkyloxy" refers to a cycloalkyloxy group containing 3 to 12 carbon atoms. 3-6 The term "cycloalkyloxy" refers to cycloalkyloxy groups containing 3 to 6 carbon atoms, including but not limited to cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and the like.

[0272] "Cycloalkoxy" or "cycloalkyloxy" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0273] "Heterocyclyloxy" or "heterocyclyloxy" refers to an -O-heterocyclyl group wherein heterocyclyl is as defined above and includes, but is not limited to, azetidinyloxy, oxetanyloxy, azopentyloxy, nitrogen, oxhexyloxy, and the like.

[0274] "Heterocyclyloxy" or "heterocyclyloxy" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more (preferably 1, 2, 3 or 4) of the following groups independently selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O)r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent.

[0275] “C 1-10 "Alkanoyl" refers to C 1-10 The monovalent atomic group remaining after removing the hydroxyl group from the alkyl acid is usually expressed as "C 0-9 "C1 alkyl-C(O)-" refers to acetyl; "C2 alkyl-C(O)-" refers to propionyl; "C3 alkyl-C(O)-" refers to butyryl or isobutyryl.

[0276] "-C 0-8 Alkyl-S(O)(=NR 10 )R 11 " refers to -S(O)(=NR 10 )R 11 The sulfur atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0277] "-C 0-8 Alkyl-N=S(O)R 11 R 12" refers to -N=S(O)R 11 R 12 The nitrogen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0278] "-C 0-8 Alkyl-N=SR 11 R 12 " refers to -N = SR 11 R 12 The nitrogen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0279] "-C 0-8 Alkyl-OS(O)2R 13 ” refers to -OS(O)2R 13 The oxygen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0280] "-C 0-8 Alkyl-S(O) r R 13 ” refers to -S(O) r R 13 The sulfur atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0281] "-C 0-8 Alkyl-OR 14 " refers to -OR 14 The oxygen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0282] "-C 0-8 Alkyl-C(O)OR 14 " refers to -C(O)OR 14 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0283] "-C 0-8 Alkyl-C(O)SR 14 ” refers to -C(O)SR 14 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0284] "-C 0-8Alkyl-SC(O)R 15 ” refers to -SC(O)R 15 The sulfur atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0285] "-C 0-8 Alkyl-C(O)R 15 ” refers to -C(O)R 15 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0286] "-C 0-8 Alkyl-OC(O)R 15 ” refers to -OC(O)R 15 The oxygen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0287] "-C 0-8 Alkyl-P(O)(R 15 )2” refers to -P(O)(R 15 )2 in which the phosphorus atom is connected to the C 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0288] "-C 0-8 Alkyl-NR 16 R 17 ” refers to -NR 16 R 17 The nitrogen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0289] "-C 0-8 Alkyl-C(=NR 16 )R 15 " refers to -C(=NR 16 )R 15 The carbon atoms in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0290] "-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 ” refers to -N(R 16 )-C(=NR 17 )R 15 The nitrogen atom in the0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0291] "-C 0-8 Alkyl-C(O)NR 16 R 17 ” refers to -C(O)NR 16 R 17 The carbonyl group is connected to C 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0292] "-C 0-8 Alkyl-N(R 16 )-C(O)R 15 ” refers to -N(R 16 )-C(O)R 15 The nitrogen atom in the 0-8 On the alkyl group, where C 0-8 Alkyl is as defined above.

[0293] "Halogen-substituted C 1-10 The term "alkyl" refers to an alkyl group of 1 to 10 carbon atoms in which the hydrogen atoms on the alkyl group are optionally replaced by fluorine, chlorine, bromine or iodine atoms, including but not limited to difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl and tribromomethyl.

[0294] "Halogen-substituted C 1-10 "Alkoxy" refers to an alkoxy group of 1-10 carbon atoms in which the hydrogen atoms on the alkyl group are optionally replaced by fluorine, chlorine, bromine or iodine atoms. It includes but is not limited to difluoromethoxy, dichloromethoxy, dibromomethoxy, trifluoromethoxy, trichloromethoxy, tribromomethoxy and the like.

[0295] "Deuterium replaces C 1-10 "Alkyl" refers to an alkyl group of 1 to 10 carbon atoms in which the hydrogen atoms on the alkyl group are optionally replaced by deuterium atoms, including but not limited to monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, etc.

[0296] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[0297] "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, i.e., includes both substituted and unsubstituted instances. 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 both instances where the heterocyclic group is substituted with an alkyl group and where the heterocyclic group is not substituted with an alkyl group.

[0298] "Substituted" means that one or more "hydrogen atoms" in a group are independently replaced by a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, consistent with chemical valence theory, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without undue effort. For example, amino or hydroxy groups with free hydrogens may be unstable when combined with carbon atoms with unsaturated bonds (such as olefins).

[0299] "Stereoisomers," whose English name is stereoisomer, refer to isomers resulting from the different spatial arrangements of atoms in a molecule. They can be divided into two types: cis-trans isomers and enantiomers, or into two major categories: enantiomers and diastereomers. Stereoisomers caused by rotation about single bonds are called conformational stereoisomers, sometimes also called rotamers. Stereoisomers caused by bond length, bond angle, the presence of double bonds or rings in the molecule are called configurational stereoisomers, which are further divided into two categories. Among them, isomers caused by the inability to rotate freely around double bonds or single bonds of ring carbon atoms are called geometric isomers, also called cis-trans isomers, and are divided into two configurations: Z and E. For example, cis-2-butene and trans-2-butene are a pair of geometric isomers. Stereoisomers with different optical rotation properties due to the lack of anti-axial symmetry in the molecule are called optical isomers and are divided into R and S configurations. In this invention, "stereoisomers," unless otherwise specified, are understood to include one or more of the aforementioned enantiomers, configurational isomers, and conformational isomers.

[0300] "Pharmaceutically acceptable salt" in the present invention refers to pharmaceutically acceptable acid addition salts, including inorganic acid salts and organic acid salts, which can be prepared by methods known in the art.

[0301] A "pharmaceutical composition" refers to a mixture containing one or more compounds described herein, or their physiologically / pharmaceutically acceptable salts or prodrugs, together with other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitating absorption of the active ingredient and thereby exerting its biological activity.

[0302] The present invention will be further described in detail and completely below with reference to the embodiments, but the present invention is by no means limited thereto, and the present invention is not limited to the contents of the embodiments.

[0303] The structures of the compounds of the present invention are determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 / 500 NMR spectrometer, using deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3) as the solvents, with tetramethylsilane (TMS) as the internal standard.

[0304] Liquid chromatography-mass spectrometry (LC-MS) was performed using an Agilent 6120 mass spectrometer. HPLC was performed using an Agilent 1200DAD high-pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-pressure liquid chromatograph (Gimini C18 150×4.6 mm column).

[0305] 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.

[0306] The starting materials in the examples of the present invention are known and can be purchased commercially, or can be synthesized using or according to methods known in the art.

[0307] Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, with dry solvents and reaction temperatures expressed in degrees Celsius (°C).

[0308] 1. Preparation of intermediates

[0309] Intermediate 1-1: Preparation of (2,6-dimethyltetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol

[0310] Step 1: Synthesis of 1-(tert-butyl) 2-methyl (S)-4-methylenepyrrolidine-1,2-dicarboxylate

[0311] (S)-1-(tert-Butoxycarbonyl)-4-methylenepyrrolidine-2-carboxylic acid (24 g, 105.61 mmol) was dissolved in DMF (240 mL). K2CO3 (21.89 g, 158.41 mmol) was added at 0°C and stirred for 1 hour. CH3I (29.98 g, 211.21 mmol) was then added and the reaction was allowed to proceed at room temperature for 18 hours. After completion of the reaction, the mixture was diluted with ethyl acetate, the organic phase was separated, and washed once with saturated brine. The organic phase was dried and filtered, and the filtrate was concentrated. The resulting residue was separated by flash silica gel column chromatography [0-50% ethyl acetate:petroleum ether] to afford 1-(tert-butyl) 2-methyl (S)-4-methylenepyrrolidine-1,2-dicarboxylate (23.6 g, yield: 92.6%). ESI-MS: 242.3 [M+1] + .

[0312] Step 2: Synthesis of 1-(tert-butyl)2-methyl(R)-2-(2-(chloromethyl)allyl)-4-methylenepyrrolidine-1,2-dicarboxylate

[0313] Dissolve 1-(tert-butyl)-2-methyl(S)-4-methylenepyrrolidine-1,2-dicarboxylate (11.8 g, 48.9 mmol) in dry THF (150 mL). Add LiHMDS / THF (73.36 mL, 73.36 mmol, 1 M) at -78°C and react for 1 hour at -78°C. Slowly add dropwise a solution of 3-chloro-2-(chloromethyl)prop-1-ene (30.56 g, 244.52 mmol) in dry THF (100 mL). After addition, slowly warm the mixture to room temperature and react for 18 hours. After completion of the reaction, dilute with ethyl acetate, separate the organic phase, and wash once with saturated brine. The organic phase was dried, filtered, and concentrated. The residue was separated by silica gel column chromatography to give 1-(tert-butyl)-2-methyl (R)-2-(2-(chloromethyl)allyl)-4-methylenepyrrolidine-1,2-dicarboxylate (10.3 g, yield: 63.9%). ESI-MS: 330.4 [M+1] + .

[0314] Step 3: Synthesis of (R)-2-(2-(chloromethyl)allyl)-4-methylenepyrrolidine-2-carboxylic acid methyl ester

[0315] 1-(tert-Butyl)-2-methyl (R)-2-(2-(chloromethyl)allyl)-4-methylenepyrrolidine-1,2-dicarboxylate (20.7 g, 62.76 mmol) was dissolved in dry dichloromethane (100 mL). A hydrochloric acid / dioxane solution (50 mL, 200 mmol) was added at 0°C and allowed to react for 3 hours. LCMS confirmed the reaction was complete. After concentration, the product was obtained to give (R)-2-(2-(chloromethyl)allyl)-4-methylenepyrrolidine-2-carboxylic acid methyl ester (14.42 g, yield: 100%). ESI-MS: 230.3 [M+1] + .

[0316] Step 4: Synthesis of methyl 2,6-dimethyltetrahydro-1H-pyrrolizine-7a(5H)-carboxylate

[0317] Methyl (R)-2-(2-(chloromethyl)allyl)-4-methylenepyrrolidine-2-carboxylate (14.42 g, 62.78 mmol) was dissolved in acetonitrile (800 mL). NaHCO₃ (26.37 g, 313.89 mmol) and KI (1.04 g, 6.28 mmol) were added under an ice-water bath. The mixture was allowed to react at room temperature for 2 hours. After completion of the reaction, the mixture was diluted with ethyl acetate, the organic phase was separated, and washed once with saturated brine. The organic phase was dried and filtered, and the filtrate was concentrated. The resulting residue was separated by flash silica gel column chromatography [0-50% ethyl acetate:petroleum ether] to afford methyl 2,6-dimethylenetetrahydro-1H-pyrrolizine-7a(5H)-carboxylate (11.3 g, yield: 93.16%). ESI-MS: 194.4 [M+1] + .

[0318] Step 5: Synthesis of (2,6-dimethyltetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol

[0319] Methyl 2,6-dimethyltetrahydro-1H-pyrrolizine-7a(5H)-carboxylate (4 g, 20.70 mmol) was dissolved in dry tetrahydrofuran (80 mL) and lithium aluminum tetrahydride solution (16.60 ml, 41.40 mmol, 2.5 M in THF) was added at 0°C. The mixture was allowed to react at 0°C for 2 hours. After the reaction, 25 ml of water was added and the mixture was stirred for 30 minutes. 75 ml of 2N sodium hydroxide solution was added and the mixture was stirred for 30 minutes. 25 ml of water was added and the mixture was stirred for 1 hour. The mixture was diluted with dichloromethane, and the organic phase was separated and washed once with saturated brine. The organic phase was dried, filtered, and the filtrate was concentrated to give (2,6-dimethyltetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol (3.1 g, yield: 90.64%). ESI-MS: 166.12 [M+1] + .

[0320] Preparation of Intermediate 1-2: (S,Z)-(2-(Fluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol and Intermediate 1-3 (S,E)-(2-(Fluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol

[0321] Step 1: Synthesis of 1-(tert-butyl)2-methyl(S)-4-(difluoromethylene)pyrrolidine-1,2-dicarboxylate

[0322] 1-(tert-Butyl)-2-methyl(S)-4-oxopyrrolidine-1,2-dicarboxylate (40 g, 164 mmol) and CF2Br2 (75.9 g, 362 mmol) were dissolved in THF (800 mL). HMPT (133 mL, 723 mmol) was added dropwise to the mixture at -5°C. The reaction mixture was stirred at 25°C for 15 hours. The reaction mixture was extracted with water (1 L) and ethyl acetate (1 L x 3). The combined organic phases were dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was separated on a flash silica gel column to afford 1-(tert-butyl)-2-methyl(S)-4-(difluoromethylene)pyrrolidine-1,2-dicarboxylate (24 g, 86.6 mmol, yield: 52.6%).

[0323] 1 H NMR (400MHz, CDCl3) δ 4.57-4.29 (m, 1H), 4.16-3.94 (m, 2H), 3.67 (s, 3H), 3.05-2.76 (m, 1H), 2.59 (br d, J = 16.4Hz, 1H), 1.44-1.33 (m, 9H).

[0324] Step 2: Synthesis of 1-(tert-butyl)2-methyl-2-(3-chloropropyl)-4-(difluoromethylene)pyrrolidine-1,2-dicarboxylate

[0325] 1-(tert-Butyl)-2-methyl(S)-4-(difluoromethylene)pyrrolidine-1,2-dicarboxylate (28 g, 100 mmol) was dissolved in THF (400 mL). LiHMDS (1 M solution in n-hexane, 111 mL, 111 mmol) was added dropwise at -78°C. The reaction solution was stirred at -78°C for 0.5 hours. 1-Chloro-3-iodopropane (16.3 mL, 151 mmol) was then added dropwise. The reaction solution was stirred at 25°C for 17.5 hours. Water (500 mL) was added at 0°C to quench the reaction, and the mixture was extracted with water (1 L) and ethyl acetate (1 L x 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to give 1-(tert-butyl)2-methyl 2-(3-chloropropyl)-4-(difluoromethylene)pyrrolidine-1,2-dicarboxylate (35.7 g), which was used directly in the next step.

[0326] Step 3: Synthesis of methyl 2-(3-chloropropyl)-4-(difluoromethylene)pyrrolidine-2-carboxylate

[0327] 1-(tert-Butyl)-2-methyl-2-(3-chloropropyl)-4-(difluoromethylene)pyrrolidine-1,2-dicarboxylate (35 g, 98.9 mmol) was dissolved in hydrochloric acid / dioxane (494 mL, 4 N), and the reaction mixture was stirred at 25°C for 3 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent to afford methyl 2-(3-chloropropyl)-4-(difluoromethylene)pyrrolidine-2-carboxylate (25 g, 98.5 mmol), which was used directly in the next step.

[0328] Step 4: Synthesis of methyl 2-(difluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate

[0329] Methyl 2-(3-chloropropyl)-4-(difluoromethylene)pyrrolidine-2-carboxylate (25 g, 98.5 mmol) was dissolved in water (300 mL). Na₂CO₃ (73.1 g, 690 mmol) was added to the mixture, and the reaction mixture was stirred at 25°C for 18 hours. The reaction mixture was extracted with water (1 L) and ethyl acetate (1 L x 3). The combined organic phases were dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was separated using a flash silica gel column to afford methyl 2-(difluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate (14 g, 64.4 mmol, yield: 65.4%).

[0330] 1H NMR (400MHz, CDCl3) δ3.80-3.61(m,4H),3.31(dd,J=1.8,14.4Hz,1H),3.18(td,J=5.3,10.0Hz,1H),2.97( tdd,J=1.5,3.0,16.0Hz,1H),2.63-2.50(m,1H),2.45-2.37(m,1H),2.36-2.28(m,1H),1.91-1.73(m,3H).

[0331] Step 5: Synthesis of (Z or E)-(2-(fluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol

[0332] Methyl 2-(difluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate (7.5 g, 34.5 mmol) was dissolved in 2-methyltetrahydrofuran (300 mL). Red-Al (49.9 g, 173 mmol) was added dropwise to the solution at -15°C, and the reaction mixture was stirred at 25°C for 18 hours. The reaction mixture was quenched by the addition of water (500 mL) at 0°C, and the mixture was extracted with water (500 mL) and ethyl acetate (500 mL x 3). The combined organic phases were dried over anhydrous magnesium sulfate, filtered, and concentrated to yield (Z or E)-(2-(fluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol (5.91 g, 34.5 mmol), which was used directly in the next step.

[0333] Step 6: Synthesis of (Z)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine and (E)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine

[0334] (Z or E)-(2-(Fluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (11.8 g, 68.9 mmol) and imidazole (9.29 mL, 138 mmol) were dissolved in dichloromethane (200 mL). TBDPSCl (26.8 mL, 103 mmol) was added portionwise to the mixture at 0°C. The reaction mixture was stirred at 25°C for 2 hours. The reaction mixture was extracted with water (200 mL) and ethyl acetate (300 mL x 3). The combined organic phases were dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was separated by flash silica gel column to give (Z)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine (10 g, yield: 35.4%) and (E)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine (8 g, yield: 28.3%), respectively. The Z and E configurations were further confirmed by two-dimensional NMR.

[0335] (Z)-7a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine:

[0336] 1 H NMR (400MHz, CDCl3) δ7.68-7.62(m,4H),7.43-7.37(m,6H),6.53-6.26(m,1H),3.76(br d,J=6.2Hz,1H),3.56-3.32(m,3H),3.13(br s,1H),2.65-2.51(m,2H),2.21(br d,J=15.8Hz,1H),2.01(dt,J=3.7,8.3Hz,1H),1.89-1.66(m,3H),1.07(s,9H).

[0337] (E)-7a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine:

[0338] 1H NMR (400MHz, CDCl3) δ7.67(td,J=1.5,7.8Hz,4H),7.45-7.32(m,1H),7.45-7.32(m,1H),7.45-7.32(m,4H),6.68-6.38(m,1H),3.59(br d,J=13.4Hz, 1H),3.50-3.32(m,2H),3.18(br d,J=13.9Hz,1H),3.05(br s,1H),2.85(br d,J=16.3Hz,1H),2.62-2.49(m,1H),2.34(br d,J=16.3Hz,1H),2.08-1.96(m,1H),1.82-1.59(m,3H),1.07(s,9H).

[0339] Step 7: Synthesis of (S,Z)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine and (S,E)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine

[0340] (Z)-7a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-(fluoromethylene)hexahydro-1H-pyrrolizine (12 g, 24.4 mmol) was separated by chiral SFC (Phenomenex-Cellulose-2 column (250 mm x 50 mm, 10 μm), mobile phase: CO₂-MeOH (0.1% NH₃·H₂O)) to afford peak 1 (4.6 g, yield: 38.3%, ee value: 99.22%) and peak 2 (4.4 g, yield: 36.6%, ee value: 99.66%). Subsequent activity verification confirmed that peak 1 exhibited the desired S-configuration.

[0341] Step 8: Synthesis of (S,Z)-(2-(fluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol and (S,E)-(2-(fluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol

[0342] The above peak 1 (2 g, 4.88 mmol) was dissolved in anhydrous methanol (25 mL), and KHF2 (7.63 g, 97.7 mmol) was added at 25°C under nitrogen protection. The reaction was carried out at 25°C for 2 hours. The reaction solution was filtered and concentrated under reduced pressure to remove the solvent. The residue was separated by flash silica gel column chromatography to obtain (S,Z)-(2-(fluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (0.6 g, yield: 71.8%).

[0343] 1H NMR(400MHz,CDCl3)δ6.66-6.35(m,1H),3.75(br d,J=15.2Hz,1H),3.51-3.40(m,1H),3.35-3.23(m,2H),3.17-3.06(m,1H),2.67( td,J=7.4,10.0Hz,1H),2.47-2.36(m,1H),2.34-2.24(m,1H),2.01-1.71(m,5H).

[0344] (S,E)-(2-(Fluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol was synthesized by referring to the formula Z compound.

[0345] Intermediate 1-3: Preparation of (S)-(2-(difluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol

[0346] Step 1: Synthesis of (2-(difluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol

[0347] Methyl 2-(difluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate (7 g, 32.2 mmol) was dissolved in anhydrous THF (100 mL). LiAlH4 (1.83 g, 48.3 mmol) was slowly added portionwise at 0°C. The reaction was continued at low temperature for 1 hour. After completion of the reaction, water (1.5 mL), 15% aqueous NaOH (4.5 mL), and water (1.5 mL) were slowly added dropwise to quench the reaction, followed by filtration. The mixture was extracted with water and ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to provide (2-(difluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol (5 g, yield: 82.0%).

[0348] 1 H NMR (400MHz, CDCl3) δ3.64 (td, J=3.7, 14.6Hz, 1H), 3.40-3.26 (m, 3H), 3.18-3.06 (m, 1H), 2.83 (br s,1H),2.65(td,J=7.5,10.1Hz,1H),2.48-2.28(m,2H),2.02-1.68(m,4H).

[0349] Step 2: Synthesis of 7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine

[0350] (2-(Difluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (1.5 g, 7.93 mmol) and imidazole (1.08 g, 15.8 mmol) were dissolved in CH2Cl2 (20 mL), and TBDPSCl (3.08 mL, 11.9 mmol) was added at 0°C under nitrogen protection. The reaction was allowed to react at room temperature for 2 hours. The reaction solution was filtered and concentrated under reduced pressure to remove the solvent. The residue was separated by flash silica gel column chromatography to obtain 7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine

[0351] (3 g, purity: 70%, yield: 61.9%).

[0352] Step 3: Synthesis of (S)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine and (R)-7a-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine

[0353] 7a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine (3 g) was subjected to chiral separation (chiral column: DAICEL CHIRALPAK AD (250 mm*30 mm, 10 μm), mobile phase: CO2-MeOH (0.1% NH3·H2O)) to give (S)-7a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine (peak 1, 1 g, yield: 33.3%, ee value: 95.68%) and (R)-7a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine (peak 2, 1 g, yield: 33.3%, ee value: 96.96%).

[0354] Step 4: Synthesis of (S)-(2-(difluoromethylene)tetrahydro-1H-pyrrolizine-7a(5H)-yl)methanol

[0355] (S)-7a-(((tert-Butyldiphenylsilyl)oxy)methyl)-2-(difluoromethylene)hexahydro-1H-pyrrolidine (1.0 g, 2.11 mmol) was dissolved in anhydrous methanol (15 mL), and KHF2 (1.64 g, 21.1 mmol) was added. The mixture was allowed to react at room temperature for 5 hours. The reaction mixture was filtered and concentrated under reduced pressure to remove the solvent. The residue was separated by flash silica gel column chromatography to obtain (S)-(2-(difluoromethylene)tetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (300 mg, yield: 71.6%).

[0356] 1H NMR (400MHz, CDCl3) δ3.70-3.61(m,1H),3.43-3.30(m,3H),3.11(ddd,J=4.3,6.6,10.4Hz, 1H), 3.05-2.93 (m, 1H), 2.66 (td, J = 7.6, 10.0Hz, 1H), 2.49-2.33 (m, 2H), 2.06-1.77 (m, 4H).

[0357] Intermediate 1-4: Preparation of (S)-(2-methylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol

[0358] Refer to the corresponding steps of intermediates 1-1 and 1-2 to select corresponding raw materials for preparation.

[0359] Intermediate 2-1: Preparation of 2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-(8-ethynyl-7-fluoro-3-(methoxymethoxy)naphthalen-1-yl)-8-fluoropyrido[4,3-d]pyrimidin-4-ol

[0360] Step 1: Synthesis of 2,7-dichloro-8-fluoro-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine

[0361] 2,4,7-Trichloro-8-fluoropyrido[4,3-d]pyrimidine (6.0 g, 23.77 mmol) was dissolved in THF (60 mL). 2-(Trimethylsilyl)ethan-1-ol (2.75 g, 23.292 mmol) and potassium tert-butoxide (29.23 mL, 29.23 mmol, 1 M THF solution) were added sequentially at -60°C. Stirring was continued at -60°C for 2 hours. TLC indicated the reaction was complete. The reaction was filtered through a pad of Celite, diluted with water (100 mL), and extracted with ethyl acetate (100 mL x 3). The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. Filtered and concentrated. The residue was separated by flash column chromatography to give 2,7-dichloro-8-fluoro-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine (3.90 g, 11.668 mmol, yield: 49.1%).

[0362] Step 2: Synthesis of 7-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine

[0363] (2,6-Dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (3.86 g, 23.34 mmol) was dissolved in 1,4-dioxane (100 mL). 60% NaH (0.93 g, 23.34 mmol) was added under ice-water cooling and stirred at room temperature for 10 minutes. 2,7-Dichloro-8-fluoro-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine (3.9 g, 11.67 mmol) was dissolved in 1,4-dioxane (100 mL) and slowly added to the reaction system. The mixture was reacted at room temperature for 2 hours. After the reaction was complete, water (200 mL) was added to quench the mixture, followed by extraction with EtOAc (200 mL). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography to give 7-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine (2.347 g, 5.069 mmol, yield: 43.5%). ESI-MS: 463.2 [M+1] + .

[0364] Step 3: Synthesis of 2-((2,6-dimethylenetetrahydro-1H-pyrrolizine-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine

[0365] ((2-Fluoro-6-(methoxymethoxy)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-1-yl)ethynyl)triisopropylsilane (3.90 g, 7.60 mmol) was added to THF (50 mL) and H2O (5 mL), followed by the addition of 7-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine (2.347 g, 5.07 mmol), K3PO4 (3.23 g, 15.21 mmol) and CataCXiμm A-Pd-G3 (3.15 mg, 0.01 mmol), and the reaction was heated at 70°C under nitrogen protection for 2 hours. The reaction was complete, cooled to room temperature, concentrated, and separated by column chromatography to give 2-((2,6-dimethylenetetrahydro-1H-pyrrolizine-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine (3.48 g, 4.28 mmol, yield: 84.5%).

[0366] Step 4: Synthesis of 2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-(8-ethynyl-7-fluoro-3-(methoxymethoxy)naphthalen-1-yl)-8-fluoropyrido[4,3-d]pyrimidin-4-ol

[0367] 2-((2,6-Dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-4-(2-(trimethylsilyl)ethoxy)pyrido[4,3-d]pyrimidine (3.48 g, 4.28 mmol) was dissolved in DMF (50 mL), and CsF (6.50 g, 42.80 mmol) was added, and the mixture was heated at 50°C for 2 hours. After the reaction was complete, the mixture was cooled to room temperature, filtered, concentrated, and separated by reverse phase column chromatography to give 2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-(8-ethynyl-7-fluoro-3-(methoxymethoxy)naphthalen-1-yl)-8-fluoropyrido[4,3-d]pyrimidin-4-ol (1.66 g, 2.97 mmol, yield: 69.5%). ESI-MS: 557.2 [M+1] + .

[0368] Intermediates 2-2 to 2-5 were prepared by selecting corresponding raw materials according to the method of Intermediate 2-1.

[0369] Intermediate 3-1: Preparation of tert-butyl 1-(methyl-d3)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0370] Step 1: Synthesis of tert-butyl 3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0371] At room temperature, tert-butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate (7.0 g, 33.0 mmol) was dissolved in 100 mL of dichloromethane, and triethylamine (4.6 mL, 33.0 mmol) and (chloromethyltriyl)triphenyl (9.2 g, 33.0 mmol) were added in sequence. After stirring at room temperature for 24 hours, 2.8 g of (chloromethyltriyl)triphenyl was added, and then stirred at room temperature for another 24 hours. Saturated sodium carbonate solution was added dropwise. The mixture was quenched, allowed to stand and the layers separated. The aqueous phase was extracted with dichloromethane (50 mL x 2). The organic phases were combined and washed sequentially with water (10 mL) and saturated sodium chloride solution (10 mL). The mixture was dried over anhydrous sodium sulfate and concentrated. The resulting crude product was separated by flash silica gel column chromatography [eluent: petroleum ether: ethyl acetate = 1:1] to give tert-butyl 3-trityl-3,8-diazabicyclo[3.2.1]octan-8-carboxylate (13.0 g, yield: 86%). ESI-MS: 243 [M+1] + .

[0372] Step 2: Synthesis of tert-butyl 1-(methyl-d3)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0373] Under nitrogen protection, sec-butyllithium solution (3.6 mL, 4.6 mmol, 1.3 M) was added dropwise to a suspension (20 mL) of tert-butyl 3-trityl-3,8-diazabicyclo[3.2.1]octan-8-carboxylate (900.0 mg, 2.0 mmol) and N,N,N',N'-tetramethylethylenediamine (526 mg, 4.6 mmol) in anhydrous ether. The reaction temperature was maintained at around -30°C. After the addition was complete, the reaction solution was stirred at 0°C for half an hour, and deuterated iodomethane (287 mg, 2.0 mmol) was added dropwise. After the addition was complete, the reaction solution was stirred at 0°C for 15 min. Saturated aqueous ammonium chloride (10 mL) was then added dropwise, and the mixture was allowed to stand for separation. The aqueous phase was extracted with dichloromethane (10 mL). The organic phases were combined and washed sequentially with saturated aqueous sodium bicarbonate (10 mL), water (10 mL), and saturated aqueous sodium chloride (10 mL). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting crude product was separated by flash silica gel column chromatography to yield tert-butyl 1-(methyl-d3)-3-trityl-3,8-diazabicyclo[3.2.1]octan-8-carboxylate (888.0 mg, yield: 77%). ESI-MS: 243 [M+1] + .

[0374] Step 3: Synthesis of tert-butyl 1-(methyl-d3)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0375] Tert-butyl 1-(methyl-d3)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (880 mg, 1.87 mmol) was dissolved in dichloromethane (5 mL). 5 mL of acetic acid was then added. The solution was heated to 50°C for 1 hour and then dried in a rotary evaporation chamber to obtain tert-butyl 1-(methyl-d3)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate, which was used directly in the next reaction. ESI-MS: 230.4 [M+1] + .

[0376] Intermediate 3-2: Preparation of tert-butyl (1S,5S)-1-cyclopropyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0377] Step 1: Synthesis of ethyl (S)-2-((tert-butoxycarbonyl)amino)-5-cyclopropyl-5-oxopentanoate

[0378] 1-(tert-Butyl)-2-ethyl (S)-5-oxopyrrolidine-1,2-dicarboxylate (25.0 g, 97.17 mmol) was dissolved in dry THF (250 mL). The reaction solution was cooled to -78°C in a dry ice-acetone bath. Under a nitrogen atmosphere, a cPrMgBr / THF solution (106.9 mL, 106.9 mmol, 1 M) was added dropwise via a constant pressure dropping funnel. After completion of the addition, the reaction was stirred at -78°C for 3 hours. The reaction was quenched with saturated ammonium chloride solution (250 mL) under cooling. The mixture was extracted with ethyl acetate (200 mL x 2). The organic phases were combined and concentrated, and the residue was separated by column chromatography (PE / EA = 15%) to afford ethyl (S)-2-((tert-butoxycarbonyl)amino)-5-cyclopropyl-5-oxopentanoate (11.0 g, yield: 38%). MS m / z(ESI):244.0[M-56+H] + .

[0379] 1 H NMR(400MHz, CDCl3)δ5.11(d,J=8.4Hz,1H),4.31–4.23(m,1H),4.19(q,J=7.1Hz,2H),2.78–2.58(m,2H),2.1 9–2.08(m,1H),1.98–1.85(m,2H),1.45(s,9H),1.28(t,J=7.2Hz,3H),1.05–1.00(m,2H),0.90–0.85(m,2H).

[0380] Step 2: Synthesis of 1-(tert-butyl) 2-ethyl (2S,5S)-5-cyano-5-cyclopropylpyrrolidine-1,2-dicarboxylate

[0381] (S)-2-((tert-Butoxycarbonyl)amino)-5-cyclopropyl-5-oxopentanoate (11.0 g, 36.74 mmol) was dissolved in dichloromethane (200 mL). The reaction solution was cooled to -78°C in a dry ice-acetone bath. Under a nitrogen atmosphere, a mixture of tris(pentafluorophenyl)borane (2.82 g, 5.51 mmol) and TMSCN (9.80 mL, 73.49 mmol) dissolved in dichloromethane (20 mL) was added dropwise via a constant pressure dropping funnel. After the addition was complete, the reaction was stirred at -78°C for half an hour. The reaction mixture was then slowly warmed to room temperature and stirred overnight. The reaction was quenched with saturated sodium bicarbonate solution (200 mL), extracted with dichloromethane (200 mL*2), the organic phases were combined and concentrated, and the residue was separated by column chromatography [PE / EA=10-13%] to give 1-(tert-butyl)2-ethyl(2S,5R)-5-cyano-5-cyclopropylpyrrolidine-1,2-dicarboxylate (3.75 g, yield: 33%, isomer 1) and 1-(tert-butyl)2-ethyl(2S,5S)-5-cyano-5-cyclopropylpyrrolidine-1,2-dicarboxylate (5.0 g, yield: 44%, isomer 2).

[0382] 1-(tert-Butyl) 2-ethyl (2S,5R)-5-cyano-5-cyclopropylpyrrolidine-1,2-dicarboxylate (Isomer 1)

[0383] MS m / z(ESI):253.2[M-56+H] + .

[0384] 1 H NMR (400MHz, CDCl3) δ4.57–4.37(m,1H),4.20(q,J=7.1Hz,2H),2.43–2.17(m,3H),2.12–1.96(m,1H),1.64–1. 40(m,10H),1.29(t,J=7.1Hz,3H),0.95-0.86(m,1H),0.84-0.77(m,1H),0.63-0.55(m,1H),0.52-0.43(m,1H).

[0385] 1-(tert-Butyl) 2-ethyl (2S,5S)-5-cyano-5-cyclopropylpyrrolidine-1,2-dicarboxylate (Isomer 2)

[0386] MS m / z(ESI):253.2[M-56+H] + .

[0387] 1H NMR (400MHz, CDCl3) δ4.48 (dd, J=8.7, 1.9Hz, 0.6H), 4.38 (dd, J=8.6, 2.4Hz, 0 .4H),4.29–4.11(m,2H),2.62-2.51(m,0.6H),2.49–2.43(m,0.4H),2.35–2.1 3(m,1.6H),2.12–2.00(m,1.4H),1.55(s,6H),1.44(s,3H),1.40–1.26(m,4H) ,0.91–0.83(m,1H),0.82–0.73(m,1H),0.63–0.52(m,1H),0.50–0.43(m,1H).

[0388] Step 3: Synthesis of 1-(tert-butyl) 2-ethyl (2S,5S)-5-(aminomethyl)-5-cyclopropylpyrrolidine-1,2-dicarboxylate

[0389] 1-(tert-Butyl)-2-ethyl (2S,5S)-5-cyano-5-cyclopropylpyrrolidine-1,2-dicarboxylate (4.90 g, 15.89 mmol) was dissolved in ethanol (60 mL), and Raney nickel (1.2 g) was added. The reaction was stirred at room temperature under a hydrogen atmosphere for 40 hours. The reaction solution was filtered through celite and washed with methanol (30 mL). The filtrate was concentrated, and the residue was separated by column chromatography [MeOH / DCM = 5%] to give 1-(tert-Butyl)-2-ethyl (2S,5S)-5-(aminomethyl)-5-cyclopropylpyrrolidine-1,2-dicarboxylate (3.51 g, yield: 71%). ESI-MS: 313.2 [M+1] + .

[0390] 1 H NMR (400MHz, CDCl3) δ4.40 (dd, J=9.4, 3.1Hz, 0.39H), 4.29 (dd, J=9.5, 2.7Hz, 0.61H), 4.26–4.10 ( m,2H),3.57(d,J=13.4Hz,0.61H),3.14(d,J=13.4Hz,0.39H),2.88(d,J=13.4Hz,0.61H),2.71(d,J =13.5Hz,0.39H),2.69(brs,2H),2.25–2.09(m,1H),1.99–1.77(m,2H),1.50(s,3H),1.48–1.44(m ,1H),1.40(s,6H),1.37–1.32(m,1H),1.28(q,J=7.1Hz,3H),0.56–0.35(m,2H),0.35–0.18(m,2H).

[0391] Step 4: Synthesis of tert-butyl (1S,5S)-1-cyclopropyl-4-oxo-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0392] 1-(tert-Butyl)-2-ethyl (2S,5S)-5-(aminomethyl)-5-cyclopropylpyrrolidine-1,2-dicarboxylate (3.50 g, 11.20 mmol) was dissolved in methanol (60 mL). Sodium methoxide (0.91 g, 16.80 mmol) was slowly added under ice-cooling and stirred at room temperature overnight. The reaction solution was concentrated, and the residue was separated by column chromatography [PE / EA = 60%] to give tert-butyl (1S,5S)-1-cyclopropyl-4-oxo-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (2.60 g, yield: 87%). MS m / z (ESI): 211.2 [M-56+H] + .

[0393] 1 H NMR (400MHz, CDCl3) δ6.07 (s, 1H), 4.41 (d, J=6.4Hz, 1H), 3.86 (d, J= 11.2Hz,1H),3.06(dd,J=11.2,2.6Hz,1H),2.03–1.91(m,2H),1.84–1.75(m,1H),1.6 0–1.50(m,2H),1.47(s,9H),0.62–0.50(m,2H),0.47–0.37(m,1H),0.29–0.24(m,1H).

[0394] Step 5: Synthesis of tert-butyl (1S,5S)-1-cyclopropyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0395] Tert-butyl (1S,5S)-1-cyclopropyl-4-oxo-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (2.30 g, 8.64 mmol) was dissolved in dry tetrahydrofuran (20 mL). Borane dimethyl sulfide solution (21.59 mL, 43.18 mmol) was slowly added dropwise under ice-cooling. The mixture was stirred at 0°C for 1 hour. The reaction mixture was allowed to warm to room temperature and stirred overnight. Methanol (20 mL) was slowly added to quench the reaction. The mixture was stirred at 50°C for 18 hours. The reaction mixture was directly concentrated by rotary evaporation, and the residue was separated by column chromatography [MeOH / DCM = 5%] to obtain tert-butyl (1S,5S)-1-cyclopropyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (1.10 g, yield: 50%). ESI-MS: 253.2 [M+1] + .

[0396] 1 H NMR (400MHz, CDCl3) δ4.26(d,J=7.3Hz,1H),3.11(d,J=12.3Hz,1H),3.04(d,J=12.5Hz,1H),2.74–2.66(m,2H),1.95–1.83(m,1H) ,1.76–1.68(m,1H),1.66–1.59(m,1H),1.48(s,9H),1.47–1.33(m,2H),0.50–0.44(m,2H),0.38–0.33(m,1H),0.28–0.23(m,1H).

[0397] Intermediates 3-3 to 3-12 were prepared by selecting corresponding raw materials according to the method of Intermediate 3-1 or 3-2.

[0398] Intermediate 3-13: Preparation of tert-butyl 1-(methoxymethyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0399] Step 1: Synthesis of tert-butyl 1-formyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0400] Under nitrogen protection, sec-butyllithium solution (14.4 mL, 18.7 mmol, 1.3 M) was slowly added dropwise to a suspension of tert-butyl 3-trityl-3,8-diazabicyclo[3.2.1]octan-8-carboxylate (5.0 g, 11.0 mmol) and TMEDA (2.2 g, 18.7 mmol) in anhydrous ether (40 mL). The reaction temperature was maintained at around 0°C. After the addition was complete, the reaction solution was stirred at 0°C for 1.5 hours, and ethyl formate (2.4 g, 33.0 mmol) was added dropwise. After the addition was complete, the reaction solution was stirred at 0°C for 15 minutes. Saturated aqueous ammonium chloride (20 mL) was then added dropwise, and the mixture was allowed to stand for separation. The aqueous phase was extracted with dichloromethane (10 mL). The organic phases were combined and washed sequentially with saturated aqueous sodium bicarbonate (10 mL), water (10 mL), and saturated aqueous sodium chloride (10 mL). The mixture was dried over anhydrous sodium sulfate and concentrated. The resulting crude product was separated by flash silica gel column chromatography to give tert-butyl 1-formyl-3-trityl-3,8-diazabicyclo[3.2.1]octan-8-carboxylate (1.9 g, yield: 36%). ESI-MS: 483.2 [M+1] + .

[0401] Step 2: Synthesis of tert-butyl 1-(hydroxymethyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0402] Tert-butyl 1-formyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (560.0 mg, 1.2 mmol) was dissolved in methanol (10 mL), and NaBH4 (78.0 mg, 2.3 mmol) was added under ice bath. The mixture was stirred at room temperature for 1 hour until the reaction was complete. Water (15 mL) and ethyl acetate (15 mL) were added to quench the reaction. The mixture was stirred at room temperature for 5 minutes. The layers were separated by standing. The aqueous phase was extracted with ethyl acetate (10 mL*2). The organic phases were combined and washed sequentially with saturated aqueous sodium bicarbonate solution (10 mL), water (10 mL), and saturated aqueous sodium chloride solution (10 mL). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to give tert-butyl 1-(hydroxymethyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (560.0 mg, yield: 91%). ESI-MS: 485.2[M+1] + .

[0403] Step 3: Synthesis of tert-butyl 1-(methoxymethyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0404] Tert-butyl 1-(hydroxymethyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (700 mg, 1.44 mmol) was dissolved in DMF (10 mL). Sodium hydroxide (69.3 mg, 1.73 mmol) was slowly added at 0°C. The reaction mixture was stirred at 0°C for 2 hours, and iodomethane (270 μL, 4.33 mmol) was added. The temperature was maintained at 0°C for another 2 hours. After completion of the reaction, water (20 mL) was added to quench the reaction, and the aqueous phase was extracted with ethyl acetate (20 mL x 2). The combined organic phases were washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to remove the solvent. The residue was separated on a flash silica gel column to afford tert-butyl 1-(methoxymethyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (440 mg, yield: 61.1%).

[0405] Step 4: Synthesis of tert-butyl 1-(methoxymethyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0406] Tert-butyl 1-(methoxymethyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (440 mg, 0.88 mmol) was dissolved in HOAc (5 mL). The mixture was reacted at 25°C for 2 hours. The solvent was concentrated under reduced pressure to obtain tert-butyl 1-(methoxymethyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (220 mg, yield: 97.3%). ESI-MS: 256 [M+1] + .

[0407] Intermediate 3-14: Preparation of tert-butyl (1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0408] Intermediate 3-14 was prepared by referring to Intermediate 3-13.

[0409] Intermediate 3-14-1 and Intermediate 3-14-2: Preparation of tert-butyl (1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate and tert-butyl (1R,5S)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0410] Step 1: Synthesis of tert-butyl (1S,5R)-1-((methoxy-d3)methyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate and tert-butyl (1R,5S)-1-((methoxy-d3)methyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0411] (+)-tert-Butyl (1S,5R)-1-((methoxy-d3)methyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (4 g, 7.97 mmol) was separated by SFC (chiral column: REGIS (s,s) WHELK-O1 (250 mm*50 mm, 10 μm); mobile phase: CO2-EtOH (0.1% NH3·H2O) to give peak 1 tert-Butyl (1S,5R)-1-((methoxy-d3)methyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (assumed configuration) (1.83 g, yield: 45.8%, purity: 97.2%, ESI-MS 524 [M+23]) +) and Peak 2 tert-butyl (1R,5S)-1-((methoxy-d3)methyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (assumed configuration) (1.81 g, yield: 45.3%, purity: 97.0%). ESI-MS: 524 [M+23] + .

[0412] Peak 1: tert-Butyl (1S,5R)-1-((methoxy-d3)methyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0413] 1 H NMR (400MHz, CDCl3) δ7.51(br s,5H),7.32-7.24(m,7H),7.19-7.13(m,3H),4.14(br s,1H),3.64(br s,2H),3.08(d,J=11.0Hz,1H),2.95(br d,J=11.0Hz,1H),2.61-2.49(m,1H),2.24(dt,J=3.4,10.4Hz,1H),2.17-1.97(m,2H),1.84(br d,J=11.0Hz,1H),1.75(br d,J=9.0Hz,1H),1.19(s,9H).

[0414] Peak 2: tert-Butyl (1R,5S)-1-((methoxy-d3)methyl)-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0415] 1 H NMR (400MHz, CDCl3) δ7.51(br s,5H),7.31-7.25(m,7H),7.19-7.14(m,3H),4.14(br s,1H),3.64(br s,2H),3.08(d,J=11.0Hz,1H),2.96(br d,J=11.4Hz,1H),2.62-2.50(m,1H),2.33-2.18(m,1H),2.15-1.99(m,2H),1.84(br d,J=11.0Hz,1H),1.75(br d,J=8.4Hz,1H),1.19(s,9H).

[0416] Step 2: Synthesis of tert-butyl (1S, 5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate or tert-butyl (1R, 5S)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0417] Refer to the fourth step of intermediate 3-13 and select the corresponding single chiral raw material for preparation.

[0418] Intermediate 3-15: Preparation of tert-butyl 1-vinyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0419] Step 1: Synthesis of tert-butyl 3-trityl-1-vinyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0420] Methyltriphenylphosphane bromide (3.66 g, 10.3 mmol) was dissolved in anhydrous tetrahydrofuran (30 mL). Potassium tert-butoxide (1.27 g, 11.3 mmol) was added and stirred at 0°C for 10 minutes. Then, a solution of tert-butyl 1-formyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (1.65 g, 3.42 mmol) in tetrahydrofuran (10 mL) was slowly added. The mixture was reacted at 25°C for 2 hours. TLC confirmed the completion of the reaction. The reaction mixture was diluted with 30 mL of water and extracted twice with 30 mL of ethyl acetate. The organic phase was washed once with 20 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue was separated by flash silica gel column to obtain tert-butyl 3-trityl-1-vinyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (1.19 g, yield: 72.4%).

[0421] 1 H NMR (400 MHz, CDCl3) δ 7.50 (br s,5H),7.33-7.25(m,7H),7.19-7.09(m,3H),6.16(dd,J=11.2,17.9Hz,1H),4 .93(d,J=11.3Hz,1H),4.81(d,J=18.1Hz,1H),4.16(d,J=5.5Hz,1H),3.19(d,J =11.0Hz,1H),2.96(d,J=11.0Hz,1H),2.58-2.46(m,1H),2.36-2.22(m,1H),2 .13-1.89(m,2H),1.92(d,J=11.0Hz,1H),1.84(d,J=11.0Hz,1H),1.15(s,9H).

[0422] Step 2: Synthesis of tert-butyl 1-vinyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0423] Dissolve tert-butyl 3-trityl-1-vinyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (550 mg, 1.14 mmol) in acetic acid (10 mL). The mixture is reacted at 25°C overnight. The solvent is removed by concentration under reduced pressure to obtain tert-butyl 1-vinyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (540 mg, crude product). The crude product can be used directly in the next reaction without isolation. ESI-MS: 183 [M+1-56] + .

[0424] Intermediate 3-16 was prepared by selecting corresponding raw materials according to the synthesis method of intermediate 3-15:

[0425] Intermediate 3-17: Preparation of tert-butyl 1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0426] Step 1: Synthesis of tert-butyl 1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0427] tert-Butyl 3-trityl-1-vinyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (550 mg, 1.14 mmol) was dissolved in anhydrous methanol (20 mL). Wet Pd / C (200 mg, 10% purity) was added under nitrogen. The atmosphere was replaced with hydrogen three times, and the mixture was allowed to react at 25°C under a hydrogen balloon for 3 hours. TLC confirmed the reaction was complete. The filtrate was filtered through celite, and the solvent was removed by concentration under reduced pressure to yield tert-butyl 1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (550 mg, 100% yield).

[0428] Step 2: Synthesis of tert-butyl 1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0429] Tert-butyl 1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (550 mg, 1.13 mmol) was dissolved in HOAc (10 mL). The mixture was reacted at 25°C overnight. The solvent was concentrated under reduced pressure to obtain tert-butyl 1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (540 mg, crude product). ESI-MS: 241 [M+1] + .

[0430] Intermediate 3-17-1 and Intermediate 3-17-2: Preparation of tert-butyl (1S,5R)-1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate and tert-butyl (1R,5S)-1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0431] Step 1: Synthesis of tert-butyl (1S,5R)-1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate and tert-butyl (1R,5S)-1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0432] Tert-butyl 1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (4 g, 7.97 mmol) was separated by SFC (chiral column: REGIS (s,s) WHELK-O1 (250 mm*50 mm, 10 μm); mobile phase: CO2-EtOH (0.1% NH3·H2O)) to give peak 1 tert-butyl (1S,5R)-1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (assumed configuration) (1.83 g, yield: 45.8%, purity: 97.2%, ESI-MS 524 [M+23]) and tert-butyl (1S,5R)-1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (assumed configuration) (1.83 g, yield: 45.8%, purity: 97.2%, ESI-MS 524 [M+23]) respectively. + ) and Peak 2 tert-butyl (1R,5S)-1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (assumed configuration) (1.81 g, yield: 45.3%, purity: 97.0%). ESI-MS 524 [M+23] + .

[0433] Peak 1: tert-Butyl (1S,5R)-1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0434] 1H NMR (400MHz, CDCl3) δ7.51(br s,5H),7.32-7.24(m,7H),7.19-7.13(m,3H),4.14(br s,1H),3.64(br s,2H),3.08(d,J=11.0Hz,1H),2.95(br d,J=11.0Hz,1H),2.61-2.49(m,1H),2.24(dt,J=3.4,10.4Hz,1H),2.17-1.97(m,2H),1.84(br d,J=11.0Hz,1H),1.75(br d,J=9.0Hz,1H),1.19(s,9H).

[0435] Peak 2: tert-Butyl (1R,5S)-1-ethyl-3-trityl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0436] 1 H NMR (400MHz, CDCl3) δ7.51(br s,5H),7.31-7.25(m,7H),7.19-7.14(m,3H),4.14(br s,1H),3.64(br s,2H),3.08(d,J=11.0Hz,1H),2.96(br d,J=11.4Hz,1H),2.62-2.50(m,1H),2.33-2.18(m,1H),2.15-1.99(m,2H),1.84(br d,J=11.0Hz,1H),1.75(br d,J=8.4Hz,1H),1.19(s,9H).

[0437] Step 2: Synthesis of tert-butyl (1S,5R)-1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate and tert-butyl (1R,5S)-1-ethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0438] Refer to the second step of intermediate 3-17 and select the corresponding single chiral raw material for preparation.

[0439] Intermediate 3-18: Preparation of tert-butyl (1S,5R)-1-(2-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0440] Refer to Intermediate 3-1 to select corresponding raw materials for preparation.

[0441] Intermediate 4-1: Preparation of (2-((tert-Butoxycarbonyl)amino)-7-fluorobenzo[d]thiazol-4-yl)boronic acid

[0442] Step 1: Synthesis of tert-butyl (4-bromo-7-fluorobenzo[d]thiazol-2-yl)carbamate

[0443] 4-Bromo-7-fluorobenzo[d]thiazol-2-amine (2.9 g, 11.74 mmol), DMAP (110 mg, 0.94 mmol), and DIPEA (2.28 g, 17.6 mmol) were dissolved in a mixture of THF (36 mL) and DMF (3 mL). Boc2O (2.82 g, 12.91 mmol) was added at 0°C and stirred at room temperature for 18 hours. LCMS monitored the reaction completion. After completion, the mixture was diluted with ethyl acetate, the organic phase separated, and washed with saturated brine. The organic phase was dried, filtered, and the filtrate concentrated. The resulting residue was separated by flash silica gel column chromatography to afford tert-butyl (4-bromo-7-fluorobenzo[d]thiazol-2-yl)carbamate (3.14 g, yield: 77.2%). ESI-MS: 348.0 [M+1]. + .

[0444] Step 2: Synthesis of (2-((tert-Butoxycarbonyl)amino)-7-fluorobenzo[d]thiazol-4-yl)boronic acid

[0445] Tert-butyl (4-bromo-7-fluorobenzo[d]thiazol-2-yl)carbamate (2.0 g, 5.76 mmol), KOAc (1.70 g, 17.28 mmol), and bis(neopentylethylene glycol)diboron (4.94 g, 21.89 mmol) were dissolved in 1,4-dioxane (40 mL). DPEpHosPdCl2 (310 mg, 0.574 mmol) was added, and the atmosphere was purged with nitrogen three times. The mixture was heated at 100°C and stirred for 18 hours. The reaction was monitored for completion by LCMS. After completion, the reaction mixture was concentrated, and the resulting residue was separated by flash silica gel column chromatography to afford (2-((tert-butoxycarbonyl)amino)-7-fluorobenzo[d]thiazol-4-yl)boronic acid (1.01 g, yield: 56%). ESI-MS: 313.1 [M+1] + .

[0446] Intermediate 4-2: Preparation of tert-butyl (3-cyano-4-(5,5-dimethyl-1,3,2-dioxaborolan-2-yl)-7-fluorobenzo[b]thiophen-2-yl)carbamate

[0447] Step 1: Synthesis of ethyl (4-bromo-3-cyano-7-fluorobenzo[b]thiophen-2-yl)carbamate

[0448] 2-(6-Bromo-2,3-difluorophenyl)acetonitrile (3.8 g, 16.38 mmol) was dissolved in DMF (70 mL). NaH (980 mg, 24.57 mmol, 60%) was added under ice-water cooling and stirring continued at 0°C for 30 minutes. Ethoxycarbonyl isothiocyanate (2.58 g, 19.65 mmol) was then added and the mixture was heated at 100°C for 18 hours. LCMS monitored the reaction completion. The mixture was cooled to room temperature, diluted with ethyl acetate, and the organic phase was separated and washed with saturated brine. The organic phase was dried, filtered, and the filtrate was concentrated. The resulting residue was separated by flash silica gel column chromatography to yield ethyl (4-bromo-3-cyano-7-fluorobenzo[b]thiophen-2-yl)carbamate (4.78 g, yield: 85.1%). ESI-MS: 344.4 [M+1] + .

[0449] Step 2: Synthesis of 2-amino-4-bromo-7-fluorobenzo[b]thiophene-3-carbonitrile

[0450] Ethyl (4-bromo-3-cyano-7-fluorobenzo[b]thiophen-2-yl)carbamate (4.78 g, 13.93 mmol) was dissolved in DMSO (19 mL). Aqueous NaOH (15.6 mL, 78 mmol, 5 N) was added at 0°C and stirred at 125°C for 18 hours. The reaction was monitored for completion by LCMS. After completion, the product was diluted with ethyl acetate, the organic phase was separated, and washed with saturated brine. The organic phase was dried, filtered, and the filtrate was concentrated. The resulting residue was separated by flash silica gel column chromatography to yield 2-amino-4-bromo-7-fluorobenzo[b]thiophene-3-carbonitrile (1.91 g, yield: 50.5%). ESI-MS: 272.3 [M+1] + .

[0451] Step 3: Synthesis of tert-butyl (4-bromo-3-cyano-7-fluorobenzo[b]thiophen-2-yl)carbamate

[0452] 2-Amino-4-bromo-7-fluorobenzo[b]thiophene-3-carbonitrile (1.91 g, 7.04 mmol), DMAP (70 mg, 0.56 mmol), and DIPEA (1.37 g, 10.6 mmol) were dissolved in a mixture of THF (60 mL) and DMF (5 mL). BoC₂O (1.69 g, 7.75 mmol) was added under ice-water cooling and stirred at room temperature for 18 hours. The reaction was monitored for completion by LCMS. After completion, the mixture was diluted with ethyl acetate, the organic phase separated, and washed once with saturated brine. The organic phase was dried, filtered, and the filtrate concentrated. The resulting residue was separated by flash silica gel column chromatography to yield tert-butyl (4-bromo-3-cyano-7-fluorobenzo[b]thiophen-2-yl)carbamate (1.69 g, yield: 64.5%). ESI-MS: 372.3 [M+1] + .

[0453] Step 4: Synthesis of tert-butyl (3-cyano-4-(5,5-dimethyl-1,3,2-dioxaborolan-2-yl)-7-fluorobenzo[b]thiophen-2-yl)carbamate

[0454] Tert-butyl (4-bromo-3-cyano-7-fluorobenzo[b]thiophen-2-yl)carbamate (1.59 g, 4.28 mmol), KOAc (1.26 g, 12.85 mmol), and bis(neopentylethylene glycol)diboron (3.68 g, 16.28 mmol) were dissolved in 1,4-dioxane (40 mL). DPEpHosPdCl2 (230 mg, 0.43 mmol) was added, and the atmosphere was purged with nitrogen three times. The mixture was heated at 95°C and stirred for 18 hours. The reaction was monitored for completion by LCMS. After completion, the reaction mixture was concentrated, and the resulting residue was separated by flash silica gel column chromatography to afford tert-butyl (3-cyano-4-(5,5-dimethyl-1,3,2-dioxaborolan-2-yl)-7-fluorobenzo[b]thiophen-2-yl)carbamate (1.08 g, yield: 62.4%). ESI-MS: 405.4 [M+1] + .

[0455] Intermediate 4-3: Preparation of tert-butyl (3-cyano-4-(5,5-dimethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)carbamate

[0456] Refer to the synthetic steps of intermediate 4-2 and select the corresponding raw materials for preparation.

[0457] Intermediate 4-4: Preparation of N-(6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-((triisopropylsilyl)ethynyl)naphthalen-2-yl)-1,1-diphenylformimine

[0458] Step 1: Synthesis of 7-fluoro-8-((triisopropylsilyl)ethynyl)naphthalene-1,3-diyl bis(trifluoromethanesulfonate)

[0459] 7-Fluoro-8-((triisopropylsilyl)ethynyl)naphthalene-1,3-diol (2.0 g, 5.58 mmol) was dissolved in CHCl (30 mL). DIPEA (5.53 mL, 33.47 mmol) and TfO (3.7 mL, 22.31 mmol) were added sequentially at 0°C. The mixture was then allowed to warm to room temperature and allowed to react for 4 hours. After the reaction was complete, the mixture was diluted with saturated aqueous NaHCO (50 mL) and extracted three times with CHCl (30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate concentrated. The residue was separated by flash silica gel column chromatography to yield 7-fluoro-8-((triisopropylsilyl)ethynyl)naphthalene-1,3-diyl bis(trifluoromethanesulfonate) (3.2 g, 5.14 mmol, yield: 92%).

[0460] 1 H NMR (400MHz, CDCl3) δ7.87 (dd, J=9.1, 5.3Hz, 1H), 7.80 (d, J=2.4Hz, 1H), 7.53–7.46 (m, 2H), 1.28–1.21 (m, 3H), 1.20–1.13 (m, 18H).

[0461] Step 2: Synthesis of 3-((diphenylmethylene)amino)-7-fluoro-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl trifluoromethanesulfonate

[0462] 7-Fluoro-8-((triisopropylsilyl)ethynyl)naphthalene-1,3-diyl bis(trifluoromethanesulfonate) (2.7 g, 4.34 mmol) was dissolved in 1,4-dioxane (20 mL), followed by the addition of Cs2CO3 (4.24 g, 13.01 mmol), XantPhos (0.5 g, 0.87 mmol), and Pd2(dba)3 (0.4 g, 0.43 mmol). The atmosphere was replaced with a nitrogen balloon three times, and the mixture was heated to 100°C under nitrogen and stirred for 5 hours. TLC analysis indicated complete reaction of the starting materials, with the formation of new spots. The reaction mixture was concentrated, and the residue was separated by flash silica gel column chromatography to obtain 3-((diphenylmethylene)amino)-7-fluoro-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl trifluoromethanesulfonate (360 mg, 0.55 mmol, yield: 13%) and a portion of the crude product (4.3 g, 1.64 mmol, purity: 25%). ESI-MS 654.5 [M+1] + .

[0463] Step 3: Synthesis of N-(6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-((triisopropylsilyl)ethynyl)naphthalen-2-yl)-1,1-diphenylformimine

[0464] 3-((Diphenylmethylene)amino)-7-fluoro-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl trifluoromethanesulfonate (200 mg, 0.31 mmol) was dissolved in 1,4-dioxane (5 mL), followed by the addition of B2(Pin)2 (155 mg, 0.61 mmol), KOAc (90 mg, 0.92 mmol), and Pd(dppf)Cl2 (45 mg, 0.06 mmol). The mixture was flushed with a nitrogen balloon three times, then heated to 100°C under nitrogen and stirred for 2 hours. LCMS monitoring indicated the reaction was complete. The reaction mixture was cooled to room temperature and concentrated. The residue was separated by flash silica gel column chromatography to obtain N-(6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-((triisopropylsilyl)ethynyl)naphthalen-2-yl)-1,1-diphenylmethanimine (100 mg, 0.16 mmol, yield: 52%). ESI-MS 632.6 [M+1] + .

[0465] 2. Specific embodiments

[0466] Example 1: Preparation of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol

[0467] Step 1: Synthesis of tert-butyl 3-(2,7-dichloro-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0468] 2,4,7-Trichloro-8-fluoropyrido[4,3-d]pyrimidine (987.0 mg, 3.91 mmol) was dissolved in CH2Cl2 (20 mL), and DIPEA (3.88 g, 30.07 mmol) and tert-butyl (1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (780 mg, 3.01 mmol) were added at 0°C. The mixture was reacted at 0°C for 2 hours. After the reaction, the mixture was diluted with ethyl acetate, and the organic phase was separated and washed once with saturated brine. The organic phase was dried, filtered, and concentrated. The resulting residue was separated by flash silica gel column chromatography to give tert-butyl 3-(2,7-dichloro-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (715 mg, yield: 50%). ESI-MS: 475.2 [M+1] + .

[0469] Step 2: Synthesis of tert-butyl 3-(7-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0470] (2,6-Dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (469.27 mg, 2.84 mmol) was dissolved in dry 1,4-dioxane (30 mL), and 60% NaH (113.60 mg, 2.84 mmol) was added. The mixture was heated at 40°C with stirring for 30 minutes, and then tert-butyl 3-(2,7-dichloro-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (675 mg, 1.42 mmol) was added. The reaction was continued at 40°C for 2 hours. After the reaction, the mixture was diluted with ethyl acetate, the organic phase was separated and washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by flash silica gel column chromatography to give tert-butyl 3-(7-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (544 mg, yield: 63.4%). ESI-MS: 604.4 [M+1] + .

[0471] Step 3: Synthesis of tert-butyl 3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0472] Tert-butyl 3-(7-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (524 mg, 0.87 mmol), ((2-fluoro-6-(methoxymethoxy)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-1-yl)ethynyl)triisopropylsilane (666.8 mg, 1.30 mmol), K3PO4 (552.34 mg, 2.60 mmol) were dissolved in THF (10 mL) and water (1 mL), and then CataxciAmPd G2 (63.2 mg, 0.087 mmol) was replaced with nitrogen three times and heated at 70°C for 2 hours. After the reaction, the mixture was diluted with ethyl acetate, the organic phase was separated and washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by flash silica gel column chromatography to give tert-butyl 3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (354 mg, yield: 42.8%). ESI-MS: 954.5 [M+1] + .

[0473] Step 4: Synthesis of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-6-fluoro-5-((triisopropylsilyl)ethynyl)naphthalen-2-ol

[0474] Tert-butyl 3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (334 mg, 0.35 mmol) was dissolved in CH2Cl2 (20 mL), and hydrochloric acid / dioxane solution (5 ml) was added, and the reaction was carried out at 0°C for 2 hours. After the reaction, the reaction mixture was concentrated to give 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-6-fluoro-5-((triisopropylsilyl)ethynyl)naphthalen-2-ol (283.54 mg, yield: 100%). ESI-MS: 810.4 [M+1] + .

[0475] Step 5: Synthesis of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol

[0476] 4-(2-((2,6-Dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-6-fluoro-5-((triisopropylsilyl)ethynyl)naphthalen-2-ol (283.54 mg, 0.35 mmol) was dissolved in DMF (10 mL), and CsF (5.32 g, 35.0 mmol) was added. The mixture was heated at 50°C with stirring for 2 hours. The reaction was monitored by LCMS for completion and filtered. After concentration, the product was separated by reverse phase column chromatography to give 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol (134.5 mg, yield: 58.8%). ESI-MS: 654.3 [M+1] + .

[0477] 1 H NMR(400MHz,MeOH-d4)δ9.00(d,J=4.3Hz,1H),7.85(dd,J=9.1,5.7Hz,1H),7.38–7.27(m,2H),7.21(d ,J=1.9Hz,1H),5.01(d,J=7.3Hz,4H),4.71–4.53(m,2H),4.33–4.30(m,2H),3.76(d,J=14.9Hz,2H),3 .70–3.62(m,2H),3.58(dd,J=12.3,8.2Hz,1H),3.51–3.48(m,2H),3.37–3.35(m,2H),3.31(s,1H),2. 78(d,J=16.5Hz,2H),2.58(d,J=16.4Hz,2H),1.97–1.89(m,1H),1.83–1.69(m,2H),1.65–1.58(m,1H).

[0478] Example 2: Preparation of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-(2-hydroxypropane-2-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol

[0479] Step 1: Synthesis of tert-butyl 3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-(8-ethynyl-7-fluoro-3-(methoxymethoxy)naphthalen-1-yl)-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-(2-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0480] 2-((2,6-Dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-(8-ethynyl-7-fluoro-3-(methoxymethoxy)naphthalen-1-yl)-8-fluoropyrido[4,3-d]pyrimidin-4-ol (190 mg, 0.34 mmol) was dissolved in CH2Cl2 (10 mL), and then DIPEA (132 mg, 1.024 mmol) and HATU (156 mg, 0.410 mmol) were added. After stirring at room temperature for 10 minutes, tert-butyl (1S,5R)-1-(2-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (101.5 mg, 0.376 mmol) was added and the reaction was allowed to react at room temperature for 2 hours. After the reaction was complete, concentration was performed and column chromatography was performed to obtain tert-butyl 3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-(8-ethynyl-7-fluoro-3-(methoxymethoxy)naphthalen-1-yl)-8-fluoropyrido[4,3-d]pyrimidin-4-yl)-1-(2-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (180 mg, yield: 65.2%). ESI-MS: 809.4 [M+1] + .

[0481] Step 2: Synthesis of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-(2-hydroxypropane-2-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol

[0482] Synthesize with reference to the fourth step of Example 1. ESI-MS: 665.4[M+1] + .

[0483] 1H NMR(400MHz,MeOH-d4)δ9.01(s,1H),7.89–7.83(m,1H),7.37–7.27(m,2H), 7.21(dd,J=7.7,2.5Hz,1H),5.02(d,J=8.4Hz,4H),4.61(s,1H),4.53(d,J=1 3.6Hz,1H),4.42–4.32(m,2H),3.86–3.67(m,4H),3.51(dd,J=28.5,12.4Hz,1H),3.40–3.32(m,3H),2.78(d,J=16.6Hz ,2H),2.59(dd,J=16.4,7.1Hz,2H),1.98–1.81(m,2H),1.80–1.64(m,2H),1.37(d,J=1.9Hz,3H),1.34(d,J=5.1Hz,3H).

[0484] Examples 3 to 172, 355 to 357, and comparative compounds 1 to 4 can be prepared by selecting corresponding intermediates according to the route of Example 1 or Example 2.

[0485] Example 173: Preparation of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-5-methoxy-4-((1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol

[0486] Step 1: Synthesis of 7-chloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidin-4(3H)-one

[0487] 5,7-Dichloro-8-fluoro-2-(methylthio)pyrido[4,3-d]pyrimidin-4(3H)-one (1.0 g, 3.57 mmol) was dissolved in DMF (50 mL). A methanol solution of sodium methoxide (1.29 g, 7.14 mmol) was added at 0°C and heated to 50°C for 2 hours. After the reaction, the mixture was diluted with ethyl acetate, the organic phase was separated, and washed once with saturated brine. The organic phase was dried and filtered, and the filtrate was concentrated. The resulting residue was separated by flash silica gel column chromatography to give 7-chloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidin-4(3H)-one (597 mg, yield: 60.7%). ESI-MS: 276.2 [M+1] + .

[0488] Step 2: Synthesis of 4,7-dichloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidine

[0489] Dissolve 7-chloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidin-4(3H)-one (597 mg, 2.17 mmol) in acetonitrile (10 mL). Add DIPEA (1.12 g, 8.66 mmol) and POCl3 (664 mg, 4.33 mmol) at 0°C. Heat to 80°C for 2 hours. After completion of the reaction, concentrate to afford 4,7-dichloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidine (637 mg, yield: 100%). ESI-MS: 294.2 [M+1] + .

[0490] Step 3: Synthesis of tert-butyl (1S,5R)-3-(7-chloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0491] 4,7-Dichloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidine (637 mg, 2.17 mmol) was dissolved in acetonitrile (10 mL), and DIPEA (1.40 g, 10.83 mmol) and tert-butyl (1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (618 mg, 2.38 mmol) were added at 0°C. The mixture was reacted at 0°C for 2 hours. After completion of the reaction, the mixture was diluted with ethyl acetate, and the organic phase was separated and washed once with saturated brine. The organic phase was dried and filtered, and the filtrate was concentrated. The resulting residue was separated by flash silica gel column chromatography to give tert-butyl (1S,5R)-3-(7-chloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (927 mg, yield: 82.8%). ESI-MS: 517.2 [M+1] + .

[0492] Step 4: Synthesis of 8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-5-methoxy-4-((1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(methylthio)pyrido[4,3-d]pyrimidine

[0493] Tert-butyl (1S,5R)-3-(7-chloro-8-fluoro-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (927 mg, 1.79 mmol), ((2-fluoro-6-(methoxymethoxy)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-1-yl)ethynyl)triisopropylsilane (919 mg, 1.79 mmol), potassium phosphate (1.52 g, 7.17 mmol) were dissolved in 1,4-dioxane (20 mL) and water (2 mL), and CataxciAmPd G2 (240 mg, 0.36 mmol), nitrogen replacement three times, heating at 100 ° C for 2 hours. After the reaction is completed, it is diluted with ethyl acetate, the organic phase is separated and washed once with saturated brine. The organic phase is dried and filtered, the filtrate is concentrated, and the residue is separated by flash silica gel column chromatography to give tert-butyl (1S, 5R) -3- (8-fluoro-7- (7-fluoro-3- (methoxymethoxy) -8- ((triisopropylsilyl) ethynyl) naphthalen-1-yl) -5-methoxy-2- (methylthio) pyrido [4,3-d] pyrimidin-4-yl) -1- ((methoxy-d3) methyl) -3,8-diazabicyclo [3.2.1] octane-8-carboxylate (923 mg, yield: 59.6%). ESI-MS: 767.4 [M+1] + .

[0494] Step 5: Synthesis of tert-butyl (1S,5R)-3-(8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-5-methoxy-2-(methylsulfinyl)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0495] Tert-butyl (1S,5R)-3-(8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-5-methoxy-2-(methylthio)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (923 mg, 1.06 mmol) was dissolved in CHCl (50 mL), and m-CPBA (303 mg, 1.49 mmol) was added at 0°C. The mixture was reacted at room temperature for 1 hour. After completion of the reaction, the mixture was diluted with ethyl acetate, and the organic phase was separated and washed once with saturated brine. The organic phase was dried and filtered, the filtrate was concentrated, and the residue was separated by rapid silica gel column chromatography to give tert-butyl (1S, 5R) -3- (8-fluoro-7- (7-fluoro-3- (methoxymethoxy) -8- ( (triisopropylsilyl) ethynyl) naphthalen-1-yl) -5-methoxy-2- (methylsulfinyl) pyrido [4,3-d] pyrimidin-4-yl) -1- ( (methoxy-d3) methyl) -3,8-diazabicyclo [3.2 .1] octane-8-carboxylate and tert-butyl (1S,5R)-3-(8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-5-methoxy-2-(methylsulfonyl)pyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (950 mg, mixture). ESI-MS: 883.4 [M+1] + ,899.4[M+1] + .

[0496] Step 6: Synthesis of tert-butyl (1S,5R)-3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-5-methoxypyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate

[0497] Dissolve (2,6-dimethyltetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (261 mg, 1.58 mmol) in dry THF (20 mL). Add 1M LiHMDS / THF solution (1.26 mL, 1.26 mmol) under ice-water cooling. Allow to react for 30 minutes, then add the crude product from the previous step (930 mg, 1.053 mmol). Allow to react at 0°C for 1 hour. After completion of the reaction, dilute with ethyl acetate, separate the organic phase, and wash once with saturated brine. The organic phase was dried and filtered, and the filtrate was concentrated. The residue was separated by flash silica gel column chromatography to give tert-butyl (1S,5R)-3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-5-methoxypyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (272 mg, yield: 26.2%). ESI-MS: 984.5 [M+1] + .

[0498] Step 7: Synthesis of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-5-methoxy-4-((1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-6-fluoro-5-((triisopropylsilyl)ethynyl)naphthalen-2-ol

[0499] Tert-butyl (1S,5R)-3-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-7-(7-fluoro-3-(methoxymethoxy)-8-((triisopropylsilyl)ethynyl)naphthalen-1-yl)-5-methoxypyrido[4,3-d]pyrimidin-4-yl)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (262 mg, 0.27 mmol) was dissolved in CH2Cl2 (4 mL), and hydrochloric acid / dioxane solution (1 mL, 1N) was added under ice-water cooling, and the reaction was carried out at 0°C for 2 hours. After the reaction, the reaction mixture was concentrated to give 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-5-methoxy-4-((1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-6-fluoro-5-((triisopropylsilyl)ethynyl)naphthalen-2-ol (223.6 mg, yield: 100%). ESI-MS: 840.4 [M+1] + .

[0500] Step 8: Synthesis of 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-5-methoxy-4-((1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol

[0501] 4-(2-((2,6-Dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-5-methoxy-4-((1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-6-fluoro-5-((triisopropylsilyl)ethynyl)naphthalen-2-ol (223.6 mg, 0.27 mmol) was dissolved in DMF (10 mL), CsF (4.04 g, 26.62 mmol) was added, and the mixture was heated at 50°C with stirring for 2 hours. The reaction was monitored to completion by LCMS. The mixture was filtered, concentrated, and then separated by reverse phase column chromatography [eluent: 0-80% acetonitrile: water] to give 4-(2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-5-methoxy-4-((1S,5R)-1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol (61.6 mg, yield: 33.8%). ESI-MS: 684.4 [M+1] + .

[0502] 1 H NMR(400MHz,MeOH-d4)δ8.71(dd,J=9.1,5.9Hz,1H),8.24–8.12(m,2H),8.03(dd,J=6.2,2.4Hz,1H),5.74(d,J=8.8Hz,4H),4.70(s,3H),4.58–4.30 (m,6H),4.26–4.09(m,4H),4.06–3.93(m,5H),3.44(d,J=16.3Hz,2H),2.60–2.48(m,2H),2.43–2.13(m,3H).

[0503] Examples 174-219, 358-359 can be prepared by selecting the corresponding intermediates according to the route of Example 173.

[0504] Example 220: Preparation of 4-(6-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)quinazolin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol

[0505] Refer to the preparation conditions of Example 1 and select the corresponding raw materials for preparation. 4-(6-chloro-2-((2,6-dimethylenetetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-8-fluoro-4-(1-((methoxy-d3)methyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)quinazolin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol: ESI-MS: 687.4 [M+1] + .

[0506] 1 H NMR(400MHz,MeOH-d4)δ7.87–7.77(m,2H),7.35–7.27(m,2H),7.04(d,J=2.0Hz ,1H),5.02(d,J=7.7Hz,4H),4.59–4.42(m,2H),4.29(d,J=11.0Hz,2H),3.78(d ,J=14.8Hz,2H),3.69–3.60(m,2H),3.57–3.45(m,4H),3.37(s,1H),2.80(d,J= 17.2Hz, 2H), 2.59 (d, J = 16.6Hz, 2H), 1.97–1.77 (m, 4H), 1.64 (d, J = 14.0Hz, 1H).

[0507] Examples 221-354, 360-363 were prepared by selecting corresponding raw materials according to the route of Example 220.

[0508] Note: Example 361 was obtained by SFC separation ((chiral column: DAICEL CHIRALPAK IG (250 mm*30 mm, 10 μm) mobile phase: CO 2 -i -PrOH (0.1% NH 3 ·H 2 O)).

[0509] The NMR data of the compound prepared in the above example are as follows:

[0510] Biological test evaluation

[0511] 1. KRAS G12D / cRAF binding assay

[0512] 1. Compound Preparation

[0513] Dissolve the compound in 100% DMSO at a starting concentration of 5 mM and serially dilute it 3-fold in DMSO for a total of 8 concentration points. At each concentration point, add 1 μL of compound or DMSO to 99 μL of assay buffer to create a 10X stock solution.

[0514] 2. Test steps

[0515] 1) Add 4 μL of His-tagged KRAS to a 384-well plate. G12D and GMPPNP working mixed solution.

[0516] 2) Add 10X compound stock solution or 1% DMSO to a 384-well plate.

[0517] 3) Centrifuge the plate at 1000 rpm for 1 minute.

[0518] 4) Add 4 μL of GST-tagged cRAF solution to the 384-well plate.

[0519] 5) Centrifuge the plate at 1000 rpm for 1 minute.

[0520] 6) Incubate the plate at room temperature for 15 minutes.

[0521] 7) Add 10 μL of assay working solution to a 384-well plate.

[0522] 8) Centrifuge the plate at 1000 rpm for 1 minute.

[0523] 9) Incubate the plate at room temperature for 60 minutes.

[0524] 10) Place the 384-well plate into Envision and acquire the assay data.

[0525] 3. Data processing

[0526] The ratio of the signal of the DMSO control group included in each assay plate to the Alphalisa signal in each compound well was calculated for each compound concentration. The 50% inhibition (IC) was determined using the four-parameter logistic dose-response equation using the test compound concentration and the ratio value. 50 ) required compound concentration. The endpoint value (IC 50 ) as a quality control measure. If the endpoint value is within three times of the expected value, the experiment is considered acceptable.

[0527] Table 1: Biological test results

[0528] The “positive compound 1” used in the biological test evaluation of this application is Example 252 in WO2021041671A1 (the positive compound 1 used in the following anti-proliferative 2D CTG test and mouse pharmacokinetic experiment is the same), and its chemical structure is as follows:

[0529] From the specific example compound KRAS G12D Based on the data of inhibitory activity of the series of compounds of the present invention on KRAS / cRAF binding, G12D Under the same test conditions, the cell inhibition activity of some of the compounds in the examples was even comparable to that of the positive compounds, or even improved to a certain extent.

[0530] 2. Anti-proliferation 2D CTG test

[0531] 1. Experimental steps:

[0532] 1.1 Day 0 Cell Culture and Plating

[0533] Harvest cells in the logarithmic growth phase and count them using a platelet counter. Assess cell viability by trypan blue exclusion to ensure viability is above 90%. Adjust the cell concentration to achieve the desired final density, and add 90 μL of the cell suspension to a 96-well plate. Incubate overnight at 37°C, 5% CO2, and 95% humidity. The cell density and cell culture status are shown in the figure below.

[0534] 1.2 Day 1 Baseline Reading

[0535] Add 10 μL of PBS to each well of the T0 plate containing cells. Thaw the CTG reagent and equilibrate the plate to room temperature for 30 minutes. Add 50 μL / well of CTG solution to each well. Shake on an orbital shaker for 5 minutes to lyse the cells. Allow the plate to stand at room temperature for 20 minutes to stabilize the luminescence signal. Read the T0 fluorescence signal.

[0536] 1.3 Compound Treatment on Day 1

[0537] Make nine serial dilutions at a 1:5 ratio from a 10 mM stock solution. Transfer 10X compound-containing medium to the corresponding wells of a 96-well plate. The final highest compound concentration is 10 μM, and the final DMSO concentration is 0.1%. Place the 96-well plate in a 37°C incubator and incubate for 4 days.

[0538] 1.4 Reading the signal on the 5th day

[0539] 50 μL / well of detection reagent (CTG) was added to the cells, and the signal was read in the Envision machine.

[0540] 2. Data processing

[0541] The percent inhibition (%) at each compound concentration was calculated based on the signals in the HPE and ZPE control wells included in each assay plate and the fluorescence signals in the individual compound wells. ZPE control wells containing enzyme and substrate had an inhibition rate of 0%, while HPE control wells containing substrate only had an inhibition rate of 100%. The 50% inhibition (IC) was determined using the four-parameter logistic dose-response equation using the test compound concentration and the percent inhibition value. 50 ) required compound concentration. The endpoint value (IC 50 ) as a quality control measure. If the endpoint value is within three times of the expected value, the experiment is considered acceptable.

[0542] Table 2: Biological test results

[0543] The "positive compound 2" used in the biological test for evaluating anti-proliferative 2D CTG test in this application is Example 54 in WO2023098425A1, and its chemical structure is as follows:

[0544] Based on the cell activity data of the compounds in the specific examples, the compounds of the present invention have a strong inhibitory effect on KRAS cell activity. Under the same test conditions, compared with the positive compounds, the cell inhibitory activity of some of the compounds in the examples is several times or even more than ten times higher.

[0545] 3. Pharmacokinetic Experiments in Mice

[0546] (1) Research objectives

[0547] The purpose of this study is to study the pharmacokinetic behavior of some compounds of the present invention. The administration method is: single oral (PO) or intravenous (IV) administration to ICR mice.

[0548] (2) Experimental plan

[0549] 1. Experimental drugs

[0550] The compounds used in this test are from the specific examples of the present invention and the listed positive compounds.

[0551] 2. Experimental Animals

[0552] ICR mice male N=9 Original source: Shanghai Xipul-Bikai Laboratory Animal Co., Ltd.

[0553] 3. Drug preparation and administration

[0554] Weigh the compounds and dissolve them in the corresponding solvents (0.5% CMC + 1% Tween aqueous solution or 10% PG + 10% 80% pH 3 citrate buffer (pH 3), shaken and sonicated to prepare a 1 mg / mL solution. Nine mice were fasted overnight and administered orally (PO) or intravenously (IV) at a dose of 10 mg / kg PO (or 2 mg / kg IV).

[0555] 4. Sample collection

[0556] Approximately 90 μL of blood was collected from the submandibular vein at each time point, anticoagulated with sodium heparin, placed on ice, and centrifuged within 1 hour to separate plasma (centrifugation conditions: 8000 rpm, 6 minutes, 2-8°C). Blood was collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours. Samples were stored at -20°C.

[0557] For each 40 μL plasma sample, add 160 μL of ice-cold acetonitrile containing an internal standard, vortex for 3 minutes, and centrifuge at 11,000 rpm for 5 minutes. 100 μL of the supernatant is added to 100 μL of water, and 5 μL is injected into the LC / MS / MS for analysis.

[0558] 5. Test results

[0559] Based on the pharmacokinetic data of the compounds in the above specific examples, the compounds of this invention, by introducing substituents on the bridged ring, exhibit excellent exposure and oral bioavailability in mice after a single oral dose (10 mg / kg). Head-to-head comparisons of multiple groups of positive compounds revealed approximately a 5-10-fold increase in exposure or oral bioavailability. These experiments demonstrate excellent oral bioavailability of the compounds of this invention, potentially addressing the issue of poor PK and unsuitability of positive compounds for oral administration.

[0560] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above disclosure, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof: in, X is CR9 or N; Ring A is C 6-10 Aryl or 5-10 membered heteroaryl, preferably, the C 6-10 aryl or 5-10 membered heteroaryl is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, indole, benzothiophene, benzimidazole, benzopyrazole, benzoxazole and benzothiazole; R1 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 ; R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 ; R3 is selected from hydrogen, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, -C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenes Base, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R4 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R 5a Selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-S(O) r NR 16 R 17 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、 -C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2R 13 、-C 0-8 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-S(O) r NR 16 R 17 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted with a substituent, provided that R 5a 、R 5b and R 5c Not simultaneously hydrogen; Or, R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-10 Cycloalkyl or 3-10 membered heterocyclic group, each of which is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Substituents, R 5a The definitions are as above; Or, R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5a The definitions are as above; Or, R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5d 、R 5e and R 5f Each independently selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-8 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 substituted by aryl and 5-10 membered heteroaryl substituents; Each R6 and R7 are independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkylene, halogen substituted C 1-10 Alkylene, deuterium substituted C 1-10 Alkylene, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, halogen-substituted C 3-12 Cycloalkylene, deuterium substituted C 3-12 Cycloalkylene, 3-12 membered heterocyclic group, C 3-12 Heterocycloalkylene, halogen-substituted C 3-12 Heterocycloalkylene, deuterium substituted C 3-12 Heterocycloalkylene, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 , provided that at least one of R6 or R7 is C 1-10 Alkylene, halogen substituted C 1-10 Alkylene, deuterium substituted C 1-10 Alkylene, C 1-10 Cycloalkylene, halogen-substituted C 1-10 Cycloalkylene, deuterium substituted C 1-10 Cycloalkylene, C 1-10 Heterocycloalkylene, halogen-substituted C 1-10 Heterocycloalkylene or deuterium substituted C 1-10 heterocycloalkylene; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 , or, when p≥2, two adjacent R8 and their directly connected parts together form C 5-12 Cycloalkyl or 5-12 membered heterocyclic group, each of which is independently optionally further substituted by one or more groups selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R9 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、 -C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-10 Cycloalkyl or 3-10 membered heterocyclic group, the above C 3-10 Cycloalkyl or 3-10 membered heterocyclic groups are independently optionally further substituted with one or more radicals selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, halogen substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-S(O)(=NR 10 )R 11 、-C 0-8 Alkyl-N=S(O)R 11 R 12 、-C 0-8 Alkyl-N=SR 11 R 12 、-C 0-8 Alkyl-OS(O)2R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-SC(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 )2. -C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; Each R 10 are each independently selected from hydrogen, deuterium, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)R 15 and -C 0-8 Alkyl-C(O)NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; Each R 11 and R 12 are independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, or R 11 and R 12 Together with the sulfur atom directly connected thereto, a 3-10 membered heterocyclic group is formed, wherein each of the above groups is independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, -C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-OR 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-OC(O)R 15 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(=NR 16 )R 15 、-C 0-8 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; Each R 13 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent; Each R 14 independently selected from hydrogen, deuterium, C 1-10 Alkyl, C 2-10 Alkenyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl, each of which is independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent; Each R 15 independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent; Each R 16 and R 17 are independently selected from hydrogen, deuterium, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl and C 1-10 Alkanoyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10 Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent; Or, R 16 and R 17 Together with the nitrogen atom directly connected thereto, a 4-10 membered heterocyclic group or a 5-10 membered heteroaryl group is formed, wherein the 4-10 membered heterocyclic group or the 5-10 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, ═O, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, halogen-substituted C 1-10 Alkyl, deuterium substituted C 1-10 Alkyl, C 1-10 Alkoxy, C 3-12 Cycloalkyl, C 3-12 Cycloalkoxy, 3-12 membered heterocyclic group, 3-12 membered heterocyclic group, C 6-10 Aryl, C 6-10 Aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono C 1-10 Alkylamino, di-C 1-10 Alkylamino and C 1-10 substituted with an alkanoyl substituent; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, 4, 5 or 6; and Each r is independently 0, 1 or 2.

2. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: X is CR9 or N; R1 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 ; R2 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 ; R3 is selected from hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R4 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 alkyl -S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-S(O) r NR 16 R 17 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2R 13 、-C 0-4 Alkyl-NH-S(O)2NR 16 R 17 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-S(O) r NR 16 R 17 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、 -C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted with a substituent, provided that R 5a 、R 5b and R 5c Not simultaneously hydrogen; Or, R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituents, R 5a The definitions are as above; Or, R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5a The definitions are as above; Or, R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5d 、R 5e and R 5f Each independently selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl and 5-8 membered heteroaryl substituents; Each R6 and R7 are independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkylene, halogen substituted C 1-4 Alkylene, deuterium substituted C 1-4 Alkylene, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkylene, halogen-substituted C 3-6 Cycloalkylene, deuterium substituted C 3-6 Cycloalkylene, 3-6 membered heterocyclic group, C 3-6 Heterocycloalkylene, halogen-substituted C 3-6 Heterocycloalkylene, deuterium substituted C 3-6 Heterocycloalkylene, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , provided that at least one of R6 or R7 is C 1-4 Alkylene, halogen substituted C 1-4 Alkylene, deuterium substituted C 1-4 Alkylene, C 3-6 Cycloalkylene, halogen-substituted C 3-6 Cycloalkylene, deuterium substituted C 3-6 Cycloalkylene, C 3-6 Heterocycloalkylene, halogen-substituted C 3-6 Heterocycloalkylene or deuterium substituted C 3-6 heterocycloalkylene; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 alkyl -N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 , or, when p≥2, two adjacent R8 and their directly connected parts together form C 5-10 Cycloalkyl or 5-10 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; R9 is selected from hydrogen, deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more radicals selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-S(O)(=NR 10 )R 11 、-C 0-4 Alkyl-N=S(O)R 11 R 12 、-C 0-4 Alkyl-N=SR 11 R 12 、-C 0-4 Alkyl-OS(O)2R 13 、-C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)SR 14 、-C 0-4 Alkyl-SC(O)R 15 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-P(O)(R 15 )2. -C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r as defined in claim 1.

3. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each R 10 are each independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)R 15 and -C 0-4 Alkyl-C(O)NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; Each R 11 and R 12 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl and 5-8 membered heteroaryl, or R 11 and R 12 Together with the sulfur atom directly connected thereto, a 3-6 membered heterocyclic group is formed, wherein each of the above groups is independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -C 0-4 Alkyl-S(O) r R 13 、-C 0-4 Alkyl-OR 14 、-C 0-4 Alkyl-C(O)OR 14 、-C 0-4 Alkyl-C(O)R 15 、-C 0-4 Alkyl-OC(O)R 15 、-C 0-4 Alkyl-NR 16 R 17 、-C 0-4 Alkyl-C(=NR 16 )R 15 、-C 0-4 Alkyl-N(R 16 )-C(=NR 17 )R 15 、-C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 substituted by a substituent; Each R 13 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent; Each R 14 independently selected from hydrogen, deuterium, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl and 5-8 membered heteroaryl, each of which is independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent; Each R 15 independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 1-4 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, cyano, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy and -NR 16 R 17 substituted by a substituent; Each R 16 and R 17 are independently selected from hydrogen, deuterium, hydroxyl, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylamino Sulfonyl and C 1-4 Alkanoyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent; Or, R 16 and R 17 Together with the nitrogen atom directly connected thereto, a 4-8 membered heterocyclic group or a 5-8 membered heteroaryl group is formed, wherein the 4-8 membered heterocyclic group or the 5-8 membered heteroaryl group is optionally further substituted with one or more selected from deuterium, halogen, hydroxyl, =O, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen-substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, 3-6 membered heterocyclic group, 3-6 membered heterocyclic group, C 6-8 Aryl, C 6-8 Aryloxy, 5-8 membered heteroaryl, 5-8 membered heteroaryloxy, amino, mono C 1-4 Alkylamino, di-C 1-4 Alkylamino and C 1-4 substituted with an alkanoyl substituent, Each r is independently 0, 1 or 2.

4. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R2 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ; R3 is selected from hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-C(O)R 15 、-OC(O)R 15 、-NR 16 R 17 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; R4 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-S-C(O)R 15 、-C(O)R 15 、-O-C(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、 -C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r as defined in claim 1; Preferably, R2 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups; R3 is selected from hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-C(O)R 15 、-OC(O)R 15 、-NR 16 R 17 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by a cycloalkyl group or a 3-6 membered heterocyclic group; R4 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, each of which is independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl, 5-8 membered heteroaryl, =O and =S; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r as defined in claim 1.

5. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIa) or a compound of formula (IIb): wherein each X is independently CR9 or N; Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole; Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ; Each R2 is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano, C 1-4 Alkyl, halogen substituted C 1-4 alkyl, Deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups; Each R 5a are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; Each R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted with a substituent, provided that R 5a 、R 5b and R 5c Not simultaneously hydrogen; Or, R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituents, R 5a The definitions are as above; Or, R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5a The definitions are as above; Or, R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached, Each R 5d and R 5e are independently selected from hydrogen, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 aryl and 5-8 membered heteroaryl substituents, provided that R 5d and R 5e Not simultaneously hydrogen; Each R 5f Each independently selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl and 5-8 membered heteroaryl substituents; In the compound of formula (IIb), R 6a and R 6b are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 Alkyl, or R 6a and R 6b Together with the carbon atom to which it is directly connected, it forms a C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 The cycloalkyl or 3-6 membered heterocyclyl is independently optionally further substituted with one or more substituents selected from deuterium or halogen; Each R 7a and R 7b are each independently selected from hydrogen, deuterium, halogen, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Or, R 7a and R 7b Together with the carbon atom to which it is directly connected, it forms a C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 The cycloalkyl or 3-6 membered heterocyclyl is independently optionally further substituted with one or more substituents which are deuterium or halogen; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , or, when p≥2, two adjacent R8 and their directly connected parts together form C 5-6 Cycloalkyl or 5-6 membered heterocyclic group, each of which is independently optionally further substituted by one or more groups selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 , p and r are as defined in claim 1.

6. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl; Or, R 7a and R 7b Together with the carbon atom to which it is directly attached, it forms a C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 The cycloalkyl or 3-6 membered heterocyclyl groups are independently optionally further substituted with one or more substituents selected from deuterium, fluorine, chlorine and bromine.

7. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: In the compound of formula (IIb), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl, or, R 6a and R 6b Together with the carbon atom to which it is directly attached, it forms a C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, the C 3-6 The cycloalkyl or 3-6 membered heterocyclyl groups are independently optionally further substituted with one or more substituents selected from deuterium, fluorine, chlorine and bromine.

8. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: X is CR9 or N; R1 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 ; R9 is selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 substituted by a substituent; Among them, R 14 、R 16 and R 17 As defined in claim 5; Preferably, X is CR9 or N; R1 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl 1-Hydroxy, ... R is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, aziridine, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino, and amino; Alternatively, R9 and R1 together with the portion to which they are directly attached form an oxetane group, which is optionally further substituted with one or more substituents selected from the group consisting of deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, azirane, oxetanyl, azetidinyl, =O, =S, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino.

9. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r as defined in claim 5; Preferably, each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -OR 14 and -NR 16 R 17 substituted by a substituent; Among them, R 14 、R 16 and R 17 As defined in claim 5; More preferably, each R8 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, aziridine, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino, and the above groups are each independently optionally further substituted by one or more deuterium, fluorine, chlorine, bromine, cyano, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, monomethylamino, dimethylamino and amino. The alkylene radicals may be substituted with fluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, azirane, oxetanyl, azetidinyl, =O, =S, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino substituents.

10. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 5a Selected from deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; R 5b and R 5c are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r as defined in claim 5; Preferably, R 5a Selected from deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -C(O)NR 16 R 17 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 substituted by cycloalkyl, 3-6 membered heterocyclyl, =O and =S; R 5b and R 5c are each independently hydrogen, deuterium, halogen or C 1-4 Alkyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, =O, =S and -OR 14 substituted by a substituent; Among them, R 14 、R 16 and R 17 As defined in claim 5.

11. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r as defined in claim 5; Preferably, R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl and -OR 14 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, =O, =S and -OR 14 substituted by a substituent; R 5b and R 5c Together with the carbon atom directly connected to it, it forms a C(O), C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, each of the above groups is independently optionally further substituted by one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 Substituents of Among them, R 14 、R 16 and R 17 As defined in claim 5.

12. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 5a Selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、 -N=SR 11 R 12 、-OS(O)2R 13 、-NH-S(O)2R 13 、-NH-S(O)2NR 16 R 17 、-S(O) r R 13 、-S(O) r NR 16 R 17 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 , the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 Aryl, 5-8 membered heteroaryl, =O, =S, -SF5, -S(O)(=NR 10 )R 11 、-N=S(O)R 11 R 12 、-N=SR 11 R 12 、-OS(O)2R 13 、-S(O) r R 13 、-OR 14 、-C(O)OR 14 、-C(O)SR 14 、-SC(O)R 15 、-C(O)R 15 、-OC(O)R 15 、-P(O)(R 15 )2、-NR 16 R 17 、-C(=NR 16 )R 15 、-N(R 16 )-C(=NR 17 )R 15 、-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by a substituent; R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5d and R 5e are independently selected from hydrogen, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 aryl and 5-8 membered heteroaryl substituents, provided that R 5d and R 5e Not simultaneously hydrogen; Among them, R 10 、R 11 、R 12 、R 13 、R 14 、R 15 、R 16 、R 17 and r as defined in claim 5; Preferably, R 5a Selected from hydrogen, deuterium, halogen and C 1-4 Alkyl, the above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, =O, =S and -OR 14 substituted by a substituent; R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5d and R 5e are independently selected from hydrogen, halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 aryl and 5-8 membered heteroaryl substituents, provided that R 5d and R 5e Not simultaneously hydrogen; Among them, R 14 、R 16 and R 17 As defined in claim 5.

13. The compound of formula (I) according to claim 5, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 5a 、R 5b and R 5c Together with the carbon atom to which it is directly attached, R 5f Selected from halogen, cyano, C 1-4 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group and -C 0-4 Alkyl-NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, nitro, azido, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, C 6-8 substituted by aryl and 5-8 membered heteroaryl substituents; Among them, R 16 and R 17 As defined in claim 5.

14. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIIa1) or a compound of formula (IIIb1): wherein each X is independently CR9 or N; Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole; Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; Each each independently selected from deuterium-substituted methyl, ethyl, isopropyl, methoxymethyl, cyclopropyloxymethyl and 1-hydroxy-1-methyl-ethyl, wherein the ethyl, isopropyl, methoxymethyl, cyclopropyloxymethyl or 1-hydroxy-1-methyl-ethyl is each independently optionally further substituted with one or more deuteriums; In the compound of formula (IIIb1), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Among them, R 14 、R 16 、R 17 and p as defined in claim 1.

15. The compound of formula (I) according to claim 14, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each Each is independently selected from deuterium-substituted methyl, ethyl, isopropyl, cyclopropyloxymethyl and 1-hydroxy-1-methyl-ethyl, and the ethyl, isopropyl, cyclopropyloxymethyl or 1-hydroxy-1-methyl-ethyl is each independently further substituted by at least 1, 2, 3, 4, 5, 6 or 7 deuterium.

16. The compound of formula (I) according to claim 14, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each Each independently selected from -CH2D, -CHD2, -CD3, 17. The compound of formula (I) according to claim 14, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each Each independently selected from -CH2D, -CHD2, -CD3, 18. The compound of formula (I) according to claim 14, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each are each independently ethyl or isopropyl.

19. The compound of formula (I) according to claim 14, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each are each independently a methoxymethyl group, which is optionally further substituted with one or more deuterium groups; provided that the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are not the following compounds:

20. The compound of formula (I) according to claim 19, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each Each is independently a methoxymethyl group, which is optionally further substituted with at least 1, 2, 3, 4 or 5 deuterium groups.

21. The compound of formula (I) according to claim 19, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each Each independently selected from 22. The compound of formula (I) according to claim 19, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each Each independently 23. The compound of formula (I) according to claim 14, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each X is independently CR9 or N; Each R1 is independently selected from methoxy, ethoxy, isopropoxy, cyclopropyloxy, trideuteriomethoxy, monomethylamino, dimethylamino and amino; Each R9 is independently selected from hydrogen, fluorine, chlorine, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

24. The compound of formula (I) according to claim 14, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each X is independently CR9, and R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Among them, R 14 、R 16 and R 17 As defined in claim 1.

25. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIIa2) or a compound of formula (IIIb2): wherein each X is independently CR9 or N; Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isocyanyl, Quinolinyl, benzothiophene, or benzothiazole; Each ring B is independently selected from oxetanyl, oxolanyl and oxhexyl; Each R a are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 ; Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; In the compound of formula (IIIb2), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; q is 0, 1, 2, or 3; Among them, R 14 、R 16 、R 17 and p as defined in claim 1.

26. The compound of formula (I) according to claim 25, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each ring B is independently oxetane or oxhexyl; Each R a Each is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

27. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIIa3) or a compound of formula (IIIb3): wherein each X is independently CR9 or N; Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole; Each ring C is independently selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; Each R b are each independently selected from hydrogen, deuterium, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, =O, =S, -OR 14 and -NR 16 R 17 ; Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; In the compound of formula (IIIb3), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; q is 0, 1, 2, or 3; Among them, R 14 、R 16 、R 17 and p as defined in claim 1.

28. The compound of formula (I) according to claim 27, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: Each ring C is independently cyclopropyl; Each R b Each is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl.

29. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIIa4) or a compound of formula (IIIb4): wherein each X is independently CR9 or N; Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole; Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; R 5a is selected from hydrogen, fluorine and methyl; R 5d is selected from hydrogen, fluorine and methyl; R 5e is selected from hydrogen, fluorine and methyl; In the compound of formula (IIIb4), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Among them, R 14 、R 16 、R 17 and p as defined in claim 1.

30. The compound of formula (I) according to claim 29, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: R 5a is hydrogen; R 5d is fluorine; R 5e is hydrogen or fluorine.

31. The compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that: The compound of formula (I) is a compound of formula (IIIa5) or a compound of formula (IIIb5): wherein each X is independently CR9 or N; Each ring A is independently phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, isoquinolyl, benzothiophene or benzothiazole; Each R1 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; R 5f is selected from hydrogen, fluorine and methyl; In the compound of formula (IIIb5), R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, C 1-3 Alkyl, halogen substituted C 1-3 Alkyl and deuterium substituted C 1-3 alkyl; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic group, -OR 14 and -NR 16 R 17 The above groups are each independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Each R9 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, -OR 14 and -NR 16 R 17 ; Alternatively, R9 and R1 together with the part to which they are directly connected form a C 3-8 Cycloalkyl or 3-8 membered heterocyclic group, the above C 3-8 Cycloalkyl or 3-8 membered heterocyclic groups are independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NR 16 R 17 substituted by a substituent; Among them, R 14 、R 16 、R 17 and p as defined in claim 1.

32. The compound of formula (I) according to claim 31, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that R 5f It is a methyl group.

33. The compound of formula (I) according to claim 14, 19, 25, 27, 29 or 31, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that Each X is independently CR9 or N; Each R1 is independently selected from hydrogen, halogen, -OR 14 and -NR 16 R 17 ; Each R9 is independently selected from hydrogen, halogen, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl and deuterium substituted C 1-4 alkyl; Alternatively, R9 and R1 together with the part to which they are directly attached form a 3-8 membered heterocyclic group containing N or O; Among them, R 14 、R 16 and R 17 As defined in claim 1; Preferably, each X is independently CR9 or N; Each R1 is independently selected from hydrogen, fluorine, chlorine, hydroxy, methoxy, ethoxy, isopropoxy, cyclopropyloxy, trideuteriomethoxy, monomethylamino, dimethylamino and amino; Each R9 is independently selected from hydrogen, fluorine, chlorine, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl; Alternatively, R9 and R1 together with the moiety to which they are directly attached form an oxacyclohexyl group.

34. The compound of formula (I) according to claim 14, 19, 25, 27, 29 or 31, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that Each ring A is independently selected from phenyl, naphthyl, pyridyl, pyrimidinyl, benzothiophene and benzothiazole; Each R8 is independently selected from hydrogen, deuterium, halogen, cyano, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, -OR 14 and -NH2, each of the above groups being independently optionally further substituted with one or more selected from deuterium, halogen, cyano, C 1-4 Alkyl, halogen substituted C 1-4 Alkyl, deuterium substituted C 1-4 Alkyl, =O, -OR 14 and -NH2 substituents; Among them, R 14 As defined in claim 1.

35. A compound of formula (I) according to claim 14, 19, 25, 27, 29 or 31, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, each Each is independently selected from the following structures: Each R 8a 、R 8b 、R 8c and R 8d each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxy, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, aziridine, oxetanyl, azetidinyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino, Methylamino and amino, each of which is independently optionally further substituted with one or more substituents selected from deuterium, fluorine, chlorine, bromine, cyano, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, ethynyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl, trideuteriomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxirane, azirane, oxetanyl, azetidinyl, =0, methoxy, ethoxy, propoxy, isopropoxy, butoxy, cyclopropyloxy, cyclobutyloxy, monomethylamino, dimethylamino and amino.

36. The compound of formula (I) according to claim 14, 19, 25, 27, 29 or 31, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that R 6a and R 6b are each independently selected from hydrogen, deuterium, fluorine, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl; Preferably, R 6a and R 6b are each independently hydrogen, deuterium or fluorine.

37. The compound of formula (I) according to claim 14, 19, 25, 27, 29 or 31, its stereoisomer or a pharmaceutically acceptable salt thereof, characterized in that Each R 7a and R 7b are each independently selected from hydrogen, deuterium, fluorine, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monodeuteriomethyl, dideuteriomethyl and trideuteriomethyl; Preferably, each R 7a and R 7b are each independently hydrogen, deuterium or fluorine.

38. The compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 37, characterized in that: Selected from the following compounds:

39. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 38, a stereoisomer thereof or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

40. Use of a compound of formula (I) according to any one of claims 1 to 38, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating and / or preventing cancer or tumor associated with KRAS G12D.

41. The compound of formula (I) according to any one of claims 1 to 38, its stereoisomer or pharmaceutically acceptable salt thereof, can be used in the preparation of a method for preventing and / or treating sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, teratoma associated with KRAS G12D; bronchial cancer (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar carcinoma) cancer, bronchial adenoma, lymphoma, chondromatous hamartoma, mesothelioma; esophageal cancer (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), gastric cancer (lymphoma, leiomyosarcoma), pancreatic cancer (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestinal cancer (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyomas, hemangiomas, lipomas, neuroendocrine tumors). fibroma, fibroma), colorectal cancer (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); kidney cancer (adenocarcinoma, Wilms' tumor (Nephroblastoma), lymphoma, leukemia), bladder and urethra cancer (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate cancer (adenocarcinoma, sarcoma), testicular cancer (seminoma, teratoma, embryonal carcinoma, teratothelioma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); liver cancer (hepatocellular carcinoma), bile duct cancer, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; gallbladder cancer, ampullary carcinoma, bile duct cancer; osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous tissue Cell tumor, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochondroma (osteocartilaginous exostosis), benign enchondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; skull cancer (osteomas, hemangiomas, granulomas, xanthomas, osteitis deformans), meningeal cancer (meningioma, meningiosarcoma, glioma), brain cancer (astrocytoma, medulloblastoma, glioma, ependymoma, blastoma (pinealoma), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors, spinal neurofibroma, meningioma, glioma Cancers of the uterus (endometrial cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa theca cell tumor, Settley-Redig cell tumor, dysgerminoma, malignant teratoma), vulvar cancer (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vaginal cancer (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma)), fallopian tube (carcinoma); blood cancers (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma);Use in medicine for the treatment of malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus, lipoma, hemangioma, dermatofibroma, keloid, psoriasis, adrenal tumor or neuroblastoma.

42. Use of a compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 38 for treating and / or preventing cancer or tumor associated with KRAS G12D.

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