Triazolopyrimidine derivative, preparation method therefor and use thereof

Abstract

A triazolopyrimidine derivative, a preparation method therefor and a use thereof. The present invention particularly relates to a compound represented by general formula (IC) or a stereoisomer thereof, a preparation method therefor, a pharmaceutical composition containing the compound, and a use of the compound in preparing a drug for treating diseases. The compound has a structure represented by formula (IC).

Description

A triazolopyrimidine derivative, its preparation method and application

[0001] This application claims the priority of Chinese Patent Application No. 2024100584923 with a filing date of January 15, 2024; the priority of Chinese Patent Application No. 2024101721627 with a filing date of February 6, 2024; the priority of Chinese Patent Application No. 2024101819911 with a filing date of February 18, 2024; the priority of Chinese Patent Application No. 2024103556304 with a filing date of March 26, 2024; the priority of Chinese Patent Application No. 2024105451218 with a filing date of April 30, 2024; the priority of Chinese Patent Application No. 2024105806484 with a filing date of May 10, 2024 Priority to Chinese Patent Application No. 2024105999241, filed on May 14, 2024; Priority to Chinese Patent Application No. 2024106135400, filed on May 16, 2024; Priority to Chinese Patent Application No. 2024107582914, filed on June 12, 2024; Priority to Chinese Patent Application No. 2024110465352, filed on July 31, 2024; Priority to Chinese Patent Application No. 2024115916705, filed on November 7, 2024, and Priority to Chinese Patent Application No. 2025100334871, filed on January 8, 2025. This application incorporates the entirety of the aforementioned Chinese patent applications. Technical Field

[0002] The present disclosure belongs to the field of medicinal chemistry, and specifically relates to a triazolopyrimidine derivative, a preparation method and application thereof. Background Art

[0003] The RecQ helicase subfamily is a class of enzymes that unwind double-stranded nucleotides. Within cells, they participate in DNA replication, repair, transcriptional recombination, RNA splicing, ribosome assembly, protein translation, and telomere stability. This family was first discovered in prokaryotes, and RecQ family members are highly conserved from prokaryotes (RecQ) to yeast (sgs1) and humans (RECQ1, BLM, WRN, RECQ4, and RECQ5). WRN, a member of the RecQ family of DNA helicases, consists of 1432 amino acids and has a molecular mass of 160 kDa. WRN is primarily localized to the nucleolus and rapidly translocates to other nuclear compartments following DNA damage. WRN is the only member of the human RecQ helicase family to possess 3'→5' exonuclease activity. Its N-terminal exonuclease domain facilitates WRN's ability to process complex nucleic acid structures, while the central unwinding domain binds and hydrolyzes ATP, providing energy for unwinding double-stranded DNA. The C-terminal HRDC domain can regulate the activity of catalyzing WRN binding to DNA.

[0004] Microsatellites (MS) are DNA sequences consisting of a few nucleotides (usually 1 to 6) repeated in tandem within the cellular genome, also known as short tandem repeats (STRs). When DNA mismatch repair (NMR) is dysfunctional, replication errors in microsatellites remain uncorrected and accumulate, leading to changes in the length or base composition of the microsatellite sequence, a phenomenon known as microsatellite instability (MSI), and a hypermutational genomic phenotype. In tumors, loss of MLH1 expression due to loss-of-function mutations in key MMR genes (MLH1, MSH2, MSH6, and PMS2) and related genes, or hypermethylation of the MLH1 promoter, often leads to MMR deficiency. Tumors can be categorized as either microsatellite-instability (MSI) or microsatellite-stable (MSS) based on their microsatellite stability. MSI is common in cancers, with solid tumors with higher incidences including endometrial cancer (about 30%), gastric cancer (about 20%), and colorectal cancer (about 15%).

[0005] There is a synthetic lethal relationship between WRN and MSI-H: in MSI tumor cell lines, knocking out WRN leads to genomic instability, cell cycle arrest, DNA double-strand breaks, and ultimately cancer cell death. Therefore, by developing small molecule inhibitors targeting WRN, it is hoped that selective killing of MSI-H tumor cells can be achieved, providing personalized anti-tumor treatment for MSI tumor patients.

[0006] The protein product encoded by the hERG gene is the inner pore-forming part of the key membrane-bound potassium ion channel in myocardial tissue. It is controlled by the membrane potential and regulates the outflow of potassium ions from the cell in a gated manner. When the compound binds to the hERG potassium channel, it blocks the outflow of potassium ions, which can prolong the repolarization time of myocardial cells, which is reflected in the electrocardiogram as a prolonged QT interval, and may induce the fatal risk of TdP. Therefore, the inhibition of hERG can lead to serious toxic side effects. The IC of the compound is 50 The larger the α, the lower the risk of hERG suppression. Summary of the Invention

[0007] The present invention aims to provide a triazolopyrimidine derivative, a preparation method and application thereof.

[0008] The present disclosure provides a compound represented by formula (IC), a stereoisomer or a pharmaceutically acceptable salt thereof:

[0009] in,

[0010] M is selected from a bond, CO, -NHCO-, -C(R 6-1 R 6-2 )-、

[0011] Ring A is selected from C 6-14 Aryl or 5-14 membered heteroaryl;

[0012] Ring B is selected from C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, C 6-14 Aryl or 5-14 membered heteroaryl; alternatively, Ring B is absent and R4 is directly attached to the parent structure;

[0013] Ring C is selected from C 3-12 Cycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl;

[0014] Ring E is selected from C 3-12 Cycloalkylene, C 3-12 Cycloalkenylene, 3-12 membered heterocycloalkylene, 3-12 membered heterocycloalkenylene, C 6-14Arylene or 5-14 membered heteroarylene; or ring E is directly connected to the parent to form

[0015] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, -C 1-6 Alkylene-C(=N-OH)NH-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3- 8-membered cycloalkylene, 3-8-membered heterocycloalkylene, 3-8-membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroaryl- or 5-14 membered heteroaryl, the imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1- 6-hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroarylene- or 5-14 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0016] Alternatively, L1, R3 and the parent form a fragment

[0017] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, thiol, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0018] R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 2a Substituted; said R 2a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0019] Alternatively, two R2 are connected to form C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, the C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0020] Alternatively, one of R2 and R3 is linked to form a 5-8 membered heterocycloalkenyl group, wherein the 5-8 membered heterocycloalkenyl group is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0021] R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6- 14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0022] L1 and R3 are connected to form a 3-8 membered heterocycloalkenyl or a 5-10 membered heteroaryl; the 3-8 membered heterocycloalkenyl or the 5-10 membered heteroaryl may be further substituted with deuterium, halogen, amino, hydroxyl, cyano, C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0023] R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl, 5-14 membered heteroaryl, -COR 4-1 、-COOR 4-1 、-OC(=O)R 4-1 、-SO2R 4-2 OR 4-3 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents in aryl or 5-14 membered heteroaryl; or, two R 4a Connected to form a 3-8 membered heterocycloalkyl or 3-8 membered heterocycloalkenyl;

[0024] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0025] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0026] R 4-3 Selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3- 8-membered cycloalkyl, 3-8-membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0027] R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, -SO2-C 1-6 Alkyl, -SF5, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1- 6-deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0028] R 6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0029] Or, R 6-1 、R 6-2 and the carbons between them form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl;

[0030] R 7-1 and R 7-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 haloalkoxy;

[0031] Or, R 7-1 and R 7-2 Connect to form C 3-8 Cycloalkyl;

[0032] x is selected from 0, 1, 2 or 3;

[0033] y is selected from 0, 1, 2, 3 or 4;

[0034] z is selected from 0, 1, 2, 3 or 4;

[0035] u is selected from 0, 1, 2, 3 or 4.

[0036] The present disclosure provides a compound represented by formula (IC), a stereoisomer or a pharmaceutically acceptable salt thereof:

[0037] in,

[0038] M is selected from a bond, CO, -NHCO-, -C(R 6-1 R 6-2 )-、

[0039] Ring A is selected from C 6-14 Aryl or 5-14 membered heteroaryl;

[0040] Ring B is selected from C 3-12Cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, C 6-14 Aryl or 5-14 membered heteroaryl; alternatively, Ring B is absent and R4 is directly attached to the parent structure;

[0041] Ring C is selected from C 3-12 Cycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl;

[0042] Ring E is selected from C 3-12 Cycloalkylene, C 3-12 Cycloalkenylene, 3-12 membered heterocycloalkylene, 3-12 membered heterocycloalkenylene, C 6-14 Arylene or 5-14 membered heteroarylene; or ring E is directly connected to the parent to form

[0043] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, -C 1-6 Alkylene-C(=N-OH)NH-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3- 8-membered cycloalkylene, 3-8-membered heterocycloalkylene, 3-8-membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroaryl- or 5-14 membered heteroaryl, the imino, C 1-6Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1- 6-hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroarylene- or 5-14 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0044] Alternatively, L1, R3 and the parent form a fragment

[0045] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, thiol, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0046] R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 2a Substituted; said R 2a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0047] Alternatively, two R2 are connected to form C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, the C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0048] Alternatively, one of R2 and R3 is linked to form a 5-8 membered heterocycloalkenyl group, wherein the 5-8 membered heterocycloalkenyl group is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0049] R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6- 14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0050] L1 and R3 are connected to form a 3-8 membered heterocycloalkenyl or a 5-10 membered heteroaryl; the 3-8 membered heterocycloalkenyl or the 5-10 membered heteroaryl may be further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0051] R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl, 5-14 membered heteroaryl, -COR 4-1 、-COOR 4-1 、-OC(=O)R 4-1 、-SO2R 4-2 OR 4-3 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents in aryl or 5-14 membered heteroaryl; or, two R 4a Connected to form a 3-8 membered heterocycloalkyl or 3-8 membered heterocycloalkenyl;

[0052] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0053] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0054] R 4-3 Selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3- 8-membered cycloalkyl, 3-8-membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0055] R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, -SO2-C 1-6 Alkyl, -SF5, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1- 6-deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0056] R 6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0057] Or, R 6-1 、R 6-2 and the carbons between them form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl;

[0058] x is selected from 0, 1, 2 or 3;

[0059] y is selected from 0, 1, 2, 3 or 4;

[0060] z is selected from 0, 1, 2, 3 or 4;

[0061] u is selected from 0, 1, 2, 3 or 4.

[0062] The present disclosure provides a compound represented by formula (IC), a stereoisomer or a pharmaceutically acceptable salt thereof:

[0063] in,

[0064] M is selected from a bond, CO, -NHCO-, -C(R 6-1 R 6-2 )-、

[0065] Ring A is selected from C 6-14 Aryl or 5-14 membered heteroaryl;

[0066] Ring B is selected from C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, C6-14 Aryl or 5-14 membered heteroaryl; alternatively, Ring B is absent and R4 is directly attached to the parent structure;

[0067] Ring C is selected from C 3-12 Cycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl;

[0068] Ring E is selected from C 3-12 Cycloalkylene, C 3-12 Cycloalkenylene, 3-12 membered heterocycloalkylene, 3-12 membered heterocycloalkenylene, C 6-14 Arylene or 5-14 membered heteroarylene; or ring E is directly connected to the parent to form

[0069] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, -C 1-6 Alkylene-C(=N-OH)NH-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3- 8-membered cycloalkylene, 3-8-membered heterocycloalkylene, 3-8-membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroaryl- or 5-14 membered heteroaryl, the imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1- 6-hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroarylene- or 5-14 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0070] Alternatively, L1, R3 and the parent form a fragment

[0071] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, thiol, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0072] R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 2a Substituted; said R 2a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0073] Alternatively, two R2 are connected to form C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, the C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0074] Alternatively, one of R2 and R3 is linked to form a 5-8 membered heterocycloalkenyl group, wherein the 5-8 membered heterocycloalkenyl group is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0075] R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6- 14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0076] L1 and R3 are connected to form a 3-8 membered heterocycloalkenyl or a 5-10 membered heteroaryl; the 3-8 membered heterocycloalkenyl or the 5-10 membered heteroaryl may be further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0077] R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl, 5-14 membered heteroaryl, -COR 4-1 、-COOR 4-1 、-OC(=O)R 4-1 、-SO2R 4-2 OR 4-3 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents in aryl or 5-14 membered heteroaryl; or, two R 4a Connected to form a 3-8 membered heterocycloalkyl or 3-8 membered heterocycloalkenyl;

[0078] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0079] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0080] R 4-3 Selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3- 8-membered cycloalkyl, 3-8-membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0081] R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0082] R 6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0083] Or, R 6-1 、R 6-2 and the carbons between them form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl;

[0084] x is selected from 0, 1, 2 or 3;

[0085] y is selected from 0, 1, 2, 3 or 4;

[0086] z is selected from 0, 1, 2, 3 or 4;

[0087] u is selected from 0, 1, 2, 3 or 4.

[0088] The present disclosure provides a compound represented by formula (IC), a stereoisomer or a pharmaceutically acceptable salt thereof:

[0089] in,

[0090] M is selected from a bond, CO, -NHCO-, -C(R 6-1 R 6-2 )-;

[0091] Ring A is selected from C 6-14 Aryl or 5-14 membered heteroaryl;

[0092] Ring B is selected from C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, C 6-14 Aryl or 5-14 membered heteroaryl; alternatively, Ring B is absent and R4 is directly attached to the parent structure;

[0093] Ring C is selected from C 6-14 Aryl or 5-14 membered heteroaryl;

[0094] Ring E is selected from C 3-12 Cycloalkylene, C 3-12 Cycloalkenylene, 3-12 membered heterocycloalkylene, 3-12 membered heterocycloalkenylene, C 6-14 Arylene or 5-14 membered heteroarylene; or ring E is directly connected to the parent to form

[0095] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6- 14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroaryl- or 5-14 membered heteroaryl, the imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroarylene- or 5-14 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0096] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0097] R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 2a Substituted; said R 2a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0098] Alternatively, two R2 are connected to form C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, the C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0099] Alternatively, one of R2 and R3 is linked to form a 5-8 membered heterocycloalkenyl group, wherein the 5-8 membered heterocycloalkenyl group is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0100] R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0101] L1 and R3 are connected to form a 3-8 membered heterocycloalkenyl or a 5-10 membered heteroaryl; the 3-8 membered heterocycloalkenyl or the 5-10 membered heteroaryl may be further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0102] R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl, 5-14 membered heteroaryl, -COR 4-1 、-COOR 4-1 、-OC(=O)R 4-1 、-SO2R 4-2 OR 4-3 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents in aryl or 5-14 membered heteroaryl; or, two R 4a Connected to form a 3-8 membered heterocycloalkyl or 3-8 membered heterocycloalkenyl;

[0103] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0104] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0105] R 4-3 Selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3- 8-membered cycloalkyl, 3-8-membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0106] R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0107] R 6-1 and R 6-2are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0108] Or, R 6-1 、R 6-2 and the carbons between them form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl;

[0109] x is selected from 0, 1, 2 or 3;

[0110] y is selected from 0, 1, 2, 3 or 4;

[0111] z is selected from 0, 1, 2, 3 or 4;

[0112] u is selected from 0, 1, 2, 3 or 4.

[0113] The present disclosure provides a compound represented by formula (IB), a stereoisomer or a pharmaceutically acceptable salt thereof:

[0114] in,

[0115] M is selected from a bond or CO;

[0116] Ring A is selected from C 6-14 Aryl or 5-14 membered heteroaryl;

[0117] Ring B is selected from C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, C 6-14 Aryl or 5-14 membered heteroaryl; alternatively, Ring B is absent and R4 is directly attached to the parent structure;

[0118] Ring C is selected from C 6-14 Aryl or 5-14 membered heteroaryl;

[0119] Ring E is selected from C 3-12 Cycloalkylene, C 3-12 Cycloalkenylene, 3-12 membered heterocycloalkylene, 3-12 membered heterocycloalkenylene, C 6-14 Arylene or 5-14 membered heteroarylene; or ring E is directly connected to the parent to form

[0120] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1- 6-halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-14 Arylene or 5-14 membered heteroarylene, the imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-14 Arylene or 5-14 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0121] R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0122] R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 2a Substituted; said R 2a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0123] Alternatively, two R2 are connected to form C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, the C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0124] Alternatively, one of R2 and R3 is linked to form a 5-8 membered heterocycloalkenyl group, wherein the 5-8 membered heterocycloalkenyl group is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0125] R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6- 14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0126] L1 and R3 are connected to form a 3-8 membered heterocycloalkenyl or a 5-10 membered heteroaryl; the 3-8 membered heterocycloalkenyl or the 5-10 membered heteroaryl may be further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0127] R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl, 5-14 membered heteroaryl, -COR 4-1 、-SO2R 4-2, the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1- 6 alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0128] R 4-1Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0129] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0130] R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0131] x is selected from 0, 1, 2 or 3;

[0132] y is selected from 0, 1, 2, 3 or 4;

[0133] z is selected from 0, 1, 2, 3 or 4;

[0134] u is selected from 0, 1, 2, 3 or 4.

[0135] In certain embodiments of the present disclosure, M is selected from CO; the definitions of other groups are as defined in any technical solution herein.

[0136] In certain embodiments of the present disclosure, M is selected from CO; the definitions of other groups are as defined in any technical solution herein.

[0137] In certain embodiments of the present disclosure, ring A is selected from 5-6 membered heteroaryl, 5-6 membered heteroaryl and C 3-6cycloalkenyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, or 5-6 membered heteroaryl and phenyl; other groups are defined as defined in any technical solution herein.

[0138] In certain embodiments of the present disclosure, ring A is selected from 5-6 membered heteroaryl, 5-6 membered heteroaryl and C 3-6 Cycloalkenyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, or 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl;

[0139] Preferably, ring A is selected from

[0140] The definitions of other groups are as defined in any technical solution herein.

[0141] In certain embodiments of the present disclosure, ring A is selected from 5-6 membered heteroaryl, preferably The definitions of other groups are as defined in any technical solution herein.

[0142] In certain embodiments of the present disclosure, ring A is selected from 5-6 membered heteroaryl and 5-6 membered heteroaryl; the definitions of other groups are as defined in any technical scheme herein.

[0143] In certain embodiments of the present disclosure, Ring A is selected from The definitions of other groups are as defined in any technical solution herein.

[0144] In certain embodiments of the present disclosure, Ring A is selected from The definitions of other groups are as defined in any technical solution herein.

[0145] In certain embodiments of the present disclosure, Ring A is selected from Alternatively, Ring A is selected from Alternatively, Ring A is selected from Alternatively, Ring A is selected from Alternatively, Ring A is selected from The definitions of other groups are as defined in any technical solution herein.

[0146] In certain embodiments of the present disclosure, Ring B is selected from C 3-10 Cycloalkenylspiro 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-6 membered heteroaryl and 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiro 3-10 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and C 3-10 Cycloalkenyl, phenyl and 3-10 membered heterocycloalkenyl, C 3-10Cycloalkenyl, 3-10 membered heterocycloalkenylphenyl, 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiroC 3-10 Cycloalkyl, 3-10 membered heterocycloalkenyl and 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, C 3-10 Cycloalkenylspiro C 3-10 Cycloalkyl, 3-10 membered heterocycloalkenyl and C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl; other groups are as defined in any technical solution herein.

[0147] In certain embodiments of the present disclosure, Ring B is selected from C 3-10 Cycloalkenylspiro 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-6 membered heteroaryl and 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiro 3-10 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and C 3-10 Cycloalkenyl, phenyl and 3-10 membered heterocycloalkenyl, C 3-10 Cycloalkenyl, 3-10 membered heterocycloalkenylphenyl, 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiroC 3-10 Cycloalkyl, 3-10 membered heterocycloalkenyl and 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, C 3-10 Cycloalkenylspiro C 3-10 The definitions of other groups are as defined in any technical solution herein.

[0148] In certain embodiments of the present disclosure, Ring B is selected from C 3-6 Cycloalkenyl spiro 3-6 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-6 membered heterocycloalkenyl spiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and C 3-6 Cycloalkenyl, phenyl and 3-6 membered heterocycloalkenyl, C 3-8 Cycloalkenyl, 3-6 membered heterocycloalkenylphenyl, 5-6 membered heteroaryl, 3-6 membered heterocycloalkenylspiro C 3-6 cycloalkyl, 3-6 membered heterocycloalkenyl and 3-6 membered heterocycloalkyl; the definitions of other groups are as defined in any technical solution herein.

[0149] In certain embodiments of the present disclosure, Ring B is selected from C 3-6 Cycloalkenyl spiro 3-6 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-6 membered heterocycloalkenyl spiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and C 3-6 Cycloalkenyl, or phenyl 3-6 membered heterocycloalkenyl;

[0150] The definitions of other groups are as defined in any technical solution herein.

[0151] In certain embodiments of the present disclosure, Ring B is selected from C 3-6 Cycloalkenyl spiro 3-6 membered heterocycloalkyl, 3-6 membered heterocycloalkenyl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-6 membered heterocycloalkenyl spiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and C 3-6 Cycloalkenyl, or phenyl 3-6 membered heterocycloalkenyl;

[0152] Preferably, ring B is selected from

[0153] The definitions of other groups are as defined in any technical solution herein.

[0154] In certain embodiments of the present disclosure, Ring B is selected from The definitions of other groups are as defined in any technical solution herein.

[0155] In certain embodiments of the present disclosure, ring B is selected from 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, preferably Preferred The definitions of other groups are as defined in any technical solution herein.

[0156] In certain embodiments of the present disclosure, ring B is selected from 3-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, preferably The definitions of other groups are as defined in any technical solution herein.

[0157] In certain embodiments of the present disclosure, Ring B is selected from Alternatively, Ring B is selected from Alternatively, Ring B is selected from Alternatively, Ring B is selected from Alternatively, Ring B is selected from The definitions of other groups are as defined in any technical solution herein.

[0158] In certain embodiments of the present disclosure, Ring B is selected from The definitions of other groups are as defined in any technical solution herein.

[0159] In certain embodiments of the present disclosure, ring C is selected from C 6-10Aryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, phenyl and 3-6 membered heterocycloalkenyl, 5-6 membered heteroaryl and phenyl, 3-6 membered heterocycloalkenyl and phenyl, 5-6 membered heteroaryl and C 3-6 Cycloalkenyl, or C 3-8 The definitions of other groups are as defined in any technical solution herein.

[0160] In certain embodiments of the present disclosure, ring C is selected from C 6-10 Aryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, phenyl and 3-6 membered heterocycloalkenyl, 5-6 membered heteroaryl and phenyl, 3-6 membered heterocycloalkenyl and phenyl, or 5-6 membered heteroaryl and C 3-6 The definitions of other groups are as defined in any technical solution herein.

[0161] In certain embodiments of the present disclosure, ring C is selected from C 6-10 aryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, phenyl and 3-6 membered heterocycloalkenyl, or 5-6 membered heteroarylphenyl.

[0162] In certain embodiments of the present disclosure, ring C is selected from C 6-10 Aryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, or phenyl and 3-6 membered heterocycloalkenyl;

[0163] Preferably, ring C is selected from phenyl,

[0164] The definitions of other groups are as defined in any technical solution herein.

[0165] In certain embodiments of the present disclosure, ring C is selected from C 6-10 Aryl, preferably phenyl; the definitions of other groups are as defined in any technical solution herein.

[0166] In certain embodiments of the present disclosure, ring C is selected from Alternatively, ring C is selected from Alternatively, ring C is selected from Alternatively, ring C is selected from Alternatively, ring C is selected from Alternatively, ring C is selected from Alternatively, ring C is selected from Alternatively, ring C is selected from Alternatively, ring C is selected from The definitions of other groups are as defined in any technical solution herein.

[0167] In certain embodiments of the present disclosure, ring C is selected from The definitions of other groups are as defined in any technical solution herein.

[0168] In certain embodiments of the present disclosure, ring E is selected from 5-6 membered heterocycloalkylene, 4-6 membered heterocycloalkylene spiro4-6 membered heterocycloalkylene, 5-6 membered heterocycloalkylene and 5-6 membered heterocycloalkylene, 5-6 membered heteroaryl and 5-6 membered heterocycloalkenyl, or 5-6 membered heterocycloalkylene and C 3-6 The definitions of other groups are as defined in any technical solution herein.

[0169] In certain embodiments of the present disclosure, ring E is selected from 5-6 membered heterocycloalkylene, 4-6 membered heterocycloalkylene spiro 4-6 membered heterocycloalkylene, 5-6 membered heterocycloalkylene and 5-6 membered heterocycloalkylene, or 5-6 membered heteroaryl and 5-6 membered heterocycloalkenyl; the definitions of other groups are as defined in any technical scheme herein.

[0170] In certain embodiments of the present disclosure, Ring E is selected from Wherein, the end with * is connected to M; the definitions of other groups are as defined in any technical solution of this article.

[0171] In certain embodiments of the present disclosure, ring E is selected from Wherein, the end with * is connected to M; the definitions of other groups are as defined in any technical solution of this article.

[0172] In certain embodiments of the present disclosure, Ring E is selected from Alternatively, ring E is selected from Wherein, the end with * is connected to M; the definitions of other groups are as defined in any technical solution of this article.

[0173] In certain embodiments of the present disclosure, ring E is selected from Wherein, the end with * is connected to M; the definitions of other groups are as defined in any technical solution of this article.

[0174] In certain embodiments of the present disclosure, the compound is as shown in formula (II),

[0175] in,

[0176] Ring B is selected from C 3-10Cycloalkenylspiro 3-10 membered heterocycloalkyl, 5-6 membered heteroaryl and 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiro 3-10 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, 7-10 membered heterocycloalkenyl, C 3-10 Cycloalkenyl, 3-10 membered heterocycloalkenylphenyl, 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiroC 3-10 Cycloalkyl, 3-10 membered heterocycloalkenyl and 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, C 3-10 Cycloalkenylspiro C 3-10 Cycloalkyl, 3-10 membered heterocycloalkenyl and C 3-10 Cycloalkyl, The definitions of other groups are as defined in any technical solution herein.

[0177] In certain embodiments of the present disclosure, the compound is as shown in formula (II),

[0178] in,

[0179] Ring B is selected from C 3-10 Cycloalkenylspiro 3-10 membered heterocycloalkyl, 5-6 membered heteroaryl and 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiro 3-10 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, 7-10 membered heterocycloalkenyl, C 3-10 Cycloalkenyl, 3-10 membered heterocycloalkenylphenyl, 5-6 membered heteroaryl, 3-10 membered heterocycloalkenylspiroC 3-10 Cycloalkyl, 3-10 membered heterocycloalkenyl and 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, C 3-10 Cycloalkenylspiro C 3-10 The definitions of other groups are as defined in any technical solution herein.

[0180] In certain embodiments of the present disclosure, the compound is as shown in formula (II),

[0181] in,

[0182] Ring B is selected from C 3-6 Cycloalkenylspiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-6 membered heterocycloalkenylspiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, 7-8 membered heterocycloalkenyl, C 3-8 Cycloalkenyl, 3-6 membered heterocycloalkenylphenyl, 5-6 membered heteroaryl, 3-6 membered heterocycloalkenylspiro C3-6 Cycloalkyl, 3-6 membered heterocycloalkenyl and 3-6 membered heterocycloalkyl, The definitions of other groups are as defined in any technical solution herein.

[0183] In certain embodiments of the present disclosure, the compound is as shown in formula (II),

[0184] in,

[0185] Ring B is selected from C 3-6 Cycloalkenyl spiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-6 membered heterocycloalkenyl spiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, or 7-8 membered heterocycloalkenyl; preferably The definitions of other groups are as defined in any technical solution herein.

[0186] In certain embodiments of the present disclosure, Ring B is selected from Alternatively, Ring B is selected from Alternatively, Ring B is selected from The definitions of other groups are as defined in any technical solution herein.

[0187] In certain embodiments of the present disclosure, when Ring B is When the structural fragment for The definitions of other groups are as defined in any technical solution herein.

[0188] In certain embodiments of the present disclosure, when Ring B is When the structural fragment for The definitions of other groups are as defined in any technical solution herein.

[0189] In certain embodiments of the present disclosure, the compound is as shown in formula (II),

[0190] in,

[0191] Ring B is selected from C 3-6 Cycloalkenyl spiro 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, 3-6 membered heterocycloalkenyl spiro 3-6 membered heterocycloalkyl, or 5-6 membered heteroaryl and 5-6 membered heteroaryl; preferably The definitions of other groups are as defined in any technical solution herein.

[0192] In certain embodiments of the present disclosure, Ring B is selected from The definitions of other groups are as defined in any technical solution herein.

[0193] In certain embodiments of the present disclosure, the structural fragment for The definitions of other groups are as defined in any technical solution herein.

[0194] In certain embodiments of the present disclosure, the compound is as shown in formula (III),

[0195] Wherein, R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, methyl, C 3-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 3-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 aryl or 5-14 membered heteroaryl, substituted by one or more substituents; the methyl group is optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 2-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 2-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C2-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0196] Preferably, R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, methyl, C3 alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C3 alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 aryl or 5-6 membered heteroaryl, substituted by one or more substituents; the methyl group is optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 2-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 2-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 2-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0197] More preferably, R3 is selected from trifluoromethoxy, vinyl, ethynyl, or cyano;

[0198] The definitions of other groups are as defined in any technical solution herein.

[0199] In certain embodiments of the present disclosure, R3 is selected from 5-6 membered heteroaryl, preferably The 5-6 membered heteroaryl group, Optionally deuterated, halogen, amino, hydroxy, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0200] In certain embodiments of the present disclosure, R3 is selected from The definitions of other groups are as defined in any technical solution herein.

[0201] In certain embodiments of the present disclosure, the compound is as shown in formula (IV),

[0202] R 1-1 Selected from deuterium, halogen, amino, hydroxyl, cyano, C 2-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, C 6-14Aryl or 5-14 membered heteroaryl, the amino, C 2-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0203] Preferably, R 1-1 Selected from deuterium, halogen, amino, hydroxyl, cyano, C 2-3 Alkyl, C2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 2-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1- 3-deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0204] More preferably, R 1-1 Selected from

[0205] w is selected from 0, 1 or 2;

[0206] The definitions of other groups are as defined in any technical solution herein.

[0207] In certain embodiments of the present disclosure, the compound is as shown in formula (IV'),

[0208] R 1-2 Selected from deuterium, halogen, amino, hydroxyl, cyano, C 2-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 2-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1- 6-hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1- 6 alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 aryl or 5-14 membered heteroaryl is substituted with one or more substituents; preferably, R 1-2 Selected from deuterium, halogen, amino, hydroxyl, cyano, C 2-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 2-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0209] More preferably, R 1-2 Selected from

[0210] w is selected from 0, 1 or 2;

[0211] The definitions of other groups are as defined in any technical solution herein.

[0212] In certain embodiments of the present disclosure, the compound is as shown in formula (V),

[0213] wherein ring A is selected from 5-6 membered heteroaryl and C3-6 cycloalkenyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, or 5-6 membered heteroaryl and phenyl, The definitions of other groups are as defined in any technical solution herein.

[0214] In certain embodiments of the present disclosure, the compound is as shown in formula (V),

[0215] wherein ring A is selected from 5-6 membered heteroaryl and C 3-6 Cycloalkenyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl, The definitions of other groups are as defined in any technical solution herein.

[0216] In certain embodiments of the present disclosure, the compound is as shown in formula (V),

[0217] wherein ring A is selected from 5-6 membered heteroaryl and C 3-6 Cycloalkenyl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, or 5-6 membered heteroaryl and 3-6 membered heterocycloalkenyl; preferably, ring A is selected from

[0218] The definitions of other groups are as defined in any technical solution herein.

[0219] In certain embodiments of the present disclosure, the compound is as shown in formula (VI),

[0220] in,

[0221] Ring C is selected from 5-membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, phenyl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and phenyl, or 5-6 membered heteroaryl and C 3-6 Cycloalkenyl, or C 3- 8 cycloalkyl; the definitions of other groups are as defined in any technical solution herein.

[0222] In certain embodiments of the present disclosure, the compound is as shown in formula (VI),

[0223] in,

[0224] Ring C is selected from 5-membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, phenyl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and phenyl, or 5-6 membered heteroaryl and C3-6 Cycloalkenyl, or C 3-8 The definitions of other groups are as defined in any technical solution herein.

[0225] In certain embodiments of the present disclosure, the compound is as shown in formula (VI),

[0226] in,

[0227] Ring C is selected from 5-membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, phenyl and 3-6 membered heterocycloalkenyl, 3-6 membered heterocycloalkenyl and phenyl, or 5-6 membered heteroaryl and C 3-6 The definitions of other groups are as defined in any technical solution herein.

[0228] In certain embodiments of the present disclosure, the compound is as shown in formula (VI),

[0229] in,

[0230] Ring C is selected from 5-membered heteroaryl, 5-6 membered heteroaryl and 5-6 membered heteroaryl, phenyl and 5-6 membered heteroaryl, or phenyl and 3-6 membered heterocycloalkenyl; preferably, ring C is selected from The definitions of other groups are as defined in any technical solution herein.

[0231] In certain embodiments of the present disclosure, the compound is as shown in formula (VI),

[0232] in,

[0233] Ring C is selected from 5-membered heteroaryl, 5-6-membered heteroaryl and 5-6-membered heteroaryl, phenyl and 5-6-membered heteroaryl, or phenyl and 3-6-membered heterocycloalkenyl; preferably, ring C is selected from

[0234] The definitions of other groups are as defined in any technical solution herein.

[0235] In certain embodiments of the present disclosure, ring C is selected from The definitions of other groups are as defined in any technical solution herein.

[0236] In certain embodiments of the present disclosure, ring C is selected from The definitions of other groups are as defined in any technical solution herein.

[0237] In certain embodiments of the present disclosure, the compound is as shown in formula (VII) or formula (VIII),

[0238] in,

[0239] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0240] Preferably, R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0241] More preferably, R 4-1 is selected from cyclopropyl, isopropyl or ethyl;

[0242] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkylthio, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0243] Preferably, R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6- 10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0244] Preferably, R 4-2 selected from methyl;

[0245] z is selected from 0, 1, 2 or 3;

[0246] The definitions of other groups are as defined in any technical solution herein.

[0247] In certain embodiments of the present disclosure, R 4-1 Selected from C 3-6 The cycloalkyl group is preferably a cyclopropyl group; the definitions of other groups are as defined in any technical solution herein.

[0248] In certain embodiments of the present disclosure, R 4-1 Selected from C 1-3 Alkyl; preferably isopropyl; or preferably ethyl; the definitions of other groups are as defined in any technical solution herein.

[0249] In certain embodiments of the present disclosure, R 4-1 Selected from -CH2CF3; or, R 4-1 Selected from -NHCH3; R 4-1 Selected from -N(CH3)2; or, R 4-1 Selected from -C(OH)(CH3)2; or, R 4-1 is selected from tert-butyl; or, R 4-1 Selected from -CH2-cyclopropyl; the definitions of other groups are as defined in any technical solution herein.

[0250] In certain embodiments of the present disclosure, the compound is as shown in formula (X),

[0251] Ring D is selected from 5-6 membered heterocyclic groups; preferably

[0252] R 4-3 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl;

[0253] Preferably, R 4-3 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6- 10 Aryl or 5-6 membered heteroaryl;

[0254] More preferably, R 4-3 selected from methyl;

[0255] z is selected from 0, 1, 2 or 3;

[0256] v is selected from 0, 1, 2 or 3;

[0257] The definitions of other groups are as defined in any technical solution herein.

[0258] In certain embodiments of the present disclosure, ring D is selected from The definitions of other groups are as defined in any technical solution herein.

[0259] In certain embodiments of the present disclosure, the compound is as shown in formula (IX),

[0260] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-C 6-14 Heterocycloalkenylene-、-C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroaryl-, 5-14 membered heteroaryl or -CH2CH2CONH-, the imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2- 6 alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-C 6-14 Heterocycloalkenylene-、-C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroarylene-, 5-14 membered heteroarylene or -CH2CH2CONH-, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0261] Preferably, L1 is selected from a bond, -O-, -S-, imino, C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, -C 1-3 Alkylene-CO-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1-3 Alkylene-5-6 membered heteroaryl-, 5-6 membered heteroaryl or -CH2CH2CONH-, the imino, C 1-3 Alkylene, -C 1-3 Alkylene-CONH-C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, -C 1-3 Alkylene-CO-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1- 3-alkylene-5-6 membered heteroarylene-, 5-6 membered heteroarylene or -CH2CH2CONH-, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0262] The definitions of other groups are as defined in any technical solution herein.

[0263] In certain embodiments of the present disclosure, the compound is as shown in formula (IX),

[0264] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, -C 1-6 Alkylene-C(=N-OH)NH-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-C 6-14 Heterocycloalkenylene-、-C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroaryl-, 5-14 membered heteroaryl or -CH2CH2CONH-, the imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-CONH-C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, -C 1-6 Alkylene-CO-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-6 Alkylene-3-8 membered heterocycloalkylene-, -C 1-6 Alkylene-C 6-14 Heterocycloalkenylene-、-C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroarylene-, 5-14 membered heteroarylene or -CH2CH2CONH-, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0265] Preferably, L1 is selected from a bond, -O-, -S-, imino, C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, -C 1-3 Alkylene-CO-, -C 1-3 Alkylene-C(=N-OH)NH-, C 2-4 Alkenylene, C 2- 4 alkynylene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1-3 Alkylene-5-6 membered heteroaryl-, 5-6 membered heteroaryl or -CH2CH2CONH-, the imino, C 1-3 Alkylene, -C 1-3 Alkylene-CONH-C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C1-3 Alkylene-NHSO2-, -C 1-3 Alkylene-CO-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1-3 Alkylene-5-6 membered heteroarylene-, 5-6 membered heteroarylene or -CH2CH2CONH-, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0266] In certain embodiments of the present disclosure, the compound is as shown in formula (IX),

[0267] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-14 Arylene or 5-14 membered heteroarylene, the imino, C 1-6 Alkylene, -CONH-, -CO-C 1-6 Alkylene-NH-, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, C 2-6 Alkenylene, C 2- 6 alkynylene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-14 Arylene or 5-14 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0268] Preferably, L1 is selected from a bond, -O-, -S-, imino, C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10 Arylene or 5-6 membered heteroarylene, the imino, C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2- 4 alkynylene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10 Arylene or 5-6 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0269] More preferably, L1 is selected from -CH2-, -CH2SO2NH-*, -COCH2NH-*, -CONH-*,

[0270] Among them, the side with * is connected to ring C;

[0271] The definitions of other groups are as defined in any technical solution herein.

[0272] In certain embodiments of the present disclosure, the compound is as shown in formula (IX),

[0273] L1 is selected from a bond, -O-, -S-, imino, C 1-6 Alkylene, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1- 6-alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-14 Arylene or 5-14 membered heteroarylene, the imino, C 1-6 Alkylene, -C 1-6 Alkylene-CONH-, -C 1-6 Alkylene-SO2NH-, -C 1-6 Alkylene-NHCONH-, -C 1-6 Alkylene-NHCO-, -C 1-6 Alkylene-NHSO2-, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Deuterated alkylene, C 1-6 Halogenated alkylene, C 1-6 Hydroxyalkylene, C 1-6 Alkyleneoxy, C 1-6 Alkylenethio, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-14 Arylene or 5-14 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-6 Alkyl, C2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0274] Preferably, L1 is selected from a bond, -O-, -S-, imino, C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10 Arylene or 5-6 membered heteroarylene, the imino, C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10Arylene or 5-6 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0275] More preferably, L1 is selected from -CH2-, -CH2SO2NH-*, Among them, the side with * is connected to ring C;

[0276] The definitions of other groups are as defined in any technical solution herein.

[0277] In certain embodiments of the present disclosure, L1 is selected from -COCH2NH-*; or, L1 is selected from -CONH-*; or, L1 is selected from Alternatively, L1 is selected from Alternatively, L1 is selected from Alternatively, L1 is selected from Alternatively, L1 is selected from Alternatively, L1 is selected from Alternatively, L1 is selected from Alternatively, L1 is selected from Alternatively, L1 is selected from -CH2CO-*, -CH2CON(CH3)-*, -CH2CONHCH2-*, -CH2CH2CONH-*, Alternatively, L1 is selected from or -CH2-C(=N-OH)NH-*; the side with * is connected to ring C; the definitions of other groups are as defined in any technical solution herein.

[0278] In certain embodiments of the present disclosure, the compound is as shown in formula (XI),

[0279] wherein ring E is selected from 4-6 membered heterocycloalkylene spiro 4-6 membered heterocycloalkylene, 5-6 membered heterocycloalkylene and 5-6 membered heterocycloalkylene, 5-6 membered heteroaryl and 5-6 membered heterocycloalkenyl, or

[0280] Alternatively, ring E is directly linked to the parent to form

[0281] In certain embodiments of the present disclosure, the compound is as shown in formula (XI),

[0282] wherein ring E is selected from 4-6 membered heterocycloalkylene spiro 4-6 membered heterocycloalkylene, 5-6 membered heterocycloalkylene and 5-6 membered heterocycloalkylene, or 5-6 membered heteroaryl and 5-6 membered heterocycloalkenyl;

[0283] Alternatively, ring E is directly linked to the parent to form

[0284] The definitions of other groups are as defined in any technical solution herein.

[0285] In certain embodiments of the present disclosure, ring E is selected from Wherein, the end with * is connected to M; the definitions of other groups are as defined in any technical solution of this article.

[0286] In certain embodiments of the present disclosure, the compound is as shown in formula (XII),

[0287] in,

[0288] L2 is selected from -CH2OCH2-, -CH2CH2CH2-, -CH2NHCH2- or -CH2CH2-, wherein said -CH2OCH2-, -CH2CH2CH2-, -CH2NHCH2- or -CH2CH2- is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0289] In certain embodiments of the present disclosure, L2 is selected from -CH2OCH2-; or, L2 is selected from -CH2CH2CH2-; or, L2 is selected from -CH2NHCH2-; or, L2 is selected from -CH2CH2-; the definitions of other groups are as defined in any technical solution herein.

[0290] In certain embodiments of the present disclosure, the compound is as shown in formula (XIII),

[0291] R4 is independently selected from hydrogen, deuterium, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6- 14 Aryl, 5-14 membered heteroaryl, -COR 4-1 、-COOR 4-1 、-OC(=O)R 4-1 、-SO2R 4-2 OR 4-3 , the amino group, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents in aryl or 5-14 membered heteroaryl; or, two R 4a Connected to form a 3-8 membered heterocycloalkyl or 3-8 membered heterocycloalkenyl;

[0292] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0293] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0294] R 4-3 Selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C3- 8-membered cycloalkyl, 3-8-membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-14 substituted by one or more substituents of aryl or 5-14 membered heteroaryl;

[0295] The definitions of other groups are as defined in any technical solution herein.

[0296] In certain embodiments of the present disclosure, R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl, 5-6 membered heteroaryl, -COR 4-1 、-COOR 4-1 、-OC(=O)R 4-1 、-SO2R 4-2 OR 4-3 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl, 5-6 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl; or, two R 4a Connected to form a 3-6 membered heterocycloalkyl or 3-6 membered heterocycloalkenyl;

[0297] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1- 3-deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0298] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkylthio, C1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0299] R 4-3 Selected from hydrogen, deuterium, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0300] In certain embodiments of the present disclosure, R4 is selected from

[0301] The definitions of other groups are as defined in any technical solution herein.

[0302] In certain embodiments of the present disclosure, the compound is as shown in formula (XIV),

[0303] R 6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0304] Or, R 6-1 、R 6-2 and the carbons between them form C 3-6 Cycloalkyl or 3-6 membered heterocycloalkyl;

[0305] The definitions of other groups are as defined in any technical solution herein.

[0306] In certain embodiments of the present disclosure, R 6-1 is selected from hydrogen, cyano or trifluoromethyl; R 6-2 is selected from hydrogen; other groups are as defined in any technical solution herein.

[0307] In certain embodiments of the present disclosure, R 6-1 、R 6-2 and the carbon links between them form (i.e. M is )or (i.e. M is ); the definitions of other groups are as defined in any technical solution herein.

[0308] In certain embodiments of the present disclosure, the compound is as shown in formula (XVII),

[0309] R 2-1 、R 2-2 and R 2-3 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Haloalkoxy; or, R 2- 2 and R 2-3 Connect to form C 3-6 Cycloalkyl or 3-6 membered heterocycloalkyl, the C 3-6 Cycloalkyl and 3-6 membered heterocycloalkyl are optionally further substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 substituted by one or more haloalkoxy groups;

[0310] The definitions of other groups are as defined in any technical solution herein.

[0311] In certain embodiments of the present disclosure, the formula (XVII) is further represented by formula (XVII-1),

[0312] The definition of the group is as defined in any technical solution herein.

[0313] In certain embodiments of the present disclosure, the compound is as shown in formula (XV),

[0314] The definition of the group is as defined in any technical solution herein.

[0315] In certain embodiments of the present disclosure, the compound is as shown in formula (XVI),

[0316] Among them, R 2-1 、R 2-2 and R 2-3 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C1-3 Haloalkoxy; or, R 2-2 and R 2-3 Connect to form C 3-6 Cycloalkyl or 3-6 membered heterocycloalkyl, the C 3-6 Cycloalkyl and 3-6 membered heterocycloalkyl are optionally further substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 substituted by one or more haloalkoxy groups;

[0317] R 7-1 and R 7-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 haloalkoxy;

[0318] Or, R 7-1 and R 7-2 Connect to form C 3-6 Cycloalkyl;

[0319] The definitions of other groups are as defined in any technical solution herein.

[0320] In certain embodiments of the present disclosure, R 2-2 and R 2-3 The cyclobutyl group is optionally further substituted with hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 The definitions of other groups are as defined in any technical solution herein.

[0321] In certain embodiments of the present disclosure, the formula (XVI) is further represented by formula (XVI-1),

[0322] The definition of the group is as defined in any technical solution herein.

[0323] In certain embodiments of the present disclosure, the structural fragment for The definitions of other groups are as defined in any technical solution herein.

[0324] In certain embodiments of the present disclosure, the structural fragment for The definitions of other groups are as defined in any technical solution herein.

[0325] In certain embodiments of the present disclosure, R 2-1 is hydrogen; or, R 2-1 The definitions of other groups are as defined in any technical solution herein.

[0326] In certain embodiments of the present disclosure, R 7-1 is hydrogen, R 7-2 is methyl; or, R 7-1 is methyl, R 7-2 is methyl; or, R 7- 1 and R 7-2 The other groups are defined as in any technical solution herein.

[0327] In certain embodiments of the present disclosure, Ring B is selected from Ring C is selected from The definitions of other groups are as defined in any technical solution herein.

[0328] In certain embodiments of the present disclosure, Ring B is selected from Ring C is selected from The definitions of other groups are as defined in any technical solution herein.

[0329] In certain embodiments of the present disclosure, Selected from The definitions of other groups are as defined in any technical solution herein. The inventors discovered that when Ring C is modified to a five-membered heteroaryl group, the thiophene ring can maintain excellent cytostatic activity, while other five-membered heteroaryl groups, such as thiazolyl, furyl, and pyrrolyl, all lead to decreased cytostatic activity, as evidenced by a comparison of Compound 295 with Compounds 342, 344, 345, and 348.

[0330] In certain embodiments of the present disclosure, Selected from The definitions of other groups are as defined in any technical solution herein.

[0331] In certain embodiments of the present disclosure, Selected from The definitions of other groups are as defined in any technical solution herein.

[0332] In certain embodiments of the present disclosure, Selected from The definitions of other groups are as defined in any technical solution herein. from Modified to The inhibitory effect of the compound on hERG potassium channel current can be significantly reduced, thereby improving safety, which can be supported by the comparison between 21A and compound 303-P4.

[0333] In certain embodiments of the present disclosure, Selected from The definitions of other groups are as defined in any technical solution herein.

[0334] In certain embodiments of the present disclosure, Selected from Selected from The definitions of other groups are as defined in any technical solution herein. from Modified to Will from Modified to The inhibitory effect of the compound on hERG potassium channel current can be further significantly reduced, thereby improving safety, which can be supported by the comparison between 21A and compound 295-P4.

[0335] In certain embodiments of the present disclosure, Selected from Selected from The definitions of other groups are as defined in any technical solution herein.

[0336] In certain embodiments of the present disclosure, Selected from Selected from The definitions of other groups are as defined in any technical solution herein.

[0337] In certain embodiments of the present disclosure, Selected from Selected from The definitions of other groups are as defined in any technical solution herein.

[0338] In certain embodiments of the present disclosure, Selected from Selected from The definitions of other groups are as defined in any technical solution herein.

[0339] In certain embodiments of the present disclosure, R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, thiol, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6- 10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0340] In certain embodiments of the present disclosure, R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 1a Substituted; said R 1a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0341] Preferably, R1 is independently selected from hydroxy, methyl, hydrogen, fluorine or

[0342] The definitions of other groups are as defined in any technical solution herein.

[0343] In certain embodiments of the present disclosure, R1 is independently selected from Alternatively, R1 is independently selected from cyclopropyl, trifluoromethyl, mercapto, -CH2OH, -CD3; or, R1 is independently selected from -N(CH3)2; the definitions of other groups are as defined in any technical solution herein.

[0344] In certain embodiments of the present disclosure, R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 2a Substituted; said R 2a independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6- 10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0345] Alternatively, two R2 are connected to form C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, the C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl;

[0346] Preferably, R2 is independently selected from hydrogen;

[0347] The definitions of other groups are as defined in any technical solution herein.

[0348] In certain embodiments of the present disclosure, R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 2a Substituted; said R 2a independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6- 10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0349] Alternatively, two R2 are connected to form C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, the C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl;

[0350] Alternatively, one of R2 and R3 is connected to form The Optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0351] In certain embodiments of the present disclosure, R2 is independently selected from methyl; the definitions of other groups are as defined in any technical solution herein.

[0352] In certain embodiments of the present disclosure, R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0353] L1 and R3 are connected to form a 3-8 membered heterocycloalkenyl or a 5-6 membered heteroaryl; the 3-8 membered heterocycloalkenyl or the 5-10 membered heteroaryl may be further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10substituted by one or more substituents of aryl or 5-10 membered heteroaryl;

[0354] R3 is selected from ethyl, trifluoromethoxy, vinyl, ethynyl, cyano or

[0355] The definitions of other groups are as defined in any technical solution herein.

[0356] In certain embodiments of the present disclosure, R3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 3a Substituted; said R 3a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0357] R3 is selected from ethyl, trifluoromethoxy, vinyl, ethynyl or cyano;

[0358] The definitions of other groups are as defined in any technical solution herein.

[0359] In certain embodiments of the present disclosure, R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl, 5-6 membered heteroaryl, -COR 4-1 、-COOR 4-1 、-OC(=O)R 4-1 、-SO2R 4-2 OR 4-3 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl, 5-6 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl; or, two R 4a Connected to form a 3-6 membered heterocycloalkyl group;

[0360] R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1- 3-deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0361] R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0362] R 4-3 Selected from hydrogen, deuterium, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0363] The definitions of other groups are as defined in any technical solution herein.

[0364] In certain embodiments of the present disclosure, R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl, 5-6 membered heteroaryl, -COR 4-1 、-SO2R 4-2 , the amino group, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 4a Substituted; said R 4a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0365] Preferably, R4 is independently selected from hydrogen, methyl, or -SO2CH3;

[0366] The definitions of other groups are as defined in any technical solution herein.

[0367] In certain embodiments of the present disclosure, R4 is independently selected from Alternatively, R4 is independently selected from -CH2CN, Phenyl, Cyclopropyl, Alternatively, R4 is independently selected from Fluorine; or, R4 is independently selected from deuterium; the definitions of other groups are as defined in any technical solution herein.

[0368] In certain embodiments of the present disclosure, R 4-1 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0369] More preferably, R 4-1 is selected from cyclopropyl, isopropyl or ethyl;

[0370] The definitions of other groups are as defined in any technical solution herein.

[0371] In certain embodiments of the present disclosure, R 4-1 Selected from -CH2CF3, -NHCH3, -N(CH3)2, -C(OH)(CH3)2, tert-butyl, or -CH2-cyclopropyl.

[0372] In certain embodiments of the present disclosure, R 4-2 Selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3- 6-membered cycloalkyl, 3-6-membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0373] Preferably, R 4-2 selected from methyl;

[0374] The definitions of other groups are as defined in any technical solution herein.

[0375] In certain embodiments of the present disclosure, R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, -SO2-C 1-3 Alkyl, -SF5, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0376] In certain embodiments of the present disclosure, R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0377] Preferably, R5 is independently selected from hydrogen, chloro or trifluoromethyl;

[0378] The definitions of other groups are as defined in any technical solution herein.

[0379] In certain embodiments of the present disclosure, R5 is independently selected from fluoro or methyl; or, R5 is independently selected from cyclopropyl; or, R5 is independently selected from -SF5, ethyl, -SO2CH3; the definitions of other groups are as defined in any technical solution of this article.

[0380] In certain embodiments of the present disclosure, L1 is selected from a bond, -O-, -S-, an imino group, a C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-CONH-C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, -C 1-3 Alkylene-CO-, C 2- 4-Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1-3 Alkylene-5-6 membered heteroaryl- or 5-6 membered heteroaryl, the imino, C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-CONH-C 1-3 Alkylene-C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, -C 1-3 Alkylene-CO-, -C 1-3 Alkylene-C(=N-OH)NH-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1- 3-alkylene-5-6 membered heteroarylene-or 5-6 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 The aryl group or the 5-6 membered heteroaryl group is substituted by one or more substituents; the definitions of other groups are as defined in any technical solution herein.

[0381] In certain embodiments of the present disclosure, L1 is selected from a bond, -O-, -S-, an imino group, a C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-CONH-C 1-3 Alkylene, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, -C1-3 Alkylene-CO-, C 2- 4-Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1-3 Alkylene-5-6 membered heteroaryl- or 5-6 membered heteroaryl, the imino, C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-CONH-C 1-3 Alkylene-C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, -C 1-3 Alkylene-CO-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -C 1-3 Alkylene-3-8 membered heterocycloalkylene-, -C 1-3 Alkylene-3-8 membered heterocycloalkenylene-, -C 1-3 Alkylene-C 6-10 Arylene-, C 6-10 Arylene, -C 1-3Alkylene-5-6 membered heteroarylene- or 5-6 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0382] The definitions of other groups are as defined in any technical solution herein.

[0383] In certain embodiments of the present disclosure, L1 is selected from a bond, -O-, -S-, an imino group, a C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10 Arylene or 5-6 membered heteroarylene, the imino, C 1-3 Alkylene, -CONH-, -CO-C 1-3 Alkylene-NH-, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, 3-8 membered heterocycloalkenylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10 Arylene or 5-6 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2- 4-Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0384] The definitions of other groups are as defined in any technical solution herein.

[0385] In certain embodiments of the present disclosure, L1 is selected from a bond, -O-, -S-, an imino group, a C 1-3 Alkylene, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10Arylene or 5-6 membered heteroarylene, the imino, C 1-3 Alkylene, -C 1-3 Alkylene-CONH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-SO2NH-, -C 1-3 Alkylene-NHCONH-, -C 1-3 Alkylene-NHCO-, -C 1-3 Alkylene-NHSO2-, C 2-4 Alkenylene, C 2-4 Alkynylidene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylene, C 1-3 Alkyleneoxy, C 1-3 Alkylenethio, C 1-3 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heterocycloalkylene, -alkylene-3-8 membered heterocycloalkylene-, C 6-10 Arylene or 5-6 membered heteroarylene, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2- 4-Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0386] More preferably, L1 is selected from -CH2-, -CH2CONH-*, -CH2SO2NH-*, Among them, the side with * is connected to ring C;

[0387] The definitions of other groups are as defined in any technical solution herein.

[0388] In certain embodiments of the present disclosure, L1 is selected from -COCH2NH-*, -CONH-*, Among them, the side with * is connected to ring C;

[0389] The definitions of other groups are as defined in any technical solution herein.

[0390] In certain embodiments of the present disclosure, R6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1- 3 alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 5a Substituted; said R 5a independently selected from deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 Aryl or 5-6 membered heteroaryl, the amino, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1- 3 haloalkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10Aryl or 5-6 membered heteroaryl, optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 substituted by one or more substituents in aryl or 5-6 membered heteroaryl;

[0391] Or, R 6-1 、R 6-2 and the carbons between them form C 3-6 Cycloalkyl or 3-6 membered heterocycloalkyl;

[0392] The definitions of other groups are as defined in any technical solution herein.

[0393] In certain embodiments of the present disclosure, R 6-1 is selected from hydrogen, cyano or trifluoromethyl; R 6-2 is selected from hydrogen; other groups are as defined in any technical solution herein.

[0394] In certain embodiments of the present disclosure, R 6-1 、R 6-2 and the carbon links between them form (i.e. M is )or (i.e. M is ); the definitions of other groups are as defined in any technical solution herein.

[0395] In certain embodiments of the present disclosure, R 7-1 and R 7-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C 1- 3 alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 The definitions of other groups are as defined in any technical solution herein.

[0396] In certain embodiments of the present disclosure, R 7-1is selected from hydrogen or methyl; other groups are as defined in any technical solution herein.

[0397] In certain embodiments of the present disclosure, R 7-2 The definitions of other groups are as defined in any technical solution herein.

[0398] In certain embodiments of the present disclosure, R 7-1 and R 7-2 Connect to form C 3-6 The definitions of other groups are as defined in any technical solution herein.

[0399] The present disclosure also provides the following compounds, stereoisomers or pharmaceutically acceptable salts thereof:

[0400] In certain embodiments of the present disclosure, ring A is selected from 5-14 membered heteroaryl; preferably 5-6 membered heteroaryl, for example

[0401] Ring B is selected from Preferably

[0402] Ring C is selected from C 6-14 Aryl or 5-14 membered heteroaryl; preferably C 6-10 Aryl or 5-6 membered heteroaryl; for example phenyl, For example

[0403] Ring E is selected from 3-12 membered heterocycloalkylene; preferably 5-6 membered heterocycloalkylene and C 3-6 Cycloalkylene; e.g.

[0404] L1, R3 and parent formation fragment Preferably

[0405] In certain embodiments of the present disclosure, M is -CO-;

[0406] Ring A is selected from 5-14 membered heteroaryl; preferably 5-6 membered heteroaryl, for example

[0407] Ring B is selected from Preferably

[0408] Ring C is selected from C 6-14 Aryl or 5-14 membered heteroaryl; preferably C 6-10 Aryl or 5-6 membered heteroaryl; for example phenyl, For example

[0409] Ring E is selected from 3-12 membered heterocycloalkylene; preferably 5-6 membered heterocycloalkylene and C 3-6 Cycloalkylene; e.g.

[0410] L1, R3 and parent formation fragment Preferably

[0411] R1 is independently selected from hydroxyl or C 1-6 alkyl;

[0412] R4 is deuterium;

[0413] R5 is independently selected from halogen, C 1- 6 alkyl or C 1-6 alkyl halide;

[0414] x is selected from 0, 1 or 2; preferably 2;

[0415] y is 0;

[0416] z is selected from 0, 1 or 2; preferably 2;

[0417] u is selected from 0, 1 or 2; preferably 2.

[0418] In certain embodiments of the present disclosure, Ring B is Ring C is phenyl or

[0419] In certain embodiments of the present disclosure, the compound is any one of the following compounds:

[0420] Preferably, the compound is any one of the following compounds:

[0421] The present disclosure also provides a crystalline form of the compound shown below,

[0422] The crystal parameters are as follows:

[0423] The present disclosure also provides a crystalline form of the compound shown below,

[0424] The crystal parameters are as follows:

[0425] The present disclosure also provides a pharmaceutical composition comprising the compound, stereoisomer or pharmaceutically acceptable salt thereof of the present disclosure and a pharmaceutically acceptable carrier.

[0426] In certain embodiments of the present invention, in the pharmaceutical composition, the content of the compound, stereoisomer or pharmaceutically acceptable salt thereof is selected from 0.1 mg to 1000 mg.

[0427] In certain embodiments of the present invention, in the pharmaceutical composition, the pharmaceutically acceptable carrier includes one or more of a filler, a disintegrant, a binder, a glidant, and a lubricant.

[0428] The present disclosure also provides a use of the above-mentioned compound, stereoisomer or pharmaceutically acceptable salt thereof or the above-mentioned pharmaceutical composition in the preparation of a drug for treating WRN-mediated diseases.

[0429] In certain embodiments of the present disclosure, the disease is selected from cancer; preferably, the cancer is selected from colorectal cancer, endometrial cancer, ovarian cancer or gastric cancer; more preferably, the cancer is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancer.

[0430] The present disclosure also provides a method for treating a WRN-mediated disease in a human, wherein the method comprises administering to a human in need thereof an effective preventive or therapeutic amount of the aforementioned compound, stereoisomer or pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition.

[0431] In certain embodiments of the present disclosure, the disease is selected from cancer; preferably, the cancer is selected from colorectal cancer, endometrial cancer, ovarian cancer or gastric cancer; more preferably, the cancer is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancer.

[0432] Technical Effects

[0433] The compounds of the present invention have good WRN enzyme and cell inhibitory activities and are selective for MSS and WRN-KO cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0434] FIG1 is the crystal structure of the DMSO solvate of compound 295-P4.

[0435] FIG2 is the crystal structure of the monohydrate of compound 303-P4.

[0436] Description and Definition

[0437] Unless otherwise specified, the following terms and phrases used herein are intended to have the following meanings. A particular term or phrase should not be considered ambiguous or unclear without a specific definition, but should be understood according to its ordinary meaning.

[0438] The term "pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications, commensurate with a reasonable benefit / risk ratio.

[0439] The term "pharmaceutically acceptable salt" refers to a derivative of a compound of the present invention prepared with a relatively non-toxic acid or base. These salts can be prepared during compound synthesis, separation, and purification, or by reacting the purified free form of the compound with a suitable acid or base. When the compound contains a relatively acidic functional group (e.g., -COOH, -OH, -SO3H, etc.), it reacts with an appropriate inorganic or organic cation (base) to form a base addition salt, including salts formed with alkali metals or alkaline earth metals, ammonium salts formed with amines or their derivatives, and salts formed with amino acids. When the compound contains a relatively basic functional group (e.g., -NH2, etc.), it reacts with an appropriate inorganic or organic anion (acid) to form an acid addition salt, including salts formed with an inorganic acid or organic acid (e.g., carboxylic acid, etc.).

[0440] The term "pharmaceutically acceptable carrier" refers to a medium generally accepted in the art for delivering biologically active agents to animals, particularly mammals, and includes, for example, adjuvants, excipients, or vehicles, such as diluents, preservatives, fillers, flow regulators, disintegrants, wetting agents, emulsifiers, suspending agents, sweeteners, flavoring agents, fragrances, antibacterial agents, antifungal agents, lubricants, and dispersants, depending on the mode of administration and the nature of the dosage form. Pharmaceutically acceptable carriers are formulated within the purview of those skilled in the art based on a wide range of factors. These include, but are not limited to, the type and nature of the active agent being formulated, the subject to whom the composition containing the agent is to be administered, the intended route of administration of the composition, and the intended therapeutic indication. Pharmaceutically acceptable carriers include both aqueous and non-aqueous media, as well as a variety of solid and semisolid dosage forms. In addition to the active agent, such carriers include a variety of different ingredients and additives, and the inclusion of such additional ingredients in a formulation for various reasons (e.g., to stabilize the active agent, binders, etc.) is well known to those skilled in the art.

[0441] The term "isotopic derivative" refers to a compound in which at least one atom is replaced by an atom having the same atomic number but a different atomic mass. Examples of isotopes in the disclosed compounds include, but are not limited to, isotopes of hydrogen (e.g., deuterium ( 2 H), tritium ( 3 H)); carbon isotopes (e.g. 11 C. 13 C and 14 C); isotopes of chlorine (e.g. 36 Cl); isotopes of fluorine (e.g.18 F); isotopes of iodine (such as 123 I and 125 I); isotopes of nitrogen (e.g. 13 N and 15 N); oxygen isotopes (e.g. 15 O. 17 O and 18 O); isotopes of phosphorus (such as 32 P); and sulfur isotopes (e.g. 35 S). Isotopically labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described herein using an appropriate isotopically labeled reagent in place of the unlabeled reagent.

[0442] The term "prodrug" refers to certain derivatives of the compounds of the present invention that have little or no pharmacological activity themselves, which have a cleavable group and decompose into the compounds of the present invention through solvent decomposition or under physiological conditions. The types of prodrugs include, but are not limited to, amides, esters, anhydrides, salts, etc. The "ester" refers to a derivative formed with a suitable alcohol when the compound of the present invention contains an acidic group (such as a carboxylic acid); when the compound of the present invention contains a hydroxyl group, it is formed with a suitable acid (including an organic acid or an inorganic acid). The preparation method of prodrugs is well known to those skilled in the art.

[0443] The term "solvate" refers to an association or complex of one or more solvent molecules with a compound of the present disclosure. The term "hydrate" may be used when the solvent is water. The solvent molecules may be present in stoichiometric or non-stoichiometric amounts. Methods for preparing solvates are known in the art.

[0444] The term "nitrogen oxide" or "N-oxide" refers to a derivative formed by further oxidation of the nitrogen atom in a nitrogen-containing group. Common N-oxides include N-oxides of tertiary amines or nitrogen atoms in nitrogen-containing heterocycles. Synthesis methods of N-oxides are well known to those skilled in the art and include oxidation of heterocycles and tertiary amines using peroxyacids such as peracetic acid and m-chloroperbenzoic acid, hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.

[0445] The compounds of the present disclosure and their salts may exist as isotopic derivatives, and the compounds of the present disclosure include various isotopic derivatives and mixtures thereof.

[0446] The compounds of the present disclosure and their salts may exist in the form of solvates, such as hydrates, and the compounds of the present disclosure include various solvates and mixtures thereof.

[0447] The compounds of the present disclosure and their salts may exist in the form of "N-oxides", and the compounds of the present disclosure include various N-oxides and mixtures thereof.

[0448] The compounds described in the present disclosure, and their pharmaceutically acceptable salts, isotopic derivatives, solvates, and N-oxides have the same or similar biological activities and are all included within the scope of the present disclosure.

[0449] The term "effective prophylactic or therapeutic amount" refers to a sufficient amount of a compound of the present disclosure, a pharmaceutically acceptable salt thereof, or a stereoisomer thereof to treat a disorder at a reasonable benefit / risk ratio applicable to any medical treatment and / or prevention. However, it should be recognized that the total daily dosage of the compound of the present disclosure, its stereoisomers, or pharmaceutically acceptable salts thereof, and compositions must be determined by the attending physician within the scope of sound medical judgment. For any particular patient, the specific therapeutically effective dosage level must be determined based on a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the patient's age, weight, general health, sex, and diet; the administration time, route of administration, and excretion rate of the specific compound employed; the duration of treatment; drugs used in combination with or concurrently with the specific compound employed; and similar factors well known in the medical field.

[0450] The absolute stereo configuration of a compound can be confirmed by conventional techniques in the art. For example, single crystal X-ray diffraction can be used. Alternatively, the absolute configuration of a compound can be confirmed based on the chiral structure of the starting material and the reaction mechanism of asymmetric synthesis. Alternatively, after resolution, the stereo configuration can be determined by comparison with a product with a confirmed absolute configuration. Compounds labeled "absolute configuration unknown / undetermined" herein are typically resolved from racemic compounds into individual isomers by chiral preparative SFC, followed by characterization and testing.

[0451] The term "optionally" means that it may be substituted or not substituted. Unless otherwise specified, the type and number of substituents can be arbitrary based on chemical feasibility. For example, the term "optionally substituted with one or more R1" means that it may be substituted with one or more R1 or not substituted with R1.

[0452] When any variable (e.g., R1) occurs more than once in a compound's composition or structure, its definition on each occurrence is independent. For example, It means that the pyrimidine group is substituted by x R1, and each R1 has independent options.

[0453] When a substituent's bond crosses two atoms in a ring, the substituent may be bonded to any atom in the ring. It means that the substituent R1 can be substituted at any position on the pyrimidinyl group.

[0454] When a substituent is listed without specifying the atom through which it is bonded to a compound included in the general chemical formula but not specifically mentioned, the substituent may be bonded through any atom thereof. For example, pyrimidine as a substituent means that any carbon atom or nitrogen atom on the pyrimidine ring is bonded to the substituted group; when a substituent appears in the structure , it indicates that the atom is a bonding atom, for example It indicates that the C atoms on the pyrimidine ring are bonding atoms.

[0455] Unless otherwise specified, the term "alkyl" refers to a group derived from a branched or straight chain saturated aliphatic alkane having the specified number of carbon atoms by removing one hydrogen. For example, "C 1-6 "Alkyl" refers to C1, C2, C3, C4, C5, C6 alkyl, "C 1-6 Alkyl", "C 1-3 "alkyl"; specific examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, sec-butyl, 2-methylbutyl, 1,1-dimethylbutyl, etc.

[0456] Unless otherwise specified, the term "alkylene" refers to a group derived from an alkyl group by removing a hydrogen atom, and the alkyl group is as defined above.

[0457] Unless otherwise specified, the term "alkenyl" refers to a radical derived from a straight-chain or branched alkene (containing at least one carbon-carbon double bond) by removing a hydrogen atom, including "C 2-6 Alkenyl", "C 2-5 Alkenyl", "C 2-4 Alkenyl", "C 2-3 "Alkenyl", specific examples include but are not limited to: -CH=CH2, -CH=CHCH3, -C(CH2)=CH2, -CH=CHCH2CH3, -CH2CH=CHCH3, etc.

[0458] Unless otherwise specified, the term "alkenylene" refers to a group derived from an alkenyl group by removing a hydrogen atom, and the alkenyl group is as defined above.

[0459] Unless otherwise specified, the term "alkynyl" refers to a radical derived from a straight-chain or branched alkyne (containing at least one carbon-carbon triple bond) by removing a hydrogen atom, including "C 2-6 Alkynyl", "C 2-4 Alkynyl", "C 2-3 Specific examples include, but are not limited to: -C≡CH, -C≡CHCH3, CH≡CHCH2-, CH≡CC≡C-, etc.

[0460] Unless otherwise specified, the term "alkynylene" refers to a radical derived from an alkynyl group by removing a hydrogen atom, and the alkynyl group is as defined above.

[0461] Unless otherwise specified, the term "alkoxy" refers to an alkyl group as defined herein attached to another group through an oxygen atom, i.e., "alkyl-O-". 1-6 Alkoxy" (structure is C 1-6 Alkyl-O-), "C 1-3 "alkoxy", specific examples include but are not limited to methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, etc.; preferably, the "alkoxy" described in the present disclosure is preferably C 1-3 Alkoxy.

[0462] Unless otherwise specified, the term "alkyleneoxy" refers to a group derived from an alkoxy group by removing a hydrogen atom, and the alkoxy group is as defined above.

[0463] Unless otherwise specified, the term "halogen" means a fluorine, chlorine, bromine or iodine atom.

[0464] Unless otherwise specified, the term "haloalkyl" refers to an alkyl group in which one or more hydrogen atoms are replaced by a halogen atom. 1-6 Halogenated alkyl, more preferably C 1-3 Examples of haloalkyl include, but are not limited to, monofluoromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, tribromomethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and the like. Alkyl is as defined above.

[0465] Unless otherwise specified, the term "haloalkylene" refers to a group derived from a haloalkyl group by removing a hydrogen atom, and the haloalkyl group is as defined above.

[0466] Unless otherwise specified, the term "hydroxyalkyl" refers to a group derived from an alkyl group in which one or more hydrogen atoms are replaced by a hydroxyl group. The "hydroxyalkyl" described in the present disclosure includes "C 1-6 Hydroxyalkyl", "C 1-3 Specific examples include, but are not limited to, -CH2OH, -CH2CH2OH, -CH(OH)CH3, -CH2CH2CH2OH, wait.

[0467] Unless otherwise specified, the term "hydroxyalkylene" refers to a group derived from a hydroxyalkyl group by removing a hydrogen atom, and the hydroxyalkyl group is as defined above.

[0468] Unless otherwise specified, the term "alkylthio" refers to an -S-alkyl group in which alkyl is as previously defined.

[0469] Unless otherwise specified, the term "alkylthio" refers to a group derived from an alkylthio group by removing a hydrogen atom, and the alkylthio group is as defined above.

[0470] Unless otherwise specified, the term "haloalkoxy" refers to a group in which one or more hydrogen atoms in an alkoxy group are replaced by halogen. Preferably, the "haloalkoxy" described in the present disclosure is preferably a "haloC 1-6 Alkoxy", "halogenated C 1-3 Alkoxy". Specific examples of the present disclosure include: fluoromethoxy (including monofluoromethoxy, difluoromethoxy, trifluoromethoxy), -OCH2CF3, -OCHFCH3, etc. Alkoxy is as defined above.

[0471] Unless otherwise specified, the term "haloalkyleneoxy" refers to a group derived from a haloalkoxy group by removing a hydrogen atom, and the haloalkoxy group is as defined above.

[0472] The group derived from the ring by removing the hydrogen atom is called a "cyclic group", which includes a monovalent ring, a divalent ring (commonly referred to as a subring), a trivalent ring, a tetravalent ring, etc., and the specific valence depends on the number of substituents connected to the ring. The present disclosure does not specifically distinguish the valence of the ring for the description of the "cyclic group". Representative "cyclic groups" include substituted or unsubstituted cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, cycloalkynyl, heterocycloalkynyl, aryl or heteroaryl.

[0473] Unless otherwise specified, the term "hetero" refers to substituted or unsubstituted heteroatoms and oxidized forms of heteroatoms (also known as heteroatomic groups), wherein the heteroatoms are generally selected from N, O, and S, and the oxidized forms generally include NO, SO, S(O)2, and P(O). The nitrogen atom may be substituted, i.e., NR (R is H or other substituents defined herein); the number of atoms in the ring is generally defined as the number of ring members, for example, "3-6 membered heterocycloalkyl" refers to a ring of 3-6 atoms arranged around, each ring optionally containing 1 to 3 heteroatoms, i.e., N, O, CO, S, NO, SO, S(O)2 or NR, each ring optionally substituted by an R group, where R is a group defined herein.

[0474] Unless otherwise specified, the term "cycloalkyl" refers to a saturated cyclic alkyl derived from a cycloalkane by removing a hydrogen atom, including monocyclic or polycyclic saturated hydrocarbon groups; the polycyclic saturated hydrocarbon group refers to a polycyclic group formed by two or more cyclic alkyl structures connected by spiro, bridge, condensation, etc. The carbon atoms in the cycloalkyl group can be further oxidized to form C(O). Unless otherwise specified, the "monocyclic cycloalkyl" described herein can be understood as a monocyclic cycloalkyl group. When it is polycyclic, it will be specifically specified as a spiro, condensation or bridged ring group. The cycloalkyl group includes "C 3-12 Cycloalkyl", "C3-8 Cycloalkyl", "C 3-6 Cycloalkyl", "C 3-5 Preferably, specific examples of the cycloalkyl group include but are not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0475] Unless otherwise specified, the term "cycloalkylene" refers to a group derived from a cycloalkyl group by removing a hydrogen atom, and the cycloalkyl group is as defined above.

[0476] Unless otherwise specified, the term "heterocycloalkyl" refers to a saturated cyclic group derived from a cycloalkyl group in which one or more ring carbon atoms are replaced by heteroatoms and / or heteroatomic groups. The heteroatoms and / or heteroatomic groups are generally selected from N, O, S, NO, SO, S(O)2, P(O), and NR, wherein the carbon atoms in the heterocyclic ring are optionally oxidized, i.e., forming -C(O); preferably, the heteroatoms are independently selected from 1-3 N and / or O. The heterocycloalkyl group includes "3-12 membered heterocycloalkyl", "3-8 membered heterocycloalkyl", "3-6 membered heterocycloalkyl", "3-5 membered heterocycloalkyl", "4-6 membered heterocycloalkyl", "5-6 membered heterocycloalkyl". Examples of heterocycloalkyl include, but are not limited to

[0477] Unless otherwise specified, the term "heterocycloalkylene" refers to a group derived from a heterocycloalkyl group by removing a hydrogen atom, and the definition of heterocycloalkyl is the same as above. Examples of heterocycloalkylene include but are not limited to

[0478] Unless otherwise specified, "cycloalkenyl" means that one or more of the ring bonds in the "cycloalkyl" is a double bond and the cycloalkenyl is not aromatic. The carbon atoms in the cycloalkenyl can be further oxidized, i.e., to form C(O). The cycloalkenyl can be fused to an aryl, heteroaryl, or heterocycloalkenyl, wherein the ring connected to the parent structure is a cycloalkenyl. The cycloalkenyl includes "3-12 membered cycloalkenyl", "3-8 membered cycloalkenyl", "3-6 membered cycloalkenyl", "3-5 membered cycloalkenyl", and "5-6 membered cycloalkenyl". The definition of "cycloalkyl" is the same as described above.

[0479] Unless otherwise specified, the term "heterocycloalkenyl" refers to a "heterocycloalkyl" in which one or more of the ring bonds is a double bond and is not aromatic. The "heterocycloalkyl" is the same as described above.

[0480] The heterocycloalkenyl group may be fused to an aryl or heteroaryl group, wherein the ring connected to the parent structure is a heterocycloalkenyl group. Preferably, the heteroatoms are independently selected from 1-3 N and / or O. The heterocycloalkenyl group includes "3-12 membered heterocycloalkenyl", "3-8 membered heterocycloalkenyl", "3-6 membered heterocycloalkenyl", "3-5 membered heterocycloalkenyl", and "5-6 membered heterocycloalkenyl". Specific examples include, but are not limited to: wait.

[0481] Unless otherwise specified, the term "aryl" refers to an unsaturated, usually aromatic hydrocarbon group, which may be a single ring or multiple rings fused together. A fused ring aryl group refers to a group in which two or more cyclic structures share two adjacent atoms, and the ring directly connected to the parent structure is aromatic (the ring not directly connected to the parent structure is an aromatic ring or a non-aromatic ring). The aryl group may be fused to a heterocycloalkenyl or cycloalkenyl group, wherein the ring connected to the parent structure is an aryl group, etc. Preferably C 6-14 Aryl, preferably C 6-10 Aryl; Examples of aryl groups include, but are not limited to, phenyl, naphthyl,

[0482] The term "arylene" refers to a group derived from an aryl group by removing a hydrogen atom, and the definition of the aryl group is the same as described above.

[0483] The "heteroaryl" described in the present invention refers to a monocyclic or polycyclic group with aromatic properties containing one or more heteroatoms in the ring, wherein the heteroatoms are generally selected from N, O, and S; preferably, the heteroatoms are independently selected from 1-3 N and / or O. In addition, the N and S atoms may be optionally oxidized and the N atoms may be optionally quaternized. The "heteroaryl" includes "monocyclic heteroaryl" and "fused-ring heteroaryl". The fused-ring heteroaryl refers to a group containing one or more heteroatoms formed by two or more cyclic structures sharing two adjacent atoms, and the ring directly connected to the parent structure has aromatic properties (the ring not directly connected to the parent structure is an aromatic ring or a non-aromatic ring). The heteroaryl group of the present invention is preferably a "nitrogen-containing heteroaryl group", preferably a "5-6 membered nitrogen-containing aryl group", wherein the heteroatom in the "nitrogen-containing heteroaryl group" contains at least one nitrogen atom, for example, only 1, 2 or 3 nitrogen atoms, or one nitrogen atom and one or two other heteroatoms (such as S and / or O atoms), or two nitrogen atoms and one or two other heteroatoms. Specific examples of the heteroaryl group include, but are not limited to, furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, pyrimidinyl, wait.

[0484] The term "heteroarylene" refers to a group derived from a heteroaryl group by removing a hydrogen atom, and the definition of the heteroaryl group is the same as described above.

[0485] In various parts of this disclosure, linking substituents are described. When the structure clearly requires a linking group, the Markush variable listed for that group should be understood to be a linking group. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl" or "aryl", it should be understood that the "alkyl" or "aryl" represents a linking alkylene group or arylene group, respectively.

[0486] Combinations of substituents and / or variables described herein are permissible only if these combinations result in stable compounds or useful synthetic intermediates. A stable compound or structure is one that is sufficiently robust to withstand chemical reactions, to be isolated to a useful degree of purity, and to be formulated into an efficacious therapeutic agent.

[0487] In the examples of this invention, the title compound names were derived from the compound structures using ChemDraw. If the compound name and structure are inconsistent, the structure can be determined by integrating relevant information and reaction routes. If other methods are unavailable for confirmation, the given compound structure will prevail.

[0488] The preparation methods of some compounds in the present invention refer to the preparation methods of the aforementioned similar compounds. Those skilled in the art should be aware that when using or referring to the preparation methods cited, the feed ratio of reactants, reaction solvent, reaction temperature, etc. can be appropriately adjusted according to the different reactants.

[0489] The compounds of the present invention can be prepared by a variety of synthetic methods well known to those skilled in the art, including the specific embodiments listed below, embodiments formed by combining them with other chemical synthesis methods, and equivalent substitutions well known to those skilled in the art. Preferred embodiments include but are not limited to the examples of the present invention. DETAILED DESCRIPTION

[0490] The structures of the compounds of the present invention were determined by nuclear magnetic resonance (NMR) mass spectroscopy. NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker Ascend 400 NMR instrument. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3), with tetramethylsilane (TMS) as the internal standard.

[0491] Thin layer chromatography silica gel plates used were HSGF254 silica gel plates from Yantai Jiangyou Silica Gel Development Co., Ltd., with a size of 0.20 mm ± 0.03 mm and a preparative size of 20 x 20 cm. Column chromatography used 200-300 mesh silica gel from Qingdao Hailang Silica Gel Desiccant Co., Ltd. as a carrier. The starting materials in the examples of the present invention are known and commercially available, or can be synthesized using or according to methods known in the art.

[0492] Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, with dry solvents and reaction temperatures in degrees Celsius.

[0493] General Preparation

[0494] The following examples were synthesized according to the general preparation method.

[0495] Intermediate 1

[0496] 2-(2-Bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4-triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide

[0497] Reaction route:

[0498] Steps:

[0499] Step A: Ethyl 3-oxopentanoate (40.0 g, 0.28 mol) was dissolved in DCM (400 ml), NBS (52 g, 0.29 mol) was added, followed by p-toluenesulfonic acid monohydrate (10.56 g, 0.056 mol), and the reaction mixture was stirred at room temperature for 2.5 hours.

[0500] After TLC monitoring showed the disappearance of the starting material, the product was filtered. The filtrate was added with water (500 ml) and stirred, and the layers were separated. The organic phase was washed with saturated brine (200 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue ethyl 2-bromo-3-oxopentanoate (63 g), which was used directly in the next step.

[0501] Step B: Ethyl 2-bromo-3-oxopentanoate (63 g, 0.28 mol) and 1-Boc-piperazine (56 g, 0.30 mol) were dissolved in acetonitrile (1.2 L), potassium carbonate (78 g, 0.57 mol) was added, and the reaction solution was stirred at room temperature for 5 hours.

[0502] LCMS monitoring showed that the starting material disappeared, and the product was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography to give tert-butyl 4-(1-ethoxy-1,3-dioxolane-2-yl)piperazine-1-carboxylate (70 g).

[0503] MS (ESI) M / Z: 329.4 [M+H] + .

[0504] Step C: 1H-1,2,4-Triazole-3,5-diamine (50 g, 0.5 mol) was dissolved in aqueous hydrobromic acid (400 mL) and cooled to 0°C in an ice-water bath. A solution of sodium nitrite (52 g, 0.76 mol) in water (130 mL) was added dropwise. The reaction was warmed to room temperature and stirred for 1 hour, then stirred at 100°C overnight.

[0505] After LCMS monitoring showed the disappearance of the starting material, the mixture was cooled to room temperature and filtered. The filtrate was adjusted to pH 7-7.5 with 10% aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate (300 ml x 5). The combined organic phases were washed with saturated brine (200 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude 3-bromo-1H-1,2,4-triazole-5-amine (27.8 g), which was used directly in the next step.

[0506] MS (ESI) M / Z: 163.0 [M+H] + .

[0507] Step D: Dissolve 2-chloro-4-(trifluoromethyl)aniline (20 g, 0.1 mol) in dichloromethane (200 mL) at 0°C. Add a solution of 2-chloroacetyl chloride (11.55 g, 0.1 mol) in dichloromethane (40 mL) dropwise. Stir the reaction at 0°C for 30 minutes, then warm to room temperature and stir overnight.

[0508] After TLC monitoring indicated the disappearance of most of the starting material, the reaction mixture was poured into saturated aqueous sodium bicarbonate (500 mL) and extracted with dichloromethane (200 mL). The organic phase was dried and concentrated to dryness. The resulting crude product was purified by column chromatography to afford 2-chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (20.1 g).

[0509] MS (ESI) M / Z: 269.8 [MH] - .

[0510] Step E: 2-Chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (20.1 g, 73.9 mmol) was dissolved in acetone (200 ml), potassium iodide (14.22 g, 85.7 mmol) was added, and the reaction mixture was heated under reflux with stirring for 4 hours.

[0511] After LCMS monitoring showed the disappearance of the starting material, the mixture was cooled and filtered, and the filtrate was concentrated under reduced pressure to dryness to give 2-iodo-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (26.8 g), which was used directly in the next step.

[0512] MS (ESI) M / Z: 362.1 [MH] - .

[0513] Step F: Dissolve 4,6-dichloro-5-methoxypyrimidine (30 g, 0.168 mol) in tetrahydrofuran (240 mL) and cool to 0°C in an ice-water bath. Add 3M methylmagnesium bromide (61.4 mL, 0.184 mol) dropwise and continue stirring in an ice-water bath for 1 hour.

[0514] After TLC monitoring indicated the disappearance of the starting material, saturated aqueous ammonium chloride was added to quench the reaction and the mixture was extracted with ethyl acetate (300 ml). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by column chromatography to afford 4-chloro-5-methoxy-6-methylpyrimidine (20.6 g).

[0515] 1 H NMR (400MHz, CDCl3) δ8.54(s,1H),3.84(s,3H),2.49(s,3H).

[0516] Step G: 4-Chloro-5-methoxy-6-methylpyrimidine (20.6 g, 0.13 mol), Pd(dppf)Cl2·DCM (5.7 g, 7 mmol), and triethylamine (26.03 g, 0.257 mol) were dissolved in methanol (300 mL). The reaction mixture was bubbled with carbon monoxide (2 MPa) and stirred at 60°C overnight.

[0517] After TLC monitoring showed that most of the starting material had disappeared, the mixture was cooled and concentrated under reduced pressure. The crude product was added with water and ethyl acetate, stirred, and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by column chromatography to give 4-chloro-5-methoxy-6-methylpyrimidine (12.4 g).

[0518] Step H: 4-Chloro-5-methoxy-6-methylpyrimidine (12.4 g, 68 mmol) was dissolved in tetrahydrofuran (124 mL), and a solution of lithium hydroxide monohydrate (3.14 g, 74.8 mmol) in water (45 mL) was added. The reaction mixture was stirred at room temperature overnight.

[0519] After TLC monitoring showed that the starting material disappeared, the reaction solution was concentrated to dryness under reduced pressure to give 5-methoxy-6-methylpyrimidine-4-carboxylic acid lithium salt (11.8 g), which was used directly in the next step.

[0520] MS (ESI) M / Z: 169.4 [M+H] + .

[0521] Step I: Dissolve 3-bromo-1H-1,2,4-triazol-5-amine (20 g, 0.12 mol) and tert-butyl 4-(1-ethoxy-1,3-dioxolane-2-yl)piperazine-1-carboxylate (44.7 g, 0.132 mol) in n-butanol (110 mL). Add 85% phosphoric acid (12.1 g, 0.12 mol). Stir the reaction mixture at 100°C overnight. Cool the mixture and concentrate it to dryness under reduced pressure. The residue is dispersed in dichloromethane (300 mL). Add triethylamine (30.3 g, 0.3 mol) and Boc2O (26.2 g, 0.12 mol). Stir the reaction mixture at room temperature overnight.

[0522] After LCMS monitoring indicated the disappearance of the starting material, water (200 mL) was added, stirred, and the layers separated. The organic phase was washed with saturated brine (100 mL), dried over sodium sulfate, and concentrated under pressure to dryness. The crude product was purified by column chromatography to yield tert-butyl 4-(2-bromo-5-ethyl-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (16 g).

[0523] MS (ESI) M / Z: 427.1 [M+H] + .

[0524] Step J: Tert-butyl 4-(2-bromo-5-ethyl-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (2.34 g, 5.49 mmol) and 2-iodo-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (2.19 g, 6.04 mmol) were dissolved in DMF (30 ml), diisopropylethylamine (1.77 g, 13.73 mmol) was added, and the reaction was stirred at 70 °C overnight.

[0525] After LCMS monitoring showed the disappearance of the starting material, the mixture was cooled, diluted with water (100 ml), and the pH was adjusted to 3-4 with dilute hydrochloric acid. The mixture was extracted with ethyl acetate (100 ml x 2). The organic phase was washed with saturated brine (50 ml), dried over sodium sulfate, and concentrated to dryness under pressure. The crude product was purified by column chromatography to yield tert-butyl 4-(2-bromo-4-(2-(2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (1.8 g).

[0526] MS (ESI) M / Z: 660.06 [MH] - .

[0527] Step K: tert-Butyl 4-(2-bromo-4-(2-(2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (1.8 g, 2.72 mmol) was dissolved in dichloromethane (20 mL) and trifluoroacetic acid (10 mL) was added. The reaction was stirred at room temperature overnight.

[0528] After LCMS monitoring showed the disappearance of the starting material, the reaction solution was concentrated to dryness under reduced pressure to give the crude product of 2-(2-bromo-5-ethyl-7-oxo-6-(piperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide trifluoroacetate, which was used directly in the next step.

[0529] MS (ESI) M / Z: 560.3 [MH] - .

[0530] Step L: The crude product of 2-(2-bromo-5-ethyl-7-oxo-6-(piperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide trifluoroacetate (2.72 mmol) and 5-methoxy-6-methylpyrimidine-4-carboxylate lithium salt (0.62 g, 3.52 mmol) from the previous step were dissolved in DMF (30 ml). Diisopropylethylamine (1 g, 7.7 mmol) and HATU (1.3 g, 3.42 mmol) were added under ice-water bath, and the reaction solution was stirred at room temperature for 1 hour.

[0531] After LCMS monitoring showed the disappearance of the starting material, the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (100 mL x 2). The organic phase was washed with saturated brine (50 mL), dried over sodium sulfate, and concentrated to dryness under reduced pressure. The crude product was purified by column chromatography to yield 2-(2-bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4-triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (1.1 g).

[0532] MS (ESI) M / Z: 712.1 [M+H] + .

[0533] Intermediate 2

[0534] 2-(6-Bromo-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide

[0535] Reaction route:

[0536] Steps:

[0537] Step A: Dissolve 5-bromo-4H-1,2,4-triazole-3-amine (10 g, 61 mmol) and ethyl propionyl acetate (11.05 g, 77 mmol) in acetic acid (35 ml), heat and stir at 80 °C overnight.

[0538] After LCMS monitoring showed the disappearance of the starting material, the mixture was cooled in an ice-water bath, stirred for 1 hour, and filtered to obtain a white solid product. The filtrate was concentrated under reduced pressure, and the residue was added with ethanol, stirred, and filtered again. The solids were combined and dried to obtain 2-bromo-5-ethyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one (5.6 g).

[0539] MS (ESI) M / Z: 243.1 [M+H] + .

[0540] Step B: 2-Bromo-5-ethyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one (5.6 g, 23 mmol) and N-(2-chloro-4-(trifluoromethyl)phenyl)-2-iodoacetamide (9.24 g, 25 mmol) were added to 1,4-dioxane (120 mL), followed by diisopropylethylamine (8.96 g, 69 mmol). The reaction mixture was stirred at 80°C overnight.

[0541] LCMS monitoring showed that the starting material disappeared, and the mixture was cooled to room temperature. Water (200 ml) and ethyl acetate (200 ml) were added, stirred and separated. The organic phase was washed with saturated brine (50 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 2-(2-bromo-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (6 g).

[0542] MS (ESI) M / Z: 478.1 [M+H] + .

[0543] Step C: 2-(2-bromo-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (6 g, 12.5 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.42 g, 16.3 mmol), potassium phosphate (7.98 g, 37.6 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (0.51 g, 0.63 mmol) were added to 1,4-dioxane (120 ml) and water (60 ml), the atmosphere was replaced with nitrogen three times, and the reaction solution was stirred at 80°C for 1 hour.

[0544] LCMS monitoring showed the disappearance of the starting material, and the mixture was cooled to room temperature. The reaction mixture was poured into water (500 ml), stirred, and filtered. The solid was slurried, filtered, and dried to obtain N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (4.9 g).

[0545] MS (ESI) M / Z: 482.1 [M+H] + .

[0546] 1 H NMR (400MHz, DMSO-d6) δ10.43(s,1H),8.05(d,J=8.6Hz,1H),7.92(s,1H),7.67(d,J=8.6Hz,1H),6.84(s,1H),5.95(s,1H), 5.26(s,2H),4.26(d,J=2.9Hz,2H),3.81(t,J=5.4Hz,2H),2.73(q,J=7.3Hz,2H),2.49–2.33(m,2H),1.23(t,J=7.3Hz,3H).

[0547] Step D: N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (2 g, 4.16 mmol) was dissolved in DMF (20 ml) and NBS (1.11 g, 6.25 mmol) was added. The reaction was stirred at 50 °C overnight.

[0548] LCMS monitoring showed that most of the starting material had disappeared. The mixture was cooled. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (100 mL x 2). The combined organic phases were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The resulting crude product was purified by silica gel column chromatography to yield 2-(6-bromo-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (1.6 g).

[0549] MS (ESI) M / Z: 558.0 [MH] - .

[0550] Intermediate 3

[0551] 4,4,5,5-Tetramethyl-2-(2,5,6,7-tetrahydrooxepin-4-yl)-1,3,2-dioxaborolane

[0552] Reaction route:

[0553] Steps:

[0554] Step A: Dissolve the compound tetrahydro-4H-pyran-4-one (15.5 g, 154.8 mmol) in ultra-dry dichloromethane (400 mL) in a three-necked flask, then cool the reaction system to -78°C. Then, slowly add boron trifluoride ether solution (22 mL) under nitrogen protection. After the addition is complete, slowly add diazomethyl (trimethyl)silane (86 mL) dropwise. The reaction solution is slowly heated from -78°C to room temperature and stirred for 3 hours.

[0555] After TLC monitoring showed the disappearance of the starting material, the reaction solution was added with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified on a silica gel column to obtain 4-oxirane-4-one (4.7 g).

[0556] 1 HNMR(400MHz,Chloroform-d)δ3.91-3.81(m,4H),2.74-2.63(m,4H),1.92-1.80(m,2H).

[0557] Step B: 4-Hexane-4-one (4.7 g, 41.2 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL), the reaction system was evacuated to replace nitrogen, and then lithium bis(trimethylsilyl)amide (45 mL, 45.0 mmol) was added dropwise at -78°C. After the addition was complete, the reaction solution was stirred at -78°C for 2 hours. Then, N-phenylbis(trifluoromethanesulfonyl)imide (16.2 g, 45.3 mmol) was dissolved in anhydrous tetrahydrofuran and then added dropwise to the reaction flask. The reaction system was slowly warmed to room temperature and stirred for 1 hour.

[0558] After TLC monitoring showed the disappearance of the starting material, the reaction mixture was quenched by adding saturated aqueous ammonium chloride solution, then extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified on a silica gel column to obtain 2,5,6,7-tetrahydrooxepin-4-yl trifluoromethanesulfonate (2.5 g).

[0559] 1 HNMR (400MHz, DMSO-d6) δ6.00(d,J=4.0Hz,1H),4.22-4.10(m,2H),3.75(t,J=5.6Hz,2H),2.62(s,2H),1.97-1.84(m,2H).

[0560] Step C: 2,5,6,7-tetrahydrooxepin-4-yl trifluoromethanesulfonate (1.0 g, 4.06 mmol) and bipyraclostrobin (1.2 g, 4.8 mmol) were dissolved in ultra-dry 1,4-dioxane (15 mL), and 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride (300 mg, 406.2 μmol) and potassium acetate (1.2 g, 12.2 mmol) were added to the reaction system. The reaction system was stirred at 80 ° C for 3 hours under nitrogen protection.

[0561] After TLC monitoring showed the disappearance of the starting material, the reaction solution was directly concentrated under reduced pressure to obtain a crude product. The resulting mixture was purified by silica gel column chromatography to give 4,4,5,5-tetramethyl-2-(2,5,6,7-tetrahydrooxepin-4-yl)-1,3,2-dioxaborolane (300 mg).

[0562] 1 HNMR (400MHz, DMSO-d6) δ6.41(t,J=4.2Hz,1H),4.13-4.12(m,2H),3.71(t,J=5.9Hz,2H),2.31-2.28(m,2H),1.74-1.69(m,2H),1.20(s,12H).

[0563] Intermediate 4

[0564] 4-Methyl-5-(trifluoromethyl)thiophen-3-amine hydrochloride

[0565] Reaction route:

[0566] Steps:

[0567] Step A: 4-Methylthiophene-3-carboxylic acid (10 g, 70.3 mmol) was dissolved in methanol (100 ml), concentrated sulfuric acid (6.89 g, 70.3 mmol) was added, and the mixture was reacted at 75 °C overnight.

[0568] After TLC monitoring showed the disappearance of the starting material, the reaction solution was concentrated under reduced pressure. Aqueous sodium bicarbonate solution was added to adjust the pH to neutral, and the mixture was extracted twice with ethyl acetate (50 ml). The organic phases were combined, washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give crude methyl 4-methylthiophene-3-carboxylate (9.5 g), which was used directly in the next step.

[0569] Step B: Methyl 4-methylthiophene-3-carboxylate (4 g, 26.3 mmol) was dissolved in chloroform (80 ml) and acetic acid (80 ml), and N-iodosuccinimide (6.51 g, 28.9 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours.

[0570] After TLC monitoring showed the disappearance of the starting material, the reaction solution was poured into a sodium sulfite solution (100 ml), extracted twice with dichloromethane (100 ml), and the organic phases were combined. The organic phase was washed with a sodium bicarbonate solution, washed with saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give methyl 5-iodo-4-methylthiophene-3-carboxylate (5.5 g).

[0571] 1 H NMR (400MHz, CDCl3) δ8.22(s,1H),3.85(s,3H),2.44(s,3H).

[0572] Step C: Methyl 5-iodo-4-methylthiophene-3-carboxylate (5.5 g, 19.5 mmol) was dissolved in tetrahydrofuran (30 ml), water (20 ml), and methanol (20 ml), and sodium hydroxide (1.56 g, 39 mmol) was added and reacted at room temperature for 2 hours.

[0573] TLC monitoring showed the disappearance of the starting material. The mixture was concentrated under reduced pressure, and water (100 ml) was added. Impurities were extracted with methyl tert-butyl ether (100 ml). The resulting aqueous phase was adjusted to pH 3-4 by adding dilute hydrochloric acid and extracted twice with ethyl acetate (100 ml). The organic phases were combined, washed with saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain crude 5-iodo-4-methylthiophene-3-carboxylic acid, which was directly used in the next step.

[0574] MS (ESI) M / Z: 267.0 [MH] - .

[0575] Step D: Dissolve 5-iodo-4-methylthiophene-3-carboxylic acid (5.1 g, 19 mmol) in tert-butanol (50 ml), add diphenylphosphoryl azide (5.5 g, 19.97 mmol) and triethylamine (2 g, 19.97 mmol), heat at 60 °C for 1 hour, and then raise the temperature to 90 °C overnight.

[0576] TLC monitoring showed that the starting material disappeared, and the mixture was cooled. Water (100 ml) was added, and the mixture was extracted twice with ethyl acetate (100 ml). The organic phases were combined, washed with saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give tert-butyl (5-iodo-4-methylthiophen-3-yl)carbamate (3.9 g).

[0577] 1 H NMR (400MHz, CDCl3) δ7.48(s,1H),6.28(s,1H),2.04(s,3H),1.46(s,9H).

[0578] Step E: Dissolve tert-butyl (5-iodo-4-methylthiophen-3-yl)carbamate (2.1 g, 6.18 mmol) in N,N-dimethylformamide (20 ml), add diphenyl(trifluoromethyl)sulfonium trifluoromethanesulfonate (5 g, 12.36 mmol) and copper powder (1.19 g, 18.58 mmol), and heat at 60°C to react overnight.

[0579] TLC monitoring showed the disappearance of the starting material, and the mixture was cooled. Filtered through celite, water (100 ml) was added, and the mixture was extracted twice with ethyl acetate (100 ml). The organic phases were combined, washed with saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give tert-butyl (4-methyl-5-(trifluoromethyl)thiophen-3-yl)carbamate (1.5 g).

[0580] 1 H NMR (400MHz, CDCl3) δ7.49(s,1H),6.29(s,1H),2.15(s,3H),1.46(s,9H).

[0581] Step F: Dissolve tert-butyl (4-methyl-5-(trifluoromethyl)thiophen-3-yl)carbamate (1.5 g, 5.33 mmol) in ethyl acetate (10 ml), add hydrogen chloride in ethyl acetate (4 M, 20 ml), and react at room temperature for 2 hours.

[0582] TLC monitoring showed that the starting material disappeared, and the residue was concentrated under reduced pressure to give 4-methyl-5-(trifluoromethyl)thiophen-3-amine hydrochloride (560 mg).

[0583] Intermediate 5

[0584] Step A: 2-(2-bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (1 g, 1.4 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaborolan-2-yl )-tert-Butyl 3,6-dihydropyridine-1(2H)-carboxylate (430 mg, 1.4 mmol), sodium carbonate (372 mg, 3.5 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (60 mg, 0.07 mmol) were added to 1,4-dioxane (20 ml) and water (2.5 ml), and the atmosphere was replaced with nitrogen three times. The reaction solution was stirred at 100 °C overnight.

[0585] After LCMS monitoring showed the disappearance of the starting material, the mixture was cooled to room temperature, and water (50 ml) and ethyl acetate (50 ml) were added, followed by stirring and separation. The aqueous phase was extracted once more with ethyl acetate (50 ml). The organic phases were combined, washed with saturated brine (50 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give tert-butyl 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (450 mg).

[0586] MS (ESI) M / Z: 813.2 [MH] - .

[0587] Step B: Tert-butyl 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (150 mg, 0.18 mmol) was dissolved in dichloromethane (2 ml), trifluoroacetic acid (1 ml) was added, and the reaction was stirred at room temperature for 2 hours.

[0588] LCMS monitoring showed that the starting material disappeared, and the reaction solution was concentrated to dryness under reduced pressure. The obtained crude N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-2-(1,2,3,6-tetrahydropyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide was used directly in the next step.

[0589] MS (ESI) M / Z: 715.3 [M+H] + .

[0590] Intermediate 6

[0591] Step A: tert-Butyl 4-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (500 mg, 1.16 mmol) and tert-butyl 2-bromoacetate (238 mg, 1.22 mmol) were dissolved in N,N-dimethylformamide (4 ml), and N,N-diisopropylethylamine (450 mg, 3.49 mmol) was added. The reaction solution was stirred at 55 °C overnight.

[0592] After LCMS monitoring showed the disappearance of the starting material, water (30 ml) was added, and the mixture was extracted twice with ethyl acetate (40 ml). The organic phases were combined, washed with saturated brine (30 ml), and then dried over anhydrous sodium sulfate. Finally, the residue was concentrated under reduced pressure and purified by silica gel column chromatography to give tert-butyl 4-(4-(2-(tert-butoxy)-2-oxoethyl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (500 mg).

[0593] MS (ESI) M / Z: 567.4 [M+Na] + .

[0594] Step B: tert-Butyl 4-(4-(2-(tert-butoxy)-2-oxoethyl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (500 mg, 0.92 mmol) was dissolved in tetrahydrofuran (10 ml) and methanol (4 ml), and 1 M aqueous sodium hydroxide solution (1.4 ml) was added. The reaction solution was stirred at room temperature overnight.

[0595] LCMS monitoring showed the disappearance of the starting material, and the mixture was cooled to room temperature. The pH was adjusted to 3 with 1 M dilute hydrochloric acid aqueous solution, and ethyl acetate (40 ml) was added for extraction twice. The organic phases were combined, washed with saturated brine (10 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 2-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetic acid (400 mg).

[0596] MS (ESI) M / Z: 487.6 [MH] - .

[0597] Example 1

[0598] N-(2-Chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-2-(2-oxaspiro[3.5]non-6-en-7-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide

[0599] You can also synthesize it according to the following steps

[0600] Reaction route:

[0601] Steps:

[0602] Step A: 2-oxaspiro[3.5]nonan-7-one (500 mg, 3.57 mmol) was dissolved in anhydrous tetrahydrofuran (10 ml), and lithium bis(trimethylsilyl)amide (1 M, 4.28 ml, 4.28 mmol) was added dropwise at -70°C, and the mixture was reacted at -70°C for 2 hours.

[0603] A solution of 1,1,1-trifluoro-N-phenyl-N-(trifluoromethyl)sulfonyl)methanesulfonamide (1.91 g, 5.35 mmol) in tetrahydrofuran (10 ml) was added dropwise to the reaction solution at -70°C, and the reaction was allowed to proceed at room temperature overnight.

[0604] After TLC monitoring showed the disappearance of the starting material, aqueous ammonium chloride solution (30 ml) was added and stirred for 10 minutes. Ethyl acetate (40 ml) was added and extracted twice. The organic phases were combined, washed with saturated brine (50 ml), then dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 2-oxaspiro[3.5]non-6-en-7-yl trifluoromethanesulfonate (800 mg).

[0605] 1 H NMR (400MHz, CDCl3) δ5.71(s,1H),4.53–4.43(m,4H),2.54(m,2H),2.41(m,2H),2.13–2.03(m,2H).

[0606] Step B: 2-oxaspiro[3.5]non-6-en-7-yl trifluoromethanesulfonate (800 mg, 2.94 mmol) and bis(boronic acid)pinacol ester (895.47 mg, 3.53 mmol) were dissolved in dioxane (20 ml), and potassium acetate (865.18 mg, 8.81 mmol) and 1,1-bis(diphenylphosphino)ferrocenepalladium dichloride dichloromethane complex (238.3 mg, 0.294 mmol) were added. The mixture was replaced with nitrogen in vacuum 2-3 times and reacted at 80°C overnight.

[0607] After TLC monitoring showed that the starting material disappeared, water (30 ml) was added and extracted with ethyl acetate (20 ml × 2). The organic phase was first washed with saturated brine (50 ml), then dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure to give 4,4,5,5-tetramethyl-2-(2-oxaspiro[3.5]non-6-en-7-yl)-1,3,2-dioxaborolane crude product (1.2 g) which was directly used in the next step.

[0608] Step C: 2-(2-Bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (200 mg, 0.28 mmol) was dissolved in dioxane (4 ml) and water (1 ml), and crude 4,4,5,5-tetramethyl-2-(2-oxaspiro[3.5]non-6-en-7-yl)-1,3,2-dioxaborolane (140.26 mg, 0.56 mmol), potassium carbonate (76 mg, 0.56 mmol), and 1,1-bis(diphenylphosphino)ferrocenepalladium dichloride dichloromethane complex (22 mg, 0.028 mmol) were added. The nitrogen atmosphere was replaced by vacuum and the reaction was carried out at 100°C for 2 hours.

[0609] After LC monitoring showed the disappearance of the starting material, water (30 ml) was added, and the mixture was extracted twice with ethyl acetate (40 ml). The organic phases were combined, washed with saturated brine (50 ml), dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-2-(2-oxaspiro[3.5]non-6-en-7-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (70 mg).

[0610] MS (ESI) M / Z: 756.4 [M+H] + .

[0611] Step D: N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-2-(2-oxaspiro[3.5]non-6-en-7-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (70 mg, 0.093 mmol) was dissolved in DMF (3 ml) and lithium chloride (39.3 mg, 0.93 mmol) was added. The reaction mixture was reacted at 140°C for 4 hours.

[0612] After LC-MS monitoring showed the disappearance of the starting material, the mixture was cooled to room temperature and concentrated to dryness under reduced pressure. The resulting residue was used to prepare N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-2-(2-oxaspiro[3.5]non-6-en-7-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (1.49 mg).

[0613] MS (ESI) M / Z: 742.3 [M+H] + .

[0614] 1 H NMR(400MHz,DMSO-d6)δ10.67(s,1H),8.38(s,1H),8.05–7.99(m,1H),7.99–7.93(m,1H),7 .76–7.67(m,1H),6.83–6.74(m,1H),5.34(s,2H),4.71–4.62(m,1H),4.58–4.46(m,2H),4. 39–4.35(m,2H),4.32–4.28(m,2H),3.49–3.48(m,2H),2.99–2.96(m,3H),2.81–2.79(m,1H ),2.68–2.67(m,1H),2.59–2.57(m,2H),2.40(s,3H),1.99–1.94(m,4H),1.19–1.16(m,3H).

[0615] Example: 18

[0616] N-(2-Chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-2-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide

[0617] It can also be synthesized using the following steps

[0618] Reaction route:

[0619] Steps:

[0620] Step A: Crude N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-2-(1,2,3,6-tetrahydropyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (0.18 mmol) was dissolved in dichloromethane (5 mL). Triethylamine (220 mg, 2.18 mmol) and isobutyryl chloride (29 mg, 0.27 mmol) were added. The reaction was stirred at room temperature overnight.

[0621] After LCMS monitoring indicated the disappearance of the starting material, water (10 mL) was added and the mixture was extracted twice with dichloromethane (20 mL). The combined organic phases were washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The resulting crude N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-2-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (77 mg) was used directly in the next step.

[0622] MS (ESI) M / Z: 785.5 [M+H] + .

[0623] Step B: The crude product of N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-2-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (77 mg, 0.098 mmol) obtained in the previous step was dissolved in dichloromethane (3 ml), and 2M boron tribromide solution in dichloromethane (0.49 ml, 0.98 mmol) was added, and the mixture was stirred at room temperature overnight.

[0624] After LCMS monitoring showed the disappearance of the starting material, the reaction mixture was poured into ice water, the pH was adjusted to neutral with aqueous sodium bicarbonate, and the mixture was extracted with dichloromethane (20 ml x 2). The organic phase was dried and concentrated to dryness. The resulting crude product was purified to yield N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-2-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (2.86 mg).

[0625] MS (ESI) M / Z: 771.6 [M+H]+ .

[0626] 1 H NMR (400MHz, DMSO-d6) δ10.38(s,1H),10.24(s,1H),8.58(s,1H),8.06(d,J=8.4Hz,1H),7.98(s ,1H),7.72(d,J=8.4Hz,1H),6.86–6.77(m,1H),5.32(s,2H),4.56–4.48(m,1H),4.32–4.24(m,1 H),4.16–4.11(m,1H),3.71–3.64(m,2H),3.51–3.45(m,3H),3.26–3.23(m,1H),3.02–2.95(m,3 H),2.84–2.78(m,1H),2.68–2.54(m,4H),2.44(s,3H),1.18(t,J=7.5Hz,3H),1.03–0.99(m,6H).

[0627] Example 33

[0628] 2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(5-(trifluoromethyl)thiophen-2-yl)acetamide

[0629] You can also synthesize it according to the following steps

[0630] Reaction route:

[0631] Steps:

[0632] Step A: 5-(Trifluoromethyl)thiophene-2-carboxylic acid (1.0 g, 5.1 mmol) was dissolved in tert-butanol (20 ml), and triethylamine (928.6 mg, 9.17 mmol) and diphenylphosphoryl azide (2.52 g, 9.17 mmol) were added and reacted at 90°C overnight.

[0633] After TLC monitoring showed the disappearance of the starting material, the tert-butanol was concentrated to dryness, an aqueous sodium bicarbonate solution (20 ml) was added and stirred for 10 minutes, and ethyl acetate (40 ml) was added for extraction. The organic phase was then washed with dilute hydrochloric acid to make the pH acidic. The layers were separated, and the organic phase was washed with saturated brine (30 ml), then dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give tert-butyl (5-(trifluoromethyl)thiophen-2-yl)carbamate (880 mg).

[0634] MS (ESI) M / Z: 266.0 [M+H] + .

[0635] Step B: Dissolve tert-butyl (5-(trifluoromethyl)thiophen-2-yl)carbamate (880 mg, 3.29 mmol) in ethyl acetate (5 mL), add 4 M hydrochloric acid in ethyl acetate (10 mL), and react at room temperature overnight.

[0636] After TLC monitoring showed that the starting material disappeared, the reaction solution was concentrated under reduced pressure to obtain crude 5-(trifluoromethyl)thiophene-2-amine hydrochloride, which was directly used in the next step.

[0637] Step C: tert-Butyl 4-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-4-(2-methoxy-2-oxoethyl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (550 mg, 1.09 mmol) was dissolved in tetrahydrofuran (10 ml) and methanol (4 ml), and 1 M aqueous sodium hydroxide solution (1.6 ml) was added and the reaction was allowed to react at room temperature overnight.

[0638] After TLC monitoring showed the disappearance of the starting material, 1 M dilute hydrochloric acid was added to adjust the pH to 3, and then ethyl acetate (20 ml * 2) was added for extraction. The organic phase was first washed with saturated brine (20 ml), then dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure to give 2-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetic acid (480 mg)

[0639] MS (ESI) M / Z: 489.0 [M+H] + .

[0640] Step D: 2-(6-(4-(tert-Butoxycarbonyl)piperazin-1-yl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetic acid (250 mg, 0.5 mmol) and 5-(trifluoromethyl)thiophen-2-amine hydrochloride (124.7 mg, 0.61 mmol) were dissolved in N,N-dimethylformamide (6 ml), and N,N-diisopropylethylamine (264.8 mg, 2.05 mmol) was added. HATU (233.7 mg, 0.61 mmol) was added under ice-water bath, and the mixture was reacted at room temperature for 1 hour.

[0641] After TLC monitoring showed the disappearance of the starting material, water (30 ml) was added and extracted with ethyl acetate (20 ml*2). The organic phase was first washed with saturated brine (30 ml), then dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give tert-butyl 4-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-4-(2-oxo-2-((5-(trifluoromethyl)thiophen-2-yl)amino)ethyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (170 mg).

[0642] MS (ESI) M / Z: 638.4 [M+H] + .

[0643] Step E: tert-Butyl 4-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-4-(2-oxo-2-((5-(trifluoromethyl)thiophen-2-yl)amino)ethyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)piperazine-1-carboxylate (170 mg, 0.26 mmol) was dissolved in dichloromethane (6 ml), trifluoroacetic acid (4.5 ml) was added, and the reaction was carried out at room temperature for 1 hour.

[0644] After TLC monitoring showed the disappearance of the starting material, the mixture was concentrated under reduced pressure to dryness to give the crude 2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-6-(piperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(5-(trifluoromethyl)thiophen-2-yl)acetamide trifluoroacetate, which was directly used in the next step.

[0645] Step F: 2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-7-oxo-6-(piperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(5-(trifluoromethyl)thiophen-2-yl)acetamide trifluoroacetate (173.7 mg, 0.26 mmol) and 5-methoxy-6-methylpyrimidine-4-carboxylic acid (49.3 mg, 0.29 mmol) were dissolved in N,N-dimethylformamide (4 ml), N,N-diisopropylethylamine (137.9 mg, 1.06 mmol) was added, and HATU (121.7 mg, 0.32 mmol) was added under ice-water bath, and the reaction was carried out at room temperature for 1 hour.

[0646] After TLC monitoring showed the disappearance of the starting material, water (30 ml) was added and extracted with ethyl acetate (20 ml*2). The organic phase was first washed with saturated brine (30 ml), then dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(5-(trifluoromethyl)thiophen-2-yl)acetamide (90 mg).

[0647] MS (ESI) M / Z: 688.3 [M+H] + .

[0648] Step G: 2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(5-(trifluoromethyl)thiophen-2-yl)acetamide (90 mg, 0.13 mmol) was dissolved in N,N-dimethylformamide (4 ml) and lithium chloride (55.5 mg, 1.3 mmol) was added. The reaction was stirred at 140 °C for 4 hours and then at 98 °C overnight.

[0649] After LCMS monitoring showed the disappearance of the starting material, the reaction mixture was cooled and concentrated to dryness under reduced pressure. The crude product was prepared and purified to give 2-(2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(5-(trifluoromethyl)thiophen-2-yl)acetamide (9.08 mg).

[0650] MS (ESI) M / Z: 674.2 [M+H] + .

[0651] 1H NMR(400MHz,DMSO-d6)δ8.57(s,1H),8.09–8.03(m,1H),7.47(s,1H),6.83–6 .72(m,2H),5.24(s,2H),4.57–4.45(m,1H),4.27–4.15(m,2H),3.82–3.74(m ,2H),3.55–3.42(m,3H),3.25–3.22(m,1H),3.03–2.92(m,3H),2.85–2.78(m ,1H),2.68–2.63(m,1H),2.50–2.50(m,2H),2.44(s,3H),1.15–1.13(m,3H).

[0652] Example 61

[0653] N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(2-(1-(2-cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide

[0654] You can also synthesize it according to the following steps

[0655] Reaction route:

[0656] Steps:

[0657] Step A: Dissolve the crude 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine trifluoroacetate (675 mg, 3.23 mmol) in dichloromethane (20 ml), add triethylamine (1.64 g, 16.17 mmol) and cyclopropylacetyl chloride (498 mg, 4.2 mmol), and react at room temperature overnight.

[0658] After TLC monitoring showed the disappearance of the starting material, the reaction solution was concentrated to dryness under reduced pressure to give crude 2-cyclopropyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl)ethan-1-one (950 mg), which was used directly in the next step.

[0659] Step B: 2-(2-bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (400 mg, 0.56 mmol), 2-cyclopropyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-yl)-2-nitropropane-1-yl)-1-nitropropane-2-yl)-1-nitropropane ... )-3,6-dihydropyridin-1(2H)-yl)ethane-1-one (131 mg, 0.45 mmol), anhydrous potassium carbonate (193 mg, 1.4 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (22.85 mg, 0.028 mmol) were added to 1,4-dioxane (6 ml) and water (0.75 ml), and the atmosphere was replaced with nitrogen three times. The reaction solution was stirred at 100°C for 2 hours.

[0660] After TLC monitoring showed the disappearance of the starting material, the mixture was cooled. Water (20 ml) was added, and the mixture was extracted twice with ethyl acetate (30 ml). The organic phases were combined, washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(2-(1-(2-cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (160 mg).

[0661] MS (ESI) M / Z: 797.4 [M+H] + .

[0662] Step C: N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(2-(1-(2-cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (130 mg, 0.16 mmol) and lithium chloride (69 mg, 1.63 mmol) were added to anhydrous N,N-dimethylformamide (4 ml) and heated at 140°C for 4 hours.

[0663] LCMS monitoring showed the disappearance of the starting material, and the mixture was cooled and concentrated to dryness under reduced pressure. The resulting residue was purified and prepared to give N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(2-(1-(2-cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (22.24 mg).

[0664] MS (ESI) M / Z: 783.4 [M+H] + .

[0665] 1 H NMR (400MHz, DMSO-d6) δ10.40(s,1H),10.25(s,1H),8.57(s,1H),8.06(d,J=8.6Hz,1H),7.98(s,1H),7.72(d,J =8.6Hz,1H),6.80(d,J=15.6Hz,1H),5.33(s,2H),4.57–4.48(m,1H),4.22–4.11(m,2H),3.70–3.60(m,2H),3.5 1–3.44(m,3H),3.27–3.22(m,1H),3.03–2.94(m,3H),2.85–2.79(m,1H),2.67–2.64(m,1H),2.61–2.57(m,2H), 2.44(s,3H),2.35–2.28(m,2H),1.19(t,J=7.5Hz,3H),1.00–0.94(m,1H),0.48–0.40(m,2H),0.17–0.07(m,2H).

[0666] Example 65

[0667] N-(2-Chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-2-(1-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,3,6-tetrahydropyridin-4-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide

[0668] You can also synthesize it according to the following steps

[0669] Reaction route:

[0670] Steps:

[0671] Step A: Dissolve 2-bromo-5-methyl-1,3,4-oxadiazole (450 mg, 2.76 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (606.24 mg, 2.9 mmol) in DMF (10 ml), add potassium carbonate (1.91 g, 13.81 mmol), and react at 50 °C for 2 hours.

[0672] After TLC monitoring showed the disappearance of the starting material, the product was filtered and washed with a small amount of DMF to obtain a DMF solution of 2-methyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl)-1,3,4-oxadiazole (14 ml, 2.76 mmol), which was used directly in the next step.

[0673] Step B: 2-(2-bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (300 mg, 0.42 mmol) was dissolved in dioxane (8 ml) and water (2 ml), and 2-methyl-5- A DMF solution of (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridin-1(2H)-yl)-1,3,4-oxadiazole (2.14 ml, 0.42 mmol), potassium carbonate (116.46 mg, 0.84 mmol), and 1,1-bis(diphenylphosphino)ferrocenepalladium dichloride (34.18 mg, 0.042 mmol) was added. The atmosphere was replaced with nitrogen, and the reaction was carried out at 100°C for 2 hours.

[0674] After LC monitoring showed the disappearance of the starting material, the mixture was cooled, water (30 ml) was added, and the mixture was extracted twice with ethyl acetate (40 ml). The organic phases were combined, washed with saturated brine (50 ml), dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-2-(1-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,3,6-tetrahydropyridin-4-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (140 mg).

[0675] MS (ESI) M / Z: 797.3 [M+H] + .

[0676] Step C: N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-2-(1-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,3,6-tetrahydropyridin-4-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (120 mg, 0.15 mmol) was dissolved in DMF (3 ml), and lithium chloride (63.82 mg, 1.51 mmol) was added. The mixture was reacted at 140°C for 4 hours.

[0677] After LC-MS monitoring showed the disappearance of the starting material, the residue was concentrated under reduced pressure to prepare N-(2-chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-2-(1-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,3,6-tetrahydropyridin-4-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide (20.12 mg).

[0678] MS (ESI) M / Z: 783.0 [M+H] + .

[0679] 1 H NMR (400MHz, DMSO-d6) δ10.44(s,1H),10.28(s,1H),8.57(s,1H),8.06(d,J=8.5Hz,1H), 7.98(s,1H),7.72(d,J=8.9Hz,1H),6.98–6.84(m,1H),5.36(s,2H),4.57–4.48(m,1H),4 .22–4.05(m,2H),3.67–3.60(m,2H),3.50–3.44(m,3H),3.29–3.21(m,1H),3.05–2.96(m ,3H),2.86–2.77(m,2H),2.69–2.67(m,2H),2.44(s,3H),2.35(s,3H),1.20–1.17(m,3H).

[0680] Example 93

[0681] Cyclopropyl 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate

[0682] You can also synthesize it according to the following steps

[0683] Reaction route:

[0684] Steps:

[0685] Step A: Cyclopropanol (600 mg, 10.32 mmol) was added to acetonitrile (100 ml), and bis(2,5-dioxopyrrolidin-1-yl) carbonate (2.91 g, 11.34 mmol) and triethylamine (2.16 ml, 15.5 mmol) were added thereto. The reaction solution was reacted at room temperature overnight.

[0686] After TLC monitoring indicated the disappearance of the starting material, dichloromethane (200 mL) and aqueous sodium bicarbonate (100 mL) were added, stirred, and the layers separated. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain crude cyclopropyl (2,5-dioxopyrrolidin-1-yl) carbonate (290 mg).

[0687] 1 H NMR (400MHz, CDCl3) δ4.58–4.24(m,1H),3.00–2.72(m,4H),1.12–0.61(m,4H).

[0688] Step B: Dissolve the crude 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine trifluoroacetate (0.97 mmol) in dichloromethane (10 ml), add triethylamine (491 mg, 4.83 mmol) and crude cyclopropyl(2,5-dioxopyrrolidin-1-yl) carbonate (290 mg, 1.46 mmol), and react at room temperature overnight.

[0689] After TLC monitoring showed the disappearance of the starting material, dilute hydrochloric acid (1 M, 10 ml) was added and the mixture was extracted twice with dichloromethane (10 ml). The organic phases were combined and washed sequentially with aqueous sodium bicarbonate (10 ml) and saturated brine (10 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude cyclopropyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (320 mg).

[0690] MS (ESI) M / Z: 294.2 [M+H] + .

[0691] Step C: 2-(2-bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (300 mg, 0.42 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- Crude cyclopropyl-3,6-dihydropyridine-1(2H)-carboxylate (123 mg, 0.42 mmol), potassium carbonate (144.9 mg, 1.05 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (17.14 mg, 0.021 mmol) were added to 1,4-dioxane (4 ml) and water (0.5 ml), and the reaction solution was refluxed at 100 degrees Celsius for 2 hours.

[0692] After TLC monitoring showed the disappearance of the starting material, the mixture was cooled. Water (20 ml) was added, and the mixture was extracted twice with ethyl acetate (30 ml). The organic phases were combined, washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give cyclopropyl 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (160 mg).

[0693] MS (ESI) M / Z: 799.2 [M+H] + .

[0694] Step D: Cyclopropyl 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (125 mg, 0.16 mmol) and lithium chloride (66.3 mg, 1.6 mmol) were added to anhydrous N,N-dimethylformamide (4 ml) and reacted at 140°C for 4 hours.

[0695] LCMS monitoring showed the disappearance of the starting material, and the mixture was cooled and concentrated to dryness under reduced pressure. The resulting residue was purified and prepared to give cyclopropyl 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (55.47 mg).

[0696] MS (ESI) M / Z: 785.3 [M+H] + .

[0697] 1 H NMR (400MHz, DMSO-d6) δ10.39(s,1H),10.26(s,1H),8.57(s,1H),8.06(d,J=8.7Hz,1H),7.98 (s,1H),7.72(d,J=8.7Hz,1H),6.90–6.66(m,1H),5.32(s,2H),4.59–4.43(m,1H),4.13–3.93 (m,3H),3.59–3.42(m,5H),3.28–3.20(m,1H),3.07–2.90(m,3H),2.84–2.76(m,1H),2.69–2. 61(m,1H),2.58–2.53(m,2H),2.44(s,3H),1.18(t,3H),0.82–0.74(m,2H),0.65–0.63(m,2H).

[0698] Example 94

[0699] 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-N,N-dimethylcyclohex-3-ene-1-carboxamide

[0700] You can also synthesize it according to the following steps

[0701] Reaction route:

[0702] Steps:

[0703] Step A: Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate (500 mg, 1.88 mmol) was dissolved in tetrahydrofuran (5 ml), water (1 ml), and methanol (2.5 ml), and lithium hydroxide monohydrate (315 mg, 7.52 mmol) was added and the reaction was carried out at room temperature overnight.

[0704] After TLC monitoring showed the disappearance of the starting material, the reaction solution was adjusted to pH 5-6 with 2M hydrochloric acid, and the reaction solution was concentrated to dryness under reduced pressure to obtain a crude product of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylic acid, which was directly used in the next step.

[0705] MS (ESI) M / Z: 275.1 [M+Na] + .

[0706] Step B: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylic acid (236 mg, 0.94 mmol) was dissolved in N,N-dimethylformamide (6 ml), and dimethylamine hydrochloride (91 mg, 1.12 mmol), N,N-diisopropylethylamine (362 mg, 2.81 mmol) and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (462 mg, 1.22 mmol) were added. The reaction solution was stirred at room temperature overnight.

[0707] After TLC monitoring showed the disappearance of the starting material, water (20 ml) was added, and the mixture was extracted twice with ethyl acetate (30 ml). The organic phases were combined, washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxamide (200 mg).

[0708] MS (ESI) M / Z: 280.2 [M+H] + .

[0709] Step C: 2-(2-bromo-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (300 mg, 0.42 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2- Dioxaborolan-2-yl)cyclohex-3-ene-1-carboxamide (106 mg, 0.38 mmol), anhydrous potassium carbonate (145 mg, 1.05 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (17 mg, 0.02 mmol) were added to 1,4-dioxane (8 ml) and water (1 ml), and the atmosphere was replaced with nitrogen three times. The reaction solution was stirred at 100 °C for 2 hours.

[0710] LCMS monitoring showed the disappearance of the starting material, and the mixture was cooled. Water (20 ml) was added, and the mixture was extracted twice with ethyl acetate (30 ml). The organic phases were combined, washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give 4-(4-(2-(2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-N,N-dimethylcyclohex-3-ene-1-carboxamide (180 mg).

[0711] MS (ESI) M / Z: 785.4 [M+H] + .

[0712] Step D: 4-(4-(2-(2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-methoxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-N,N-dimethylcyclohex-3-ene-1-carboxamide (180 mg, 0.23 mmol) and lithium chloride (97 mg, 2.29 mmol) were added to anhydrous N,N-dimethylformamide (8 ml) and heated at 140°C for 4 hours.

[0713] LCMS monitoring showed the disappearance of the starting material, and the mixture was cooled and concentrated to dryness under reduced pressure. The resulting residue was purified and prepared to give 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-N,N-dimethylcyclohex-3-ene-1-carboxamide (63.08 mg).

[0714] MS (ESI) M / Z: 771.2 [M+H] + .

[0715] 1 H NMR (400MHz, DMSO-d6) δ10.37(s,1H),10.28(s,1H),8.56(s,1H),8.06(d,J=8.6Hz,1H),8.01– 7.90(m,1H),7.72(d,J=8.7Hz,1H),6.88(s,1H),5.32(s,2H),4.60–4.44(m,1H),3.58–3.44(m ,3H),3.26–3.20(m,1H),3.05(s,3H),3.02–2.94(m,3H),2.93–2.76(m,6H),2.68–2.60(m,2H) ,2.44(s,3H),2.35–2.26(m,2H),1.95–1.85(m,1H),1.61–1.51(m,1H),1.19(t,J=7.5Hz,3H).

[0716] Step E: 4-(4-(2-((2-chloro-4-(trifluoromethyl)phenyl)amino)-2-oxoethyl)-5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-N,N-dimethylcyclohex-3-ene-1-carboxamide (60 mg, 0.078 mmol) was separated by chiral HPLC preparative separation. Preparative column: CHIRALPAK IC (5 μm, 30 mm I.D.*250 mmL), mobile phase gradient: 90% acetonitrile / 10% water (containing 0.1% trifluoroacetic acid), flow rate: 30 ml / min, to obtain Example 94-peak 1 (16.64 mg; retention time: 46 minutes) and Example 94-peak 2 (15.24 mg; retention time: 60 minutes).

[0717] Example 94-peak 1:

[0718] MS (ESI) M / Z: 771.5 [M+H] + .

[0719] 1 H NMR (400MHz, DMSO-d6) δ10.37(s,1H),10.21(s,1H),8.56(s,1H),8.06(d,J=8.6Hz,1H),8.01– 7.90(m,1H),7.72(d,J=8.7Hz,1H),6.88(s,1H),5.32(s,2H),4.60–4.44(m,1H),3.58–3.44(m ,3H),3.26–3.20(m,1H),3.05(s,3H),3.02–2.94(m,3H),2.93–2.76(m,6H),2.68–2.60(m,2H) ,2.44(s,3H),2.35–2.26(m,2H),1.95–1.85(m,1H),1.61–1.51(m,1H),1.19(t,J=7.5Hz,3H).

[0720] Example 94-peak 2:

[0721] MS (ESI) M / Z: 771.5 [M+H] + .

[0722] 1 H NMR(400MHz,DMSO-d6)δ10.39(s,1H),10.24(s,1H),8.56(s,1H),8.06(d,J=8.6Hz,1H),8.01– 7.90(m,1H),7.72(d,J=8.7Hz,1H),6.88(s,1H),5.32(s,2H),4.60–4.44(m,1H),3.58–3.44(m ,3H),3.26–3.20(m,1H),3.05(s,3H),3.02–2.94(m,3H),2.93–2.76(m,6H),2.68–2.60(m,2H) ,2.44(s,3H),2.35–2.26(m,2H),1.95–1.85(m,1H),1.61–1.51(m,1H),1.19(t,J=7.5Hz,3H).

[0723] Example 95

[0724] N-(2-Chloro-4-(trifluoromethyl)phenyl)-2-(5-ethyl-6-(4-(5-hydroxy-6-methylpyrimidine-4-carbonyl)piperazin-1-yl)-2-(4-(methylsulfonyl)cyclohex-1-en-1-yl)-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidin-4(7H)-yl)acetamide

[0725] You can also synthesize it according to the following steps

[0726] Reaction route:

[0727] Steps:

[0728] Step A: Dissolve 4-(Methylsulfonyl)cyclohexane-1-one (200 mg, 1.14 mmol) and 2,6-di-tert-butyl-4-methylpyridine (513.2 mg, 2.5 mmol) in dichloromethane (15 ml). Add trifluoromethanesulfonic anhydride (641 mg, 2.27 mmol) dropwise under ice-cooling and react at 40°C overnight.

[0729] After TLC monitoring showed the disappearance of the starting material, the reaction solution was concentrated to dryness under reduced pressure, petroleum ether (10 ml) was added and filtered, the filtrate was spin-dried and the resulting residue was purified by silica gel column chromatography to give 4-(methylsulfonyl)cy...

Claims

1. A compound, stereoisomer or pharmaceutically acceptable salt thereof of the formula (IC): Wherein, M is selected from a bond, CO, -NHCO-, -C(R 6-1 R 6-2 )-, Ring A is selected from C 6-14 aryl or 5- to 14-membered heteroaryl; Ring B is selected from C 3-12 cycloalkyl, C 3-12 cycloalkenyl, 3- to 12-membered heteroalkyl, 3- to 12-membered heteroalkenyl, C 6-14 aryl or 5- to 14-membered heteroaryl; or, Ring B is absent and R4 is directly attached to the parent structure; Ring C is selected from C 3-12 cycloalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl; Ring E is selected from C 3-12 subcycloalkyl, C 3-12 subcycloalkenyl, 3- to 12-membered subheterocycloalkyl, 3- to 12-membered subheterocycloalkenyl, C 6-14 subaryl or 5- to 14-membered subheteroaryl; or Ring E is directly connected to the parent to form L1 is selected from a bond, -O-, -S-, an imino group, C 1-6 an alkylene group, -CONH-, -CO-C 1-6 an alkylene group-NH-, -C 1-6 an alkylene group-CONH-, -C 1-6 an alkylene group-CONH-C 1-6 an alkylene group, -C 1-6 an alkylene group-SO2NH-, -C 1-6 an alkylene group-NHCONH-, -C 1-6 an alkylene group-NHCO-, -C 1-6 an alkylene group-NHSO2-, -C 1-6 an alkylene group-CO-, -C 1-6 an alkylene group-C(=N-OH)NH-, C 2-6 an alkenylene group, C 2-6 an alkynylene group, C 1-6 a deuterated alkylene group, C 1-6 a halogenated alkylene group, C 1-6 a hydroxyalkylidene group, C 1-6 an alkoxyalkylidene group, C 1-6 an alkylthioalkylidene group, C 1-6 a halogenated alkoxyalkylidene group, C 3- a cycloalkylidene group having 8 members, a heteroalkylidene group having 3 to 8 members, a heteroalkenylene group having 3 to 8 members, -C 1-6 an alkylene group-a heteroalkylidene group having 3 to 8 members-, -C 1-6 an alkylene group-a heteroalkenylene group having 3 to 8 members-, -C 1-6 an alkylene group-C 6-14 an arylidene group-, C 6-14 an arylidene group, -C 1-6 an alkylene group-a heteroaryl group having 5 to 14 members- or a heteroaryl group having 5 to 14 members, the imino group, C 1-6 an alkylene group, -CONH-, -CO-C 1-6 an alkylene group-NH-, -C 1-6 an alkylene group-CONH-, -C 1-6 an alkylene group-CONH-C 1-6 an alkylene group, -C 1-6 an alkylene group-SO2NH-, -C 1-6 an alkylene group-NHCONH-, -C 1-6 an alkylene group-NHCO-, -C 1-6 an alkylene group-NHSO2-, -C 1-6 an alkylene group-CO-, C 2-6 an alkenylene group, C 2-6 an alkynylene group, C 1-6 a deuterated alkylene group, C 1-6 a halogenated alkylene group, C 1- a hydroxyalkylidene group having 6 members, C 1-6 Alkyleneoxy, C 1-6 Alkylthioxy, C 1-6 Halogenated alkyleneoxy, C 3-8 Cycloalkylene, 3-8 membered heteroalkylene, 3-8 membered heteroalkenylene, -C 1-6 Alkylene-3-8 membered heteroalkylene-, -C 1-6 Alkylene-3-8 membered heteroalkenylene-, -C 1-6 Alkylene-C 6-14 Arylene-, C 6-14 Arylene, -C 1-6 Alkylene-5-14 membered heteroarylene- or 5-14 membered heteroarylene, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, oxo, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered heteroalkyl, C 6-14 Aryl or 5-14 membered heteroaryl; Alternatively, L1, R3, and the parent form a fragment R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, mercapto, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 1a ; said R 1a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered hetero cycloalkyl, C 6-14 substituted by one or more substituents selected from aryl or 5-14 membered heteroaryl; R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, said amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 2a ; said R 2a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, said amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 substituted by one or more substituents selected from aryl or 5-14 membered heteroaryl; Alternatively, two R2s are connected to each other to form C 3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, and the C 3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C 6-14 aryl or one or more substituents selected from 5- to 14-membered heteroaryl; Alternatively, one of R2 and R3 is connected to form a 5- to 8-membered heteroalkenyl group, and the 5- to 8-membered heteroalkenyl group is optionally further substituted with one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl; R3 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6- 14 aryl or 5- to 14-membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, optionally further substituted by one or more R 3a ; said R 3a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 substituted by one or more substituents selected from aryl or 5- to 14-membered heteroaryl; L1 and R3 are connected to form a 3- to 8-membered heteroalkenyl group or a 5- to 10-membered heteroaryl group; the 3- to 8-membered heteroalkenyl group and the 5- to 10-membered heteroaryl group are optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl; R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl, 5-14 membered heteroaryl, -COR 4-1 , -COOR 4-1 , -OC(=O)R 4-1 , -SO2R 4-2 or -OR 4-3 , said amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 4a ; said R 4a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, said amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered hetero cycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 3-8 Cycloalkyl, 3-8 membered hetero cycloalkyl, C 6-14 Aryl or 5-14 membered heteroaryl, substituted by one or more substituents; or, two R 4a Are linked to form a 3-8 membered hetero cycloalkyl or 3-8 membered hetero cycloalkenyl; R 4-1 selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1- 6-haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl; R 4-2 selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1- 6-haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, wherein said amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl; R 4-3 selected from hydrogen, deuterium, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 3- cycloalkyl, 3- to 8-membered heterocycloalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl; R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, -SO2-C 1-6 alkyl, -SF5, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1- 6-deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, optionally further substituted by one or more R 5a substituents; said R 5a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 aryl or 5-14 membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heteroalkyl, C 6-14 An aryl or 5- to 14-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C 6-14 aryl or one or more substituents in 5- to 14-membered heteroaryl; R 6-1 and R 6-2 each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, optionally further substituted by one or more R 5a substituents; said R 5a independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 aryl or 5- to 14-membered heteroaryl, the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heteroalkyl, C 6-14 An aryl or 5- to 14-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C 6-14 aryl or one or more substituents in 5- to 14-membered heteroaryl; Alternatively, R 6-1 , R 6-2 and the carbon linkage therebetween form a C 3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl; R 7-1 and R 7-2 each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkoxy; Alternatively, R 7-1 and R 7-2 are connected to form C 3-8 cycloalkyl; x is selected from 0, 1, 2 or 3; y is selected from 0, 1, 2, 3 or 4; z is selected from 0, 1, 2, 3 or 4; u is selected from 0, 1, 2, 3 or 4.

2. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, characterized in that, Ring A is selected from 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl fused to C 3-6 cycloalkenyl, 5- to 6-membered heteroaryl fused to 5- to 6-membered heteroaryl, or 5- to 6-membered heteroaryl fused to 3- to 6-membered cycloalkenyl, or 5- to 6-membered heteroaryl fused to phenyl; Preferably, ring A is selected from 3. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that, Ring B is selected from C 3-10 cycloalkenyl spiro 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- or 6-membered heteroaryl fused to 3- to 10-membered heterocycloalkenyl, 3- to 10-membered heterocycloalkenyl fused to 5- or 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl spiro 3- to 10-membered heterocycloalkyl, 5- or 6-membered heteroaryl fused to 5- or 6-membered heteroaryl, phenyl fused to C 3- 10 cycloalkenyl, phenyl fused to 3- to 10-membered heterocycloalkenyl, C 3-10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl fused to phenyl, 5- or 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl spiro C 3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl fused to 3- to 10-membered heterocycloalkyl, phenyl fused to 5- or 6-membered heteroaryl, C 3-10 cycloalkenyl spiro C 3- 10 cycloalkyl, 3- to 10-membered heterocycloalkenyl fused to C 3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl; Preferably, ring B is selected from 4. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-3, characterized in that, Ring C is selected from C 6-10 aryl, 5- or 6-membered heteroaryl, 5- or 6-membered heteroaryl fused to 5- or 6-membered heteroaryl, phenyl fused to 5- or 6-membered heteroaryl, phenyl fused to 3- to 6-membered heteroannulenyl, 5- or 6-membered heteroaryl fused to phenyl, 3- to 6-membered heteroannulenyl fused to phenyl, 5- or 6-membered heteroaryl fused to C 3-6 cycloalkenyl, or C 3-8 cycloalkyl; Preferably, ring C is selected from phenyl 5. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-4, characterized in that, Ring E is selected from 5- or 6-membered heteroalkylidene, 4- to 6-membered heteroalkylidenespiro4-6-membered heteroalkylidene, 5- to 6-membered heteroalkylidenebi5-6-membered heteroalkylidene, 5- to 6-membered heteroarylbi5-6-membered heteroalkenyl, or 5- to 6-membered heteroalkylidenebiC 3-6 subcycloalkylidene; Preferably, ring E is selected from Or, wherein the end with * is connected to M; Alternatively, ring E is directly connected to the parent body to form 6. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1, 3 and 4, characterized in that, The compound described is shown by formula (XVI), Wherein, R 2-1 , R 2-2 and R 2-3 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy; or, R 2-2 and R 2-3 are linked to form a C 3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl, and the C 3-6 cycloalkyl and the 3- to 6-membered heterocycloalkyl are optionally further substituted by one or more of hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy; R 7-1 and R 7-2 each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy; Alternatively, R 7-1 and R 7-2 are connected to form C 3-6 cycloalkyl group.

7. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to claim 6, characterized in that, The compound described is represented by formula (XVI), 8. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to claim 6 or 7, wherein Structural fragment For 9. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 6 - 8, wherein Selected from Selected from Or, Selected from Selected from Or, Selected from Selected from Alternatively, Selected from Selected from 10. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, wherein, The compound described is as shown in formula (II). Wherein, Ring B is selected from C 3-10 cycloalkenyl spiro 3- to 10-membered heterocycloalkyl, 5- or 6-membered heteroaryl fused to 3- to 10-membered cycloalkenyl, 3- to 10-membered cycloalkenyl fused to 5- or 6-membered heteroaryl, 3- to 10-membered cycloalkenyl spiro 3- to 10-membered heterocycloalkyl, 5- or 6-membered heteroaryl fused to 5- or 6-membered heteroaryl, 7- to 10-membered cycloalkenyl, C 3-10 cycloalkenyl, 3- to 10-membered cycloalkenyl fused to phenyl, 5- or 6-membered heteroaryl, 3- to 10-membered cycloalkenyl spiro C 3-10 cycloalkyl, 3- to 10-membered cycloalkenyl fused to 3- to 10-membered heterocycloalkyl, Phenyl and 5- or 6-membered heteroaryl, C 3-10 Cycloalkenyl spiro C 3-10 Cycloalkyl, 3- to 10-membered heteroalkenyl fused to C 3-10 Cycloalkyl, Preferably 11. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, wherein, The described compound is shown by formula (VI), Wherein, Ring C is selected from 5-membered heteroaryl, 5- or 6-membered heteroaryl fused to 5- or 6-membered heteroaryl, phenyl fused to 5- or 6-membered heteroaryl, phenyl fused to 3- or 6-membered heterocycloalkenyl, 3- or 6-membered heterocycloalkenyl fused to phenyl, or 5- or 6-membered heteroaryl fused to C 3-6 cycloalkenyl, or C 3- 8 cycloalkyl; preferably, ring C is selected from 12. A compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1, 3 and 4, characterized in that, The described compound is as shown in formula (XV).

13. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 12, wherein R1 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, mercapto, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, optionally further substituted by one or more R 1a substituents; said R 1a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 substituted by one or more substituents selected from aryl or 5- to 6-membered heteroaryl; Preferably, R1 is independently selected from hydroxy, methyl, hydrogen, fluorine, cyclopropyl, trifluoromethyl, mercapto, -CH2OH, -CD3, -N(CH3)2.

14. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 13, wherein R2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 2a ; said R 2a is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 substituted by one or more substituents selected from aryl or 5-6 membered heteroaryl; Alternatively, two R2 are connected to each other to form C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, said C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C 6-10 aryl or 5-6 membered heteroaryl; Alternatively, one of R2 and R3 is connected to form The described Optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1- 3-alkyl, C 2-4 -alkenyl, C 2-4 -alkynyl, C 1-3 -deuterated alkyl, C 1-3 -haloalkyl, C 1-3 -hydroxyalkyl, C 1-3 -alkoxy, C 1-3 -haloalkoxy, C 3-6 -cycloalkyl, 3-6 membered heteroalkyl, C 6-10 -aryl or one or more substituents selected from 5-6 membered heteroaryl; Preferably, R2 is independently selected from hydrogen or methyl.

15. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 14, wherein R3 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6- 10 aryl or 5- to 6-membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, optionally further substituted by one or more R 3a substituents; said R 3a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1- 3-haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered hetero cycloalkyl, C 6-10 substituted by one or more substituents selected from aryl or 5-6 membered heteroaryl; L1 and R3 are connected to form a 3-8-membered heteroalkenyl or 5-6-membered heteroaryl; the 3-8-membered heteroalkenyl and 5-10-membered heteroaryl are optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6-membered heteroalkyl, C 6-10 aryl or 5-10-membered heteroaryl; R3 is selected from ethyl, trifluoromethoxy, vinyl, ethynyl, cyano or 16. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 15, wherein R4 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl, 5-6 membered heteroaryl, -COR 4-1 , -COOR 4-1 , -OC(=O)R 4-1 , -SO2R 4-2 or -OR 4-3 , the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl, 5-6 membered heteroaryl, optionally further substituted by one or more R 4a ; the R 4a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3- to 6-membered heterocycloalkyl, C 6-10 Aryl or 5- to 6-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3- to 6-membered heterocycloalkyl, C 6-10 Aryl or 5- to 6-membered heteroaryl, substituted by one or more substituents; or, two R 4a Groups are joined to form a 3- to 6-membered heterocycloalkyl; R 4-1 selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1- 3-haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1- 3-deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl; R 4-2 selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1- 3-haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heteroalkyl, C 6-10 aryl or 5- to 6-membered heteroaryl; R 4-3 selected from hydrogen, deuterium, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 3- cycloalkyl, 3-6 membered hetero cycloalkyl, C 6-10 aryl or 5-6 membered heteroaryl, wherein the C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 3-6 cycloalkyl, 3-6 membered hetero cycloalkyl, C 6-10 aryl or 5-6 membered heteroaryl, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered hetero cycloalkyl, C 6-10 aryl or 5-6 membered heteroaryl; Preferably, R4 is independently selected from hydrogen, methyl, -SO2CH3, -CH2CN, phenyl Cyclopropyl, fluorine, deuterium.

17. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 16, wherein R5 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, -SO2-C 1-3 alkyl, -SF5, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1- 3-deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 5a ; said R 5a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1- 3-hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, said amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 An aryl or 5- or 6-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C 6-10 aryl or 5- or 6-membered heteroaryl, substituted by one or more substituents; Preferably, R5 is independently selected from hydrogen, chlorine, trifluoromethyl, fluorine, methyl, cyclopropyl, -SF5, ethyl, -SO2CH3.

18. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 17, wherein L1 is selected from a bond, -O-, -S-, imino, C 1-3 alkylene, -CONH-, -CO-C 1-3 alkylene-NH-, -C 1-3 alkylene-CONH-, -C 1-3 alkylene-CONH-C 1-3 alkylene, -C 1-3 alkylene-SO2NH-, -C 1-3 alkylene-SO2NH-, -C 1-3 alkylene-NHCONH-, -C 1-3 alkylene-NHCO-, -C 1-3 alkylene-NHSO2-, -C 1-3 alkylene-CO-, C 2-4 alkenylene, C 2-4 alkynylene, C 1-3 deuterated alkylene, C 1-3 haloalkylene, C 1-3 hydroxyalkylene, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-8 cycloalkylene, 3-8 membered heteroalkylene, 3-8 membered heteroalkenylene, -C 1-3 alkylene-3-8 membered heteroalkylene-, -C 1-3 alkylene-3-8 membered heteroalkenylene-, -C 1-3 alkylene-C 6-10 arylene-, C 6-10 arylene, -C 1-3 alkylene-5-6 membered heteroarylene- or 5-6 membered heteroarylene, the imino, C 1-3 alkylene, -CONH-, -CO-C 1-3 alkylene-NH-, -C 1-3 alkylene-CONH-, -C 1-3 alkylene-CONH-C 1-3 alkylene-C 1-3 alkylene-SO2NH-, -C 1-3 alkylene-SO2NH-, -C 1-3 alkylene-NHCONH-, -C 1-3 alkylene-NHCO-, -C 1-3 alkylene-NHSO2-, -C 1-3 alkylene-CO-, -C 1-3 alkylene-C(=N-OH)NH-, C 2-4 alkenylene, C 2-4 alkynylene, C 1-3 Deuterated alkylene, C 1-3 Halogenated alkylene, C 1-3 Hydroxyalkylidene, C 1-3 Alkoxyalkylidene, C 1-3 Alkylthioalkylidene, C 1-3 Halogenated alkoxyalkylidene, C 3- 8-membered cycloalkylidene, 3-8-membered hetero cycloalkylidene, 3-8-membered hetero cycloalkenyl, -C 1-3 Alkylene-3-8-membered hetero cycloalkylidene-, -C 1-3 Alkylene-3-8-membered hetero cycloalkenyl-, -C 1-3 Alkylene-C 6-10 Arylidene-, C 6-10 Arylidene, -C 1-3 Alkylene-5-6-membered hetero arylidene- or 5-6-membered hetero arylidene, optionally further substituted by one or more substituents selected from deuterium, halogen, amino, hydroxy, cyano, oxo, C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Deuterated alkyl, C 1-3 Halogenated alkyl, C 1-3 Hydroxyalkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 3-6 Cycloalkyl, 3-6-membered hetero cycloalkyl, C 6- 10 Aryl or 5-6-membered hetero aryl; More preferably, L1 is selected from -CH2-, -CH2CONH-*, -CH2SO2NH-*, -COCH2NH-*, -CONH-*, -CH2CO-*, -CH2CON(CH3)-*, -CH2CONHCH2-*, -CH2CH2CONH-*, or -CH2-C(=N-OH)NH-*, wherein the side with * is connected to ring C.

19. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 18, wherein R 6-1 and R 6-2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, optionally further substituted by one or more R 5a ; said R 5a is independently selected from deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 aryl or 5-6 membered heteroaryl, the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-6 membered heteroalkyl, C 6-10 An aryl or 5- or 6-membered heteroaryl, optionally further substituted by deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C 6-10 substituted by one or more substituents selected from aryl or 5- or 6-membered heteroaryl; Alternatively, R 6-1 , R 6-2 and the carbon linkage therebetween form C 3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl; Preferably, R 6-1 is selected from hydrogen, cyano or trifluoromethyl; R 6-2 is selected from hydrogen; Alternatively, preferably, R 6-1 , R 6-2 and the carbon linkage between them form 20. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 19, wherein R 7-1 and R 7-2 each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 haloalkoxy; preferably, R 7-1 is selected from hydrogen or methyl; R 7-2 is selected from methyl; Alternatively, R 7-1 and R 7-2 are connected to form C 3-6 cycloalkyl; preferably, R 7-1 and R 7-2 are connected to form cyclopropyl.

21. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-20, characterized in that, The described compound is as follows:

22. The compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 6-9, characterized in that, it satisfies one or more of the following conditions: (1) R1 is independently selected from hydroxy or C 1-6 alkyl; (2) R4 is deuterium; (3) R5 is independently selected from halogen, C 1-6 alkyl or C 1-6 haloalkyl; (4) x is selected from 0, 1 or 2; preferably 2; (5)R 2-1 is hydrogen; (6)R 7-1 and R 7-2 are each independently selected from hydrogen or C 1-6 alkyl; (7) z is selected from 0, 1 or 2; preferably 2; (8) u is selected from 0, 1 or 2; preferably 2.

23. A pharmaceutical composition comprising the compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 22 and a pharmaceutically acceptable carrier.

24. Use of the compound, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1 - 22 or the pharmaceutical composition according to claim 23 in the preparation of a medicament for treating cancer; the cancer is selected from colorectal cancer, endometrial cancer, ovarian cancer or gastric cancer; more preferably, the cancer is a cancer with high microsatellite instability or defective mismatch repair.

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