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

SPECIFICATION

[0001] The present application claims priority to Chinese Patent Application No. 2024100584923 filed on January 15, 2024; Chinese Patent Application No. 2024101721627 filed on February 6, 2024; Chinese Patent Application No. 2024101819911 filed on February 18, 2024; Chinese Patent Application No. 2024103556304 filed on March 26, 2024; Chinese Patent Application No. 2024105451218 filed on April 30, 2024; Chinese Patent Application No. 2024105806484 filed on May 10, 2024; Chinese Patent Application No. 2024105999241 filed on May 14, 2024; Chinese Patent Application No. 2024106135400 filed on May 16, 2024; Chinese Patent Application No. 2024107582914 filed on June 12, 2024; Chinese Patent Application No. 2024110465352 filed on July 31, 2024; Chinese Patent Application No. 2024115916705 filed on November 7, 2024; and Chinese Patent Application No. 2025100334871 filed on January 8, 2025. The contents of the above Chinese patent applications are incorporated herein by reference in their entirety. TECHNICAL FIELD

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

[0003] The RecQ helicase subfamily is a class of enzymes capable of unwinding nucleotide double strands. Within cells, they are involved in DNA replication, repair, transcription, recombination, as well as RNA splicing, ribosome assembly, protein translation, and telomere stability. This family was first discovered in prokaryotes. The members of the RecQ family are highly conserved from prokaryotes (RecQ) to yeast (sgs1) and humans (five RecQ helicases: RECQ1, BLM, WRN, RECQ4, and RECQ5). WRN is a member of the RecQ family of DNA helicases, consisting of 1432 amino acids with a molecular mass of 160 KD. WRN is primarily localized in the nucleolus and rapidly translocates to other nuclear regions upon DNA 1 damage. WRN is the only member of the human RecQ helicase family that possesses 3'^5' exonuclease activity. Its N-terminal exonuclease domain facilitates WRN in processing complex nucleic acid structures, while the central helicase domain can bind and hydrolyze ATP, thereby providing energy to unwind double-stranded DNA. The C-terminal HRDC domain can regulate the catalytic activity of WRN binding to DNA.

[0004] Microsatellite (MS) refers to DNA sequences composed of tandem repeats of a few nucleotides (mostly 1 to 6) as a unit in the cellular genome, also known as short tandem repeat (STR). When the function of DNA mismatch repair (NMR) is abnormal, replication errors occurring in microsatellites are not corrected and accumulate continuously, resulting in changes in the length or base composition of microsatellite sequences, which is termed microsatellite instability (MSI), and simultaneously leading to a hypermutable phenotype in the genome. In tumors, functional deletion mutations of key MMR genes (MLH1, MSH2, MSH6, and PMS2) and their related genes, or loss of MLH1 expression caused by hypermethylation of the MLH1 promoter region, often result in defects in the DNA mismatch repair (MMR) function. Based on the microsatellite stability status of tumor cells, tumors can be classified into microsatellite instability (MSI) tumors and microsatellite stability (MSS) tumors. MSI is prevalent in cancers, with solid tumors having high incidence rates including endometrial cancer (approximately 30%), gastric cancer (approximately 20%), and colorectal cancer (approximately 15%), among others.

[0005] There is a synthetic lethal relationship between WRN and MSI-H: in MSI tumor cell lines, knockout of WRN leads to characteristics such as genomic instability, cell cycle arrest, and DNA double-strand breaks in these cancer cells, ultimately resulting in the death of the cancer cells. Therefore, by developing small molecule inhibitors targeting WRN, it is expected to achieve selective killing of MSI-H tumor cells, providing personalized anti-tumor therapy for MSI tumor patients.

[0006] The protein product encoded by the hERG gene is the inner pore-forming part of a key membrane-bound potassium ion channel in myocardial tissue, which is controlled by membrane potential and regulates the efflux of potassium ions from cells in a gated manner. When a compound binds to the hERG potassium channel, it blocks the efflux of potassium ions, thereby prolonging the repolarization time of cardiomyocytes, which is reflected as QT interval 2 prolongation on an electrocardiogram, and may further induce the fatal risk of TdP. Therefore, inhibition of hERG can lead to severe toxic side effects. The larger the IC50 of a compound, the lower the risk of hERG inhibition. SUMMARY

[0007] The present disclosure aims to provide a triazolopyrimidine derivative, a preparation method therefor, and a use thereof.

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

[0009] wherein

[0010] M is selected from the group consisting of a bond, CO, -NHCO-, -C(R6-1R6-2)-, and

[0011] ring A is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;

[0012] ring B is selected from the group consisting of C3-12 cycloalkyl, C3-12 cycloalkenyl, 3-to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-14 aryl, and 5- to 14-membered heteroaryl; alternatively, ring B is absent, and R4 is directly attached to the parent structure;

[0013] ring C is selected from the group consisting of C3-12 cycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0014] ring E is selected from the group consisting of C3-12 cycloalkylene, C3-12 cycloalkenylene, 3- to 12-membered heterocycloalkylene, 3- to 12-membered heterocycloalkenylene, C6-14 arylene, and 5- to 14-membered heteroarylene; alternatively, ring E is directly attached to the parent to form or

[0015] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, - CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, -C1-6 alkylene-C(=N-OH)NH-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, and 5- to 14membered heteroarylene, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, or 5- to 14-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5-to 14-membered heteroaryl; 0           0 HN        HN

[0016] alternatively, L1, R3, and the parent form a moiety O HN 5 or         X

[0017] R1 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, mercapto, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0018] R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0019] alternatively, two R2 are connected to each other to form a C3-8 cycloalkyl or a 3- to 8membered heterocycloalkyl, wherein the C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0020] alternatively, one R2 and R3 are connected to form a 5- to 8-membered heterocycloalkenyl, wherein the 5- to 8-membered heterocycloalkenyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0021] R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0022] L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 10membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0023] R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 147 membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl; alternatively, two R4a are connected to form a 3- to 8-membered heterocycloalkyl or a 3- to 8-membered heterocycloalkenyl;

[0024] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0025] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 8 or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0026] R4-3 is selected from the group consisting of hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0027] R5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, -SO2-C1-6 alkyl, -SF5, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, 9 C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0028] R6-1 and R6-2 are independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0029] alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-8 cycloalkyl or a 3- to 8-membered heterocycloalkyl;

[0030] R7-1 and R7-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, and C1-6 haloalkoxy;

[0031] alternatively, R7-1 and R7-2 are connected to form a C3-8 cycloalkyl;

[0032] x is selected from the group consisting of 0, 1, 2, and 3;

[0033] y is selected from the group consisting of 0, 1, 2, 3, and 4;

[0034] z is selected from the group consisting of 0, 1, 2, 3, and 4; 10

[0035] u is selected from the group consisting of 0, 1, 2, 3, and 4.

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

[0037] wherein

[0038] M is selected from the group consisting of a bond, CO, -NHCO-, -C(R6-1R6-2)-, and ;

[0039] ring A is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;

[0040] ring B is selected from the group consisting of C3-12 cycloalkyl, C3-12 cycloalkenyl, 3-to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-14 aryl, and 5- to 14-membered heteroaryl; alternatively, ring B is absent, and R4 is directly attached to the parent structure;

[0041] ring C is selected from the group consisting of C3-12 cycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0042] ring E is selected from the group consisting of C3-12 cycloalkylene, C3-12 cycloalkenylene, 3- to 12-membered heterocycloalkylene, 3- to 12-membered heterocycloalkenylene, C6-14 arylene, and 5- to 14-membered heteroarylene; alternatively, ring E is directly attached to the parent to form or

[0043] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, - CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, -C1-6 alkylene-C(=N-OH)NH-, C2-6 alkenylene, C2-6 alkynylene, 11 C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene- C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, and 5- to 14- membered heteroarylene, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2- 6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8- membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, - C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, or 5- to 14-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl; 0 HN /

[0044] alternatively, Li, R3, and the parent form a moiety                ~ or 0 0¾ HNx . ;

[0045] Ri is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, mercapto, cyano, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0046] R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted 13 with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0047] alternatively, two R2 are connected to each other to form a C3-8 cycloalkyl or a 3- to 8membered heterocycloalkyl, wherein the C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0048] alternatively, one R2 and R3 are connected to form a 5- to 8-membered heterocycloalkenyl, wherein the 5- to 8-membered heterocycloalkenyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0049] R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents 14 selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0050] L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 10membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0051] R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl; alternatively, two R4a are connected to form a 3- to 8-membered 15 heterocycloalkyl or a 3- to 8-membered heterocycloalkenyl;

[0052] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0053] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0054] R4-3 is selected from the group consisting of hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 16 C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0055] R5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, -SO2-C1-6 alkyl, -SF5, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0056] R6-1 and R6-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, 17 C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0057] alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-8 cycloalkyl or a 3- to 8-membered heterocycloalkyl;

[0058] x is selected from the group consisting of 0, 1, 2, and 3;

[0059] y is selected from the group consisting of 0, 1, 2, 3, and 4;

[0060] z is selected from the group consisting of 0, 1, 2, 3, and 4;

[0061] u is selected from the group consisting of 0, 1, 2, 3, and 4.

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

[0063]

[0064]

[0065] wherein M is selected from the group consisting of a bond, CO, -NHCO-, -C(R6-1R6-2)-, and ; ring A is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;

[0066] ring B is selected from the group consisting of C3-12 cycloalkyl, C3-12 cycloalkenyl, 3-to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-14 aryl, and 5- to 14-membered heteroaryl; or, ring B is absent, and R4 is directly attached to the parent structure;

[0067] ring C is selected from the group consisting of C3-12 cycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0068] ring E is selected from the group consisting of C3-12 cycloalkylene, C3-12 cycloalkenylene, 3- to 12-membered heterocycloalkylene, 3- to 12-membered heterocycloalkenylene, C6-14 arylene, and 5- to 14-membered heteroarylene; alternatively, ring E is directly attached to the parent to form                         or                         ;

[0069] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, -C1-6 alkylene-C(=N-OH)NH-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, and 5- to 14membered heteroarylene, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, or 5- to 14-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0070] alternatively, L1, R3, and the parent form a moiety

[0071] R1 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, mercapto, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0072] R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0073] alternatively, two R2 are connected to each other to form a C3-8 cycloalkyl or a 3- to 8membered heterocycloalkyl, wherein the C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0074] alternatively, one R2 and R3 are connected to form a 5- to 8-membered heterocycloalkenyl, wherein the 5- to 8-membered heterocycloalkenyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0075] R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 21 or 5- to 14-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0076] L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 10membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0077] R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered 22 heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl; alternatively, two R4a are connected to form a 3- to 8-membered heterocycloalkyl or a 3- to 8-membered heterocycloalkenyl;

[0078] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0079] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 1423 membered heteroaryl;

[0080] R4-3 is selected from the group consisting of hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0081] R5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0082] R6-1 and R6-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 24 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0083] alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-8 cycloalkyl or a 3- to 8-membered heterocycloalkyl;

[0084] x is selected from the group consisting of 0, 1, 2, and 3;

[0085] y is selected from the group consisting of 0, 1, 2, 3, and 4;

[0086] z is selected from the group consisting of 0, 1, 2, 3, and 4;

[0087] u is selected from the group consisting of 0, 1, 2, 3, and 4.

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

[0089] wherein

[0090] M is selected from the group consisting of a bond, CO, -NHCO-, and -C(R6-1R6-2)-;

[0091] ring A is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;

[0092] ring B is selected from the group consisting of C3-12 cycloalkyl, C3-12 cycloalkenyl, 3- to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-14 aryl, and 5- to 14-membered heteroaryl; or, ring B is absent, and R4 is directly attached to the parent structure;

[0093] ring C is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;

[0094] ring E is selected from the group consisting of C3-12 cycloalkylene, C3-12 cycloalkenylene, 3- to 12-membered heterocycloalkylene, 3- to 12-membered heterocycloalkenylene, C6-14 arylene, and 5- to 14-membered heteroarylene; alternatively, ring E is directly attached to the parent to form

[0095] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, and 5- to 14-membered heteroarylene, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, or 5- to 14membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0096] R1 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0097] R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 27 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0098] alternatively, two R2 are connected to each other to form a C3-8 cycloalkyl or a 3- to 8membered heterocycloalkyl, wherein the C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0099] alternatively, one R2 and R3 are connected to form a 5- to 8-membered heterocycloalkenyl, wherein the 5- to 8-membered heterocycloalkenyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0100] R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, 28 C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0101] L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 10membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0102] R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 29 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl; alternatively, two R4a are connected to form a 3- to 8-membered heterocycloalkyl or a 3- to 8-membered heterocycloalkenyl;

[0103] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0104] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, 30 C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0105] R4-3 is selected from the group consisting of hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0106] R5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0107] R6-1 and R6-2 are each independently selected from the group consisting of hydrogen, 31 deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0108] alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-8 cycloalkyl or a 3- to 8-membered heterocycloalkyl;

[0109] x is selected from the group consisting of 0, 1, 2, and 3;

[0110] y is selected from the group consisting of 0, 1, 2, 3, and 4;

[0111] z is selected from the group consisting of 0, 1, 2, 3, and 4;

[0112] u is selected from the group consisting of 0, 1, 2, 3, and 4.

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

[0114] wherein

[0115] M is selected from the group consisting of a bond and CO;

[0116] ring A is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;

[0117] ring B is selected from the group consisting of C3-12 cycloalkyl, C3-12 cycloalkenyl, 3-to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-14 aryl, and 5- to 14-membered heteroaryl; alternatively, ring B is absent, and R4 is directly attached to the parent structure;

[0118] ring C is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;

[0119] ring E is selected from the group consisting of C3-12 cycloalkylene, C3-12 cycloalkenylene, 3- to 12-membered heterocycloalkylene, 3- to 12-membered heterocycloalkenylene, C6-14 arylene, and 5- to 14-membered heteroarylene; alternatively, ring E is directly attached to the parent to form

[0120] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-14 arylene, and 5- to 14-membered heteroarylene, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8membered heterocycloalkylene-, C6-14 arylene, or 5- to 14-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0121] R1 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0122] R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of deuterium, 34 halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0123] alternatively, two R2 are connected to each other to form a C3-8 cycloalkyl or a 3- to 8membered heterocycloalkyl, wherein the C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0124] alternatively, one R2 and R3 are connected to form a 5- to 8-membered heterocycloalkenyl, wherein the 5- to 8-membered heterocycloalkenyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0125] R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, 35 cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0126] L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 10membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0127] R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, -COR4-1, and -SO2R4-2, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 36 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0128] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0129] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0130] R5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 37 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0131] x is selected from the group consisting of 0, 1, 2, and 3;

[0132] y is selected from the group consisting of 0, 1, 2, 3, and 4;

[0133] z is selected from the group consisting of 0, 1, 2, 3, and 4;

[0134] u is selected from the group consisting of 0, 1, 2, 3, and 4.

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

[0136] In certain embodiments of the present disclosure, M is 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 the group consisting of 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, 5- to 6membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, and 5- to 6-membered heteroaryl-fused phenyl; the definitions of other groups are as defined in any technical solution herein.

[0138] In certain embodiments of the present disclosure, ring A is selected from the group 38 consisting of 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, and 5- to 6- membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl;

[0139] preferably, ring A is selected from the group consisting of N^>N and

[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 5- to 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 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl; the definitions of other groups are as defined in any technical solution herein. nNH

[0143] In certain embodiments of the present disclosure, ring A is       N-A ; the definitions of other groups are as defined in any technical solution herein.

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

[0145] In certain embodiments of the present disclosure, ring A is HN-N or, ring A is HN—N ; or, ring A is ; or, ring A is selected from the group consisting of in any technical solution herein.

[0146] In certain embodiments of the present disclosure, ring B is selected from the group consisting of C3-10 cycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused 3- to 10-membered heterocycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused C3-10 cycloalkenyl, benzo-fused 3- to 10membered heterocycloalkenyl, C3-10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl-fused 3- to 10-membered heterocycloalkyl, benzo-fused 5- to 6-membered heteroaryl, C3-10 cycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10membered heterocycloalkenyl-fused C3-10 cycloalkyl, and 3- to 10-membered heterocycloalkyl; the definitions of other groups are as defined in any technical solution herein.

[0147] In certain embodiments of the present disclosure, ring B is selected from the group consisting of C3-10 cycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused 3- to 10-membered heterocycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 5- to 6-membered heteroaryl-40 fused 5- to 6-membered heteroaryl, benzo-fused C3-10 cycloalkenyl, benzo-fused 3- to 10membered heterocycloalkenyl, C3-10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl-fused 3- to 10-membered heterocycloalkyl, benzo-fused 5- to 6-membered heteroaryl, and C3-10 cycloalkenyl-spiro-C3-10 cycloalkyl; 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 the group consisting of C3-6 cycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 3- to 8-membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused C3-6 cycloalkenyl, benzo-fused 3- to 6membered heterocycloalkenyl, C3-8 cycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkenyl-fused 3- to 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 the group consisting of C3-6 cycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 3- to 8-membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused C3-6 cycloalkenyl, and benzo-fused 3- to 6membered 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 the group consisting of C3-6 cycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused C3-6 cycloalkenyl, and benzo-fused 3- to 641 membered heterocycloalkenyl; ° X       0 Af-

[0152] preferably, ring B is selected from the group consisting of V "   ,  \"   , °co^ xa hn? N , \^n   ,            , and           ;

[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           ; the definitions of other groups are as defined in any technical solution herein.

[0155] In certain embodiments of the present disclosure, ring B is 5- to 6-membered O A heteroaryl-fused 3- to 6-membered heterocycloalkenyl, preferably         N     , or preferably ; the definitions of other groups are as defined in any technical solution herein.

[0156] In certain embodiments of the present disclosure, ring B is 3- to 6-membered N heterocycloalkenyl-fused 5- to 6-membered heteroaryl, preferably definitions of other groups are as defined in any technical solution herein. ; the n-n

[0157] In certain embodiments of the present disclosure, ring B is is ; or, ring B ; or, ring B is selected from the group consisting of and consisting of ; or, ring B is selected from the group group consisting of ; or, ring B is selected from the , and ; the definitions of other groups are as defined in any technical solution herein.

[0158] In certain embodiments of the present disclosure, ring B is ; 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 the group consisting of C6-10 aryl, 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused phenyl, 3- to 6-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, and C3-8 cycloalkyl; 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 the group consisting of C6-10 aryl, 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused phenyl, 3- to 6-membered heterocycloalkenyl-fused phenyl, and 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl; 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 the group consisting of C6-10 aryl, 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6membered heterocycloalkenyl, and 5- to 6-membered heteroaryl-fused phenyl.

[0162] In certain embodiments of the present disclosure, ring C is selected from the group consisting of C6-10 aryl, 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, and benzo-fused 3- to 6membered heterocycloalkenyl; nr z'n

[0163] preferably, ring C is selected from the group consisting of phenyl, N-- /  ,

[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 C6-10 aryl, preferably phenyl; the definitions of other groups are as defined in any technical solution herein. In certain embodiments of the present disclosure, ring C is or, ring C is

[0166] ; or, ring C is Yj Yn Yn ; or, ring C is           ; or, ring C is           ; or, ring C is selected from the group consisting of and s , and HN-- / ; or, ring C is selected from the group consisting of or, ring C is selected from the group consisting of and ; or, ring C is selected from the group consisting of s , and ; the definitions of other groups are as defined in any technical solution herein.

[0167] In certain embodiments of the present disclosure, ring C is S-— / ; 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 the group consisting of 5- to 6-membered heterocycloalkylene, 4- to 6-membered heterocycloalkylene-spiro-4- to 6-membered heterocycloalkylene, 5- to 6-membered heterocycloalkylene-fused 5-to 6-membered heterocycloalkylene, 5- to 6-membered heteroaryl-fused 5- to 6-membered heterocycloalkenyl, and 5- to 6-membered heterocycloalkylene-fused C3-6 cycloalkylene; 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 the group consisting of 5- to 6-membered heterocycloalkylene, 4- to 6-membered heterocycloalkylene-spiro-4- to 6-membered heterocycloalkylene, 5- to 6-membered heterocycloalkylene-fused 5-to 6-membered heterocycloalkylene, and 5- to 6-membered heteroaryl-fused 5- to 6-membered heterocycloalkenyl; the definitions of other groups are as defined in any technical solution herein.

[0170] In certain embodiments of the present disclosure, ring E is selected from the group consisting of wherein the end with * is connected to M; the definitions of other groups are as defined in any technical solution herein.

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

[0172] In certain embodiments of the present disclosure, ring E is selected from the group consisting of n-n ; or, ring E is selected from the group consisting of and ; wherein the end with * is connected to M; the definitions of other groups are as defined in any technical solution herein.

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

[0174] In certain embodiments of the present disclosure, the compound is represented by formula (II),

[0175] wherein

[0176] ring B is selected from the group consisting of C3-10 cycloalkenyl-spiro-3- to 10 membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 3- to 10-membered heterocycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 5- to 6membered heteroaryl-fused 5- to 6-membered heteroaryl, 7- to 10-membered heterocycloalkenyl, C3-10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl-fused 3- to 10-membered heterocycloalkyl, , benzo-fused 5- to 6-membered heteroaryl, C3-10 cycloalkenyl- spiro-C3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl-fused C3-10 cycloalkyl, and ; the definitions of other groups are as defined in any technical solution herein.

[0177] In certain embodiments of the present disclosure, the compound is represented by formula (II),

[0178] wherein

[0179] ring B is selected from the group consisting of C3-10 cycloalkenyl-spiro-3- to 10membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 3- to 10-membered heterocycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 5- to 6membered heteroaryl-fused 5- to 6-membered heteroaryl, 7- to 10-membered heterocycloalkenyl, C3-10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl-fused 3- to 10-membered heterocycloalkyl, o^, HN        ,     HN        , benzo-fused 5- to 6-membered heteroaryl, and C3-10 cycloalkenyl-spiro-C3-10 cycloalkyl; the definitions of other groups are as defined in any technical solution herein.

[0180] In certain embodiments of the present disclosure, the compound is represented by formula (II),

[0181] wherein

[0182] ring B is selected from the group consisting of C3-6 cycloalkenyl-spiro-3- to 6membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 5- to 6membered heteroaryl-fused 5- to 6-membered heteroaryl, 7- to 8-membered heterocycloalkenyl, C3-8 cycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused phenyl, 5-to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-C3-6 cycloalkyl, 3- to 6- HN membered heterocycloalkenyl-fused 3- to 6-membered heterocycloalkyl,    \"    , O . HN       , and HN       ; the definitions of other groups are as defined in any technical solution herein.

[0183] In certain embodiments of the present disclosure, the compound is represented by formula (II),

[0184] wherein

[0185] ring B is selected from the group consisting of C3-6 cycloalkenyl-spiro-3- to 6- membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, 5- to 6- membered heteroaryl-fused 5- to 6-membered heteroaryl, and 7- to 8-membered heterocycloalkenyl; preferably and ; 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 the group nn consisting of , and ; or, ring B is selected from the ; or, ring B is selected from the group consisting of and 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 , the (4 structural moiety is ; 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 , the (r4) r4 / zH- structural moiety           is       '—J    ; the definitions of other groups are as defined in any technical solution herein.

[0189] In certain embodiments of the present disclosure, the compound is represented by formula (II),

[0190] wherein

[0191] ring B is selected from the group consisting of C3-6 cycloalkenyl-spiro-3- to 6membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 6-membered heterocycloalkenyl-spiro-3- to 6-membered heterocycloalkyl, and 5- to 6- membered heteroaryl-fused 5- to 6-membered heteroaryl; preferably N ,         N , and               ; 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 group consisting of ; the definitions of other groups are as defined in any technical solution herein. Wz

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

[0194] In certain embodiments of the present disclosure, the compound is represented by formula (III), O (HI)

[0195] wherein R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, methyl, C3-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-51 6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3-to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C3-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl; the methyl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0196] preferably, R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, methyl, C3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 352 to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; the methyl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C2-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0197] more preferably, R3 is selected from the group consisting of trifluoromethoxy, vinyl, ethynyl, and 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 5- to 6-membered heteroaryl, 53 preferably      NH; the 5- to 6-membered heteroaryl or      NH is optionally substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; The definitions of other groups are as defined in any technical solution herein. '^zN

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

[0201] In certain embodiments of the present disclosure, the compound is represented by formula (IV),

[0202] R1-1 is selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, or C3-8 cycloalkyl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0203] preferably, R1-1 is selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C2-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0204] more preferably, R1-1 is △;

[0205] w is selected from the group consisting of 0, 1, and 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 represented by formula (IV'), o (IV)

[0208] R1-2 is selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl; preferably, R1-2 is selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C2-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C2-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; ro

[0209] more preferably, R1-2 is        ;

[0210] w is selected from the group consisting of 0, 1, and 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 represented by formula (V),

[0213] wherein ring A is selected from the group consisting of 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, 5- to 6-membered nL X N- J M B 0 heteroaryl-fused phenyl,      N ,      N , and      M      ; the definitions of other groups are as defined in any technical solution herein.

[0214] In certain embodiments of the present disclosure, the compound is represented by 57 formula (V),

[0215] wherein ring A is selected from the group consisting of 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, 5- to N 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl,     N ,     N , and N. A- N^O H      ; the definitions of other groups are as defined in any technical solution herein.

[0216] In certain embodiments of the present disclosure, the compound is represented by formula (V),

[0217] wherein ring A is selected from the group consisting of 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, and 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl; preferably, ring A is selected from the group consisting of               and              ;

[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 represented by formula (VI), 0 (VI)

[0220] wherein ring C is selected from the group consisting of 5-membered heteroaryl,

[0221] 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo- fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6-membered heterocycloalkenyl, 3- to 6membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, and C3-8 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 represented by formula (VI), (VI)

[0223] wherein

[0224] ring C is selected from the group consisting of 5-membered heteroaryl, , 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, and C3-8 cycloalkyl; the definitions of other groups are as defined in any technical solution herein.

[0225] In certain embodiments of the present disclosure, the compound is represented by formula (VI), N R: L .0 (VI)

[0226] wherein

[0227] ring C is selected from the group consisting of 5-membered heteroaryl,         , 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused phenyl, and 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl; the definitions of other groups are as defined in any technical solution herein.

[0228] In certain embodiments of the present disclosure, the compound is represented by formula (VI), (VI)

[0229] wherein

[0230] ring C is selected from the group consisting of 5-membered heteroaryl 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, and benzo-fused 3- to 6-membered heterocycloalkenyl; preferably, ring C is 60 selected from the group consisting of , and ; the definitions of other groups are as defined in any technical solution herein.

[0231] In certain embodiments of the present disclosure, the compound is represented by formula (VI), o (VI)

[0232] wherein

[0233] ring C is selected from the group consisting of 5-membered heteroaryl, 5- to 6membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, and benzo-fused 3- to 6-membered heterocycloalkenyl; preferably, ring C is selected from the group consisting of , and

[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 group V) V;n consisting of        ,          , and          ; the definitions of other groups are as defined in any technical solution herein.

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

[0237] In certain embodiments of the present disclosure, the compound is represented by formula (VII) or formula (VIII), o                                      o

[0238] wherein

[0239] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0240] preferably, R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6- membered heteroaryl;

[0241] more preferably, R4-1 is selected from the group consisting of cyclopropyl, isopropyl, and ethyl;

[0242] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkylthio, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0243] preferably, R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0244] preferably, R4-2 is methyl;

[0245] z is selected from the group consisting of 0, 1, 2, and 3;

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

[0247] In certain embodiments of the present disclosure, R4-1 is C3-6 cycloalkyl, preferably cyclopropyl; the definitions of other groups are as defined in any technical solution herein. 63

[0248] In certain embodiments of the present disclosure, R4-1 is C1-3 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, R4-1 is -CH2CF3; or, R4-1 is -NHCH3; R4-1 is -N(CH3)2; or, R4-1 is -C(OH)(CH3)2; or, R4-1 is tert-butyl; or, R4-1 is -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 represented by formula (X),

[0251] ring D is 5- to 6-membered heterocyclyl; preferably 0    ;

[0252] R4-3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0253] preferably, R4-3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0254] more preferably, R4-3 is methyl;

[0255] z is selected from the group consisting of 0, 1, 2, and 3;

[0256] v is selected from the group consisting of 0, 1, 2, and 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 group consisting of HN and ; the definitions of other groups are as defined in any technical solution herein.

[0259] In certain embodiments of the present disclosure, the compound is represented by formula (IX),

[0260] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-C6-14 heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, 5- to 14-membered heteroarylene, and -CH2CH2CONH-, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-C6-14 heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, 5- to 14-membered heteroarylene, or -CH2CH2CONH- is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0261] preferably, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, 5- to 6-membered heteroarylene, and -CH2CH2CONH-, wherein the imino, C1-3 alkylene, -C1-3 alkylene-CONH-C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, 5- to 6-membered heteroarylene, or -CH2CH2CONH- is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered 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 represented by formula (IX), o

[0264] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, -C1-6 alkylene-C(=N-OH)NH-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-C6-14 heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, 5- to 14-membered heteroarylene, and -CH2CH2CONH-, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene,   -C1-6   alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-C6-14 heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, 5- to 14-membered heteroarylene, or -CH2CH2CONH- is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0265] preferably, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, -C1-3 alkylene-C(=N-OH)NH-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, 5- to 6-membered heteroarylene, and -CH2CH2CONH-, wherein the imino, C1-3 alkylene, -C1-3 alkylene-CONH-C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, 5-to 6-membered heteroarylene, or -CH2CH2CONH- is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; the definitions of other groups are as defined in any technical solution herein.

[0266] In certain embodiments of the present disclosure, the compound is represented by formula (IX), o

[0267] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, - CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-14 arylene, and 5-to 14-membered heteroarylene, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-14 arylene, or 5-to 14-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5-to 14-membered heteroaryl;

[0268] preferably, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-10 arylene, and 5- to 6-membered heteroarylene, wherein the imino, C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-10 arylene, or 5-to 6-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 69 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5-to 6-membered heteroaryl;

[0269] more preferably, L1 is selected from the group consisting of -CH2-, -CH2SO2NH-*, - COCH2NH-*, -CONH-*, wherein the side with * is connected to ring C;

[0270] the definitions of other groups are as defined in any technical solution herein.

[0271] In certain embodiments of the present disclosure, the compound is represented by formula (IX),

[0272] L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-14 arylene, and 5- to 14-membered heteroarylene, wherein the imino, C1-6 alkylene, -C1-6 alkylene-CONH-, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-14 arylene, or 5- to 14-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;

[0273] preferably, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, -alkylene-3- to 8membered heterocycloalkylene-, C6-10 arylene, and 5- to 6-membered heteroarylene, wherein the imino, C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-10 arylene, or 5- to 6-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0274] more preferably, L1 is selected from the group consisting of -CH2-, -CH2SO2NH-*, , wherein the side with * is connected to ring C;

[0275] the definitions of other groups are as defined in any technical solution herein.

[0276] In certain embodiments of the present disclosure, L1 is -COCH2NH-*; or, L1 is - CONH-*; or, Li is          ; or, Li is ; or, Li is or, Li is ; or, L1 is ; or, Li is       * ; or, Li is selected from the group consisting of -CH2CO-*,  -CH2CON(CH3)-*,  -CH2CONHCH2-*,  -CH2CH2CONH-*, and ; or, Li is selected from the group consisting of and -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.

[0277] In certain embodiments of the present disclosure, the compound is represented by formula (XI), (XI)

[0278] wherein ring E is selected from the group consisting of 4- to 6-membered heterocycloalkylene-spiro-4- to 6-membered heterocycloalkylene, 5- to 6-membered heterocycloalkylene-fused 5- to 6-membered heterocycloalkylene, 5- to 6-membered heteroaryl-fused 5- to 6-membered heterocycloalkenyl, and

[0279] alternatively, ring E is directly connected to the parent to form * N.

[0280] In certain embodiments of the present disclosure, the compound is represented by formula (XI), (XI)

[0281] wherein ring E is selected from the group consisting of 4- to 6-membered heterocycloalkylene-spiro-4- to 6-membered heterocycloalkylene, 5- to 6-membered heterocycloalkylene-fused 5- to 6-membered heterocycloalkylene, and 5- to 6-membered heteroaryl-fused 5- to 6-membered heterocycloalkenyl;

[0282] alternatively, ring E is directly connected to the parent to form                     ;

[0283] the definitions of other groups are as defined in any technical solution herein.

[0284] In certain embodiments of the present disclosure, ring E is selected from the group consisting of HN-N wherein the end with * is connected to M; the definitions of other groups are as defined in any technical solution herein.

[0285]

[0286] In certain embodiments of the present disclosure, the compound is represented by formula (XII),

[0287] wherein

[0288] L2 is selected from the group consisting of -CH2OCH2-, -CH2CH2CH2-, -CH2NHCH2-, and -CH2CH2-, wherein the -CH2OCH2-, -CH2CH2CH2-, -CH2NHCH2-, or -CH2CH2- is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; the definitions of other groups are as defined in any technical solution herein.

[0289] In certain embodiments of the present disclosure, L2 is -CH2OCH2-; or, L2 is -CH2CH2CH2-; or, L2 is -CH2NHCH2-; or, L2 is -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 represented by formula (XIII),

[0291] R4 is independently selected from the group consisting of hydrogen, deuterium, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl; alternatively, two R4a are connected to form a 3- to 8-membered heterocycloalkyl or a 3- to 8-membered heterocycloalkenyl;

[0292] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0293] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, 75 C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;

[0294] R4-3 is selected from the group consisting of hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 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 the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, 5-to 6-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 76 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; or, two R4a are connected to form a 3- to 6-membered heterocycloalkyl or a 3- to 6-membered heterocycloalkenyl;

[0297] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0298] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0299] R4-3 is selected from the group consisting of hydrogen, deuterium, C1-3 alkyl, C2-4 77 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; 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 the group consisting of ; the definitions of other groups are as defined in any technical solution herein.

[0301] In certain embodiments of the present disclosure, the compound is represented by formula (XIV), (XIV)

[0302] R6-1 and R6-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6- membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0303] alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl;

[0304] the definitions of other groups are as defined in any technical solution herein.

[0305] In certain embodiments of the present disclosure, R6-1 is selected from the group consisting of hydrogen, cyano, and trifluoromethyl; R6-2 is hydrogen; the definitions of other groups are as defined in any technical solution herein.

[0306] In certain embodiments of the present disclosure, R6-1 and R6-2, together with the carbon atom to which they are attached, form (i.e., M is |— 0 (i.e., M is ); the definitions of other groups are as defined in any technical solution herein.

[0307] In certain embodiments of the present disclosure, the compound is represented by formula (XVII),

[0308] R2-1, R2-2, and R2-3 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy; or, R2-2 and R2-3 are connected to form a C3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl, wherein the C3-6 cycloalkyl and 3- to 6-membered heterocycloalkyl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy;

[0309] the definitions of other groups are as defined in any technical solution herein.

[0310] In certain embodiments of the present disclosure, the formula (XVII) is further represented by formula (XVII-1),

[0311] the definitions of groups are as defined in any technical solution herein.

[0312] In certain embodiments of the present disclosure, the compound is represented by formula (XV),

[0313] the definitions of groups are as defined in any technical solution herein.

[0314] In certain embodiments of the present disclosure, the compound is represented by formula (XVI), (XVI)

[0315] wherein R2-1, R2-2, and R2-3 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy; or, R2-2 and R2-3 are connected to form a C3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl, wherein the C3-6 cycloalkyl and 3- to 6-membered heterocycloalkyl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy;

[0316] R7-1 and R7-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy;

[0317] alternatively, R7-1 and R7-2 are connected to form a C3-6 cycloalkyl;

[0318] the definitions of other groups are as defined in any technical solution herein.

[0319] In certain embodiments of the present disclosure, R2-2 and R2-3 are connected to form a cyclobutyl, wherein the cyclobutyl is optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy; the definitions of other groups are as defined in any technical solution herein.

[0320] In certain embodiments of the present disclosure, the formula (XVI) is further represented by formula (XVI-1), ( XVI-1 )

[0321] the definitions of groups are as defined in any technical solution herein.

[0322] In certain embodiments of the present disclosure, the structural moiety R2-3 R2-2 R2-1 is R2-1 the definitions of other groups are as defined in any technical solution herein.

[0323] In certain embodiments of the present disclosure, the structural moiety R R2-2 K2-3 -. R2-1 is 2-1 • ; the definitions of other groups are as defined in any technical solution herein.

[0324] In certain embodiments of the present disclosure, R2-1 is hydrogen; or, R2-1 is methyl; the definitions of other groups are as defined in any technical solution herein.

[0325] In certain embodiments of the present disclosure, R7-1 is hydrogen, R7-2 is methyl; or, R7-1 is methyl, R7-2 is methyl; or, R7-1 and R7-2 are connected to form a cyclopropyl; the 82 definitions of other groups are as defined in any technical solution herein. In certain embodiments of the present disclosure, ring B is ; ring C is

[0326] ; the definitions of other groups are as defined in any technical solution herein. In certain embodiments of the present disclosure, ring B is ; ring C is

[0327] the definitions of other groups are as defined in any technical solution herein.

[0328] In certain embodiments of the present disclosure, the definitions of other groups are as defined in any technical solution herein. The inventors have found that when ring C is modified into 5-membered heteroaryl, the thiophene ring can maintain excellent cell inhibitory activity, while other 5-membered heteroaryl groups, such as thiazolyl, furanyl, and pyrrolyl, all lead to a decrease in cell inhibitory activity, as evidenced by the comparison of compound 295 with compounds 342, 344, 345, and 348. Cc X / V^(r5) T>CHF2

[0329] In certain embodiments of the present disclosure,               u is S /       ; the definitions of other groups are as defined in any technical solution herein. ^f^CF3

[0330] In certain embodiments of the present disclosure,               u is      s      ; the definitions of other groups are as defined in any technical solution herein.

[0331] In certain embodiments of the present disclosure, is ; the definitions of other groups are as defined in any technical solution herein. The inventors have found that modifying from can significantly reduce the inhibitory effect of the compound on hERG potassium channel current, thereby improving safety, as evidenced by the comparison of 21A and compound 303-P4.

[0332] H In certain embodiments of the present disclosure,           is ; the definitions of other groups are as defined in any technical solution herein. H

[0333] In certain embodiments of the present disclosure,            is is the definitions of other groups are as defined in any technical solution herein. The inventors have found that modifying from , and modifying from to can further significantly reduce the inhibitory effect of the compound on hERG potassium channel current, thereby improving safety, as evidenced by the comparison of 21A and compound 295-P4.

[0334] In certain embodiments of the present disclosure, solution herein. ; the definitions of other groups are as defined in any technical W In certain embodiments of the present disclosure,            is

[0335] CF3 ; the definitions of other groups are as defined in any technical solution herein.

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

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

[0338] In certain embodiments of the present disclosure, R1 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, mercapto, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl; 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 the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, 86 C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0340] preferably, R1 is independently selected from the group consisting of hydroxyl, methyl, hydrogen, fluorine, and ;

[0341] the definitions of other groups are as defined in any technical solution herein. r°

[0342] In certain embodiments of the present disclosure, Ri is independently        ; or, Ri is independently selected from the group consisting of cyclopropyl, trifluoromethyl, mercapto, -CH2OH, and -CD3; or, Ri is independently -N(CH3)2; the definitions of other groups are as defined in any technical solution herein.

[0343] In certain embodiments of the present disclosure, R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, Ci-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-3 deuterated alkyl, Ci-3 haloalkyl, Ci-3 hydroxyalkyl, Ci-3 alkoxy, Ci-3 alkylthio, Ci-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-i0 aryl, and 5- to 6-membered heteroaryl, wherein the amino, Ci-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-3 deuterated alkyl, Ci-3 haloalkyl, Ci-3 hydroxyalkyl, Ci-3 alkoxy, Ci-3 alkylthio, Ci-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-i0 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, Ci-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, Ci-3 deuterated alkyl, Ci-3 haloalkyl, Ci-3 hydroxyalkyl, Ci-3 alkoxy, Ci- 3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0344] alternatively, two R2 are connected to each other to form a C3-6 cycloalkyl or a 3- to 6membered heterocycloalkyl, wherein the C3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl;

[0345] preferably, R2 is independently hydrogen;

[0346] the definitions of other groups are as defined in any technical solution herein.

[0347] In certain embodiments of the present disclosure, R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl 88 is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0348] alternatively, two R2 are connected to each other to form a C3-6 cycloalkyl or a 3- to 6membered heterocycloalkyl, wherein the C3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl;

[0349] alternatively, one R2 and R3 are connected to form or wherein the or is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; the definitions of other groups are as defined in any technical solution herein.

[0350] In certain embodiments of the present disclosure, R2 is independently methyl; the definitions of other groups are as defined in any technical solution herein.

[0351] In certain embodiments of the present disclosure, R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0352] L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 6membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl;

[0353] R3 is selected from the group consisting of ethyl, trifluoromethoxy, vinyl, ethynyl, cyano, and       \ ;

[0354] the definitions of other groups are as defined in any technical solution herein.

[0355] In certain embodiments of the present disclosure, R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is 90 optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0356] R3 is selected from the group consisting of ethyl, trifluoromethoxy, vinyl, ethynyl, and cyano;

[0357] the definitions of other groups are as defined in any technical solution herein.

[0358] In certain embodiments of the present disclosure, R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, 5-to 6-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, 91 hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; or, two R4a are connected to form a 3- to 6-membered heterocycloalkyl;

[0359] R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0360] R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0361] R4-3 is selected from the group consisting of hydrogen, deuterium, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, 92 C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl; the definitions of other groups are as defined in any technical solution herein.

[0362] the definitions of other groups are as defined in any technical solution herein.

[0363] In certain embodiments of the present disclosure, R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2- 4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1- 3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, 5- to 6-membered heteroaryl, -COR4-1, and -SO2R4-2, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6- membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6- membered heteroaryl;

[0364] preferably, R4 is independently selected from the group consisting of hydrogen, methyl, 0 , and -SO2CH3;

[0365] the definitions of other groups are as defined in any technical solution herein.

[0366] In certain embodiments of the present disclosure, R4 is independently selected from o o     m,n     o          y f CP”        61 “A the group consisting of F3C      , d 0   ,   NH , and HO F,C          « / °+ d y selected from the group consisting of        ,^    , o A-                  04 A d ^^0 a ,     ,    ,, fN m-N      m-N     ^-x     \ M vl 1A 1A p4 T CH2CN,      *, / 0 , / S , N , W 0 0 0=H 0 TM £d °f 61A phenyl, / 0   , Ao   ,   △ , \d ,       , -..^ / 0 O   OO      66 \ 1° L A 0    1 N1          < z ,                , dv    , cyclopropyl,           , 0 Vn^" \ / °6 rN            n^N      \ ? / A / H  JAA FA 1a   / nA /  , f 0 , As , As , As , and   0 rT d1 ( selected from the group consisting of £--3    ,           ,   ' ; or, R4 is independently 1- H A ,,   , hn4- A Af Id        _ ,,   , A .nA ,                            ,                           , -m- <A^ ,                                            , 0       °H- / p F           F ,, ; or, R4 is independently °1 3 O°f ,                                         , F  \— /        , and fluorine; or, R4 is independently deuterium; the definitions of other groups are as defined in any technical solution herein.

[0367] In certain embodiments of the present disclosure, R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0368] more preferably, R4-1 is selected from the group consisting of cyclopropyl, isopropyl, and ethyl;

[0369] the definitions of other groups are as defined in any technical solution herein.

[0370] In certain embodiments of the present disclosure, R4-1 is selected from the group consisting of -CH2CF3, -NHCH3, -N(CH3)2, -C(OH)(CH3)2, tert-butyl, and -CH2-cyclopropyl.

[0371] In certain embodiments of the present disclosure, R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0372] preferably, R4-2 is methyl;

[0373] the definitions of other groups are as defined in any technical solution herein.

[0374] In certain embodiments of the present disclosure, R5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, -SO2-C1-3 alkyl, -SF5, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl; 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 the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-96 4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0376] preferably, R5 is independently selected from the group consisting of hydrogen, chlorine, and trifluoromethyl;

[0377] the definitions of other groups are as defined in any technical solution herein.

[0378] In certain embodiments of the present disclosure, R5 is independently selected from the group consisting of fluorine and methyl; or, R5 is independently cyclopropyl; or, R5 is F 4-^F independently selected from the group consisting of \  , -SF5, ethyl, and -SO2CH3; the definitions of other groups are as defined in any technical solution herein.

[0379] In certain embodiments of the present disclosure, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-CONH-C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 97 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, and 5- to 6-membered heteroarylene, wherein the imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-CONH-C1-3 alkylene-C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, -C1-3 alkylene-C(=N-OH)NH-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, or 5- to 6-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10aryl, and 5- to 6-membered heteroaryl; the definitions of other groups are as defined in any technical solution herein.

[0380] In certain embodiments of the present disclosure, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-CONH-C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, and 5- to 6-membered heteroarylene, wherein the imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-CONH-C1-3 alkylene-C1-3  alkylene-SO2NH-,  -C1-3  alkylene-SO2NH-, -C1-3 alkylene- NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, or 5-to 6-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5-to 6-membered heteroaryl;

[0381] the definitions of other groups are as defined in any technical solution herein.

[0382] In certain embodiments of the present disclosure, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-10 arylene, and 5- to 6-membered heteroarylene, wherein the imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -alkylene-3- to 8membered heterocycloalkylene-, C6-10 arylene, or 5- to 6-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;

[0383] the definitions of other groups are as defined in any technical solution herein.

[0384] In certain embodiments of the present disclosure, L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -C1-3 alkylene-CONH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-10 arylene, and 5- to 6-membered heteroarylene, wherein the imino, C1-3 alkylene, -C1-3 alkylene-CONH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, -alkylene-3- to 8-membered heterocycloalkylene-, C6-10 arylene, or 5- to 6-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5-to 6-membered heteroaryl;

[0385] more preferably, L1 is selected from the group consisting of -CH2-, -CH2CONH-*, - CH2SO2NH-*, wherein the side with * is connected to ring C;

[0386] the definitions of other groups are as defined in any technical solution herein.

[0387] In certain embodiments of the present disclosure, L1 is selected from the group consisting of -COCH2NH-*, -CONH-*,

[0388]

[0389] ,    1 * , and      * , wherein the side with * is connected to ring C; thedefinitions of other groupsareasdefined in any technical solution herein. In certain embodiments of the present disclosure, R6-1 and R6-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;

[0390] alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl;

[0391] the definitions of other groups are as defined in any technical solution herein.

[0392] In certain embodiments of the present disclosure, R6-1 is selected from the group consisting of hydrogen, cyano, and trifluoromethyl; R6-2 is hydrogen; the definitions of other groups are as defined in any technical solution herein.

[0393] In certain embodiments of the present disclosure, R6-1 and R6-2, together with the carbon atom to which they are attached, form (i.e., M is |— 0 (i.e., M is 0 __I ); the definitions of other groups are as defined in any technical solution herein.

[0394] In certain embodiments of the present disclosure, R7-1 and R7-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy; the definitions of other groups are as defined in any technical solution herein.

[0395] In certain embodiments of the present disclosure, R7-1 is selected from the group consisting of hydrogen and methyl; the definitions of other groups are as defined in any technical solution herein.

[0396] In certain embodiments of the present disclosure, R7-2 is methyl; the definitions of other groups are as defined in any technical solution herein.

[0397] In certain embodiments of the present disclosure, R7-1 and R7-2 are connected to form a C3-6 cycloalkyl; the definitions of other groups are as defined in any technical solution herein.

[0398] The present disclosure also provides the following compounds, stereoisomers thereof, or pharmaceutically acceptable salts thereof:

[0399] In certain embodiments of the present disclosure, ring A is 5- to 14-membered 102 heteroaryl; preferably 5- to 6-membered heteroaryl, for

[0400] ring B is selected from the group consisting of preferably

[0401] ring C is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl; preferably C6-10 aryl or 5- to 6-membered heteroaryl; for example, phenyl, or more particularly

[0402] ring E is 3- to 12-membered heterocycloalkylene; preferably 5- to 6-membered heterocycloalkylene-fused C3-6 cycloalkylene; for example,

[0403] HN 3 L1, R3, and the parent form a moiety                ; preferably

[0404] In certain embodiments of the present disclosure, M is -CO-;

[0405] ring A is 5- to 14-membered heteroaryl; preferably 5- to 6-membered heteroaryl, for example,

[0406] ring B is selected from the group consisting of , and preferably

[0407] ring C is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl; preferably C6-10 aryl or 5- to 6-membered heteroaryl; for example, phenyl, or more particularly

[0408] ring E is 3- to 12-membered heterocycloalkylene; preferably 5- to 6-membered heterocycloalkylene-fused C3-6 cycloalkylene; for example, HN j                       HN

[0409] L1, R3, and the parent form a moiety                 ; preferably          '

[0410] R1 is independently selected from the group consisting of hydroxyl and C1-6 alkyl;

[0411] R4 is deuterium;

[0412] R5 is independently selected from the group consisting of halogen, C1-6 alkyl, and C1- 6 haloalkyl;

[0413] x is selected from the group consisting of 0, 1, and 2; preferably 2;

[0414] y is 0;

[0415] z is selected from the group consisting of 0, 1, and 2; preferably 2;

[0416] u is selected from the group consisting of 0, 1, and 2; preferably 2.

[0417] In certain embodiments of the present disclosure, ring B is , and ring C is phenyl or

[0418] In certain embodiments of the present disclosure, the compound is any one of the following compounds:

[0419] preferably, the compound is any one of the following compounds:

[0420] The present disclosure also provides a crystal form of a compound shown below,

[0421] the parameters of the crystal form are shown below: C34H34D2F3N9O5S^ C2H6OS D x = 1.399 Mg m-3 Mr = 819.92 Cu Ka radiation, X = 1.54178 A Orthorhombic, P 212121 Cell parameters from 9935 reflections a = 11.3002 (3) A 0 = 3.5-63.8° b = 15.9609 (4) A li = 1.86 mm-1 c = 21.5818 (6) A T = 150 K V = 3892.52 (18) A3 Block, colourless Z = 4 0.15 x 0.06 x 0.05 mm F(000)= 1712

[0422]  .

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

[0424] the parameters of the crystal form are shown below: C35H35ClF3N9O5^H2O F(000)= 1608 Mr = 772.18 D x = 1.421 Mg m-3 Monoclinic, P21 Cu Ka radiation, X = 1.54178 A a = 14.4250 (8) A Cell parameters from 2512 reflections b = 19.2839 (10) A 0 = 4.1-60.8° c = 14.1565 (9) A p = 1.58 mm-1 p = 113.585 (4)° T = 170 K V = 3609.0 (4)  A3 Block, colourless Z = 4 0.09 x 0.06 x 0.04 mm

[0425]  .

[0426] The present disclosure also provides a pharmaceutical composition comprising the compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof of the present disclosure, and a pharmaceutically acceptable carrier.

[0427] In certain embodiments of the present disclosure, in the pharmaceutical composition, the content of the compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof is selected from 0.1 mg to 1000 mg.

[0428] In certain embodiments of the present disclosure, in the pharmaceutical composition, the pharmaceutically acceptable carrier comprises one or more selected from the group consisting of a filler, a disintegrant, a binder, a glidant, and a lubricant.

[0429] The present disclosure also provides a use of the aforementioned compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition in the manufacture of a medicament for treating a WRN-mediated disease.

[0430] In certain embodiments of the present disclosure, the disease is cancer; preferably, the cancer is selected from the group consisting of colorectal cancer, endometrial cancer, ovarian cancer, and gastric cancer; more preferably, the cancer is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancer.

[0431] The present disclosure also provides a method of treating a WRN-mediated disease in a human, wherein the method comprises administering to a human in need thereof an effective prophylactic or therapeutic amount of the aforementioned compound, the stereoisomer, or the pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition.

[0432] In certain embodiments of the present disclosure, the disease is cancer; preferably, the cancer is selected from the group consisting of colorectal cancer, endometrial cancer, ovarian cancer, and gastric cancer; more preferably, the cancer is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancer.

[0433] Technical effects

[0434] The compounds of the present disclosure have good WRN enzyme and cell inhibitory activities, and have selectivity for MSS and WRN-KO cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0435] FIG. 1 shows the crystal structure of a DMSO solvate of compound 295-P4.

[0436] FIG. 2 shows the crystal structure of a monohydrate of compound 303-P4. DESCRIPTION AND DEFINITION

[0437] Unless otherwise specified, the following terms and phrases used herein have the following meanings. A specific term or phrase should not be considered indefinite or unclear in the absence of a particular definition, but should be understood in the ordinary sense.

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

[0439] The term "pharmaceutically acceptable salt" refers to a derivative prepared by the compound of the present disclosure with a relatively nontoxic acid or base. These salts may be prepared during the synthesis, separation and purification of the compound, or the free form of the purified compound may be used alone to react with a suitable acid or base. When the compound contains relatively acidic functional groups (e.g., -COOH, -OH, or -SO3H), the compound reacts with appropriate inorganic or organic cations (bases) to form base addition salts, including salts formed with alkali metals or alkaline earth metals, ammonium salts formed 107 with amines or their derivatives, salts formed with amino acids, etc. When the compound contains relatively basic functional groups (e.g., -NH2,), the compound reacts with appropriate inorganic or organic anions (acids) to form acid addition salts, including salts formed with inorganic acids or organic acids (e.g., carboxylic acids).

[0440] The term "pharmaceutically acceptable carrier" refers to a medium generally acceptable in the art for delivering a biologically active agent to animals, particularly mammals, including, for example, an adjuvant, an excipient or a vehicle, such as a diluent, a preservative, a filler, a flow regulator, a disintegrant, a wetting agent, an emulsifier, a suspending agent, a sweetener, a flavor, a fragrance, an antibacterial agent, an antifungal agent, a lubricants agent and a dispersant, according to the mode of administration and the nature of dosage forms. The pharmaceutically acceptable carrier is formulated according to a number of factors that are within the purview of those skill in the art. The factors include, but are not limited to, the type and nature of the active agent formulated, the subjects to which the composition containing the agent is to be administered, the expected route of administration of the composition, and the target therapeutic indication. The pharmaceutically acceptable carriers include both aqueous and non-aqueous media and various solid and semisolid dosage forms. In addition to the active agent, such carriers include many different ingredients and additives, and such additional ingredients included in prescriptions for a variety of reasons (e.g., stabilizing the active agent and an adhesive, etc.) are well known to those of ordinary skill 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 compounds of the present disclosure include, but are not limited to, isotopes of hydrogen (e.g., deuterium (2H), tritium (3H)); isotopes of carbon (e.g., 11C, 13C, and 14C); isotopes of chlorine (e.g., 36Cl); isotopes of fluorine (e.g., 18F); isotopes of iodine (e.g., 123I and 125I); isotopes of nitrogen (e.g., 13N and 15N); isotopes of oxygen (e.g., 15O, 17O, and 18O); isotopes of phosphorus (e.g., 32P); and isotopes of sulfur (e.g., 35S). Isotopically labeled compounds of the present disclosure can generally be prepared by conventional techniques known to those skilled in the art, or can be prepared by methods analogous to those described herein using an appropriate isotopically labeled reagent in place of an unlabeled reagent.

[0442] The term "prodrug" refers to certain derivatives of the compounds of the present 108 disclosure that themselves have little or no pharmacological activity, which contain a cleavable group and decompose into the compounds of the present disclosure by solvolysis or under physiological conditions. Such prodrug types include, but are not limited to, amides, esters, anhydrides, salts, and the like. The term "ester" refers to a derivative formed when a compound of the present disclosure contains an acidic group (such as a carboxylic acid) and reacts with a suitable alcohol; or when a compound of the present disclosure contains a hydroxyl group and reacts with a suitable acid (including organic or inorganic acids). Methods for preparing prodrugs are 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. When the solvent is water, the term "hydrate" may be used. The solvent molecules may be stoichiometric or non-stoichiometric. 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 a nitrogen atom in a nitrogen-containing group. Common N-oxides include N-oxides of tertiary amines or N-oxides of nitrogen atoms in nitrogen-containing heterocycles. Methods for synthesizing N-oxides are well known to those skilled in the art, including oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic acid and m-chloroperoxybenzoic 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 in the form of 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, for example, 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, their pharmaceutically acceptable salts, isotopic derivatives, solvates, and N-oxides have the same or similar biological activities, 109 and all of them are included within the scope of the present disclosure.

[0449] The term "prophylactically or therapeutically effective amount" refers to a sufficient amount of the compound of the present disclosure, a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, to treat a disorder with 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 compounds of the present disclosure, stereoisomers thereof, or pharmaceutically acceptable salts and compositions thereof must be determined by the attending physician within the scope of sound medical judgment. For any specific patient, the specific therapeutically effective dose level depends on a variety of factors, including a disorder being treated and the severity of the disorder; activity of a specific compound used; a specific composition used; age, weight, general health status, sex and diet of the patient; administration time, administration route and excretion rate of the specific compound used; duration of treatment; drugs used in combination or simultaneously with the specific compounds used; and similar factors known in the medical field.

[0450] The absolute stereo configuration of a compound may be confirmed by conventional technical means in the art. For example, a single crystal X-ray diffraction method may also confirm the absolute configuration of the compound by the chiral structure of the raw material and the reaction mechanism of asymmetric synthesis. Alternatively, after resolution, the stereochemical configuration may be determined by comparison with a product of determined absolute configuration.     Compounds marked herein as “absolute configuration unknown / undetermined” are typically split from racemic compounds into single isomers by chiral preparative SFC, which are then characterized and tested.

[0451] The term "optionally" means that it may be substituted or may not be substituted. Unless otherwise specified, the type and number of substituents may be arbitrary, provided they are chemically feasible. For example, the term "optionally substituted with one or more R1" means that it may be substituted with one or more R1 or may not be substituted with R1.

[0452] When any variable (such as R1) occurs more than once in the composition or structure of a compound, the definition of the variable at each occurrence is independent. For example, x indicates that the pyrimidinyl group is substituted with x Ri groups, and each 110 R1 is independently selected.

[0453] When the bond of a substituent may be cross-connected to two atoms on a ring, the substituent may be bonded to any atom on the ring. For example, the structure moiety x indicates that the substituent Ri may be substituted at any position on the pyrimidinyl group.

[0454] When a listed substituent does not indicate through which atom it is attached to a compound included in the general formula but not specifically mentioned, such substituent may be bonded through any of its atoms. For example, pyrimidine as a substituent means that any carbon atom or nitrogen atom on the pyrimidine ring is attached to the substituted group; when — appears in the structure, it indicates that the atom is a bonding atom, for example, indicates that the C atom on the pyrimidine ring is the bonding atom.

[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 removal of one hydrogen atom. For example, "C1-6 alkyl" refers to including C1, C2, C3, C4, C5, and C6 alkyl, "C1-6 alkyl", and "C1-3 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 removal of one hydrogen atom, wherein the alkyl is as defined above.

[0457] Unless otherwise specified, the term "alkenyl" refers to a group derived from a straight-chain or branched alkene (containing at least one carbon-carbon double bond) by removal of one hydrogen atom, including "C2-6 alkenyl", "C2-5 alkenyl", "C2-4 alkenyl", and "C2-3 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 removal of one hydrogen atom, wherein the alkenyl is as defined above.

[0459] Unless otherwise specified, the term "alkynyl" refers to a group derived from a straight-chain or branched alkyne (containing at least one carbon-carbon triple bond) by removal of one hydrogen atom, including "C2-6 alkynyl", "C2-4 alkynyl", and "C2-3 alkynyl". 111 Specific examples include, but are not limited to: -C=CH, -C=CHCH3, CH=CHCH2-, CH=C-C=C-, etc.

[0460] Unless otherwise specified, the term "alkynylene" refers to a group derived from an alkynyl group by removal of one hydrogen atom, wherein the alkynyl is as defined above.

[0461] Unless otherwise specified, the term "alkoxy" refers to an alkyl group as defined herein attached to another group via an oxygen atom, i.e., "alkyl-O-". "C1-6 alkoxy" (structure: C1-6 alkyl-O-) and "C1-3 alkoxy” are included. 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 C1-3 alkoxy.

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

[0463] Unless otherwise specified, the term “halogen” refers to fluorine, chlorine, bromine or iodine atom.

[0464] Unless otherwise specified, the term “haloalkyl” refers to alkyl in which one or more hydrogen atoms are substituted with halogen atoms. C1-6 haloalkyl is preferred, and C1-3 haloalkyl is more preferred. Examples of haloalkyl include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, tribromomethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, etc. The alkyl is as defined above.

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

[0466] Unless otherwise specified, the term "hydroxyalkyl" refers to a group derived by substituting one or more hydrogen atoms in an alkyl group with a hydroxyl group. The "hydroxyalkyl" described in the present disclosure includes "C1-6 hydroxyalkyl" and "C1-3 hydroxyalkyl"; specific examples include, but are not limited to, -CH2OH, -CH2CH2OH, - OH OH H0T x CH(OH)CH3, -CH2CH2CH2OH,    \   ,   ^^,      1    ,     0H, etc.

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

[0468] Unless otherwise specified, the term "alkylthio" refers to -S-alkyl, wherein the alkyl is as defined above.

[0469] Unless otherwise specified, the term "alkylenethio" refers to a group derived from an alkylthio group by removal of one hydrogen atom, wherein the alkylthio is as defined above.

[0470] Unless otherwise specified, the term "haloalkoxy" refers to an alkoxy group in which one or more hydrogen atoms are substituted with halogen. Preferably, the "haloalkoxy" described in the present disclosure is preferably "C1-6 haloalkoxy" or "C1-3 haloalkoxy". Specific examples described in the present disclosure include: fluoromethoxy (including monofluoromethoxy, difluoromethoxy, trifluoromethoxy), -OCH2CF3, -OCHFCH3, etc. The alkoxy is as defined above.

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

[0472] A group derived from a ring by removal of a hydrogen atom is referred to as a "cyclic group", which includes monovalent rings, divalent rings (commonly referred to as cycloalkylene), trivalent rings, tetravalent rings, etc., with the specific valence depending on the number of substituents attached to the ring. In the present disclosure, the description of “cyclic group” does not specifically distinguish between different valences of the ring. Representative “cyclic group” includes 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 heteroatom groups), the heteroatoms being generally selected from N, O, and S, and the oxidized forms generally including NO, SO, S(O)2, and P(O). Nitrogen atoms may be substituted, namely NR (R is H or other substituents defined herein); the number of atoms on the ring is usually defined as the number of the ring members, for example, "3- to 6-membered heterocycloalkyl" refers to a ring formed by 3 to 6 atoms arranged around it, and each ring optionally contains 1 to 3 heteroatoms, namely N, O, CO, S, NO, SO, S(O)2, or NR, and each ring is optionally substituted with R, and 113 R is a group as defined herein.

[0474] Unless otherwise specified, the term "cycloalkyl" refers to a saturated cyclic alkyl group derived from cycloalkane by removal of one hydrogen atom, including monocyclic or polycyclic saturated hydrocarbon groups; the polycyclic saturated hydrocarbon groups refer to polycyclic groups formed by connecting two or more cyclic alkyl structures via spiro, bridged, fused, or other linking modes. The carbon atom(s) in the cycloalkyl may be further substituted with oxo, i.e., forming C(O). Unless otherwise specified, the term "certain- membered cycloalkyl" as described herein can be understood as a monocyclic cycloalkyl, and when it is polycyclic, it will be specifically indicated as a spiro, fused, or bridged ring group. The cycloalkyl includes "C3-12 cycloalkyl," "C3-8 cycloalkyl," "C3-6 cycloalkyl", and "C3-5 cycloalkyl". Preferably, specific examples of the cycloalkyl 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 removal of one hydrogen atom, wherein the cycloalkyl is as defined above.

[0476] Unless otherwise specified, the term "heterocycloalkyl" refers to a saturated cyclic group derived from a cycloalkyl group by replacing one or more ring carbon atoms with heteroatoms and / or heteroatom groups. The heteroatoms and / or heteroatom groups are generally selected from N, O, S, NO, SO, S(O)2, P(O), and NR, wherein the carbon atoms in the heterocycle are optionally oxidized, i.e., forming -C(O); preferably, the heteroatoms are independently selected from 1 to 3 N and / or O. The heterocycloalkyl includes "3- to 12- membered heterocycloalkyl", "3- to 8-membered heterocycloalkyl", "3- to 6-membered heterocycloalkyl", "3- to 5-membered heterocycloalkyl", "4- to 6-membered heterocycloalkyl", and "5- to 6-membered heterocycloalkyl". Examples of heterocycloalkyl include, but are not 0 >NH v o 3. T\ limited to: o O <f

[0477] Unless otherwise specified, the term "heterocycloalkylene" refers to a group derived from a heterocycloalkyl group by removal of one hydrogen atom, wherein the heterocycloalkyl is as defined above. Examples of heterocycloalkylene include, but are not limited to, or

[0478] Unless otherwise specified, "cycloalkenyl" refers to a "cycloalkyl" in which one or more ring-forming bonds are double bonds and the cycloalkenyl is non-aromatic. The carbon atoms in the cycloalkenyl may be further substituted with oxo, i.e., forming C(O). The cycloalkenyl may be fused to aryl, heteroaryl, or heterocycloalkenyl, wherein the ring attached to the parent structure is cycloalkenyl. The cycloalkenyl includes "3- to 12-membered cycloalkenyl", "3- to 8-membered cycloalkenyl", "3- to 6-membered cycloalkenyl", "3- to 5- membered cycloalkenyl", and "5- to 6-membered cycloalkenyl". The “cycloalkyl” is as defined above.

[0479] Unless otherwise specified, the term "heterocycloalkenyl" refers to a "heterocycloalkyl" in which one or more ring-forming bonds are double bonds and which is non-aromatic. The "heterocycloalkyl" is as described above.

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

[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. Fused-ring aryl refers to a group formed by two or more cyclic structures sharing two adjacent atoms with each other, wherein the ring directly attached to the parent structure is aromatic (the ring not directly attached to the parent structure is an aromatic ring or a non-aromatic ring). The aryl may be fused to heterocycloalkenyl or cycloalkenyl, wherein the ring connected to the parent structure is aryl, etc. Preferably C6-14 aryl, preferably C6-10 aryl; examples of aryl include, but are not limited to, phenyl, naphthyl,

[0482] The term "arylene" refers to a group derived from an aryl group by removal of one hydrogen atom, wherein the aryl is as defined above.

[0483] The "heteroaryl" in the present disclosure refers to an aromatic monocyclic or polycyclic group 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 to 3 N and / or O. Additionally, the N and S atoms may optionally be oxidized, and the N atoms may optionally be quaternized. The “heteroaryl” includes “monocyclic heteroaryl” and “fused heteroaryl”. The fused heteroaryl refers to a group formed by two or more cyclic structures sharing two adjacent atoms with each other, containing one or more heteroatoms, wherein the ring directly attached to the parent structure is aromatic (the ring not directly attached the parent structure is an aromatic ring or a non-aromatic ring). The heteroaryl in the present disclosure is preferably “nitrogen-containing heteroaryl” and preferably “5- to 6membered nitrogen-containing aryl”. The heteroatom in the “nitrogen-containing heteroaryl” comprises at least one nitrogen atom, for example, only one, two, or three nitrogen atoms; or one nitrogen atom and one or two other heteroatoms (e.g., S and / or O atoms); or two nitrogen atoms and one or two other heteroatoms. Specific examples of the heteroaryl include, but are not limited to, furanyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, pyrimidinyl,

[0484] The term "heteroarylene" refers to a group derived from a heteroaryl group by removal of one hydrogen atom, wherein the heteroaryl is as defined above.

[0485] In various sections of the present disclosure, linking substituents are described. When the structure clearly requires a linking group, the Markush variables listed for that group should be understood as linking groups. 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 connecting alkylene group or arylene group, respectively.

[0486] Combinations of substituents and / or variables in the present disclosure are permissible only when such combinations yield stable compounds or usable synthetic intermediates. A stable compound or stable structure refers to a compound that is sufficiently stable to undergo chemical reactions, be isolated in a useful purity, and be formulated into an efficacious therapeutic agent.

[0487] In the examples of the present disclosure, the nomenclature of the title compound is converted from the compound structure by means of Chemdraw. If there is any inconsistency between the compound name and the compound structure, it may be determined by synthesizing relevant information and reaction routes; if it cannot be confirmed by other methods, the given structural formula of the compound shall prevail.

[0488] The preparation methods of some compounds in the present disclosure refer to the preparation methods of the aforementioned similar compounds. Those skilled in the art 117 should know that when using or referring to the preparation methods cited therein, the feed ratio of reactants, reaction solvent, reaction temperature, etc. may be appropriately adjusted according to the different reactants.

[0489] The compounds of the present disclosure can be prepared by a variety of synthetic methods known to those skilled in the art, including the specific embodiments listed below, the embodiments formed by their combination with other chemical synthesis methods, and equivalent alternatives known to those skilled in the art, and preferred embodiments include, but are not limited to, the examples of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0490] The compound structure of the present disclosure was determined by nuclear magnetic resonance (NMR) mass spectrometry. NMR chemical shift (5) was given in units of parts per million (ppm). NMR was determined using a Bruker Ascend 400 NMR instrument with deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), deuterated chloroform (CDCl3), and deuterium oxide (D2O) as solvents and tetramethylsilane (TMS) as an internal standard.

[0491] Thin-layer chromatography (TLC) silica gel plates were HSGF254 silica gel plates from Yantai Jiangyou Silica Gel Development Co., Ltd. The specification of TLC was 0.20 mm ± 0.03 mm, and preparative plate was 20 x 20 cm. For column chromatography, 200300 mesh silica gel from Qingdao Hailang Silicone Desiccant Co., Ltd. was used as the carrier.

[0492] The starting materials in the examples of the present disclosure are known and commercially available, or can be synthesized by using or following methods known in the art.

[0493] Unless otherwise specified, all reactions in the present disclosure are carried out under continuous magnetic stirring and dry nitrogen or argon atmosphere. The solvent is a dry solvent, and the unit of reaction temperature is Celsius.

[0494] General Procedures for Preparation

[0495] The following examples were synthesized according to the general procedures for preparation. Example No. Structure Example No. 1 0 OH o N^N V HN^zx XjLxF cr If f 173-1 0 OH 0 N n -' N ,,     N N .......... P" \ / W7 J L QJyz vz m-S-K / L^O HN.^x 2 0 OH 0 N*N 0     N^NJx0'CF3 S^° XJ-zf P 173-2 O OH O n.nAyU <\ / °-\    A 1 l'Y° HN^^^ „x\; F 3 O OH 0 / ^-         / n^n of jT ¥ | ¥ N^n^Ya^ HNY¥ «Y1 F 174 0 OH ¥ o     o ¥?XXx ¥ /   N n' ¥    n^n ¥ 0 \ a I. \    « nn- / v° hnx¥;X F 4 0 OH o YN’^Sr^ / ^a,>Xn¥ n N °\ / ?—X k N ? o         T ¥\; F 174-1 0 OH Y °     ? yAAt' N,wA.N^ N^N /   \    /   \   / , N T Y °"\ / Y ¥ 1 , S^° HN¥\ ..¾ 5 O OH o X^^SAX __ N X. ¥, J N^N \XYYY ¥¥a N nYX / x^° HN'¥\ ¥¥ F 174-2 0 OH ¥ ,°     ? P^-W ¥ AA        N^N Y Y / Y ¥ 1 , ^Y° hn¥\ ¥f; 6 O OH O Y"N^Y^YY ,-' N Y    J N^Y-X / \ ^'nY nYY / X^° ¥1,- F 175 O OH o Y'n”,^yY^ vcYY N^N <]           y° HN,. x\ ■¥: 7 O OH ° pn ^yV ¥ / ,-' ¥N °, f¥ A 1 ., Y 176 0 OH ° YN'%rY' o    »■¥¥ n^n H / ¥¥ I .-0       N'A'A / ¥ XY Cl    Yf 8 Y ¥z             IL LL ?• / .: :: 177 0 OH a /    S ¥NXV C¥o aa / .n^'V^ n^n vA'nAnA_^ ^° HN,z\ XY 9 O OH o AA N n ¥ n    N / N W¥nL ¥ HN 0 CI^L F F 177-1 Y} ° ¥ °Y o¥ z—' ¥ z, z d °^° z ¥ 10 )—Z               LL IL ¥¥ ?¥ z. z 5 177-2 O z oY :: ¥X Y° 11 O OH 0 N nz' X    AN ° / / ^ A X n N £^° F F 178 0 OH o            o A   n.nXnX n^n °x a\<X X , N^NA^ £^° HN^^x. A; 12 0 OH O NWXN   N / N ° yx x x n fN k^.0 HN, z^x -Ai F 178-1 0 OH P        o              o £<>£ ^vJ^Ar^ n^n °" \ / —X. 1 £^° Xv 13 0 OH h O iiT% / ^"-N'k'^'X NX~~Z ° A 4 k X^o HN -x XLf c'^Af F 178-2 0 OH q       o X^7^\^£ X>£ / ^        n^n 0       K / -'  N^N'^XX £jA° Xf; 14 0 OH 0 ,--v N JL .N. X N .._ aXa 'F /  \  ,n'N^ V y ££ a £ / Ly HNXZ-X ■A F 179 O OH □           o >—k n,nA.n^> N^N V_ / v_ / xnAnX^ / V ..XX 15 O OH 0   |'-^N'''^^ / -\ N.„XNJ N^N °\ yx a x 7 n n s^° HN^ £ / xf O^ F 179-1 O OH □      f? AvXXx <A / —\ N-»X"X n~^n < .N"\ A X nn-£^° HNxX-Xtrf F 16 O OH O N.„A,nA n ,s n OyXXX x---- /      N L^o HN O X > N^ cf3 179-2 O OH □      fl A?XXx °A / —\ "-hXA an ( ,N~\ / Xzj I „ £^° A; F 17 0 OH ? x^W o x~\ n.nA,n^> n^n 4avX HN -;x A; F 180 0 OH F A / fl     n X? W fKjX aaAn YnX an °AjXAnA / V X,. 18 0 OH o O / —\ N „.-,N ,.- N N >naJ XX —<   '—' N n -X £f o HN. <x A= 180-1 0 OH ,= / -x o       o rySAr n-n N^n-£a V HN,_X F 19 O OH ° o     "..AM n^n bN n'1 L x^.0 HN / X XV f h 180-2 0 OH P o       o V^'XAX X A AA A»£A n^n °¥ / Ha ¥ , S^° c.Xx F 20 0 OH o YV^^X-X O    / ---\    N W     N        N N °¥a aa J / / V^Z X^-O HN^^ =¾ F 181 O OH o     '^Xf^ / --. KI XL      J N^^.N WxXX VA / 'x^0 HN. .¾ F 21 0 OH O    N^Y^X" N^N I / —X 1 X^o XVr cr    X f h 182 0 OH ° x^n ^SAx ,--« N JX     J N-^N aZAJXX ^ZZ\XZ-- s^° hnaa XXf cr    X 22 n-nh O (¾¾¾ n,¥N\'N-J °\ x^ V I / n^n-aa x^o HN.a\ XX-f ci^Af F 183 0 OH 0 X'^^XXX^ N'NX_n^J n^n °\ / XX x 1 / N'V-'X / "X 23 n-nh A >a O        N v \ n / ¥NXN^ N W X / x^0 W cr    A F 184 O OH ° r^N / --. N A ,N 1 N N °\ XA A X „ n n, , XjA0 HNaA\. XX^F o Y Xf 24 O OH O / —\   N N1 ,N -   N ,N ° W X „ n n' ' 0 F 185 HO N'°\ / XV ? xxo n>XNX ¥ Ha £ X^0 HN^zx ^OkxF cr V If f 25 0 OH • AV .aaX^ / V n^nV / X Cl vX X^ F F 186 HO XX?Z 0 W X\ N _ ^a / J n-Z^-nanX / 25-1 O OH nn'A   n^n °\ v—A X "    N N CHxJ ^f F F 187 0 OH ° x^N',\r\ / XosX ~ '         V XX cr v x 25-2 0 OH 0 / -^ N P ,N / N^N Oli IX <x Cl "vx \-F F F 188 0 OH O 0. l~\  N-,-X"J N N / —\ XN. )—<z A X , O Ao   —J   n N '-- 1^-° hnA\ A; 26 0 OH 0 ( N N    -^        N = N 0 Az J i n n <> “X fTf 189 0 OH ^o    ° rjXV 0          "-nA-nA n^n °vXXa A ' N 'Nzx / S^° 27 O OH 0 N ,N °' a I X F 189-1 O OH o           o O nX; / -\ n^A.nX n^n °" \     A 1 / HN'A'\ AX; F 27-1 0 OH 0 / —\ N „,N    N.N AA ex "X fXf 189-2 0 OH / —\ o      ? x^XX 0           n.nA^N^> N^N °X Aa 1 1° hn-aa XX F 27-2 0 OH 0 I^A / V / —\ N M„N    N .N 0 a XI N N X F 190 9 z z n           ^=° “         2=9 <Qs 28 0 OH ° o^VV ,—, N A. ,N. J N ,N / \ An y °x          1 . VX N^n^-A 0 191 O OH 0 X^N N nPN X N^N ° Xx j T <- nn^ y7 hn\^( r >-cf3 s-x 29 O OH O / --\   N n     N        N   N °\ A I N V 13 ci° ■      A J--NH p^XS F F 192 0 OH 0 £''n'^£^£^ n^n dX^nA(M L .0 y Cl HN J T £-cf3 ^s 30 0 OH ,.        N N                N .N °\ Zx j J hn£x £f F F 193 O OH ° o-^n-nAt^ N^N k / O Y ci HN^^l rycF3 S-# 31 0 OH 0 N N - , N      N.N ° Hx I nn- L ,N^ / \ xxv P 194 0 OH ° £'N Ox      n~mA.n^ n^n / —\ K\ )—'<   £ £>° 32 O OH 0 \ N-nA^N^J n^n ° ZX j £ N^N / / 3 cf3 195 O OH o ° / —\ n.„A,n^J n^n f-zA      XI F> / Vo      n-^n-^' £^° e,X£: 33 0 OH 0 ,--N Jk .N, J N -N / \ / ZN'N V o Mi £ V HN. _ S \ cf3 196 0 OH ? oW n.wA_n^> n^n °C^N^ IS S / O y Cl HNx_£ r Vcf3 0-3 34 O OH °xh3£^nA^" £^° 0.¾ 197 0 OH F F      0  £' 3' ££^^ N J£    J N ^N I / )--3 £^° XX; F 35 0 OH o £ N / —\              n^n °XHa i£ x-' NN^ Hn£ 2. F F F 198 0 OH 0 £''n^ --—-A N A- ^N. J N. -N c__1     / /      _.£ Ji F3x_3 n^n^ / v XI / F F 36 0 OH o n.nJ£-N^J n^n °\ / Hl 1 Cl £^0 Xr F F 199 0 OH 37     0 £'^ oAn^n-V"—J N^N 3 / XanJL- £x-° «X£ 37 O OH po ° Z’ZyZZ ' / -A N-NZNZ N^N °\ / Hx 1 x^>° e,X\: F 200 O OH O y^N^yZy 0^n-nAnA n^n A, / / —A 1 n^N'A- Zy° hn-^a XL cr  A 38 0 OH Z'naXX O     r—\ 1     I' । II    1 \—1    N .N ,--,   N A N, / / \ z / N Y °x / / ^ ^ I . n-^n-A / l^.o A F 201 0 OH o ? nW nYn^ n-^n n^n-A / y hnA'x -A; F 39 0 HN-N o / Zy ° / U JY X^o XL cr 202 O OH o yA^yU^y cT^n-AA n^n dX / Xl, l ^. yn n nA / L^o A 40 0 OH / ■aW o zz n l ,—, N A N J / \ An y °\ WY I A n^-nA / V hnY\ A; F 203 0 OH d d         o OWW'NJAN'Z n^n Zl nZnZ_ / Zy° A F 41 0 OH ? / XL ,—» N A ,N^ J N.-N / \ XirY vZZz 1, —z N^n - / fZo ^z Cl aa F F 204 O OH d D     o yA^^Zy- oYn-AA n^n dX / X=X L / AA n nA / X / ° XA ci     y< 42 HO i 'A °\ W a 1 , n^nA / V hny\ Ai 205 O OH o AA N A ^N. J N_ ^,N o< A A aZnn. Zy° 43 HO , A A / —wZZ 0. W J £ N'-'YA / x^.0 A 206 o OH o y^NZ-yZy" oYA’A1'1'^ n^n Zy° HN'AA A; 44 O OH o ynZyXy 0   / —\  n-n / ,n / n'^n Y / / A 1 *z° c.xz F 206-1 O OH o y^NZyZy" o-yanLA n^n n^n-V ly^° A- F 45 O OH 0 z N N ;N °\ a £ - HN r Vcf3 S-^7 206-2 O OH O N^N X- / ■ S^° F 46 0 OH / —\  n-n-\'N'-^  n-^-n °\ / H a 1 - y HN N r n cf3 207 O OH X7        ° N^N — / n n^ ' =.XY F 47 0 OH 0 n n'NJ N.N ° Xx a £ - L^.o hn n r n s^ cf3 208 z z £< Qg 48 X O^                LL U. z. z 6 209 O OH / ~~~A N -IL N. L o yyzN'N"Y X n^nL\^ .xy F 49 O HN-N ? q-VV n^A-N^J n^n 0 / W J £ V A; 209-1 O OH ° N^N N^nX / «xy 50 0 OH ? yXrV n-nAnJ n^n 0 .H XI / ^£ Cl^ 209-2 o OH o'Yn^A^nY n^n .....££^ n’Xn-X- '''yx-0 ..1¾. 51 0 OH O N^N 0 X X n-<-n--V / N"£ ^N c|-^_ 210 o OH \                O □yN-NXy-X N^N Xv' hXN,X- 52 O OH ° A"n"A N,nAxN^ n^n °x / W -j 1 V^ / N^N ^-N Cl"^^ 210-1 O OH tWc7"*' S^0 HN,,-rx 53 O OH 0 / --\               n^n °\ HIX, N^S N=i'^ CI^VJ 210-2 A A ° A ■" z . z .....f 54 O OH O ,--v N Jk ,N„. A N. ,N / \   / >N >< WU A N-N 211 O OH O ,__, N Jk      J N, _N / \ An'y AAa A / "A / 55-1 HO r-N    \   / -, A k / A ii ( i1 ij^n .-an-nA^ A^nAnA_ / HN, zx 212 0 OH O ___. N A ^N. J N,„N / \ AnM AA A '---'     N 'N ^M° AA,f o j af nA f 55-2 HO r~N    \   / . Iwa O NM V , N II ।      1 N-A oAY V M F 213 0 OH O N.nA,N^J N N °\ A A 1 , n n hn\A\ aM °y_ ' Af 55 HO j'XA ,--, N A ,N. J / / N V °\ -A 1 . VA N'^n'A / V A 214 0 OH o p^N’^Ak^ / / -,              n^n °\ / A a A , M 56 HO • / V / A^ °, / )—\ J II VA N^n-A / V HN\Ax A: 215 0 OH 0 A        n^n °\ / ^ A 1 . A NAnA / ^A° HN\^\ XM N 1 Ac Vo F F 57 HO N=\N A / o <AznA n II ।             N- / " ^xN-nAa^ o. Ma I A-0 HN..,,, ■A 216 O OH ° a'A'^ax^ / —\ n.nAn-^ n~^n °\ A X , HN, ,\ AM N-O F F 58 9 z z A / AAf° < ■ 1 '■ 217 0 OH O [-'^'N'^AA’^ o-^A,n-nAA n^n mm HN^-, ,A; 59-1 HO °       j ' n n      -' Y^0 HN , Xjv 01-^ F 217-1 O OH O X"'N'^Y^^ n^n xX£xjv ^x° HN^-, 59-2 HO oyC"^ V HN. ,7, .¾ 217-2 0 OH ° rN\V X'-a N A. „N, J N^^N 0   \ t,N'N y I / XX X X . ^° hnaYa V; 59 HO . -A-A ozr'Y " V HN ,r,,, XV CI¾F F 218 0 OH <x6X^ HNA'Z\ .,¾ F 60 O OH o p^N-^y^Y^ 0 / -\ "■.A'A n^n ^£Vz a £ „ -        N^'-u'V / |^x° •'V 219 0 OH o-X°X X^-0 hnaYa ,¾ F 61 0 OH o yv^x^ 1^,0 HN =¾ F 220 0 OH <xX°X s^° HNz_A<\ w cr    y 62 0 OH o y^n'^\^T' O      n.mA_n^J n^n VOaiX- __ /   \--Z    N ^N ^^=-° HN^-. «V; F 221 0 OH a XjXX o^xV^ n6 VjZ n^n-^ / ^'X° HNaYY .,¾ F 63 O OH o y^n^S^ (TV-\ N.nA^N^J n^n "'XHajC X---'     N N '' k^° HN, ,-a 222 O OH _ N / \ Z / N'TA        N xm °\     v I        v / N 64 O OH o y^^^v'^X" 1,¾. n.nA,nX n^n \ / ¾ A 1 , V^7  n'S^A,' L^,o HN,,-, "•V 223 0 OH '---' N N hnaYY A; 65 O OH 0 X'^'X N-V              N^N L X\    X 1 . / 0      n^X'X- s^° xax = F 224 0 OH HN^ XL cr'^K PF 66 ' i, ■n m             2=( Q° 225 0 OH €AxX°L A” HNX^X X; F 67 O OH 0 L~'N^L^ 0      N'N'X'H N^N Fn. X j if — NH ^7  N^''NZX / "t° =X; F 226 0 OH cAGLi* V HNxXx X; F 68 A XH XX / 1 O oH z—7 X z. z 6 o^’X o 227 HO 0 Lx o PnXAnJ / —\ n.nA^n^> >«n-° G a L x n^nX / HN. zx F H 69 0 HN-N A qLY / -^n^X^ ° / Ha 1 V -X 228 O OH A O'-^N-X’1''''1 N^N HA7 nAnA^- ^T”0 HN~XX xx^ C'^X F 70-1 ° HX o XxX. / X^° HN, 229 □ H z z X -r-   / -2   )=O 3 *aT >X rt Q? o 70-2 ° Hx / A~NZG\. ,,N <xgV^ ^y° C,X\; 230 O OH O oA,AnGnJ N-^N Ha7 nAnA^ V HN'X\ X 70 ° X 0 ( \ N"^ <xgM n-^'n'X-o ^y° X 230-1 O OH o-X^nA-J N^N 7—z' Hb ^y° HN'A\ X: 71 HO O \     / / "N^V / ZN 0 (  \ NY ocOO V HN'YY, XLf F 230-2 0 OH ° r'~'N'xr^^ / --- N X. „N^ J N .N 0    __ / / 'N y LZ n^mZ V HN'YY F 71-1 0 V O ,_, N a Y / \ / zn y -. °x / Hk 1 / VA- / s^° HN.^ Z 231 O OH qzOZ -XV z 71-2 HO 0 / Vl , N O (    \ <Zd L^o HN-^\ A; 232 0 OH 0 N^N ZY n^nZ HN WCF3 ciAs 72 HO 0 Vz AN '' ZN Q / X N-J' Q-tfo V F H 233 0 SH O / -<  N -N,  N,N °\ / Hz £ z / nn^ HN'-.ZZ A: F 72-1 0 V 0 Y UN °\ x 11 / — NZZh Vo HNW-\ XLf CI^F 234 ° X O / —z n-AZ n^n XXX V XV c'^Z<F F 72-2 °H y Z'N / *~k  N 0 (  \ NY °vxX^ X:>° hnY'. .¾ F F 235 0 OH a GNXV oy«-AnJ nH V^O hna\ •A; 73 0 OH 0 VN'W / oW HNv>^ 236 O OH / -a"AnJ Zn zu z x-'  N^N'^YA HNYY •z 73-1 O OH N^N vZ»A Z X>° .¾ F 237 O OH a oXS oYA v» \—' N^n-''YA hn-zy •Z 73-2 O OH oW V A: F 238 O OH O Y^^^X'^X N A.    J N. ^N o v£££f dY     Yi^A. X ^- cT^ N Y / O Y Cl hn^.a\ r>-CF3 o~Y 74 0 OH ? r?XfV x£ N^N N*<NX / d F 239 O OH O n-mA-nA n>n °CAya X / '---'     N N '-^ £^° HN-^^\ X y-CFa cY° 75 0 OH 0 r ' ,--> N A ,N^ J N .N / \ / zn'n y       z 0     ■ -A £ . ^zy X 240 O OH ° £'~'N^Sr^^^ n.nYNY n^n yHna I XxN HU £ / 1 cr"^ 'CFj 76 O OH O Y" N Y / -^ N.nA-NZ n^n °. a? j t X .N I N A 241 O OH n'■'Y'^ n N^N °\ Ya 1 S^0 Y-F 77 HO N-N \ / ? N^nXy £^° HNxYY X 242 0 OH / —\  N.„Yn J N^.N K Y A I nn- ^x° £ A SY'CFs 78 O OH ? । >££< nn- Y n ,; n yya X HN A X; F 243 0 OH o y^n^Y£^£ n~nA^nY n5=n \ Y A X / <' n A -" £^° HH, / ^ ££>^3 79 0 OH 0 £ ' n ^£^ >--X N A. ,N^ J N.aN / \ "'nX^ Y YYA X^- '—z   N 'N '-^ £^° .N __ mQ F " 244 O OH ° yx^Yi^X" N n J - n         n - n Y.Y- Y ciA cf3 80 O OH 0 XWx ,--X N A ,N, J N ,N XXXX.X VJ N^nYy V ■ cf3 245 0 OH / -ay-XYnY n-^n °yanL £^° HNx^\ Y y-cf3 z s 81 0 OH o 11 KJ          N-ON °\      >1 1 X X^-O HN,^ “XX 246 0 OH 0 OYPr / —\ ".XU O« \ XX X z O' N'A'O' X>° HN   z. X Vcf3 A1's 82 O OH . X’XX AOX Yzs-O HN^z-. =¾ 247 0 OH S^0 HKI. / ^ 1A CI^^XFa 83 O OH ° o-nV-J o~ XU X '---' N N Y “Y 248 H0-N oh n^A.n^ n^n °x X 1 / x° HNx^Xx I / 1 CI'X^ / ^CF3 84 O OH O / -\ n-nA,nA n^n ° XX X z N n Y^N HN— ciYX F F 249 O OH 044¾ YN'°h Hhl^^. 1A ci^^xf3 85 0 OH O. «XU On °vXXy X / x° .¾ F 250 0 OH o o     o AnX / Y003 oX^’-nX"^ On “Xa^nY zk / Yy° .¾ F 86 0 OH 0 N-n2AnA On °OxX XL ---' N N ^---- / HN^-. syX 251 O OH D D         0 Xo N JX ,N„ J N.z,N O \ / / N^r" o^xxY Y° HN,^\ Xk; F 87 0 OH 0 N.„ zNJ N.N °f X X z O' ONOz- I___.0 "X cf3 252 0 OH a ? xyW03 oXJ'nXX on dXXn^nX D                        । \X° HNoXX «XX; 88 0 OH »X"J n^n ° X 4 L O iAn.\z HN_N TX cf3 253 0 OH o Y^'^Yr Y"' n.nA«J on °\ OA X z On-Oz- Y^0 HN-x\ T I n^Yx^x'CF3 o-n 89 O OH 0 n-AX n^n IL- x—' N n ^A° HNX / , I N S4 cf3 254 O OH O <axYj N sN \—I n^n-^— HN I 1 O 01=3 90 0 OH AA "'NVk NA / ° \ / O' A 1 i N ¢1 Xlo 255 0 OH ? r^W AO N A.    J N ,N o y^'N'y L_I n^nA / v II cr n cf3 90-1 0 OH O / —\ n.hA«J n^n o"-< OX [ 4     Ny A F 256 O OH 0 M N^LV-N^J n^n °\ 1 , n-^N'>xa L1 f£t CF3 Vo 90-2 O OH 0 L""N"X^ / ^ x\NJ n^n 0-( XY 1 £ i    ¢1 HN,_XO XA F 257 O OH o Ao N JL    J N. ,N o y^'N^Y nInIa HN'O-X 1.1 Vo 91 $ A = M-aL° - ■ \ T -n            O=< O IX 258 0 OH oxv^^V^ N^N ko 'nXnV / HNVX T 1 ly^ Vs 92 0 OH o F,C     »XnJ N^N X oA 1 HN. ,^._ X\; F 259 z z i r\-r° Ui ZY> ?-- V ° Q:> oz            Vo w            Z= / i£g 93 O OH o I"~N^ O ,-v "-AA n^n . xVa-xI^ HN. .jO V; 260 O OH o 00^1^ N^N d-Vo-nA A / Io° HN^^. 1 1 N0N CF3 94 1 o^,z^ z^z 1°¾ x    z£° 1(° 261 0 OH oOn-nAA n^n “-VAX A / 1^° HN^^. X X N b-N 94 in a single configuration 1 O^,z^ 9 z z ....' 262 O OH ? x^'XXx n^n XXXX <,o HN-^xx X 1 N / f^CF3 S'N 94 in a single configuration O OH -1 / / —,                n^n H H X L yy HNxz;-x X\; F 263 0 OH O^'N^ / X N^N XX 'nXnX^ HN. WCF3 95 O OH ° 0 .--v N A     J N.^N ii /  \ J N W O=S^( / )—e | HN, 264 0 OH 0    ^''"''N''^'Y'X'|X mXX - V Y Vcf3 J"s 95-1 O OH o .--, M A ,N, J N, ,, N " / \ / / N T X^0 HN.^ xv F 265 o-X0^' F 95-2 0 OH o 0 ,--, kj A ,N, J N, ,N "  / \ z- N r 1 Vj N^-N-V^ HNX\ A; 266 O OH ? vx- i^T n; y D-X / \|X^ A. ✓- X—1 N Y>° c1xy F 96 O OH O N J-L ,N, J N ,N X-Y O —'       Y XV F 267 0 OH / —\ N Y ,N. J N, Y. Y O V / nY -X-dMx ?X / XV F 97 O OH O p-^N'XfXyX N-XX N"^N VV nXnA^ o— /       y 268 0 OH 0 □■'-V / VnXxX n^X dX^x n®xnX^- J^° HN,_^ X,; 98 0 OH 0 7\___^X^X n^n N n -'-- HNvX. XX; F 269 O OH ? x^YSx o^VXn'X'X n^nX Xx nxnX / ^Y° HNxZk,z xv 99 O OH 0 N „,N   NN x^0 V cr X< 270 O OH yxJX XrN \A iAnAa X^o XI ■= cr    A; 100 O OH N.p.KzU n^n A'XX d N v HN / \ A; F 271 O OH ? oXX^, □ X. / dV X / A>° F 101 O OH ° an"^StS / 0 N-MANJ n^n hXL ^N N^NV ( )    A0 o—     y A F 272 O OH ° x^N-,drAx\ / —N X J N^X^X o A__ / / n V            s dX, / Jx X / Y-7 N X^0 .A; F 102 0 OH ? x^W N.A / U N^N hnA i I 6"' “X o—'       y HN,,^ JJX.F / / F F 273 O OH 1 5 XNdV" oY / nV n-^n dA 7 mX A / XV n^-n-A / A>° HNX / -- 103 9 z z x< * VA° .- . n -n             z=< <Q° 274 O OH o ^v^a^AtA O^Y / zN'nVNX dA^xv °“V 104 X OH 0   |-^N''X'Y^ oA-VdA n-n x—X n^n-Aa S^° HN -x c,X\F F F 275 O OH 0 N A   J N^^N o va □X / ^mA A / d^0 HN,,^ I 1 AAV^ 105 OH ° d^^AdA^" nA"^ N^N o J—( Ji II x—X NyA / ^d° HN _-\ A; F 276 0 o hnV o QXV N X ,N. J N. ,N o vJvAr ddVnaX A>° HN’X'\ x\;- 106 CN OH 0 — n.mAU M \'nAnAx / - V HN^^. F 277 O OH O YN^Sf^P / —\ N Y   J N. <N o AA" A AJMX x° Y Vcf3 C|As 106-1 CN OH O / —\  N M,N    N^N ° AA XX / - nn / L^O HNx „xa F 278 O OH D D         O / aXX "" HN\^\ YVCF3 cAs 106-2 CN OH 0 Y^N^Y^X^ n.„AnA n^n ° AA J X z v^z N N z' X^O «XA; 279 O OH D D         O OaXX -" V HM , A VCF3 ci / s 107 cf3 oh ° pXV <qaAm N^n^^ ^A° «XA; 280 O OH O    1^--^ N'''^^ oAA'N^Y N^N <>° HN^N A ACF= c / s 107-1 cf3 oh 0 P N^1V n^A.n^J n^n O / W J 1 / VA N'^NA\A X^,o A; 281 O OH o p'^N'^Y^X'" o AAA dY^na y Y>° HN 1VCI f3c s 107-2 cf3 oh O        ■'Xj'X'-'' n.nAnJ n^n ° Xa XX / N N V HN / AF If f 282 O OH ° r^'N^Sr^r' / —-. N J-l      J N^^.N o A'An iT dY^nA A / k / O y Cl HN^ J Y f3c s 108 O OH 8^yP V hn^A\ f h 283 O OH O N;N dx^nA y Ya° HN ^\ T Vcf3 109 0 OH ° o                  n^n HN       N^n'^x / 1^.0 HN^>. A F 284 O OH 0 AnVy o^n-nY^ N^N "V^n^y A>° him. J YXCF3 sX 109-1 O OH ? aV V^YVkY N-N 1^0 HN.^X 285 O OH o o'-^.n-hY"^ N^N □X. ) Su=X X / - X^° HN^ / . ,F TVAf cr s 109-2 O OH O Y~’N^Y o      N^A / Nj n^.n J. 1 . HN    —J   n N '-' 'Y>o HN.z\ F 286 0 OH ? r>W ■eV ■"'" D V HN. / . IVSF’ cXs 110 O OH o AA n'nXnX n-^n „ pY vy । i| [>— /            N-^' N- . H N., xr -. 0.¾ 287 O OH o v'n'^yHy^' o^n-nY"''^ N^N dXzYjv Xa° HN Y Vcf3 '-X'3 110-1 O OH o YN^S' / —\ N.NA_N^J n^n o-YY t L / 0 HN. / .¾ F 288 0 OH ? vW " V VCFj 110-2 O OH O / —\ N.NA.N^J n^n V |>-- —    N N '- L^-0 HN.,^ .,¾ 289 O OH 0 Y^N"^Sf Zz^\ N X ^N. J N. / N 0 Y / / NX T D-k / W X / Aa° HN^ / / ^ jf ?| 0 s' o' 111 0 OH ? n»Y"J n^n / Mj 1 , NC       N-^N'^ / ^° HN, / ,, XV Y 290 O OH ° Y"N^kf v^ o-^A / N-nY"^ N^N DXV\YX / \<>o HN, - F tkf y^s 112 O OH XX    □  r^N'^Y^Y' LN n,mA / NJ n-X Mil n^'Y-' y° HN, / / . •V; 291 O OH O ^'N^Y^A o-^,n,nYnX n^n “XVn^V A^° HN^ 1 f 113 0 OH o / '’Ay h-nt^a-ny"^ N^N x Y / Y x 1 , x^o HN. / ,, XV cr Y 292 O OH D D O ^N^Sf^A oY-nX"^ n^n “VVY-X A>° hnA, r Ycf3 sJ 113-1 0 OH ° r n at / V N ,--K N JI N J N.,N N'^   / \ / ZN'N Y A A'\ / A A 1 , S^0 HN, / , F H 293 ,    0 OH 0 n^n hn^X r >~cf3 sX 113-2 O OH 0 N -- N JL N, J N^N N'^ / \ YN Y / X AA^V'n-'L / L / O HN^ / / V F 294 ,    O OH 0 / ""A N JL    J o A / An'A- - /  — D Ja nA Y Xa° HN , Y YCF3 cAs 114 0 OH 0 N .--- N JL N, J N.,,N N'\ / \ Yn Y JL M Y £ / Ys VJ n^nYa V HN, / / V F 295 0 OH ? r ^ArV' 0 X X'nY^-NY N / N dX 2 X H D Y HN^ / s3~CF3 115 O OH O n-„A,nA n^n O A V A 1 , ''T>0 hn, / ,, F 295 in a single configuration / , O OH 0 oA^Y1 N / N DjYYi..... °Y hn / SYCFj 115-1 O OH o pN YJ Y" . N_NA / —n^n L .N,,,\ / z a 1, X>° HN, / , •V F 295 in a single configuration / ,,    0 OH ? r o y Yn'xUyNx^ n-y ddYYyl^ 0^' HN^ / sXCF3 115-2 0 OH o ^n r~\ n-n-\,nA n / nA z)—(z । | A Az n / , / x>0 HN, / ,, CIY^ 295 in a single configuration /   0 OH _  ? r?W o Y / ^''^YaY n / N dY / \ Y !l Nojp..... HN, / sly cp3 116 0 OH O "n-" = / VA N^N A2 \AnA^ L^o HN, / / XY Y 295 in a single configuration / ,   0 OH j Y^YY o X             nx / N dX 2 J Y !l d Ly HNs__ / sZvCF3 117 O OH o y^nX-^-X N / / AAnVJ N^N Wa V /       x'   N   N ^A-A 'X^o v 296 / -, ° 0H 0 N^N VV JnyYCF3 Ys c / 118 O OH N ,--. N .J "        N N n£x<J-<nx IL k^o HN,-X IX cr   X f r 296 in a single configuration o OH 0 o'-'xxnXX'^ n^n •x^x..... O=x HN^^XCF3 / s ciz 119 O OH . n,XX n^n ° / H'- a £ . L-0 Y Cl r n cf3 296 in a single configuration -,    0 OH 0 [^N ]|Y^ oX^-N-Jf^ N^N DDXxxxN^y °x' hn^VCF3 / s CIZ 120 O OH O ,--« N Jk -N, J N_—N °\ <H A A / n^n-X / - S^0 HN^J, r n s~k cf3 296 in a single configuration -, o OH ° t^N^SrS^ oX / nXX n->n HN^VCF3 / s CIZ 121 0 OH 0 PnAyV ,---k ,---k N JI N J N — N O / \ / XN X '-' \ hNx          I k^>0 HN.-7- JX F 296 in a single configuration -, o OH 0 oXxY^ N^N •xxx HN^YCF3 / s Cl 122 O OH O N'Ar~\zN-NArNX N^N A xk / / ^ X. 1 - / ^0 X n ^ ''.-kx XX F 297 O OH ° N,X«J N^N V Xx 1 , N^X HNx-X r Vdx 122-1 0 OH 0 ,—. N JI N J N, —N NX / ^^ / / n t x >"k / Hk 1 / ^0 VX n^-n / Xx XV; 298 0 OH 0 N-X"-J N--N V / X a £ , N-X'^ V HNX\ k 122-2 0 OH ° n'\ / -^n--nX'X n-n A)XXnX k^° XX.F c,>-XF 299 0 OH ° oxU / m'nj£n£'. n^n d£Xn^X kx° HN--k r ycF3 SX 123 0 HN— 0 n-n-Xnx n--n °xXx X k^-° X-V; 300 0 OH oXX'^'V^"' N^N kx° HN -. WCF3 ci As 124 O OH , N    ,---.    N ,,      N        "  / X n H11 y-o 'J n n X^o HN,XX XX^ F H 301 O OH 0 / —x    N J£      J . N. ,-,N o ¾, / N-N¾   -- -• D¾¾N¾-¾ D              7 X^° HN, / ^ 1 J. CI-^^^OPj 124-1 O OH ° x~'N'Yf^ ,N     .---.     N ..    . N         N N A~o        n N £^° HNxz;-x =¾ F 302 o          Vo w            z— / Q° 124-2 O OH 0 ,N / —, n.nA-n^ N^N AiVJV' n x^o HNZ,<-X =¾ F 303 ,,    O OH □ °x / XnJ n^n OsX / HN XV 0(--¾^¾ cf3 125 0 OH 0 0    / .¾^ N^N O-SX / / —1   || HN_-, F 303 in a single configuration ,    O OH ° \^n'Y|Y;x / yyiV ■-■ °x HN XV cf3 125-1 0 OH o X'N^vfY 0 ,--. N A ,N, J N, , N „ "  / \ X'N V °=S"\ / ¾ J II , A .¾ 303 in a single configuration ,    O OH .oXX’1-3” °Y HN XV CI-^W, CF3 125-2 O OH 0 r nJVV 0 ,--, M A ,N, J N , N ,-¾ / \ / / N^Y °-H £— HN^-, .¾ 303 in a single configuration ,    o OH " oX'“ HN XV cl'^v=X cf3 126 Y >=z u. u. Y>Y z, z Y o=^Aj O -- 303 in a single configuration ,, o OH “.X HN XV a-'W, cf3 126-1 O OH ° r-SV O ,--, N ,X,N„ J N.N „ H /  \    / , 'N >r °=S"\ .¾ / 1¾ 6 ' X HN'^\, 304 O OH .x^ / XVV' a- ■ o..... °Y HN XV 0(-¾^¾ cf3 126-2 0 OH 0 AN^V o ,--. M A ,N. J N.^N « JI     \ / / n Y °=s~< / Y A 1 6 v HNaY Y F 305 O OH D'J / Y L £^n 6..... °£ HN JY CI-YY cf3 127 0 OH 0 0                 N^N O=SJ / / —(z 1 II 1 \^7 HN.^. A; F 306 O OH ° A 'N^£r£ □ ‘’'YY'A"'N;N djY£,an£' oA / HN __ / S A^cf3 127-1 O OH o Y'n'^yy O .--, M A ,N J N.-N ~ JJ / \ zN~n Y °=S" < ££y £ 1 VJ' £^° F 306 in a single configuration O OH o A'n’^A nn ..... °£ HN / s^ / £cf3 127-2 O OH o y~y£y£ 0  ,--, N A .N. J N_ .N o=sY YY j II ~£° HN. £A F 306 in a single configuration 0 OH o """ °A nH s / ' cf3 128 O OH o a^n*^^£^A^ <ty£An^ n^n £^° HN., r Vcf3 sA Cl 306 in a single configuration 0 OH o a^n^a^A oY^'n\n£''- n-*n D£ 2 £ !L ■A..... ■M S / CF:1 129 0 OH o A^AA' N w         N;N °CAX A N---' N N £ / 0 Y Cl hn / r £cf3 s£ 306 in a single configuration O OH 0 / ~~a N A ^N. J. N .N 0        J I ' -  o£ HN / S-A^CF3 130 0 OH ° an^£T^A «3aYY """ N^n Ay £^° HN^^ AVCF3 cr s 307 O OH 0 A'n'"A o / XJ,.n'1Yn'J n^n D-J, / -J H N l£ °A HN / S-A^CF3 131 0 OH ? r,NW AA n'YNa nan ° Y A £ , A n / n / / £° HN 1YCF3 s 307 in a single configuration O OH O A'n"^A£^ oY^'N-V"^ N-^N D'J / \ Y 1 ..... °£' HN / S A^CF3 132 O OH 0 n.„A,n^J n^n °\ A" A A y HN '. h F 307 in a single configuration O OH o Y'n^y^Y o^N'nANA n^n dJ / X A L °Y HN __ / s^YCf3 133 0 OH 0 0^NYN^ N sN n^a^ y HNX. TY N-7 / 307 in a single configuration O OH o Y'^y^y" °anAnJ n^n dA ) / A X ■Ay..... HN __ / sY^cf3 134 0 OH 0  ^'''N'^YY'" / -^  N-N-X'"^ N~A o A j i z ^7  N'S'A-' HN^q A fYf 307 in a single configuration O OH o YN Vy <TV-nA"X n^n dA / A X N A °Y^ HN __ / sYk'CF3 135 o Z. Z^ X z z . Ya . / • / . <Y 308 O OH o d o y^AAy / A N A J N. ,N AA' °A HN A ci^AA cf3 136 0 OH 0 Yn'YYt" / ^AnYnY N^N ° Ya 1 . Y ANAz A    Y° A' F 309 0 OH D D    O YnAyYy AAA - °Y HN / S Y^CF3 137 O OH o yn "Yt^y AY'Y^ n^n °\ Y a 1 . Y n-^n-Aa a  y A, 310 0 OH D D      O y N TlY AAA °Y HN / S Y^CF3 138 0 OH ° y^YAt n-nY^nY n^n A7   hA-A^ y XAf C'^Af 311 ,,    O OH D d     o y-N'YYY oA^ / 'nA^ N^N d A ) Su A. Y / Y° HN^^ / r Ycf3 s A 139 0 OH 0 ^N YYx / —\    n.nYY n^n °x y^^A i. n^nA / y HN. .-.. AA c,^F 312 O OH d p o ynJS / y oA^-nA^ - N N ddAAn^nA Y>° hn.Y a Ycf3 sA 140 O OH 0 O. / -x  N u'N1  N N H X I . <^o Aa HN,_,<\ XjLf cr    yC 313 0 OH D D         O 73X3'“-" °Y' HN __ / s^^cf3 141 O OH O / —X n.mA.nX n^n r\_ K<A XX., y HN -x =3; F 314 ,,    O OH D D     0 Y^N^XpAY Xx y" - °Y HN XX cf3 142 O OH o        9 A'V'Sr^A Jj ,--N X ,N. J N. ,N oX XwxA L ,N3 / )—A 1 s^° HN,.\ F 315 ,,    0 OH D D         0 oYaA^ n^n dA / mA J-A / AjO HN^,^ JI ci''"'^-''cf3 142-1 O OH o        9 A^'SfS^' JJ -- N A N J N, ,N 3,.=° HN,., ’3 316 0 0H D D o Y^N^\fS / oYn'»XnX n >n DA / ''mA A. / Ax>0 hn, / ^ JI cr''^ 142-2 0 OH o            ° o4               n^n yn<Hx I, \- /  N'N-.' L^O HN,,^ =,A; F 317 O OH D d      o Y'N'^Af^A °Y HN XX d-^XY. cf3 143 0 OH N^N o^    AnA / x° HN^,,c. =,¾ F 318 .,    0 OH 0 oXx / AX N^N dY^xA Aa hn^1 YycF3 ^s 143-1 0 OH 0 A"N'AX O      "..'“v’J N„N A XI 1 , o__;—'  » 'k-^-^ '         s^° HN^^ 319 .,    O OH o r^N->liA3” c / XAnY^ N^N dX..3X3nJX' D                         । Aa HN^ J ,F Xxxf 143-2 0 OH 0 A'n"A °, / ^X N-nA_N^J n^n K 3"A X , HN^-. Af 320 .,    0 OH D D      O |^'N^11A'1 A~a m JA,.hX J 3..N dXXnXA D                          । Aa HN\A, 1¼0^ us 144 O OH 0 A'X^XA"' “n^o ,—. n.nA,n^J n^n X<° F 321 .,    0 OH D D         0 oA"'N\nJ N^N dA^nAa A>0 HN^ J ,F YMF 144-1 0 OH M      ° o^vV 0^.0 X n.nAnJ n^n n^X Ya JL . X*0 HN,^ F 322 .,    0 OH 0 S 0^".nYnJ N^N °AA HN __ / YA3 144-2 O OH 0^.0 ?—X n^nA.nA N^N nX\ Ya JL / y^° F 322 in a single configuration .,    0 OH ..... °A HN / X / ^CF3 A 3 145 O OH o An'XXA n,„A,n^J n^n ■hYHA x^o hn,., 0,¾ F 322 in a single configuration .,    0 OH °A HN A XVCF3 145-1 0 OH 0 AN'XfX / O — f—. n~mAn___J N^N °a x xa a a X^0 HN. zx F 322 in a single configuration ,,    O OH o-VJsV^ N^N dY }    -<1 !1 N^0..... HN A A- 145-2 0 OH 0 A’N'^XyX^ o-x     n~mA.nA n^n °a X / / a X ao HN,^ F 322 in a single configuration .,    O OH ° xX'XXa V—A N A .N^ J N. .N □YA A N lA °A HN A A- 146 O OH □       ° a^^SXa Ao / —\ n.nAM n^n ~nJCA A X^° Af 323 .,    0 OH ►n-fsA -¾..... 0=- HN x__ / SA—f~F 146-1 O OH °»     » r^W Vo ,     N ,    N      N N ' / / ^-1 1 \ /          N-^ ' N-^ - -^ X^o HN,.. XL' F 324 ,,    O OH ° an aXa °Y hm / sA-cf3 146-2 O OH 0              9 N.MAyN.J N^.N AAANX / X,>° HN ^ e,X\; F 325 ,    0 OH A n a °A HN / S,JAf3 147 0 OH ? nW / —\^\ AAj n^n °\ X / / x a 1 , nAA / V hn-ax A: F 326 O OH <---N A ,N, J N. ,,N d4Aa N NX~ °A HN __ / srACF3 148 0 OH o XnaA / n—t                            II । | il l ? A   u A ,N, J N ,N n^nAa V HN\AA ■A 327 O OH 0 i^^nX^Xa^ <HxA' °A HN / sXacf3 149 O OH oa        ii l 1      N A ,N, J N ,N Maa, n^n-A / Xa HN. ,<x A F 328 0 OH 4~HxA' A N Xy °A' HN __ / sXacf3 150 0 OH ° pnAtV 0-\  N„-,.N ,- N .N A I , 4   A HN ,--x A F 329 O OH ° r'~'N'^ aaxXA n^n N nA °x HN    / saX~cf3 151 0 OH 0 n^n °A X^ A 1 / N—7 N N '“' 4   A HAX'x A F 330 ,,    O OH O o-^n-nA^ n^n d -4     / \ A R A7 N x °x HN A C|'\AX cf3 152 O OH °  A O J—, N^WA,N^J N'-^N ___ /    \____¢-   ™ ll N \N A N A.^- AX ZLf c1aa^f 331 O OH 0 " 'ty °x HN A ci'xA. cf3 152 in a single configuration O OH o an^A^A O / -\ nAnJ N.A >{><n / XX HN 332 O OH ° X"'N^xrx o-^n-nA"^'- N N A 2 \ A 11 A7 n^A °x HN A^ d-AA. CF3 152 in a single configuration O OH XX N^N ,-N X      LyO HN, .,, ..¾ 333 O OH O N X J dIVI °Y HN JY ci"W. cf3 153 0 OH ? r«Vv 0 / —\ N.nXX n^n XI N     N^N^ / Fv    v F              HN^^, .¾ 334 O OH O   |-^''N'^Y''XpJ z~-\ N X    J- N. ,N oiVXl v7 - "Y op HN X ci XX, cf3 153-1 O OH ; r^W VXX n^n N VJ7 N -< N-V^- fP    V F              HN,.,, X F 335 O OH o y^NXpYp / —N X    J N, ,N □ wx o7^7 nAX Oy' HN X ci xx, cf3 153-2 O OH 0      N.NA,N^J  n^n . H—? N N rv    Y F                     HN, .,, 336 ., o OH 0 □■XInX n^n “YXXV °X / HN I cf3 154 0 OH 0 0   / -y N^NA.NX N^N y 'X'    N X  Y F              HN'X<X XV cr X 337 ., o OH 0 oxyX^ n n XX "-i> cf3 154-1 0 OH 0 XX 0. / —\ n.^JVn-^J n^n >XIT r- N       n'^h'V. X ir F 338 .,    0 OH 0 Y^xi n^n XX hm h I CF3 154-2 O OH 0 |-'"^nX O / —\ n,nA,n^J N^N Fp    y F F                  HN'_>"', F 339 .,    0 OH .ON-nX n-^n XX HN Xn cf3 155 0 OH o v^'W' o / —\ n.XxV n^n \ xTy^XX Vn X—N-^N-X / / ^       ^Y0 .Xl< 340 .,    0 OH 0 1 NXi o'YxX^'1 N^N XX xXcf3 X 155-1 O OH 0 0.     N.AzM n^n \         ajC,- Vn     n^nXa r~ F 341 ., o OH 0 HN XXcFs 155-2 O OH o x~’N'Xfk v.KBnaX ' a ..¼ 342 ., o OH ° I N^N Xa^nX Cl HN^J X N SX cf3 156 O OH ° xyk / n^n \ / 0-\ / / ^ A £ , 0 X HN. X F 343 .,    o OH XXcf’ 156-1 O OH o X"N'"y »-,£,"£ n^,n \ °" ( A? u £ , 0         iyo ..¼ 344 .,    o OH 0 r^N o-AA1 / -1 N^n HN XXcFj 156-2 0 OH o .-, N-A^-J n_n \ °~\ Az A X . n^ x— /   n'^'N-x<-—x °         k^o HN ,.x X 345 ., o OH o XyNX^y-- / —x N JX.X X N ,N O vJX X-Xxx 0= / ' hnvn 1 XCF3 CI-^S 157 O OH o x^n'X^ 0 / —\ ".AA n^n ^-N       N'^n'V. / ^° HN,.-.. ..¼. 346 .,    O OH o XXV N X.N, > N. N dXXanx oy2 HN^^ XXcF> Cl 158 0 OH o X n ° / —\ «■«£ / "£ n-.n A. Ha £ , .N '-J x^o HN. .-,, .¾ 347 ., o OH ° i^N'>\rkx oa^xA^ n^n •XX HN X^cf= 159 0 OH o X~~'N'ky^^ 0 r~\ ".AM n^n ^X HA 1 , N      N^n-^V X     x° F                HN,_,-X X£; 348 ., o OH 0 Y^N oA£nYJ N^N xy HNX^\ JXX3 160 O OH ° ,N       N.mA,N^J N^N X H V XI . N^'N'V / v HN., / .. XV F K 349 _-- ° 0H 0 o^axV"^ n^n ddW V V o^X ' HN XX-cf> / "S 160-1 O OH 0 ^nX^X^ ,N       N.mA,N^J N^N X> / Hi L N^N--V / HN. / ^ =XX; F 350 0 OH ° y^n'^'yXv N^N ddWn=xnX_ O;=X HN^ / 1 XVCFi 160-2 O OH ° x^n"^xt^X^ ,N ,-. N.MA,N^J N / N X M V X X. v HN^ 0¾ F 351 O OH 0 X^^'XX^ o'^n-n'XV N^N dXJW D                         । X^° HN.^\ X VCFs SX 161 O OH ° X'n^XXV' ---,   N A ,N J N.N XVXXL y^o HN . / ^ V F 352 O OH । 0 X^^X^X^''' N X ^N. J N^ -N o y^x* |f hrXN-X / XXf F 161-1 0 OH ° k'N^V _   ,___ M A N J N. / N NV    \ / / "N V x / "X / HX 1 k^o HN. , / ., ..V; F 353 0 OH ? aW / —>   N X ,N,. J     ,N 0 XvXNyr rrXN-k / S^0 V; F 161-2 O OH 0 ,--„ N JL ,N, J N.N XWXI / k / ° HN^. V: F 354 / < 0 0H 0 / ""TV N X ^N. J N .N o yX'iV :V HN JF^? ei-W. CF3 162 O OH o x^N’^V^X / N-N V HN,.,,, XjL F C'^F 354-1 .,    O OH ° i^n”'FFx / o'-A^n-nXy"-^ n / n ..... °x HN V) O'W. CF3 162-1 0 OH o p^nX^Xj / n-n                    n^n u XX XX u 1 . V-S W n^n-V / v .■V; 355 .,    O OH D D      O Y^N'lfx^' oV / z^nV^ V-V / X O^k'"^ HN JV d-v-v CF3 162-2 0 OH n^n AAAY V HN .x C.XY F H 355-1 ,    O OH D D          0       N 0^' HN JT^ ci'^XsX cf3 163 0 OH o          ° ■AxXX k^o XY c^F 356 ,    0 OH D d    o y^N 'yy •AY HN Jr^ cf3 163-1 O OH o          ? N =N A / AA <^° HN, _.<x “A 356-1 ,    0 OH o d      o        ti^Y "" o==x HN CI'XS=Y cf3 163-2 0 OH o     ? yxFFt \ JI ,--. N A. .N, J N..N N \ / \ / / N iT 1 A / / —\ A JI _ v- /  n-^na^ / Xa hna\ JA F 357 ,,    0 OH □ YnVy / A N A ,N. J N. ,,N 0  \ 4N'nA / 'A   -A l / ^ A A °Y ' HN JA C|AA cf3 164 0 OH 0 r'N \ ? n n-nAA n-^n aAAa a o — N n a / ~A° HN ,Xx •A; F 357-1 ,,    0 OH O I^N'^YYY Z"-\ N A ,N. J N.. ,N 0   \ / / N ,A ’A    A ..... °A HN JA d-^A-A cf3 164-1 0 OH 0        N'''^’^^ . 0 , ,   N JX.N,J N,.N \ n / \ z, N A rs-WU I, S^° HN .X A; 358 .,    0 OH D □      0 \^N J|Y^ HN JF^ ci'^YX cf3 164-2 0 OH 0 p^N^A^UyA . o ,—, N Y.N^ J N^^N A-vJaa I ' o '-- N N A / ^0 HN.^. F 358-1 .,    0 OH D D       0        IlY^ ° / Aa..... °Y HN JF d-^A-A cf3 165 -n m             z=< Q° 359 0 OH D D         0 n^n HN JP ci'xA. cf3 165-1 --Z                   LL U. k.: k z. z .- 359-1 / -, 0 0H D D         0 | N ifj o^S / N-n-V^ n-n ..... °x HN JP? ci"\A. cf3 165-2 —z                u. u. k.: k z. z s 360 / ', 0 0H 0 Y^N>]iX / N^N ° / ^-w HN JP cf3 166 °x* )--Z                  IL IL k,:.< °') 360-1 1 ° XpX A z ° 1 o 166-1 0 OH ° rO \             n^n L X Xx XI. n n-' / HN / \ ..¾ F 361 / -, 0 0H N^N N^N-k, HN x___ / s^Xcf3 166-2 O OH rO     N.NAVN^J N / N L X Xxz X / .O HN\ / / clBy 361 in a single configuration / -, 0 0H 0 i N o'^A^'n'X^ N^N ..... °x' HN / sP-cf3 167 :.: -. . z. z : 362 / -, 0 0H Dp    0 f nX|X A / kVJ N^N °HNX S / ~-CF3 168 0 OH ,o ? xH n-XnJ n^n 1^,0 HNX\ xT, 362-1 .,    0 OH D □    0   Yl oXzN^X'X N^N ■XX °Y "H sXa 169 O OH O p^N''^ n-XnX n^>n °x / X a !1 x XX Lx> y ci hn^I. r Vcf3 sx Cl 363 .,    0 OH D D         0   [ XN —X nXnJx °HM sX"CF3 170 O OH N n L ,N , N A Ny 363-1 .,    0 OH D D       0        ]lT^ °Y HN __ / s^Ycf3 170-1 0 OH 0 p^N Y^Y^ .xxY N N I N' Ny HN. zxx -X; 364 .,    O OH 0 r N O-XX'N'V^ XN L / / \ Y A N^N'AX_ OaY^^ HN __ / sY^cf3 170-2 0 OH o p^fy AA n'nX^ N"^N H / / —A 1 z d ”pX HN .x Af Ff 364-1 .,    0 OH 0 r N id oX / ^'nInJ XN x»X..... °Y HN __ / S^d"CF3 171 O OH / N MXN ' N N xO^X Id -- /   \-- /   N ^N^\X xx HN^.\ 365 .,    0 OH d D           o | oAj<.nA,»A ».,>■ “AXpX HN __ / sY"cf3 171-1 O OH ° r n'W AA N m'N X N # N rx xH. X VA XX         Ya° HN. ,a ILf ci^Xf F 365-1 .,    0 OH D D     0 V^N IlY A, ^jaa <X\x..... °Y HN __ / sY^cf3 171-2 °Y> )—Z u. LL Ik Z Z 366 / -, 0 0H D D     0 f^NTiY^ Y / N Ax J N^N O   \ zXN |< x-x nX-n>\. n"X s / -cf3 172 0 OH 0 ___v N Jk ,N^ J N,„,N / \ z / N T °y hy £ d> " v HN. x- 366-1 X-,    0 0H D D       o        IlY" . / S"-. / -,1 N^N / X)..... °Y HN __ / S^X"CF3 172-1 Y=Z                LL IL z. z 6 367 / -, 0 0H 0 OXX'N^^ N^N °°kY HN / ^>CF3 172-2 J . *n ti                z=Z 367-1 / ', 0 0H 0 r^N”iiY^ o / n^n^nX n^n XX..... °Y HN __ / S^Z"CF3 368 ,, O OH o^X_ / / N'n        nX kx^ YNA, OX HN JCKcf cXs CF3 368-1 ,,    0 OH o o / X\^ / N~N'X-N^k N,X XX)..... 0^'' HN IVCF cksz 3 368-2 ,    O OH o Vn-W N^N kX^ N^N-k^. o^ HN XVcF CI S7 c 3 368-3 ,    0 OH o Nx Yp..... HN JTKf ci s7 c 3 368-4 ,    o OH o w N A.    J N^ / N o yAi A   - 0^ HN JTVcF CI 'S7 CF3 369 ,,    0 OH ? Yy^V Oz   ^~N^ /     N / N A- / n^A^A, °A hm / Acf cp3 369-1 ,    0 OH o Vn-W N / A ^N. J N^ / N o yAT |T NO..... 0¾^ HN    / tXcF CF3 369-2 / ,    0 OH o \A W O / '~A_ / / N'N^^N'^ n^n aa7 aa °A'' HN / TAf s CF3 369-3 ,, o OH ? \A^V N A    J N. / N o yyAA "AA..... HN / tV-CF s cp3 369-4 / ,    0 OH Oz                 N^N —A' AA o^Z HN / TAf CF3 370 ,    0 OH 0 t N TA / --. N A ,N. J N ,N ° A_Jy if □A \.=A A °     AA OA HN A cf3 370-1 ,    0 OH 0 r N TA 0^X / N-nAN^ N s;N ..... °A HN AN cf3 371 0 OH o . N A ,N. ) N ,N o V'fY DTA nAnA^ oyA HN N     CF3 / n'N 3 371-1 ,    O OH o yyArV N A. ,N. J N. / N o V'A ..... °A' HN ,nZ^ cf3 N 372 ,    O OH 0 V<N iTn N A    ) N^ / N o AA'nA dA / mA A yA o^=A HN ,CI 372-1 ,    0 OH o A^AV o / ~~y, / N,NA,N' / N / N ..... °A HN / Cl 373 ,,    0 OH 0 ""if 373-1 ,,    0 OH ° '"a N Jk ,N-     N^N ”.^^"•^6..... O^ HN    Br • 374 ,    O OH ° ‘O^'N'V'^ N^N HN — 374-1 ,    O OH ° । N^SrS^ / —A N Jk ^N, J N^ ,N 0 a_7'n"y ..... 0¾^ HN sZ^— 375 0 “7 ~ z z 0 \\ ' :' 7 v° Qs 375-1 ,    O OH 0 0 y7'n if ..... HN sI^Br 376 0 ■ 2  2 0 \\ 1 ^0 Qs 376-1 ,    0 OH 0 o^YN-n-\n-> n^n ”.^"*7..... 0^'

[0496] Intermediate 1

[0497] 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

[0498] Reaction scheme: step F step G step H Intermediate 1

[0499] Procedure:

[0500] Step A: Ethyl 3-oxopentanoate (40.0 g, 0.28 mol) was dissolved in DCM (400 mL), and NBS (52 g, 0.29 mol) was added, followed by the addition of p-toluenesulfonic acid monohydrate (10.56 g, 0.056 mol). The reaction mixture was stirred at room temperature for 2.5 hours.

[0501] After TLC monitoring indicated the disappearance of the starting material, the mixture was filtered. The filtrate was added with water (500 mL) and stirred, and the phases were 155 separated. The organic phase was washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue, ethyl 2-bromo-3-oxopentanoate (63 g), was used directly in the next step.

[0502] 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), and potassium carbonate (78 g, 0.57 mol) was added. The reaction mixture was stirred at room temperature for 5 hours.

[0503] LCMS monitoring showed the disappearance of the starting material. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography to obtain tert-butyl 4-(1-ethoxy-1,3-dioxolan-2-yl)piperazine-1-carboxylate (70 g).

[0504] MS (ESI) M / Z: 329.4 [M+H] +.

[0505] Step C: 1H-1,2,4-triazole-3,5-diamine (50 g, 0.5 mol) was dissolved in aqueous hydrobromic acid solution (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 thereto. The reaction was warmed to room temperature and stirred for 1 hour, and then stirred at 100°C overnight.

[0506] 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), and the combined organic phases were washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure to obtain crude 3-bromo-1H-1,2,4-triazol-5-amine (27.8 g), which was used directly in the next step.

[0507] MS (ESI) M / Z: 163.0 [M+H] +.

[0508] Step D: At 0°C, 2-chloro-4-(trifluoromethyl)aniline (20 g, 0.1 mol) was dissolved in dichloromethane (200 mL). A solution of 2-chloroacetyl chloride (11.55 g, 0.1 mol) in dichloromethane (40 mL) was added dropwise. The reaction mixture was stirred at 0°C for 30 minutes, then warmed to room temperature and stirred overnight.

[0509] After TLC monitoring indicated the disappearance of most of the starting material, the reaction mixture was poured into saturated aqueous sodium bicarbonate solution (500 mL), extracted with dichloromethane (200 mL), and the organic phase was dried and concentrated 156 to dryness. The resulting crude product was purified by column chromatography to obtain 2-chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (20.1 g).

[0510] MS (ESI) M / Z: 269.8 [M-H] -.

[0511] Step E: 2-Chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (20.1 g, 73.9 mmol) was dissolved in acetone (200 mL), then potassium iodide (14.22 g, 85.7 mmol) was added, and the reaction mixture was heated to reflux and stirred for 4 hours.

[0512] After LCMS monitoring showed the disappearance of the starting material, the mixture was cooled and filtered. The filtrate was concentrated to dryness under reduced pressure to obtain 2-iodo-N-(2-chloro-4-(trifluoromethyl)phenyl)acetamide (26.8 g), and the crude product was used directly in the next step.

[0513] MS (ESI) M / Z: 362.1 [M-H] -.

[0514] Step F: 4,6-Dichloro-5-methoxypyrimidine (30 g, 0.168 mol) was dissolved in tetrahydrofuran (240 mL) and cooled to 0°C in an ice-water bath. 3 M methylmagnesium bromide (61.4 mL, 0.184 mol) was added dropwise, and after the addition, the mixture was stirred for 1 hour in the ice-water bath.

[0515] After TLC monitoring indicated the disappearance of the starting material, the reaction was quenched by adding saturated aqueous ammonium chloride solution and 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 obtain 4-chloro-5-methoxy-6-methylpyrimidine (20.6 g).

[0516] 1H NMR (400 MHz, CDCI3) 5 8.54 (s, 1H), 3.84 (s, 3H), 2.49 (s, 3H).

[0517] Step G:   4-Chloro-5-methoxy-6-methylpyrimidine (20.6 g, 0.13 mol), Pd(dppf)Ch^DCM (5.7 g, 7 mmol), and triethylamine (26.03 g, 0.257 mol) were dissolved in methanol (300 mL). Carbon monoxide (2M Pa) was introduced into the reaction mixture, and the reaction mixture was stirred at 60°C overnight.

[0518] After TLC monitoring indicated the disappearance of most of the starting material, the mixture was cooled. The mixture was concentrated under reduced pressure. The crude product was added to water and ethyl acetate, stirred, and the phases were 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 obtain 4157 chloro-5-methoxy-6-methylpyrimidine (12.4 g).

[0519] 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.

[0520] After TLC monitoring indicated the disappearance of the starting material, the reaction mixture was concentrated to dryness under reduced pressure to obtain the lithium salt of 5-methoxy-6-methylpyrimidine-4-carboxylic acid (11.8 g), and the crude product was used directly in the next step.

[0521] MS (ESI) M / Z: 169.4 [M+H] +.

[0522] Step I: 3-Bromo-1H-1,2,4-triazol-5-amine (20 g, 0.12 mol) and tert-butyl 4-(1-ethoxy-1,3-dioxolan-2-yl)piperazine-1-carboxylate (44.7 g, 0.132 mol) were dissolved in n-butanol (110 mL), and 85% phosphoric acid (12.1 g, 0.12 mol) was added. The reaction mixture was stirred at 100°C overnight. After cooling, the reaction mixture was concentrated to dryness under reduced pressure. The residue was dispersed in dichloromethane (300 mL), and triethylamine (30.3 g, 0.3 mol) and Boc2O (26.2 g, 0.12 mol) were added. The reaction mixture was stirred at room temperature overnight.

[0523] After LCMS monitoring indicated the disappearance of the starting material, water (200 mL) was added, stirred, and the phases were separated. The organic phase was washed with saturated brine (100 mL), dried over sodium sulfate, and concentrated to dryness under pressure. The crude product was purified by column chromatography to obtain 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).

[0524] MS (ESI) M / Z: 427.1 [M+H] +.

[0525] 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), and diisopropylethylamine (1.77 g, 13.73 mmol) was added. The reaction mixture was stirred at 70°C overnight.

[0526] After LCMS monitoring indicated the disappearance of the starting material, the mixture was cooled, diluted with water (100 mL), and adjusted to pH 3-4 with dilute 158 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 obtain 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).

[0527] MS (ESI) M / Z: 660.06 [M-H] -.

[0528] 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 mixture was stirred at room temperature overnight.

[0529] After LCMS monitoring indicated the disappearance of the starting material, the reaction mixture was concentrated to dryness under reduced pressure to obtain crude 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.

[0530] MS (ESI) M / Z: 560.3 [M-H] -.

[0531] Step L: The crude 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) from the previous step and lithium 5-methoxy-6-methylpyrimidine-4-carboxylate (0.62 g, 3.52 mmol) were dissolved in DMF (30 mL). Diisopropylethylamine (1 g, 7.7 mmol) and HATU (1.3 g, 3.42 mmol) were added in an ice-water bath, and the reaction mixture was stirred at room temperature for 1 hour.

[0532] After LCMS monitoring indicated 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 obtain 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).

[0533] MS (ESI) M / Z: 712.1 [M+H] +.

[0534] Intermediate 2

[0535] 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

[0536] Reaction scheme:

[0537] Procedure:

[0538] Step A:  5-Bromo-4H-1,2,4-triazol-3-amine  (10 g, 61 mmol) and ethyl propionylacetate (11.05 g, 77 mmol) were dissolved in acetic acid (35 mL), and the mixture was heated and stirred at 80°C overnight.

[0539] After LCMS monitoring indicated 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, the residue was stirred with ethanol, then filtered again, and the combined solids were dried to obtain 2-bromo-5-ethyl-160 [1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one (5.6 g).

[0540] MS (ESI) M / Z: 243.1 [M+H] +.

[0541] 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), and then diisopropylethylamine (8.96 g, 69 mmol) was added. The reaction mixture was stirred at 80°C overnight.

[0542] After LCMS monitoring indicated the disappearance of the starting material, the mixture was cooled to room temperature. Water (200 mL) and ethyl acetate (200 mL) were added. The mixture was stirred, and the phases were 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 obtain 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).

[0543] MS (ESI) M / Z: 478.1 [M+H] +.

[0544] 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(II) dichloromethane complex (0.51 g, 0.63 mmol) were added to 1,4-dioxane (120 mL) and water (60 mL). The reaction system was purged three times with nitrogen, and the reaction mixture was stirred at 80°C for 1 hour.

[0545] After LCMS monitoring indicated the disappearance of the starting material, 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).

[0546] MS (ESI) M / Z: 482.1 [M+H] +.

[0547] 1H NMR (400 MHz, DMSO-d6) 5 10.43 (s, 1H), 8.05 (d, J = 8.6 Hz, 1H), 7.92 (s, 1H), 7.67 (d, J = 8.6 Hz, 1H), 6.84 (s, 1H), 5.95 (s, 1H), 5.26 (s, 2H), 4.26 (d, J = 2.9 Hz, 2H), 3.81 (t, J = 5.4 Hz, 2H), 2.73 (q, J = 7.3 Hz, 2H), 2.49 - 2.33 (m, 2H), 1.23 (t, J = 7.3 Hz, 3H). 161

[0548] 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 mixture was stirred at 50°C overnight.

[0549] After LCMS monitoring indicated the disappearance of most of the starting material, 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 obtain         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).

[0550] MS (ESI) M / Z: 558.0 [M-H] -.

[0551] Intermediate 3

[0552] 4,4,5,5-Tetramethyl-2-(2,5,6,7-tetrahydrooxepin-4-yl)-1,3,2-dioxaborolane o^\

[0553] Reaction scheme:

[0554] Procedure:

[0555] Step A: In a three-neck flask, compound tetrahydro-4H-pyran-4-one (15.5 g, 154.8 mmol) was dissolved in ultra-dry dichloromethane (400 mL). The reaction system was then cooled to -78°C, followed by the slow addition of boron trifluoride etherate solution (22 mL) under a nitrogen atmosphere.     After the dropwise addition was completed, (trimethylsilyl)diazomethane (86 mL) was slowly added dropwise. The reaction mixture was slowly warmed from -78°C to room temperature and stirred for 3 hours.

[0556] After TLC monitoring indicated the disappearance of the starting material, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, then filtered, and concentrated under 162 reduced pressure. The crude product was purified by silica gel column chromatography to obtain oxepan-4-one (4.7 g).

[0557] 1HNMR (400 MHz, Chloroform-d) 5 3.91 - 3.81 (m, 4H), 2.74 - 2.63 (m, 4H), 1.92 - 1.80 (m, 2H).

[0558] Step B: Oxepan-4-one (4.7 g, 41.2 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL). The reaction system was evacuated and purged with nitrogen, and then lithium bis(trimethylsilyl)amide (45 mL, 45.0 mmol) was added dropwise at -78°C. After the dropwise addition was completed, the reaction mixture was stirred at -78°C for 2 hours. Subsequently, N-phenylbis(trifluoromethanesulfonyl)imide (16.2 g, 45.3 mmol) dissolved in anhydrous tetrahydrofuran was added dropwise to the reaction flask. The reaction system was slowly warmed to room temperature and then stirred for 1 hour.

[0559] After TLC monitoring indicated the disappearance of the starting material, the reaction mixture was quenched with saturated aqueous ammonium chloride solution, and then extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, then filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 2,5,6,7-tetrahydrooxepin-4-yl trifluoromethanesulfonate (2.5 g).

[0560] 1HNMR (400 MHz, DMSO-d6) 5 6.00 (d, J = 4.0 Hz, 1H), 4.22 - 4.10 (m, 2H), 3.75 (t, J = 5.6 Hz, 2H), 2.62 (s, 2H), 1.97 - 1.84 (m, 2H).

[0561] Step C: 2,5,6,7-Tetrahydrooxepin-4-yl trifluoromethanesulfonate (1.0 g, 4.06 mmol) and bis(pinacolato)diboron (1.2 g, 4.8 mmol) were dissolved in ultra-dry 1,4-dioxane (15 mL). Then, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (300 mg, 406.2 pmol) 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 a nitrogen atmosphere.

[0562] After TLC monitoring indicated the disappearance of the starting material, the reaction mixture was directly concentrated under reduced pressure to obtain the crude product. The resulting mixture was purified by silica gel column chromatography to obtain 4,4,5,5-tetramethyl-2-(2,5,6,7-tetrahydrooxepin-4-yl)-1,3,2-dioxaborolane (300 mg).

[0563] 1H NMR (400 MHz, DMSO-d6) 5 6.41 (t, J = 4.2 Hz, 1H), 4.13 - 4.12 (m, 2H), 3.71 (t, J = 5.9 Hz, 2H), 2.31-2.28 (m, 2H), 1.74-1.69 (m, 2H), 1.20 (s, 12H). 163

[0564] Intermediate 4

[0565] 4-Methyl-5-(trifluoromethyl)thiophen-3-amine hydrochloride H2Nx7 HCI Lf"3

[0566] Reaction scheme:

[0567] Procedure:

[0568] Step A: 4-Methylthiophene-3-carboxylic acid (10 g, 70.3 mmol) was dissolved in methanol (100 mL), then concentrated sulfuric acid (6.89 g, 70.3 mmol) was added, and the reaction was carried out at 75°C overnight.

[0569] After TLC monitoring indicated the disappearance of the starting material, the reaction mixture was concentrated under reduced pressure. Aqueous sodium bicarbonate solution was then added to adjust the pH to neutral, and the mixture was extracted twice with ethyl acetate (50 mL). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to obtain crude methyl 4-methylthiophene-3-carboxylate (9.5 g), which was used directly in the next step.

[0570] 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.

[0571] After TLC monitoring indicated the disappearance of the starting material, the reaction mixture was poured into sodium sulfite solution (100 mL) and extracted twice with dichloromethane (100 mL). The combined organic phases were washed with sodium bicarbonate solution and saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain methyl 5-iodo-4-methylthiophene-3-carboxylate (5.5 g).

[0572] 1H NMR (400 MHz, CDCI3) 5 8.22 (s, 1H), 3.85 (s, 3H), 2.44 (s, 3H).

[0573] 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 then sodium hydroxide (1.56 g, 39 mmol) was added. The reaction was carried out at room temperature for 2 hours.

[0574] After TLC monitoring indicated the disappearance of the starting material, the mixture was concentrated under reduced pressure. Water (100 mL) and methyl tert-butyl ether (100 mL) were added to extract impurities. The resulting aqueous phase was adjusted to pH 3-4 with dilute hydrochloric acid, and extracted twice with ethyl acetate (100 mL). The combined organic phases were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to obtain crude 5-iodo-4-methylthiophene-3-carboxylic acid, which was used directly in the next step.

[0575] MS (ESI) M / Z: 267.0 [M-H] -.

[0576] Step D: 5-Iodo-4-methylthiophene-3-carboxylic acid (5.1 g, 19 mmol) was dissolved in tert-butanol (50 mL), and diphenylphosphoryl azide (5.5 g, 19.97 mmol) and triethylamine (2 g, 19.97 mmol) were added. The mixture was heated at 60°C and reacted for 1 hour, then the temperature was raised to 90°C and the reaction was carried out overnight.

[0577] After TLC monitoring indicated the disappearance of the starting material, the mixture was cooled. Water (100 mL) was added, and the mixture was extracted twice with ethyl acetate (100 mL). The combined organic phases were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain tert-butyl (5-iodo-4-methylthiophen-3-yl)carbamate (3.9 g).

[0578] 1H NMR (400 MHz, CDCl3) 5 7.48 (s, 1H), 6.28 (s, 1H), 2.04 (s, 3H), 1.46 (s, 9H).

[0579] Step E: tert-Butyl (5-iodo-4-methylthiophen-3-yl)carbamate (2.1 g, 6.18 mmol) was dissolved in N,N-dimethylformamide (20 mL), and diphenyl(trifluoromethyl)sulfonium trifluoromethanesulfonate (5 g, 12.36 mmol) and copper powder (1.19 g, 18.58 mmol) were added. The mixture was heated at 60°C and reacted overnight. 165

[0580] After TLC monitoring indicated the disappearance of the starting material, the mixture was cooled. The mixture was filtered through diatomite. Water (100 mL) was added, and the mixture was extracted twice with ethyl acetate (100 mL). The combined organic phases were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain tert-butyl (4-methyl-5-(trifluoromethyl)thiophen-3-yl)carbamate (1.5 g).

[0581] 1H NMR (400 MHz, CDCI3) 6 7.49 (s, 1H), 6.29 (s, 1H), 2.15 (s, 3H), 1.46 (s, 9H).

[0582] Step F: tert-Butyl (4-methyl-5-(trifluoromethyl)thiophen-3-yl)carbamate (1.5 g, 5.33 mmol) was dissolved in ethyl acetate (10 mL), and hydrogen chloride in ethyl acetate (4 M, 20 mL) was added. The reaction was carried out at room temperature for 2 hours.

[0583] After TLC monitoring indicated the disappearance of the starting material, the mixture was concentrated under reduced pressure to obtain 4-methyl-5-(trifluoromethyl)thiophen-3-amine hydrochloride (560 mg).

[0584] Intermediate 5 step B

[0585] 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), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (430 mg, 1.4 mmol), sodium 166 carbonate         (372         mg,         3.5         mmol),         and         [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (60 mg, 0.07 mmol) were added to 1,4-dioxane (20 mL) and water (2.5 mL). The reaction system was purged three times with nitrogen, and the reaction mixture was stirred at 100°C overnight.

[0586] After LCMS monitoring indicated the disappearance of the starting material, the mixture was cooled to room temperature. Water (50 mL) and ethyl acetate (50 mL) were added for extraction, stirred, and the phases were separated. The aqueous phase was extracted once more with ethyl acetate (50 mL). The combined organic phases were 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 obtain 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).

[0587] MS (ESI) M / Z: 813.2 [M-H] -.

[0588] 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), then trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours.

[0589] After LCMS monitoring indicated the disappearance of the starting material, the reaction mixture was concentrated to dryness under reduced pressure. The resulting 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.

[0590] MS (ESI) M / Z: 715.3 [M+H] +.

[0591] Intermediate 6 step B

[0592] 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 tertbutyl 2-bromoacetate (238 mg, 1.22 mmol) were dissolved in N,N-dimethylformamide (4 mL). Then, N,N-diisopropylethylamine (450 mg, 3.49 mmol) was added, and the reaction mixture was stirred at 55°C overnight.

[0593] After LCMS monitoring indicated the disappearance of the starting material, water (30 mL) was added, and the mixture was extracted twice with ethyl acetate (40 mL). The combined organic phases were first washed with saturated brine (30 mL), then dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain 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).

[0594] MS (ESI) M / Z: 567.4 [M+Na] +.

[0595] 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 then 1 M aqueous sodium hydroxide solution (1.4 mL) was added. The reaction mixture was stirred at room temperature overnight.

[0596] After LCMS monitoring ind...

Claims

1. A compound of formula (IC), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof:whereinM is selected from the group consisting of a bond, CO, -NHCO-, -C(R6-1R6-2)-, andring A is selected from the group consisting of C6-14 aryl and 5- to 14-membered heteroaryl;ring B is selected from the group consisting of C3-12 cycloalkyl, C3-12 cycloalkenyl, 3- to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-14 aryl, and 5- to 14-membered heteroaryl; or, ring B is absent, and R4 is directly attached to the parent structure;ring C is selected from the group consisting of C3-12 cycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;ring E is selected from the group consisting of C3-12 cycloalkylene, C3-12 cycloalkenylene, 3- to 12-membered heterocycloalkylene, 3- to 12-membered heterocycloalkenylene, C6-14 arylene, and 5- to 14-membered heteroarylene; alternatively, ring E is directly attached to theparent to formN R3 orN R3L1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, -C1-6 alkylene-C(=N-OH)NH-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene,3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, and 5- to 14membered heteroarylene, wherein the imino, C1-6 alkylene, -CONH-, -CO-C1-6 alkylene-NH-, -C1-6 alkylene-CONH-, -C1-6 alkylene-CONH-C1-6 alkylene, -C1-6 alkylene-SO2NH-, -C1-6 alkylene-NHCONH-, -C1-6 alkylene-NHCO-, -C1-6 alkylene-NHSO2-, -C1-6 alkylene-CO-, C2-6 alkenylene, C2-6 alkynylene, C1-6 deuterated alkylene, C1-6 haloalkylene, C1-6 hydroxyalkylene, C1-6 alkyleneoxy, C1-6 alkylenethio, C1-6 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-6 alkylene-3- to 8-membered heterocycloalkylene-, -C1-6 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-6 alkylene-C6-14 arylene-, C6-14 arylene, -C1-6 alkylene-5- to 14-membered heteroarylene-, or 5- to 14-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5-to 14-membered heteroaryl;0            0HJQ      HN<alternatively, Li, R3, and the parent form a moiety           ^,                , or0HNX;Ri is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, mercapto, cyano, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 deuterated alkyl, Ci-6 haloalkyl, Ci-6 hydroxyalkyl, Ci-6 alkoxy, Ci-6 alkylthio, Ci-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-i4 aryl, and 5- to i4-membered heteroaryl, wherein the amino, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 deuterated alkyl, Ci-6 haloalkyl, Ci-6 hydroxyalkyl, Ci-6 alkoxy, Ci-6 alkylthio, Ci-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered 375heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;R2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;alternatively, two R2 are connected to each other to form a C3-8 cycloalkyl or a 3- to 8membered heterocycloalkyl, wherein the C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;alternatively, one R2 and R3 are connected to form a 5- to 8-membered heterocycloalkenyl, wherein the 5- to 8-membered heterocycloalkenyl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 10membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl; alternatively, two R4a are connected to form a 3- to 8-membered heterocycloalkyl or a 3- to 8-membered heterocycloalkenyl;R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered 378heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14membered heteroaryl;R4-3 is selected from the group consisting of hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;R5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 379haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, -SO2-C1-6 alkyl, -SF5, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;R6-1 and R6-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-14 aryl, or 5- to 14-membered heteroaryl is optionally further 380substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, 3- to 8membered heterocycloalkyl, C6-14 aryl, and 5- to 14-membered heteroaryl;alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-8 cycloalkyl or a 3- to 8-membered heterocycloalkyl;R7-1 and R7-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C1-6 alkylthio, and C1-6 haloalkoxy;alternatively, R7-1 and R7-2 are connected to form a C3-8 cycloalkyl;x is selected from the group consisting of 0, 1, 2, and 3;y is selected from the group consisting of 0, 1, 2, 3, and 4;z is selected from the group consisting of 0, 1, 2, 3, and 4;u is selected from the group consisting of 0, 1, 2, 3, and 4.

2. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to claim 1, wherein ring A is selected from the group consisting of 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, 5- to 6-memberedheteroaryl-fused 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused 3- to 6-membered heterocycloalkenyl, and 5- to 6-membered heteroaryl-fused phenyl;preferably, ring A is selected from the group consisting of3. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to claim 1 or 2, wherein ring B is selected from the group consisting of C3-10cycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 3- to 10-memberedheterocycloalkenyl, 5- to 6-membered heteroaryl-fused 3- to 10-membered heterocycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused C3-10 cycloalkenyl, benzo-fused 3- to 10membered heterocycloalkenyl, C3-10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl-fused 3- to 10-membered heterocycloalkyl, benzo-fused 5- to 6-membered heteroaryl, C3-10 cycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10membered heterocycloalkenyl-fused C3-10 cycloalkyl, and 3- to 10-membered heterocycloalkyl;preferably, ring B is selected from the group consisting of,,, and,,.

4. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to any one of claims 1 to 3, wherein ring C is selected from the groupconsisting of C6-10 aryl, 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl-fused 5- to6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6-membered heterocycloalkenyl, 5- to 6-membered heteroaryl-fused phenyl, 3- to 6-memberedheterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, and C3-8 cycloalkyl;preferably, ring C is selected from the group consisting of, phenyl,and5. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to any one of claims 1 to 4, wherein ring E is selected from the groupconsisting of 5- to 6-membered heterocycloalkylene, 4- to 6-membered heterocycloalkylenespiro-4- to 6-membered heterocycloalkylene, 5- to 6-membered heterocycloalkylene-fused 5-to 6-membered heterocycloalkylene, 5- to 6-membered heteroaryl-fused 5- to 6-memberedheterocycloalkenyl, and 5- to 6-membered heterocycloalkylene-fused C3-6 cycloalkylene;preferably, ring E is selected from the group consisting ofwherein theend with * is connected to M;alternatively, ring E is directly connected to the parent to form6. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1, 3, and 4, wherein the compound is represented by formula (XVI),(XVI)wherein R2-1, R2-2, and R2-3 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy; or, R2-2 and R2-3 are connected to form a C3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl, wherein the C3-6 cycloalkyl and 3- to 6-membered heterocycloalkyl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy;R7-1 and R7-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy;alternatively, R7-1 and R7-2 are connected to form a C3-6 cycloalkyl.

7. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to claim 6, wherein the compound is represented by formula (XVI),( XVI-1 )8. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to claim 6 or 7, whereinthe structural moiety^2-1.

9. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to any one of claims 6 to 8, whereinor,        z isor,is;isor,        z is;10. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to claim 1, wherein the compound is represented by formula (II),owhereinring B is selected from the group consisting of C3-10 cycloalkenyl-spiro-3- to 10membered heterocycloalkyl, 5- to 6-membered heteroaryl-fused 3- to 10-membered heterocycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-3- to 10-membered heterocycloalkyl, 5- to 6membered heteroaryl-fused 5- to 6-membered heteroaryl, 7- to 10-membered heterocycloalkenyl, C3-10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl, 3- to 10-membered heterocycloalkenyl-spiro-C3-10 cycloalkyl, 3-to 10-membered heterocycloalkenyl-fused 3- to 10-membered heterocycloalkyl,, benzo-fused 5- to 6-membered heteroaryl, C3-10 cycloalkenyl-spiro-C3-10 cycloalkyl, 3- to 10-membered heterocycloalkenyl-fused C3-10 cycloalkyl, and11. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to claim 1, wherein the compound is represented by formula (VI),0(VI)whereinring C is selected from the group consisting of 5-membered heteroaryl,5- to 6-membered heteroaryl-fused 5- to 6-membered heteroaryl, benzo-fused 5- to 6-membered heteroaryl, benzo-fused 3- to 6-membered heterocycloalkenyl, 3- to 6-membered heterocycloalkenyl-fused phenyl, 5- to 6-membered heteroaryl-fused C3-6 cycloalkenyl, and C3-8 cycloalkyl; preferably, ring C is selected from the group consisting ofs , and12. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to any one of claims 1, 3, and 4, wherein the compound is represented byformula (XV),13. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, whereinR1 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, mercapto, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R1a; the R1a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;preferably, R1 is independently selected from the group consisting of hydroxyl, methyl,hydrogen, fluorine, △, cyclopropyl, trifluoromethyl, mercapto, -CH2OH, -CD3,and -N(CH3)2.

14. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 13, whereinR2 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R2a; the R2a is independently selected from the group consisting of hydrogen, deuterium,halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;alternatively, two R2 are connected to each other to form a C3-6 cycloalkyl or a 3- to 6membered heterocycloalkyl, wherein the C3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl is optionally further substituted with deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl,or 5- to 6-membered heteroaryl;alternatively, one R2 and R3 are connected to formwherein theoroptionally further substituted with one or more substituents selected from the group consistingof deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl,3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;preferably, R2 is independently hydrogen and methyl.

15. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, whereinR3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R3a; the R3a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;L1 and R3 are connected to form a 3- to 8-membered heterocycloalkenyl or a 5- to 6membered heteroaryl; wherein the 3- to 8-membered heterocycloalkenyl or 5- to 10-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl;R3 is selected from the group consisting of ethyl, trifluoromethoxy, vinyl, ethynyl, cyano,16. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to any one of claims 1 to 15, whereinR4 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, 5- to 6-membered heteroaryl, -COR4-1, -COOR4-1, -OC(=O)R4-1, -SO2R4-2, and -OR4-3, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6membered heteroaryl is optionally further substituted with one or more R4a; the R4a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl; or, two R4a are connected to form a 3- to 6-membered heterocycloalkyl;R4-1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6393membered heteroaryl;R4-2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6membered heteroaryl;R4-3 is selected from the group consisting of hydrogen, deuterium, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C3-6 cycloalkyl, 3- to 6membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;preferably, R4 is independently selected from the group consisting of hydrogen, methyl,-CH2CN,, phenyl,,, cyclopropyl,, fluorine, and deuterium.

17. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 16, whereinR5 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, -SO2-C1-3 alkyl, -SF5, 395C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;preferably, R5 is independently selected from the group consisting of hydrogen, chlorine,Ftrifluoromethyl, fluorine, methyl, cyclopropyl, \  , -SF5, ethyl, and -SO2CH3.

18. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 17, whereinL1 is selected from the group consisting of a bond, -O-, -S-, imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-CONH-C1-3 alkylene, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8 cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-membered heterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, and 5- to 6-membered heteroarylene, wherein the 396imino, C1-3 alkylene, -CONH-, -CO-C1-3 alkylene-NH-, -C1-3 alkylene-CONH-, -C1-3 alkylene-CONH-C1-3 alkylene-C1-3 alkylene-SO2NH-, -C1-3 alkylene-SO2NH-, -C1-3 alkylene-NHCONH-, -C1-3 alkylene-NHCO-, -C1-3 alkylene-NHSO2-, -C1-3 alkylene-CO-, -C1-3 alkylene-C(=N-OH)NH-, C2-4 alkenylene, C2-4 alkynylene, C1-3 deuterated alkylene, C1-3 haloalkylene, C1-3 hydroxyalkylene, C1-3 alkyleneoxy, C1-3 alkylenethio, C1-3 haloalkyleneoxy, C3-8  cycloalkylene, 3- to 8-membered heterocycloalkylene, 3- to 8-memberedheterocycloalkenylene, -C1-3 alkylene-3- to 8-membered heterocycloalkylene-, -C1-3 alkylene-3- to 8-membered heterocycloalkenylene-, -C1-3 alkylene-C6-10 arylene-, C6-10 arylene, -C1-3 alkylene-5- to 6-membered heteroarylene-, or 5- to 6-membered heteroarylene is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, oxo, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;more preferably, L1 is selected from the group consisting of -CH2-, -CH2CONH-*, -CH2SO2NH-*, -COCH2NH-*, -CONH-*, -CH2CO-*, -CH2CON(CH3)-*, -CH2CONHCH2-*, -CH2CH2CONH-*,, and -CH2-C(=N-OH)NH-*, wherein the side with * is connected to ring C.

19. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 18, whereinR6-1 and R6-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 397deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy,C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more R5a; the R5a is independently selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl, wherein the amino, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C6-10 aryl, or 5- to 6-membered heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 haloalkoxy, C3-6 cycloalkyl, 3- to 6membered heterocycloalkyl, C6-10 aryl, and 5- to 6-membered heteroaryl;alternatively, R6-1 and R6-2, together with the carbon atom to which they are attached, form a C3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl;preferably, R6-1 is selected from the group consisting of hydrogen, cyano, and trifluoromethyl; R6-2 is hydrogen;or preferably, R6-1, R6-2, together with the carbon atom to which they are attached, form < or <20. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 19, whereinR7-1 and R7-2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxyl, cyano, C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 deuterated alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl, C1-3 alkoxy, C1-3 alkylthio, and C1-3 haloalkoxy; preferably, R7-1 is selected from the group consisting of hydrogen and methyl; R7-3982 is methyl;alternatively, R7-1 and R7-2 are connected to form a C3-6 cycloalkyl; preferably, R7-1 and R7-2 are connected to form a cyclopropyl.

21. The compound, the stereoisomer thereof, or the pharmaceutically acceptable saltthereof according to any one of claims 1 to 20, wherein the compound is as shown below:0 OHO OH0 OHO OHO OH22. The compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 6 to 9, wherein the compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof satisfies one or more of the following conditions:(1) R1 is independently selected from the group consisting of hydroxyl and C1-6 alkyl;(2) R4 is deuterium;(3) R5 is independently selected from the group consisting of halogen, C1-6 alkyl, and C1-6 haloalkyl;(4) x is selected from the group consisting of 0, 1, and 2; preferably 2;(5) R2-1 is hydrogen; (6) R7-1 and R7-2 are each independently selected from the group consisting of hydrogen and C1-6 alkyl;(7) z is selected from the group consisting of 0, 1, and 2; preferably 2;(8) u is selected from the group consisting of 0, 1, and 2; preferably 2.

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

24. Use of the compound, the stereoisomer thereof, or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 22, or the pharmaceutical composition 415according to claim 23 in the manufacture of a medicament for treating cancer; the cancer is selected from the group consisting of colorectal cancer, endometrial cancer, ovarian cancer, and gastric cancer; more preferably, the cancer is microsatellite instability-high or mismatch repair-deficient cancer.

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