Combination therapy of KRAS modulators

Abstract

Provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II). Formula (II)

Description

[0001] Cross-references This application claims the benefit of U.S. Provisional Patent Application No. 63 / 518,177, filed August 8, 2023, the entire contents of which are incorporated herein by reference. Background Technology

[0002] The small GTPase protein Kirsten rat sarcoma type 2 virus oncogene homolog (KRAS) is a member of the Ras cell signaling switch family, which regulates the growth and survival of normal and cancer cells (see, for example, Cully, M. and J. Downward, SnapShot: Ras Signaling. Cell, 2008. 133(7): p. 1292-1292 e1). KRAS mutations drive approximately 25% of human cancers by aberrantly regulating the mitogen-activated protein kinase (MAPK) signaling cascade and other effector pathways (see, for example, Stephen, AG et al., Dragging ras back in the ring. Cancer Cell, 2014. 25(3): p. 272-81). Although Ras has been considered a cancer target for about 40 years, Ras-driven cancers remain among the most difficult to treat due to their lack of responsiveness to available targeted therapies. Ras is encoded by three major genes, KRAS, NRAS, and HRAS, and mutations in any of these oncogenes are most frequent. All oncogenic Ras mutations drive the accumulation of switches in the active GTP-binding state. The most common Ras mutation found in human tumor types is KRAS G12D (see, for example, The AACR Project GENIE Consortium. Cancer Discovery, 2017. 7(8): p. 818-831. Dataset Version 4). Activating mutations in codon 12 impair the ability of small GTPases to hydrolyze GTP. This regulatory impairment is crucial for initiating and maintaining tumor progression.

[0003] Despite significant efforts, no small molecules have yet been identified that block effector binding or restore sensitivity to GTPase-activated proteins (GAPs). However, some small molecules, such as SOS, have been found that block the interaction between Ras and guanine nucleotide exchange factor (GEF), activating Ras in the plasma membrane. The KRAS G12C mutation, most commonly found in lung adenocarcinoma, has been clinically demonstrated to be more readily inhibited by covalent modification with small-molecule inhibitors, trapping the protein in an inactive GDP-binding state. The KRAS G12D mutation results in a significantly slower rate of intrinsic GTP hydrolysis than G12C, leading to more constitutive activation. Therefore, while a similar binding pocket exists in the GDP state, pharmacological targeting of the inactive state is unlikely to yield similar results for G12D. Furthermore, the presence of cysteine ​​residues at the site of activation mutations generates covalent chemistry, while aspartic acid does not provide a typical medicinal chemical approach for selective covalent modification.

[0004] To potentially exploit the accumulation of GTP-bound KRAS G12D and other mutant variants as a weakness for selective inhibition of cancer cells while preserving normal Ras function, it is attractive for small molecule inhibitors to bind to the GTP state and stabilize the conformation that prevents interaction with oncogenic signaling pathways of effector proteins. Furthermore, it has been demonstrated that only constitutive activation of Raf, MEK, and ERK kinases in the downstream MAPK cascade can bypass the requirement for Ras protein in proliferation signaling (see, e.g., Drosten, M. et al., Genetic analysis of Rassignalling pathways in cell proliferation, migration, and survival. EMBO J, 2010. 29(6): p. 1091-104). Since all evidence indicates that MAPK signaling is crucial for the growth of Ras in cancer, selective inhibition of KRAS mutants in this pathway is considered a key functional indication of the potential clinical benefits of novel therapeutic approaches. Summary of the Invention

[0005] While the compounds disclosed herein are potent inhibitors of KRas signaling and exhibit single-agent activity in inhibiting the in vitro proliferation of cell lines carrying KRas mutations or other KRas-activating gene alterations, the relative potency and / or observed maximum effect of any given KRas inhibitor may vary among KRas-mutant cell lines. The reasons for the range of potency and the observed maximum effect are not fully understood, but some cell lines appear to possess different intrinsic resistance to the mechanism of action, depending on binding to certain conformational states of the KRAS protein. Therefore, it is necessary to develop alternative approaches to maximize the potency, efficacy, therapeutic index, and / or clinical benefit of KRas inhibitors in vitro and in vivo. Due to the known feedback loops in the Ras signaling pathway, in the presence of a KRas inhibitor, it may be necessary to inhibit upstream RTK signaling or downstream MAPK signaling to completely block KRas-mutant activity.

[0006] In one aspect, this disclosure provides a method for treating cancer in a subject in need, comprising administering to the subject a combination of a therapeutically effective amount of an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (I): Formula (I) Or its pharmaceutically acceptable salt, wherein: R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20-C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R)20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from hydrogen, -N(R) 21 )2、-LN(R 21 )2、-L-OR 21 Heterocyclic rings, C l -C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R) 21 )2、-LC l -C6 haloalkyl, -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and -LC(=O)OC l -C6 alkyl, wherein heterocyclic and -L-NR 5 The aryl moiety of the C(O)-aryl group and the heterocyclic moiety of the -L-heterocyclic group and the cycloalkyl moiety of the -L-cycloalkyl group are optionally separated by one or more R groups. 6 Substitution, wherein the aryl or heteroaryl groups of -L-aryl and -L-heteroaryl are optionally replaced by one or more R 7 replace; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 5 Independently selected from hydrogen or C1-C6 alkyl; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l-C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl group of the -C3 alkyl)phenyl group is optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl, or -N(R) 5 )2; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each Q is independently selected from the bond, S, and O; B is selected from heterocycles and carbocycles, wherein the heterocycles and carbocycles are optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C. l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted, wherein B forms a spirocyclic ring with ring A; and Ring A is selected from heterocycles and carbocycles, wherein the heterocycle or carbocycle is optionally composed of one or more rings selected from R. 4 Substituents are substituted.

[0007] In one aspect, this disclosure provides a method for treating cancer in a subject in need, comprising administering to the subject a combination of an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (II): Equation (II) Or its pharmaceutically acceptable salt, wherein: M is selected from O, S, SO, SO2, and NR. 3 ; R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl-SO2R 20 C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from -LN(R) 21 )2、-L-OR 21 Heterocyclic rings, C l-C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R) 21 )2、-LC l -C6 haloalkyl, -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and -LC(=O)OC l -C6 alkyl, wherein heterocyclic, -L-NR 21 The aryl moiety of the C(O)-aryl group, the heterocyclic moiety of the -L-heterocyclic group, and the cycloalkyl moiety of the -L-cycloalkyl group are each optionally surrounded by one or more R groups. 6 Substitution, wherein the aryl moiety of -L-aryl and the heteroaryl moiety of -L-heteroaryl are each optionally replaced by one or more R 7 Replacement, where R is a bond, O, or S. 2 Further selected from hydrogen; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; R 3 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-N(R)20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; n is selected from 0 to 2; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, including C1-C6 alkyl groups, ... 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; Each R 5 Independently selected from hydrogen or C1-C6 alkyl; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)Cl -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are each optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl, or -N(R) 5 )2; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and B is selected from heterocycles and carbocycles, wherein the heterocycle and carbocycle are each optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C. l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C 3- C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups.

[0008] In one aspect, this disclosure provides a method for treating cancer in a subject in need, comprising administering to the subject a combination of a therapeutically effective amount of an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (II): Equation (II) Or its pharmaceutically acceptable salt, wherein: M is selected from O, S, SO, SO2, and NR.3 ; R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl-SO2R 20 C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from -LN(R) 21 )2、-L-OR 21 Heterocyclic rings, C l -C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R) 21 )2、-LC l -C6 haloalkyl, -L-NR 21C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and -LC(=O)OC l -C6 alkyl, wherein heterocyclic, -L-NR 21 The aryl moiety of the C(O)-aryl group, the heterocyclic moiety of the -L-heterocyclic group, and the cycloalkyl moiety of the -L-cycloalkyl group are each optionally surrounded by one or more R groups. 6 Substitution, wherein the aryl moiety of -L-aryl and the heteroaryl moiety of -L-heteroaryl are each optionally replaced by one or more R 7 Replacement, where R is a bond, O, or S. 2 Further selected from hydrogen; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; R 3 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6Alkoxyalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; n is selected from 0 to 2; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, including C1-C6 alkyl groups, ... 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; Each R 5 Independently selected from hydrogen or C1-C6 alkyl; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5)2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are each optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl, or -N(R) 5 )2; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and B is selected from heterocycles and carbocycles, wherein the heterocycle and carbocycle are each optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C. l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C 3- C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups.

[0009] In one aspect, this disclosure provides a method for treating cancer in a subject in need, comprising administering to the subject a combination of a therapeutically effective amount of an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (III): Equation (III) Or its pharmaceutically acceptable salt, wherein: R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; R 2 Selected from -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and L-bicyclic heterocycles, wherein the bicyclic heterocycles are optionally composed of one or more R 6 replace; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; n is selected from 0 to 3; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, including C1-C6 alkyl groups, ... 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; B is selected from heterocycles and carbocycles, wherein the heterocycle or carbocycle is optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; Y is selected from bonds, O, S, and NR. 5 ; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl group of the -C3 alkyl)phenyl group is optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and Each R 5 It is independently selected from hydrogen or C1-C6 alkyl.

[0010] Incorporation All publications, patents and patent applications mentioned in this specification are incorporated by reference to the same extent that each individual publication, patent or patent application is specifically and individually indicated to be incorporated by reference. Attached Figure Description

[0011] The novel features of the invention are set forth in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by referring to the following detailed description of illustrative embodiments utilizing the principles of the invention, and the accompanying drawings (also referred to herein as “Figures” and “illustrations”): Figure 1 The illustration shows that, compared to single-agent therapy, combination therapy enhances tumor growth inhibition and tumor regression. Detailed Implementation

[0012] The following description illustrates many exemplary configurations, methods, parameters, etc. However, it should be understood that such description is not intended to limit the scope of this disclosure, but is provided as a description of exemplary embodiments.

[0013] In the following description, certain specific details are set forth to provide a comprehensive understanding of various embodiments of this disclosure. However, those skilled in the art will understand that this disclosure can be practiced without these details.

[0014] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. All patents and publications cited herein are incorporated herein by reference.

[0015] "Alkyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, without unsaturation, and preferably having one to fifteen carbon atoms (i.e., C1-C1). 15 alkyl) 。 In some embodiments, the alkyl group comprises one to thirteen carbon atoms (i.e., C1-C1). 13 Alkyl group. In some embodiments, the alkyl group comprises one to eight carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl group comprises one to five carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl group comprises one to four carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl group comprises one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl group comprises one to two carbon atoms (i.e., C1-C2 alkyl). In other embodiments, the alkyl group comprises one carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group comprises five to fifteen carbon atoms (i.e., C5-C6 alkyl). 15 Alkyl group. In other embodiments, the alkyl group comprises five to eight carbon atoms (i.e., C5-C8 alkyl). In other embodiments, the alkyl group comprises two to five carbon atoms (i.e., C2-C5 alkyl). In other embodiments, the alkyl group comprises three to five carbon atoms (i.e., C3-C5 alkyl). In some embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl group is attached to the rest of the molecule by a single bond.

[0016] Term "C" x-y When used in conjunction with a chemical part (such as alkyl, alkenyl, or alkynyl), it means to include a group containing x to y carbons in the chain. For example, the term "C 1-6 "Alkyl" refers to a substituted or unsubstituted saturated hydrocarbon group, including straight-chain alkyl and branched-chain alkyl groups containing 1 to 6 carbons. Term -C x-y Alkylene refers to an alkylene chain containing x to y carbons, whether substituted or unsubstituted. For example, -C 1-6The alkylene group can be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any of which may be optionally substituted.

[0017] "Alkoxy" refers to a group of the formula -O-alkyl that is bonded by an oxygen atom, wherein the alkyl group is an alkyl chain as defined above.

[0018] "Alkenyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having two to twelve carbon atoms (i.e., C2-C). 12 Alkenyl group. In some embodiments, the alkenyl group comprises two to eight carbon atoms (i.e., C2-C8 alkenyl). In some embodiments, the alkenyl group comprises two to six carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, the alkenyl group comprises two to four carbon atoms (i.e., C2-C4 alkenyl). The alkenyl group is attached to the rest of the molecule by a single bond, such as ethenyl, propyl-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, pent-1,4-dienyl, etc.

[0019] "Alkyne group" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having two to twelve carbon atoms (i.e., C2-C). 12 The alkynyl group (C2-C8 alkynyl group) comprises two to eight carbon atoms in some embodiments. In other embodiments, it comprises two to six carbon atoms (C2-C6 alkynyl group). In still other embodiments, it comprises two to four carbon atoms (C2-C4 alkynyl group). The alkynyl group is attached to the rest of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentyynyl, hexynyl, etc.

[0020] Term "C" x-y "Alkenyl" and "C" x-y "Alkyne" refers to an alkyl group of similar length and possible substitution as described above, but containing at least one substituted or unsubstituted aliphatic group with a double or triple bond. Term -C x-y An alkenyl group refers to an alkenyl chain containing x to y substituted or unsubstituted carbons. For example, -C 2-6 The alkenyl group can be selected from vinylene, propenene, butenene, pentenene, and hexenene, any of which are optionally substituted. The alkenyl chain may have one or more double bonds. Terminology - C x-y Amyynyl group refers to a substituted or unsubstituted ynyl chain containing x to y carbons. For example, -C 2-6The alkenyl group can be selected from alkenylene, propynylene, butynylene, pentylyne, and hexynylene, any of which are optionally substituted. The alkenylene chain can have one or more triple bonds.

[0021] "alkylene" or "alkylene chain" refers to a straight-chain or branched divalent hydrocarbon chain, consisting only of carbon and hydrogen, without unsaturation, and preferably having one to twelve carbon atoms, with the remainder of the molecule attached to a group. Examples include methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is attached to the remainder of the molecule and to the group via single bonds. The attachment points of the alkylene chain to the remainder of the molecule and to the group can be through any two carbons within the chain. In some embodiments, the alkylene comprises one to ten carbon atoms (i.e., C1-C8 alkylene). In some embodiments, the alkylene comprises one to eight carbon atoms (i.e., C1-C8 alkylene). In other embodiments, the alkylene comprises one to five carbon atoms (i.e., C1-C5 alkylene). In other embodiments, the alkylene comprises one to four carbon atoms (i.e., C1-C4 alkylene). In other embodiments, the alkylene comprises one to three carbon atoms (i.e., C1-C3 alkylene). In other embodiments, the alkylene group comprises one or two carbon atoms (i.e., C1-C2 alkylene). In other embodiments, the alkylene group comprises one carbon atom (i.e., C1 alkylene). In other embodiments, the alkylene group comprises five to eight carbon atoms (i.e., C5-C8 alkylene). In other embodiments, the alkylene group comprises two to five carbon atoms (i.e., C2-C5 alkylene). In other embodiments, the alkylene group comprises three to five carbon atoms (i.e., C3-C5 alkylene).

[0022] "Alkenyl" or "alkenyl chain" refers to a straight-chain or branched divalent hydrocarbon chain consisting only of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having two to twelve carbon atoms, to which the remainder of the molecule is attached via single bonds, and also to the group via single bonds. The attachment points of the alkenyl chain to the remainder of the molecule and to the group can be through any two carbons within the chain. In some embodiments, the alkenyl group comprises two to ten carbon atoms (i.e., C2-C). 10(Alkenyl group). In some embodiments, the alkenyl group comprises two to eight carbon atoms (i.e., C2-C8 alkenyl). In other embodiments, the alkenyl group comprises two to five carbon atoms (i.e., C2-C5 alkenyl). In other embodiments, the alkenyl group comprises two to four carbon atoms (i.e., C2-C4 alkenyl). In other embodiments, the alkenyl group comprises two to three carbon atoms (i.e., C2-C3 alkenyl). In other embodiments, the alkenyl group comprises two carbon atoms (i.e., C2 alkenyl). In other embodiments, the alkenyl group comprises five to eight carbon atoms (i.e., C5-C8 alkenyl). In other embodiments, the alkenyl group comprises three to five carbon atoms (i.e., C3-C5 alkenyl).

[0023] "Alynyl" or "alynyl chain" refers to a straight-chain or branched divalent hydrocarbon chain in which the rest of a molecule is attached to a group, consisting only of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having two to twelve carbon atoms. The alynyl chain is attached to the rest of the molecule and to the group via single bonds. The attachment points of the alynyl chain to the rest of the molecule and to the group can be through any two carbons within the chain. In some embodiments, the alynyl group contains two to ten carbon atoms (i.e., C2-C). 10 The ynyl group (C2-C8 ynyl group) comprises two to eight carbon atoms in some embodiments. In other embodiments, the ynyl group comprises two to five carbon atoms (C2-C5 ynyl group). In other embodiments, the ynyl group comprises two to four carbon atoms (C2-C4 ynyl group). In other embodiments, the ynyl group comprises two to three carbon atoms (C2-C3 ynyl group). In other embodiments, the ynyl group comprises two carbon atoms (C2 ynyl group). In other embodiments, the ynyl group comprises five to eight carbon atoms (C5-C8 ynyl group). In other embodiments, the ynyl group comprises three to five carbon atoms (C3-C5 ynyl group).

[0024] "Aryl" refers to a group derived from an aromatic monocyclic or polycyclic aromatic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. An aromatic monocyclic or polycyclic aromatic hydrocarbon ring system contains only hydrogen and carbon, with five to eighteen carbon atoms, wherein at least one ring in the ring system is aromatic, that is, according to Hückel theory, it contains a cyclic, delocalized (4n+2) π-electron system. Ring systems from which aryl groups are derived include, but are not limited to, groups such as those in benzene, fluorene, indene, indene, tetrahydronaphthalene, and naphthalene.

[0025] "Aryl group" refers to the formula -R c -aryl groups, where R c It is an alkylene chain as defined above, such as methylene, ethylene, etc.

[0026] "Aryl" refers to the formula -R d -aryl groups, where R d This refers to an alkenyl group as defined above. "Arynyl group" refers to the formula -R e -aryl groups, where R e It is an alkyne chain as defined above.

[0027] A "carbocyclic ring" refers to a saturated, unsaturated, or aromatic ring in which every atom of the ring is carbon. Carbocyclic rings can include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocyclic ring can be selected from saturated, unsaturated, and aromatic rings. An aromatic ring (e.g., phenyl) can be fused with a saturated or unsaturated ring (e.g., cyclohexane, cyclopentane, or cyclohexene). Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of a carbocyclic ring, where valence allows. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Bicyclic carbocyclic rings can be fused ring systems, bridged ring systems, or spirocyclic systems. In some cases, spirocyclic carbocyclic rings have at least two molecular rings with only one common atom.

[0028] The term "unsaturated carbide ring" refers to a carbide ring that has at least one degree of unsaturation and does not contain an aromatic carbide ring. Examples of unsaturated carbide rings include cyclohexadiene, cyclohexene, and cyclopentene.

[0029] "Cycloalkyl" refers to a fully saturated monocyclic or polycyclic hydrocarbon group consisting only of carbon and hydrogen atoms, including fused or bridged ring systems, and preferably having three to twelve carbon atoms. In some embodiments, the cycloalkyl group contains three to ten carbon atoms. In other embodiments, the cycloalkyl group contains five to seven carbon atoms. The cycloalkyl group can be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl groups include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptyl), norbornenyl, decahydronaphthyl, 7,7-dimethylbicyclo[2.2.1]heptyl, etc.

[0030] "Cycloalkenyl" refers to an unsaturated non-aromatic monocyclic or polycyclic hydrocarbon group consisting only of carbon and hydrogen atoms, including fused or bridged ring systems, preferably having three to twelve carbon atoms, and containing at least one double bond. In some embodiments, the cycloalkenyl group contains three to ten carbon atoms. In other embodiments, the cycloalkenyl group contains five to seven carbon atoms. The cycloalkenyl group can be attached to the rest of the molecule via a single bond. Examples of monocyclic cycloalkenyl groups include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0031] "Cycloalkylalkyl" refers to the formula -R c -cycloalkyl groups, wherein R cIt is an alkylene chain as described above.

[0032] "Cycloalkylalkoxy" refers to the formula -OR c - A cycloalkyl group bonded by an oxygen atom, wherein R c It is an alkylene chain as described above.

[0033] "Halogen" or "halogenated" refers to halogenated substituents, such as bromine, chlorine, fluorine, and iodine substituents.

[0034] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl group as defined above that is substituted with one or more halogen groups, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl group is further optionally substituted. Examples of halogen-substituted alkanes (“haloalkanes”) include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), dihalomethanes and trihalomethanes (e.g., chloroform, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, I, etc.). When an alkyl group is substituted by more than one halogen group, each halogen can be chosen independently, for example, 1-chloro,2-fluoroethane.

[0035] "Fluoroalkyl" refers to an alkyl group as defined above that is substituted with one or more fluorine groups, such as trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc.

[0036] "Aminoalkyl" refers to an alkyl group as defined above that is substituted with one or more amine groups, such as propane-2-amine, butane-1,2-diamine, pentane-1,2,4-triamine, etc.

[0037] "Hydroxyalkyl" refers to an alkyl group as defined above that is replaced by one or more hydroxyl groups, such as propan-1-ol, butan-1,4-diol, pentan-1,2,4-triol, etc.

[0038] "Alkoxyalkyl" refers to an alkyl group as defined above that is substituted with one or more alkoxy groups, such as methoxymethane, 1,3-dimethoxybutane, 1-methoxypropane, 2-ethoxypentane, etc.

[0039] As used in this article, "cyanoalkyl" refers to an alkyl group as defined above that is substituted with one or more cyano groups, such as acetonitrile, 2-ethyl-3-methylsuccinate, butyronitrile, etc.

[0040] As used herein, "heterocycle" refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Where valence permits, a heterocycle can be attached to the remainder of the molecule by any atom of the heterocycle, such as a carbon or nitrogen atom. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Where valence permits, bicyclic heterocycles include any combination of saturated bicyclic, unsaturated bicyclic, and aromatic bicyclic rings. In one exemplary embodiment, an aromatic ring (e.g., a pyridyl group) may be fused with a saturated or unsaturated ring (e.g., cyclohexane, cyclopentane, morpholine, piperidine, or cyclohexene). Bicyclic heterocycles include any combination of ring sizes, such as 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Bicyclic heterocycles can be fused ring systems, bridged ring systems, or spirocyclic systems. Spirocyclic systems can be called "spiroheterocycles (spiro heterocycles or spiro-heterocycles)". In some cases, spiroheterocycles have at least two molecular rings with only one common atom. Spiroheterocycles contain one or more heteroatoms.

[0041] "Subheterocyclic" refers to a divalent heterocycle in which the rest of the molecule is attached to a group.

[0042] "Heteroaryl" or "aromatic heterocycle" refers to a group derived from a heteroaryl ring group containing one to eleven carbon atoms and at least one heteroatom, wherein each heteroatom may be selected from N, O, and S. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems, wherein at least one ring in the ring system is aromatic, i.e., according to Hückel theory, it contains a cyclic, delocalized (4n+2) π-electron system. The heteroatom in the heteroaryl group may optionally be oxidized. One or more nitrogen atoms (if present) may optionally be quaternized. Where valence permits, the heteroaryl group may be attached to the remainder of the molecule by any atom of the heteroaryl group (such as the carbon or nitrogen atom of the heteroaryl group). Examples of heteroaryl groups include, but are not limited to, pyridine, pyrimidine, oxazole, furan, pyran, thiophene, isoxazole, benzimidazole, benzothiazole, and imidazopyridine.

[0043] "X-membered heteroaryl" refers to the number of inner ring atoms in the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 inner ring atoms, such as triazole, oxazole, thiophene, etc.

[0044] The term "unsaturated heterocycle" refers to a heterocycle having at least one degree of unsaturation and not containing aromatic heterocycles. Examples of unsaturated heterocycles include dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydropyridine. The heterocycle may optionally be substituted with one or more substituents (such as those described herein).

[0045] The term "substituted" refers to a portion having a substituent that replaces a hydrogen atom or a substituted heteroatom (e.g., NH) on one or more carbons of the structure. It should be understood that "substituted" or "replaced by" includes the implicit precondition that such substitution conforms to the permissible valence of the substituted atom and the substituent, and that the substitution produces a stable compound, i.e., a compound that does not spontaneously undergo transformations such as rearrangement, cyclization, or elimination. In some embodiments, "substituted" refers to a portion having a substituent that replaces two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon atom with an oxo, imino, or thio group. As used herein, the term "substituted" is envisioned to include all permissible substituents in organic compounds. In a broad sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents in organic compounds. For suitable organic compounds, permissible substituents can be one or more and can be the same or different. For the purposes of this disclosure, heteroatoms (such as nitrogen) may have hydrogen substituents and / or any permitted substituents of the organic compounds described herein that satisfy the valence of the heteroatoms.

[0046] In some embodiments, the substituents may include any substituents described herein, such as: halogen, hydroxyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)-R a -R b -OC(O)-OR a -R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N(Ra )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, areneyl, arynyl, cycloalkyl, cycloalkylalkyl and heterocyclic, any of which may optionally be converted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)-R a -R b -OC(O)-OR a -R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N(R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O)t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2) replace; where each R a Independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each R is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein, where the valence allows, each R a It can be optionally divided by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)-R a -R b -OC(O)-OR a -R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N(R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b-S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2) replace; and where each R b Independently selected from direct bonds or straight-chain or branched alkylene, alkenyl, or ynylene chains, and each R c It is a straight-chain or branched alkylene, alkenyl, or ynylene chain.

[0047] As used herein, the term "electrophile" or "electrophilic moiety" refers to any moiety capable of reacting with a nucleophile (e.g., a moiety having a lone pair of electrons, a negative charge, a partially negative charge, and / or an excess of electrons, such as a -SH group). Electrophiles are typically electron-deficient or contain electron-deficient atoms. In some embodiments, the electrophile contains a positive charge or a partially positive charge, has a resonance structure containing a positive charge or a partially positive charge, or is a moiety where electron delocalization or polarization results in one or more atoms containing a positive charge or a partially positive charge. In some embodiments, the electrophile comprises a conjugated double bond, such as an α,β-unsaturated carbonyl group or an α,β-unsaturated thiocarbonyl compound.

[0048] As used herein, the terms “optional” or “optionally” mean that the event described below may or may not occur, and the description includes both the occurrence and non-occurrence of the event or situation. For example, “optionally substituted aryl” means that the aryl group may be substituted or unsubstituted, and the description includes both substituted aryl groups and unsubstituted aryl groups.

[0049] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” as used in the specification and claims include plural indicators.

[0050] The term "salt" or "pharmaceutically acceptable salt" refers to a salt derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed from inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Pharmaceutically acceptable base addition salts can be formed from inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, basic ion exchange resins, and particularly isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, pharmaceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0051] As used herein, the phrase “parenteral administration” means any administration mode that is normally administered by injection other than enteral and local administration, and includes, but is not limited to, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intra-bursal, intraorbital, intracardiac, intradermal, intraperitoneal, tracheal, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, intravertebral, and intrasternal injections and infusions.

[0052] The phrase “pharmaceutically acceptable” in this article refers to compounds, materials, compositions, and / or dosage forms that, within reasonable medical judgment, are suitable for contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, and in proportion to a reasonable benefit / risk ratio.

[0053] As used herein, the phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” means a pharmaceutically acceptable material, composition, or medium, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be “acceptable” in the sense of compatibility with the other components of the formulation and not cause harm to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; (4) powdered tragacanth gum; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and corn oil. Oils and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffer solution; and (21) other non-toxic compatible substances used in pharmaceutical preparations.

[0054] In some implementations, the term “prevention” in relation to a disease or condition may refer to the compound reducing the incidence of the disease or condition in a treated sample relative to an untreated control sample, or delaying the onset of one or more symptoms of the disease or condition or reducing its severity relative to an untreated control sample.

[0055] As used herein, the term “treatment” can include reducing, alleviating or improving symptoms of a disease or condition; preventing additional symptoms; improving or preventing the underlying cause of symptoms; suppressing a disease or condition, for example, preventing the development of a disease or condition, alleviating a disease or condition, causing a disease or condition to subside, alleviating the condition caused by a disease or condition, or stopping the symptoms of a disease or condition in a preventive and / or therapeutic manner.

[0056] As used in this article, the term “G12 mutant” refers to the other KRAS oncogenic allele at amino acid position 12 (i.e., G12X).

[0057] The term "RTK-MAPK pathway" refers to the signaling cascade between receptor tyrosine kinases (RTKs) (including positive regulators of RTK activity, such as SHP2 or SOS1) and the RAF-MEK-ERK (i.e., MAPK) pathway.

[0058] The term "RTK-MAPK pathway inhibitor" refers to an agent, such as a compound or antibody, that can negatively regulate or inhibit all or part of the activity of at least one protein in the RTK-MAPK pathway.

[0059] The term "RAF-MEK-ERK pathway" refers to a series of kinases that are sequentially activated downstream of the RAS family of small GTPases.

[0060] The term "RAF-MEK-ERK pathway inhibitor" refers to an agent, such as a compound or antibody, that can negatively regulate or inhibit all or part of the activity of at least one protein in the RAF-MEK-ERK pathway.

[0061] As used in this article, “KRas G12D-associated cancer” refers to cancer that is associated with, mediated by, or has a KRas G12D mutation.

[0062] As used in this article, “KRas G12V-associated cancer” refers to cancer that is associated with, mediated by, or has a KRas G12V mutation.

[0063] As used in this article, “cancer associated with KRas wild type” refers to cancer that is associated with, mediated by, or has KRas G12D wild type.

[0064] The term “ERBB family” or “ERBB family members” refers to members of the mammalian transmembrane protein tyrosine kinase family, including: EGFR, ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4).

[0065] The term "ERBB family inhibitor" refers to an agent, such as a compound or antibody, that can negatively regulate or inhibit all or part of the activity of at least one member of the ERBB family.

[0066] The term "EGFR inhibitor" refers to an agent, such as a compound or antibody, that can negatively regulate or inhibit all or part of the activity of the epidermal growth factor receptor (EGRF).

[0067] The term “SHP-2” or “SHP2” refers to a mammalian non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which participates in signal transduction through the Ras mitogen-activated protein kinase, JAK-STAT, or phosphatidylinositol 3-kinase-AKT pathway.

[0068] The term "SHP-2 inhibitor" or "SHP2 inhibitor" refers to a compound that can negatively regulate or inhibit all or part of the enzyme activity of SHP-2 phosphatase.

[0069] The term “SOS1” refers to the mammalian sevenless homolog 1 (SOS1) enzyme.

[0070] The term "SOS1 inhibitor" refers to a compound that can negatively regulate or inhibit all or part of the interaction between SOS1 and Ras family mutants or SOS1 activating mutations, thereby reducing and / or regulating the nucleotide exchange activity of the Ras family member-SOS1 complex.

[0071] The terms “object,” “individual,” and “patient” are used interchangeably and refer to humans as well as non-human mammals (e.g., non-human primates, canines, equines, felines, suidae, bovids, ungulates, lagomorphs, etc.). In various implementations, an object can be a person under the care of a physician or other healthcare worker in a hospital, as an outpatient or in another clinical setting (e.g., adult male, adult female, adolescent male, adolescent female, boy, girl). In some implementations, the object may not be under the care or prescription of a physician or other healthcare worker.

[0072] As used herein, the phrase “objects in need” refers to those who are at risk of having or being treated with the compounds or salts described herein for preventative or therapeutic purposes.

[0073] The terms “determine,” “measure,” “assess,” “evaluate,” “assess,” “determine,” and “analyze” are used interchangeably in this document to refer to forms of measurement. These terms include determining the presence of an element (e.g., detection). These terms can include quantitative, qualitative, or a combination of quantitative and qualitative determination. Assessment can be relative or absolute. “Detecting the presence of…” can include determining the quantity of a substance present, in addition to determining its presence in context.

[0074] The term "administration" is defined as providing a composition to a subject via a route known in the art, including but not limited to intravenous, intra-arterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, mucosal, or intraperitoneal administration. In some embodiments, an oral administration route may be used. The term "administration" of a compound should be understood as intended to provide an individual in need with a compound of this disclosure or a prodrug of a compound of this disclosure.

[0075] The term "effective amount" or "therapeutic effective amount" refers to the amount of the compound or salt described herein sufficient to affect the intended application, including but not limited to the treatment of diseases as defined below. Therapeutic effective amounts can vary depending on the intended application (in vitro or in vivo) or the subject and disease condition being treated, such as the subject's weight and age, the severity of the disease condition, the method of administration, etc., which can be readily determined by those skilled in the art. The term can also be applied to doses that can induce a specific response in target cells, such as reducing proliferation or downregulating the activity of target proteins. Specific doses can vary depending on the particular compound selected, the dosing regimen to be followed, whether it is administered in combination with other compounds, the time of administration, the tissue of administration, and the physical delivery system carrying it.

[0076] As used in this article, the “therapeutic efficacy of the combination” of two compounds is the amount by which they synergistically increase the combined activity compared to the therapeutic efficacy of each compound in the combination, i.e., greater than the sum of their individual effects.

[0077] As used herein, “synergistic effect” or “synergistic effect” refers to two or more compounds or combinations that, when produced individually, produce an effect that, when combined, is greater than the individual effects of each compound.

[0078] The terms “about” or “approximately” can refer to an acceptable range of error for a particular value as determined by a person skilled in the art, depending in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, according to practice in the art, “about” can refer to within one or more standard deviations. Alternatively, “about” can refer to a range of up to 20%, up to 15%, up to 10%, up to 5%, or up to 1% of a given value.

[0079] Every maximum numerical limit given throughout this specification is intended to include every lower numerical limit as if those lower numerical limits were explicitly stated herein. Every minimum numerical limit given throughout this specification includes every higher numerical limit as if those higher numerical limits were explicitly stated herein. Every numerical range given throughout this specification will include every narrower numerical range falling within this wider range as if those narrower numerical ranges were explicitly stated herein.

[0080] The chapter titles used in this article are for organizational purposes only and should not be construed as limiting the subject matter.

[0081] Any aspect or implementation described herein may be combined with any other aspect or implementation disclosed herein.

[0082] Compositions and Inhibitors RTK-MAPK pathway inhibitors In one respect, this article provides methods for treating diseases or conditions in objects in need, including applying the following combination to the object: i) RTK-MAPK pathway inhibitors or their pharmaceutically acceptable salts or drug compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0083] In one respect, this article provides methods for treating diseases or conditions in subjects who require them, including administering the following combinations of therapeutically effective amounts to the subject: i) RTK-MAPK pathway inhibitors or their pharmaceutically acceptable salts or drug compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0084] In one respect, this paper provides methods for treating cancer in subjects who require it, including administering the following combination to the subject: i) RTK-MAPK pathway inhibitors or their pharmaceutically acceptable salts or drug compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0085] In one aspect, this article provides a method for treating cancer in a subject in need, comprising administering a therapeutically effective amount of the following combination to said subject: i) RTK-MAPK pathway inhibitors or their pharmaceutically acceptable salts or drug compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0086] In some implementations, equation (II) is represented by equation (II*).

[0087] RAF-MEK-ERK pathway inhibitors In one respect, this article provides methods for treating diseases or conditions in objects in need, including applying the following combination to the object: i) RAF-MEK-ERK pathway inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0088] In one respect, this article provides methods for treating diseases or conditions in subjects who require them, including administering the following combinations of therapeutically effective amounts to the subject: i) RAF-MEK-ERK pathway inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0089] In one respect, this paper provides methods for treating cancer in subjects who require it, including administering the following combination to the subject: i) RAF-MEK-ERK pathway inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0090] In one aspect, this article provides a method for treating cancer in a subject in need, comprising administering a therapeutically effective amount of the following combination to said subject: i) RAF-MEK-ERK pathway inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0091] In some implementations, equation (II) is represented by equation (II*).

[0092] ERBB family inhibitors In one respect, this article provides methods for treating diseases or conditions in objects in need, including applying the following combination to the object: i) ERBB family inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0093] In one respect, this article provides methods for treating diseases or conditions in subjects who require them, including administering the following combinations of therapeutically effective amounts to the subject: i) ERBB family inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0094] In one respect, this paper provides methods for treating cancer in subjects who require it, including administering the following combination to the subject: i) ERBB family inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions. ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0095] In one aspect, this article provides a method for treating cancer in a subject in need, comprising administering a therapeutically effective amount of the following combination to said subject: i) ERBB family inhibitors or their pharmaceutically acceptable salts or pharmaceutical compositions, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0096] In some implementations, equation (II) is represented by equation (II*).

[0097] The ERBB family inhibitors used in the methods described herein can be reversible or irreversible ERBB family inhibitors. In one embodiment, the ERBB family inhibitor inhibits the activity of more than one ERBB family member.

[0098] Regulation or inhibition of one or more ERBB family members can be achieved by regulating or inhibiting the kinase activity of one or more ERBB family members or by blocking the homodimerization or heterodimerization of ERBB family members. In some embodiments of the methods described herein, ERBB inhibitor refers to the use of a single ERBB inhibitor. In some embodiments of the methods described herein, the term ERBB inhibitor refers to the use of two ERBB inhibitors.

[0099] In some implementations, ERBB family inhibitors are irreversible inhibitors. In some cases, irreversible ERBB family inhibitors inhibit the activity of EGFR and HER2 by forming covalent bonds with the sulfhydryl groups of cysteine ​​797 and cysteine ​​773, respectively, thereby blocking the binding of ATP to the intracellular catalytic domain. Therefore, these inhibitors are active against cell lines, for example, those with EGFR exon 19 deletions / insertions and L858R and T790M resistance mutations.

[0100] In some embodiments, exemplary irreversible ERBB family inhibitors used in this method include afatinib ((E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide); dacomitinib ((2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolin-6-enamide) (N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-morpholinopropoxy)quinazolin-6-yl)acrylamide); (N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-morpholinopropoxy)quinazolin-6-yl)acrylamide); (N-(4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)prop-2-en-1-one); AV 412 (N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4-methyl-1-piperazinyl)-1-butyl-1-yl]-6-quinazolinyl]-2-acrylamide); PF 6274484 (N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]-2-acrylamide) and HKI 357 ((2E)-N-[[4-[(3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide) and pharmaceutically acceptable salts or pharmaceutical compositions thereof. In some cases, the irreversible ERBB family inhibitor is afatinib. In one embodiment, the irreversible ERBB family inhibitor is dacomitinib. In some cases, the irreversible ERBB family inhibitors suitable for the provided compositions and methods include, but are not limited to, afatinib; dacomitinib; canertinib; poziotinib; AV 412; PF 6274484 and HKI 357.

[0101] In some implementations, ERBB family inhibitors are reversible inhibitors. In some cases, reversible inhibitors include erlotinib ([6,7-bis-(2-methoxy-ethoxy)-quinazoline-4-yl]-(3-ethynyl-phenyl)-amine), gefitinib (4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline), sapitinib (2-((4-(((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazoline-6-yl)oxy)piperidin-1-yl)-N-methylacetamide); varlitinib ((R)-N4-(3-chloro-4-(thiazolyl-2-ylmethoxy)phenyl)-N6-(4-methyl-4,5-dihydrooxazol-2-yl)quinazolin-4,6-diamine); TAK-285(N-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl)-3-hydroxy-3-methylbutyramide); AEE788((S)-6-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine); tarloxotinib 3-[N-[4-(3-bromo-4-chlorophenylamino)pyridin[3,4-d]pyrimidin-6-yl]carbamoyl]-N,N-dimethyl-N-(l-methyl-4-nitro-1H-imidazol-5-ylmethyl)-2(E)-propen-l-ammonium bromide); BMS 599626 ((3S)-3-morpholinylmethyl-[4-[[1-[(3-fluorophenyl)methyl]-1H-indazol-5-yl]amino]-5-methylpyrrole[2,1-f][1,2,4]triazin-6-yl]-carbamate dihydrochloride); and GW 583340 HCl (N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[[2-(methylsulfonyl)ethyl]amino]methyl]-4-thiazolyl]-4-quinazolinamine dihydrochloride) and pharmaceutically acceptable salts or pharmaceutical compositions thereof.

[0102] In some implementations, the reversible ERBB family inhibitor is sapitinib. In other cases, the reversible ERBB family inhibitor is tarloxotinib.

[0103] In some implementations, the ERBB family inhibitor is a combination of an EGFR inhibitor and a HER2 inhibitor, wherein the EGFR inhibitor and the HER2 inhibitor are a combination of the following two: AG 1478 HC1 (7V-(3-chlorophenyl)-6,7-dimethoxy-4-quinazolinamine hydrochloride); AG 494 ( E)-2-cyano-3-(3,4-dihydroxyphenyl)- N -Phenylacetamide; AG 555 ( E )-2-cyano-3-(3,4-dihydroxyphenyl)- N -(3-Phenylacetyl)-2-Acrylamide; AG 556 ( E )-2-cyano-3-(3,4-dihydroxyphenyl)- N -(4-Phenylacetyl)-2-Acrylamide; AG 825 ( E )-3-[3-[(2-benzothiazolyl)methyl]-4-hydroxy-5-methoxyphenyl]-2-cyano-2-acrylamide; CP 724714 (2-methoxy- N -[(2 E )-3-[4-[[3-methyl-4-[(6-methyl-3-pyridyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide; BIBU 1361 diHCl ( N -(3-chloro-4-fluorophenyl)-6-[4-[(diethylamino)methyl]-1-piperidinyl]pyrimidine[5,4- d ]Pyrimidine-4-amine dihydrochloride); BIBU 1382 ( N 8 -(3-Chloro-4-fluorophenyl)- N 2 -(1-Methyl-4-piperidinyl)-pyrimidine[5,4-]pyrimidine-2,8-diamine dihydrochloride); JNJ 28871063 Hydrochloride (5 E -4-Amino-6-(4-benzyloxy-3-chlorophenylamino)pyrimidine-5-carboxaldehyde N -(2-morpholino-4-ylethyl)oxime hydrochloride); PD 153035 (4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline hydrochloride); PD 158780 ( N 4 -(3-Bromophenyl)- N 6 -Methylpyridine[3,4- d Pyrimidine-4,6-diamine and its pharmaceutically acceptable salts or pharmaceutical compositions thereof.

[0104] In some implementations, ERBB family inhibitors are anti-EGFR antibodies, anti-HER2 antibodies, or a combination of anti-EGFR and anti-HER2 antibodies, or pharmaceutical compositions thereof. In some cases, antibodies targeting EGFR and / or HER-2 are used, including monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies.

[0105] In some implementations, exemplary anti-EGFR monoclonal antibodies approved for human clinical use include, but are not limited to, necitumumab (Eli Lilly), panitumumab (Amgen), and cetuximab (ImClone). Other anti-EGFR antibodies suitable for this method include EP384, H11, 11.6, 225, and 199.12 (Thermo Fisher), or GT133 (GeneTex).

[0106] In some implementations, the anti-EGFR monoclonal antibody is cetuximab.

[0107] In some implementations, exemplary anti-HER-2 monoclonal antibodies include, but are not limited to, pertuzumab (Roche), trastuzumab (Roche), and trastuzumab emtansine (Roche).

[0108] In some embodiments, the ERBB family inhibitor is an anti-EGFR antibody, an anti-HER2 antibody, or a combination of anti-EGFR and anti-HER2 antibodies, or a pharmaceutical composition thereof. In one embodiment, the anti-EGFR antibody is necitumumab, panitumumab, or cetuximab. In another embodiment, the anti-EGFR antibody is cetuximab. In some cases, the anti-HER2 antibody suitable for the methods described herein is pertuzumab, trastuzumab, or trastuzumab emtansine.

[0109] In some implementations, the ERBB family inhibitors are EGFR inhibitors and HER2 inhibitors, wherein the EGFR inhibitor and HER2 inhibitor are independently selected from two agents chosen from the following: AG 1478 HC1 ( N -(3-chlorophenyl)-6,7-dimethoxy-4-quinazolinamine hydrochloride); AG 494 ( E )-2-cyano-3-(3,4-dihydroxyphenyl)- N -Phenylacetamide; AG 555 ( E )-2-cyano-3-(3,4-dihydroxyphenyl)- N -(3-Phenylacetyl)-2-Acrylamide; AG 556 ( E)-2-cyano-3-(3,4-dihydroxyphenyl)- N -(4-Phenylacetyl)-2-Acrylamide; AG 825 ( E )-3-[3-[(2-benzothiazolyl)methyl]-4-hydroxy-5-methoxyphenyl]-2-cyano-2-acrylamide; CP 724714 (2-methoxy- N -[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide; BIBU 1361 diHCl (N-(3-chloro-4-fluorophenyl)-6-[4-[(diethylamino)methyl]-1-piperidinyl]-pyrimidine[5,4]pyrimidine-4-amine dihydrochloride); BIBU 1382 ( N 8 -(3-Chloro-4-fluorophenyl)- N 2 -(1-methyl-4-piperidinyl)-pyrimidine[5,4-J]pyrimidine-2,8-diamine dihydrochloride); JNJ 28871063 HCl (5 E -4-amino-6-(4-benzyloxy-3-chlorophenylamino)pyrimidine-5-carboxaldehyde N-(2-morpholin-4-ylethyl)oxime hydrochloride); PD 153035 (4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline hydrochloride); PD 158780 ( N 4 -3-bromophenyl)- N 6 -Methylpyridine[3,4- d Pyrimidine-4,6-diamine) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0110] EGFR inhibitors In one respect, this article provides methods for treating diseases or conditions in objects in need, including applying the following combination to the object: i) EGFR inhibitors or pharmaceutically acceptable salts or drug compositions thereof ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0111] In one respect, this article provides methods for treating diseases or conditions in subjects who require them, including administering the following combinations of therapeutically effective amounts to the subject: i) EGFR inhibitors or pharmaceutically acceptable salts or drug compositions thereof ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0112] In one respect, this paper provides methods for treating cancer in subjects who require it, including administering the following combination to the subject: i) EGFR inhibitors or pharmaceutically acceptable salts or drug compositions thereof, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0113] In one aspect, this article provides methods for treating cancer in subjects in need, comprising administering to the subject a therapeutically effective amount of the following combination: i) an EGFR inhibitor or a pharmaceutically acceptable salt or pharmaceutical composition thereof, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0114] In some implementations, equation (II) is represented by equation (II*).

[0115] In some implementations, the epidermal growth factor receptor (EGFR) is a transmembrane protein tyrosine kinase of the ERBB receptor family. Upon binding to epidermal growth factor (EGF), the EGFR receptor can homodimerize with another EGFR molecule or heterodimerize with another family member such as ErbB2 (HER2), ErbB3 (HER3), or ErbB4 (HER4). Homodimerization and / or heterodimerization of the ERBB receptor leads to phosphorylation of key tyrosine residues in its intracellular domains, resulting in stimulation of numerous intracellular signaling pathways involved in cell proliferation and survival. Overexpression of the EGFR gene has been identified in several cancers, including bladder cancer, brain cancer, head and neck cancer, pancreatic cancer, lung cancer, breast cancer, ovarian cancer, colon cancer, prostate cancer, and kidney cancer.

[0116] In some implementations, the EGFR inhibitor is cetuximab.

[0117] SHP-2 inhibitors In one respect, this article provides methods for treating diseases or conditions in objects in need, including applying the following combination to the object: i) SHP-2 inhibitors or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0118] In one respect, this article provides methods for treating diseases or conditions in subjects who require them, including administering the following combinations of therapeutically effective amounts to the subject: i) SHP-2 inhibitors or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0119] In one respect, this paper provides methods for treating cancer in subjects who require it, including administering the following combination to the subject: i) SHP-2 inhibitors or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0120] In one aspect, this article provides a method for treating cancer in a subject in need, comprising administering a therapeutically effective amount of the following combination to said subject: i) SHP-2 inhibitors or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0121] In some cases, equation (II) is represented by equation (II*).

[0122] Src homology 2 (SH2) domain-containing phosphatase 2 (“SHP-2”) is a mammalian non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene. It participates in signal transduction through the Ras mitogen-activated protein kinase, JAK-STAT, or phosphatidylinositol 3-kinase (P13K)-AKT-mTOR pathway. The SHP-2 polypeptide consists of two Src homology 2 (SH2) domains (N-SH2 and C-SH2) located in the N-terminal region and two potential Grb2 SH2 domain binding sites located in the C-terminal region.

[0123] In some implementations, SHP-2 has been shown to exhibit a non-mutant resistance mechanism in response to anti-tyrosine kinase inhibitors (TKIs). In some cases, increased SHP-2 phosphatase activity has been shown to induce resistance to the TKI inhibitor imatinib (e.g., see Li et al. ah, (2018) Toxicol. Appl. Pharmacol. 360-249-256). Adding an SHP-2 inhibitor has been shown to overcome resistance by blocking the RAF / MEK / ERK pathway and the PI3K / AKT / mTOR pathway.

[0124] Several inhibitors exhibiting anti-SHP-2 activity have been developed. Exemplary SHP-2 inhibitors include, but are not limited to, SHP-099 (6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazine-2-amine dihydrochloride); RMC-4550 (3-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]dec-8-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazine-2-yl)methanol), RMC-4630 (Revolution Medicine), and TNO155 (Novartis). RMC-4630 and TNO155 are undergoing Phase 1 human clinical trials in adult patients with specific advanced solid tumors.

[0125] In some embodiments, methods for manufacturing SHP-2 inhibitors are well known to those skilled in the art, and SHP-2 inhibitors are available from various commercial suppliers in forms suitable for research or human use. Furthermore, suitable SHP-2 inhibitors for the compositions and methods disclosed herein, as well as methods for preparing such inhibitors, are disclosed in the following U.S. Patent Application Publications: US20190127378; US20180251471; US20180201623; US20180186770; US20180170862; US US20180065949; US20170204080; US20170166510; US20170011975; US201200334186; US20120257184; US20110190315; US20090042788; US20080194563; US20080058431; US20080058431; US20040121384; US20040043434; and US20040110800.

[0126] SOS1 inhibitors In one respect, this article provides methods for treating diseases or conditions in objects in need, including applying the following combination to the object: i) SHP-2 inhibitors or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0127] In one respect, this article provides methods for treating diseases or conditions in subjects who require them, including administering the following combinations of therapeutically effective amounts to the subject: i) SOS1 inhibitors or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) and compounds of formula (II) or their pharmaceutically acceptable salts or pharmaceutical compositions.

[0128] In one respect, this paper provides methods for treating cancer in subjects who require it, including administering the following combination to the subject: i) an SOS1 inhibitor or a pharmaceutically acceptable salt or pharmaceutical composition thereof, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0129] In one aspect, this article provides a method for treating cancer in a subject in need, comprising administering a therapeutically effective amount of the following combination to said subject: i) an SOS1 inhibitor or a pharmaceutically acceptable salt or pharmaceutical composition thereof, and ii) A compound of formula (II) or a pharmaceutically acceptable salt or pharmaceutical composition thereof.

[0130] In some cases, equation (II) is expressed by equation (II*).

[0131] In some implementations, SOS1 inhibitors block the interaction between SOS1 and Ras family members and prevent KRas from recycling to its active GTP-bound form, thus providing therapeutic benefits for a variety of cancers, particularly those associated with Ras family members. These compounds negatively regulate KRas activity by blocking the SOS1-KRas interaction in cells to treat various forms of cancer, including Ras-related cancers, SOS1-related cancers, and NF1 / NF2-related cancers.

[0132] In some implementations, one SOS1 inhibitor that can be used in the methods described herein is BI-I-13 (also known as BI-3406). Its structure is as follows: KRAS regulator The following is a discussion of compounds and their salts that may be used in the methods of this disclosure. These compounds and salts may be used in combination with at least one other inhibitor (e.g., an RTK-MAPK pathway inhibitor, a RAF-MEK-ERK pathway inhibitor, an ERBB family inhibitor, an EGFR inhibitor, an SHP-2 inhibitor, or an SOS1 inhibitor). These compounds and salts may be used in combination with one other inhibitor (e.g., an RTK-MAPK pathway inhibitor, a RAF-MEK-ERK pathway inhibitor, an ERBB family inhibitor, an EGFR inhibitor, an SHP-2 inhibitor, or an SOS1 inhibitor). In some cases, compounds of formula (I), formula (II), formula (III), or their sub-formulas may be used in the methods of this disclosure. In some cases, compounds of formula (I), formula (II), formula (III), or their sub-formulas may be referred to as KRAS inhibitors. In some cases, compounds of formula (I), formula (II), formula (III), or formula (II*) may be referred to as KRAS inhibitors. In some cases, compounds of formula (I), formula (II), formula (III), or formula (II*) may be referred to as KRAS modulators.

[0133] In some implementations, the compound is represented by the structure of formula (I): Formula (I) Or its pharmaceutically acceptable salt, wherein: R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R)20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20-CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from hydrogen, -N(R) 21 )2、-LN(R 21 )2、-L-OR 21 Heterocyclic rings, C l -C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -LN(R) 21 )2, -L-NHC(=NH)NH2, -LC(O)N(R 21 )2、-LC l -C6 haloalkyl, -L-OR 21 -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2, or -LC(=O)OC l -C6 alkyl, wherein heterocyclic and -L-NR 5 The aryl moiety of the C(O)-aryl group and the heterocyclic moiety of the -L-heterocyclic group and the cycloalkyl moiety of the -L-cycloalkyl group are optionally separated by one or more R groups. 6 Substitution, wherein the aryl or heteroaryl groups of -L-aryl and -L-heteroaryl are optionally replaced by one or more R 7 replace; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 5 Independently selected from hydrogen and C1-C6 alkyl groups; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)Cl -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl group of the -C3 alkyl)phenyl group is optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl, or -N(R) 5 )2; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each Q is independently selected from the bond, S, and O; B is selected from heterocycles and carbocycles, wherein the heterocycles and carbocycles are optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C. l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C 3- C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted, wherein B forms a spirocyclic ring with ring A; and Ring A is selected from heterocycles and carbocycles, wherein the heterocycle or carbocycle is optionally composed of one or more rings selected from R. 4 Substituents are substituted.

[0134] In some implementations, formula (I) is represented by formula (II), formula (II*), or formula (III).

[0135] In some embodiments, for compounds or salts of formula (I), ring A is selected from heterocycles, wherein the heterocycle is optionally surrounded by one or more elements selected from R. 4 The ring A is substituted with a substituent. In some cases, ring A includes at least one heteroatom selected from nitrogen, sulfur, and oxygen. In some cases, the heteroatom of ring A is nitrogen, wherein nitrogen is optionally replaced by R. 3 Replace, where R 3 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substituents in the carbon ring and 3 to 12-membered heterocycles. In some cases, the heteroatom of ring A is sulfur, wherein sulfur is optionally substituted by one or two oxygen atoms. In some cases, the heteroatom of ring A is oxygen.

[0136] In some embodiments, for compounds or salts of formula (I), ring A is selected from a carbide ring, wherein the carbide ring is optionally surrounded by one or more elements selected from R. 4 Substituents are substituted.

[0137] In some implementations, for compounds or salts of formula (I), R 2 Selected from -L-NR 21 S(O)2(R 21 ) and -LS(O)2N(R 21 )2.

[0138] In some implementations, for compounds or salts of formula (I), R 2 Selected from -LN(R) 21 )C(O)(OR 21 ) and -L-OC(O)N(R 21 )2.

[0139] In some implementations, for compounds or salts of formula (I), each R 21Independently selected from hydrogen; C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl and oxo substituents. In some cases, each R... 21 Independently selected from hydrogen; C 1-6 Alkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles. In some cases, each R... 21 Independently selected from hydrogen and C 1-6 alkyl.

[0140] In some implementations, for compounds or salts of formula (I), R 2 Selected from L-bicyclic heterocycles, wherein the bicyclic heterocycle is optionally separated by one or more R 6 replace.

[0141] In some implementations, for compounds or salts of formula (I), R 2 Selected from L-pyrrolizine, wherein the pyrrolizine is optionally reacted with one or more R 6 replace.

[0142] In some embodiments, for compounds or salts of formula (I), each L is independently selected from optionally substituted C. l -C4 alkylene; wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring, wherein the C3-C6 carbon ring is optionally permeated by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of the haloalkyl group. In some cases, the optional substituents of L are selected from C. l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring; wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are optionally pertaining to one or more elements selected from halogens and C 1-6 Substituents of haloalkyl groups.

[0143] In some embodiments, for compounds or salts of formula (I), each L is independently selected from substituted C. l-C4 alkylene, wherein two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, the C3-C6 carbon ring is optionally replaced by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substitution of alkyl halogens.

[0144] In some embodiments, for compounds or salts of formula (I), each L is independently selected from substituted C. l -C4 alkylene, wherein the two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, each L is independently selected from substituted C3 alkylene, wherein the two substituents on the same carbon atom of L together form a C3 carbon ring. In some cases, each L is independently selected from... .

[0145] In some implementations, for compounds or salts of formula (I), R 2 Selected from -L-heterocycles, wherein the heterocyclic portion of the -L-heterocycle is optionally separated by one or more R... 6 Substitution. In some cases, the heterocycle is a saturated heterocycle. In some cases, the heterocycle has at least one nitrogen atom and at least one sulfur atom. In some cases, the heterocycle has at least one nitrogen atom. In some cases, the heterocycle has at least one sulfur atom.

[0146] In some implementations, for compounds or salts of formula (I), R 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0147] In some implementations, for compounds or salts of formula (I), YR 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0148] In some implementations, for compounds or salts of formula (I), YR 2 Selected from , and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0149] In some implementations, for compounds or salts of formula (I), YR 2 Selected from , , , , and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0150] In some implementations, for compounds or salts of formula (I), R 2 Selected from -L-saturated heterocycles, wherein the saturated heterocyclic portion of the -L-saturated heterocycle is optionally separated by one or more R 6 It is substituted and contains one nitrogen atom and one sulfur atom. In some cases, YR 2 Selected from , and The heterocyclic portion is optionally separated by one or more R 6 Replacement. In some cases, YR 2 Selected from , and The heterocyclic moiety is optionally substituted by one or more substituents selected from C1-C3 alkyl and oxo groups. In some cases, YR 2 Selected from , and In some cases, YR 2 Selected from , and .

[0151] In some implementations, for compounds or salts of formula (I), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN, C l -C3 aminoalkyl, -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5)2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are optionally substituted with -C(O)H and OH, and the heterocycles of the -CH2 heterocyclic groups are optionally substituted with oxo groups.

[0152] In some implementations, for compounds or salts of formula (I), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN and C l -C3 aminoalkyl.

[0153] In some implementations, for compounds or salts of formula (I), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 aminoalkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -N(R) 5 )2 and oxygenation. In some cases, each R 6 Independently selected from -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 aminoalkyl, C l -C3 alkoxy groups and -N(R) 5 2. In some cases, each R 6 Selected independently from C l -C3 alkyl, C l -C3 alkoxy groups and -N(R) 5 )2.

[0154] In some implementations, for compounds or salts of formula (I), R 6 Selected from halogens, -OH, Cl -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN and C l -C3 aminoalkyl. In some cases, R 6 Selected from halogens and C l -C3 alkyl. In some cases, R 6 It is a halogen. In some cases, R 6 It is a C1-C3 alkyl group. In some cases, R 6 Selected from halogens and C l -C3 alkyl. In some cases, R 6 Selected from methyl and fluorine.

[0155] In some implementations, for compounds or salts of formula (I), R 2 Selected from , and .

[0156] In some implementations, for compounds or salts of formula (I), YR 2 Selected from , and .

[0157] In some implementations, for compounds or salts of formula (I), YR 2 Selected from , , and .

[0158] In some implementations, for compounds or salts of formula (I), YR 2 yes .

[0159] In some implementations, for compounds or salts of formula (I), YR 2 Selected from , , , , , and .

[0160] In some embodiments, for compounds or salts of formula (I), B is an optionally substituted 5- to 15-membered heterocycle or an optionally substituted C3-C ring. 15 Carbon ring. In some cases, B is an optionally substituted 5- to 15-membered heterocycle. In some cases, B is an optionally substituted C3-C... 15 Carbon ring.

[0161] In some embodiments, for compounds or salts of formula (I), B is an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C... 15 Fused carbon ring. In some cases, B is an optionally substituted 8- to 15-membered fused heterocycle. In some cases, B is an optionally substituted C8-C... 15 Fused carbon rings.

[0162] In some embodiments, for compounds of formula (I) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 The fused carbocyclic rings are each bicyclic or tricyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic rings are each bicyclic or tricyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic rings or optionally substituted C8-C... 15 Each of the fused carbon rings is either bicyclic or tricyclic.

[0163] In some embodiments, for compounds or salts of formula (I), B, the heterocycle or the carbocyclic ring, is independently bicyclic. In some cases, the heterocycle is bicyclic. In some cases, the carbocyclic ring is bicyclic.

[0164] In some embodiments, for compounds or salts of formula (I), B, the heterocycle or the carbocyclic ring, is independently tricyclic. In some cases, the heterocycle is tricyclic. In some cases, the carbocyclic ring is tricyclic.

[0165] In some embodiments, for compounds or salts of formula (I), B is an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C... 15 Fused carbon rings are selected from , , , , , and Each of these may be optionally substituted by one or more substituents.

[0166] In some embodiments, for compounds of formula (I) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 Fused carbon rings are selected from , , , , and Each of these may be optionally substituted by one or more substituents.

[0167] In some embodiments, for compounds of formula (I) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 Fused carbon rings are selected from and Each of these may be optionally substituted by one or more substituents.

[0168] In some embodiments, for compounds or salts of formula (I), for B, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogens, C1-C3 alkyl groups, -B(OR) 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group. In some cases, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OR) groups. 20 )2、-OH、-C(O)N(R 20 )2、=O、-CN、C 1-6 Alkoxy and C 2-6 Alkyne group. In some cases, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy and C 2-6 Alkynyl. In some cases, one or more optional substituents of the heterocycle and carbocyclic ring are independently selected each time they appear, from oxo, -NH2, -CN, halogen, and C1-C3 alkyl groups. In some cases, one or more optional substituents of the heterocycle or carbocyclic ring are independently selected, from oxo, -NH2, halogen, and C1-C3 alkyl groups.

[0169] In some implementations, for compounds or salts of formula (I), B is selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0170] In some embodiments, for compounds or salts of formula (I), for B, one or more optional substituents of the heterocyclic or carbocyclic ring are independently selected from oxo, -NH2, CN, halogen, C1-C3 alkyl.

[0171] In some implementations, for compounds or salts of formula (I), B is selected from... , , , , , , , and .

[0172] In some implementations, for compounds or salts of formula (I), each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen. In some cases, each R... 4 Selected independently from C 1-6 Alkyl, oxo, and halogen.

[0173] In some implementations, for compounds or salts of formula (I), n is selected from 1 and 2. In some cases, n is 0.

[0174] In some implementations, Y is O for compounds or salts of formula (I).

[0175] In some implementations, for compounds or salts of formula (I), R 1 Selected from 5 to 12-membered heterocycles with optional substitution.

[0176] In some implementations, for compounds or salts of formula (I), R 1 Selected from C3-C 12A carbon ring and 5 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=NO(R 20 ), CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0177] In some implementations, for compounds or salts of formula (I), R 1 Selected from C3-C 12 A carbon ring and 5 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 SR 20 -S(O)2(R 20 ), C(O)N(R 20 )2、-C(O)NR 20 -OR 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、N(R20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 OC(O)N(R) 20 )2、-NO2、=O、=NO(R 20 -CN, -NHCN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0178] In some implementations, for compounds or salts of formula (I), R 1 Selected from C3-C 12 Carbon rings and 5 to 12-membered heterocycles, each of which is optionally composed of one or more independently selected from -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)OR 20 and -OC(O)N(R 20 Substituents of )2.

[0179] In some implementations, for compounds or salts of formula (I), R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0180] In some implementations, for compounds or salts of formula (I), R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0181] In some implementations, for compounds or salts of formula (I), R 1 R 20 Selected from hydrogen and C 1-3 alkyl.

[0182] In some implementations, for compounds or salts of formula (I), R 1 The 5- to 12-membered heterocycles are unsaturated heterocycles.

[0183] In some implementations, for compounds or salts of formula (I), R 1 The 5- to 12-membered heterocycles are saturated heterocycles.

[0184] In some implementations, for compounds or salts of formula (I), R 1 The 5- to 12-membered heterocycles are bridging heterocycles.

[0185] In some implementations, for compounds or salts of formula (I), R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0186] In some implementations, for compounds or salts of formula (I), R1 Selected from , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0187] In some implementations, for compounds or salts of formula (I), R 1 Selected from , and .

[0188] In some embodiments, for compounds or salts of formula (I), L is selected from C1-C4 alkylene groups.

[0189] In some embodiments, for compounds or salts of formula (I), L is selected from unsubstituted C1-C4 alkylene compounds.

[0190] In some implementations, for compounds or salts of formula (I), R 2 It is an L-heterocyclic ring, which is optionally bounded by one or more R-rings. 6 The substitution occurs when the heterocyclic portion is a bicyclic heterocycle. In some cases, the bicyclic heterocycle contains at least one nitrogen atom. In other cases, the bicyclic heterocycle contains at most one nitrogen atom.

[0191] In some implementations, for compounds or salts of formula (I), YR 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0192] In some implementations, for compounds or salts of formula (I), R 2 R 6 Each time it appears, it is independently selected from halogen, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl.

[0193] In some implementations, for compounds or salts of formula (I), R 2 R 6Each time it appears, it is independently selected from C1-C3 alkyl groups and halogens.

[0194] In some implementations, for compounds or salts of formula (I), YR 2 Selected from , and .

[0195] In some implementations, the compound is represented by the structure of formula (II): Equation (II) Or its pharmaceutically acceptable salt, wherein: M is selected from O, S, SO, SO2, and NR. 3 ; R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl-SO2R 20 C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from -LN(R) 21 )2、-L-OR 21 Heterocyclic rings, C l -C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R) 21 )2、-LC l -C6 haloalkyl, -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and -LC(=O)OC l -C6 alkyl, wherein heterocyclic, -L-NR 21 The aryl moiety of the C(O)-aryl group, the heterocyclic moiety of the -L-heterocyclic group, and the cycloalkyl moiety of the -L-cycloalkyl group are each optionally surrounded by one or more R groups. 6 Replacement, wherein the aryl moiety of -L-aryl and the heteroaryl moiety of -L-heteroaryl are each optionally replaced by one or more R 7 Replacement, and where R is a bond, O, or S. 2 Further selected from hydrogen; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbocyclic or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; R 3 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; n is selected from 0 to 2; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, including C1-C6 alkyl groups, ... 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; Each R 5 Independently selected from hydrogen or C1-C6 alkyl; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5-Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are each optionally substituted with one or more substituents selected from -C(O)H and OH, and wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl or -N(R) 5 )2; Each R 9 Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R)20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-NO2、=O、=NO(R 20 -CN, -NHCN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Halogenated alkyl groups; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and B is selected from heterocycles and carbocycles, wherein the heterocycle and carbocycle are each optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C. l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l-C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C 3- C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups.

[0196] In some implementations, for compounds or salts of formula (II), when M is NR 3 Y is O, and R 1 When it is piperazine, piperazine is reacted with one or more R 9 replace.

[0197] In some implementations, for compounds or salts of formula (II), R 2 Selected from -L-NR 21 S(O)2(R 21 ) and -LS(O)2N(R 21 )2.

[0198] In some implementations, for compounds or salts of formula (II), R 2 Selected from -LN(R) 21 )C(O)(OR 21 ) and -L-OC(O)N(R 21 )2.

[0199] In some implementations, for compounds or salts of formula (II), each R 21 Independently selected from hydrogen; C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10Halogenated alkyl groups, -OC 1-10 Alkyl and oxo substituents. In some cases, each R... 21 Independently selected from hydrogen; C 1-6 Alkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles. In some cases, each R... 21 Independently selected from hydrogen and C 1-6 alkyl.

[0200] In some implementations, for compounds or salts of formula (II), R 3 Selected from hydrogen and C 1-6 alkyl.

[0201] In some embodiments, for compounds or salts of formula (II), M is selected from O, NH, and NMe. In some cases, M is O. In some cases, M is selected from NH and NMe.

[0202] In some embodiments, for compounds or salts of formula (II), B is an optionally substituted 5- to 15-membered heterocycle or an optionally substituted C3-C ring. 15 Carbon ring. In some cases, B is an optionally substituted 5- to 15-membered heterocycle. In some cases, B is an optionally substituted C3-C... 15 Carbon ring. In some cases, B is an optionally substituted 8- to 15-membered heterocycle. In some cases, B is an optionally substituted C8-C... 15 Carbon ring.

[0203] In some embodiments, for compounds or salts of formula (II), B is an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C... 15 Fused carbon ring. In some cases, B is an optionally substituted 8- to 15-membered fused heterocycle. In some cases, B is an optionally substituted C8-C... 15 Fused carbon rings.

[0204] In some embodiments, for compounds of formula (II) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 The fused carbocyclic rings are each bicyclic or tricyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic rings are each bicyclic or tricyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic rings or optionally substituted C8-C... 15 Each of the fused carbon rings is either bicyclic or tricyclic.

[0205] In some embodiments, for compounds or salts of formula (II), for B, the optionally substituted 8- to 15-membered heterocycle contains at least one nitrogen atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at least one sulfur atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at most one nitrogen atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at most one sulfur atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at least two heteroatoms.

[0206] In some embodiments, for compounds or salts of formula (II), B, the heterocycle or the carbocyclic ring, is independently bicyclic. In some cases, the heterocycle is bicyclic. In some cases, the carbocyclic ring is bicyclic.

[0207] In some embodiments, for compounds or salts of formula (II), B, the heterocycle or the carbocyclic ring, is independently tricyclic. In some cases, the heterocycle is tricyclic. In some cases, the carbocyclic ring is tricyclic.

[0208] In some embodiments, for compounds or salts of formula (II), B is an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C... 15 Fused carbon rings are selected from , , , , , and Each of these may be optionally substituted by one or more substituents.

[0209] In some embodiments, for compounds of formula (I) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 Fused carbon rings are selected from , , , , , and Each of these may be optionally substituted by one or more substituents.

[0210] In some embodiments, for compounds of formula (II) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 Fused carbon rings are selected from and Each of these may be optionally substituted by one or more substituents.

[0211] In some embodiments, for compounds or salts of formula (II), for B, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogens, C1-C3 alkyl groups, -B(OR) 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group. In some cases, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OR) groups. 20 )2、-OH、-C(O)N(R 20 )2、=O、-CN、C 1-6 Alkoxy and C 2-6 Alkyne group. In some cases, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy and C 2-6 Alkynyl. In some cases, one or more optional substituents of the heterocycle and carbocyclic ring are independently selected each time they appear, from oxo, -NH2, -CN, halogen, and C1-C3 alkyl groups. In some cases, one or more optional substituents of the heterocycle or carbocyclic ring are independently selected, from oxo, -NH2, halogen, and C1-C3 alkyl groups.

[0212] In some embodiments, for compounds or salts of formula (II), B is selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0213] In some embodiments, for compounds or salts of formula (II), B is selected from... , , , , , , and .

[0214] In some implementations, for compounds or salts of formula (II), each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen. In some cases, each R... 4 Selected independently from C 1-6 Alkyl, oxo, and halogen.

[0215] In some implementations, for compounds or salts of formula (II), n is selected from 1 and 2. In some cases, n is 0.

[0216] In some implementations, Y is O for compounds or salts of formula (II).

[0217] In some implementations, for compounds or salts of formula (II), R 1 Selected from 5 to 12-membered heterocycles with optional substitution.

[0218] In some implementations, for compounds or salts of formula (II), R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0219] In some implementations, for compounds or salts of formula (II), R 1 Selected from C3-C 12A carbon ring and 5 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=NO(R 20 ), CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0220] In some implementations, for compounds or salts of formula (II), R 1 Selected from C3-C 12 Carbon rings and 5 to 12-membered heterocycles, each of which is optionally composed of one or more independently selected from -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)OR 20 and -OC(O)N(R 20 Substituents of )2.

[0221] In some implementations, for compounds or salts of formula (II), R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、C1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0222] In some implementations, for compounds or salts of formula (II), R 1 R 20 Selected from hydrogen and C 1-3 alkyl.

[0223] In some implementations, for compounds or salts of formula (II), R 1 The 5- to 12-membered heterocycles are unsaturated heterocycles.

[0224] In some implementations, for compounds or salts of formula (II), R 1 The 5- to 12-membered heterocycles are saturated heterocycles.

[0225] In some implementations, for compounds or salts of formula (II), R 1 The 5- to 12-membered heterocycles are bridging heterocycles.

[0226] In some implementations, for compounds or salts of formula (II), R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0227] In some implementations, for compounds or salts of formula (II), R 1 Selected from , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0228] In some implementations, for compounds or salts of formula (II), R 1 Selected from , and .

[0229] In some implementations, for compounds or salts of formula (II), R 1 Selected from optionally substituted saturated 6- to 7-membered heterocycles. In some cases, R 1 Selected from saturated 6-membered heterocycles with optional substitution. In some cases, R 1 Selected from Optionally, it is substituted. In some cases, one or more optional substituents are independently selected from halogens, -CN, -NHCN, C 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -CN, -NHCN, C... 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -CN, -NHCN, C... 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -NHCN and C. 1-6 Alkyl group. In some cases, R 1 Selected from It is selected from one or more of -NHCN and C 1-6 Alkyl substituents. In some cases, R 1 Selected from and .

[0230] In some implementations, for compounds or salts of formula (II), R 1 Selected from substituted saturated 6-membered heterocycles, wherein the substituted saturated 6-membered heterocycle is substituted with at least one -NHCN and optionally one or more C. 1-6 Alkyl substitution; M is O; n is 0; B is selected from optionally substituted 8- to 15-membered fused heterocycles and optionally substituted C8-C 15 Fused carbocyclic rings, each of which is optionally composed of one or more independently selected from halogen, oxo, -NH2, C1-C3 alkyl, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkyne substituent substitution; Y is O; R 2 Selected from -L-heterocycles, wherein the heterocyclic moiety is optionally composed of one or more elements independently selected from halogens, hydroxyl groups, C-elements, and L-heterocycles. l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl or -N(R) 5 Substituents of )2; and L is selected from C l -C4 alkylene. In some cases, R 1 Selected from and In some cases, B is selected from... , , , , , and In some cases, B is selected from... , and In some cases, B is... .

[0231] In some implementations, for compounds or salts of formula (II), each R 9 Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20)C(O)OR 20 -N(R) 20 )2、-NO2、=O、=NO(R 20 -CN, -NHCN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Halogenated alkyl groups. In some cases, each R... 9 Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-NO2、=O、=NO(R 20 -CN, -NHCN. In some cases, each R 9 Independently selected from halogens, -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-N(R 20 )2, -NO2, =O and =NO(R 20 In some cases, each R 9 Independently selected from halogens and -N(R) 20 )2.

[0232] In some embodiments, for compounds or salts of formula (II), each L is independently selected from optionally substituted C. l -C4 alkylene; and wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring, wherein the C3-C6 carbon ring is optionally permeated by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of the haloalkyl group. In some cases, the optional substituents of L are selected from C. l -C4 hydroxyalkyl, C l-C4 alkyl, C3-C6 carbon ring; and wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are optionally pertaining to one or more elements selected from halogens and C 1-6 Substitution of alkyl halogens.

[0233] In some embodiments, for compounds or salts of formula (II), each L is independently selected from the substituted C. l -C4 alkylene, wherein two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, the C3-C6 carbon ring is optionally replaced by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substitution of alkyl halogens.

[0234] In some embodiments, for compounds or salts of formula (II), each L is independently selected from substituted C. l -C4 alkylene, wherein the two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, each L is independently selected from substituted C3 alkylene, wherein the two substituents on the same carbon atom of L together form a C3 carbon ring. In some cases, each L is independently selected from... .

[0235] In some implementations, for compounds or salts of formula (II), R 2 Selected from -L-heterocycles, wherein the heterocyclic portion of the -L-heterocycle is optionally separated by one or more R... 6 Substitution. In some cases, the heterocycle is a saturated heterocycle. In some cases, the heterocycle has at least one nitrogen atom and at least one sulfur atom. In some cases, the heterocycle has at least one nitrogen atom. In some cases, the heterocycle has at least one sulfur atom.

[0236] In some implementations, for compounds or salts of formula (II), R 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0237] In some implementations, for compounds or salts of formula (II), YR 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0238] In some implementations, for compounds or salts of formula (II), YR 2 Selected from , and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0239] In some implementations, for compounds or salts of formula (II), YR 2 Selected from , , , , and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0240] In some implementations, for compounds or salts of formula (II), R 2 Selected from -L-saturated heterocycles, wherein the saturated heterocyclic portion of the -L-saturated heterocycle is optionally separated by one or more R 6 It is substituted and contains one nitrogen atom and one sulfur atom. In some cases, YR 2 Selected from , and The heterocyclic portion is optionally separated by one or more R 6 Replacement. In some cases, YR 2 Selected from , and The heterocyclic moiety is optionally substituted by one or more substituents selected from C1-C3 alkyl and oxo groups. In some cases, YR 2 Selected from , and In some cases, YR 2 Selected from , and .

[0241] In some implementations, for compounds or salts of formula (II), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN, C l -C3 aminoalkyl, -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, -N(R5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are each optionally substituted with -C(O)H and OH, and the heterocycles of the -CH2 heterocyclic groups are optionally substituted with oxo groups.

[0242] In some implementations, for compounds or salts of formula (II), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN and C l -C3 aminoalkyl.

[0243] In some implementations, for compounds or salts of formula (II), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 aminoalkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -N(R) 5 )2 and oxygenation. In some cases, each R 6 Independently selected from -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l-C3 aminoalkyl, C1-C3 alkoxy and -N(R 5 2. In some cases, each R 6 Selected independently from C l -C3 alkyl, C1-C3 alkoxy and -N(R 5 )2.

[0244] In some implementations, for compounds or salts of formula (II), R 6 Selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN and C l -C3 aminoalkyl. In some cases, R 6 Selected from halogens and C l -C3 alkyl. In some cases, R 6 It is a halogen. In some cases, R 6 C l -C3 alkyl. In some cases, R 6 Selected from halogens and C l -C3 alkyl. In some cases, R 6 Selected from methyl and fluorine.

[0245] In some implementations, for compounds or salts of formula (II), R 2 Selected from , and .

[0246] In some implementations, for compounds or salts of formula (II), YR 2 Selected from , and .

[0247] In some implementations, for compounds or salts of formula (II), YR 2 Selected from , , and .

[0248] In some implementations, for compounds or salts of formula (II), YR 2 for .

[0249] In some implementations, for compounds or salts of formula (II), YR 2 Selected from , , , , , and .

[0250] In some embodiments, for compounds or salts of formula (II), L is selected from C1-C4 alkylene groups.

[0251] In some embodiments, for compounds or salts of formula (II), L is selected from unsubstituted C1-C4 alkylene compounds.

[0252] In some implementations, for compounds or salts of formula (II), R 2 It is an -L-heterocyclic ring, which is optionally bounded by one or more R... 6 The substitution occurs when the heterocyclic portion is a bicyclic heterocycle. In some cases, the bicyclic heterocycle contains at least one nitrogen atom. In other cases, the bicyclic heterocycle contains at most one nitrogen atom.

[0253] In some implementations, for compounds or salts of formula (II), R 2 Selected from L-bicyclic heterocycles, wherein the bicyclic heterocycle is optionally separated by one or more R 6 replace.

[0254] In some implementations, for compounds or salts of formula (II), R 2 Selected from L-pyrrolizine, wherein the pyrrolizine is optionally reacted with one or more R 6 replace.

[0255] In some implementations, for compounds or salts of formula (II), YR 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0256] In some implementations, for compounds or salts of formula (II), R 2 R 6 Each time it appears, it is independently selected from halogen, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl. In some cases, R 2 R 6 Each time it appears, it is independently selected from C1-C3 alkyl groups and halogens. In some cases, YR 2 Selected from , and .

[0257] In some embodiments, for compounds or salts of formula (II), M is selected from NR. 3 In some cases, M is selected from NH and NMe. In some cases, M is selected from NMe and NCH2CH3. In some cases, M is NMe. In some cases, M is selected from C. 1-6 Cyanoalkyl. In some cases, M is selected from C2-cyanoalkyl. In some cases, M is selected from NH. In some cases, R 3 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl and C 1-6 Haloalkyl. In some cases, R 3 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl and C 1-6 Haloalkyl. In some cases, R 3 Selected from C 1-6 Alkyl, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl and C 1-6 Haloalkyl. In some cases, R 3 Selected from C 2-6 Alkyl, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl and C 1-6 Haloalkyl. In some cases, R 3 Selected from C 1-6 Alkyl-N(R) 202. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl and C 1-6 Haloalkyl. In some cases, R 3 Selected from C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl and C 1-6 Haloalkyl. In some cases, R 3 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl and C 1-6 Haloalkyl. In some cases, R 3 Selected from C 1-6 Alkoxyalkyl, C 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, R 3 for In some cases, R 3 Selected from C 2-6 alkyl.

[0258] In some implementations, for compounds or salts of formula (II), M is NR. 3 B is selected from and Each of them is arbitrarily replaced; n is 0; Y is 0; R 2 Selected from L-heterocycles. The heterocycle may optionally be separated by one or more R... 6 Replace; R 1 Selected from and , which is optionally replaced. In some cases, R 1 for It may optionally be selected independently by one or more halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )2、-C(O)R20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Substituents in the alkynyl group. In some cases, R 1 for In some cases, R 1 for In some cases, R 1 for In some cases, R 1 for In some cases, the L-heterocyclic ring is bicyclic. In some cases, the L-heterocyclic ring is monocyclic. In some cases, L is selected from C1-C4 alkylene oxides. In some cases, L is selected from unsubstituted C1-C4 alkylene oxides. In some cases, L is independently selected from substituted C1-C4 alkylene oxides. l -C4 alkylene, wherein two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, YR 2 Selected from , , , and In some cases, YR 2 Selected from and In some cases, B is selected from... and It is substituted by one or more substituents. In some cases, B is... It is substituted by one or more substituents. In some cases, B is selected from... It is substituted by one or more substituents. In some cases, for B, one or more substituents are independently selected from halogens, oxo groups, -NH2, C1-C3 alkyl groups, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, -OC. l -C3 haloalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkynyl group. In some cases, B is substituted with at least one halogen. In some cases, B is substituted with at least one chlorine. In some cases, B is substituted with at least one fluorine. In some cases, B is selected from... , , , , , , , , , , , , , , and In some cases, B is selected from... It is selected from one or more halogens, -OC l -C3 haloalkyl and C 1-6 Substituents of haloalkyl groups. In some cases, B is... It is substituted by one or more substituents selected from halogens. In some cases, B is selected from... , , , , and In some cases, B is... It is substituted with one or more substituents selected from fluorine. In some cases, B is selected from... , and In some cases, B is... It is substituted with one or more substituents selected from chlorine. In some cases, B is selected from... and In some cases, R 3 Selected from hydrogen and C 1-6 Alkyl group. In some cases, R 3 Selected from C 1-6 Alkyl group. In some cases, R 3 It is methyl. In some cases, each R 6 Selected from halogens, oxometalates, and C 1-6 Alkyl groups. In some cases, each R 6 Selected from halogens and C 1-6 Alkyl groups. In some cases, each R... 6 Selected from halogens. In some cases, R 1 Selected from and In some cases, R 1 for In some cases, B is... .

[0259] In some implementations, the compound is represented by the structure of formula (III): Equation (III) Or its pharmaceutically acceptable salt, wherein: R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; R 2 Selected from -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and L-bicyclic heterocycles, wherein the bicyclic heterocycle is optionally separated by one or more R 6 replace; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbocyclic or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; n is selected from 0 to 3; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, including C1-C6 alkyl groups, ... 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; B is selected from heterocycles and carbocycles, wherein the heterocycle or carbocycle is optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated Cl -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; Y is selected from bonds, O, S, and NR. 5 ; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l-C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl group of the -C3 alkyl)phenyl group is optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and Each R 5 It is independently selected from hydrogen or C1-C6 alkyl.

[0260] In some implementations, for compounds or salts of formula (III), R 1 Selected from C3-C 12 A carbon ring and 5 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -C(O)N(R) 20 )2、-C(O)NR 20 -OR 20 -S(O)2N(R) 20 )2、-NR20 S(O)2R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=NO(R 20 -CN, -NHCN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0261] In some implementations, for compounds or salts of formula (III), R 2 Selected from -L-NR 21 S(O)2(R 21 ) and -LS(O)2N(R 21 )2.

[0262] In some implementations, for compounds or salts of formula (III), R 2 Selected from -LN(R) 21 )C(O)(OR 21 ) and -L-OC(O)N(R 21 )2.

[0263] In some implementations, for compounds or salts of formula (III), each R 21 Independently selected from hydrogen; C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl and oxo substituents. In some cases, each R... 21 Independently selected from hydrogen; C 1-6 Alkyl, C 3-12Carbon rings and 3 to 12-membered heterocycles. In some cases, each R... 21 Independently selected from hydrogen and C 1-6 alkyl.

[0264] In some implementations, for compounds or salts of formula (III), R 2 Selected from L-bicyclic heterocycles, wherein the bicyclic heterocycle is optionally separated by one or more R 6 replace.

[0265] In some implementations, for compounds or salts of formula (III), R 2 Selected from L-pyrrolizine, wherein the pyrrolizine is optionally reacted with one or more R 6 replace.

[0266] In some embodiments, for compounds or salts of formula (III), B is an optionally substituted 5- to 15-membered heterocycle or an optionally substituted C3-C ring. 15 Carbocyclic ring. In some cases, B is an optionally substituted 5- to 15-membered heterocycle. In some cases, B is an optionally substituted 8- to 15-membered heterocycle. In some cases, B is an optionally substituted C3-C... 15 Carbon ring. In some cases, B is an optionally substituted C8-C ring. 15 Carbon ring.

[0267] In some embodiments, for compounds or salts of formula (III), B is an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C... 15 Fused carbon ring. In some cases, B is an optionally substituted 8- to 15-membered fused heterocycle. In some cases, B is an optionally substituted C8-C... 15 Fused carbon rings.

[0268] In some embodiments, for compounds or salts of formula (III), for B, the optionally substituted 8- to 15-membered heterocycle contains at least one nitrogen atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at least one sulfur atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at most one nitrogen atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at most one sulfur atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at least two heteroatoms.

[0269] In some embodiments, for compounds of formula (III) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 The fused carbocyclic rings are each bicyclic or tricyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic rings are each bicyclic or tricyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic rings or optionally substituted C8-C... 15The fused carbon rings are either bicyclic or tricyclic.

[0270] In some embodiments, for compounds or salts of formula (III), B, the heterocycle or the carbocyclic ring, is independently bicyclic. In some cases, the heterocycle is bicyclic. In some cases, the carbocyclic ring is bicyclic.

[0271] In some embodiments, for compounds or salts of formula (III), B, the heterocycle or the carbocyclic ring, is independently tricyclic. In some cases, the heterocycle is tricyclic. In some cases, the carbocyclic ring is tricyclic.

[0272] In some embodiments, for compounds or salts of formula (III), B is an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C... 15 Fused carbon rings are selected from , , , , , and Each of these may be optionally substituted by one or more substituents.

[0273] In some embodiments, for compounds of formula (III) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 Fused carbon rings are selected from , , , , , and Each of these may be optionally substituted by one or more substituents.

[0274] In some embodiments, for compounds of formula (III) or salts, for B, an optionally substituted 8- to 15-membered fused heterocycle or an optionally substituted C8-C 15 Fused carbon rings are selected from and Each of these may be optionally substituted by one or more substituents.

[0275] In some embodiments, for compounds or salts of formula (III), for B, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogens, C1-C3 alkyl groups, -B(OR) 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group. In some cases, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OR) groups. 20 )2、-OH、-C(O)N(R 20 )2、=O、-CN、C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkyne group. In some cases, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkynyl. In some cases, one or more optional substituents of the heterocycle and carbocyclic ring are independently selected each time they appear, from oxo, -NH2, -CN, halogen, and C1-C3 alkyl groups. In some cases, one or more optional substituents of the heterocycle or carbocyclic ring are independently selected, from oxo, -NH2, halogen, and C1-C3 alkyl groups.

[0276] In some embodiments, for compounds or salts of formula (III), B is selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0277] In some embodiments, for compounds or salts of formula (III), for B, one or more optional substituents of the heterocyclic or carbocyclic ring are independently selected from oxo, -NH2, halogen, C1-C3 alkyl.

[0278] In some embodiments, for compounds or salts of formula (III), B is selected from... , , , , , , and .

[0279] In some implementations, for compounds or salts of formula (III), each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen. In some cases, each R... 4 Selected independently from C 1-6 Alkyl, oxo, and halogen.

[0280] In some implementations, for compounds or salts of formula (III), n is selected from 1 and 2. In some cases, n is 0.

[0281] In some implementations, Y is O for compounds or salts of formula (III).

[0282] In some implementations, for compounds or salts of formula (III), R 1 Selected from 5 to 12-membered heterocycles with optional substitution.

[0283] In some implementations, for compounds or salts of formula (III), R 1 Selected from C3-C 12 A carbon ring and 5 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20-N(R) 20 )2、-C(O)R 20 C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=NO(R 20 ), CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0284] In some implementations, for compounds or salts of formula (III), R 1 Selected from C3-C 12 A carbon ring and 5 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=NO(R 20 ), CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0285] In some implementations, for compounds or salts of formula (III), R1 Selected from C3-C 12 Carbon rings and 5 to 12-membered heterocycles, each of which is optionally composed of one or more independently selected from -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)OR 20 and -OC(O)N(R 20 Substituents of )2.

[0286] In some implementations, for compounds or salts of formula (III), R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0287] In some implementations, for compounds or salts of formula (III), R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0288] In some implementations, for compounds or salts of formula (III), R 1 R 20 Selected from hydrogen and C 1-3 alkyl.

[0289] In some implementations, for compounds or salts of formula (III), R 1 The 5- to 12-membered heterocycles are unsaturated heterocycles.

[0290] In some implementations, for compounds or salts of formula (III), R 1 The 5- to 12-membered heterocycles are saturated heterocycles.

[0291] In some implementations, for compounds or salts of formula (III), R 1 The 5- to 12-membered heterocycles are bridging heterocycles.

[0292] In some implementations, for compounds or salts of formula (III), R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0293] In some implementations, for compounds or salts of formula (III), R 1 Selected from , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

[0294] In some implementations, for compounds or salts of formula (III), R 1 Selected from , and .

[0295] In some implementations, for compounds or salts of formula (III), R 1 Selected from optionally substituted saturated 6- to 7-membered heterocycles. In some cases, R 1 Selected from saturated 6-membered heterocycles with optional substitution. In some cases, R 1 Selected from Optionally, it is substituted. In some cases, one or more optional substituents are independently selected from halogens, -CN, -NHCN, C 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -CN, -NHCN, C... 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -CN, -NHCN, C... 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -NHCN and C. 1-6 Alkyl group. In some cases, R 1 Selected from It is selected from one or more of -NHCN and C 1-6 Alkyl substituents. In some cases, R 1 Selected from and .

[0296] In some implementations, for compounds or salts of formula (III), R 1 Selected from substituted saturated 6-membered heterocycles, wherein the substituted saturated 6-membered heterocycle is substituted with at least one -NHCN and optionally one or more C. 1-6 Alkyl substitution; M is O; n is 0; B is selected from optionally substituted 8- to 15-membered fused heterocycles and optionally substituted C8-C 15 Fused carbocyclic rings, each of which is optionally composed of one or more independently selected from halogen, oxo, -NH2, C1-C3 alkyl, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkyne substituent substitution; Y is O; R 2 Selected from -L-bicyclic heterocycles, wherein the bicyclic heterocycle moiety is optionally composed of one or more elements independently selected from halogens, hydroxyl groups, C... l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl or -N(R)5 Substituents of )2; and L is selected from C l -C4 alkylene. In some cases, R 1 Selected from and In some cases, B is selected from... , , , , , and In some cases, B is selected from... , and In some cases, B is... .

[0297] In some embodiments, for compounds or salts of formula (III), L is selected from C1-C4 alkylene groups.

[0298] In some embodiments, for compounds or salts of formula (III), each L is independently selected from optionally substituted C. l -C4 alkylene; and wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring, wherein the C3-C6 carbon ring is optionally permeated by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of the haloalkyl group. In some cases, the optional substituents of L are selected from C. l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring; and wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are optionally pertaining to one or more elements selected from halogens and C 1-6 Substitution of alkyl halogens.

[0299] In some embodiments, for compounds or salts of formula (III), each L is independently selected from the substituted C. l -C4 alkylene, wherein two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, the C3-C6 carbon ring is optionally replaced by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substitution of alkyl halogens.

[0300] In some embodiments, for compounds or salts of formula (III), each L is independently selected from substituted C. l -C4 alkylene, wherein the two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, each L is independently selected from substituted C3 alkylene, wherein the two substituents on the same carbon atom of L together form a C3 carbon ring. In some cases, each L is independently selected from... .

[0301] In some implementations, for compounds or salts of formula (III), R 2 Selected from -L-heterocycles, wherein the heterocyclic portion of the -L-heterocycle is optionally separated by one or more R... 6 Substitution. In some cases, the heterocycle is a saturated heterocycle. In some cases, the heterocycle has at least one nitrogen atom and at least one sulfur atom. In some cases, the heterocycle has at least one nitrogen atom. In some cases, the heterocycle has at least one sulfur atom.

[0302] In some implementations, for compounds or salts of formula (III), R 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0303] In some implementations, for compounds or salts of formula (III), YR 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0304] In some implementations, for compounds or salts of formula (III), YR 2 Selected from , and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0305] In some implementations, for compounds or salts of formula (III), YR 2 Selected from , , , , and The heterocyclic portion is optionally separated by one or more R 6 replace.

[0306] In some implementations, for compounds or salts of formula (III), R 2Selected from -L-saturated heterocycles, wherein the saturated heterocyclic portion of the -L-saturated heterocycle is optionally separated by one or more R 6 It is substituted and contains one nitrogen atom and one sulfur atom. In some cases, YR 2 Selected from , and The heterocyclic portion is optionally separated by one or more R 6 Replacement. In some cases, YR 2 Selected from , and The heterocyclic moiety is optionally substituted by one or more substituents selected from C1-C3 alkyl and oxo groups. In some cases, YR 2 Selected from , and In some cases, YR 2 Selected from , and .

[0307] In some implementations, for compounds or salts of formula (III), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN, C l -C3 aminoalkyl, -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l-C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are each optionally substituted with -C(O)H and OH, and the heterocycles of the -CH2 heterocyclic groups are optionally substituted with oxo groups.

[0308] In some implementations, for compounds or salts of formula (III), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN and C l -C3 aminoalkyl.

[0309] In some implementations, for compounds or salts of formula (III), each R 6 Independently selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 aminoalkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -N(R) 5 )2 and oxygenation. In some cases, each R 6 Independently selected from -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 aminoalkyl, C1-C3 alkoxy and -N(R 5 2. In some cases, each R 6 Selected independently from C l -C3 alkyl, C1-C3 alkoxy and -N(R 5 )2.

[0310] In some implementations, for compounds or salts of formula (III), R 6 Selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, -CN and C l -C3 aminoalkyl. In some cases, R 6 Selected from halogens and C l -C3 alkyl. In some cases, R 6 It is a halogen. In some cases, R6 C l -C3 alkyl. In some cases, R 6 Selected from halogens and C l -C3 alkyl. In some cases, R 6 Selected from methyl and fluorine.

[0311] In some implementations, for compounds or salts of formula (III), R 2 Selected from , and .

[0312] In some implementations, for compounds or salts of formula (III), YR 2 Selected from , and .

[0313] In some implementations, for compounds or salts of formula (III), YR 2 Selected from , , and .

[0314] In some implementations, for compounds or salts of formula (III), YR 2 for .

[0315] In some embodiments, for compounds or salts of formula (III), L is selected from unsubstituted C1-C4 alkylene compounds.

[0316] In some implementations, for compounds or salts of formula (III), YR 2 Selected from The heterocyclic portion is optionally separated by one or more R 6 replace.

[0317] In some implementations, for compounds or salts of formula (III), R 2 R 6 Each time it appears, it is independently selected from halogen, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl.

[0318] In some implementations, for compounds or salts of formula (III), R 2 R 6 Each time it appears, it is independently selected from C1-C3 alkyl groups and halogens.

[0319] In some implementations, for compounds or salts of formula (III), YR 2 Selected from and .

[0320] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The carbon rings are selected from C3-C 12 Carbon rings, C3-C 10 Carbon rings, C3-C9 carbon rings, C3-C8 carbon rings, or C3-C6 carbon rings. In some cases, R... 1 The carbon rings are selected from C3-C 12 Carbon rings, C4-C 12 Carbon rings, C5-C 12 Carbon rings, C6-C 12 Carbon ring, C7-C 12 Carbon rings, C8-C 12 Carbon ring or C9-C 12 Carbon ring.

[0321] In some implementations, for compounds of formula (I), R 1 The heterocycles are 5- to 12-membered, 6- to 12-membered, 7- to 12-membered, or 8- to 12-membered heterocycles. In some cases, R... 1 The heterocycles are 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, or 5- to 8-membered heterocycles. In some cases, R... 1 The heterocycles are 6- to 11-membered, 6- to 10-membered, 6- to 9-membered, or 6- to 8-membered heterocycles. In some cases, R... 1 The heterocycles are 7- to 11-membered, 7- to 10-membered, 7- to 9-membered, or 7- to 8-membered heterocycles. In some cases, R... 1 The heterocycle is a 5- to 6-membered heterocycle or a 5- to 9-membered heterocycle. In some cases, R 1 The heterocycle is an 8- to 9-membered heterocycle. In some cases, R 1 The heterocycle is saturated. The heterocycle can be optionally substituted as described elsewhere in this document.

[0322] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The heterocycles are 5- to 12-membered monocyclic heterocycles, 6- to 12-membered monocyclic heterocycles, 7- to 12-membered monocyclic heterocycles, or 8- to 12-membered monocyclic heterocycles. In some cases, R... 1 The heterocycles are 5- to 11-membered monocyclic heterocycles, 5- to 10-membered monocyclic heterocycles, 5- to 9-membered monocyclic heterocycles, or 5- to 8-membered monocyclic heterocycles. In some cases, R... 1The heterocycles are 6- to 11-membered monocyclic heterocycles, 6- to 10-membered monocyclic heterocycles, 6- to 9-membered monocyclic heterocycles, or 6- to 8-membered monocyclic heterocycles. In some cases, R... 1 The heterocycles are 7- to 11-membered monocyclic heterocycles, 7- to 10-membered monocyclic heterocycles, 7- to 9-membered monocyclic heterocycles, or 7- to 8-membered monocyclic heterocycles. In some cases, R... 1 The heterocycle is a 5- to 6-membered monocyclic heterocycle or a 5- to 9-membered monocyclic heterocycle. In some cases, R 1 The heterocycle is an 8- to 9-membered monocyclic heterocycle. In some cases, R 1 The heterocycle is saturated. Monocyclic heterocycles can be optionally substituted as described elsewhere in this document.

[0323] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The heterocyclic rings are 5- to 12-membered bridged heterocyclic rings, 6- to 12-membered bridged heterocyclic rings, 7- to 12-membered bridged heterocyclic rings, or 8- to 12-membered bridged heterocyclic rings. In some cases, R 1 The heterocyclic rings are 5- to 11-member bridged heterocyclic rings, 5- to 10-member bridged heterocyclic rings, 5- to 9-member bridged heterocyclic rings, or 5- to 8-member bridged heterocyclic rings. In some cases, R 1 The heterocyclic rings are 6- to 11-member bridged heterocyclic rings, 6- to 10-member bridged heterocyclic rings, 6- to 9-member bridged heterocyclic rings, or 6- to 8-member bridged heterocyclic rings. In some cases, R 1 The heterocyclic rings are 7- to 11-member bridged heterocyclic rings, 7- to 10-member bridged heterocyclic rings, 7- to 9-member bridged heterocyclic rings, or 7- to 8-member bridged heterocyclic rings. In some cases, R 1 The heterocycles are 5- to 6-membered bridged heterocycles or 5- to 9-membered bridged heterocycles. In some cases, R 1 The heterocycle is an 8- to 9-membered bridging heterocycle. In some implementations, R 1 The heterocycle is saturated. The bridging heterocycle can be optionally substituted, as described elsewhere in this document.

[0324] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 It is a 5- to 9-membered heterocycle, containing at most one nitrogen atom. In some embodiments, R 1 The heterocycles are selected from 5 to 9 members, each of which is optionally substituted.

[0325] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The heterocycle contains at most one nitrogen atom. In some embodiments, R 1 The heterocycle contains at most one heteroatom. In some embodiments, R 1The heterocycle contains at most two heteroatoms. In some cases, the heteroatoms are selected from nitrogen, oxygen, and sulfur. In some cases, the heterocycle is a monocyclic heterocycle or a bridged heterocycle. In some cases, the heterocycle is a monocyclic heterocycle. In some cases, the heterocycle is a bridged heterocycle. In some cases, the heterocycle is selected from... and In some cases, heterocycles are selected from... , , , and In some cases, bridging heterocycles are selected from... , and Heterocyclic rings can be substituted arbitrarily, as described elsewhere in this document.

[0326] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The spiroheterocycle contains at most one nitrogen atom. In some embodiments, R 1 The spiroheterocycle contains at most two heteroatoms. In some embodiments, R 1 The spiroheterocycle contains at most three heteroatoms. In some embodiments, R 1 The spiroheterocycle contains at most one heteroatom. In some cases, R 1 The spirocyclic heterocycle contains at least two heteroatoms. In some cases, R 1 The spirocyclic heterocycle contains at least three heteroatoms. In some cases, R 1 The spirocyclic heterocycle contains at least four heteroatoms. In some cases, R 1 The spiroheterocycle contains at least two nitrogen atoms. In some embodiments, R 1 The spiroheterocycle contains at most one heteroatom. In some cases, R 1 The spiroheterocycle contains at most one sulfur atom. In some cases, the heteroatom is selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 The spiroheterocycles are selected from , , , , , , , , , , , , , , , and In some implementations, R 1The spiroheterocycles are selected from and Spirohexanes can be optionally substituted, as described elsewhere in this document.

[0327] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from optionally substituted 7- to 8-membered spiroheterocycles. In some cases, R 1 Selected from optionally substituted 7-membered spiroheterocycles. In some cases, R 1 Selected from arbitrarily substituted 8-membered spiroheterocycles.

[0328] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The fused heterocycles are 6- to 12-membered fused heterocycles, 7- to 12-membered fused heterocycles, or 8- to 12-membered fused heterocycles. In some cases, R 1 The fused heterocycles are 6- to 11-membered fused heterocycles, 6- to 10-membered fused heterocycles, 6- to 9-membered fused heterocycles, or 6- to 8-membered fused heterocycles. In some cases, R 1 The fused heterocycles are 7- to 11-membered fused heterocycles, 7- to 10-membered fused heterocycles, 7- to 9-membered fused heterocycles, or 7- to 8-membered fused heterocycles. In some cases, R 1 The fused heterocycles are 8 to 11-membered fused heterocycles. In some cases, R 1 The fused heterocycle is a 6-membered fused heterocycle. The fused heterocycle can be optionally substituted as described elsewhere in this document.

[0329] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The fused heterocycles are selected from 6-, 9-, 10-, 11-, and 12-membered fused heterocycles. In some cases, R... 1 The fused heterocycles are selected from 9- to 12-membered fused heterocycles. In some cases, R 1 The fused heterocycle is selected from 10 to 12-membered fused heterocycles. The fused heterocycle may optionally be composed of one or more elements independently selected from halogens, -OR 20 -N(R) 20 )2、-NO2、=O、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents. The fused heterocycle is optionally replaced by one or more groups independently selected from halogens, -OR 20 -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl substituents.

[0330] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The fused heterocycle contains at most one nitrogen atom. In some embodiments, R 1 The fused heterocycle contains at most one heteroatom. In some cases, the heteroatom is selected from nitrogen, oxygen, and sulfur. In some cases, the fused heterocycle is... The fused heterocycle can be optionally substituted, as described elsewhere in this document.

[0331] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The components are selected from C6-C7 carbon rings, 5- to 10-membered heterocycles, 7- to 8-membered spiroheterocycles, and 6, 9, 10, 11, and 12-membered fused heterocycles, each of which may be optionally substituted.

[0332] In some implementations, for compounds of formula (I), R 1 Selected from C6-C7 carbon rings, 5- to 10-membered heterocycles, 7- to 8-membered spirocyclic heterocycles, and 6, 8- to 12-membered fused heterocycles, each of which is optionally selected independently by one or more halogens, -OR 20 -N(R) 20 )2、-NO2、=O、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl substituents.

[0333] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from C6-C7 carbon rings, 5- to 10-membered heterocycles, 7- to 8-membered spirocyclic heterocycles, and 6, 8- to 12-membered fused heterocycles, each of which is optionally selected independently by one or more halogens, -OR 20 -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl substituents.

[0334] In some implementations, for compounds or salts of formula (I), (II), or (III), for R 1 -OR20 and -N(R) 20 )2 of R 20 Selected from hydrogen and C 1-6 alkyl.

[0335] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from C6-C7 carbon rings and 5- to 10-membered heterocycles, each of which may be optionally substituted. In some cases, the heterocycle contains at most one nitrogen atom. In some cases, R 1 Selected from C6-C7 carbon rings, each of which may be optionally substituted.

[0336] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 One or more optional substituents are independently selected from halogens, -OR 20 -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Haloalkyl, -N(R) 20 )C(O)N(R 20 )2 and C 1-6 alkyl.

[0337] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 One or more optional substituents are independently selected from halogens, -OR 20 -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl group. In some cases, R 1 One or more optional substituents are independently selected from -OR 20 -N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents of R1 are independently selected from -OR. 20 -N(R) 20 2. C 1-6 aminoalkyl and C 1-6 Hydroxyalkyl. In some cases, one or more optional substituents of R1 are independently selected from -OR.20 -N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkyl and C 1-6 Hydroxyalkyl. In some cases, R 1 One or more optional substituents are independently selected from -OR 20 -N(R) 20 )2 and C 1-6 Alkyl group. In some cases, R 1 One or more optional substituents are independently selected from -N(R) 20 )C(O)N(R 20 )2.

[0338] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from C3-C 12 A carbon ring and a 5- to 12-membered heterocycle, wherein the 5- to 12-membered heterocycle contains at most one nitrogen atom and optionally one or more additional heteroatoms selected from oxygen, boron, and sulfur; or R 1 Further selected from 7-, 8-, 10-, and 11-membered spirochetes and 6-, 9-, 10-, 11-, and 12-membered fused heterocycles, wherein C3-C 12 The carbon ring, 5- to 12-membered heterocycles, 7, 8, 10, 11-membered spirocyclic heterocycles, and 6, 9, 10, 11, and 12-membered fused heterocycles are each optionally selected independently from one or more halogens, -OR 20 -SR 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -NO2, =O, =N(R) 20 -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0339] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from C3-C 12Carbon rings and 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles contain at most one nitrogen atom and optionally one or more additional heteroatoms selected from oxygen, boron, and sulfur; or R 1 Further selected from 7-, 8-, 10-, and 11-membered spirochetes and 6-, 9-, 10-, 11-, and 12-membered fused heterocycles, wherein C3-C 12 The carbon ring, 5- to 12-membered heterocycles, 7, 8, 10, 11-membered spirocyclic heterocycles, and 6, 9, 10, 11, and 12-membered fused heterocycles are each optionally selected independently by one or more halogens, -B(OR) 20 )2、-OR 20 -SR 20 -N(R) 20 ), S(O)2(R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -NO2, =O, =S, =N(R) 20 -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0340] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 5- to 10-membered heterocycles, 7, 8, 10, 11-membered spiroheterocycles, and 6, 9, 10, 11, and 12-membered fused heterocycles, and each of which is optionally selected by one or more independently selected from halogens, -N(R) 20 2. C 1-6 Alkyl, -OR 20 -N(R) 20 )C(O)N(R 20 2. -B(OR) 20 )2、-N(R 20 )C(O)N(R 20 )2、=O、C 1-6 Hydroxyalkyl, halogen, -N(R) 20 )C(O)R 20 -N(R)20 )S(O)2(R 20 ) and C 1-6 Substituents of aminoalkyl groups.

[0341] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 5- to 10-membered heterocycles, 7, 8, 10, 11-membered spiroheterocycles, and 6, 9, 10, 11, and 12-membered fused heterocycles, and each of which is optionally selected by one or more independently selected from halogens, -N(R) 20 2. C 1-6 Alkyl, -OR 20 -N(R) 20 )C(O)N(R 20 2. -B(OR) 20 2. C 1-6 Cyanoalkyl, -N(R) 20 )C(O)N(R 20 )2、=O、C 1-6 Hydroxyalkyl, halogen, -N(R) 20 )C(O)R 20 -N(R) 20 ), S(O)2(R 20 ) and C 1-6 Substituents of aminoalkyl groups. In some cases, R 1 Selected from , , , , , , , , , , , and Each of which is optionally selected independently from one or more halogens, -N(R) 20 2. C 1-6 Alkyl, -OR 20 -N(R) 20 )C(O)N(R 20 2. -B(OR) 20 2. C 1-6 Cyanoalkyl, -N(R) 20 )C(O)N(R 20 )2、=O、C 1-6 Hydroxyalkyl, halogen, -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2(R20 ) and C 1-6 Substituents of aminoalkyl groups. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0342] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 5- to 10-membered heterocycles, wherein the 5- to 10-membered heterocycles are optionally selected independently from one or more of -OR 20 -N(R) 20 2. C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C1-6 aminoalkyl, -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)R 20 and -B(OR) 20 Substituents of )2. In some cases, R 1 Selected from , , , and Each of these may be optionally selected independently from one or more -OR 20 -N(R) 20 2. C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)R 20 and -B(OR) 20 Substituents of )2.

[0343] In some implementations, for compounds of formula (I), formula (II), or formula (III), R 1 Selected from , , , , , , , , , , , and .

[0344] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 5- to 10-membered heterocycles, wherein the 5- to 10-membered heterocycles are optionally selected by one or more independently selected from -N(R) 20 )2、-OR 20 and C 1-6 Alkyl substituents. In some cases, the 5- to 10-membered heterocycle is optionally replaced by one or more independently selected from -OR 20 and C 1-6 Alkyl substituents. In some embodiments, for compounds of formula (I), (II), or (III), R 1 Selected from and Each of these may be optionally selected independently from one or more -OR 20 and C 1-6 Alkyl substituents. In some cases, R 1 Selected from , and .

[0345] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , and Each of these can be arbitrarily replaced.

[0346] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , and Each of these may optionally be selected independently from one or more of -OH, -CN, oxo, C 1-6 Substitution of cyanoalkyl groups.

[0347] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , , , , , , and .

[0348] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , and Each of these can be arbitrarily replaced.

[0349] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , , and Each of these can be arbitrarily replaced.

[0350] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , , , , , , , , , , , , , , and Each of these can be arbitrarily replaced.

[0351] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 For being arbitrarily replaced .

[0352] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0353] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , , , and In some cases, R 1 for In some cases, R 1 for .

[0354] In some embodiments, for compounds or salts of formula (I), (II), or (III), wherein R 1 The 5- to 12-membered heterocycles are unsaturated and bridged heterocycles. In some cases, R... 1 Selected from optionally substituted 7- to 8-membered unsaturated and bridged heterocyclic rings. In some cases, R 1 Selected from .

[0355] In some implementations, for compounds of formula (I) or formula (II), R 1Selected from 5- to 10-membered heterocycles, 7, 8, 10, 11-membered spiroheterocycles, and 6, 9, 10, 11, and 12-membered fused heterocycles, and each of which is optionally selected by one or more independently selected from halogens, -N(R 20 2. C 1-6 Alkyl, -OR 20 -N(R) 20 )C(O)N(R 20 2. -B(OR) 20 2. C 1-6 Cyanoalkyl, -N(R) 20 )C(O)N(R 20 )2、=O、C 1-6 Hydroxyalkyl, halogen, -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2(R 20 ) and C 1-6 Substituents of aminoalkyl groups; R 3 Naphthalene is optionally selected from one or more elements independently chosen from halogens, -OH, -NH2, -NO2, =O, C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups; R 4 Selected from hydrogen, halogen or C l -C3 alkyl; Y is O; L is independently C l -C4 alkylene; R 2 Selected from -L-heterocycles, wherein the heterocyclic moiety is optionally composed of one or more elements independently selected from halogens, hydroxyl groups, C-elements, and L-heterocycles. l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl or -N(R) 5 Substituents of )2. In some cases, YR 2 Selected from and The heterocyclic portion is optionally replaced.

[0356] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The heterocycle is selected from 5- to 12-membered unsaturated heterocycles with optional substitutions, wherein the heterocycle has at most one nitrogen atom. In some cases, the 5- to 12-membered unsaturated heterocycle has at least one nitrogen atom. In some cases, the 5- to 12-membered unsaturated heterocycle has at most one nitrogen atom.

[0357] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 6- to 7-membered heterocycles. In some cases, R 1 Selected from 7-membered heterocycles. In some cases, R 1 Selected from 6-membered heterocycles. In some cases, the 6- to 7-membered heterocycle contains only one nitrogen atom and optional one or more additional heteroatoms selected from oxygen and sulfur. In some cases, the optional one or more additional heteroatoms are selected from sulfur. In some cases, the optional one or more additional heteroatoms are selected from oxygen. In some cases, the 6- to 7-membered heterocycle contains only one nitrogen atom and no additional heteroatoms. In some cases, the 6- to 7-membered heterocycle is a non-aromatic 6- to 7-membered heterocycle. In some cases, R... 1 The 6- to 7-membered heterocycles are bonded to formula (I) via only one nitrogen atom. In some cases, R 1 The 6- to 7-membered heterocycles are bonded to formula (II) via only one nitrogen atom. In some cases, R 1 The 6- to 7-membered heterocycles are bonded to formula (III) via only one nitrogen atom. In some cases, R 1 Selected from , , , , , and Each of them is replaced. In some cases, R 1 Selected from , , , , , and Each of them is replaced. In some cases, R 1 The substituents are each selected from one or more halogens, -OR 20 -SR 20 -N(R) 20 )2, -NHCN, -NO2, =O, -CN, C 1-6 fluoroalkyl and C 2-6 Alkyne group; and further optionally, one or more groups independently selected from -C(O)N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkyl and C 2-6 Alkenyl substituent substitution. In some cases, R 1 The substituents are each selected from one or more halogens, -OR 20 -N(R)20 2. -NHCN, =O, -CN and C 2-6 Alkyne group; and further optionally, one or more groups independently selected from -C(O)N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl and C 1-6 Alkyl substituents. In some cases, R 1 The substituents are each selected from one or more halogens, -OH, -NHCN, =O, -CN, and C. 2-6 Alkyne group; and optionally further selected independently from C10 and C20. 1-6 Alkyl substituents. In some cases, R 1 Selected from , , , , , , , and In some cases, R 1 Selected from , , , , , and Each of these can be arbitrarily replaced. In some cases, R 1 Selected from , , and Each of these can be arbitrarily replaced. In some cases, R 1 Selected from , , , , Each of these can be arbitrarily replaced. In some cases, R 1 One or more optional substituents are each independently selected from fluorine, -OH, -C(O)NH2, -NH-C(O)-(C 1-6 alkoxy), -NH-C(O)-(C 1-6 Hydroxyalkyl), -NH2, -NH(CN), =O, -CN, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1One or more optional substituents are independently selected from halogens, -OH, -CN, C 1-6 Cyanoalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1 One or more optional substituents are each independently selected from halogens, -OH, and -CN. In some cases, R 1 One or more optional substituents are each independently selected from fluorine, -OH, -CN, C 1-6 Cyanoalkyl, C 1-6 Alkyl, oxo and C 2-6 Alkyne group. In some cases, R 1 One or more optional substituents are each independently selected from fluorine, -OH, -CN, C 1-6 Cyanoalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , and In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , and In some cases, R 1 Selected from , , , , , , , , , , , and In some cases, R 1 Selected from , , , , , , , and .

[0358] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from optionally substituted unsaturated 6- to 8-membered heterocycles. In some cases, R 1 Selected from optionally substituted unsaturated 6-membered heterocycles. In some cases, R 1 Selected from optionally substituted unsaturated 7-membered heterocycles. In some cases, the heterocycle has 1 or 2 double bonds. In some cases, the heterocycle has only 1 double bond. In some cases, the heterocycle has only 2 double bonds. In some cases, R... 1 Selected from , , , and Each of which is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents. In some cases, R 1 Selected from , , and Each of which is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents. In some cases, R 1 Selected from , , and Each of which is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents. In some cases, R 1 Selected from , , , , , , , , , , , and In some cases, R 1 Selected from , , , , , , , and In some cases, R 1 Selected from In some cases, R 1 for In some cases, R 1 Selected from , , and Each of them is substituted by one or more substituents independently selected from halogens.

[0359] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1The unsaturated 6- or 7-membered heterocycle is selected from unsaturated 6- or 7-membered heterocycles, wherein the unsaturated 6- or 7-membered heterocycle is substituted by one or more substituents selected from halogens. In some cases, the unsaturated 6- or 7-membered heterocycle is substituted by at least one halogen. In some cases, the unsaturated 6- or 7-membered heterocycle is substituted by only one halogen. In some cases, R... 1 Selected from unsaturated 6-membered heterocycles, which are substituted with at least one halogen. In some cases, R 1 Selected from unsaturated 7-membered heterocycles, which are substituted with at least one halogen. In some cases, R 1 Selected from , , , , , , , and In some cases, R 1 Selected from , , , , and In some cases, R 1 Selected from , and In some cases, R 1 Selected from and In some cases, R 1 for In some cases, R 1 for In some cases, R 1 for .

[0360] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from optionally substituted unsaturated 6- to 8-membered heterocycles. In some cases, R 1 Selected from optionally substituted unsaturated 7-membered heterocycles. In some cases, R 1 Selected from and Each of which is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents. In some cases, R1 Selected from , , and .

[0361] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from substituted 6-membered heterocycles. In some cases, the 6-membered heterocycle contains only one nitrogen atom. In some cases, R... 1 The 6-membered heterocycle is bonded to formula (I) via only one nitrogen atom. In some cases, R 1 The 6-membered heterocycle is bonded to formula (II) via only one nitrogen atom. In some cases, R 1 The 6-membered heterocycle is bonded to formula (III) via only one nitrogen atom. In some cases, R 1 Selected from and Either of these can be arbitrarily replaced. In some cases, R 1 One or more optional substituents are each independently selected from halogens, -OR 20 -N(R) 20 )2、=O、-CN、C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1 One or more optional substituents are each independently selected from fluorine, -OH, -NH2, -NH(CN), =O, -CN, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1 One or more optional substituents are each independently selected from fluorine, -OH, -NH2, -NH(CN), =O, -CN, C 1-6 Hydroxyalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, the 6-membered heterocycle is a partially unsaturated or saturated 6-membered heterocycle. In some cases, the 6-membered heterocycle is partially unsaturated. In some cases, the 6-membered heterocycle is saturated. In some cases, the 6-membered heterocycle is a monocyclic 6-membered heterocycle. In some cases, the 6-membered heterocycle is not a bridged heterocycle. In some cases, R... 1 Selected from , , , , , , , , , , , and .

[0362] In some implementations, for compounds of formula (I), formula (II), or formula (III), R 1 Selected from substituted 6-membered unsaturated heterocycles and 6-membered saturated heterocycles.

[0363] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from and Each of which is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents.

[0364] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from and Each of which is optionally selected independently from one or more halogens and C 1-6 Substituents of haloalkyl groups.

[0365] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , and .

[0366] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from and Each of these is optionally selected from two independent elements chosen from halogen, -OH, -NH2, -NO2, C. 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents.

[0367] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from and Each of them is optionally selected from two independent elements chosen from halogen and C. 1-6 Substituents of haloalkyl groups. In some cases, R 1 for .

[0368] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from substituted 6- to 10-membered heterocycles. In some cases, the 6- to 10-membered heterocycle contains at least one nitrogen atom. In some cases, R 1 Selected from , , , , , , and Each of these may optionally be selected independently from one or more halogens, =O, -OH, -CN, -NHCN, -C(O)N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl and C 1-6 Alkyl substituents. In some cases, each R... 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substituents in the carbocyclic ring and 3- to 12-membered heterocycles. In some cases, R... 1 Selected from , , , , , , , , , and .

[0369] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1Selected from 10-membered heterocycles with optional substitution. In some cases, the 10-membered heterocycle is a bicyclic heterocycle. In some cases, the 10-membered heterocycle is a spirocyclic heterocycle. In some cases, the 10-membered heterocycle is a fused heterocycle. In some cases, the 10-membered heterocycle is a saturated heterocycle. In some cases, the 10-membered heterocycle is a non-aromatic heterocycle. In some cases, the 10-membered heterocycle contains at least one nitrogen atom. In some cases, the 10-membered heterocycle contains at least two nitrogen atoms. In some cases, the 10-membered heterocycle contains at least three nitrogen atoms. In some cases, the 10-membered heterocycle contains at least one sulfur atom. In some cases, R... 1 Selected from , and Each of these may optionally be selected independently from one or more halogens, =O, -OH, -CN, -NHCN, -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl and C 1-6 Alkyl substituents. In some cases, R 1 Selected from , and In some cases, R 1 Selected from and In some cases, R 1 Selected from and In some cases, R 1 Selected from In some cases, R 1 Selected from It is optionally selected by one or more independently chosen from halogen, -OR 20 -SR 20 -N(R) 20 )2、-NO2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

[0370] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1Selected from optionally substituted unsaturated 9- to 11-membered heterocycles. In some cases, R 1 Selected from optionally substituted unsaturated 10-membered heterocycles. In some cases, R 1 Selected from optionally substituted unsaturated 10-membered fused heterocycles. In some cases, R 1 for It is optionally substituted. In some cases, one or more optional substituents are selected from halogens, -OH, -C(O)N(R) 20 )2、-N(R 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1 for It is optionally selected by one or more of -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Substituents in the alkynyl group. In some cases, each R... 20 Independently selected from hydrogen; and C 1-6 Alkyl and C 3-12 A carbon ring, and each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 3-12 Substitution of carbon rings and 3 to 12-membered heterocycles.

[0371] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 7- to 11-membered spirochetes. In some cases, R 1 Selected from 10-membered spiroheterocycles. In some cases, the spiroheterocycle has at least 3 nitrogen atoms. In some cases, the spiroheterocycle has at least 1 sulfur atom. In some cases, R...1 Selected from and Each of these may be optionally substituted. In some cases, one or more optional substituents are independently selected from halogens, -OH, -N(R) 20 )2, -NO2, =O, -CN, -NHCN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group. In some cases, R 1 Selected from and In some cases, R 1 for In some cases, R 1 for In some cases, M is selected from O and NR. 3 In some cases, M is selected from O. In some cases, M is selected from NR. 3 In some cases, R 3 Selected from C 1-6 Alkyl group. In some cases, R 3 Selected from C 1-2 Alkyl group. In some cases, R 3 Selected from methyl.

[0372] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from optionally substituted 8- to 10-membered fused heterocycles. In some cases, the 8- to 10-membered fused heterocycle is a bicyclic heterocycle. In some cases, the 8- to 10-membered fused heterocycle is a saturated heterocycle. In some cases, the 8- to 10-membered fused heterocycle is an unsaturated heterocycle. In some cases, the 8- to 10-membered heterocycle is a non-aromatic heterocycle. In some cases, R... 1 Selected from optionally substituted 9-membered fused heterocycles. In some cases, R 1Selected from 10-membered fused heterocycles with optional substitution. In some cases, the 10-membered fused heterocycle is a bicyclic heterocycle. In some cases, the 10-membered fused heterocycle is a saturated heterocycle. In some cases, the 9-membered heterocycle is a non-aromatic heterocycle. In some cases, the 10-membered heterocycle is a non-aromatic heterocycle. In some cases, the fused heterocycle has one saturated ring and one aromatic ring. In some cases, the fused heterocycle has one saturated ring and one unsaturated ring. In some cases, the fused heterocycle has two saturated rings. In some cases, the 10-membered heterocycle contains at least one nitrogen atom. In some cases, the 10-membered heterocycle contains at least two nitrogen atoms. In some cases, the 10-membered heterocycle contains at least three nitrogen atoms. In some cases, the 9-membered heterocycle contains at least one nitrogen atom. In some cases, the 9-membered heterocycle contains at least two nitrogen atoms. In some cases, the 9-membered heterocycle contains at least three nitrogen atoms. In some cases, R... 1 Selected from and Each of these may be optionally substituted with one or more substituents. In some cases, R 1 for It is optionally substituted with one or more substituents. In some cases, R 1 for It is optionally substituted with one or more substituents. In some cases, R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(=NR) 20 )N(R 20 )2、-C(O)N(R 20 )2、-C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group and 5 to 12-membered heterocycles, wherein each of the 5 to 12-membered heterocycles is optionally and independently bounded by one or more R groups. 1* Replacement. In some cases, R 1One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, one or more optional substituents are independently selected from halogen, =O, -OH, -CN, -NHCN, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from halogens, =O, C. 1-6 Alkyl-N(R) 20 )2、-S(O)2(R 20 ), -S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)R 20 -C(O)N(R) 20 )2 and -C(O)NR 20 OR 20In some cases, one or more optional substituents are independently selected from halogens, =O, -S(O)2(R). 20 ), -S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)R 20 -C(O)N(R) 20 )2 and -C(O)NR 20 OR 20 In some cases, one or more optional substituents are independently selected from -C(O)R. 20 -C(O)N(R) 20 )2 and -C(O)NR 20 OR 20 In some cases, one or more optional substituents are independently selected from -S(O)2(R). 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 In some cases, one or more optional substituents are independently selected from -S(O)N(R). 20 2. In some cases, one or more optional substituents are independently selected from S(O)2(R 20 In some cases, one or more optional substituents are independently selected from S(O)R. 20 (=NR 20 In some cases, one or more optional substituents are independently selected from -C(O)R. 20 In some cases, one or more optional substituents are independently selected from -C(O)N(R). 20 2. In some cases, one or more optional substituents are independently selected from -C(O)NR. 20 OR 20 In some cases, R 1 Selected from , , , , , , and Each of these may be further optionally substituted. In some cases, one or more additional optional substituents are selected from halogens, -OH, =O, -CN, C. 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, one or more additional optional substituents are selected from halogens, -CN, C2-alkenyl, and C... 1-6 Alkyl group. In some cases, one or more additional optional substituents are selected from halogens and C. 1-6 Alkyl group. In some cases, one or more additional optional substituents are selected from halogens. In some cases, each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles. In some cases, each R... 20 Independently selected from hydrogen; and C 1-6 Alkyl groups and 3 to 12-membered heterocycles. In some cases, each R... 20 Independently selected from hydrogen; and C 1-6 Alkyl groups and 3 to 12-membered saturated heterocycles. In some cases, each R... 20 Independently selected from 5- to 6-membered saturated heterocycles. In some cases, R 20 The heterocycle has at least one nitrogen atom. In some cases, R 20 The heterocycle has at least one sulfur atom. In some cases, R 20 The heterocycle has at least one oxygen atom. In some cases, R 20 The heterocycle contains only one heteroatom. In some cases, R 20 The heterocycle has at least two heteroatoms. In some cases, R 20 The heterocycle contains only two heteroatoms. In some cases, R 1 One or more optional substituents are independently selected from halogens, -CN, C2-alkenyl groups, , , , , , , , , and In some cases, R 1 One or more optional substituents are independently selected from halogens, , , , , , , , , and In some cases, R 1The optional one or more substituents are independently selected from , , , , , , , , , , , , , , and In some cases, R 1 One or more optional substituents are independently selected from halogens, , , , , , , , , and In some cases, R 1 Selected from , , , , , , , , , and In some cases, R 1 Selected from , , , , , , , , , and In some cases, R 1 Selected from and In some cases, R 1 Selected from , , , , , , , , , and In some cases, R 1 One or more optional substituents are independently selected from halogens and C. 1-6 Alkyl-N(R) 20 2. In some cases, R 1 One or more optional substituents are independently selected from halogens, , and In some cases, R 1 Selected from In some cases, each R 20 Independently selected from hydrogen and C 1-6 Alkyl and C 3-6 Carbon rings. In some cases, R 1 Selected from , and In some cases, R 1 Selected from , , , , , , , , , , , , , , and In some cases, R 1 Selected from It may optionally be selected independently by one or more halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 The alkynyl group or a 5- to 12-membered heterocycle is substituted, wherein the 5- to 12-membered heterocycle is optionally replaced by one or more substituents selected from halogens, -OR 20 and C 1-6 Alkyl substituents. In some cases, R 1 Selected from It may optionally be selected independently from one or more halogens and C 1-6 Alkyl substituents. In some cases, R 1 Selected from and In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from ,in Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally and independently bound by one or more R... 1* Replace; and R B Selected from hydrogen, halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkyne group and -CN. In some cases, R B Selected from hydrogen and halogens. In some cases, R B It is chlorine. In some cases, R B It is hydrogen. In some cases, It has at least 1, 2, 3, or 4 heteroatoms. In some cases, It has at least 1, 2, 3, or 4 nitrogen atoms. In some cases, It has at least one oxygen atom. In some cases, It is a monocyclic heterocyclic ring. In some cases, It is a bicyclic heterocyclic ring. In some cases, Selected from arbitrarily substituted 5-membered heterocycles. In some cases, Selected from substituted 9-membered heterocycles. In some cases, Selected from , , , , , , , and Each of them is optionally controlled by one or more R 1* Replacement. In some cases, Selected from , , , , , , , and Each of them is optionally controlled by one or more R 1* Replacement. In some cases, each R 1* Independently selected from halogens, -OR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens and C 1-6 Alkyl groups. In some cases, Selected from , , , , , , , , and .

[0373] In some implementations, for compounds or salts of formula (I), (II), (II*), or (III), when R 1 -C(O)R 20 When replacing, R 20 Selected from 5- to 12-membered heterocycles, which are optionally substituted. In some cases, R 1 -C(O)R 20 Replacement. In some cases, R 20 Selected from 5 to 12 unsubstituted heterocycles. In some cases, R 20 Selected from 5- to 6-membered heterocycles, which may optionally be substituted. In some cases, the heterocycle has at least one nitrogen atom. In some cases, the heterocycle has at least one sulfur atom. In some cases, the heterocycle has at least one oxygen atom. In some cases, the heterocycle has two heteroatoms. In some cases, R 20 The heterocycles are selected from , , and Each of these can be arbitrarily replaced. In some cases, R 20 Selected from , , , , In some cases, the optional substituents are selected from C. 1-10 Alkyl, oxo, and =NH.

[0374] In some implementations, for compounds or salts of formula (I), formula (II), formula (II*), or formula (III), each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, and =NH substituents. In some cases, each R... 20 Independently selected from hydrogen; and unsubstituted C 1-6 Alkyl groups and one or more elements independently selected from halogens, -OH, -CN, -NO2, -NH2, -N(C) 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 The alkyl, oxo, and =NH substituents are optionally substituted into 3 to 12-membered heterocycles.

[0375] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 For optional substitution of 12 to 15-membered heterocyclic rings. In some cases, R 1 For optional substituted 12-membered heterocycles. In some cases, R 1 For optional substituted 13-membered heterocycles. In some cases, R 1 For optional substituted 14-membered heterocycles. In some cases, R 1 For optional substituted 15-membered heterocyclic rings. In some cases, R 1 The heterocycle is tricyclic. In some cases, R 1 The heterocycle contains fused heterocycles. In some cases, R 1 The heterocycle contains spiroheterocycles. In some cases, R 1 The heterocycles contain fused and spiroheterocycles. In some cases, R 1 The heterocycle is an unsaturated heterocycle. In some cases, R 1 The heterocycle is a non-aromatic heterocycle. In some cases, R 1 The heterocycle has at least one double bond. In some cases, R 1 The heterocyclic ring has at least two double bonds. In some cases, R 1 The heterocycle has at least two heteroatoms. In some cases, R 1 The heterocycle has at least three heteroatoms. In some cases, R 1 The heterocycle has at least four heteroatoms. In some cases, R 1 The heterocycle has at least 5 heteroatoms. In some cases, R 1 The heterocycle has at least six heteroatoms. In some cases, R 1 The heterocycle has at least seven heteroatoms. In some cases, the heteroatoms are selected from oxygen, nitrogen, and sulfur. In some cases, R... 1 The heterocycle has at least 3, 4, or 5 nitrogen atoms and at least 1 sulfur atom. In some cases, R 1The heterocycle has at least 3, 4, or 5 nitrogen atoms and at least 1 oxygen atom. In some cases, R 1 The heterocycle has 3, 4, or 5 nitrogen atoms. In some cases, R 1 The heterocycle has 3, 4, or 5 nitrogen atoms and no other heteroatoms. In some cases, the heteroatoms are selected from nitrogen and sulfur. In some cases, the heteroatoms are selected from nitrogen and oxygen. In some cases, R... 1 Selected from , , , , , , , , , , , , , , and Each of these may be optionally substituted with one or more substituents. In some cases, R 1 Selected from , , , , , , , , , , , , , , , and Each of these may be optionally substituted with one or more substituents. In some cases, R 1 One or more optional substituents are independently selected from halogens, -OH, -NHCN, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, =NH, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1 One or more optional substituents are independently selected from halogens, -OH, -NHCN, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, R 1 One or more optional substituents are independently selected from halogens, -OH, C 1-6 Alkyl groups and -C(O)N(R) 20 2. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , and .

[0376] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 For optional substitution of 12 to 15-membered heterocyclic rings. In some cases, R 1 for In some cases, ring W is an optionally substituted heterocycle, and ring P is an optionally substituted carbocyclic ring or an optionally substituted heterocycle, wherein ring P and ring W form a spirocycle. In some cases, ring W is an optionally substituted fused heterocycle. In some cases, ring P and ring W are combined to form a heterocycle having at least 12 atoms and at most 15 atoms. In some cases, ring P and ring W have a total of at least 12 atoms and at most 15 atoms. In some cases, ring W is an optionally substituted 10-membered fused heterocycle. In some cases, R... 1 for Where ring P is an optionally substituted carbocyclic ring or an optionally substituted heterocyclic ring. In some cases, R 1 for In some cases, ring P is an optionally substituted carbon ring. In some cases, ring P is an optionally substituted heterocycle. In some cases, ring P forms an optionally substituted C3-C6 carbon ring or an optionally substituted 4- to 6-membered heterocycle. In some cases, ring P forms an optionally substituted C3 carbon ring. In some cases, ring P forms an optionally substituted C4 carbon ring. In some cases, ring P forms an optionally substituted C5 carbon ring. In some cases, ring P forms an optionally substituted 4-membered heterocycle. In some cases, ring P forms an optionally substituted 5-membered heterocycle. In some cases, ring P has at least 1, 2, or 3 heteroatoms. In some cases, the heteroatoms are selected from oxygen, nitrogen, and sulfur. In some cases, ring P has 1 sulfur atom. In some cases, ring P has 1 nitrogen atom. In some cases, ring P has 1 oxygen atom. In some cases, one or more optional substituents of ring P are independently selected from halogens, -OH, -NHCN, =O, =NR. 20 -CN,C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, one or more optional substituents of the ring P are independently selected from halogen, -OH, =O, =NH, -CN, and C. 1-6 Alkyl group. In some cases, one or more optional substituents of the ring W are independently selected from halogens, -OH, -NHCN, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(O)NHOR 20 -N(R)20 )2、-C(O)R 20 -NO2, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group. In some cases, one or more optional substituents of the ring W are independently selected from halogens, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 and C 1-6 Alkyl group. In some cases, one or more optional substituents of the ring W are independently selected from -C(O)R. 20 In some cases, ring P is substituted. In some cases, ring W is substituted.

[0377] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Each of these may optionally be substituted by one or more substituents. In some cases, one or more of the optional substituents are independently selected from halogens, -OH, -N(R) 20 )2、-B(OH)2、-C(O)N(R 20 )2、-NHCN、-NO2、C 1-6 Alkoxy, =O, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl and C 1-6 Haloalkyl. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0378] In some implementations, for compounds or salts of formula (I), (II), or (III), R 2 Selected from optionally substituted -L-heterocycles. In some cases, the heterocycle is a bicyclic heterocycle. In some cases, the heterocycle is a monocyclic heterocycle. In some cases, the heterocycle has only one nitrogen atom. In some cases, the heterocycle has only one nitrogen atom and no other heteroatoms. In some cases, YR 2 Selected from and In which the heterocyclic moiety is optionally substituted, R 2Selected from and In which the heterocyclic moiety is optionally substituted, YR 2 Selected from In which the heterocyclic moiety is optionally substituted, YR 2 Selected from The heterocyclic moiety is optionally substituted. In some cases, the heterocycle is optionally replaced by one or more elements selected from halogens, hydroxyl groups, and C. l -C3 alkyl, -N(R) 5 )S(O)2(R 5 ), -OC(O)N(R 5 2. Oxygenation, =CH2, =NO-C l -C3 alkyl, -CH2OC(O) heterocyclic, -CH2 heterocyclic, -CH2OC(O)N(R) 5 )2 and -OC l -C3 alkyl substituents, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocyclic, oxo, and hydroxyl groups. In some cases, YR 2 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , and In some cases, YR 2 Selected from , and In some cases, YR 2 Selected from , , , , , , , , , , , , , , and .

[0379] In some implementations, for compounds or salts of formula (I), (II), or (III), R 2 Selected from -LN(R) 21 2. In some cases, each R 21 Selected from hydrogen and C 1-6 Alkyl groups. In some cases, each R 21 Selected from C 1-6 Alkyl group. In some cases, L is independently selected from substituted C. l -C4 alkylene, wherein the two substituents on the same carbon atom of L together form a C3-C6 carbon ring, wherein the C3-C6 carbon ring is optionally substituted by one or more substituents selected from halogens. In some cases, L is In some cases, R 2 for In some cases, YR 2 for .

[0380] In some implementations, for compounds or salts of formula (I), (II), or (III), each R 21 Independently selected from hydrogen. In some cases, each R... 21 Independently selected from hydrogen and C 1-6 Alkyl groups. In some cases, each R 21 Selected independently from C 1-6 Alkyl groups. In some cases, each R 21 Independently selected from hydrogen; and C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl or oxo substituents.

[0381] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1Selected from optionally substituted 8- to 10-membered fused heterocycles. In some cases, the 8- to 10-membered fused heterocycle is a bicyclic heterocycle. In some cases, the 8- to 10-membered fused heterocycle is a saturated heterocycle. In some cases, the 8- to 10-membered heterocycle is a non-aromatic heterocycle. In some cases, R... 1 Selected from optionally substituted 9-membered fused heterocycles. In some cases, R 1 Selected from 10-membered fused heterocycles with optional substitution. In some cases, the 10-membered fused heterocycle is a bicyclic heterocycle. In some cases, the 10-membered fused heterocycle is a saturated heterocycle. In some cases, the 10-membered heterocycle is a non-aromatic heterocycle. In some cases, the fused heterocycle has one saturated ring and one aromatic ring. In some cases, the fused heterocycle has one saturated ring and one unsaturated ring. In some cases, the fused heterocycle has two saturated rings. In some cases, the 10-membered heterocycle contains at least one nitrogen atom. In some cases, the 9-membered heterocycle contains at least two nitrogen atoms. In some cases, the 9-membered heterocycle contains at least three nitrogen atoms. In some cases, the 10-membered heterocycle contains at least two nitrogen atoms. In some cases, the 10-membered heterocycle contains at least three nitrogen atoms. In some cases, R... 1 Selected from and Each of these may be optionally substituted with one or more substituents. In some cases, R 1 Selected from , , and Each of these may be optionally substituted with one or more substituents. In some cases, R 1 for It is optionally substituted with one or more substituents. In some cases, the optional one or more substituents are independently selected from halogens, =O, -OH, -CN, -NHCN, -C(O)R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from halogens, =O, -C(O)R. 20 -C(O)N(R) 20 )2 and -C(O)NR 20 OR 20 In some cases, one or more optional substituents are independently selected from -C(O)R. 20 -C(O)N(R) 20 )2 and -C(O)NR20 OR 20 In some cases, one or more optional substituents are independently selected from -C(O)R. 20 In some cases, one or more optional substituents are independently selected from -C(O)N(R). 20 2. In some cases, one or more optional substituents are independently selected from -C(O)NR. 20 OR 20 In some cases, each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles. In some cases, each R... 20 Independently selected from hydrogen; and C 1-6 Alkyl groups and 3 to 12-membered heterocycles. In some cases, each R... 20 Independently selected from hydrogen; and C 1-6 Alkyl groups and 3 to 12-membered saturated heterocycles. In some cases, R 1 The optional one or more substituents are independently selected from , , , , and In some cases, R 1 Selected from , , , , , , , and In some cases, R 1 Selected from , , , , , and In some cases, R 1 for .

[0382] In some implementations, for compounds or salts of formula (I), R 1 Selected from optionally substituted saturated 6- to 7-membered heterocycles. In some cases, R 1 Selected from saturated 6-membered heterocycles with optional substitution. In some cases, R 1 Selected from Optionally, it is substituted. In some cases, one or more optional substituents are independently selected from halogens, -CN, -NHCN, C 1-6Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -CN, -NHCN, C... 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -CN, -NHCN, C... 1-6 Cyanoalkyl and C 1-6 Alkyl group. In some cases, one or more optional substituents are independently selected from -NHCN and C. 1-6 Alkyl group. In some cases, R 1 Selected from It is selected from one or more of -NHCN and C 1-6 Alkyl substituents. In some cases, R 1 Selected from and .

[0383] In some implementations, for compounds or salts of formula (I), R 1 Selected from substituted saturated 6-membered heterocycles, wherein the saturated 6-membered heterocycle is coupled with at least one -NHCN and optionally one or more C24-C ... 1-6 Alkyl substitution; B is selected from optionally substituted 8- to 15-membered fused heterocycles and optionally substituted C8-C 15 Fused carbocyclic rings, each of which is optionally composed of one or more independently selected from halogen, oxo, -NH2, C1-C3 alkyl, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkyne substituent; ring A is selected from optionally substituted heterocycles; Y is O; R 2 Selected from -L-heterocycles, wherein the heterocyclic moiety is optionally composed of one or more elements independently selected from halogens, hydroxyl groups, C-elements, and L-heterocycles. l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl or -N(R) 5 Substituents of )2; and L is selected from C l -C4 alkylene. In some cases, R 1 Selected from and In some cases, B is selected from... , , , , , and In some cases, B is selected from... , and In some cases, B is... .

[0384] In some embodiments, for compounds or salts of formula (I), (II), or (III), B is an optionally substituted 8- to 10-membered fused carbide ring. In some cases, B is a substituted 8- to 10-membered fused carbide ring. In some cases, B is an unsubstituted 8- to 10-membered fused carbide ring. In some cases, B is an optionally substituted 9-membered fused carbide ring. In some cases, B is... It is optionally substituted by one or more substituents. In some cases, B is... It is substituted by one or more substituents. In some cases, for B, one or more substituents are independently selected from halogens, oxo groups, -NH2, C1-C3 alkyl groups, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkynyl group. In some cases, B is substituted with at least one halogen. In some cases, B is substituted with at least one chlorine. In some cases, B is substituted with at least one fluorine. In some cases, B is selected from... , , , , , , , , , , , , and In some cases, B is... It is selected from one or more halogens and C 1-6 Substituents of haloalkyl groups. In some cases, B is... It is substituted by one or more substituents selected from halogens. In some cases, B is selected from... , , , , and In some cases, B is... It is substituted with one or more substituents selected from fluorine. In some cases, B is selected from... , and In some cases, B is... It is substituted with one or more substituents selected from chlorine. In some cases, B is selected from... and In some cases, B is a substituted 10-membered fused carbide ring. In some cases, for the 10-membered fused carbide ring of B, one or more substituents are independently selected from halogens, -NH2, C1-C3 alkyl groups, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkyne group. In some cases, B is selected from... , , , , , , , , , , and In some cases, for the 10-membered fused carbon ring of B, it is substituted with at least one halogen. In some cases, B is selected from... , , , and In some cases, B is an unsubstituted 9- to 10-membered fused carbon ring. In other cases, B is selected from... and Each of these is unsubstituted. In some cases, B is... In some cases, B is... .

[0385] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group, 5 to 12-membered heterocycle, wherein the 5 to 12-membered heterocycle is optionally composed of one or more elements selected from halogen and C. 1-6 Alkyl substituents.

[0386] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 for And R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group and optionally substituted 5- to 12-membered heterocycles. In some cases, R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NHOR20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group and optionally substituted 5- to 12-membered heterocycles. In some cases, R 1 One or more optional substituents are independently selected from halogens, -CN, C 2-6 alkynyl group, -C(=NR) 20 )N(R 20 )2 and optionally substituted 5- to 12-membered heterocycles. In some cases, R 1 One or more optional substituents are independently selected from halogens, -C(=NR) 20 )N(R 20 )2 and optionally substituted 5- to 12-membered heterocycles. In some cases, R 1 One or more optional substituents are independently selected from -C(=NR) 20 )N(R 20 )2 and optionally substituted 5- to 12-membered heterocycles. In some cases, R 1 One or more optional substituents are independently selected from optionally substituted 5- to 12-membered heterocycles. In some cases, R 1 One or more optional substituents are independently selected from 5-membered and 9-membered heterocycles, each of which is optionally and independently substituented by one or more R 1* Replacement. In some cases, R 1 It is substituted with at least one halogen atom, and optionally with one or more atoms independently selected from -CN, C 2-6 alkynyl group, -C(=NR) 20 )N(R 20 Substitution of 2 and 5 to 12-membered heterocycles, wherein the 5 to 12-membered heterocycles are optionally and independently substituted by one or more R groups. 1* Substitution. In some cases, the heterocycle has at least one nitrogen atom. In some cases, the heterocycle has at least one oxygen atom. In some cases, the heterocycle has at least one nitrogen atom and at least one oxygen atom. In some cases, the heterocycle has at least two heteroatoms. In some cases, the heterocycle has at least three heteroatoms. In some cases, the heterocycle has at least four heteroatoms. In some cases, R 1The heterocycle with one or more optional substituents is selected from , , , , , , , , and Each of them is optionally controlled by one or more R 1* Replacement. In some cases, R 1 The heterocycle with one or more optional substituents is selected from It is optionally controlled by one or more R 1* Replacement. In some cases, each R 1* Independently selected from halogens, -OR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens, -OR 20-S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens. In some cases, each R... 1* Selected independently from C 1-6 Alkyl groups. In some cases, each R1* Independently selected from -OR 20 In some cases, each R 1* Independently selected from -OH. In some cases, each R 1* Independently selected from -OMe. In some cases, R 1 The heterocycle with one or more optional substituents is selected from , , , , , , , , , , , , and .

[0387] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 One or more optional substituents are independently selected from -C(=NR) 20 )N(R 20 )2 and optionally substituted 5- to 12-membered heterocycles. In some cases, R 1 One or more optional substituents are independently selected from optionally substituted 5- to 12-membered heterocycles. In some cases, the heterocycle is selected from... , , , , , , , and Each of them is optionally controlled by one or more R 1* Replacement. In some cases, R 1 One or more optional substituents are selected from , , , , , , , , and .

[0388] In some implementations, for compounds or salts of formula (I), (II), or (III), each R 1* Independently selected from halogens, -OR 20 -S(O)2(R 20 -S(O)2N(R)20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens, -OR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens, C 1-6 Halogenated alkyl and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens and C 1-6 Alkyl groups. In some cases, each R 1* Independently selected from halogens. In some cases, each R... 1* Selected independently from C 1-6 alkyl.

[0389] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 5 to 15-membered heterocycles (preferably 8 to 10-membered heterocycles or preferably 10-membered heterocycles), each of which is optionally selected independently by one or more of halogens, oxo-, -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -SO2R 20 -NHCN, C 1-6 Cyanoalkyl, C 1-6 Alkyl, C 1-6 Alkyl-N(R) 20 2. C 2-6Substituents of the alkynyl group and 5 to 12-membered heterocycles (preferably 5 to 9-membered heterocycles), wherein each of the 5 to 12-membered heterocycles is optionally and independently replaced by one or more R groups. 1* Replace; each R 1* Independently selected from halogens, C 1-6 Halogenated alkyl and C 1-6 Alkyl group. In some cases, the 8- to 10-membered heterocycle is bicyclic. In some cases, the 10-membered heterocycle is substituted. In some cases, R... 1 Selected from , , , and Each of these can be arbitrarily replaced. In some cases, R 1 Selected from , which is optionally replaced. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , and In some cases, R 1 Selected from , and In some cases, R 1 for .

[0390] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Selected from 5- to 15-membered heterocycles (preferably 8- to 10-membered heterocycles or preferably 10-membered heterocycles), each of which is optionally selected independently by one or more halogens, -C(O)N(R) 20 )2、-C(O)NR 20OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -NHCN, C 1-6 Cyanoalkyl, C 1-6 Alkyl, C 2-6 Substituents of the alkynyl group and 5 to 12-membered heterocycles (preferably 5 to 6-membered heterocycles), wherein each of the 5 to 12-membered heterocycles is optionally and independently replaced by one or more R groups. 1* Replace; each R 1* Independently selected from halogens, C 1-6 Halogenated alkyl and C 1-6 Alkyl group. In some cases, the 8- to 10-membered heterocycle is bicyclic. In some cases, the 10-membered heterocycle is substituted. In some cases, R... 1 Selected from , and Each of these can be arbitrarily replaced. In some cases, R 1 Selected from , which is optionally replaced. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , and In some cases, R 1 Selected from and In some cases, M is chosen from O and NMe. In some cases, M is O. In some cases, M is NMe. In some cases, R... 2 Selected from -LN(R) 21 )2 and -L-heterocycles, which are optionally separated by one or more R 6 Replacement. In some cases, YR 2 Selected from , , and In some cases, B is selected from optionally substituted carbocyclic rings. and Each of these can be arbitrarily replaced. In some cases, B is selected from... , , , , , and In some cases, B is... In some cases, B is... In some cases, n is 0.

[0391] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 The compounds are selected from the compounds in the Examples section. In some cases, Y is selected from the compounds in the Examples section. In some cases, L is selected from the compounds in the Examples section. In some cases, R... 2 Compounds selected from the Examples section. In some cases, B is selected from the compounds in the Examples section. In some cases, M is selected from the compounds in the Examples section. In some cases, R... 1 The optional substituents of the heterocycle are selected from the compounds in the Examples section.

[0392] In some implementations, for compounds or salts of formula (I), (II), or (III), R 2 -LN(R) 21 2. In some cases, R 2 For -L-OR 21 In some cases, R 2 It is a heterocyclic ring. In some cases, R 2 C l -C6 alkyl. In some cases, R 2 It is an L-heterocyclic ring. In some cases, R 2 It is -L-aryl. In some cases, R 2 It is an -L-heteroaryl group. In some cases, R... 2 It is an -L-cycloalkyl group. In some cases, R 2 -LN(R) 21 2. In some cases, R 2 It is -L-NHC(=NH)NH2. In some cases, R 2 -LC(O)N(R) 21 2. In some cases, R 2 For -LC l -C6 haloalkyl. In some cases, R 2 For -L-OR 21 In some cases, R 2 -L-NR21 C(O)-aryl. In some cases, R 2 It is -L-COOH. In some cases, R 2 -L-NR 21 S(O)2(R 21 In some cases, R 2 -LS(O)2N(R) 21 2. In some cases, R 2 -LN(R) 21 )C(O)(OR 21 In some cases, R 2 -L-OC(O)N(R) 21 2. In some cases, R 2 -LC(=O)OC l -C6 alkyl. In some cases, heterocyclic, -L-NR 21 The aryl moiety of the C(O)-aryl group, the heterocyclic moiety of the -L-heterocyclic group, and the cycloalkyl moiety of the -L-cycloalkyl group are each optionally surrounded by one or more R groups. 6 Replacement, wherein the aryl moiety of -L-aryl and the heteroaryl moiety of -L-heteroaryl are each optionally replaced by one or more R 7 Replacement. In some cases, when Y is a bond, O, or S, R 2 Further selected from hydrogen.

[0393] In some implementations, equation (I) or equation (II) is represented by equation (II*): Equation (II*) Or its pharmaceutically acceptable salt, wherein: M is selected from O and NR 3 ; R 3 Selected from hydrogen, C 1-6 Alkyl and C 1-6 Cyanoalkyl; R 1 Selected from 7- to 10-membered heterocycles, wherein the 7- to 10-membered heterocycles are optionally selected independently by one or more halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R)20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group and the substituents of the 5- to 12-membered heterocycle are substituted, wherein the 5- to 12-membered heterocycle is optionally and independently substituted by one or more R groups. 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; B is selected from C6-C 15 Carbon rings, where C6-C 15 The carbon ring is optionally composed of one or more elements independently selected from halogens, C1-C3 alkyl groups, -B(OR) groups. 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group; R 2 Selected from -L-heterocycles, wherein the heterocycle of the -L-heterocycle is optionally separated by one or more R 6 replace; L is independently selected from C l -C4 alkylene, where C l -C4 alkylene groups are optionally surrounded by one or more molecules selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl substituents; and wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring; Each R 20 Independently selected from hydrogen; and C 1-6Alkyl, C 3-6 A carbocyclic ring and 3 to 6-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbon rings and 3 to 12-membered heterocycles.

[0394] In some implementations, for compounds or salts of formula (II*), R 1 Selected from optionally substituted 7- to 10-membered spiroheterocycles and optionally substituted 7- to 10-membered fused heterocycles. In some cases, R 1 The heterocycle has at least one nitrogen atom. In some cases, R 1 At least one nitrogen atom of the heterocycle is incorporated into formula (II*). In some cases, R 1 Selected from optionally substituted 10-membered spirocyclic rings and optionally substituted 10-membered fused heterocyclic rings. In some cases, R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group, 5 to 12-membered heterocycle, wherein the 5 to 12-membered heterocycle is optionally composed of one or more elements selected from halogen and C. 1-6 Alkyl substituents. In some cases, R 1 Selected from It is selected independently by one or more halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 The alkynyl group or a 5- to 12-membered heterocycle is substituted, wherein the 5- to 12-membered heterocycle is optionally replaced by one or more substituents selected from halogens and C. 1-6 Alkyl substituents. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , and In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , and In some cases, R 1 for In some cases, M is selected from O. In some cases, M is NCH2CH3. In some cases, M is NMe. In some cases, R... 2 The heterocycle is a saturated heterocycle. In some cases, R 2 R 6 Each time it appears, it is independently selected from halogen, =CH2, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl. In some cases, R 2 L is selected from C1-C4 alkylene groups and In some cases, R 2 Selected from , , , , and In some cases, B is selected from the optionally substituted C9-C. 10 Fused carbon rings. In some cases, B is selected from... and Each of these may be optionally substituted. In some cases, B may be optionally replaced by one or more elements independently selected from halogens, oxo-, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -OC. l -C3 haloalkyl, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Substituents of the alkynyl group. In some cases, B is optionally substituted by one or more substituents independently selected from halogens. In some cases, B is... In some cases, B is... In some cases, B is unsubstituted. In other cases, B is substituted.

[0395] In some implementations, for compounds or salts of formula (II*), R 1 Selected from optionally substituted 7- to 10-membered spiroheterocycles and optionally substituted 7- to 10-membered fused heterocycles. In some cases, R 1Selected from optionally substituted 10-membered spirocyclic rings and optionally substituted 10-membered fused heterocyclic rings. In some cases, R 1 Selected from arbitrarily substituted 10-membered spiroheterocycles. In some cases, R 1 Selected from arbitrarily substituted 10-membered fused heterocycles. In some cases, R 1 The heterocycle has at least three heteroatoms. In some cases, R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 ), -S(O)N(R 20 )2、-S(O)2N(R 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group, 5 to 12-membered heterocycle, wherein the 5 to 12-membered heterocycle is optionally composed of one or more elements selected from halogen and C. 1-6 Alkyl substituents. In some cases, R 1 Selected from It is selected independently by one or more halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20)2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 The alkynyl group or a 5- to 12-membered heterocycle is substituted, wherein the 5- to 12-membered heterocycle is optionally replaced by one or more substituents selected from halogens and C. 1-6 Alkyl substituents. In some cases, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , In some cases, R 1 Selected from and In some cases, R 1 for In some cases, M is chosen from O. In some cases, M is NMe. In some cases, R... 2 The heterocycle is a saturated heterocycle. In some cases, R 2 R 6 Each time it appears, it is independently selected from halogen, =CH2, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl. In some cases, R 2 L is selected from C1-C4 alkylene groups and In some cases, R 2 Selected from , , , , and In some cases, B is selected from the optionally substituted C9-C. 10 Fused carbon rings. In some cases, B is selected from... and Each of these may be optionally substituted. In some cases, B may be optionally replaced by one or more elements independently selected from halogens, oxo-, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -OC. l -C3 haloalkyl, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Substituents of the alkynyl group. In some cases, B is optionally substituted by one or more substituents independently selected from halogens. In some cases, B is... In some cases, B is... In some cases, B is unsubstituted. In other cases, B is substituted.

[0396] In some implementations, for compounds or salts of formula (I), formula (II), formula (II*), or formula (III), R 1 Heterocyclic or carbocyclic rings are not C 1-6 Cyanoalkyl substitution. In some embodiments, for compounds or salts of formula (I), R 1 Heterocyclic or carbocyclic rings are not C 1-6 Cyanoalkyl substitution. In some embodiments, for compounds or salts of formula (II), R 1 Heterocyclic or carbocyclic rings are not C 1-6 Cyanoalkyl substitution. In some embodiments, for compounds or salts of formula (III), R 1 Heterocyclic or carbocyclic rings are not C1-6 Cyanoalkyl substitution.

[0397] In some implementations, for compounds or salts of formula (I), formula (II), formula (II*), or formula (III), each R 20 Independently selected from hydrogen; and C 1-6 alkyl.

[0398] In some implementations, for compounds or salts of formula (I), formula (II), formula (II*), or formula (III), C is not used. 1-6 Cyanoalkyl substitution.

[0399] In some implementations, for compounds or salts of formula (I), (II), or (III), R 1 Not piperazine. In some cases, R 1 Piperazine that is not substituted.

[0400] In some implementations, for compounds of formula (I), the compound is not a Michael acceptor.

[0401] In some implementations, for compounds of formula (I), the compound or salt does not include an electrophilic substituent.

[0402] In some implementations, the compounds or salts of formula (I), (II), (II*), or (III) do not contain an electrophilic portion.

[0403] In some implementations, the compounds or salts of formula (I), (II), (II*), or (III) do not contain covalent modifiers.

[0404] In some implementations, for compounds or salts of formula (I), formula (II), formula (II*), or formula (III), R 1 One or more optional substituents are not electrophilic.

[0405] In some embodiments, the compounds of formula (I), (II), (III) or sub-forms used in the method include trifluoroacetates of the compounds described above.

[0406] In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 5 mg to about 500 mg. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 10 mg to about 150 mg. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 10 mg to about 125 mg. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 10 mg to about 100 mg. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 25 mg to about 100 mg. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 50 mg to about 100 mg. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 5 mg to about 75 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, or about 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at about 15 mg, about 30 mg, about 45 mg, or about 60 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at about 15 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at about 30 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at about 45 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at about 60 mg. In some embodiments, the subject is between 12 and 18 years of age. In some embodiments, the subject is between 12 years of age and older and 18 years of age and younger. In some embodiments, the subject is an adult. In some embodiments, the subject is 18 years of age or older.

[0407] In some embodiments, the compound (II) or salt is applied once daily. In some embodiments, the compound (II) or salt is applied twice daily. In some embodiments, the compound (II) or salt is applied three times daily. In some embodiments, the compound (II) or salt is applied once weekly. In some embodiments, the compound (II) or salt is applied every other day. In some embodiments, the compound (II) or salt is applied every three days.

[0408] In some embodiments, the compound or salt of formula (II) is administered to the subject at a dose of 10 mg to 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at a dose of 10 mg to 125 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at a dose of 10 mg to 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at a dose of 25 mg to 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at a dose of 50 mg to 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at a dose of 5 mg to 75 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at doses of 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, or 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at doses of 15 mg, 30 mg, 45 mg, or 60 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at doses of 15 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at doses of 30 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at doses of 45 mg. In some embodiments, a compound of formula (II) or its salt is administered to the subject at a dose of 60 mg. In some embodiments, the subject is between 12 and 18 years of age. In some embodiments, the subject is between 12 and 18 years of age or older. In some embodiments, the subject is an adult. In some embodiments, the subject is 18 years of age or older.

[0409] In some embodiments, the compound (II) or its salt is administered to the subject daily at a dose of about 10 mg to about 150 mg. In some embodiments, the compound (II) or its salt is administered to the subject daily at a dose of about 10 mg to about 125 mg. In some embodiments, the compound (II) or its salt is administered to the subject daily at a dose of about 10 mg to about 100 mg. In some embodiments, the compound (II) or its salt is administered to the subject daily at a dose of about 25 mg to about 100 mg. In some embodiments, the compound (II) or its salt is administered to the subject daily at a dose of about 50 mg to about 100 mg. In some embodiments, the compound (II) or its salt is administered to the subject daily at a dose of about 5 mg to about 75 mg. In some embodiments, a compound of formula (II) or its salt is administered to the subject daily at a dose of about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, or about 150 mg. In some embodiments, a compound of formula (II) or its salt is administered to the subject daily at a dose of about 15 mg, about 30 mg, about 45 mg, or about 60 mg. In some embodiments, a compound of formula (II) or its salt is administered to the subject daily at a dose of about 15 mg. In some embodiments, the subject is given approximately 30 mg of compound (II) or its salt daily. In some embodiments, the subject is given approximately 45 mg of compound (II) or its salt daily. In some embodiments, the subject is given approximately 60 mg of compound (II) or its salt daily. In some embodiments, compound (II) or its salt is administered once daily. In some embodiments, the subject is between 12 and 18 years of age. In some embodiments, the subject is between 12 and 18 years of age. In some embodiments, the subject is an adult. In some embodiments, the subject is 18 years of age or older.

[0410] In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 10 mg to about 150 mg twice daily. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 10 mg to about 125 mg twice daily. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 10 mg to about 100 mg twice daily. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 25 mg to about 100 mg twice daily. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 50 mg to about 100 mg twice daily. In some embodiments, the compound (II) or its salt is administered to the subject at a dose of about 5 mg to about 75 mg twice daily. In some embodiments, the compound of formula (II) or its salt is administered to the subject twice daily at a dose of about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, or about 150 mg. In some embodiments, the compound of formula (II) or its salt is administered to the subject twice daily at a dose of about 15 mg, about 30 mg, about 45 mg, or about 60 mg. In some embodiments, the compound of formula (II) or its salt is administered to the subject twice daily at a dose of about 15 mg. In some embodiments, the compound (II) or its salt is administered to the subject at about 30 mg twice daily. In some embodiments, the compound (II) or its salt is administered to the subject at about 45 mg twice daily. In some embodiments, the compound (II) or its salt is administered to the subject at about 60 mg twice daily. In some embodiments, the subject is between 12 and 18 years of age. In some embodiments, the subject is between 12 and 18 years of age. In some embodiments, the subject is an adult. In some embodiments, the subject is 18 years of age or older.

[0411] In some implementations, the compound of formula (II) is administered as a capsule over a period of time. In some cases, tablet or capsule formulations of compound (II) contain about 10 mg to about 100 mg (e.g., about 10 mg to about 95 mg, about 10 mg to about 90 mg, about 10 mg to about 85 mg, about 10 mg to about 80 mg, about 10 mg to about 75 mg, about 10 mg to about 70 mg, about 10 mg to about 65 mg, about 10 mg to about 60 mg, about 10 mg to about 55 mg, about 10 mg to about 50 mg, about 10 mg to about 45 mg, about 10 mg to about 40 mg, about 10 mg to about 35 mg, about 10 mg to about 30 mg, about 10 mg to about 25 mg, about 10 mg to about 20 mg, about 10 mg to about 15 mg, about 15 mg to about 100 mg, about 15 mg to about 95 mg, about 15 mg to about 90 mg, about 15 mg to about 85 mg, about 15 mg to about 80 mg, about 15 mg to about 7 ... mg to about 70 mg, about 15 mg to about 65 mg, about 15 mg to about 60 mg, about 15 mg to about 55 mg, about 15 mg to about 50 mg, about 15 mg to about 45 mg, about 15 mg to about 40 mg, about 15 mg to about 35 mg, about 15 mg to about 30 mg, about 15 mg to about 25 mg, about 15 mg to about 20 mg, about 20 mg to about 100 mg, about 20 mg to about 95 mg, about 20 mg to about 90 mg, about 20 mg to about 85 mg, about 20 mg to about 80 mg, about 20 mg to about 75 mg, about 20 mg to about 70 mg, about 20 mg to about 65 mg, about 20 mg to about 60 mg, about 20 mg to about 55 mg, about 20 mg to about 50 mg, about 20 mg to about 45 mg, about 20 mg to about 40 mg, about 20 mg to about 35 mg, about 20 mg to about 30 mg, about 20 mg to about 25 mg, about 25 mg to about 25 mg, about 25 mg to about 25 mg, about 20 ... mg to about 100 mg, about 25 mg to about 95 mg, about 25 mg to about 90 mg, about 25 mg to about 85 mg, about 25 mg to about 80 mg, about 25 mg to about 75 mg, about 25 mg to about 70 mg, about 25 mg to about 65 mg, about 25 mg to about 60 mg, about 25 mg to about 55 mg, about 25 mg to about 50 mg, about 25 mg to about 45 mg, about 25 mg to about 40 mg, about 25 mg to about 35 mg, about 25 mg to about 30 mg, about 30 mg to about 100 mg, about 30 mg to about 95 mgmg, about 30 mg to about 90 mg, about 30 mg to about 85 mg, about 30 mg to about 80 mg, about 30 mg to about 75 mg, about 30 mg to about 70 mg, about 30 mg to about 65 mg, about 30 mg to about 60 mg, about 30 mg to about 55 mg, about 30 mg to about 50 mg, about 30 mg to about 45 mg, about 30 mg to about 40 mg, about 30 mg to about 35 mg, about 35 mg to about 100 mg, about 35 mg to about 95 mg, about 35 mg to about 90 mg, about 35 mg to about 85 mg, about 35 mg to about 80 mg, about 35 mg to about 75 mg, about 35 mg to about 70 mg, about 35 mg to about 65 mg, about 35 mg to about 60 mg, about 35 mg to about 55 mg, about 35 mg to about 50 mg, about 35 mg to about 45 mg, about 35 mg to about 40 mg, about 40 mg to about 100 mg, about 40 mg to about 95 mg mg, about 40 mg to about 90 mg, about 40 mg to about 85 mg, about 40 mg to about 80 mg, about 40 mg to about 75 mg, about 40 mg to about 70 mg, about 40 mg to about 65 mg, about 40 mg to about 60 mg, about 40 mg to about 55 mg, about 40 mg to about 50 mg, about 40 mg to about 45 mg, about 45 mg to about 100 mg, about 45 mg to about 95 mg, about 45 mg to about 90 mg, about 45 mg to about 85 mg, about 45 mg to about 80 mg, about 45 mg to about 75 mg, about 45 mg to about 70 mg, about 45 mg to about 65 mg, about 45 mg to about 60 mg, about 45 mg to about 55 mg, about 45 mg to about 50 mg, about 50 mg to about 100 mg, about 50 mg to about 95 mg, about 50 mg to about 90 mg, about 50 mg to about 85 mg, about 50 mg to about 80 mg, about 50 mg to about 75 mg mg, about 50 mg to about 70 mg, about 50 mg to about 65 mg, about 50 mg to about 60 mg, about 50 mg to about 55 mg, about 55 mg to about 100 mg, about 55 mg to about 95 mg, about 55 mg to about 90 mg, about 55 mg to about 85 mg, about 55 mg to about 80 mg, about 55 mg to about 75 mg, about 55 mg to about 70 mg, about 55 mg to about 65 mg, about 55 mg to about 60 mg, about 60 mg to about 100 mg, about 60 mg to about 95 mg, about 60 mg to about 90 mg, about 60 mg to about 85 mg, about 60 mg to about 80 mgmg, about 60 mg to about 75 mg, about 60 mg to about 70 mg, about 60 mg to about 65 mg, about 65 mg to about 100 mg, about 65 mg to about 95 mg, about 65 mg to about 90 mg, about 65 mg to about 85 mg, about 65 mg to about 80 mg, about 65 mg to about 75 mg, about 65 mg to about 70 mg, about 70 mg to about 100 mg, about 70 mg to about 95 mg, about 70 mg to about 90 mg, about 70 mg to about 85 mg, about 70 mg to about 80 mg, about 70 mg to about 75 mg, about 75 mg to about 100 mg, about 75 mg to about 95 mg, about 75 mg to about 90 mg, about 75 mg to about 85 mg, about 75 mg to about 80 mg, about 80 mg to about 100 mg, about 80 mg to about 95 mg, about 80 mg to about 90 mg, about 80 mg to about 85 mg, about 85 mg to about 100 mg, about 85 mg to about 95 mg, about 80 ... Compounds of formula (II) (e.g., compounds 53, 61, 63, 64, 69 and 96) or pharmaceutically acceptable salts thereof, ranging from about 10 mg to about 95 mg, about 85 mg to about 90 mg, about 90 mg to about 100 mg, about 90 mg to about 95 mg, about 95 mg to about 100 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg or about 100 mg).

[0412] In some embodiments, the compound of formula (II) is administered orally once daily for a period of time (QD). In one embodiment, the compound of formula (II) is administered orally twice daily for a period of time (BID). In one embodiment, the compound of formula (II) is administered at a concentration of about 20 mg to about 500 mg over a period of time (e.g., about 20 mg to about 480 mg, about 20 mg to about 460 mg, about 20 mg to about 440 mg, about 20 mg to about 420 mg, about 20 mg to about 400 mg, about 20 mg to about 380 mg, about 20 mg to about 360 mg, about 20 mg to about 340 mg, about 20 mg to about 320 mg, about 20 mg to about 300 mg, about 20 mg to about 280 mg, about 20 mg to about 260 mg, about 20 mg to about 240 mg, about 20 mg to about 220 mg, about 20 mg to about 200 mg, about 20 mg to about 180 mg, about 20 mg to about 160 mg, about 20 mg to about 140 mg, about 20 mg to about 120 mg, about 20 mg to about 100 mg, about 20 mg to about 80 mg, about 20 mg to about 6 ...100 mg, about 20 mg to about 100 mg, about 20 mg to about 100 mg to about 40 mg, about 40 mg to about 500 mg, about 40 mg to about 480 mg, about 40 mg to about 460 mg, about 40 mg to about 440 mg, about 40 mg to about 420 mg, about 40 mg to about 400 mg, about 40 mg to about 380 mg, about 40 mg to about 360 mg, about 40 mg to about 340 mg, about 40 mg to about 320 mg, about 40 mg to about 300 mg, about 40 mg to about 280 mg, about 40 mg to about 260 mg, about 40 mg to about 240 mg, about 40 mg to about 220 mg, about 40 mg to about 200 mg, about 40 mg to about 180 mg, about 40 mg to about 160 mg, about 40 mg to about 140 mg, about 40 mg to about 120 mg, about 40 mg to about 100 mg, about 40 mg to about 80 mg, about 40 mg to about 60 mg, about 60 mg to about 500 mg mg, about 60 mg to about 480 mg, about 60 mg to about 460 mg, about 60 mg to about 440 mg, about 60 mg to about 420 mg, about 60 mg to about 400 mg, about 60 mg to about 380 mg, about 60 mg to about 360 mg, about 60 mg to about 340 mg, about 60 mg to about 320 mg, about 60 mg to about 300 mg, about 60 mg to about 280 mg, about 60 mg to about 260 mg, about 60mg to about 240 mg, about 60 mg to about 220 mg, about 60 mg to about 200 mg, about 60 mg to about 180 mg, about 60 mg to about 160 mg, about 60 mg to about 140 mg, about 60 mg to about 120 mg, about 60 mg to about 100 mg, about 60 mg to about 80 mg, about 80 mg to about 500 mg, about 80 mg to about 480 mg, about 80 mg to about 460 mg, about 80 mg to about 440 mg, about 80 mg to about 420 mg, about 80 mg to about 400 mg, about 80 mg to about 380 mg, about 80 mg to about 360 mg, about 80 mg to about 340 mg, about 80 mg to about 320 mg, about 80 mg to about 300 mg, about 80 mg to about 280 mg, about 80 mg to about 260 mg, about 80 mg to about 240 mg, about 80 mg to about 220 mg, about 80 mg to about 200 mg mg, about 80 mg to about 180 mg, about 80 mg to about 160 mg, about 80 mg to about 140 mg, about 80 mg to about 120 mg, about 80 mg to about 100 mg, about 100 mg to about 500 mg, about 100 mg to about 480 mg, about 100 mg to about 460 mg, about 100 mg to about 440 mg, about 100 mg to about 420 mg, about 100 mg to about 400 mg, about 100 mg to about 380 mg, about 100 mg to about 360 mg, about 100 mg to about 340 mg, about 100 mg to about 320 mg, about 100 mg to about 300 mg, about 100 mg to about 280 mg, about 100 mg to about 260 mg, about 100 mg to about 240 mg, about 100 mg to about 220 mg, about 100 mg to about 200 mg, about 100 mg to about 180 mg, about 100 mg to about 200 mg. mg to about 160 mg, about 100 mg to about 140 mg, about 100 mg to about 120 mg, about 120 mg to about 500 mg, about 120 mg to about 480 mg, about 120 mg to about 460 mg, about 120 mg to about 440 mg, about 120 mg to about 420 mg, about 120 mg to about 400 mg, about 120 mg to about 380 mg, about 120 mg to about 360 mg, about 120 mg to about 340 mg, about 120 mg to about 320 mg, about 120 mg to about 300 mg, about 120 mg to about 280 mg, about 120 mg to about 260 mg, about 120 mg to about 240 mg, about 120 mg to about 220 mg, about 120 mg to about 220 mg, about 120 mg to about 220 mg, about 120 mg to about 220 mg, about 120 mg to about 260 mg, about 120 mg to about 240 mg, about 120 mg to about 220 mg, about 120 mg to about 220 mg, about 120 mg to about 26 ...mg to about 200 mg, about 120 mg to about 180 mg, about 120 mg to about 160 mg, about 120 mg to about 140 mg, about 140 mg to about 500 mg, about 140 mg to about 480 mg, about 140 mg to about 460 mg, about 140 mg to about 440 mg, about 140 mg to about 420 mg, about 140 mg to about 400 mg, about 140 mg to about 380 mg, about 140 mg to about 360 mg, about 140 mg to about 340 mg, about 140 mg to about 320 mg, about 140 mg to about 300 mg, about 140 mg to about 280 mg, about 140 mg to about 260 mg, about 140 mg to about 240 mg, about 140 mg to about 220 mg, about 140 mg to about 200 mg, about 140 mg to about 180 mg, about 140 mg to about 160 mg, about 160 mg mg to about 500 mg, about 160 mg to about 480 mg, about 160 mg to about 460 mg, about 160 mg to about 440 mg, about 160 mg to about 420 mg, about 160 mg to about 400 mg, about 160 mg to about 380 mg, about 160 mg to about 360 mg, about 160 mg to about 340 mg, about 160 mg to about 320 mg, about 160 mg to about 300 mg, about 160 mg to about 280 mg, about 160 mg to about 260 mg, about 160 mg to about 240 mg, about 160 mg to about 220 mg, about 160 mg to about 200 mg, about 160 mg to about 180 mg, about 180 mg to about 500 mg, about 180 mg to about 480 mg, about 180 mg to about 460 mg, about 180 mg to about 440 mg, about 180 mg to about 42 ... mg to about 400 mg, about 180 mg to about 380 mg, about 180 mg to about 360 mg, about 180 mg to about 340 mg, about 180 mg to about 320 mg, about 180 mg to about 300 mg, about 180 mg to about 280 mg, about 180 mg to about 260 mg, about 180 mg to about 240 mg, about 180 mg to about 220 mg, about 180 mg to about 200 mg, about 200 mg to about 500 mg, about 200 mg to about 480 mg, about 200 mg to about 460 mg, about 200 mg to about 440 mg, about 200 mg to about 420 mg, about 200 mg to about 400 mg, about 200 mg to about 380 mg, about 200 mg to about 360 mg, about 200 mg to about 340 mgmg, about 200 mg to about 320 mg, about 200 mg to about 300 mg, about 200 mg to about 280 mg, about 200 mg to about 260 mg, about 200 mg to about 240 mg, about 200 mg to about 220 mg, about 220 mg to about 500 mg, about 220 mg to about 480 mg, about 220 mg to about 460 mg, about 220 mg to about 440 mg, about 220 mg to about 420 mg, about 220 mg to about 400 mg, about 220 mg to about 380 mg, about 220 mg to about 360 mg, about 220 mg to about 340 mg, about 220 mg to about 320 mg, about 220 mg to about 300 mg, about 220 mg to about 280 mg, about 220 mg to about 260 mg, about 220 mg to about 240 mg, about 240 mg to about 500 mg, about 240 mg to about 480 mg mg, about 240 mg to about 460 mg, about 240 mg to about 440 mg, about 240 mg to about 420 mg, about 240 mg to about 400 mg, about 240 mg to about 380 mg, about 240 mg to about 360 mg, about 240 mg to about 340 mg, about 240 mg to about 320 mg, about 240 mg to about 300 mg, about 240 mg to about 280 mg, about 240 mg to about 260 mg, about 260 mg to about 500 mg, about 260 mg to about 480 mg, about 260 mg to about 460 mg, about 260 mg to about 440 mg, about 260 mg to about 420 mg, about 260 mg to about 400 mg, about 260 mg to about 380 mg, about 260 mg to about 360 mg, about 260 mg to about 340 mg, about 260 mg to about 320 mg, about 260 mg to about 300 mg mg, about 260 mg to about 280 mg, about 280 mg to about 500 mg, about 280 mg to about 480 mg, about 280 mg to a...

Claims

1. A method of treating cancer in a subject in need, comprising administering to said subject a therapeutically effective amount of a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II): Equation (II) Or its pharmaceutically acceptable salt, wherein: M is selected from O, S, SO, SO2, and NR. 3 ; R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl-SO2R 20 C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of the carbocyclic ring and 5- to 12-membered heterocycles, wherein the C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from -LN(R) 21 )2、-L-OR 21 Heterocyclic rings, C l -C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R) 21 )2、-LC l -C6 haloalkyl, -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and -LC(=O)OC l -C6 alkyl, wherein the heterocycle, the -L-NR 21 The aryl moiety of the C(O)-aryl group, the heterocyclic moiety of the -L-heterocyclic group, and the cycloalkyl moiety of the -L-cycloalkyl group are each optionally surrounded by one or more R groups. 6 Replacement, wherein the aryl portion of the -L-aryl group and the heteroaryl portion of the -L-heteroaryl group are each optionally replaced by one or more R 7 Replacement, where R is a bond, O, or S. 2 Further selected from hydrogen; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; R 3 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; n is selected from 0 to 2; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, wherein the C1-C6 alkyl, C 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; Each R 5 Independently selected from hydrogen or C1-C6 alkyl; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are each optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl, or -N(R) 5 )2; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and B is selected from heterocycles and carbocycles, wherein the heterocycle and carbocycle are each optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C. l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C 3- C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally separated by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups.

2. The method of claim 1, wherein the combination exhibits a synergistic effect.

3. The method according to claim 1 or 2, wherein the therapeutically effective amount of the combination of the RTK-MAPK pathway inhibitor with the compound or salt of formula (II) results in prolonged overall survival, prolonged progression-free survival, increased tumor growth regression, increased tumor growth inhibition, and prolonged duration of stable disease in the subject relative to treatment with the compound or salt of formula (II) alone or any combination thereof.

4. The method according to any one of claims 1 to 3, wherein the therapeutically effective amount of the compound or salt of formula (II) in the combination is about 0.01 to 100 mg / kg per day.

5. The method according to any one of claims 1 to 4, wherein the therapeutically effective amount of the combined compound of formula (II) or salt is about 0.1 to 50 mg / kg per day.

6. The method according to any one of claims 1 to 5, wherein the therapeutically effective amount of the combined RTK-MAPK pathway inhibitor is about 0.01 to 100 mg / kg per day.

7. The method according to any one of claims 1 to 6, wherein the therapeutically effective amount of the combined RTK-MAPK pathway inhibitor is about 0.1 to 50 mg / kg per day.

8. The method according to any one of claims 1 to 7, wherein the RTK-MAPK pathway inhibitor and the compound or salt of formula (II) are administered on different dates.

9. The method according to any one of claims 1 to 8, wherein the compound or salt of formula (II) is administered at the maximum tolerated dose.

10. The method according to any one of claims 1 to 9, wherein the RTK-MAPK pathway inhibitor is administered at the maximum tolerated dose.

11. The method according to any one of claims 1 to 10, wherein the RTK-MAPK pathway inhibitor and the compound or salt of formula (II) are each administered at the maximum tolerated dose.

12. The method according to any one of claims 1 to 11, wherein the RTK-MAPK pathway inhibitor is a RAF-MEK-ERK pathway inhibitor.

13. The method according to any one of claims 1 to 11, wherein the RTK-MAPK pathway inhibitor is an ERBB family inhibitor.

14. The method according to any one of claims 1 to 13, wherein the inhibitor is selected from afatinib, dacomitinib, poziotinib, erlotinib, gefitinib, saprotinib, tarloxotinib, and cetuximab.

15. The method according to any one of claims 1 to 14, wherein the inhibitor is cetuximab.

16. The method according to any one of claims 1 to 15, wherein the RTK-MAPK pathway inhibitor is an epidermal growth factor receptor (EGFR) inhibitor.

17. The method according to any one of claims 1 to 11, wherein the RTK-MAPK pathway inhibitor is an SHP-2 inhibitor.

18. The method according to claim 17, wherein the SHP-2 inhibitor is SHP-099 (6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazine-2-amine dihydrochloride); RMC-4550 (3-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]dec-8-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazine-2-yl)methanol), RMC-4360, or TNO155 (Novartis).

19. The method of claim 17, wherein the SHP-2 inhibitor is RMC-4550.

20. The method of claim 17, wherein the SHP-2 inhibitor is RMC-4360.

21. The method of claim 17, wherein the SHP-2 inhibitor is TNO155.

22. The method of claim 17, wherein the SHP-2 inhibitor is SHP-099.

23. The method according to any one of claims 1 to 11, wherein the RTK-MAPK pathway inhibitor is an SOS1 inhibitor.

24. The method of claim 23, wherein the SOS1 inhibitor is BI-3406.

25. The method according to any one of claims 1 to 24, wherein the RTK-MAPK pathway inhibitor is administered orally.

26. The method according to any one of claims 1 to 25, wherein the cancer is selected from: Heart: Sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, and teratoma; Lungs: Bronchial carcinoma (squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma; Gastrointestinal tract: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vasoactive intestinal peptide tumor), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); Urogenital tract: Kidneys (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), Bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), Prostate (adenocarcinoma, sarcoma), Testes (seminomatous seminoma, teratoma, embryonal carcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenoid tumor, lipoma); Liver: Hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Biliary tract cancer: gallbladder cancer, ampullary cancer, bile duct cancer; Bone: Osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondrofibroma (osteochondrogenic exostosis), benign chondroma, chondroblastoma, chondromycinoma, osteomyxoid fibroma, osteoid osteoma, and giant cell tumor; Nervous system: Skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningeal sarcoma, glioma), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germ cell tumor (pineal tumor), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumor), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecology: Uterus (endometrial cancer), Cervix (cervical cancer, pretumoral cervical dysplasia), Ovary (ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-theca cell tumor, ovarian male cell tumor, dysgerminoma, malignant teratoma), Vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), Vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonic rhabdomyosarcoma), Fallopian tube (cancer); Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma). Skin conditions: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevus of dysplasia, lipoma, hemangioma, dermatofibroma, keloid, psoriasis; and Adrenal gland: neuroblastoma.

27. The method according to any one of claims 1 to 26, wherein the cancer is non-small cell lung cancer, small cell lung cancer, colorectal cancer, rectal cancer, or pancreatic cancer.

28. The method according to any one of claims 1 to 26, wherein the cancer is non-small cell lung cancer.

29. The method according to any one of claims 1 to 26, wherein the cancer is small cell lung cancer.

30. The method according to any one of claims 1 to 26, wherein the cancer is colorectal cancer.

31. The method according to any one of claims 1 to 26, wherein the cancer is rectal cancer.

32. The method according to any one of claims 1 to 26, wherein the cancer is pancreatic cancer.

33. The method according to any one of claims 1 to 26, wherein the cancer is a solid tumor cancer.

34. The method according to any one of claims 1 to 26, wherein the cancer is selected from cancers associated with KRas mutations.

35. The method according to any one of claims 1 to 26, wherein the cancer is selected from KRas wild-type related cancers.

36. The method according to any one of claims 1 to 26, wherein the cancer is selected from KRas G12D-associated cancer, KRas G12V-associated cancer, and KRas wild-type-associated cancer.

37. The method according to any one of claims 1 to 26, wherein the cancer is a KRas G12D-associated cancer.

38. The method according to any one of claims 1 to 26, wherein the cancer is a KRas G12V-related cancer.

39. The method according to any one of claims 1 to 26, wherein the cancer is a KRas wild-type related cancer.

40. The method according to any one of claims 1 to 39, wherein the RTK-MAPK pathway inhibitor synergistically increases the sensitivity of cancer cells to the compound or salt of formula (II).

41. The method of claim 1, wherein when M is NR 3 Y is O, and R 1 When it is piperazine, the piperazine is reacted with one or more R 9 Replace, where each R 9 Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-NO2、=O、=NO(R 20 -CN, -NHCN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Halogenated alkyl groups.

42. The method according to any one of claims 1 to 41, wherein the compound or salt is selected from: , or any of these salts.

43. The method according to any one of claims 1 to 41, wherein the compound is selected from: , or any of these salts.

44. The method according to any one of claims 1 to 42, wherein the compound is selected from: , or any of these salts.

45. The method according to any one of claims 1 to 43, wherein the compound is selected from: , or any of these salts.

46. ​​The method according to any one of claims 1 to 41, wherein the compound is selected from... , , , , and , or any of these salts.

47. The method according to any one of claims 1 to 41, wherein the compound is selected from... Or any of these salts.

48. The method according to any one of claims 1 to 41, wherein the compound is selected from... Or any of these salts.

49. The method according to any one of claims 1 to 41, wherein the compound is selected from... , or any of these salts.

50. The method according to any one of claims 1 to 41, wherein the compound is selected from... Or any of these salts.

51. The method according to any one of claims 1 to 41, wherein the compound is selected from... Or any of these salts.

52. The method according to any one of claims 1 to 41, wherein the compound is selected from... Or any of these salts.

53. The method according to any one of claims 1 to 51, wherein M is selected from O, NH and NMe.

54. The method of claim 52, wherein M is O.

55. The method according to any one of claims 1 to 51, wherein M is selected from NR. 3 .

56. The method of claim 54, wherein M is selected from NH and NMe.

57. The method of claim 55, wherein M is NMe.

58. The method according to any one of claims 1 to 56, wherein B is selected from optionally substituted 5- to 15-membered heterocycles and optionally substituted C3-C. 15 Carbon ring.

59. The method of claim 57, wherein B is selected from optionally substituted 8- to 15-membered fused heterocycles and optionally substituted C8-C. 15 Fused carbon rings.

60. The method of claim 59, wherein B is an optionally substituted 8- to 15-membered fused heterocycle.

61. The method of claim 60, wherein B is an optionally substituted unsaturated C8-C. 15 Fused carbon rings.

62. The method according to any one of claims 59 to 61, wherein for B, the optionally substituted 8- to 15-membered fused heterocycle and the optionally substituted C8-C 15 Each fused carbon ring is independently bicyclic or tricyclic.

63. The method of claim 62, wherein for B, the heterocyclic ring and the carbocyclic ring are each independently bicyclic.

64. The method of claim 62, wherein for B, the heterocyclic ring and the carbocyclic ring are each independently tricyclic.

65. The method according to any one of claims 59 to 64, wherein B is selected from... , , , , , and Each of these may be optionally substituted by one or more substituents.

66. The method of claim 65, wherein B is selected from... , , , , , and Each of these may be optionally substituted by one or more substituents.

67. The method of claim 66, wherein B is selected from... and Each of these may be optionally substituted by one or more substituents.

68. The method according to any one of claims 58 to 67, wherein for B, one or more optional substituents are independently selected from oxo, -NH2, halogen, C1-C3 alkyl.

69. The method according to any one of claims 1 to 68, wherein B is selected from... , , , , , , and .

70. The method according to any one of claims 58 to 67, wherein for B, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogens, C1-C3 alkyl groups, -B(OR) 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

71. The method according to any one of claims 58 to 67, wherein for B, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -OC l -C3 haloalkyl, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkyne group.

72. The method according to any one of claims 58 to 71, wherein B is selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

73. The method according to any one of claims 1 to 72, wherein each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen.

74. The method of claim 73, wherein each R 4 Selected independently from C 1-6 Alkyl, oxo, and halogen.

75. The method according to any one of claims 1 to 74, wherein n is selected from 1 and 2.

76. The method according to any one of claims 1 to 75, wherein n is 0.

77. The method according to any one of claims 1 to 76, wherein R 1 Selected from 5 to 12-membered heterocycles with optional substitution.

78. The method of claim 77, wherein R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycle is optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

79. The method of claim 78, wherein R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycle is optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

80. The method according to claim 78 or 79, wherein R 20 Selected from hydrogen and C 1-3 alkyl.

81. The method according to any one of claims 77 to 79, wherein R 1 The 5- to 12-membered heterocycles are unsaturated.

82. The method according to any one of claims 77 to 79, wherein R 1 The 5- to 12-membered heterocycles are saturated.

83. The method according to any one of claims 77 to 79, wherein R 1 The 5- to 12-membered heterocycles are bridging heterocycles.

84. The method according to any one of claims 77 to 83, wherein R 1 Selected from , , , , , , , , , , . , , , , , , , , , , , , , , , , , and Each of these can be arbitrarily replaced.

85. The method of claim 84, wherein one or more optional substituents are each independently selected from halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Halogenated alkyl groups.

86. The method of claim 84, wherein R 1 Selected from , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

87. The method of claim 86, wherein R 1 Selected from , and .

88. The method according to any one of claims 77 to 83, wherein R 1 Selected from 6- to 8-membered heterocycles, which are optionally substituted.

89. The method of claim 88, wherein R 1 It is selected from 7-membered saturated heterocycles, 8-membered bridging heterocycles and 6- to 7-membered unsaturated heterocycles, each of which may be optionally substituted.

90. The method of claim 89, wherein R 1 Selected from , , and Each of these can be arbitrarily replaced.

91. The method of claim 90, wherein one or more optional substituents are independently selected from -OH, -CN, oxo, C 1-6 Cyanoalkyl.

92. The method according to claim 90 or 91, wherein R 1 Selected from , , , , , , , and .

93. The method according to any one of claims 1 to 76, wherein R 1 Selected from 6- to 7-membered heterocycles with optional substitution.

94. The method of claim 93, wherein the 6- or 7-membered heterocycle contains only one nitrogen atom, and wherein the 6- or 7-membered heterocycle is optionally substituted.

95. The method of claim 94, wherein R 1 The 6- to 7-membered heterocycles are bonded to formula (II) via only one nitrogen atom.

96. The method according to any one of claims 93 to 95, wherein R 1 Selected from optional substituted unsaturated 6-membered heterocycles.

97. The method according to any one of claims 93 to 95, wherein R 1 Selected from optional substituted unsaturated 7-membered heterocycles.

98. The method according to any one of claims 93 to 97, wherein R 1 Selected from , , , , , and Either of them may be replaced.

99. The method according to any one of claims 93 to 98, wherein R 1 Selected from , , , , and Either of them may be replaced.

100. The method according to any one of claims 93 to 99, wherein R 1 One or more optional substituents are each independently selected from halogens, -OR 20 -N(R) 20 )2、=O、-CN、C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkyl, -NHCN and C 2-6 Alkyne group.

101. The method according to any one of claims 93 to 100, wherein each is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents.

102. The method according to any one of claims 93 to 101, wherein R 1 One or more optional substituents are each independently selected from halogens.

103. The method according to any one of claims 93 to 102, wherein R 1 Selected from , , , , , , , , , , and .

104. The method according to any one of claims 93 to 101, wherein R 1 Selected from , , Each of which is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents.

105. The method of claim 104, wherein R 1 Selected from and Each of which is optionally selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents.

106. The method of claim 105, wherein R 1 Selected from and Each of which is optionally selected independently from one or more halogens and C 1-6 Substituents of haloalkyl groups.

107. The method of claim 106, wherein R 1 Selected from , , and .

108. The method according to any one of claims 93 to 101, wherein R 1 Selected from It may optionally be selected independently by one or more elements chosen from halogens, -OH, -NH2, -NO2, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Halogenated alkyl and C 1-6 Alkyl substituents.

109. The method of claim 108, wherein R 1 Selected from It may optionally be substituted by one or more substituents independently selected from halogens.

110. The method of claim 109, wherein R 1 Selected from and .

111. The method of claim 93, wherein R 1 Selected from 6- to 7-membered heterocycles.

112. The method of claim 111, wherein the 6- or 7-membered heterocycle contains only one nitrogen atom and one or more additional heteroatoms selected from oxygen and sulfur.

113. The method of claim 112, wherein the optional one or more additional heteroatoms are selected from sulfur.

114. The method according to any one of claims 111 to 113, wherein the 6- or 7-membered heterocycle contains only one nitrogen atom and contains no other heteroatoms.

115. The method according to any one of claims 111 to 114, wherein the 6- or 7-membered heterocycle is a non-aromatic 6- or 7-membered heterocycle.

116. The method according to any one of claims 112 to 115, wherein R 1 The 6- to 7-membered heterocycles are bonded to formula (II) via only one nitrogen atom.

117. The method according to any one of claims 111 to 116, wherein R 1 Selected from , , , , and Each of these can be arbitrarily replaced.

118. The method of claim 117, wherein R 1 One or more optional substituents are each independently selected from halogens, -OH, -CN, C 1-6 Cyanoalkyl, -NHCN, C 1-6 Alkyl, oxo and C 2-6 Alkyne group.

119. The method of claim 113, wherein R 1 Selected from 6- to 10-membered heterocycles with optional substitution.

120. The method of claim 119, wherein R 1 Selected from , , , , , , , , and Each of them is optionally replaced.

121. The method of claim 120, wherein one or more optional substituents are independently selected from halogens, =O, -OH, -C(O)N(R) 20 2. C 2-6 Alkyne group, -NHCN, -CN, C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl and C 1-6 alkyl.

122. The method of claim 121, wherein R 1 Selected from , , , , , , , , , , and .

123. The method of claim 77, wherein R 1 Selected from 7- to 11-membered spirochetal heterocycles.

124. The method of claim 123, wherein R 1 Selected from 10-membered spiral heterocycles.

125. The method according to claim 123 or 124, wherein the spiroheterocycle has at least 3 nitrogen atoms.

126. The method of claim 125, wherein R 1 Selected from and Each of them is optionally replaced.

127. The method of claim 126, wherein R 1 Selected from and Each of these is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2, -NO2, =O, -CN, -NHCN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group.

128. The method of claim 127, wherein R 1 Selected from and Preferred .

129. The method of claim 77, wherein R 1 Selected from optional substituted unsaturated 9- to 11-membered heterocycles.

130. The method of claim 129, wherein R 1 Selected from optional substituted unsaturated 10-membered heterocycles.

131. The method of claim 130, wherein R 1 yes , which is arbitrarily replaced.

132. The method of claim 131, wherein R 1 yes It is optionally influenced by one or more elements selected from halogens, -OH, -C(O)N(R) 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Substitution of the alkynyl group.

133. The compound or salt according to claim 132, wherein R 1 Selected from and , and Each of them is optionally selected from one or more halogens, -OH, -N(R) 20 ) 2、 =O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Substitution of the alkynyl group.

134. The method of claim 77, wherein R 1 Selected from optional substituted unsaturated 9- to 11-membered heterocycles.

135. The method of claim 134, wherein R 1 Selected from optional substituted unsaturated 10-membered heterocycles.

136. The method of claim 135, wherein R 1 yes , which is arbitrarily replaced.

137. The method of claim 136, wherein R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group, 5 to 12-membered heterocycle, wherein the 5 to 12-membered heterocycle is optionally composed of one or more elements selected from halogen, -OR 20 and C 1-6 Alkyl substituents.

138. The method according to any one of claims 134 to 137, wherein R 1 Selected from , , , , , , , , , and Each of them is optionally replaced.

139. The method according to any one of claims 134 to 138, wherein R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

140. The method according to any one of claims 134 to 137, wherein R 1 One or more optional substituents are independently selected from halogens, -OH, -N(R) 20 )2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, -C(O)N(R) 20 2. C 1-6 Alkyl and C 2-6 Alkyne group.

141. The method of claim 140, wherein R 1 One or more optional substituents are independently selected from halogens and -C(O)N(R) 20 )2.

142. The method of claim 141, wherein R 1 Selected from .

143. The method according to any one of claims 134 to 137, wherein R 1 One or more optional substituents are independently selected from halogens, -N(R) 20 )2、-CN、C 1-6 Alkyl, C 1-6 Cyanoalkyl, C 1-6 Alkyl-N(R) 20 2. C 1-6 Alkyl-SO 2- C 1-6 Alkyl, C 2-6 alkenyl, -C(O)NR 20 OR 20 -C(O)N(R) 20 )2、-C(O)R 20 and 5- to 10-membered heterocycles, wherein the 5- to 10-membered heterocycles are optionally and independently composed of one or more R 1* Replace, where each R 1* Independently selected from halogens, -OR 20 and C 1-6 alkyl.

144. The method of claim 143, wherein R 1 One or more optional substituents are selected from chlorine, -NH2, -CN, C1 alkyl, C2 alkenyl, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

145. The method of claim 144, wherein R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

146. The method according to any one of claims 1 to 76, wherein R 1 It is a 12- to 15-membered heterocyclic ring that can be substituted.

147. The method of claim 146, wherein R 1 It is a 12-membered heterocyclic ring that can be substituted by choice.

148. The method of claim 146, wherein R 1 It is a 13-membered heterocyclic ring that can be substituted by choice.

149. The method of claim 146, wherein R 1 It is a 14-membered heterocyclic ring that can be substituted by choice.

150. The method of claim 146, wherein R 1 It is a 15-membered heterocyclic ring that can be substituted at will.

151. The method according to any one of claims 146 to 150, wherein R 1 The heterocycle is tricyclic.

152. The method according to any one of claims 146 to 151, wherein R 1 The heterocycle contains fused heterocycles.

153. The method according to any one of claims 146 to 152, wherein R 1 The heterocycles contain spiroheterocycles.

154. The method according to any one of claims 146 to 153, wherein R 1 The heterocycles contain fused heterocycles and spiroheterocycles.

155. The method according to any one of claims 146 to 154, wherein R 1 The heterocycle is an unsaturated heterocycle.

156. The method according to any one of claims 146 to 155, wherein R 1 The heterocycle is a non-aromatic heterocycle.

157. The method according to any one of claims 146 to 156, wherein R 1 The heterocycle has at least one double bond.

158. The method according to any one of claims 146 to 157, wherein R 1 The heterocycle has at least two double bonds.

159. The method according to any one of claims 146 to 158, wherein R 1 The heterocyclic ring has two double bonds.

160. The method according to any one of claims 146 to 159, wherein R 1 Selected from , , , , , , , , , , , , , , , and Each of these may be optionally substituted by one or more substituents.

161. The method of claim 160, wherein one or more optional substituents are selected from halogens, -OH, -NHCN, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl and C 2-6 Alkyne group.

162. The method of claim 161, wherein the optional one or more substituents are selected from halogens, -OH, C 1-6 Alkyl groups and -C(O)N(R) 20 )2.

163. The method according to any one of claims 146 to 162, wherein R 1 Selected from , , , , , , , , , , , , , , , , , , and .

164. The method of claim 93, wherein R 1 Selected from substituted 6- to 7-membered heterocycles, wherein the 6- to 7-membered heterocycle is substituted with at least one -NHCN, and further optionally with one or more C... 1-6 Alkyl substitution.

165. The method of claim 164, wherein R 1 Selected from and .

166. The method according to any one of claims 1 to 75, wherein R 1 Selected from 8 to 10-membered heterocycles, each of which is optionally selected independently by one or more halogens, -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -NHCN, C 1-6 Cyanoalkyl, C 1-6 Alkyl, C 2-6 Substituents of alkynyl group and 5 to 12-membered heterocycles (preferably 5 to 6-membered heterocycles), wherein each of the 5 to 12-membered heterocycles is optionally and independently replaced by one or more R groups. 1* Replace; each R 1* Independently selected from halogens, C 1-6 Halogenated alkyl and C 1-6 alkyl.

167. The method of claim 166, wherein R 1 Selected from , and Each of these can be arbitrarily replaced.

168. The method of claim 167, wherein R 1 Selected from , which is arbitrarily replaced.

169. The method of claim 168, wherein R 1 Selected from , , , , , , , , , , , , , , , , , and .

170. The method of claim 167, wherein R 1 Selected from and .

171. The method according to any one of claims 1 to 170, wherein Y is O.

172. The method according to any one of claims 1 to 171, wherein R 2 It is an L-heterocyclic ring, optionally bounded by one or more R-rings. 6 replace.

173. The method according to claim 172, wherein L is selected from C1-C4 alkylene groups.

174. The method of claim 173, wherein L is selected from unsubstituted C1-C4 alkylene groups.

175. The method of claim 173, wherein each L is independently selected from optionally substituted C. l -C4 alkylene; and wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring, wherein the C3-C6 carbon ring is optionally permeated by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups.

176. The method of claim 175, wherein the optional substituents of L are selected from C. l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring; wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are optionally pertaining to one or more elements selected from halogens and C 1-6 Substituents of haloalkyl groups.

177. The method according to claims 1 to 176, wherein YR 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

178. The method of claim 177, wherein R 2 R 6 Each time it appears, it is independently selected from halogen, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl.

179. The method of claim 178, wherein R 2 R 6 Each time it appears, it is independently selected from C1-C3 alkyl groups and halogens.

180. The method according to claims 177 to 179, wherein YR 2 Selected from , and .

181. The method according to any one of claims 171 to 175, wherein YR 2 Selected from , , , , , , , , The heterocyclic portion is optionally separated by one or more R 6 replace.

182. The method of claim 181, wherein R 6 Selected from halogens, -OH, C l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, oxo, C1-C3 alkoxy, -CN and C l -C3 aminoalkyl.

183. The method of claim 182, wherein R 6 Selected from halogens and C l -C3 alkyl.

184. The method of claim 183, wherein YR 2 Selected from , , and .

185. The method according to claim 181, YR 2 Selected from , , , , and .

186. The method according to claims 1 to 171, wherein R 2 Selected from -L-heterocycles, wherein the heterocyclic portion of the -L-heterocycle is optionally surrounded by one or more R... 6 replace.

187. The method of claim 186, wherein each L is independently selected from the substituted C. l -C4 alkylene; and wherein two substituents on the same carbon atom of L together form a C3-C6 carbon ring, wherein the C3-C6 carbon ring is optionally permeated by one or more substituents selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups.

188. The method of claim 187, wherein each L is independently selected from the substituted C. l -C4 alkylene, wherein two substituents on the same carbon atom of L together form a C3-C6 carbon ring.

189. The method of claim 188, wherein each L is independently selected from substituted C3 alkylene groups, and wherein two substituents on the same carbon atom of L together form a C3 carbide ring.

190. The method of claim 189, wherein each L is independently selected from... .

191. The method of claim 190, wherein YR 2 yes .

192. The method according to claims 1 to 176, wherein YR 2 Selected from In which the heterocyclic ring is optionally substituted.

193. The method of claim 192, wherein the heterocycle is optionally separated by one or more elements selected from halogens, hydroxyl groups, C... l -C3 alkyl, -N(R) 5 )S(O)2(R 5 ), -OC(O)N(R 5 )2、=CH2、Oxygenation、=NO-C l -C3 alkyl, -CH2OC(O) heterocyclic, -CH2 heterocyclic, -CH2OC(O)N(R) 5 )2 and -OC l -C3 alkyl substituents, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocyclic, oxo, and hydroxyl groups.

194. The method of claim 193, wherein YR 2 Selected from , , , , , , , , , , , , , , , , , , , , , , , , and .

195. The method according to any one of claims 1 to 176 or 186 to 190, wherein R 2 Selected from -LN(R) 21 )2.

196. The method of claim 195, wherein L is independently selected from the substituted C. l -C4 alkylene; and wherein two substituents on the same carbon atom of L together form a C3-C6 carbon ring, wherein the C3-C6 carbon ring is optionally substituted by one or more substituents selected from halogens.

197. The method according to claim 1, 195, or 196, wherein L is .

198. The method according to claim 1, or any one of 195 to 197, wherein R 2 yes .

199. The method according to claim 1, or any one of 195 to 197, wherein YR 2 yes .

200. The method of claim 1, wherein the compound is selected from: Or any of its pharmaceutically acceptable salts.

201. A method of treating cancer in a subject in need, comprising administering to said subject a therapeutically effective amount of a combination of an RTK-MAPK pathway inhibitor and a compound of formula (III): Equation (III) Or its pharmaceutically acceptable salt, wherein: R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of the carbocyclic ring and 5- to 12-membered heterocycles, wherein the C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; R 2 Selected from -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and L-bicyclic heterocycles, wherein the bicyclic heterocycles are optionally composed of one or more R 6 replace; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene rings, wherein the C3-C6 carbon rings and 3- to 8-membered heterocycles are optionally composed of one or more elements selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; n is selected from 0 to 3; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, wherein the C1-C6 alkyl, C 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; B is selected from heterocycles and carbocycles, wherein the heterocycle or carbocycle is optionally selected independently by one or more halogens, cyano, hydroxyl, =O, -NO2, C l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally separated by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; Y is selected from bonds, O, S, and NR. 5 ; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl group of the -C3 alkyl)phenyl group is optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and Each R 5 It is independently selected from hydrogen or C1-C6 alkyl.

202. The method of claim 201, wherein R 2 Selected from -L-pyrrolizine, wherein the pyrrolizine is optionally reacted with one or more R 6 replace.

203. The method according to any one of claims 201 to 202, wherein B is selected from optionally substituted 5- to 15-membered heterocycles and optionally substituted C3-C. 15 Carbon ring.

204. The method of claim 203, wherein B is selected from optionally substituted 8- to 15-membered fused heterocycles and optionally substituted C8-C. 15 Fused carbon rings.

205. The method of claim 204, wherein B is selected from optionally substituted 8- to 15-membered fused heterocycles.

206. The method of claim 204, wherein B is selected from optionally substituted unsaturated C8-C. 15 Fused carbon rings.

207. The method according to any one of claims 203 to 206, wherein for B, the optionally substituted 8- to 15-membered fused heterocycles and the optionally substituted C8-C 15 Each of the fused carbon rings is either bicyclic or tricyclic.

208. The method of claim 207, wherein for B, the heterocyclic ring and the carbocyclic ring are each independently bicyclic.

209. The method of claim 207, wherein for B, the heterocyclic ring and the carbocyclic ring are each independently tricyclic.

210. The method according to any one of claims 201 to 209, wherein B is selected from... , , , , , and Each of these may be optionally substituted by one or more substituents.

211. The method of claim 210, wherein B is selected from... , , , , , and Each of these may be optionally substituted by one or more substituents.

212. The method of claim 211, wherein B is selected from... and Each of these may be optionally substituted by one or more substituents.

213. The method according to any one of claims 201 to 212, wherein for B, one or more optional substituents of the heterocycle and carbide ring are independently selected from oxo, -NH2, halogen, C1-C3 alkyl.

214. The method according to any one of claims 201 to 213, wherein B is selected from... , , , , , , and .

215. The method according to any one of claims 201 to 212, wherein for B, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogens, C1-C3 alkyl groups, -B(OR) 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

216. The method of claim 205, wherein for B, one or more optional substituents of the heterocycle and carbide ring are independently selected each time they appear from halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Alkyne group.

217. The method according to any one of claims 215 to 216, wherein B is selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

218. The method according to any one of claims 201 to 217, wherein each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen.

219. The method of claim 218, wherein each R 4 Selected independently from C 1-6 Alkyl, oxo, and halogen.

220. The method according to any one of claims 201 to 219, wherein n is selected from 1 and 2.

221. The method according to any one of claims 201 to 219, wherein n is 0.

222. The method according to any one of claims 201 to 211, wherein Y is O.

223. The method according to any one of claims 201 to 212, wherein R 1 Selected from 5 to 12-membered heterocycles with optional substitution.

224. The method of claim 223, wherein R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycle is optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

225. The method of claim 224, wherein R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycle is optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

226. The method according to claim 224 or 225, wherein R 20 Selected from hydrogen and C 1-3 alkyl.

227. The method according to claims 201 to 226, wherein R 1 The 5- to 12-membered heterocycles are unsaturated.

228. The method according to claims 201 to 226, wherein R 1 The 5- to 12-membered heterocycles are saturated.

229. The method according to claims 201 to 226, wherein R 1 The 5- to 12-membered heterocyclic rings are bridged.

230. The method according to claims 201 to 226, wherein R 1 The 5- to 12-membered heterocycles are spiroheterocycles.

231. The method according to claims 201 to 230, wherein R 1 Selected from , , , , , , , , , , . , , , , , , , , , , , , , , , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

232. The method of claim 231, wherein R 1 Selected from , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

233. The method of claim 232, wherein R 1 Selected from , and .

234. The method according to claims 201 to 233, wherein R 2 It is an L-heterocyclic ring, optionally bounded by one or more R-rings. 6 replace.

235. The method of claim 234, wherein L is selected from C1-C4 alkylene groups.

236. The method of claim 235, wherein L is selected from unsubstituted C1-C4 alkylene groups.

237. The method according to any one of claims 234 to 236, wherein YR 2 Selected from The heterocyclic portion is optionally separated by one or more R 6 replace.

238. The method of claim 237, wherein R 2 R 6 Each time it appears, it is independently selected from halogen, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl.

239. The method of claim 238, wherein R 2 R 6 Each time it appears, it is independently selected from C1-C3 alkyl groups and halogens.

240. The method of claim 239, wherein YR 2 Selected from and .

241. A method of treating cancer in a subject in need, comprising administering to said subject a therapeutically effective amount of a combination of an RTK-MAPK pathway inhibitor and a compound of formula (I): Equation (I) Or its pharmaceutically acceptable salt, wherein: R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of the carbocyclic ring and 5- to 12-membered heterocycles, wherein the C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from hydrogen, -N(R) 21 )2、-LN(R 21 )2、-L-OR 21 Heterocyclic rings, C l -C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -LN(R) 21 )2、-L-NHC(=NH)NH 2 -LC(O)N(R) 21 )2、-LC l -C6 haloalkyl, -L-OR 21 -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and -LC(=O)OC l -C6 alkyl, wherein the heterocycle and -L-NR 5 The aryl moiety of the C(O)-aryl group, the heterocyclic moiety of the -L-heterocyclic group, and the cycloalkyl moiety of the -L-cycloalkyl group may optionally be replaced by one or more R groups. 6 Substitution, wherein the aryl or heteroaryl group of said -L-aryl and said -L-heteroaryl may optionally be replaced by one or more R 7 replace; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene rings, wherein the C3-C6 carbon rings and 3- to 8-membered heterocycles are optionally composed of one or more elements selected from halogens, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 5 Independently selected from hydrogen or C1-C6 alkyl; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl group of the -C3 alkyl)phenyl group is optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl, or -N(R) 5 )2; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each Q is independently selected from the bond, S, and O; B is selected from heterocycles and carbocycles, wherein the heterocycles and carbocycles are optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C 3- C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally separated by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and wherein B forms a spirocyclic ring with ring A; and Ring A is selected from heterocycles and carbocycles, wherein the heterocycle or carbocycle is optionally composed of one or more rings selected from R. 4 Substituents are substituted.

242. The method of claim 241, wherein B is selected from optionally substituted 5- to 15-membered heterocycles and optionally substituted C3-C. 15 Carbon ring.

243. The method of claim 242, wherein B is selected from optionally substituted 8- to 15-membered fused heterocycles and optionally substituted C8-C. 15 Fused carbon rings.

244. The method of claim 243, wherein B is an optionally substituted 8- to 15-membered fused heterocycle.

245. The method of claim 243, wherein B is an optionally substituted unsaturated C8-C. 15 Fused carbon rings.

246. The method according to any one of claims 241 to 245, wherein for B, the optionally substituted 8- to 15-membered fused heterocycle and the optionally substituted C8-C 15 Each fused carbon ring is independently bicyclic or tricyclic.

247. The method of claim 246, wherein for B, the heterocyclic ring and the carbocyclic ring are each independently bicyclic.

248. The method of claim 246, wherein for B, the heterocyclic ring and the carbocyclic ring are each independently tricyclic.

249. The method according to any one of claims 241 to 248, wherein B is selected from... , , , , , and Each of these may be optionally substituted by one or more substituents.

250. The method of claim 249, wherein B is selected from... , , , , , and Each of these may be optionally substituted by one or more substituents.

251. The method of claim 250, wherein B is selected from... and Each of these may be optionally substituted by one or more substituents.

252. The method according to any one of claims 241 to 251, wherein for B, one or more optional substituents of the heterocycle and carbide ring are independently selected from oxo, -NH2, halogen, C1-C3 alkyl.

253. The method according to any one of claims 241 to 252, wherein B is selected from... , , , , , , and .

254. The method according to any one of claims 241 to 253, wherein each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen.

255. The method of claim 254, wherein each R 4 Selected independently from C 1-6 Alkyl, oxo, and halogen.

256. The method according to any one of claims 241 to 255, wherein Y is O.

257. The method according to any one of claims 241 to 256, wherein R 1 Selected from 5- to 5-membered heterocycles with optional substitution.

258. The method of claim 257, wherein R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycle is optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、=O、-CN、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

259. The method of claim 258, wherein R 1 Selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycle is optionally selected independently by one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

260. The method according to claims 258 to 259, wherein R 20 Selected from hydrogen and C 1-3 alkyl.

261. The method according to any one of claims 241 to 260, wherein R 1 The 5- to 12-membered heterocycles are unsaturated.

262. The method according to any one of claims 241 to 260, wherein R 1 The 5- to 12-membered heterocycles are saturated.

263. The method according to any one of claims 241 to 260, wherein R 1 The 5- to 12-membered heterocyclic rings are bridged.

264. The method according to any one of claims 245 to 260, wherein R 1 Selected from , , , , , , , , , , . , , , , , , , , , , , , , , , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

265. The method of claim 264, wherein R 1 Selected from , , , , and Each of them is optionally selected independently from one or more halogens, -OH, -N(R) 20 )2、-NO2、C 1-6 aminoalkyl, C 1-6 Alkoxy, =O, -CN, C 1-6 Hydroxyalkyl and C 1-6 Substituents of haloalkyl groups.

266. The method of claim 265, wherein R 1 Selected from , and .

267. The method according to any one of claims 241 to 266, wherein R 2 It is an L-heterocyclic ring, optionally bounded by one or more R-rings. 6 replace.

268. The method according to any one of claims 241 to 267, wherein L is selected from C1-C4 alkylene groups.

269. The method according to claim 267 or 268, wherein L is selected from unsubstituted C1-C4 alkylene groups.

270. The method according to any one of claims 231 to 259, wherein YR 2 Selected from and The heterocyclic portion is optionally separated by one or more R 6 replace.

271. The method of claim 270, wherein R 2 R 6 Each time it appears, it is independently selected from halogen, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl.

272. The method of claim 271, wherein R 2 R 6 Each time it appears, it is independently selected from C1-C3 alkyl groups and halogens.

273. The method of claim 272, wherein YR 2 Selected from , and .

274. A method of treating cancer in a subject in need, comprising administering to said subject a therapeutically effective amount of a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II*): Equation (II*) Or its pharmaceutically acceptable salt, wherein: M is selected from O and NR 3 ; R 3 Selected from hydrogen, C 1-6 Alkyl and C 1-6 Cyanoalkyl; R 1 Selected from 7- to 10-membered heterocycles, wherein the 7- to 10-membered heterocycle is optionally selected independently by one or more halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group and the substituents of the 5- to 12-membered heterocycle are substituted, wherein the 5- to 12-membered heterocycle is optionally and independently substituted by one or more R groups. 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; B is selected from C6-C 15 Carbon rings, wherein the C6-C 15 The carbon ring is optionally composed of one or more elements independently selected from halogens, C1-C3 alkyl groups, -B(OR) groups. 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group; R 2 Selected from -L-heterocycles, wherein the heterocycle of the -L-heterocycle is optionally divided by one or more R 6 replace; L is independently selected from C l -C4 alkylene, wherein the C l -C4 alkylene groups are optionally surrounded by one or more molecules selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl substituents; wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-6 A carbocyclic ring and 3 to 6-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbon rings and 3 to 12-membered heterocycles.

275. The method of claim 274, wherein R 1 Selected from optionally substituted 7- to 10-membered spiroheterocycles and optionally substituted 7- to 10-membered fused heterocycles.

276. The method according to claim 274 or 275, wherein R 1 The heterocycle has at least one nitrogen atom.

277. The method of claim 276, wherein R 1 At least one nitrogen atom in the heterocycle is bonded to formula (II*).

278. The method according to any one of claims 275 to 277, wherein R 1 Selected from substituted 10-membered spiroheterocycles and substituted 10-membered fused heterocycles.

279. The method according to any one of claims 275 to 278, wherein R 1 One or more optional substituents are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group, 5 to 12-membered heterocycle, wherein the 5 to 12-membered heterocycle is optionally composed of one or more elements selected from halogens and C. 1-6 Alkyl substituents.

280. The method according to any one of claims 275 to 279, wherein one or more optional substituents of R1 are independently selected from halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycles are optionally composed of one or more elements selected from halogens and C. 1-6 Alkyl substituents.

281. The method according to any one of claims 275 to 280, wherein R 1 Selected from the replacement .

282. The method according to any one of claims 275 to 281, wherein R 1 Selected from one or more independently selected halogens, -OH, -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)OR 20 -C(O)NHOR 20 -N(R) 20 )2、-C(O)R 20 -NO2, =O, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Alkoxyalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 Alkyne group, 5- to 12-membered heterocyclic substituents The 5- to 12-membered heterocycle is optionally composed of one or more elements selected from halogens and C. 1-6 Alkyl substituents.

283. The method according to any one of claims 275 to 281, wherein R 1 Selected from , , , , , , , , , , , , , , , , , and .

284. The method according to any one of claims 275 to 282, wherein R 1 Selected from , , , , , , , , , , , , , , , , , and .

285. The method of claim 278, wherein R 1 yes .

286. The method of claim 274, wherein M is selected from O.

287. The method of claim 274, wherein M is selected from NCH3 and NCH2CH3.

288. The method of claim 287, wherein M is NMe.

289. The method according to any one of claims 224 to 238, wherein R 2 The heterocycle is a saturated heterocycle.

290. The method of claim 289, wherein R 2 The heterocycle is a saturated heterocycle.

291. The method of claim 290, wherein R 2 R 6 Each time it appears, it is independently selected from halogen, =CH2, hydroxyl, C. l -C3 hydroxyalkyl, C l -C3 alkyl, C l -C3 haloalkyl, C1-C3 alkoxy, cyano and C l -C3 aminoalkyl.

292. The method of claim 291, wherein R 2 L is selected from C1-C4 alkylene groups and .

293. The method according to any one of claims 274 to 292, wherein R 2 Selected from , , , , and .

294. The method according to any one of claims 274 to 293, wherein B is selected from optionally substituted C9-C. 10 Fused carbon rings.

295. The method according to any one of claims 274 to 294, wherein B is selected from... and Each of these can be arbitrarily replaced.

296. The method according to any one of claims 274 to 295, wherein B is optionally composed of one or more elements independently selected from halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -OC. l -C3 haloalkyl, -C(O)NH2, -NH2, =O, -CN, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 2-6 Substitution of the alkynyl group.

297. The method of claim 296, wherein B is optionally substituted with one or more substituents independently selected from halogens.

298. The method of claim 296, wherein B is selected from... and .

299. The method of claim 298, wherein B is .

300. The method of claim 298, wherein B is .

301. The method of claim 274, wherein B is unsubstituted.

302. The method of claim 274, wherein B is substituted.

303. A method of treating cancer in a subject in need, comprising administering to the subject a therapeutically effective amount of a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41, 4 2, 43, 44, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

304. A method of treating cancer in a subject in need, comprising administering to the subject a therapeutically effective amount of a combination of a RAF-MEK-ERK pathway inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41 42, 43, 44, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

305. A method of treating cancer in a subject in need, comprising administering to the subject a therapeutically effective amount of a combination of an ERBB family inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41, 42. 43, 44, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

306. A method of treating cancer in a subject in need, comprising administering to the subject a therapeutically effective amount of a combination of an EGFR inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41, 42, 4 3, 44, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

307. A method of treating cancer in a subject in need, comprising administering to the subject a therapeutically effective amount of a combination of an SHP-2 inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41, 42. 43, 44, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

308. A method of treating cancer in a subject in need, comprising administering to the subject a therapeutically effective amount of a combination of an SOS1 inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41, 42, 4 3, 44, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

309. The method according to any one of claims 303 to 308, wherein the compound of formula (II) is selected from compounds 53, 61, 63, 64, 69 and 96, or a pharmaceutically acceptable salt of any one of them.

310. The method according to any one of claims 303 to 309, wherein the compound of formula (II) is selected from compound 53, or a pharmaceutically acceptable salt thereof.

311. The method according to any one of claims 303 to 309, wherein the compound of formula (II) is selected from compound 61, or a pharmaceutically acceptable salt thereof.

312. The method according to any one of claims 303 to 309, wherein the compound of formula (II) is selected from compound 63, or a pharmaceutically acceptable salt thereof.

313. The method according to any one of claims 303 to 309, wherein the compound of formula (II) is selected from compound 64, or a pharmaceutically acceptable salt thereof.

314. The method according to any one of claims 303 to 309, wherein the compound of formula (II) is selected from compound 69, or a pharmaceutically acceptable salt thereof.

315. The method according to any one of claims 303 to 309, wherein the compound of formula (II) is selected from compound 96, or a pharmaceutically acceptable salt thereof.

316. The method according to any one of claims 303 to 315, wherein the combination exhibits a synergistic effect.

317. The method according to any one of claims 303 to 306 & 309 to 315, wherein the inhibitor is selected from afatinib, dacomitinib, poziotinib, erlotinib, gefitinib, saprotinib, tarloxotinib, and cetuximab.

318. The method according to any one of claims 303 to 306 and 309 to 315, wherein the inhibitor is cetuximab.

319. A method of treating cancer in a subject in need, comprising administering to said subject a therapeutically effective amount of a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II*): Equation (II*) Or its pharmaceutically acceptable salt, wherein: M is selected from O and NR 3 ; R 3 Selected from hydrogen, C 1-6 Alkyl and C 1-6 Cyanoalkyl; R 1 Selected from 7- to 10-membered heterocycles, wherein the 7- to 10-membered heterocycle is optionally selected independently by one or more halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group and the substituents of the 5- to 12-membered heterocycle are substituted, wherein the 5- to 12-membered heterocycle is optionally and independently substituted by one or more R groups. 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; B is selected from C6-C 15 Carbon rings, wherein the C6-C 15 The carbon ring is optionally composed of one or more elements independently selected from halogens, C1-C3 alkyl groups, -B(OR) groups. 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group; R 2 Selected from -L-heterocycles, wherein the heterocycle of the -L-heterocycle is optionally divided by one or more R 6 replace; L is independently selected from C l -C4 alkylene, wherein the C l -C4 alkylene groups are optionally surrounded by one or more molecules selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl substituents; wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-6 A carbocyclic ring and 3 to 6-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbon rings and 3 to 12-membered heterocycles.

320. The method according to any one of claims 303 to 319, wherein the combination exhibits a synergistic effect.

321. The method of claim 303 or 319, wherein the therapeutically effective amount of the combination of the inhibitor with the compound or salt results in prolonged overall survival, prolonged progression-free survival, increased tumor growth regression, increased tumor growth inhibition, and prolonged duration of stable disease in the subject relative to treatment with the compound or salt alone or any combination thereof.

322. The method according to any one of claims 303 to 321, wherein the therapeutically effective amount of the compound or salt in the combination is about 0.01 to 100 mg / kg per day.

323. The method according to any one of claims 303 to 322, wherein the therapeutically effective amount of the compound or salt in the combination is about 0.1 to 50 mg / kg per day.

324. The method according to any one of claims 303 to 323, wherein the therapeutically effective amount of the inhibitor in the combination is about 0.01 to 100 mg / kg per day.

325. The method according to any one of claims 303 to 324, wherein the therapeutically effective amount of the inhibitor in the combination is about 0.1 to 50 mg / kg per day.

326. The method according to any one of claims 303 to 325, wherein the inhibitor and the compound or salt are administered on different dates.

327. The method according to any one of claims 303 to 326, wherein the compound or salt is administered at the maximum tolerated dose.

328. The method according to any one of claims 303 to 327, wherein the inhibitor is administered at the maximum tolerated dose.

329. The method according to any one of claims 303 to 328, wherein the inhibitor and the compound or salt are each administered at the maximum tolerated dose.

330. The method of claim 319, wherein the RTK-MAPK pathway inhibitor is a RAF-MEK-ERK pathway inhibitor.

331. The method of claim 319, wherein the RTK-MAPK pathway inhibitor is an ERBB family inhibitor.

332. The method according to claim 319 or 331, wherein the inhibitor is selected from afatinib, dacomitinib, poziotinib, erlotinib, gefitinib, saprotinib, tarloxotinib, and cetuximab.

333. The method of claim 319 or 332, wherein the inhibitor is cetuximab.

334. The method of claim 319, wherein the RTK-MAPK pathway inhibitor is an epidermal growth factor receptor (EGFR) inhibitor.

335. The method of claim 319, wherein the RTK-MAPK pathway inhibitor is an SHP-2 inhibitor.

336. The method of claim 335, wherein the SHP-2 inhibitor is SHP-099 (6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazine-2-amine dihydrochloride); RMC-4550 (3-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]dec-8-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazine-2-yl)methanol), RMC-4360, or TNO155 (Novartis).

337. The method of claim 335, wherein the SHP-2 inhibitor is RMC-4550.

338. The method of claim 335, wherein the SHP-2 inhibitor is RMC-4360.

339. The method of claim 335, wherein the SHP-2 inhibitor is TNO155.

340. The method of claim 335, wherein the SHP-2 inhibitor is SHP-099.

341. The method of claim 319, wherein the RTK-MAPK pathway inhibitor is an SOS1 inhibitor.

342. The method of claim 341, wherein the SOS1 inhibitor is BI-3406.

343. The method according to any one of claims 319 to 342, wherein the RTK-MAPK pathway inhibitor is administered orally.

344. The method according to any one of claims 303 to 343, wherein the cancer is selected from: Heart: Sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, and teratoma; Lungs: Bronchial carcinoma (squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma; Gastrointestinal tract: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vasoactive intestinal peptide tumor), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); Urogenital tract: Kidneys (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), Bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), Prostate (adenocarcinoma, sarcoma), Testes (seminomatous seminoma, teratoma, embryonal carcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenoid tumor, lipoma); Liver: Hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Biliary tract cancer: gallbladder cancer, ampullary cancer, bile duct cancer; Bone: Osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondrofibroma (osteochondrogenic exostosis), benign chondroma, chondroblastoma, chondromycinoma, osteomyxoid fibroma, osteoid osteoma, and giant cell tumor; Nervous system: Skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningeal sarcoma, glioma), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germ cell tumor (pineal tumor), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumor), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecology: Uterus (endometrial cancer), Cervix (cervical cancer, pretumoral cervical dysplasia), Ovary (ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-theca cell tumor, ovarian male cell tumor, dysgerminoma, malignant teratoma), Vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), Vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonic rhabdomyosarcoma), Fallopian tube (cancer); Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma). Skin conditions: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevus of dysplasia, lipoma, hemangioma, dermatofibroma, keloid, psoriasis; and Adrenal gland: neuroblastoma.

345. The method according to any one of claims 303 to 343, wherein the cancer is non-small cell lung cancer, small cell lung cancer, colorectal cancer, rectal cancer, or pancreatic cancer.

346. The method according to any one of claims 303 to 343, wherein the cancer is non-small cell lung cancer.

347. The method according to any one of claims 303 to 343, wherein the cancer is small cell lung cancer.

348. The method according to any one of claims 303 to 343, wherein the cancer is colorectal cancer.

349. The method according to any one of claims 303 to 343, wherein the cancer is rectal cancer.

350. The method according to any one of claims 303 to 343, wherein the cancer is pancreatic cancer.

351. The method according to any one of claims 303 to 343, wherein the cancer is a solid tumor cancer.

352. The method according to any one of claims 303 to 351, wherein the cancer is selected from cancers associated with KRas mutations.

353. The method according to any one of claims 303 to 351, wherein the cancer is selected from KRas wild-type related cancers.

354. The method according to any one of claims 303 to 351, wherein the cancer is selected from KRas G12D-associated cancer, KRas G12V-associated cancer, and KRas wild-type-associated cancer.

355. The method according to any one of claims 303 to 351, wherein the cancer is a KRas G12D-associated cancer.

356. The method according to any one of claims 303 to 351, wherein the cancer is a KRas G12V-related cancer.

357. The method according to any one of claims 303 to 351, wherein the cancer is a KRas wild-type related cancer.

358. The method according to any one of claims 303 to 351, wherein the RTK-MAPK pathway inhibitor synergistically increases the sensitivity of cancer cells to the compound or salt.

359. The method according to any one of claims 1 to 40, wherein the compound is selected from: Or, or a pharmaceutically acceptable salt thereof.

360. A method of treating cancer in a subject in need, comprising administering to said subject a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II): Equation (II) Or its pharmaceutically acceptable salt, wherein: M is selected from O, S, SO, SO2, and NR. 3 ; R 1 Selected from C3-C 12 A carbon ring and 5 to 15-membered heterocycles, each of which is optionally selected independently by one or more halogens, -B (OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl-SO2R 20 C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Substitution of the carbocyclic ring and 5- to 12-membered heterocycles, wherein the C3-C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally and independently construed by one or more R 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C1-6 alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl and C3-C 12 Carbon rings; Y is selected from bonds, O, S, and NR. 5 ; R 2 Selected from -LN(R) 21 )2、-L-OR 21 Heterocyclic rings, C l -C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R) 21 )2、-LC l -C6 haloalkyl, -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 -LS(O)2N(R) 21 )2、-LN(R 21 )C(O)(OR 21 -L-OC(O)N(R) 21 )2 and -LC(=O)OC l -C6 alkyl, wherein the heterocycle, the -L-NR 21 The aryl moiety of the C(O)-aryl group, the heterocyclic moiety of the -L-heterocyclic group, and the cycloalkyl moiety of the -L-cycloalkyl group are each optionally surrounded by one or more R groups. 6 Replacement, wherein the aryl portion of the -L-aryl group and the heteroaryl portion of the -L-heteroaryl group are each optionally replaced by one or more R 7 Replacement, where R is a bond, O, or S. 2 Further selected from hydrogen; Each L is independently selected from, optionally by, one or more elements selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl, C3-C6 carbon ring, or 3 to 8-membered heterocyclic substituents l -C4 alkylene ring, wherein the C3-C6 carbide ring and the 3- to 8-membered heterocycle are optionally composed of one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 The alkyl halogroup is substituted; and any two substituents on the same carbon atom of L together form a C3-C6 carbon ring or a 3- to 8-membered heterocycle, wherein the C3-C6 carbon ring and the 3- to 8-membered heterocycle are each optionally substituted by one or more elements selected from halogen, -OH, -NO2, =O, =S, -CN, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups; R 3 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxyalkyl, C 3-12 Carbon rings and 3 to 12-membered heterocycles, of which C 3-12 The carbide ring and the 3 to 12-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; n is selected from 0 to 2; Each R 4 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne, oxo, hydroxyl, halogen, C 3-12 Carbocyclic rings and 3 to 12-membered heterocycles, wherein the C1-C6 alkyl, C 3-12 The carbon ring and the 3 to 12-membered heterocycle are each optionally selected independently from cyano, halogen, -OR 5 and -N(R) 5 Substitution of )2 by substituents; Each R 5 Independently selected from hydrogen or C1-C6 alkyl; Each R 6 Independently selected from halogens, hydroxyl groups, and C l -C3 hydroxyalkyl, C l -C3 alkyl, oxo, C l -C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C l -C3 alkyl, C l -C3 aminoalkyl, -N(R) 5 )S(O)2(R 5 -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxyCH2-, -N(R 5 2. (C1-C3 alkoxy)C l -C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, (C1-C3 haloalkyl)C(=O)-, -SO2F, (C1-C3 alkoxy)C l -C3 alkoxy group, -CH2OC(O)N(R) 5 )2、-CH2NHC(O)OC1-C6 alkyl、-CH2NHC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O) heterocyclic、-OC(O)N(R 5 )2、-OC(O)NH(C1-C3 alkyl)O(C l -C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C l -C3alkyl)phenyl(C1-C3alkyl)N(CH3)2、-OC(O)NH(C1-C3alkyl)O(C l -C3 alkyl)phenyl, -OC(O) heterocyclic, -OC l -C3 alkyl and -CH2 heterocyclic, of which -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C l The phenyl groups of the -C3 alkyl)phenyl groups are each optionally substituted with one or more substituents selected from -C(O)H and OH, wherein -OC l The alkyl group of the -C3 alkyl group is optionally substituted with a substituent selected from heterocycles, oxo groups and hydroxyl groups; and the heterocycle of the -CH2 heterocyclic group is optionally substituted with an oxo group; Each Q is independently selected from the bond, S, and O; Each R 7 Independently selected from halogens, hydroxyl groups, HC(=O)-, C l -C4 alkyl, C l -C4 alkoxy group, C l -C4 haloalkyl, C l -C4 hydroxyalkyl, or -N(R) 5 )2; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; Each R 21 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Substitution of carbocyclic rings and 3 to 12-membered heterocycles; and B is selected from heterocycles and carbocycles, wherein the heterocycle and carbocycle are each optionally selected independently by one or more halogens, cyano groups, hydroxyl groups, =O, -NO2, C. l -C4 alkyl, C 1-6 aminoalkyl, -SC l -C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 hydroxyalkynyl, C1-C3 cyanoalkyl, triazolyl, C l -C3 haloalkyl, -OC l -C3 haloalkyl, -SC l -C3 haloalkyl, C1-C3 alkoxy, C l -C3 hydroxyalkyl, -CH2C(=O)N(R) 5 )2、-C3-C4 ynyl group (NR 5 )2、-N(R 5 2. (C1-C3 alkoxy)halogenated C l -C3 alkyl-, C 1-6 Alkyl-N(R) 20 2. C3-C 12 Substitution of carbocyclic rings and 5- to 12-membered heterocycles, wherein C 3- C 12 The carbon ring and the 5- to 12-membered heterocycle are each optionally separated by one or more elements selected from halogen, -OH, -NO2, -NH2, =O, =S, -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Substituents of haloalkyl groups.

361. A method of treating cancer in a subject in need, comprising administering to said subject a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II*): Equation (II*) Or its pharmaceutically acceptable salt, wherein: M is selected from O and NR 3 ; R 3 Selected from hydrogen, C 1-6 Alkyl and C 1-6 Cyanoalkyl; R 1 Selected from 7- to 10-membered heterocycles, wherein the 7- to 10-membered heterocycle is optionally selected independently by one or more halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group and the substituents of the 5- to 12-membered heterocycle are substituted, wherein the 5- to 12-membered heterocycle is optionally and independently substituted by one or more R groups. 1* replace; Each R 1* Independently selected from halogens, -B(OR) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, -NHCN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C3-C 12 Carbon rings; B is selected from C6-C 15 Carbon rings, wherein the C6-C 15 The carbon ring is optionally composed of one or more elements independently selected from halogens, C1-C3 alkyl groups, -B(OR) groups. 20 )2、-OR 20 -C(O)N(R) 20 )2、-N(R 20 )2、=O、-CN、-NHCN、C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Substitution of the alkynyl group; R 2 Selected from -L-heterocycles, wherein the heterocycle of the -L-heterocycle is optionally divided by one or more R 6 replace; L is independently selected from C l -C4 alkylene, wherein the C l -C4 alkylene groups are optionally surrounded by one or more molecules selected from hydroxyl, C l -C4 hydroxyalkyl, C l -C4 alkyl substituents; wherein any two substituents on the same carbon atom of L together form a C3-C6 carbon ring; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 3-6 A carbocyclic ring and 3 to 6-membered heterocycles, each of which is optionally selected independently by one or more halogens, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, =NH, C 3-12 Substitution of carbon rings and 3 to 12-membered heterocycles.

362. A method of treating cancer in a subject in need, comprising administering to the subject a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41, 42, 4 3, 44, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

363. A method of treating cancer in a subject in need, comprising administering to the subject a combination of an EGFR inhibitor and a compound of formula (II), wherein the compound is selected from: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24A, 26, 23A, 23B, 27A, 27B, 28A, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 39A, 39B, 40, 41, 42, 43, 4 4, 45, 46A, 46B, 47, 48, 49, 50, 51A, 51B, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 64B, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, and 103, or a pharmaceutically acceptable salt of any of them.

364. A method of treating cancer in a subject in need, comprising administering to the subject a combination of an EGFR inhibitor and a compound of formula (II), wherein the compound is selected from compounds 53, 61, 63, 64, 65, 69 and 96, or a pharmaceutically acceptable salt of any one thereof.

365. The method of claim 364, wherein the compound is compound 53.

366. The method of claim 364, wherein the compound is compound 61.

367. The method of claim 364, wherein the compound is compound 63.

368. The method of claim 364, wherein the compound is compound 64.

369. The method of claim 364, wherein the compound is compound 65.

370. The method of claim 364, wherein the compound is compound 69.

371. The method of claim 364, wherein the compound is compound 96.

372. The method according to any one of claims 360 to 371, wherein the cancer is selected from: Heart: Sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyosarcoma, fibroma, lipoma, and teratoma; Lungs: Bronchial carcinoma (squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma; Gastrointestinal tract: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vasoactive intestinal peptide tumor), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); Urogenital tract: Kidneys (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), Bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), Prostate (adenocarcinoma, sarcoma), Testes (seminomatous seminoma, teratoma, embryonal carcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenoid tumor, lipoma); Liver: Hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Biliary tract cancer: gallbladder cancer, ampullary cancer, bile duct cancer; Bone: Osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondrofibroma (osteochondrogenic exostosis), benign chondroma, chondroblastoma, chondromycinoma, osteomyxoid fibroma, osteoid osteoma, and giant cell tumor; Nervous system: Skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningeal sarcoma, glioma), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germ cell tumor (pineal tumor), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumor), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecology: Uterus (endometrial cancer), Cervix (cervical cancer, pretumoral cervical dysplasia), Ovary (ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-theca cell tumor, ovarian male cell tumor, dysgerminoma, malignant teratoma), Vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), Vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonic rhabdomyosarcoma), Fallopian tube (cancer); Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma). Skin conditions: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevus of dysplasia, lipoma, hemangioma, dermatofibroma, keloid, psoriasis; and Adrenal gland: neuroblastoma.

373. The method according to any one of claims 360 to 371, wherein the cancer is non-small cell lung cancer, small cell lung cancer, colorectal cancer, rectal cancer, or pancreatic cancer.

374. The method according to any one of claims 360 to 371, wherein the cancer is non-small cell lung cancer.

375. The method according to any one of claims 360 to 371, wherein the cancer is small cell lung cancer.

376. The method according to any one of claims 360 to 371, wherein the cancer is colorectal cancer.

377. The method according to any one of claims 360 to 371, wherein the cancer is rectal cancer.

378. The method according to any one of claims 360 to 371, wherein the cancer is pancreatic cancer.

379. The method according to any one of claims 360 to 371, wherein the cancer is a solid tumor cancer.

380. The method according to any one of claims 360 to 371, wherein the cancer is selected from cancers associated with KRas mutations.

381. The method according to any one of claims 360 to 371, wherein the cancer is selected from KRas wild-type related cancers.

382. The method according to any one of claims 360 to 371, wherein the cancer is selected from KRas G12D-associated cancer, KRas G12V-associated cancer, and KRas wild-type-associated cancer.

383. The method according to any one of claims 360 to 371, wherein the cancer is a KRas G12D-associated cancer.

384. The method according to any one of claims 360 to 371, wherein the cancer is a KRas G12V-associated cancer.

385. The method according to any one of claims 360 to 371, wherein the cancer is a KRas wild-type related cancer.

386. The method according to any one of claims 360 to 371, wherein the combination exhibits a synergistic effect.

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