Combination therapy using KRAS modulators

Abstract

A method for treating cancer in a subject requiring such treatment is provided herein, comprising the step of administering to the subject a therapeutically effective combination of an RTK-MAPK pathway inhibitor and a compound of formula (II). In some embodiments, the pharmaceutical composition comprises a RAF-MEK-ERK inhibitor or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable additive. In some cases, the pharmaceutical composition comprises a compound of formula (II) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable additive. In some cases, the pharmaceutical composition may be used simultaneously, individually, or sequentially in the method. TIFF2026527617000603.tif1628

Description

[Technical Field]

[0001] cross reference This application claims the interests of U.S. Provisional Patent Application No. 63 / 518,177, filed on August 8, 2023, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Background of the Invention The small GTPase protein Kirsten rat sarcoma 2 virus oncogene homolog (KRAS) is a member of the Ras family of cellular signaling switches that regulate the growth and survival of both normal and cancer cells (see, e.g., 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 dysregulating the mitogenic factor-activated protein kinase (MAPK) signaling cascade and other effector pathways (see, e.g., Stephen, AG, et al., Dragging ras back in the ring. Cancer Cell, 2014. 25(3): p. 272-81). Although Ras has been recognized as a target in cancer for about 40 years, Ras-driven cancers remain among the most difficult to treat due to their insensitivity to available targeted therapies. Ras, encoded by three main genes—KRAS, NRAS, and HRAS—have the most frequent mutations of any oncogene. All oncogenic Ras mutations drive a switch that results in accumulation in an active GTP-bound state. The most common Ras mutation found across human tumor types is KRAS G12D (see, e.g., The AACR Project GENIE Consortium. Cancer Discovery, 2017. 7(8): p. 818-831. Dataset Version 4). The activating mutation at codon 12 impairs the ability of low-molecular-weight GTPases, which play their role in hydrolyzing GTP. This dysregulation is fundamental to initiating and maintaining tumor progression.

[0003] Despite extensive efforts, no small molecules have been identified that block effector binding or restore sensitivity to GTPase-activated protein (GAP), although several have been found that block the interaction between Ras and SOS, a guanine nucleotide exchange factor (GEF) that activates Ras in the plasma membrane. The KRAS G12C mutation, the most common in lung adenocarcinoma, has been clinically shown to be sensitive to direct inhibition by covalent modification with small molecule inhibitors that trap the protein in an inactive GDP-bound state. KRAS G12D mutations result in an intrinsic rate of GTP hydrolysis that is significantly slower than G12C, leading to further constitutive activation. Therefore, pharmacological targeting of the inactive state is unlikely to achieve similar results for G12D, despite the presence of a similar binding pocket in the GDP state. Furthermore, while cysteine ​​present at the site of the activating mutation provides cysteine ​​itself for covalent chemistry, aspartic acid does not provide a typical medicinal chemistry approach for selective covalent modification. To achieve selective inhibition of cancer cells by potentially exploiting the accumulation of KRAS G12D and other mutant variants in the GTP-bound state as a vulnerability while preserving normal Ras function, it is appealing for small molecule inhibitors to bind to the GTP state and stabilize a conformation that prevents interaction with effector proteins and oncogenic signaling. Furthermore, it has been shown that only constitutive activation of Raf, MEK, and ERK kinases in the downstream MAPK cascade of Ras can bypass the requirements of the Ras protein in proliferative signaling (see, e.g., Drosten, M., et al., Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival. EMBO J, 2010. 29(6): p. 1091-104). All evidence indicates that MAPK signaling is essential for the growth action of Ras in cancer, so selective inhibition of KRAS mutants in this pathway is considered an important functional leadout for the potential clinical benefits of novel therapeutic approaches. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Cully, M. and J. Downward, SnapShot: Ras Signaling. Cell, 2008. 133(7): p. 1292-1292 e1 [Non-Patent Document 2] Stephen, AG, et al., Dragging ras back in the ring. Cancer Cell, 2014. 25(3): p. 272-81 [Non-Patent Document 3] The AACR Project GENIE Consortium. Cancer Discovery, 2017. 7(8): p. 818-831. Dataset Version 4 [Non-Patent Document 4] Drosten, M., et al., Genetic analysis of Ras signaling pathways in cell proliferation, migration and survival. EMBO J, 2010. 29(6): p. 1091-104 [Overview of the Initiative] [Means for solving the problem]

[0005] Summary of the Invention The compounds disclosed herein are potent inhibitors of KRas signaling and exhibit monotherapy activity in vitro, inhibiting the proliferation of cell lines harboring KRas mutations or other KRAS activity genetic alterations. However, the relative potency and / or observed maximum effect of any given KRas inhibitor may vary among KRAS mutant cell lines. The reasons for this range in potency and observed maximum effect (one or more) are not fully understood, but certain cell lines appear to have different intrinsic resistances to the mechanism of action, which depends on binding to certain conformational states of the KRAS protein. Therefore, there is a need to develop alternative methods to maximize the potency, efficacy, therapeutic index, and / or clinical benefit of KRas inhibitors in vitro and in vivo. Due to known feedback loops in the Ras signaling pathway, inhibition upstream of RTK signaling or downstream of MAPK signaling may require complete blockade of KRas mutant activity in the presence of a KRas inhibitor.

[0006] In some embodiments, the present disclosure relates to a method for treating cancer in a subject requiring such treatment, comprising: an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (I): [Chemical] administering a therapeutically effective amount of a combination with or a pharmaceutically acceptable salt thereof, a method comprising (wherein, R 20 , 20 , 20 , 1~6 , 20 , 20 , 20 , 1~6 , 20 , 20 , 20 , 1~6 , 12 , 20 , 20 , 20 , 20 , 20 , 20 , 2~6 , 20 , 20 , 20 , 20 , 20 , 20 , 20 , 2~6 , 20 , 20 , 20 , 1~6 , 20 , 20 , 1~6 , 20 , 20 , 1~6 , 12 , 1~6 is selected from C3-C 12 carbocyclic rings and 5- to 15-membered heterocyclic rings, each of which is independently halogen, -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<00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 membered heterocycles contain one or more R 1* Each is replaced independently as needed. R 1* These are halogen, -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 Ure 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 Alkenil, C 2~6 Alkinyl, and C3~C 12 Selected independently from the carbon ring, Y is a bond, O, S and NR 5 Selected from, R 2 is selected from hydrogen, -N(R 21 )2, -L-N(R 21 )2, -L-OR 21 , a heterocyclic ring, C1-C6 alkyl, -L-heterocyclic ring, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -L-C(O)N(R 21 )2, -L-C1-C6 haloalkyl, -L-NR 21 C(O)-aryl, -L-COOH, -L-NR 21 S(O)2(R 21 )、-L-S(O)2N(R 21 )2, -L-N(R 21 )C(O)(OR 21 )、-L-OC(O)N(R 21 )2 and -LC(=O)OC1-C6 alkyl, and the aryl moiety of the heterocyclic ring and -L-NR 5 C(O)-aryl and the heterocyclic moiety of -L-heterocyclic ring and the cycloalkyl moiety of -L-cycloalkyl are optionally substituted by one or more R 6 s, and the aryl or heteroaryl of -L-aryl and -L-heteroaryl are optionally substituted by one or more R 7 s, Each L is independently selected from C1-C4 alkylene optionally substituted by one or more substituents selected from hydroxy, C1-C四环素hydroxyalkyl, C1-C4 alkyl, C3-C6 carbocyclic ring or 3-8 member heterocyclic ring, and the C3-C6 carbocyclic ring and 3-8 member heterocyclic ring are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 haloalkyl, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or 3-8 member heterocyclic ring, and the C3-C6 carbocyclic ring and 3-8 member heterocyclic ring are halogen, -OH, -NO2, =O, =S, -CN, C 1~6Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyl groups. R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, C 3~12 Carbon rings and 3- to 12-membered heterocycles are halogens, -OH, -CN, -NO2, -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 Each molecule is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. R 5 Each is independently selected from hydrogen or C1-C6 alkyl groups. R 6 These are halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C1-C3 alkyl, C1-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)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5 )2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, -OC(O) heterocycle, -O-C1~C3 alkyl and -CH2 heterocycle are independently selected, the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, the alkyl in -O-C1~C3alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy, and the heterocycle of -CH2 heterocyclil is optionally substituted with oxo, R 7 These are halogen, hydroxyl, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, or -N(R) 5 ) Selected independently from 2, R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, =NH, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 21 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, Q is selected independently from the join, S, and O, respectively. B is selected from heterocycles and carbocycles, and heterocycles and carbocycles are halogen, cyano, hydroxy, =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 alkynyl (NR 5 )2, -N(R 5 )2, (C1~C3 alkoxy) Halo C l ~C3 alkyl-, C 1~6 alkyl-N(R 20 )2, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 member heterocycles are halogens, -OH, -NO2, -NH2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each is optionally substituted with one or more substituents selected from haloalkyl groups, and B forms a spiro ring with ring A. Ring A is selected from heterocycles and carbocycles, and the heterocycle or carbocycle is R 4 (Optionally substituted by one or more substituents selected from the following.)

[0007] In some embodiments, the present disclosure relates to a method for treating cancer in a subject requiring such treatment, comprising: an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (II): [ka] The present invention provides a method comprising the step of administering a combination thereof with a pharmaceutically acceptable salt thereof (in the formula, M stands for O, S, SO, SO2 and NR 3 Selected from, R 1 C3~C 12 Selected from carbon rings and 5-15 member heterocycles, these are 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 Ure 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 Haloalkyl, C 1~6 Alkyl-SO2R 20 , C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 membered heterocycles contain one or more R 1* Each is replaced independently as needed. R 1* These are halogen, -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 Ure 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)OR20 -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 Alkenil, C 2~6 Alkinyl, and C3~C 12 Selected independently from the carbon ring, Y is a bond, O, S and NR 5 Selected from, R 2 is -LN(R 21 )2, -L-OR 21 , heterocyclic, C1-C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R 21 )2, -L-C1~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)OC1~C6 alkyl selected from heterocyclic, -L-NR 21 The aryl portion of C(O)-aryl, the heterocyclic portion of -L-heterocyclic, and the cycloalkyl portion of -L-cycloalkyl are one or more R 6 Each is substituted as needed, and the aryl portion of -L-aryl and the heteroaryl portion of -L-heteroaryl are replaced by one or more R 7 Each is substituted as necessary, and if Y is a bond, O or S, then R2 It is further selected from hydrogen, L is independently selected from C1-C4 alkylenes, each optionally substituted with one or more substituents selected from hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbon rings, or 3-8 membered heterocycles, where C3-C6 carbon rings and 3-8 membered heterocycles are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, where the C3-C6 carbon ring and 3-8 membered heterocycle are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, 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 Selected from carbon rings and 3- to 12-membered heterocycles, C 3~12 Carbon rings and 3- to 12-membered heterocycles are halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12Each molecule is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. n is selected from 0 to 2. R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynyl, oxo, hydroxyl, halogen, C 3~12 Independently selected from carbon rings and 3-12 membered heterocycles, C1-C6 alkyl, C 3~12 Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR 5 and -N(R 5 )2 is optionally replaced by one or more substituents independently selected from 2, R 5 Each is independently selected from hydrogen or C1-C6 alkyl groups. R 6 These are halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C1-C3 alkyl, C1-C3 aminoalkyl, and -N(R) respectively. 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)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, -OC(O) heterocycle, -O-C1~C3 alkyl and -CH2 heterocycle are independently selected, the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl are optionally substituted with one or more substituents selected from -C(O)H and OH, respectively, the alkyl in -O-C1~C3alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy, and the heterocycle of -CH2 heterocyclil is optionally substituted with oxo, Q is selected independently from the join, S, and O, respectively. R 7 These are halogen, hydroxyl, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, or -N(R) 5 ) Selected independently from 2, R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, =NH, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 21 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, B is selected from heterocycles and carbocycles, and heterocycles and carbocycles are halogen, cyano, hydroxy, =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 alkynyl (NR 5 )2, -N(R 5 )2, (C1~C3 alkoxy) Halo C l ~C3 alkyl-, C 1~6 alkyl-N(R 20 )2, C3~C 12 Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 member heterocycles are halogens, -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 (Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups.)

[0008] In some embodiments, the present disclosure relates to a method for treating cancer in a subject requiring such treatment, comprising: an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (II): [ka] The present invention provides a method comprising the step of administering a therapeutically effective amount of a combination of the salt or a pharmaceutically acceptable salt thereof (wherein the formula, M stands for O, S, SO, SO2 and NR 3 Selected from, R 1 C3~C 12 Selected from carbon rings and 5-15 member heterocycles, these are 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 Ure 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 1~6Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 1~6 Alkyl-SO2R 20 , C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 membered heterocycles contain one or more R 1* Each is replaced independently as needed. R 1* These are halogen, -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 Ure 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 1~6Cyanoalkyl, C 1~6 Haloalkyl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, and C3~C 12 Selected independently from the carbon ring, Y is a bond, O, S and NR 5 Selected from, R 2 is -LN(R 21 )2, -L-OR 21 , heterocyclic, C1-C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R 21 )2, -L-C1~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)OC1~C6 alkyl selected from heterocyclic, -L-NR 21 The aryl portion of C(O)-aryl, the heterocyclic portion of -L-heterocyclic, and the cycloalkyl portion of -L-cycloalkyl are one or more R 6 Each is substituted as needed, and the aryl portion of -L-aryl and the heteroaryl portion of -L-heteroaryl are replaced by one or more R 7 Each is substituted as necessary, and if Y is a bond, O or S, then R 2 It is further selected from hydrogen, L is independently selected from C1-C4 alkylenes, each optionally substituted with one or more substituents selected from hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbon rings, or 3-8 membered heterocycles, where C3-C6 carbon rings and 3-8 membered heterocycles are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, where the C3-C6 carbon ring and 3-8 membered heterocycle are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, 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 Selected from carbon rings and 3- to 12-membered heterocycles, C 3~12 Carbon rings and 3- to 12-membered heterocycles are halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 Each molecule is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. n is selected from 0 to 2. R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynyl, oxo, hydroxyl, halogen, C 3~12Independently selected from carbon rings and 3-12 membered heterocycles, C1-C6 alkyl, C 3~12 Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR 5 and -N(R 5 )2 is optionally replaced by one or more substituents selected independently of 2, R 5 Each is independently selected from hydrogen or C1-C6 alkyl groups. R 6 These are halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C1-C3 alkyl, C1-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)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, -OC(O) heterocycle, -O-C1~C3 alkyl and -CH2 heterocycle are independently selected, the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl are optionally substituted with one or more substituents selected from -C(O)H and OH, respectively, the alkyl in -O-C1~C3alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy, and the heterocycle of -CH2 heterocyclil is optionally substituted with oxo, Q is selected independently from the join, S, and O, respectively. R 7 These are halogen, hydroxyl, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, or -N(R) 5 ) Selected independently from 2, R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, =NH, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 21 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, B is selected from heterocycles and carbocycles, and heterocycles and carbocycles are halogen, cyano, hydroxy, =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 alkynyl (NR 5 )2, -N(R 5 )2, (C1~C3 alkoxy) Halo C l ~C3 alkyl-, C 1~6 alkyl-N(R 20 )2, C3~C 12 Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 member heterocycles are halogens, -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 (Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups.)

[0009] In some embodiments, the present disclosure relates to a method for treating cancer in a subject requiring such treatment, comprising: an RTK-MAPK pathway inhibitor and a compound represented by the structure of formula (III): [ka] The present invention provides a method comprising the step of administering a therapeutically effective amount of a combination of the salt or a pharmaceutically acceptable salt thereof (wherein the formula, R 1 C3~C 12 Selected from carbon rings and 5-15 member heterocycles, these are 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 Ure 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 1~6Haloalkyl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 membered heterocycles contain one or more R 1* Each is replaced independently as needed. R 1* These are halogen, -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 Ure 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 Alkenil, C 2~6Alkinyl, and C3~C 12 Selected independently from the carbon ring, R 2 is, -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 ) Selected from 2 and L-bicyclic heterocycles, the bicyclic heterocycle is one or more R 6 It is replaced as needed, L is independently selected from C1-C4 alkylenes, each optionally substituted with one or more substituents selected from hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbon rings, or 3-8 membered heterocycles, where C3-C6 carbon rings and 3-8 membered heterocycles are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, where the C3-C6 carbon ring and 3-8 membered heterocycle are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. n is selected from 0 to 3. R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynyl, oxo, hydroxyl, halogen, C 3~12 Independently selected from carbon rings and 3-12 membered heterocycles, C1-C6 alkyl, C 3~12Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR 5 and -N(R 5 )2 is optionally replaced by one or more substituents independently selected from 2, B is selected from heterocycles and carbocycles, and heterocycles or carbocycles are halogen, cyano, hydroxy, =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 alkynyl (NR 5 )2, -N(R 5 )2, (C1~C3 alkoxy) Halo C l ~C3 alkyl-, C 1~6 alkyl-N(R 20 )2, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 member heterocycles are halogens, -OH, -NO2, -NH2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. Y is a bond, O, S and NR 5 Selected from, R 6These are halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C1-C3 alkyl, C1-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)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5 )2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, -OC(O) heterocycle, -O-C1~C3 alkyl and -CH2 heterocycle are independently selected, the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, the alkyl in -O-C1~C3alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy, and the heterocycle of -CH2 heterocyclil is optionally substituted with oxo, Q is selected independently from the join, S, and O, respectively. R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 21 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 5 (Each element is independently selected from hydrogen or C1-C6 alkyl groups). Embedding by reference

[0010] All publications, patents, and patent applications specified herein are incorporated herein by reference to the same extent as each individual publication, patent, or patent application is specifically and individually incorporated herein by reference.

[0011] Novel features of the present invention are specifically described in the appended claims. A better understanding of the features and advantages of the present invention is obtained by referring to the following detailed description of the invention illustrating exemplary embodiments utilizing the principles of the present invention, and to the appended drawings (as such, “Figure” and “Fig.” in this specification). [Brief explanation of the drawing]

[0012] [Figure 1]Figure 1 illustrates how combination therapy enhances tumor growth inhibition and tumor regression compared to monotherapy. [Modes for carrying out the invention]

[0013] Detailed description of the present invention The following description illustrates numerous exemplary configurations, methods, parameters, etc. However, it should be recognized that such descriptions are not intended to limit the scope of this disclosure, but rather are presented as exemplary embodiments.

[0014] In the following description, certain specific details are explained in order to provide a full understanding of the various embodiments of this disclosure. However, those skilled in the art will understand that this disclosure may be made without these details. definition

[0015] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this invention pertains. All patents and publications referenced herein are incorporated by reference.

[0016] "Alkyl" refers to a linear or branched hydrocarbon chain radical (i.e., C1-C) consisting only of carbon atoms and hydrogen atoms, not containing unsaturated atoms, and preferably having 1 to 15 carbon atoms. 15 This refers to alkyl. In certain embodiments, alkyl contains 1 to 13 carbon atoms (i.e., C1 to C13). 13Alkyl). In certain embodiments, the alkyl group contains 1 to 8 carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl group contains 1 to 5 carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl group contains 1 to 4 carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl group contains 1 to 3 carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl group contains 1 to 2 carbon atoms (i.e., C1-C2 alkyl). In other embodiments, the alkyl group contains 1 carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group contains 5 to 15 carbon atoms (i.e., C5-C 15 Alkyl). In other embodiments, the alkyl group contains 5 to 8 carbon atoms (i.e., C5 to C8 alkyl). In other embodiments, the alkyl group contains 2 to 5 carbon atoms (i.e., C2 to C5 alkyl). In other embodiments, the alkyl group contains 3 to 5 carbon atoms (i.e., C3 to C5 alkyl). In certain embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl group is bonded to the rest of the molecule by a single bond.

[0017] The term “C x~y When used in conjunction with chemical moieties such as alkyl, alkenyl, or alkynyl groups, the term "C" is intended to contain a group with x to y carbon atoms in the chain. For example, the term "C" 1~6 "Alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including linear and branched alkyl groups containing 1 to 6 carbon atoms. (Terminology - C) x~y Alkylene- refers to a substituted or unsubstituted alkylene chain having x to y carbon atoms in the alkylene chain. For example, -C 1~6The alkylene can be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, and any one of these can be substituted as needed.

[0018] "Alkoxy" refers to a radical in which the oxygen atom of the formula -O-alkyl is bonded, and alkyl is an alkyl chain as defined above.

[0019] "Alkenyl" refers to a linear or branched hydrocarbon chain radical group (i.e., C2-C2) consisting only of carbon atoms and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms. 12 This refers to an alkenyl. In certain embodiments, an alkenyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkenyls). In certain embodiments, an alkenyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkenyls). In other embodiments, an alkenyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkenyls). The alkenyl is bonded to the rest of the molecule by a single bond, such as ethenyl (i.e., vinyl), propa-1-enyl (i.e., allyl), buta-1-enyl, penta-1-enyl, penta-1,4-dienyl, etc.

[0020] "Alkynyl" refers to a linear or branched hydrocarbon chain radical group (i.e., C2-C) consisting only of carbon atoms and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms. 12 This refers to alkynyl atoms. In certain embodiments, alkynyl atoms contain 2 to 8 carbon atoms (i.e., C2-C8 alkynyl atoms). In other embodiments, alkynyl atoms contain 2 to 6 carbon atoms (i.e., C2-C6 alkynyl atoms). In other embodiments, alkynyl atoms contain 2 to 4 carbon atoms (i.e., C2-C4 alkynyl atoms). Alkynnyl atoms are bonded to the remainder of the molecule by single bonds, such as ethynyl, propynyl, butynyl, pentynyl, and hexynyl.

[0021] The term “Cx~y "Alkenil" and "C x~y "Alkynyl" refers to a substituted or unsubstituted unsaturated aliphatic group that is similar to the alkyl groups described above in terms of length and possible substitutions, but each contains at least one double or triple bond. Term-C x~y Alkenylene- refers to an alkenylene chain containing x to y carbon atoms, whether substituted or unsubstituted. For example, -C 2~6 Alkenylenes can be selected from etenylene, propenylene, butenylene, pentenylene, and hexenylene, and any one of these may be substituted as needed. Alkenylene chains may have one or more double bonds within them. (Terminology - C) x~y Alkynylene- refers to a substituted or unsubstituted alkynylene chain containing x to y carbon atoms. For example, -C 2~6 The alkenylene- can be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, and any one of these may be substituted as needed. The alkynylene chain may have one or more triple bonds in the alkynylene chain.

[0022] "Alkylene" or "alkylene chain" refers to a linear or branched divalent hydrocarbon chain that links the remainder of a molecule to a radical group, consisting only of carbon and hydrogen, being unsaturated, and preferably having 1 to 12 carbon atoms, such as methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is bonded to the remainder of the molecule via single bonds and to the radical group via single bonds. The bonding points of the alkylene chain to the remainder of the molecule and to the radical group can be via any two carbon atoms in the chain. In certain embodiments, the alkylene contains 1 to 10 carbon atoms (i.e., C1-C8 alkylene). In certain embodiments, the alkylene contains 1 to 8 carbon atoms (i.e., C1-C8 alkylene). In other embodiments, the alkylene contains 1 to 5 carbon atoms (i.e., C1-C5 alkylene). In other embodiments, the alkylene contains 1 to 4 carbon atoms (i.e., C1-C4 alkylene). In other embodiments, the alkylene contains 1 to 3 carbon atoms (i.e., C1-C3 alkylene). In other embodiments, the alkylene contains 1 to 2 carbon atoms (i.e., C1-C2 alkylene). In other embodiments, the alkylene contains 1 carbon atom (i.e., C1 alkylene). In other embodiments, the alkylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkylene). In other embodiments, the alkylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkylene). In other embodiments, the alkylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkylene).

[0023] "Alkenylene" or "alkenylene chain" refers to a linear or branched divalent hydrocarbon chain that links the remainder of a molecule to a radical group, consisting only of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms. The alkenylene chain is bonded to the remainder of the molecule via single bonds and to the radical group via single bonds. The bonding points of the alkenylene chain to the remainder of the molecule and to the radical group can be via any two carbon atoms in the chain. In certain embodiments, the alkenylene contains 2 to 10 carbon atoms (i.e., C2 to C2). 10 Alkenylenes). In certain embodiments, alkenylenes contain 2 to 8 carbon atoms (i.e., C2-C8 alkenylenes). In other embodiments, alkenylenes contain 2 to 5 carbon atoms (i.e., C2-C5 alkenylenes). In other embodiments, alkenylenes contain 2 to 4 carbon atoms (i.e., C2-C4 alkenylenes). In other embodiments, alkenylenes contain 2 to 3 carbon atoms (i.e., C2-C3 alkenylenes). In other embodiments, alkenylenes contain 2 carbon atoms (i.e., C2 alkenylenes). In other embodiments, alkenylenes contain 5 to 8 carbon atoms (i.e., C5-C8 alkenylenes). In other embodiments, alkenylenes contain 3 to 5 carbon atoms (i.e., C3-C5 alkenylenes).

[0024] "Alkynylene" or "alkynylene chain" refers to a linear or branched divalent hydrocarbon chain that links the remainder of a molecule to a radical group, consisting only of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms. The alkynylene chain is bonded to the remainder of the molecule via single bonds and to the radical group via single bonds. The bonding points of the alkynylene chain to the remainder of the molecule and to the radical group can be via any two carbon atoms in the chain. In certain embodiments, the alkynylene contains 2 to 10 carbon atoms (i.e., C2 to C2). 10Alkynylene). In certain embodiments, the alkynylene contains 2 to 8 carbon atoms (i.e., C2-C8 alkynylene). In other embodiments, the alkynylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, the alkynylene contains 2 to 4 carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, the alkynylene contains 2 to 3 carbon atoms (i.e., C2-C3 alkynylene). In other embodiments, the alkynylene contains 2 carbon atoms (i.e., C2 alkynylene). In other embodiments, the alkynylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, the alkynylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkynylene).

[0025] The term "aryl" refers to a radical derived from an aromatic monocyclic or aromatic polycyclic hydrocarbon system by removing a hydrogen atom from a ring carbon atom. An aromatic monocyclic or aromatic polycyclic hydrocarbon system contains only hydrogen and carbon (5 to 18 carbon atoms), and at least one of the rings in the system is aromatic; that is, it contains a delocalized (4n+2)π-electron system of the ring, according to Hückel's theory. Examples of ring systems from which an aryl group is derived include, but are not limited to, benzene, fluorene, indan, indene, tetralin, and naphthalene.

[0026] "Aralkill" is the formula -R c -The aryl radical, R c However, this refers to radicals, such as the alkylene chains defined above, for example, methylene and ethylene.

[0027] "Aralkenyl" is derived from formula -R d -The aryl radical, R d However, this refers to the radical, which is an alkenylene chain as defined above. "Aralkyl" is defined by formula -R e -The aryl radical, R e However, this refers to the radical, which is an alkynylene chain as defined above.

[0028] A "carbocyclic ring" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocyclic rings can include monocyclic rings with 3 to 10 members, bicyclic rings with 6 to 12 members, and bridging rings with 6 to 12 members. Each ring in a bicyclic carbocyclic ring can be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, such as phenyl, may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. The definition of a carbocyclic ring includes any combination of saturated, unsaturated, and aromatic bicyclic rings with acceptable valencies. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Bicyclic carbocyclic rings may be fused ring systems, bridging ring systems, or spirocyclic systems. In some cases, the carbocyclic rings of a spirocyclic ring have at least two molecular rings, each having only one covalent atom.

[0029] The term "unsaturated carbocyclic ring" refers to a carbocyclic ring that has at least 1 degree of unsaturation and excludes aromatic carbocyclic rings. Examples of unsaturated carbocyclic rings include cyclohexadiene, cyclohexene, and cyclopentene.

[0030] "Cycloalkyl" refers to a fully saturated monocyclic or polycyclic hydrocarbon radical consisting only of carbon and hydrogen atoms, which includes fused or bridging ring systems and preferably has 3 to 12 carbon atoms. In certain embodiments, the cycloalkyl contains 3 to 10 carbon atoms. In other embodiments, the cycloalkyl contains 5 to 7 carbon atoms. The cycloalkyl may be bonded to the remainder of the molecule by single bonds. Examples of monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norborneyl, dekalinyl, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl.

[0031] A "cycloalkenyl" refers to an unsaturated, non-aromatic monocyclic or polycyclic hydrocarbon radical consisting only of carbon and hydrogen atoms, which includes fused or bridging ring systems, preferably having 3 to 12 carbon atoms and containing at least one double bond. In certain embodiments, the cycloalkenyl contains 3 to 10 carbon atoms. In other embodiments, the cycloalkenyl contains 5 to 7 carbon atoms. The cycloalkenyl may be bonded to the remainder of the molecule by single bonds. Examples of monocyclic cycloalkenyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0032] "Cycloalkylalkyl" refers to the compound of the formula -R c -A cycloalkyl radical, R c This refers to the radical, which is the alkylene chain mentioned above.

[0033] "Cycloalkylalkoxy" refers to the formula -OR c -A radical bonded via the oxygen atom of a cycloalkyl group, R c This refers to the radical, which is the alkylene chain mentioned above.

[0034] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents.

[0035] As used herein, the terms “haloalkyl” or “haloalkane” refer to the alkyl radicals defined above, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc., which are substituted with one or more halogen radicals. In some embodiments, the alkyl portion of the fluoroalkyl radical is further substituted as needed. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), dihalomethanes and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethanes, 2-haloethanes, 1,2-dihaloethanes, 1-halopropanes, 2-halopropanes, 3-halopropanes, 1,2-dihalopropanes, 1,3-dihalopropanes, 2,3-dihalopropanes, 1,2,3-trihalopropanes, 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 with more than one halogen radical, each halogen can be independently selected, for example, 1-chloro,2-fluoroethane.

[0036] "Fluoroalkyl" refers to alkyl radicals as defined above that are substituted with one or more fluoro radicals, such as trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, and 1-fluoromethyl-2-fluoroethyl.

[0037] "Aminoalkyl" refers to the alkyl radicals defined above that are substituted with one or more amine radicals, such as propan-2-amine, butane-1,2-diamine, and pentane-1,2,4-triamine.

[0038] "Hydroxyalkyl" refers to the alkyl radicals defined above that are substituted by one or more hydroxyl radicals, such as propan-1-ol, butane-1,4-diol, pentane-1,2,4-triol, etc.

[0039] "Alkoxyalkyl" refers to alkyl radicals as defined above that are substituted by one or more alkoxy radicals, such as methoxymethane, 1,3-dimethoxybutane, 1-methoxypropane, and 2-ethoxypentane.

[0040] As used herein, "cyanoalkyl" refers to the alkyl radicals defined above, which are substituted with one or more cyano radicals, such as acetonitrile, 2-ethyl-3-methylsuccinonitrile, and butyronitrile.

[0041] 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. The heterocycle may be bonded to the remainder of the molecule via any heterocycle atom, such as a carbon or nitrogen atom, that is valence-tolerant. Examples of heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridging rings. Examples of bicyclic heterocycles include any combination of saturated, unsaturated, and aromatic bicyclic rings that is valence-tolerant. In exemplary embodiments, an aromatic ring, such as pyridyl, may be condensed to a saturated or unsaturated ring, such as 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 may be fused ring systems, bridging ring systems, or spiro ring systems. Spiro ring systems are sometimes referred to as "spiroheterocycles," "spiro heterocycles," or "spiro-heterocycles." In some cases, a spiro-heterocycle, spiro-heterocycle, or spiro-heterocycle has at least two molecular rings, each having only one shared atom. A spiro-heterocycle, spiro-heterocycle, or spiro-heterocycle contains one or more heteroatoms.

[0042] A "heterocyclene" refers to a divalent heterocycle in which the remainder of a molecule is linked to a radical group.

[0043] "Heteroaryl" or "aromatic heterocyclic" refers to a radical derived from a heteroaromatic ring radical containing 1 to 11 carbon atoms and at least one heteroatom, the heteroatom of which may be selected from N, O, and S. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic ring systems and fused or bridging ring systems, wherein at least one of the rings in the ring system is aromatic, i.e., it contains a delocalized (4n+2)π-electron system of the ring according to Hückel's theory. The heteroatom(s) in the heteroaryl radical may be oxidized as necessary. One or more nitrogen atoms, if present, may be quaternized as necessary. The heteroaryl may be bonded to the remainder of the molecule via any atom of the heteroaryl, such as the carbon or nitrogen atom of the heteroaryl, whose valence is acceptable. Examples of heteroaryls include, but are not limited to, pyridines, pyrimidines, oxazoles, furans, pyrans, thiophenes, isoxazoles, benzimidazoles, benzthiazoles, and imidazopyridines.

[0044] "X-membered heteroaryl" refers to the number of atoms in the ring, i.e., X within the ring. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 atoms in the ring, such as triazoles, oxazoles, and thiophenes.

[0045] The term "unsaturated heterocycle" refers to a heterocycle having at least one degree of unsaturation and excluding aromatic heterocycles. Examples of unsaturated heterocycles include dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydropyridine. The heterocycle may be optionally substituted with one or more substituents, such as those described herein.

[0046] The term “substituted” means that a part has a substituent that replaces hydrogen atoms on one or more carbon atoms of the structure, or on a replaceable heteroatom, for example, on an NH group. “Substitution” or “substituted by” should be understood to imply that such substitution is subject to the allowable valencies of the substituted atom and substituent, and that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, etc. In certain embodiments, “substituted” means that a part has a substituent that replaces two hydrogen atoms on the same carbon atom, such as substituting two hydrogen atoms on a single carbon atom with an oxo, imino, or thioxo group. As used herein, the term “substituted” is intended to include all allowable substituents of an organic compound. In broad embodiments, allowable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. The permissible substituents may be one or more for a given organic compound, and may be the same or different. For the purposes of this disclosure, a heteroatom such as nitrogen may have any permissible substituent of the organic compound described herein that satisfies the valence of the hydrogen substituent and / or the heteroatom.

[0047] In some embodiments, the substituent may be any substituent listed herein, such as halogen, hydroxyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazino (=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 (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t Ure a (t is 1 or 2) and -R b -S(O) t N(R a )2(t is 1 or 2); and may also include alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralquinyl, cycloalkyl, cycloalkylalkyl, and heterocycles, any of which may include alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=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 (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t Ure a (t is 1 or 2) and -R b -S(O) t N(R a )2(t is 1 or 2) may be substituted as needed by R a Each is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, and R a These are the valencies that are permissible for alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=N-NH2), and -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 -ORc -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 (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t Ure a (t is 1 or 2) and -R b -S(O) t N(R a )2(t is 1 or 2) may be substituted as needed, R b Each is independently selected from directly bonded, linear, or branched alkylene, alkenylene, or alkynylene chains, and R c These are linear or branched alkylene, alkenylene, or alkynylene chains, respectively. It will be understood by those skilled in the art that substituents can be substituted themselves where appropriate.

[0048] As used herein, the terms “electrophile” or “electrophilic moiety” refer to any moiety capable of reacting with a nucleophile (e.g., a moiety having lone pairs of electrons, a negative charge, a partially negative charge, and / or excess electrons, e.g., an -SH group). Electrophiles typically consist of electron-deficient or electron-deficient atoms. In certain embodiments, the electrophile is a moiety having a positive charge or partially positive charge, having a resonance structure with a positive charge or partially positive charge, or resulting in one or more atoms having a positive charge or partially positive charge through electron delocalization or polarization. In some embodiments, the electrophile consists of a conjugated double bond and is, for example, an α,β-unsaturated carbonyl compound or an α,β-unsaturated thiocarbonyl compound.

[0049] As used herein, the terms "optional" or "optionally" mean that the events of the circumstances described thereafter may or may not occur, and that this statement includes both the cases in which such events or circumstances occur and the cases in which they do not occur. For example, "optionally substituted aryl" means that the aryl group may or may not be substituted, and that this statement includes both substituted and unsubstituted aryl groups.

[0050] As used herein and in the claims, the singular forms "a," "an," and "the" include multiple references unless the context specifically indicates otherwise.

[0051] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from various organic and inorganic counterions known in this art. Pharmacovigilantly acceptable acid addition salts can be formed with inorganic and organic acids. Examples of inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids from which salts can be derived include 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. Pharmacovigilantly acceptable base addition salts can be formed with inorganic and organic bases. Examples of inorganic bases from which salts can be derived include sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum. Organic bases from which salts can be derived include, specifically, primary, secondary, and tertiary amines such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine, as well as substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins. In some embodiments, pharmaceutically acceptable base addition salts are selected from salts of ammonium, potassium, sodium, calcium, and magnesium.

[0052] As used herein, the terms "parenteral administration" and "administered parenterally" mean a mode of administration other than enteral and topical administration, usually by injection, and include, but is not limited to, injections and infusions into veins, muscles, arteries, thetherosclerotics, capsules, orbits, hearts, skin, peritoneal cavity, trachea, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, intrathecal, and sternal regions.

[0053] The term "pharmaceutically acceptable" is used herein to mean a compound, substance, composition and / or dosage form that is suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions or other problems or complications, and that is commensurate with a reasonable benefit / risk ratio, within the bounds of reasonable medical judgment.

[0054] The terms “pharmaceutically acceptable additive” or “pharmaceutically acceptable carrier” as used herein mean a pharmaceutically acceptable substance, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense that it is compatible with the other components of the formulation and is not harmful to the patient. Some examples of substances that can act 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 carboxymethylcellulose, ethylcellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository wax; (9) peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and dye This includes oils such as (10) propylene glycol, polyols such as glycerin, sorbitol, mannitol and polyethylene glycol, esters such as ethyl oleate and ethyl laurate, agar, buffering agents such as magnesium hydroxide and aluminum hydroxide, alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, phosphate buffer solution, and other non-toxic substances used in pharmaceutical formulations.

[0055] In certain embodiments, the terms “prevent” or “prevent” in relation to a disease or disorder may refer to a compound that reduces the occurrence of a disorder or condition in a treated sample compared to an untreated control sample, or a compound that delays the occurrence of a disorder or condition, or reduces the severity of one or more of its symptoms, compared to an untreated control sample.

[0056] The terms “to treat,” “to treat,” or “treatment” as used herein may include, either preventively or / or therapeutically, reducing, neutralizing, or improving the symptoms of a disease or condition, preventing further symptoms, improving or preventing the underlying cause of symptoms, inhibiting a disease or condition, for example, suppressing the onset of a disease or condition, alleviating a disease or condition, inducing a regression of a disease or condition, alleviating a condition caused by a disease or condition, or cessating the symptoms of a disease or condition.

[0057] As used herein, the term "G12 mutant" refers to another oncogenic allele of KRAS at the 12th amino acid position (i.e., G12X).

[0058] 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.

[0059] The term "RTK-MAPK pathway inhibitor" refers to a drug, such as a compound or antibody, that is capable of negatively modulating or inhibiting all or part of the activity of at least one protein in the RTK-MAPK pathway.

[0060] The term "RAF-MEK-ERK pathway" refers to a series of kinases that are sequentially activated downstream of the activation of the RAS family of small GTPases.

[0061] The term "RAF-MEK-ERK pathway inhibitor" refers to a drug, such as a compound or antibody, that is capable of negatively modulating or inhibiting all or part of the activity of at least one protein in the RAF-MEK-ERK pathway.

[0062] The term "KRas G12D-related cancer," as used herein, refers to cancer that is associated with, mediated by, or has a KRas G12D mutation.

[0063] The term "KRas G12V-related cancer," as used herein, refers to cancer that is associated with, mediated by, or has a KRas G12V mutation.

[0064] The term "KRas wild-type associated cancer," as used herein, refers to cancer that is associated with, mediated by, or has KRas wild-type.

[0065] The term "ERBB family" or "ERBB family member" refers to the members of the mammalian transmembrane protein tyrosine kinase family, including EGFR, ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4).

[0066] The term "ERBB family inhibitor" refers to a drug, such as a compound or antibody, that is capable of negatively modulating or inhibiting all or part of the activity of at least one member of the ERBB family.

[0067] The term "EGFR inhibitor" refers to a drug, such as a compound or antibody, that can negatively modulate or inhibit all or part of the activity of the epidermal growth factor receptor (EGFR).

[0068] The term "SHP-2" or "SHP2" refers to a mammalian non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which is involved in signal transduction via the Ras mitogen-activated protein kinase, JAK-STAT, or phosphoinositol 3-kinase-AKT pathway.

[0069] The term "SHP-2 inhibitor" or "SHP2 inhibitor" refers to a compound that can negatively modulate or inhibit all or part of the enzymatic activity of SHP-2 phosphatase.

[0070] The term "SOS1" refers to the Son of Sevenless homolog 1 (SOS1) enzyme in mammals.

[0071] The term "SOS1 inhibitor" refers to a compound that negatively modulates or inhibits all or part of the interaction between SOS1 and Ras family mutants or SOS1 activating mutants, thereby reducing and / or modulating the nucleotide exchange activity of the Ras family member-SOS1 complex.

[0072] The terms “subject,” “individual,” and “patient” may be used interchangeably and refer to humans and non-human mammals (e.g., non-human primates, dogs, horses, cats, pigs, cattle, ungulates, rabbits, etc.). In various embodiments, the subject may be a human (e.g., adult male, adult female, adolescent male, adolescent female, boy, girl) under the care of a physician or other healthcare professional in a hospital, as an outpatient or in other clinical setting. In certain embodiments, the subject may not be under the care or prescription of a physician or other healthcare professional.

[0073] As used herein, the phrase “subjects requiring it” means subjects described below that are suffering from, or at risk of suffering from, a pathology that is treated prophylactically or therapeutically with the compounds or salts described herein.

[0074] The terms “determining,” “measuring,” “evaluating,” “assessing,” and “analyzing” are often used interchangeably herein and refer to forms of measurement. This term includes determining whether or not an element is present (e.g., detection). These terms may include quantitative determination, qualitative determination, or both quantitative and qualitative determination. Assessment may be relative or absolute. “Detecting the presence of ~” may, depending on the context, include determining the quantity of something in addition to determining whether or not something is present.

[0075] The terms “administer,” “administered,” “administers,” and “administering” are defined as supplying a composition to a subject via a route known in the art, including, but not limited to, intravenous, intra-arterial, oral, parenteral, oral, topical, transdermal, intrarectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal administration routes. In certain embodiments, an oral route for administering the composition may be used. It should be understood that “administering,” “administered,” “administering,” and “administering” a compound mean supplying the compound of the Disclosure or a prodrug of the compound of the Disclosure to an individual in need.

[0076] The term “effective dose” or “therapeutic effective dose” refers to the amount of a compound or salt described herein that is sufficient to produce the intended use, including, but not limited to, disease treatment as defined below. The therapeutic effective dose may vary depending on the intended use (in vitro or in vivo), or the subject and disease state being treated, e.g., the subject’s weight and age, the severity of the disease state, the method of administration, etc., which can be readily determined by those skilled in the art. The term may also be applied to doses that can induce a specific response in target cells, e.g., a decrease in the proliferation of a target protein or downregulation of its activity. Specific doses may vary depending on the particular compound selected, the administration regimen followed, whether the compound is administered in combination with other compounds, the timing of administration, the tissue to which the compound is administered, and the physical delivery system through which the compound is carried.

[0077] As used herein, the "therapeutic effective amount of a combination" of two compounds means an amount that, compared to the therapeutic effective amount of each compound in the combination, synergistically enhances the activity of the combination, that is, an amount that exceeds mere addition.

[0078] As used herein, “synergistic effect,” “synergistic,” “synergistic nature,” or “synergistic effect” refers to two or more compounds or compositions that produce a combined effect that surpasses the individual effects of each other.

[0079] The terms “about” or “approximately” can mean within an acceptable range of error for a particular value as determined by those skilled in the art, and which depends in part on the method by which the value is measured or determined, i.e., on the limits of the measuring system. For example, “about” can mean within a range of 1 or greater than 1 standard deviation per work. Alternatively, “about” can mean a range of up to 20%, up to 15%, up to 10%, up to 5%, or up to 1% of a given value.

[0080] Throughout this specification, every maximum numerical limit is intended to include all lower numerical limits, as if they were explicitly stated herein. Every minimum numerical limit is intended to include all higher numerical limits, as if they were explicitly stated herein. Every numerical range is intended to include all narrower numerical ranges that fall within such broader ranges, as if they were all explicitly stated herein.

[0081] The headings used in this specification are for systematization purposes only and should not be interpreted as limiting the subjects described.

[0082] Any aspect or embodiment described herein may be combined with any other aspect or embodiment disclosed herein. Compositions and Inhibitors RTK-MAPK pathway inhibitors

[0083] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) RTK-MAPK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof. ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0084] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) RTK-MAPK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof. ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0085] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) RTK-MAPK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof. ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0086] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) RTK-MAPK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof. ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0087] In some embodiments, formula (II) is formula (II * It is represented by ). RAF-MEK-ERK pathway inhibitors

[0088] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) RAF-MEK-ERK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof. ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0089] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) RAF-MEK-ERK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof. ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0090] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) RAF-MEK-ERK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof. ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0091] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) RAF-MEK-ERK pathway inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0092] In some embodiments, formula (II) is formula (II * It is represented by ). ERBB family inhibitors

[0093] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) ERBB family inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0094] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) ERBB family inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0095] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) ERBB family inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0096] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) ERBB family inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0097] In some embodiments, formula (II) is formula (II * It is represented by ).

[0098] The ERBB family inhibitors used in the methods described herein may be reversible or irreversible ERBB family inhibitors. In one embodiment, the ERBB family inhibitor inhibits the activity of more than one ERBB family member.

[0099] Modulation or inhibition of one or more ERBB family members may be carried out by modulating or inhibiting the kinase enzyme activity of one or more ERBB family members, or by blocking homodimerization or heterodimerization of ERBB family members. In some embodiments of the methods described herein, the term 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.

[0100] In some embodiments, 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, which block the binding of ATP to the intracellular catalytic domain. Therefore, these inhibitors are active against cell lines that, for example, EGFR exon 19 deletion / insertion, as well as L858R and T790M resistance mutations.

[0101] In some embodiments, exemplary irreversible ERBB family inhibitors for use in this method include afatinib ((E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)buta-2-enamide); dacomitinib ((2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl}-4-(1-piperidinyl)-2-butazolinyl) Tenamide); Canertinib (N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-morpholinopropoxy)quinazolin-6-yl)acrylamide); Poziotinib (1-(4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidine-1-yl)propa-2-en-1-one); AV412 (N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4 -Methyl-1-piperazinyl)-1-butyn-1-yl]-6-quinazolinyl]-2-propenamide); PF6274484 (N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]-2-propenamide) and HKI357 ((2E)-N-[[4-[[(3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide) Examples include 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, suitable irreversible ERBB family inhibitors for the compositions and methods provided include, but are not limited to, afatinib; dacomitinib; canertinib; poziotinib; AV412; PF6274484 and HK357.

[0102] In some embodiments, ERBB family inhibitors are reversible inhibitors. In some cases, as reversible inhibitors, erlotinib ([6,7-bis-(2-methoxyethoxy)-quinazoline-4-yl]-(3-ethynylphenyl)-amine) is used, gefitinib (4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline) is used, and sapitinib (2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazoline-6-yl) is used. (Oxy)piperidine-1-yl)-N-methylacetamide); Vallitinib((R)-N4-(3-chloro-4-(thiazole-2-ylmethoxy)phenyl)-N6-(4-methyl-4,5-dihydroxazole-2-yl)quinazoline-4,6-diamine); TAK-285(N-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pi Limidine-5-yl)ethyl)-3-hydroxy-3-methylbutanamide); AEE788((S)-6-(4-((4-ethylpiperazine-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine); talloxotinib 3-[N-[4-(3-bromo-4-chlorophenylamino)pyrido[3,4-d]pyrimidine-6-yl]carbamoyl]-N,N-dimethyl Tyl-N-(1-methyl-4-nitro-1H-imidazole-5-ylmethyl)-2(E)-propene-1-aminium bromide); BMS599626((3S)-3-morpholinylmethyl-[4-[[1-[(3-fluorophenyl)methyl]-1H-indazole-5-yl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-yl]-carbamate dihydrochloride); and GW583340HCl Examples include (N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[[[2-(methylsulfonyl)ethyl]amino]methyl]-4-thiazolyl]-4-quinazolineamine dihydrochloride), as well as pharmaceutically acceptable salts or pharmaceutical compositions thereof.

[0103] In some embodiments, the reversible ERBB family inhibitor is sapitinib. In some cases, the reversible ERBB family inhibitor is tarloxotinib.

[0104] In some embodiments, the ERBB family inhibitor is a combination of an EGFR inhibitor and a HER2 inhibitor, where the EGFR inhibitor and HER2 inhibitor are: AG1478HCl(7V-(3-chlorophenyl)-6,7-dimethoxy-4-quinazolinanine hydrochloride); AG494(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-phenyl-2-propenamide; AG555(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-phenylpropyl)-2-propenamide; AG556(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(4-phenylbutyl)-2 -Propenamide;AG825(E)-3-[3-[2-benzothiazolythio(benzothiazolythio)methyl]-4-hydroxy-5-methoxyphenyl]-2-cyano-2-propenamide;CP724714(2-methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide;BIBU1361diHCl(N-(3-chloro-4-fluorophenyl)-6-[4-[(diethylamino)methyl]-1-piperidinyl]-pyrimido[5,4-d]pyrimidine-4-amine dihydrochloride);BIBU1382(N 8 -(3-chloro-4-fluorophenyl)-N 2 -(1-methyl-4-piperidinyl)-pyrimido[5,4-]pyrimidine-2,8-diamine dihydrochloride);JNJ28871063HCl(5E-4-amino-6-(4-benzyloxy-3-chlorophenylamino)pyrimidine-5-carboxyaldehyde N-(2-morpholine-4-ylethyl)oxime hydrochloride);PD153035(4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline hydrochloride);PD158780(N 4 -(3-bromophenyl)-N 6-Methylpyrido[3,4-d]pyrimidine-4,6-diamine), and combinations of two of their salts or pharmaceutical compositions that are pharmaceutically acceptable.

[0105] In some embodiments, ERBB family inhibitors are anti-EGFR antibodies, anti-HER2 antibodies, combinations of anti-EGFR antibodies 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.

[0106] In some embodiments, 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 suitable anti-EGFR antibodies for use in this method include EP384, H1, 11.6, 225, and 199.12 (Thermo Fisher) or GT133 (GeneTex).

[0107] In some embodiments, the anti-EGFR monoclonal antibody is cetuximab.

[0108] In some embodiments, exemplary anti-HER-2 monoclonal antibodies include, but are not limited to, pertuzumab (Roche), trastuzumab (Roche), and trastuzumab emtansine (Roche).

[0109] In some embodiments, the ERBB family inhibitor is an anti-EGFR antibody, an anti-HER2 antibody, a combination of an anti-EGFR antibody and an anti-HER2 antibody, or a pharmaceutical composition thereof. In one embodiment, the anti-EGFR antibody is nesitumumab, panitumumab, or cetuximab. In one embodiment, the anti-EGFR antibody is cetuximab. In some cases, the anti-HER2 antibody suitable for use in the methods described herein is pertuzumab, trastuzumab, or trastuzumab emtansine.

[0110] In some embodiments, ERBB family inhibitors are EGFR inhibitors and HER2 inhibitors, and the EGFR inhibitors and HER2 inhibitors are as follows: AG1478HCl(N-(3-chlorophenyl)-6,7-dimethoxy-4-quinazolinamine hydrochloride); AG494(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-phenyl-2-propenamide; AG555(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-phenylpropyl)-2-propenamide; AG556(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(4-phenylbutyl)-2- Propenamide; AG825(E)-3-[3-[2-benzothiazolylthio)methyl]-4-hydroxy-5-methoxyphenyl]-2-cyano-2-propenamide; CP724714(2-methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide; BIBU1361 diHCl(N-(3-chloro-4-fluorophenyl)-6-[4-[(diethylamino)methyl]-1-piperidinyl]-pyrimido[5,4-]pyrimidine-4-amine dihydrochloride); BIBU1382(N 8 -(3-chloro-4-fluorophenyl)-N 2 -(1-methyl-4-piperidinyl)-pyrimido[5,4-J]pyrimidine-2,8-diamine dihydrochloride);JNJ28871063HCl(5E-4-amino-6-(4-benzyloxy-3-chlorophenylamino)pyrimidine-5-carboxyaldehyde N-(2-morpholine-4-ylethyl)oxime hydrochloride);PD153035(4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline hydrochloride);PD158780(N 4 -3-bromophenyl)-N 6 Two drugs are independently selected from the group consisting of methylpyrido[3,4-d]pyrimidine-4,6-diamine, or pharmaceutically acceptable salts or pharmaceutically acceptable compositions thereof. EGFR inhibitors

[0111] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) EGFR inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0112] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) EGFR inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0113] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) EGFR inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0114] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) EGFR inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0115] In some embodiments, formula (II) is formula (II * It is represented by ).

[0116] In some embodiments, 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 results in phosphorylation of key tyrosine residues in the intracellular domain, leading to stimulation of numerous intracellular signaling pathways involved in cell proliferation and survival. In some cases, overexpression of the EGFR gene has been identified in a variety of cancers, including bladder, brain, head and neck, pancreas, lung, chest, ovarian, colon, prostate, and kidney cancers.

[0117] In some embodiments, the EGFR inhibitor is cetuximab. SHP-2 inhibitors

[0118] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) SHP-2 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0119] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) SHP-2 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination.

[0120] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) SHP-2 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0121] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) SHP-2 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0122] In some cases, equation (II) is equation (II * It is represented by ).

[0123] Src homology 2 (SH2) domain-containing phosphatase 2 ("SHP-2") is a mammalian non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which is involved in signal transduction via the Ras mitogen-activated protein kinase, JAK-STAT, or phosphoinositol 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.

[0124] In some embodiments, SHP-2 has been shown to exhibit non-mutagenic drug resistance mechanisms in response to anti-tyrosine kinase inhibitors (TKIs). In some cases, increased SHP-2 phosphatase activity has been shown to confer resistance to the TKI inhibitor imatinib (see, e.g., Li et. ah, (2018) Toxicol. Appl. Pharmacol. 360-249-256). The addition of SHP-2 inhibitors has been shown to overcome resistance by blocking both the RAF / MEK / ERK pathway and the PI3K / AKT / mTOR pathway.

[0125] Several inhibitors that show activity against SHP-2 have been developed. Exemplary SHP-2 inhibitors include, but are not limited to, SHP-099 (6-(4-amino-4-methylpiperidine-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]decane-8-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazine-2-yl)methanol), RMC-4630 (Revolution Medicine), and TNO155 (Novartis). RMC-4630 and TNO155 are in Phase 1 human clinical trials in adult patients with certain progressive solid tumors.

[0126] In some embodiments, methods for producing SHP-2 inhibitors are well known to those skilled in the art, and SHP-2 inhibitors are available from a wide range of commercial suppliers in forms suitable for both research and human use. Furthermore, suitable SHP-2 inhibitors for use in the compositions and methods disclosed herein, as well as methods for preparing such inhibitors, are published in U.S. Patent Applications: US20190127378; US20180251471; US20180201623; US20180186770; US20180170862; US20180065949; US20170204080; Disclosed in US20170166510;US20170011975;US201200334186;US20120257184;US20110190315;US20090042788;US20080194563;US20080058431;US20080058431;US20040121384;US20040043434; and US20040110800. SOS1 inhibitors

[0127] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) SHP-2 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0128] In one aspect, a method for treating a disease or disorder in a subject requiring it, wherein the subject is: i) SOS1 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof ii) The compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0129] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) SOS1 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a combination of the following.

[0130] In one aspect, a method for treating cancer in a subject requiring it, wherein the subject is: i) SOS1 inhibitors, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, and ii) Compound of formula (II), or a pharmaceutically acceptable salt or pharmaceutical composition thereof. A method is provided herein that includes the step of administering a therapeutically effective amount of the combination of the following:

[0131] In some cases, equation (II) is equation (II * It is represented by ).

[0132] In some embodiments, SOS1 inhibitors can block the interaction between SOS1 and Ras-family members, preventing the recycling of KRas into an active GTP-bound form, and thus providing therapeutic benefits against a wide range of cancers, particularly those associated with Ras family members. These compounds negatively modulate KRas activity by blocking the SOS1-KRas interaction in cells, thus treating various forms of cancer, including Ras-associated cancers, SOS1-associated cancers, and NF1 / NF2-associated cancers.

[0133] In some embodiments, one of the SOS1 inhibitors that can be used in the methods described herein is BI-I-13 (also known as BI-3406). It has the following structure: [ka] KRAS Modulator

[0134] The following is a discussion of compounds and salts that may be used in the methods of the present disclosure. The compounds and salts may be used in combination with at least one other inhibitor (e.g., RTK-MAPK pathway inhibitors, RAF-MEK-ERK pathway inhibitors, ERBB family inhibitors, EGFR inhibitors, SHP-2 inhibitors, or SOS1 inhibitors). The compounds and salts may be used in combination with one other inhibitor (e.g., RTK-MAPK pathway inhibitors, RAF-MEK-ERK pathway inhibitors, ERBB family inhibitors, EGFR inhibitors, SHP-2 inhibitors, or SOS1 inhibitors). In some cases, compounds of formula (I), formula (II), formula (III) or their subformulas may be used in the methods of the present disclosure. In some cases, compounds of formula (I), formula (II), formula (III) or their subformulas may be referred to as KRAS inhibitors. In some cases, compounds of formula (I), formula (II), formula (III) or formula (II * Compounds of formula (I), formula (II), formula (III), or formula (II) are sometimes referred to as KRAS inhibitors. * The compounds in this context are sometimes referred to as KRAS modulators.

[0135] In some embodiments, the compound represented by the structure of formula (I): [ka] or a pharmaceutically acceptable salt thereof (in the formula, R 1 C3~C 12 Selected from carbon rings and 5-15 member heterocycles, these are 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 Ure 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 Alkenil, C 2~6 Alkinyl, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 membered heterocycles contain one or more R 1* Each is replaced independently as needed. R 1* These are halogen, -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 Ure20 , -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 or -LC(=O)OC1~C6 alkyl selected, heterocyclic and -L-NR 5 The aryl moiety of C(O)-aryl, the heterocyclic moiety of -L-heterocyclic, and the cycloalkyl moiety of -L-cycloalkyl are one or more R 6 The aryl or heteroaryl in -L-aryl and -L-heteroaryl is replaced as needed, and one or more R 7 It is replaced as needed, L is independently selected from C1-C4 alkylenes, each optionally substituted with one or more substituents selected from hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbon rings, or 3-8 membered heterocycles, where C3-C6 carbon rings and 3-8 membered heterocycles are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, where the C3-C6 carbon ring and 3-8 membered heterocycle are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyl groups. R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, C 3~12The carbon ring and the 3- to 12-membered heterocyclic ring are each optionally substituted by one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 carbon ring and 3- to 12-membered heterocyclic ring, and each R is independently selected from hydrogen and C1-C6 alkyl, and each R 5 is independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C1-C3 alkyl, C1-C3 aminoalkyl, -N(R 6 =20 6 )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)C1-C3 alkyl-、(C1-C3 alkyl)C(=O)、oxo、(C1-C3 haloalkyl)C(=O)-、-SO2F、(C1-C3 alkoxy)C1-C3 alkoxy、-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 ring、-OC(O)N(R 5 )2、-CH2NHC(O)C1-C6 alkyl、-CH2(pyrazolyl)、-CH2NHSO2C1-C6 alkyl、-CH2OC(O)heterocyclic ring、-OC(O)N(R 5)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, -OC(O) heterocycle, -O-C1~C3 alkyl and -CH2 heterocycle are independently selected, the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, the alkyl in -O-C1~C3alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy, and the heterocycle of -CH2 heterocyclil is optionally substituted with oxo, R 7 These are halogen, hydroxyl, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, or -N(R) 5 ) Selected independently from 2, R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, =NH, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 21 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, Q is selected independently from the join, S, and O, respectively. B is selected from heterocycles and carbocycles, and heterocycles and carbocycles are halogen, cyano, hydroxy, =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 alkynyl (NR 5 )2, -N(R 5 )2, (C1~C3 alkoxy) Halo C l ~C3 alkyl-, C 1~6 alkyl-N(R 20 )2, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 member heterocycles are halogens, -OH, -NO2, -NH2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each is optionally substituted with one or more substituents selected from haloalkyl groups, and B forms a spiro ring with ring A. Ring A is selected from heterocycles and carbocycles, and the heterocycle or carbocycle is R 4 (Optionally substituted by one or more substituents selected from the following.)

[0136] In some embodiments, formula (I) is replaced by formula (II), and formula (II * It is expressed by (III) or by formula (III).

[0137] In some embodiments relating to the compound or salt of formula (I), ring A is selected from a heterocycle, and the heterocycle is R 4 It is optionally substituted with one or more substituents selected from. In some cases, ring A contains at least one heteroatom selected from nitrogen, sulfur, and oxygen. In some cases, the heteroatom of ring A is nitrogen, and nitrogen is R 3 It is replaced as needed by R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, 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 Selected from carbon rings and 3- to 12-membered heterocycles, C 3~12 Carbon rings and 3- to 12-membered heterocycles are halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 The rings are optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 12-membered heterocycle. In some cases, the heteroatom of ring A is sulfur, which is optionally substituted with one or two oxygen atoms. In some cases, the heteroatom of ring A is oxygen.

[0138] In some embodiments relating to compounds or salts of formula (I), ring A is selected from a carbocyclic ring, and the carbocyclic ring is R 4It is optionally replaced by one or more substituents selected from the following.

[0139] In some embodiments relating to compounds or salts of formula (I), R 2 is, -L-NR 21 S(O)2(R 21 ) and -LS(O)2N(R 21 ) Selected from 2.

[0140] In some embodiments relating to compounds or salts of formula (I), R 2 is -LN(R 21 )C(O)(OR 21 ) and -L-OC(O)N(R 21 ) Selected from 2.

[0141] In some embodiments relating to compounds or salts of formula (I), R 21 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 They are independently selected from carbon rings and 3- to 12-membered heterocycles, which are halogens, -OH, -CN, -NO2, -NH2, and -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 It is optionally substituted with one or more substituents independently selected from alkyl and oxo. In some cases, R 21 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 It is independently selected from carbon rings and 3- to 12-membered heterocycles. In some cases, R 21 These are hydrogen and C, respectively. 1~6 It is selected independently of alkyl.

[0142] In some embodiments relating to compounds or salts of formula (I), R 2 The R is selected from L-bicyclic heteroalgebras, and the bicyclic heteroalgebra is one or more R 6 It is replaced as needed.

[0143] In some embodiments relating to compounds or salts of formula (I), R 2 It is selected from L-pyrrolidine, and pyrrolidine is one or more R 6 It is replaced as needed.

[0144] In some embodiments relating to the compound or salt of formula (I), L is independently selected from C1-C4 alkylenes, which are optionally substituted, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring, where the C3-C6 carbon ring is halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyls. In some cases, the optional substituents of L are selected from C1-C4 hydroxyalkyl, C1-C4 alkyl, and C3-C6 carbon rings, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, and the C3-C6 carbon ring and 3-8 membered heterocycle are halogen and C 1~6 They are optionally substituted with one or more substituents selected from haloalkyl groups.

[0145] In some embodiments relating to the compound or salt of formula (I), L is independently selected from substituted C1-C4 alkylenes, and two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring. In some cases, the C3-C6 carbon ring is halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 They are optionally substituted with one or more substituents selected from haloalkyl groups.

[0146] In some embodiments relating to the compound or salt of formula (I), L is independently selected from substituted C1-C4 alkylenes, and two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, L is independently selected from substituted C3 alkylenes, and two substituents on the same carbon atom of L together form a C3 carbon ring. In some cases, L is independently, [ka] It is selected independently of others.

[0147] In some embodiments relating to compounds or salts of formula (I), R 2 is selected from the -L-heterogenetic rings, and the heterogenetic portion of the -L-heterogenetic ring is one or more R 6 Substitutions are made as necessary. 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.

[0148] In some embodiments relating to compounds or salts of formula (I), R 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0149] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0150] In some embodiments relating to compounds or salts of formula (I), YR2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0151] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0152] In some embodiments relating to compounds or salts of formula (I), R 2 is selected from -L-saturated heterocycles, and the saturated heterocycle portion of the -L-saturated heterocycle is one or more R 6 It is substituted as needed and contains one nitrogen atom and one sulfur atom. In some cases, YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed. In some cases, YR 2 teeth, [ka] Selected from, the heterocyclic portion is optionally substituted with one or more substituents selected from C1-C3 alkyl and oxo. In some cases, YR 2 teeth, [ka] Selected from. In some cases, YR 2 teeth, [ka] Selected from.

[0153] In some embodiments relating to compounds or salts of formula (I), R 6 These are halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, C1-C3 aminoalkyl, -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, -N(R 5 )2, (C1~C3 alkoxy)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5 )2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, independently selected from the -OC(O) heterocycle and the -CH2 heterocycle, where the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl are optionally substituted with -C(O)H and OH, respectively, and the heterocycle of the -CH2 heterocyclil is optionally substituted with oxo.

[0154] In some embodiments relating to compounds or salts of formula (I), R 6 Each of these is independently selected from halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, and C1-C3 aminoalkyl.

[0155] In some embodiments relating to compounds or salts of formula (I), R 6 These are halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and -N(R) respectively. 5 )2 and oxo are selected independently. In some cases, R 6 These are -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 alkoxy, and -N(R) respectively. 5 ) Selected independently from 2.

[0156] In some embodiments relating to compounds or salts of formula (I), R 6 The elements are selected from halogens, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, and C1-C3 aminoalkyl. In some cases, R 6 The halogen is selected from halogens and C1-C3 alkyl groups. 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 The halogen is selected from halogens and C1-C3 alkyl groups. In some cases, R 6 It is selected from methyl and fluorine.

[0157] In some embodiments relating to compounds or salts of formula (I), R 2 teeth, [ka] Selected from.

[0158] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] Selected from.

[0159] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] Selected from.

[0160] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] That is the case.

[0161] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] Selected from.

[0162] In some embodiments relating to compounds or salts of formula (I), B is a 5- to 15-membered heterocycle or a C3- to C3 ring which is optionally substituted. 15 It is a carbon ring. In some cases, B is a 5-15 member heterocycle which is substituted as needed. In some cases, B is a C3-C which is substituted as needed. 15 It is a carbon ring.

[0163] In some embodiments relating to compounds or salts of formula (I), B is an 8-15 member fused heterocycle or a C8-C ring which is optionally substituted. 15 It is a condensed carbon ring. In some cases, B is an 8-15 member condensed heterocycle which is substituted as needed. In some cases, B is a C8-C which is substituted as needed. 15 It is a condensed carbocyclic ring.

[0164] In some embodiments relating to compounds or salts of formula (I), B is optionally substituted with an 8- to 15-membered condensed heterocycle or optionally substituted with C8-C 15The fused carbon rings are each bicyclic or tricyclic. In some cases, the 8-15 member fused heterocycles, which are optionally substituted with respect to B, are each bicyclic or tricyclic. In some cases, the 8-15 member fused heterocycles, which are optionally substituted with respect to B, or the optionally substituted C8-C 15 The condensed carbocyclic rings are either bicyclic or tricyclic.

[0165] In some embodiments relating to the compound or salt of formula (I), B, the heterocycle or the carbocycle is independently bicyclic. In some cases, the heterocycle is bicyclic. In some cases, the carbocycle is bicyclic.

[0166] In some embodiments relating to the compound or salt of formula (I), B, the heterocycle or the carbocycle is independently a tricyclic ring. In some cases, the heterocycle is a tricyclic ring. In some cases, the carbocycle is a tricyclic ring.

[0167] In some embodiments relating to the compound or salt of formula (I), B, an 8- to 15 member fused heterocycle or a C8- to C8 compound which is optionally substituted. 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0168] In some embodiments relating to compounds or salts of formula (I), B is optionally substituted with an 8- to 15-membered condensed heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0169] In some embodiments relating to compounds or salts of formula (I), B is optionally substituted with an 8- to 15-membered condensed heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0170] In some embodiments relating to compounds or salts of formula (I), with respect to B, one or more optional substituents on the heterocycle and carbocyclic rings are halogens, C1-C3 alkyls, -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 Each alkynyl is independently selected for each occurrence. In some cases, one or more substituents on the heterocycle and carbocyclic ring as needed are halogen, oxo, -NH2, C1-C3 alkyl, -B(OR 20 )2, -OH, -C(O)N(R 20 )2, =O, -CN, C 1~6 Alkoxy and C 2~6 Each substituent is independently selected from the alkynyl group. In some cases, one or more substituents as needed on the heterocycle and carbocyclic rings are halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1~6 Alkoxy and C 2~6Each substituent is independently selected from the alkynyl group. In some cases, one or more optional substituents on the heterocycle and carbocycle are independently selected from oxo, -NH2, -CN, halogen, and C1-C3 alkyl groups. In some cases, one or more optional substituents on the heterocycle or carbocycle are independently selected from oxo, -NH2, halogen, and C1-C3 alkyl groups.

[0171] In some embodiments relating to the compound or salt of formula (I), B is [ka] Selected from.

[0172] In some embodiments relating to the compound or salt of formula (I), with respect to B, one or more optional substituents of the heterocycle or carbocyclic ring are independently selected from oxo, -NH2, CN, halogen, and C1-C3 alkyl groups.

[0173] In some embodiments relating to the compound or salt of formula (I), B is [ka] Selected from.

[0174] In some embodiments relating to compounds or salts of formula (I), R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 It is independently selected from alkynyl, oxo, hydroxyl, and halogen. In some cases, R 4 These are C 1~6 It is independently selected from alkyl, oxo, and halogen elements.

[0175] In some embodiments relating to the compound or salt of formula (I), n is selected from 1 and 2. In some cases, n is 0.

[0176] In some embodiments relating to the compound or salt of formula (I), Y is O.

[0177] In some embodiments relating to compounds or salts of formula (I), R 1 The `x` is selected from 5- to 12-membered complex rings, which are substituted as needed.

[0178] In some embodiments relating to compounds or salts of formula (I), R 1 C3~C 12 Selected from carbon rings and 5-12 membered heterocycles, these are 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 It is optionally substituted with one or more substituents selected independently of the alkynyl molecule.

[0179] In some embodiments relating to compounds or salts of formula (I), R 1 C3~C 12Selected from carbon rings and 5-12 membered heterocycles, these are 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(R 20 )C(O)OR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 -OC(O)R 20 , OCN(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 It is optionally substituted with one or more substituents selected independently of the alkynyl molecule.

[0180] In some embodiments relating to compounds or salts of formula (I), R 1 C3~C 12 Selected from carbocyclic and 5- to 12-membered heterocycles, these are respectively -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 ) may be optionally replaced by one or more substituents selected independently of 2.

[0181] In some embodiments relating to compounds or salts of formula (I), R 1 These are selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens, -OH, and -N(R). 20 )2, -NO2, =O, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0182] In some embodiments relating to compounds or salts of formula (I), R 1 These are selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens, -OH, and -N(R). 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0183] In some embodiments relating to compounds or salts of formula (I), R 1 R 20 is hydrogen and C 1~3 Selected from alkyl groups.

[0184] In some embodiments relating to compounds or salts of formula (I), R 1 The 5- to 12-membered hetero rings are unsaturated hetero rings.

[0185] In some embodiments relating to compounds or salts of formula (I), R 1 The 5- to 12-membered complex algebras are saturated complex algebras.

[0186] In some embodiments relating to compounds or salts of formula (I), R 1 The 5- to 12-membered complex rings are bridged complex rings.

[0187] In some embodiments relating to compounds or salts of formula (I), R 1 teeth, [ka] These are selected from halogen, -OH, and -N(R) respectively. 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, =O, -CN, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0188] In some embodiments relating to compounds or salts of formula (I), R 1 teeth, [ka] These are selected from halogen, -OH, and -N(R) respectively. 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, =O, -CN, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0189] In some embodiments relating to compounds or salts of formula (I), R 1 teeth, [ka] Selected from.

[0190] In some embodiments relating to the compound or salt of formula (I), L is selected from C1-C4 alkylenes.

[0191] In some embodiments relating to the compound or salt of formula (I), L is selected from unsubstituted C1-C4 alkylenes.

[0192] In some embodiments relating to compounds or salts of formula (I), R 2 is one or more R 6 It is a -L-heterocycle that is substituted as needed, and the heterocycle portion is a bicyclic heterocycle. In some cases, the bicyclic heterocycle contains at least one nitrogen atom. In some cases, the bicyclic heterocycle contains up to one nitrogen atom.

[0193] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0194] In some embodiments relating to compounds or salts of formula (I), R 2 R 6 Each element is independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and C1-C3 aminoalkyl.

[0195] In some embodiments relating to compounds or salts of formula (I), R 2 R 6 Each of these is independently selected from C1-C3 alkyl groups and halogens.

[0196] In some embodiments relating to compounds or salts of formula (I), YR 2 teeth, [ka] Selected from.

[0197] In some embodiments, the compound has the structure of formula (II): [ka] or represented by a pharmaceutically acceptable salt thereof (in the formula, M stands for O, S, SO, SO2 and NR 3 Selected from, R 1 C3~C 12 Selected from carbon rings and 5-15 member heterocycles, these are 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 Ure 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 Alkenil, C 2~6 Alkinyl, C3~C 12It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 membered heterocycles contain one or more R 1* Each is replaced independently as needed. R 1* These are halogen, -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 Ure 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 Alkenil, C 2~6 Alkinyl, and C3~C 12 Selected independently from the carbon ring, Y is a bond, O, S and NR 5 Selected from, R 2 is -LN(R 21 )2, -L-OR 21 , heterocyclic, C1-C6 alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -LC(O)N(R 21 )2, -L-C1~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)OC1~C6 alkyl selected from heterocyclic, -L-NR 21 The aryl portion of C(O)-aryl, the heterocyclic portion of -L-heterocyclic, and the cycloalkyl portion of -L-cycloalkyl are one or more R 6 Each is substituted as needed, and the aryl portion of -L-aryl and the heteroaryl portion of -L-heteroaryl are replaced by one or more R 7 Each is substituted as necessary, and if Y is a bond, O or S, then R 2 It is further selected from hydrogen, L is independently selected from C1-C4 alkylenes, each optionally substituted with one or more substituents selected from hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbon rings, or 3-8 membered heterocycles, where C3-C6 carbon rings and 3-8 membered heterocycles are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, where the C3-C6 carbon ring and 3-8 membered heterocycle are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, 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 Selected from carbon rings and 3- to 12-membered heterocycles, C 3~12 Carbon rings and 3- to 12-membered heterocycles are halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 Each molecule is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. n is selected from 0 to 2. R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynyl, oxo, hydroxyl, halogen, C 3~12 Independently selected from carbon rings and 3-12 membered heterocycles, C1-C6 alkyl, C 3~12Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR 5 and -N(R 5 )2 is optionally replaced by one or more substituents selected independently of 2, R 5 Each is independently selected from hydrogen or C1-C6 alkyl groups. R 6 These are halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C1-C3 alkyl, C1-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)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, -OC(O) heterocycle, -O-C1~C3 alkyl and -CH2 heterocycle are independently selected, the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl are optionally substituted with one or more substituents selected from -C(O)H and OH, respectively, the alkyl in -O-C1~C3alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy, and the heterocycle of -CH2 heterocyclil is optionally substituted with oxo, Q is selected independently from the join, S, and O, respectively. R 7 These are halogen, hydroxyl, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, or -N(R) 5 ) Selected independently from 2, R 9 These are halogen, -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 Selected independently from haloalkyl groups, R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, =NH, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 21 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, B is selected from heterocycles and carbocycles, and heterocycles and carbocycles are halogen, cyano, hydroxy, =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 alkynyl (NR 5 )2, -N(R 5 )2, (C1~C3 alkoxy) Halo C l ~C3 alkyl-, C1~6 alkyl-N(R 20 )2, C3~C 12 Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 member heterocycles are halogens, -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 (Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups.)

[0198] In some embodiments relating to compounds or salts of formula (II), M is NR 3 And Y is O, R 1 If it is piperazine, then piperazine contains one or more R 9 It has been replaced by [this].

[0199] In some embodiments relating to compounds or salts of formula (II), R 2 is, -L-NR 21 S(O)2(R 21 ) and -LS(O)2N(R 21 ) Selected from 2.

[0200] In some embodiments relating to compounds or salts of formula (II), R 2 is -LN(R 21 )C(O)(OR 21 ) and -L-OC(O)N(R 21 ) Selected from 2.

[0201] In some embodiments relating to compounds or salts of formula (II), R 21 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 They are independently selected from carbon rings and 3- to 12-membered heterocycles, which are halogens, -OH, -CN, -NO2, -NH2, and -N(C)1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 It is optionally substituted with one or more substituents independently selected from alkyl and oxo. In some cases, R 21 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 It is independently selected from carbon rings and 3- to 12-membered heterocycles. In some cases, R 21 These are hydrogen and C, respectively. 1~6 It is selected independently of alkyl.

[0202] In some embodiments relating to compounds or salts of formula (II), R 3 is hydrogen and C 1~6 Selected from alkyl groups.

[0203] In some embodiments relating to the compound or salt 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.

[0204] In some embodiments relating to the compound or salt of formula (II), B is a 5- to 15-membered heterocycle or a C3- to C3 ring which is optionally substituted. 15 It is a carbon ring. In some cases, B is a 5-15 member heterocycle which is substituted as needed. In some cases, B is a C3-C which is substituted as needed. 15 It is a carbon ring. In some cases, B is an 8-15 member heterocycle which is substituted as needed. In some cases, B is a C8-C which is substituted as needed. 15 It is a carbon ring.

[0205] In some embodiments relating to the compound or salt of formula (II), B is an 8-15 member fused heterocycle or a C8-C ring which is optionally substituted. 15It is a condensed carbon ring. In some cases, B is an 8-15 member condensed heterocycle which is substituted as needed. In some cases, B is a C8-C which is substituted as needed. 15 It is a condensed carbocyclic ring.

[0206] In some embodiments relating to the compound or salt of formula (II), B is optionally substituted with an 8- to 15-membered condensed heterocycle or optionally substituted with C8-C 15 The fused carbon rings are each bicyclic or tricyclic. In some cases, the 8-15 member fused heterocycles, which are optionally substituted with respect to B, are each bicyclic or tricyclic. In some cases, the 8-15 member fused heterocycles, which are optionally substituted with respect to B, or the optionally substituted C8-C 15 The condensed carbocyclic rings are either bicyclic or tricyclic, respectively.

[0207] In some embodiments relating to the compound or salt of formula (II), with respect to 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 up to one nitrogen atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains up to one sulfur atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at least two heteroatoms.

[0208] In some embodiments relating to the compound or salt of formula (II), with respect to B, the heterocycle or the carbocycle is independently bicyclic. In some cases, the heterocycle is bicyclic. In some cases, the carbocycle is bicyclic.

[0209] In some embodiments relating to the compound or salt of formula (II), with respect to B, the heterocycle or the carbocycle is independently tricyclic. In some cases, the heterocycle is tricyclic. In some cases, the carbocycle is tricyclic.

[0210] In some embodiments relating to the compound or salt of formula (II), B is optionally substituted with an 8- to 15-membered condensed heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0211] In some embodiments relating to the compound or salt of formula (II), B is optionally substituted with an 8- to 15-membered condensed heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0212] In some embodiments relating to the compound or salt of formula (II), B is optionally substituted with an 8- to 15-membered condensed heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0213] In some embodiments relating to compounds or salts of formula (II), with respect to B, one or more optional substituents on the heterocycle and carbocyclic ring are halogens, C1-C3 alkyls, -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, C1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl and C 2~6 Each alkynyl is independently selected for each occurrence. In some cases, one or more substituents on the heterocycle and carbocyclic ring as needed are halogen, oxo, -NH2, C1-C3 alkyl, -B(OR 20 )2, -OH, -C(O)N(R 20 )2, =O, -CN, C 1~6 Alkoxy and C 2~6 Each substituent is independently selected from the alkynyl group. In some cases, one or more substituents as needed on the heterocycle and carbocyclic rings are halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1~6 Alkoxy and C 2~6 Each substituent is independently selected from the alkynyl group. In some cases, one or more optional substituents on the heterocycle and carbocycle are independently selected from oxo, -NH2, -CN, halogen, and C1-C3 alkyl groups. In some cases, one or more optional substituents on the heterocycle or carbocycle are independently selected from oxo, -NH2, halogen, and C1-C3 alkyl groups.

[0214] In some embodiments relating to the compound or salt of formula (II), B is [ka] Selected from.

[0215] In some embodiments relating to the compound or salt of formula (II), B is [ka] Selected from.

[0216] In some embodiments relating to compounds or salts of formula (II), R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6It is independently selected from alkynyl, oxo, hydroxyl, and halogen. In some cases, R 4 These are C 1~6 It is independently selected from alkyl, oxo, and halogen elements.

[0217] In some embodiments relating to the compound or salt of formula (II), n is selected from 1 and 2. In some cases, n is 0.

[0218] In some embodiments relating to the compound or salt of formula (II), Y is O.

[0219] In some embodiments relating to compounds or salts of formula (II), R 1 The `x` is selected from 5- to 12-membered complex rings, which are substituted as needed.

[0220] In some embodiments relating to compounds or salts of formula (II), R 1 These are selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens, -OH, and -N(R). 20 )2, -NO2, =O, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0221] In some embodiments relating to compounds or salts of formula (II), R 1 C3~C 12 Selected from carbon rings and 5-12 membered heterocycles, these are 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(R20 )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 It is optionally substituted with one or more substituents selected independently of the alkynyl molecule.

[0222] In some embodiments relating to compounds or salts of formula (II), R 1 C3~C 12 Selected from carbocyclic and 5- to 12-membered heterocycles, these are respectively -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 ) may be optionally replaced by one or more substituents selected independently of 2.

[0223] In some embodiments relating to compounds or salts of formula (II), R 1 These are selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens, -OH, and -N(R). 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 1~6It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0224] In some embodiments relating to compounds or salts of formula (II), R 1 R 20 is hydrogen and C 1~3 Selected from alkyl groups.

[0225] In some embodiments relating to compounds or salts of formula (II), R 1 The 5- to 12-membered hetero rings are unsaturated hetero rings.

[0226] In some embodiments relating to compounds or salts of formula (II), R 1 The 5- to 12-membered complex algebras are saturated complex algebras.

[0227] In some embodiments relating to compounds or salts of formula (II), R 1 The 5- to 12-membered complex rings are bridged complex rings.

[0228] In some embodiments relating to compounds or salts of formula (II), R 1 teeth, [ka] These are selected from halogen, -OH, and -N(R) respectively. 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, =O, -CN, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments relating to compounds or salts of formula (II), R 1 teeth, [ka] These are selected from halogen, -OH, and -N(R) respectively. 20 )2, -NO2, C 1~6Aminoalkyl, C 1~6 Alkoxy, =O, -CN, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0229] In some embodiments relating to compounds or salts of formula (II), R 1 teeth, [ka] Selected from.

[0230] In some embodiments relating to compounds or salts of formula (II), R 1 It is selected from saturated hetero rings of 6-7 members, which are substituted as needed. In some cases, R 1 It is selected from a 6-member saturated hetero ring, which is substituted as needed. In some cases, R 1 teeth, [ka] Selected from these, which are substituted as needed. In some cases, one or more substituents as needed are halogen, -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed may be -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed may be -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed are -NHCN and C 1~6 Selected independently of alkyl. In some cases, R 1 teeth, [ka] Selected from, this is -NHCN and C 1~6 It is substituted with one or more substituents selected from alkyl groups. In some cases, R 1 teeth, [ka] Selected from.

[0231] In some embodiments relating to compounds or salts of formula (II), R 1 The 6-membered saturated heterocycle is selected from the substituted 6-membered saturated heterocycles, the 6-membered saturated heterocycle being at least one -NHCN and optionally one or more C 1~6 It is alkyl-substituted, M is O, n is 0, and B is an optionally substituted 8-15 member fused heterocycle and optionally substituted C8-C 15 Selected from condensed carbocyclic rings, these are halogen, oxo, -NH2, C1-C3 alkyl, -OH, -C(O)NH2, -NH2, =O, -CN, and C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 2~6 It is optionally substituted with one or more substituents independently selected from the alkynyl, where Y is O and R 2 The heterocyclic portion is selected from -L-heterocycles, and the heterocyclic portion is halogen, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl or -N(R 5 ) is optionally substituted by one or more substituents independently selected from 2, where L is selected from C1-C4 alkylenes. In some cases, R 1 teeth, [ka] Selected from. In some cases, B is [ka] Selected from. In some cases, B is [ka] Selected from. In some cases, B is [ka] That is the case.

[0232] In some embodiments relating to compounds or salts of formula (II), R 9 These are halogen, -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 Selected independently from haloalkyl groups. In some cases, R 9 These are halogen, -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 are selected independently. In some cases, R 9These are halogen and -SR respectively. 20 -S(O)2(R 20 ), -S(O)2N(R 20 )2, -N(R 20 )2, -NO2, =O and =NO(R 20 ) is selected independently of R. In some cases, R 9 These are halogen and -N(R) respectively. 20 ) Selected independently from 2.

[0233] In some embodiments relating to the compound or salt of formula (II), L is independently selected from C1-C4 alkylenes, which are optionally substituted, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring, where the C3-C6 carbon ring is halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyls. In some cases, the optional substituents of L are selected from C1-C4 hydroxyalkyl, C1-C4 alkyl, and C3-C6 carbon rings, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, and the C3-C6 carbon ring and 3-8 membered heterocycle are halogen and C 1~6 They are optionally substituted with one or more substituents selected from haloalkyl groups.

[0234] In some embodiments relating to the compound or salt of formula (II), L is independently selected from substituted C1-C4 alkylenes, and two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring. In some cases, the C3-C6 carbon ring consists of halogen, -OH, -NO2, =O, =S, -CN, and C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6They are optionally substituted with one or more substituents selected from haloalkyl groups.

[0235] In some embodiments relating to the compound or salt of formula (II), L is independently selected from substituted C1-C4 alkylenes, and two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, L is independently selected from substituted C3 alkylenes, and two substituents on the same carbon atom of L together form a C3 carbon ring. In some cases, L is independently, [ka] It is selected independently of others.

[0236] In some embodiments relating to compounds or salts of formula (II), R 2 is selected from the -L-heterogenetic rings, and the heterogenetic portion of the -L-heterogenetic ring is one or more R 6 Substitutions are made as necessary. 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.

[0237] In some embodiments relating to compounds or salts of formula (II), R 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0238] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6It is replaced as needed.

[0239] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0240] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0241] In some embodiments relating to compounds or salts of formula (II), R 2 is selected from -L-saturated heterocycles, and the saturated heterocycle portion of the -L-saturated heterocycle is one or more R 6 It is substituted as needed and contains one nitrogen atom and one sulfur atom. In some cases, YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed. In some cases, YR 2 teeth, [ka] Selected from, the heterocyclic portion is optionally substituted with one or more substituents selected from C1-C3 alkyl and oxo. In some cases, YR 2 teeth, [ka] Selected from. In some cases, YR 2 teeth, [ka] Selected from.

[0242] In some embodiments relating to compounds or salts of formula (II), R 6 These are halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, C1-C3 aminoalkyl, -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, -N(R 5 )2, (C1~C3 alkoxy)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5 )2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, independently selected from the -OC(O) heterocycle and the -CH2 heterocycle, where the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl are optionally substituted with -C(O)H and OH, respectively, and the heterocycle of the -CH2 heterocyclil is optionally substituted with oxo.

[0243] In some embodiments relating to compounds or salts of formula (II), R 6Each of these is independently selected from halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, and C1-C3 aminoalkyl.

[0244] In some embodiments relating to compounds or salts of formula (II), R 6 These are halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and -N(R) respectively. 5 )2 and oxo are selected independently. In some cases, R 6 These are -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 alkoxy, and -N(R) respectively. 5 ) is selected independently from 2. In some cases, R 6 These are C1-C3 alkyl, C1-C3 alkoxy, and -N(R) respectively. 5 ) Selected independently from 2.

[0245] In some embodiments relating to compounds or salts of formula (II), R 6 The elements are selected from halogens, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, and C1-C3 aminoalkyl. In some cases, R 6 The halogen is selected from halogens and C1-C3 alkyl groups. 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 The halogen is selected from halogens and C1-C3 alkyl groups. In some cases, R 6 It is selected from methyl and fluorine.

[0246] In some embodiments relating to compounds or salts of formula (II), R 2 teeth, [ka] Selected from.

[0247] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] Selected from.

[0248] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] Selected from.

[0249] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] That is the case.

[0250] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] Selected from.

[0251] In some embodiments relating to the compound or salt of formula (II), L is selected from C1-C4 alkylenes.

[0252] In some embodiments relating to the compound or salt of formula (II), L is selected from unsubstituted C1-C4 alkylenes.

[0253] In some embodiments relating to compounds or salts of formula (II), R 2 is one or more R 6It is a -L-heterocycle that is substituted as needed, and the heterocycle portion is a bicyclic heterocycle. In some cases, the bicyclic heterocycle contains at least one nitrogen atom. In some cases, the bicyclic heterocycle contains up to one nitrogen atom.

[0254] In some embodiments relating to compounds or salts of formula (II), R 2 The R is selected from L-bicyclic heteroalgebras, and the bicyclic heteroalgebra is one or more R 6 It is replaced as needed.

[0255] In some embodiments relating to compounds or salts of formula (II), R 2 It is selected from L-pyrrolidine, and pyrrolidine is one or more R 6 It is replaced as needed.

[0256] In some embodiments relating to the compound or salt of formula (II), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0257] In some embodiments relating to compounds or salts of formula (II), R 2 R 6 Each of the following is independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and C1-C3 aminoalkyl. In some cases, R 2 R 6 Each of the C1-C3 alkyl and halogen elements is independently selected. In some cases, YR 2 teeth, [ka] Selected from.

[0258] In some embodiments relating to compounds or salts of formula (II), M is NR 3 It is selected from. 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 C 1~6 Selected from cyanoalkyl groups. In some cases, M is selected from C2 cyanoalkyl groups. In some cases, M is selected from NH groups. In some cases, R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, 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 Selected from haloalkyls. In some cases, R 3 is 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 Selected from haloalkyls. In some cases, R 3 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 Selected from haloalkyls. In some cases, R 3 C 2~6 Alkyl, C 1~6 alkyl-N(R 20 )2, C1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Alkoxyalkyl and C 1~6 Selected from haloalkyls. In some cases, R 3 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 Selected from haloalkyls. In some cases, R 3 C 1~6 Cyanoalkyl, C 1~6 Alkoxyalkyl and C 1~6 Selected from haloalkyls. In some cases, R 3 is 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 Selected from haloalkyls. In some cases, R 3 C 1~6 Alkoxyalkyl, C 1~6 Cyanoalkyl and C 1~6 Selected from alkyl groups. In some cases, R 3 teeth, [ka] In some cases, R 3 C 2~6 Selected from alkyl groups.

[0259] In some embodiments relating to compounds or salts of formula (II), M is NR 3 And B is, [ka] Selected from, these are each substituted as necessary, where n is 0, Y is O, and R 2 is selected from L-heterogenetic rings, and the heterogenetic ring is one or more R 6 It is replaced as needed by R 1 teeth, [ka] Selected from, which is replaced as needed. In some cases, R 1 teeth, [ka] This is a halogen, -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 Ure 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 and C 2~6 It is optionally substituted with one or more substituents independently selected from the alkynyl. In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] In some cases, the heterocycle of the L-heterocycle is bicyclic. In some cases, the heterocycle of the L-heterocycle is monocyclic. In some cases, L is selected from C1-C4 alkylenes. In some cases, L is selected from unsubstituted C1-C4 alkylenes. In some cases, L is independently selected from substituted C1-C4 alkylenes, and the two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring. In some cases, YR 2 teeth, [ka] [ka] Selected from. In some cases, YR 2 teeth, [ka] Selected from. In some cases, B is [ka] Selected from, which is substituted by one or more substituents. In some cases, B is [ka] This is substituted by one or more substituents. In some cases, B is [ka] Selected from, which is substituted by one or more substituents. In some cases, with respect to B, one or more substituents are halogen, oxo, -NH2, C1~C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, -O-C1~C3 haloalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 2~6 Selected independently of alkynyl. 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 [ka] Selected from. In some cases, B is [ka] Selected from, this includes halogens, -O-C1~C3 haloalkyls and C 1~6 It is substituted with one or more substituents selected from haloalkyl groups. In some cases, B is [ka] This is substituted by one or more substituents selected from halogens. In some cases, B is [ka] Selected from. In some cases, B is [ka] This is substituted with one or more substituents selected from fluorine. In some cases, B is [ka] Selected from. In some cases, B is [ka] This is substituted with one or more substituents selected from chlorine. In some cases, B is [ka] Selected from. In some cases, R 3 is hydrogen and C 1~6 Selected from alkyl groups. In some cases, R 3 C 1~6 Selected from alkyl groups. In some cases, R 3 It is methyl. In some cases, R 6 These are halogen, oxo, and C, respectively. 1~6 Selected from alkyl groups. In some cases, R 6 These are halogen and C, respectively. 1~6 Selected from alkyl groups. In some cases, R 6 Each is selected from halogens. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] In some cases, B is [ka] That is the case.

[0260] In some embodiments, the compound has the structure of formula (III): [ka] or represented by a pharmaceutically acceptable salt thereof (in the formula, R 1 C3~C 12 Selected from carbon rings and 5-15 member heterocycles, these are 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 Ure 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 Alkenil, C 2~6 Alkinyl, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 membered heterocycles contain one or more R 1* Each is replaced independently as needed. R 1* These are halogen, -B(OR 20 )2, -OR 20 , -SR 20 -S(O)2(R20 ), -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 Ure 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 Alkenil, C 2~6 Alkinyl, and C3~C 12 Selected independently from the carbon ring, R 2 is, -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 ) Selected from 2 and L-bicyclic heterocycles, the bicyclic heterocycle is one or more R 6 It is replaced as needed, L is independently selected from C1-C4 alkylenes, each optionally substituted with one or more substituents selected from hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbon rings, or 3-8 membered heterocycles, where C3-C6 carbon rings and 3-8 membered heterocycles are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, where the C3-C6 carbon ring and 3-8 membered heterocycle are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. n is selected from 0 to 3. R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynyl, oxo, hydroxyl, halogen, C 3~12 Independently selected from carbon rings and 3-12 membered heterocycles, C1-C6 alkyl, C 3~12 Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR 5 and -N(R 5 )2 is optionally replaced by one or more substituents independently selected from 2, B is selected from heterocycles and carbocycles, and heterocycles or carbocycles are halogen, cyano, hydroxy, =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 alkynyl (NR 5 )2, -N(R 5 )2, (C1~C3 alkoxy) Halo C l ~C3 alkyl-, C 1~6 alkyl-N(R 20 )2, C3~C 12 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5-12 membered heterocycle, C3-C 12 Carbon rings and 5-12 member heterocycles are halogens, -OH, -NO2, -NH2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. Y is a bond, O, S and NR 5 Selected from, R 6 These are halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, =CH2, =NO-C1-C3 alkyl, C1-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)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5 )2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, -OC(O) heterocycle, -O-C1~C3 alkyl and -CH2 heterocycle are independently selected, the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, the alkyl in -O-C1~C3alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy, and the heterocycle of -CH2 heterocyclil is optionally substituted with oxo, Q is selected independently from the join, S, and O, respectively. R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 21These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 Independently selected from carbon rings and 3- to 12-membered heterocycles, R 5 (Each element is independently selected from hydrogen or C1-C6 alkyl groups).

[0261] In some embodiments relating to compounds or salts of formula (III), R 1 C3~C 12 Selected from carbon rings and 5-12 membered heterocycles, these are 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(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 1~6Haloalkyl, C 1~6 Alkyl, C 2~6 Alkenyl and C 2~6 It is optionally substituted with one or more substituents selected independently of the alkynyl molecule.

[0262] In some embodiments relating to compounds or salts of formula (III), R 2 is -L-NR 21 S(O)2(R 21 ) and -LS(O)2N(R 21 ) Selected from 2.

[0263] In some embodiments relating to compounds or salts of formula (III), R 2 is -LN(R 21 )C(O)(OR 21 ) and -L-OC(O)N(R 21 ) Selected from 2.

[0264] In some embodiments relating to compounds or salts of formula (III), R 21 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 They are independently selected from carbon rings and 3- to 12-membered heterocycles, which are halogens, -OH, -CN, -NO2, -NH2, and -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 It is optionally substituted with one or more substituents independently selected from alkyl and oxo. In some cases, R 21 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 It is independently selected from carbon rings and 3- to 12-membered heterocycles. In some cases, R 21 These are hydrogen and C, respectively. 1~6 It is selected independently of alkyl.

[0265] In some embodiments relating to compounds or salts of formula (III), R 2The R is selected from L-bicyclic heteroalgebras, and the bicyclic heteroalgebra is one or more R 6 It is replaced as needed.

[0266] In some embodiments relating to compounds or salts of formula (III), R 2 It is selected from L-pyrrolidine, and pyrrolidine is one or more R 6 It is replaced as needed.

[0267] In some embodiments relating to the compound or salt of formula (III), B is a 5- to 15-membered heterocycle or a C3- to C3 ring which is optionally substituted. 15 It is a carbon ring. In some cases, B is a 5-15 member heterocycle which is substituted as needed. In some cases, B is an 8-15 member heterocycle which is substituted as needed. In some cases, B is a C3-C ring which is substituted as needed. 15 It is a carbon ring. In some cases, B is substituted as needed. C8~C 15 It is a carbon ring.

[0268] In some embodiments relating to the compound or salt of formula (III), B is an 8-15 member fused heterocycle or a C8-C ring which is optionally substituted. 15 It is a condensed carbocyclic ring. In some cases, B is an 8-15 member condensed heterocyclic ring that is substituted as needed. In some cases, B is a C8-C 15 It is a condensed carbocyclic ring.

[0269] In some embodiments relating to the compound or salt of formula (III), with respect to 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 up to one nitrogen atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains up to one sulfur atom. In some cases, the optionally substituted 8- to 15-membered heterocycle contains at least two heteroatoms.

[0270] In some embodiments relating to the compound or salt of formula (III), B is optionally substituted with an 8-15 member fused heterocycle or optionally substituted with C8-C 15 The fused carbon rings are each bicyclic or tricyclic. In some cases, the 8-15 member fused heterocycles, which are optionally substituted with respect to B, are each bicyclic or tricyclic. In some cases, the 8-15 member fused heterocycles, which are optionally substituted with respect to B, or the optionally substituted C8-C 15 The condensed carbocyclic rings are either bicyclic or tricyclic.

[0271] In some embodiments relating to the compound or salt of formula (III), with respect to B, the heterocycle or the carbocycle is independently bicyclic. In some cases, the heterocycle is bicyclic. In some cases, the carbocycle is bicyclic.

[0272] In some embodiments relating to the compound or salt of formula (III), with respect to B, the heterocycle or the carbocycle is independently tricyclic. In some cases, the heterocycle is tricyclic. In some cases, the carbocycle is tricyclic.

[0273] In some embodiments relating to the compound or salt of formula (III), B is optionally substituted with an 8-15 member fused heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0274] In some embodiments relating to the compound or salt of formula (III), B is optionally substituted with an 8-15 member fused heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0275] In some embodiments relating to the compound or salt of formula (III), B is optionally substituted with an 8-15 member fused heterocycle or optionally substituted with C8-C 15 Condensed carbocyclic rings are [ka] These are selected from, and each is optionally substituted with one or more substituents.

[0276] In some embodiments relating to compounds or salts of formula (III), with respect to B, one or more optional substituents on the heterocycle and carbocyclic rings are halogens, C1-C3 alkyls, -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 2~6Each alkynyl is independently selected for each occurrence. In some cases, one or more substituents on the heterocycle and carbocyclic ring as needed are halogen, oxo, -NH2, C1-C3 alkyl, -B(OR 20 )2, -OH, -C(O)N(R 20 )2, =O, -CN, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 2~6 Each substituent is independently selected from the alkynyl group. In some cases, one or more substituents as needed on the heterocycle and carbocyclic rings are 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 Each substituent is independently selected from the alkynyl group. In some cases, one or more optional substituents on the heterocycle and carbocycle are independently selected from oxo, -NH2, -CN, halogen, and C1-C3 alkyl groups. In some cases, one or more optional substituents on the heterocycle or carbocycle are independently selected from oxo, -NH2, halogen, and C1-C3 alkyl groups.

[0277] In some embodiments relating to the compound or salt of formula (III), B is [ka] [ka] Selected from.

[0278] In some embodiments relating to the compound or salt of formula (III), with respect to B, one or more optional substituents of the heterocycle or carbocyclic ring are independently selected from oxo, -NH2, halogen, and C1-C3 alkyl groups.

[0279] In some embodiments relating to the compound or salt of formula (III), B is [ka] Selected from.

[0280] In some embodiments relating to compounds or salts of formula (III), R 4 These are C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 It is independently selected from alkynyl, oxo, hydroxyl, and halogen. In some cases, R 4 These are C 1~6 It is independently selected from alkyl, oxo, and halogen elements.

[0281] In some embodiments relating to the compound or salt of formula (III), n is selected from 1 and 2. In some cases, n is 0.

[0282] In some embodiments relating to the compound or salt of formula (III), Y is O.

[0283] In some embodiments relating to compounds or salts of formula (III), R 1 The `x` is selected from 5- to 12-membered complex rings, which are substituted as needed.

[0284] In some embodiments relating to compounds or salts of formula (III), R 1 C3~C 12 Selected from carbon rings and 5-12 membered heterocycles, these are 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)R20 , 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 It is optionally substituted with one or more substituents selected independently of the alkynyl molecule.

[0285] In some embodiments relating to compounds or salts of formula (III), R 1 C3~C 12 Selected from carbon rings and 5-12 membered heterocycles, these are 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 C2~6 It is optionally substituted with one or more substituents selected independently of the alkynyl molecule.

[0286] In some embodiments relating to compounds or salts of formula (III), R 1 C3~C 12 Selected from carbocyclic and 5- to 12-membered heterocycles, these are respectively -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 ) may be optionally replaced by one or more substituents selected independently of 2.

[0287] In some embodiments relating to compounds or salts of formula (III), R 1 These are selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens, -OH, and -N(R). 20 )2, -NO2, =O, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0288] In some embodiments relating to compounds or salts of formula (III), R 1 These are selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens, -OH, and -N(R). 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0289] In some embodiments relating to compounds or salts of formula (III), R 1R 20 is hydrogen and C 1~3 Selected from alkyl groups.

[0290] In some embodiments relating to compounds or salts of formula (III), R 1 The 5- to 12-membered hetero rings are unsaturated hetero rings.

[0291] In some embodiments relating to compounds or salts of formula (III), R 1 The 5- to 12-membered complex algebras are saturated complex algebras.

[0292] In some embodiments relating to compounds or salts of formula (III), R 1 The 5- to 12-membered complex rings are bridged complex rings.

[0293] In some embodiments relating to compounds or salts of formula (III), R 1 teeth, [ka] These are selected from halogen, -OH, and -N(R) respectively. 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, =O, -CN, C 1~6 Hydroxyalkyl and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0294] In some embodiments relating to compounds or salts of formula (III), R 1 teeth, [ka] These are selected from halogen, -OH, and -N(R) respectively. 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, =O, -CN, C 1~6 Hydroxyalkyl and C 1~6It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0295] In some embodiments relating to compounds or salts of formula (III), R 1 teeth, [ka] Selected from.

[0296] In some embodiments relating to compounds or salts of formula (III), R 1 It is selected from saturated hetero rings of 6-7 members, which are substituted as needed. In some cases, R 1 It is selected from a 6-member saturated hetero ring, which is substituted as needed. In some cases, R 1 teeth, [ka] Selected from these, which are substituted as needed. In some cases, one or more substituents as needed are halogen, -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed may be -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed may be -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed are -NHCN and C 1~6 Selected independently of alkyl. In some cases, R 1 teeth, [ka] Selected from, this is -NHCN and C 1~6 It is substituted with one or more substituents selected from alkyl groups. In some cases, R 1 teeth, [ka] Selected from.

[0297] In some embodiments relating to compounds or salts of formula (III), R 1 The 6-membered saturated heterocycle is selected from the substituted 6-membered saturated heterocycles, the 6-membered saturated heterocycle being at least one -NHCN and optionally one or more C 1~6 It is substituted with alkyl, M is O, n is 0, and B is an optionally substituted 8-15 member fused heterocycle and optionally substituted C8-C 15 Selected from condensed carbocyclic rings, these are halogen, oxo, -NH2, C1-C3 alkyl, -OH, -C(O)NH2, -NH2, =O, -CN, and C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 2~6 It is optionally substituted with one or more substituents independently selected from the alkynyl, where Y is O and R 2 The -L-bicyclic heterocycle is selected from the bicyclic heterocycle, and the bicyclic heterocycle portion is halogen, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl or -N(R 5 ) is optionally substituted by one or more substituents independently selected from 2, where L is selected from C1-C4 alkylenes. In some cases, R 1 teeth, [ka] Selected from. In some cases, B is [ka] [ka] Selected from. In some cases, B is [ka] Selected from. In some cases, B is [ka] That is the case.

[0298] In some embodiments relating to the compound or salt of formula (III), L is selected from C1-C4 alkylenes.

[0299] In some embodiments relating to the compound or salt of formula (III), L is independently selected from C1-C4 alkylenes, which are optionally substituted, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring, where the C3-C6 carbon ring contains halogen, -OH, -NO2, =O, =S, -CN, and C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 It is optionally substituted with one or more substituents selected from haloalkyls. In some cases, the optional substituents of L are selected from C1-C4 hydroxyalkyl, C1-C4 alkyl, and C3-C6 carbon rings, and optionally, two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring or a 3-8 membered heterocycle, and the C3-C6 carbon ring and 3-8 membered heterocycle are halogen and C 1~6 They are optionally substituted with one or more substituents selected from haloalkyl groups.

[0300] In some embodiments relating to the compound or salt of formula (III), L is independently selected from substituted C1-C4 alkylenes, and two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring. In some cases, the C3-C6 carbon ring is halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 They are optionally substituted with one or more substituents selected from haloalkyl groups.

[0301] In some embodiments relating to the compound or salt of formula (III), L is independently selected from substituted C1-C4 alkylenes, and two substituents on the same carbon atom of L together form a C3-C6 carbon ring. In some cases, L is independently selected from substituted C3 alkylenes, and two substituents on the same carbon atom of L together form a C3 carbon ring. In some cases, L is independently, [ka] It is selected independently of others.

[0302] In some embodiments relating to compounds or salts of formula (III), R 2 is selected from the -L-heterogenetic rings, and the heterogenetic portion of the -L-heterogenetic ring is one or more R 6 Substitutions are made as necessary. 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.

[0303] In some embodiments relating to compounds or salts of formula (III), R 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0304] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0305] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0306] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0307] In some embodiments relating to compounds or salts of formula (III), R 2 is selected from -L-saturated heterocycles, and the saturated heterocycle portion of the -L-saturated heterocycle is one or more R 6 It is substituted as needed and contains one nitrogen atom and one sulfur atom. In some cases, YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed. In some cases, YR 2 teeth, [ka] Selected from, the heterocyclic portion is optionally substituted with one or more substituents selected from C1-C3 alkyl and oxo. In some cases, YR 2 teeth, [ka] Selected from. In some cases, YR 2 teeth, [ka] Selected from.

[0308] In some embodiments relating to compounds or salts of formula (III), R 6 These are halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, C1-C3 aminoalkyl, -Q-phenyl, -Q-phenylSO2F, -NHC(O)phenyl, -NHC(O)phenylSO2F, C1-C3 alkyl-substituted pyrazolyl, -N(R 5 )2, (C1~C3 alkoxy)C1~C3 alkyl-, (C1~C3 alkyl)C(=O), oxo, (C1~C3 haloalkyl)C(=O)-, -SO2F, (C1~C3 alkoxy)C1~C3 alkoxy, -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) heterocycle, -OC(O)N(R 5 )2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl), -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl(C1~C3alkyl)N(CH3)2, -OC(O)NH(C1~C3alkyl)O(C1~C3alkyl)phenyl, independently selected from the -OC(O) heterocycle and the -CH2 heterocycle, where the phenyl in -NHC(O)phenyl and -OC(O)NH(C1~C3alkyl)(C1~C3alkyl)phenyl are optionally substituted with -C(O)H and OH, respectively, and the heterocycle of the -CH2 heterocyclil is optionally substituted with oxo.

[0309] In some embodiments relating to compounds or salts of formula (III), R 6Each of these is independently selected from halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, and C1-C3 aminoalkyl.

[0310] In some embodiments relating to compounds or salts of formula (III), R 6 These are halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and -N(R) respectively. 5 )2 and oxo are selected independently. In some cases, R 6 These are -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 alkoxy, and -N(R) respectively. 5 ) is selected independently from 2. In some cases, R 6 These are C1-C3 alkyl, C1-C3 alkoxy, and -N(R) respectively. 5 ) Selected independently from 2.

[0311] In some embodiments relating to compounds or salts of formula (III), R 6 The elements are selected from halogens, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN, and C1-C3 aminoalkyl. In some cases, R 6 The halogen is selected from halogens and C1-C3 alkyl groups. 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 The halogen is selected from halogens and C1-C3 alkyl groups. In some cases, R 6 It is selected from methyl and fluorine.

[0312] In some embodiments relating to compounds or salts of formula (III), R 2 teeth, [ka] Selected from.

[0313] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] Selected from.

[0314] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] Selected from.

[0315] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] That is the case.

[0316] In some embodiments relating to the compound or salt of formula (III), L is selected from unsubstituted C1-C4 alkylenes.

[0317] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] Selected from, the complex ring portion is one or more R 6 It is replaced as needed.

[0318] In some embodiments relating to compounds or salts of formula (III), R 2 R 6 Each element is independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and C1-C3 aminoalkyl.

[0319] In some embodiments relating to compounds or salts of formula (III), R 2 R 6 Each of these is independently selected from C1-C3 alkyl groups and halogens.

[0320] In some embodiments relating to the compound or salt of formula (III), YR 2 teeth, [ka] Selected from.

[0321] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The carbon ring is C3~C 12 Carbocycle, C3~C 10 Selected from a carbon ring, C3-C9 carbon ring, C3-C8 carbon ring, or C3-C6 carbon ring. In some cases, R 1 The carbon ring is C3~C 12 Carbocycle, C4~C 12 Carbocycle, C5~C 12 Carbocycle, C6~C 12 Carbocycle, C7~C 12 Carbocyclic, C8~C 12 Carbon ring or C9~C 12 Selected from the carbocyclic ring.

[0322] In some embodiments relating to the compound of formula (I), R 1 The complex rings of are 5-12 member complex rings, 6-12 member complex rings, 7-12 member complex rings, or 8-12 member complex rings. In some cases, R 1 The complex rings of are 5-11 member complex rings, 5-10 member complex rings, 5-9 member complex rings, or 5-8 member complex rings. In some cases, R 1 The complex rings of are 6-11 member complex rings, 6-10 member complex rings, 6-9 member complex rings, or 6-8 member complex rings. In some cases, R 1 The complex rings of are 7-11 member complex rings, 7-10 member complex rings, 7-9 member complex rings, or 7-8 member complex rings. In some cases, R 1The complex rings of are 5-6 member complex rings or 5-9 member complex rings. In some cases, R 1 The complex ring of is a complex ring with 8 to 9 members. In some cases, R 1 The heterocycle of is saturated. The heterocycle may be substituted as needed, as described elsewhere in this specification.

[0323] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The complex rings of are monoring complex rings with 5 to 12 members, monoring complex rings with 6 to 12 members, monoring complex rings with 7 to 12 members, or monoring complex rings with 8 to 12 members. In some cases, R 1 The complex rings of are monoring complex rings with 5 to 11 members, monoring complex rings with 5 to 10 members, monoring complex rings with 5 to 9 members, or monoring complex rings with 5 to 8 members. In some cases, R 1 The complex rings of are monoring complex rings with 6 to 11 members, monoring complex rings with 6 to 10 members, monoring complex rings with 6 to 9 members, or monoring complex rings with 6 to 8 members. In some cases, R 1 The complex rings of are monoring complex rings with 7 to 11 members, monoring complex rings with 7 to 10 members, monoring complex rings with 7 to 9 members, or monoring complex rings with 7 to 8 members. In some cases, R 1 The complex rings of are monoring complex rings with 5 to 6 members or monoring complex rings with 5 to 9 members. In some cases, R 1 The complex ring of is a monoring complex ring with 8 to 9 members. In some cases, R 1 The heterocyclic ring of is saturated. Monocyclic heterocyclic rings may be substituted as needed, as described elsewhere in this specification.

[0324] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The hetero rings of are 5-12 member bridging hetero rings, 6-12 member bridging hetero rings, 7-12 member bridging hetero rings, or 8-12 member bridging hetero rings. In some cases, R 1 The hetero rings of are 5-11 member bridging hetero rings, 5-10 member bridging hetero rings, 5-9 member bridging hetero rings, or 5-8 member bridging hetero rings. In some cases, R 1The hetero rings of are 6-11 member bridging hetero rings, 6-10 member bridging hetero rings, 6-9 member bridging hetero rings, or 6-8 member bridging hetero rings. In some cases, R 1 The hetero rings of are 7-11 member bridging hetero rings, 7-10 member bridging hetero rings, 7-9 member bridging hetero rings, or 7-8 member bridging hetero rings. In some cases, R 1 The heterocyclic rings are 5-6 member bridging heterocyclic rings or 5-9 member bridging heterocyclic rings. In some cases, R 1 The heterocycle is an 8-9 member bridging heterocycle. In some embodiments, R 1 The heterocycle of is saturated. The bridging heterocycle may be substituted as needed, as described elsewhere in this specification.

[0325] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 R is a 5- to 9-membered heterocycle, and a 5- to 9-membered heterocycle contains at most one nitrogen atom. In some embodiments, R 1 These are selected from 5- to 9-membered heterogeneous rings, each of which is substituted as needed.

[0326] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (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 1 The 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 bridging heterocycle. In some cases, the heterocycle is a monocyclic heterocycle. In some cases, the heterocycle is a bridging heterocycle. In some cases, the heterocycle is, [ka] Selected from. In some cases, the complex algebra is [ka] Selected from. In some cases, the bridging heterocycle is [ka] The complex rings are selected from the following. The complex rings may be substituted as needed, as described elsewhere in this specification.

[0327] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The spiroheterocycle contains at most one nitrogen atom. In some embodiments, R 1 The spiroheterocycle contains a maximum of two heteroatoms. In some embodiments, R 1 The spiroheterocycle contains up to three heteroatoms. In some embodiments, R 1 The spiroheterocycle contains at most one heteroatom. In some cases, R 1 The spiroheterocycle contains at least two heteroatoms. In some cases, R 1 The spiroheterocycle contains at least three heteroatoms. In some cases, R 1 The spiroheterocycle 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 spiroheterogene is, [ka] [ka] Selected from. In some embodiments, R 1 The spiroheterogene is, [ka] The spiroheterocycle may be substituted as needed, as described elsewhere in this specification.

[0328] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is selected from 7-8 member spiroheterocycles, which are substituted as needed. In some cases, R 1 It is selected from a 7-membered spiroheterocycle, which is substituted as needed. In some cases, R 1 It is selected from an 8-membered spiroheterocyclic ring, which is substituted as needed.

[0329] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The condensed hetero rings of are 6-12 member condensed hetero rings, 6-12 member condensed hetero rings, 7-12 member condensed hetero rings, or 8-12 member condensed hetero rings. In some cases, R 1 The condensed hetero rings of are 6-11 member condensed hetero rings, 6-10 member condensed hetero rings, 6-9 member condensed hetero rings, or 6-8 member condensed hetero rings. In some cases, R 1 The condensed hetero rings of are 7-11 member condensed hetero rings, 7-10 member condensed hetero rings, 7-9 member condensed hetero rings, or 7-8 member condensed hetero rings. In some cases, R 1 The condensed heteroalgebra of is a condensed heteroalgebra with 8 to 11 members. In some cases, R 1 The fused heterocycle is a six-membered fused heterocycle. The fused heterocycle may be substituted as needed, as described elsewhere in this specification.

[0330] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The condensed heteroalgebra of R is selected from 6-membered, 9-membered, 10-membered, 11-membered, and 12-membered condensed heteroalgebras. In some cases, R 1 The condensed heteroalgebra of is selected from 9- to 12-membered condensed heteroalgebras. In some cases, R 1 The condensed heterocycle is selected from 10-12 member condensed heterocycles. The condensed heterocycle is a halogen, -OR 20 , -N(R 20)2, -NO2, =O,C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 The alkyl group is optionally substituted with one or more substituents independently selected from the alkyl group. The condensed heterocycle is halogen, -OR 20 , -N(R 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group.

[0331] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The condensed 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 [ka] The condensed heterocycle may be substituted as needed, as described elsewhere in this specification.

[0332] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 These are selected from C6-C7 carbon rings, 5-10 membered heterocycles, 7-8 membered spiroheterocycles, and 6-, 9-, 10-, 11-, and 12-membered fused heterocycles, each of which is substituted as needed.

[0333] In some embodiments relating to the compound of formula (I), R 1These are selected from C6-C7 carbon rings, 5-10 membered heterocycles, 7-8 membered spiroheterocycles, and 6-membered and 8-12 membered fused heterocycles, which are halogens, -ORs, and so on, respectively. 20 , -N(R 20 )2, -NO2, =O,C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group.

[0334] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 These are selected from C6-C7 carbon rings, 5-10 membered heterocycles, 7-8 membered spiroheterocycles, and 6-membered and 8-12 membered fused heterocycles, which are halogens, -ORs, and so on, respectively. 20 , -N(R 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group.

[0335] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 Regarding -OR 20 and -N(R 20 )2 R 20 is selected hydrogen and C 1~6 It is alkyl.

[0336] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 These are selected from C6-C7 carbon rings and 5-10 membered heterocycles, each of which is substituted as needed. In some cases, the heterocycle contains up to one nitrogen atom. In some cases, R 1These are selected from C6-C7 carbon rings, each of which is substituted as needed.

[0337] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 One or more substituents as needed may be 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 It is selected independently of alkyl.

[0338] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 One or more substituents as needed may be halogens, -OR 20 , -N(R 20 )2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 Selected independently of alkyl. In some cases, R 1 One or more substituents as needed are -OR 20 , -N(R 20 )2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more optional substituents of R1 are -OR 20 , -N(R 20 )2, C 1~6 Aminoalkyl and C 1~6 Selected independently from hydroxyalkyl. In some cases, one or more optional substituents of R1 are -OR 20 , -N(R20 )2, C 1~6 Aminoalkyl, C 1~6 Alkyl and C 1~6 Selected independently from hydroxyalkyl. In some cases, R 1 One or more substituents as needed are -OR 20 , -N(R 20 )2 and C 1~6 Selected independently of alkyl. In some cases, R 1 One or more substituents as needed are -N(R 20 )C(O)N(R 20 ) Selected independently from 2.

[0339] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 C3~C 12 Selected from carbocyclic and 5- to 12-membered heterocycles, 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 These are further selected from 7-membered, 8-membered, 10-membered, and 11-membered spiroheterocycles, as well as 6-membered, 9-membered, 10-membered, 11-membered, and 12-membered condensed heterocycles, C3~C 12 Carbon rings, 5-12 membered heterocycles, 7-, 8-, 10-, and 11-membered spiroheterocycles, and 6-, 9-, 10-, 11-, and 12-membered condensed heterocycles are 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 1~6Alkyl, C 2~6 Alkenyl and C 2~6 Each substituent is optionally substituted with one or more substituents independently selected from the alkynyl molecule.

[0340] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 C3~C 12 Selected from carbocyclic and 5- to 12-membered heterocycles, 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 These are further selected from 7-membered, 8-membered, 10-membered, and 11-membered spiroheterocycles, as well as 6-membered, 9-membered, 10-membered, 11-membered, and 12-membered condensed heterocycles, C3~C 12 Carbon rings, 5-12 membered heterocycles, 7-, 8-, 10-, and 11-membered spiroheterocycles, and 6-, 9-, 10-, 11-, and 12-membered condensed heterocycles are 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 Each substituent is optionally substituted with one or more substituents independently selected from the alkynyl molecule.

[0341] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 These are selected from 5-10 member heterocycles, 7-, 8-, 10-, and 11-member spiroheterocycles, and 6-, 9-, 10-, 11-, and 12-member condensed heterocycles, respectively, and are composed of 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 It is optionally substituted with one or more substituents independently selected from the aminoalkyl group.

[0342] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 These are selected from 5-10 member heterocycles, 7-, 8-, 10-, and 11-member spiroheterocycles, and 6-, 9-, 10-, 11-, and 12-member condensed heterocycles, respectively, and are composed of 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 1~6It is optionally substituted with one or more substituents independently selected from the aminoalkyl group. In some cases, R 1 teeth, [ka] Selected from, respectively, halogen, -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 It is optionally substituted with one or more substituents independently selected from the aminoalkyl group. In some cases, R 1 teeth, [ka] [ka] Selected from.

[0343] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The 5- to 10-membered complex rings are selected from the 5- to 10-membered complex rings, and the 5- to 10-membered complex rings are -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)2 is optionally replaced by one or more substituents selected independently of 2. In some cases, R 1 teeth, [ka] These are selected from, and each is -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 ) may be optionally replaced by one or more substituents selected independently of 2.

[0344] In some embodiments relating to compounds of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from.

[0345] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The complex rings are selected from 5- to 10-membered rings, and these 5- to 10-membered rings are -N(R 20 )2, -OR 20 and C 1~6 They are optionally substituted with one or more substituents independently selected from the alkyl group. In some cases, the 5-10 membered heterocycle is -OR 20 and C 1~6 It is optionally substituted with one or more substituents independently selected from the alkyl. In some embodiments relating to compounds of formula (I), formula (II), or formula (III), R 1 teeth, [ka] These are selected from, and each is -OR 20 and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group. In some cases, R 1 teeth, [ka] Selected from.

[0346] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] [ka] These are selected from the options, and each is replaced as needed.

[0347] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] These are selected from -OH, -CN, oxo, and C respectively. 1~6 It is optionally substituted with one or more substituents independently selected from the cyanoalkyl group.

[0348] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from.

[0349] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] These are selected from the options, and each is replaced as needed.

[0350] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] These are selected from the options, and each is replaced as needed.

[0351] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] These are selected from the options, and each is replaced as needed.

[0352] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] This is replaced as needed.

[0353] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] [ka] Selected from.

[0354] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] That is the case.

[0355] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The 5- to 12-membered heterocycles are unsaturated bridging heterocycles. In some cases, R 1 It is selected from 7-8 member unsaturated bridged heterocycles, which are substituted as needed. In some cases, R 1 teeth, [ka] Selected from.

[0356] In some embodiments relating to compounds of formula (I) or formula (II), R 1 These are selected from 5-10 member heterocycles, 7-, 8-, 10-, and 11-member spiroheterocycles, and 6-, 9-, 10-, 11-, and 12-member condensed heterocycles, respectively, and are composed of 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 1~6It is optionally substituted with one or more substituents independently selected from aminoalkyl, R 3 is naphthalene, and naphthalene is a halogen, -OH, -NH2, -NO2, =O, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl and C 1~6 R is optionally substituted with one or more substituents independently selected from the haloalkyl group. 4 is selected from hydrogen, halogen or C1-C3 alkyl, Y is O, L is independently C1-C4 alkylene, and R 2 The heterocyclic portion is selected from -L-heterocycles, and the heterocyclic portion is halogen, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl or -N(R 5 ) may be optionally replaced by one or more substituents independently selected from 2. In some cases, YR 2 teeth, [ka] The complex ring portion is selected from the available options, and the complex ring portion is substituted as needed.

[0357] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The 5- to 12-membered unsaturated heterocycles are selected as needed, and 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.

[0358] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is selected from 6-7 member complex rings. In some cases, R 1 It is selected from a 7-member complex ring. In some cases, R 1R is selected from 6-membered heterocycles. In some cases, 6- to 7-membered heterocycles contain only one nitrogen atom and, optionally, 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, 6- to 7-membered heterocycles contain only one nitrogen atom and no further additional heteroatoms. In some cases, 6- to 7-membered heterocycles are 6- to 7-membered non-aromatic heterocycles. In some cases, R 1 The 6-7 member heterocycle is bonded to formula (I) via only one nitrogen atom. In some cases, R 1 The 6-7 member heterocycle is bonded in formula (II) via only one nitrogen atom. In some cases, R 1 The 6-7 member heterocycle is bonded in formula (III) via only one nitrogen atom. In some cases, R 1 teeth, [ka] They are selected from and each is replaced. In some cases, R 1 teeth, [ka] They are selected from and each is replaced. In some cases, R 1 The substituents are one or more halogens, -OR 20 , -SR 20 , -N(R 20 )2, -NHCN, -NO2, =O, -CN, C 1~6 Fluoroalkyl and C 2~6 Each is selected from alkinyl, -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 It is further optionally substituted with one or more substituents independently selected from the alkenyl. In some cases, R1 The substituents are one or more halogens, -OR 20 , -N(R 20 )2, -NHCN, =O, -CN and C 2~6 Each is selected from alkinyl, -C(O)N(R 20 )2, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl and C 1~6 It is further optionally substituted with one or more substituents independently selected from the alkyl group. In some cases, R 1 The substituents are one or more halogens, -OH, -NHCN, =O, -CN, and C 2~6 Each is selected from Alkinyl, C 1~6 It is further optionally substituted with one or more substituents independently selected from the alkyl group. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] They are selected from and each is replaced as needed. In some cases, R 1 teeth, [ka] They are selected from and each is replaced as needed. In some cases, R 1 teeth, [ka] They are selected from and each is replaced as needed. In some cases, R 1 One or more substituents as needed are fluorine, -OH, -C(O)NH2, -NH-C(O)-(C 1~6 Alkoxy), -NH-C(O)-(C 1~6Hydroxyalkyl), -NH2, -NH(CN), =O, -CN, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Alkyl and C 2~6 Each is independently selected from the alkinyls. In some cases, R 1 One or more substituents as needed may be halogen, -OH, -CN, C 1~6 Cyanoalkyl, C 1~6 Alkyl and C 2~6 Each is independently selected from the alkinyls. In some cases, R 1 One or more substituents as needed are independently selected from halogens, -OH, and -CN, respectively. In some cases, R 1 One or more substituents as needed may be fluorine, -OH, -CN, C 1~6 Cyanoalkyl, C 1~6 Alkyl, oxo, and C 2~6 Each is independently selected from the alkinyls. In some cases, R 1 One or more substituents as needed may be fluorine, -OH, -CN, C 1~6 Cyanoalkyl, C 1~6 Alkyl and C 2~6 Each is independently selected from the alkinyls. In some cases, R 1 teeth, [ka] [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from.

[0359] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is selected from 6- to 8-member unsaturated hetero rings, which are substituted as needed. In some cases, R 1 It is selected from a 6-member unsaturated hetero ring, which is substituted as needed. In some cases, R 1 R is selected from seven-membered unsaturated heterocycles, which are substituted as needed. In some cases, the heterocycle has one or two double bonds. In some cases, the heterocycle has only one double bond. In some cases, the heterocycle has only two double bonds. In some cases, R 1 teeth, [ka] Selected from, respectively, halogen, -OH, -NH2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group. In some cases, R 1 teeth, [ka] Selected from, respectively, halogen, -OH, -NH2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group. In some cases, R 1 teeth, [ka] Selected from, respectively, halogen, -OH, -NH2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] [ka] They are selected from and each is substituted with one or more substituents independently selected from halogens.

[0360] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1The compound is selected from a 6- to 7-membered unsaturated heterocycle, which is substituted with one or more substituents selected from halogens. In some cases, the 6- to 7-membered unsaturated heterocycle is substituted with at least one halogen. In some cases, the 6- to 7-membered unsaturated heterocycle is substituted with only one halogen. In some cases, the 7-membered unsaturated heterocycle is substituted with one fluorine atom. In some cases, R 1 R is selected from a 6-membered unsaturated heterocycle substituted with at least one halogen. In some cases, R 1 R is selected from a 7-membered unsaturated heterocycle substituted with at least one halogen. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] That is the case.

[0361] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is selected from 6- to 8-member unsaturated hetero rings, which are substituted as needed. In some cases, R 1 It is selected from a 7-member unsaturated hetero ring, which is substituted as needed. In some cases, R 1 teeth, [ka] Selected from, respectively, halogen, -OH, -NH2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group. In some cases, R 1 teeth, [ka] Selected from.

[0362] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is selected from a 6-membered heterocycle which is substituted as needed. In some cases, the 6-membered heterocycle contains only one nitrogen atom. In some cases, R 1 The six-membered heterocycle is bonded to the ring in formula (I) via only one nitrogen atom. In some cases, R 1 The six-membered heterocycle is bonded in formula (II) via only one nitrogen atom. In some cases, R 1 The six-membered heterocycle is bonded in formula (III) via only one nitrogen atom. In some cases, R 1 teeth, [ka] Selected from these, any of which are replaced as needed. In some cases, R 1 One or more substituents as needed may be 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 Each is independently selected from the alkinyls. In some cases, R 1 One or more substituents as needed may be fluorine, -OH, -NH2, -NH(CN), =O, -CN, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Alkyl and C 2~6 Each is independently selected from the alkinyls. In some cases, R 1 One or more substituents as needed may be fluorine, -OH, -NH2, -NH(CN), =O, -CN, C 1~6 Hydroxyalkyl, C 1~6 Alkyl and C 2~6 Each is independently selected from the alkynyls. In some cases, a 6-membered heterocycle is either a 6-membered partially unsaturated heterocycle or a 6-membered saturated heterocycle. In some cases, a 6-membered heterocycle is partially unsaturated. In some cases, a 6-membered heterocycle is a 6-membered saturated heterocycle. In some cases, a 6-membered heterocycle is a 6-membered monocyclic heterocycle. In some cases, a 6-membered heterocycle is not a bridging heterocycle. In some cases, R 1 teeth, [ka] Selected from.

[0363] In some embodiments relating to compounds of formula (I), formula (II), or formula (III), R 1 These are selected from six-membered unsaturated hetero rings and six-membered saturated hetero rings, which are substituted as needed.

[0364] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R1 teeth, [ka] Selected from, respectively, halogen, -OH, -NH2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group.

[0365] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from, halogen and C 1~6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0366] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from.

[0367] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from, respectively, halogen, -OH, -NH2, -NO2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 1~6These are two substituents, independently selected from the alkyl group and substituted as needed.

[0368] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from, halogen and C 1~6 It is optionally substituted with two substituents independently selected from the haloalkyl group. In some cases, R 1 teeth, [ka] That is the case.

[0369] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The 6- to 10-membered heterocycle is selected as needed, and is substituted as necessary. In some cases, the 6- to 10-membered heterocycle contains at least one nitrogen atom. In some cases, R 1 teeth, [ka] These are selected from halogen, -O, -OH, -CN, -NHCN, and -C(O)N(R) respectively. 20 )2, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group. In some cases, R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, C 3~12C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~12 It is independently selected from carbon rings and 3- to 12-membered heterocycles. In some cases, R 1 teeth, [ka] Selected from.

[0370] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The 10-membered heterocycle is selected from substituted 10-membered heterocycles as needed. In some cases, the 10-membered heterocycle is a bicyclic heterocycle. In some cases, the 10-membered heterocycle is a spiroheterocycle. 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 teeth, [ka] These are selected from halogen, -O, -OH, -CN, -NHCN, and -C(O)N(R) respectively. 20 )2, -C(O)NR 20 Ure 20 , C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl and C 1~6 It is optionally substituted with one or more substituents selected independently of the alkyl group. In some cases, R 1 teeth, [ka] [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from, this is 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 It is optionally substituted with one or more substituents selected independently of the alkynyl molecule.

[0371] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is selected from 9- to 11-member unsaturated hetero rings, which are substituted as needed. In some cases, R 1 It is selected from a 10-membered unsaturated hetero ring, which is substituted as needed. In some cases, R 1 It is selected from 10-membered unsaturated condensed heterocycles, which are substituted as needed. In some cases, R 1 teeth, [ka] This is substituted as needed. In some cases, one or more substituents as needed are 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 Selected from alkinyl. In some cases, R 1 is -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 Substituted as needed with one or more substituents selected from alkynyls. [ka] In some cases, R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, and C, respectively. 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, C 2~10 Alkenil, C 2~10 Alkinyl, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl and C 3~12 It is selected independently of the carbon ring.

[0372] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is selected from 7- to 11-membered spirohetall rings. In some cases, R 1 R is selected from a 10-membered spiroheterocycle. 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 teeth, [ka] These are selected from and are substituted as needed. In some cases, one or more substituents as needed are 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 Selected independently of alkinyl. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] In some cases, R 1 teeth, [ka] In some cases, M is O and NR. 3 Selected from. In some cases, M is selected from O. In some cases, M is NR 3 Selected from. In some cases, R 3 C 1~6 Selected from alkyl groups. In some cases, R3 C 1~2 Selected from alkyl groups. In some cases, R 3 It is selected from methyl.

[0373] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 The 8-10 member fused heterocycle is selected from 8-10 member fused heterocycles, which are substituted as needed. In some cases, the 8-10 member fused heterocycle is a bicyclic heterocycle. In some cases, the 8-10 member fused heterocycle is a saturated heterocycle. In some cases, the 8-10 member fused heterocycle is an unsaturated heterocycle. In some cases, the 8-10 member heterocycle is a non-aromatic heterocycle. In some cases, R 1 It is selected from a 9-member condensed heteroring, which is substituted as needed. In some cases, R 1 The 10-membered fused heterocycle is selected from 10-membered heterocycles that are substituted as needed. 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, a nine-membered heterocycle contains at least two nitrogen atoms. In some cases, a nine-membered heterocycle contains at least three nitrogen atoms. In some cases, R 1 teeth, [ka] These are selected from, and each is optionally substituted with one or more substituents. In some cases, R 1 teeth, [ka] This is substituted as needed by one or more substituents. In some cases, R 1 teeth, [ka] This is substituted as needed by one or more substituents. In some cases, R 1 One or more substituents as needed may be halogen, -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 Independently selected from alkynnyls and 5- to 12-membered heterorings, the 5- to 12-membered heterorings are one or more R 1* Each is substituted independently as needed. In some cases, R 1 One or more substituents as needed may be halogen, -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)R20 -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 Selected independently of alkynyl. In some cases, one or more substituents as needed are 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 Ure 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 Selected independently of alkyl. In some cases, one or more substituents as needed may be 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 Ure 20 Selected independently from. In some cases, one or more substituents as needed are 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(R20 )2 and -C(O)NR 20 Ure 20 Selected independently from. In some cases, one or more substituents as needed are -C(O)R 20 ,-C(O)N(R 20 )2 and -C(O)NR 20 Ure 20 It is selected independently from. In some cases, one or more substituents as needed are -S(O)2(R 20 ), -S(O)2N(R 20 )2, -S(O)N(R 20 )2, -S(O)R 20 (=NR 20 ) are selected independently. In some cases, one or more substituents as needed may be -S(O)N(R 20 )2 is independently selected. In some cases, one or more substituents as needed may be S(O)2(R 20 ) are selected independently. In some cases, one or more substituents as needed may be added to S(O)R 20 (=NR 20 ) are selected independently. In some cases, one or more substituents as needed may be -C(O)R 20 Selected independently from. In some cases, one or more substituents as needed are -C(O)N(R 20 )2 is selected independently. In some cases, one or more substituents as needed may be -C(O)NR 20 Ure 20 It is selected independently of R. In some cases, R 1 teeth, [ka] These are selected from and are further substituted as needed. In some cases, this additional one or more as needed substituents are halogen, -OH, =O, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 1~6Alkyl and C 2~6 Selected from alkynyls. In some cases, this additional one or more as-needed substituents may be halogens, -CN, C2 alkenyls, and C 1~6 Selected from alkyl groups. In some cases, this additional one or more optional substituents may be halogens and C 1~6 Selected from alkyl groups. In some cases, this additional one or more optional substituent is selected from halogens. In some cases, R 20 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 It is independently selected from carbon rings and 3- to 12-membered heterocycles. In some cases, R 20 These are hydrogen and C, respectively. 1~6 It is independently selected from alkyl groups and 3- to 12-membered heterocycles. In some cases, R 20 These are hydrogen and C, respectively. 1~6 A alkyl group and a saturated heterocycle with 3 to 12 members are independently selected. In some cases, R 20 Each of these is independently selected from saturated hetero rings of 5-6 members. In some cases, R 20 The heterocycle has at least one nitrogen atom. In some cases, R 20 The heterocycle of has at least one sulfur atom. In some cases, R 20 The heterocycle of has at least one oxygen atom. In some cases, R 20 The heterocycle contains only one heteroatom. In some cases, R 20 The heterocycle of has at least two heteroatoms. In some cases, R 20 The heterocycle contains only two heteroatoms. In some cases, R 1 One or more substituents as needed may be halogens, -CN, C2 alkenyls, [ka] It is selected independently of R. In some cases, R 1 One or more substituents as needed may be halogens, [ka] It is selected independently of R. In some cases, R 1 One or more substituents as needed are [ka] It is selected independently of R. In some cases, R 1 One or more substituents as needed may be halogens, [ka] It is selected independently of R. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 One or more substituents as needed include halogens and C 1~6 alkyl-N(R 20 ) is selected independently from 2. In some cases, R 1 One or more substituents as needed may be halogens, [ka] It is selected independently of R. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 20 These are hydrogen and C, respectively. 1~6 Alkyl and C 3~6 It is independently selected from the carbon ring. In some cases, R 1 is selected [ka] In some cases, R 1 is selected [ka] In some cases, R 1 teeth, [ka] Selected from, this is halogen, -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, optionally substituted with one more substituent independently selected from the 5-12 membered heterocycle, where the 5-12 membered heterocycle is a halogen, -OR 20 and C1~6 It is optionally substituted with one or more substituents selected from alkyl groups. In some cases, R 1 teeth, [ka] Selected from, this is halogen and C 1~6 It is optionally substituted with one more substituent independently selected from the alkyl group. In some cases, R 1 teeth, [ka] Selected from.

[0374] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] Selected from, [ka] The R is selected from 5- to 12-membered hetero rings, and one or more R are 5- to 12-membered hetero rings. 1* It is substituted independently as needed by R B is hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Selected from alkynyl and -CN. In some cases, R B R is selected from hydrogen and halogens. In some cases, B It is chlorine. In some cases, R B It is hydrogen. In some cases, [ka] It has at least one, two, three, or four heteroatoms. In some cases, [ka] It has at least one, two, three, or four nitrogen atoms. In some cases, [ka] It has at least one oxygen atom. In some cases, [ka] It is a monoring complex ring. In some cases, [ka] It is a biring complex algebra. In some cases, [ka] It is selected from a 5-membered complex ring, which is substituted as needed. In some cases, [ka] It is selected from a 9-member complex ring, which is substituted as needed. In some cases, [ka] teeth, [ka] These are selected from, and each of them is one or more R 1* It is replaced as needed. In some cases, [ka] teeth, [ka] These are selected from, and each of them is one or more R 1* It is replaced as needed by R. 1* These are halogen and -OR respectively. 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 Ure 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 and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 alkyl-N(R 20 )2, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 It is selected independently of alkyl. In some cases, [ka] teeth, [ka] Selected from.

[0375] Formula (I) Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III), R 1 However, -C(O)R 20 If it is replaced by R 20 It is selected from 5- to 12-membered heterorings, which are substituted as needed. In some cases, R 1 is -C(O)R 20 It is replaced by R. In some cases, 20 It is selected from 5- to 12-member unsubstituted heteroalgebras. In some cases, R 20 The heterocycle is selected from 5-6 membered heterocycles which are substituted as needed. 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 complex ring of is [ka] They are selected from and each is replaced as needed. In some cases, R 20 teeth, [ka] Selected from. In some cases, substituents as needed are C 1~10 Selected from alkyl, oxo, and =NH.

[0376] Formula (I) Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III), R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10C is optionally substituted with one or more substituents independently selected from alkyl, oxo, and =NH. 1~6 Alkyl, C 3~12 It is independently selected from carbon rings and 3- to 12-membered heterocycles. In some cases, R 20 These are hydrogen and unsubstituted C, respectively. 1~6 They are independently selected from alkyl and 3- to 12-membered heterocycles, and these 3- to 12-membered heterocycles include halogens, -OH, -CN, -NO2, -NH2, and -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 It is optionally substituted with one or more substituents independently selected from alkyl, oxo, and =NH groups.

[0377] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is a 12-15 member complex ring that is substituted as needed. In some cases, R 1 It is a 12-membered complex ring that is substituted as needed. In some cases, R 1 It is a 13-member complex ring that is substituted as needed. In some cases, R 1 It is a 14-membered complex ring that is substituted as needed. In some cases, R 1 This is a 15-membered complex ring that is substituted as needed. In some cases, R 1 The complex ring of is a triring. In some cases, R 1 The heterocycle of includes fused heterocycles. In some cases, R 1 The heterocycle of contains a spiroheterocycle. In some cases, R 1 The heterocycle contains a fused spiroheterocycle. In some cases, R 1 The complex algebra of is an unsaturated complex algebra. In some cases, R 1 The heterocycle of is a non-aromatic heterocycle. In some cases, R 1 The heterocycle of has at least one double bond. In some cases, R 1 The heterocycle of has at least two double bonds. In some cases, R 1The heterocycle of has at least two heteroatoms. In some cases, R 1 The heterocycle of 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 of has at least 6 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 1 The heterocycle has at least 3, 4, or 5 nitrogen atoms and at least 1 oxygen atom. In some cases, R 1 The heterocycle has at least 3, 4, or 5 nitrogen atoms. In some cases, R 1 The heterocycle has at least 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 teeth, [ka] These are selected from, and each is optionally substituted with one or more substituents. In some cases, R 1 teeth, [ka] These are selected from, and each is optionally substituted with one or more substituents. In some cases, R 1 One or more substituents as needed may be halogen, -OH, -NHCN, -S(O)2(R 20 ), -S(O)2N(R 20 )2, -S(O)N(R 20 )2, -S(O)R 20 (=NR20 ), -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 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 1~6 Alkyl, and C 2~6 Selected independently of alkinyl. In some cases, R 1 One or more substituents as needed may be halogen, -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 Selected independently of alkinyl. In some cases, R 1 One or more substituents as needed include halogen, -OH, and C. 1~6 Alkyl and -C(O)N(R) 20 ) is selected independently from 2. In some cases, R 1 teeth, [ka] Selected from.

[0378] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1It is a 12-15 member complex ring that is substituted as needed. In some cases, R 1 teeth, [ka] Ring W is a heterocycle which is substituted as necessary, and ring P is a carbon ring which is substituted as necessary or a heterocycle which is substituted as necessary, and ring P forms a spiro ring with ring W. In some cases, ring W is a fused heterocycle which is substituted as necessary. In some cases, rings P and W together form a heterocycle which has at least 12 and up to 15 atoms. In some cases, rings P and W together have at least 12 and up to 15 atoms. In some cases, ring W is a 10-membered fused heterocycle which is substituted as necessary. In some cases, R 1 teeth, [ka] The ring P is a carbon ring or a hetero ring, which may be substituted as needed. In some cases, R 1 teeth, [ka] In some cases, ring P is a carbon ring which is optionally substituted. In some cases, ring P is a heterocycle which is optionally substituted. In some cases, ring P forms an optionally substituted C3-C6 carbon ring or an optionally substituted 4-6 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 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 on ring P are halogen, -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 The substituents are selected independently of the alkynyl group. In some cases, one or more optional substituents on ring P are halogens, -OH, =O, =NH, -CN, and C 1~6 Selected independently of alkyl. In some cases, one or more optional substituents on ring W may be halogen, -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)R20 -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 Selected independently from alkynyl. In some cases, one or more optional substituents on ring W are 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 Ure 20 -C(O)NHOR 20 , -N(R 20 )2, -C(O)R 20 and C 1~6 Selected independently of alkyl. In some cases, one or more optional substituents on ring W are -C(O)R 20 They are selected independently. In some cases, ring P is substituted. In some cases, ring W is substituted.

[0379] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] These are selected from and each is optionally substituted with one or more substituents. In some cases, one or more substituents as needed are 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 Alkenil, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl and C1~6 Selected independently from haloalkyl groups. In some cases, R 1 teeth, [ka] [ka] [ka] [ka] Selected from.

[0380] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 2 The heterocycle is selected from the -L-heterocycles which are substituted as needed. 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 teeth, [ka] Selected from, the complex ring portion is substituted as needed. In some cases, R 2 teeth, [ka] Selected from, the complex ring portion is substituted as needed. In some cases, YR 2 teeth, [ka] Selected from, the complex ring portion is substituted as needed. In some cases, YR 2 teeth, [ka] Selected from the above, the heterocyclic portion is substituted as needed. In some cases, the heterocyclic portion is halogen, hydroxyl, C1-C3 alkyl, -N(R) 5 )S(O)2(R 5 ), -OC(O)N(R 5 )2, oxo, =CH2, =NO-C1~C3 alkyl, -CH2OC(O) heterocycle, -CH2 heterocycle, -CH2OC(O)N(R 5 ) optionally substituted with one or more substituents selected from 2 and -O-C1~C3 alkyl groups, where the alkyl group of the -O-C1~C3 alkyl group is optionally substituted with substituents selected from heterocyclic, oxo, and hydroxyl groups. In some cases, YR 2 teeth, [ka] Selected from. In some cases, YR 2 teeth, [ka] Selected from. In some cases, YR 2 teeth, [ka] [ka] Selected from.

[0381] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 2 is -LN(R 21 ) Selected from 2. In some cases, R 21 These are hydrogen and C, respectively. 1~6 Selected from alkyl groups. In some cases, R 21 These are C 1~6Selected from alkyl groups. In some cases, L is independently selected from substituted C1-C4 alkylenes, and two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring, which is optionally substituted with one or more substituents selected from halogens. In some cases, L is, [ka] In some cases, R 2 teeth, [ka] In some cases, YR 2 teeth, [ka] That is the case.

[0382] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 21 Each is selected independently of hydrogen. In some cases, R 21 These are hydrogen and C, respectively. 1~6 Selected independently of alkyl. In some cases, R 21 These are C 1~6 Selected independently of alkyl. In some cases, R 21 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 C is optionally substituted with one or more substituents independently selected from alkyl and oxo groups. 3~12 They are independently selected from carbon rings and 3- to 12-membered heterocycles.

[0383] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1R is selected from 8-10 member fused heterocycles, which are substituted as needed. In some cases, the 8-10 member fused heterocycle is a bicyclic heterocycle. In some cases, the 8-10 member fused heterocycle is a saturated heterocycle. In some cases, the 8-10 member heterocycle is a non-aromatic heterocycle. In some cases, R 1 It is selected from a 9-member condensed heteroring, which is substituted as needed. In some cases, R 1 The 10-membered fused heterocycle is selected from 10-membered heterocycles that are substituted as needed. 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 teeth, [ka] These are selected from, and each is optionally substituted with one or more substituents. In some cases, R 1 teeth, [ka] These are selected from, and each is optionally substituted with one or more substituents. In some cases, R 1 teeth, [ka] This is substituted as needed by one or more substituents. In some cases, the one or more substituents as needed are halogens, =O, -OH, -CN, -NHCN, -C(O)R 20 ,-C(O)N(R 20 )2, -C(O)NR 20 Ure 20 , C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed are halogens, =O, -C(O)R 20 ,-C(O)N(R 20 )2 and -C(O)NR 20 Ure 20 Selected independently from. In some cases, one or more substituents as needed are -C(O)R 20 ,-C(O)N(R 20 )2 and -C(O)NR 20 Ure 20 Selected independently from. In some cases, one or more substituents as needed are -C(O)R 20 Selected independently from. In some cases, one or more substituents as needed are -C(O)N(R 20 )2 is selected independently. In some cases, one or more substituents as needed may be -C(O)NR 20 Ure 20 It is selected independently of R. In some cases, R 20 These are hydrogen and C, respectively. 1~6 Alkyl, C 3~12 It is independently selected from carbon rings and 3- to 12-membered heterocycles. In some cases, R 20 These are hydrogen and C, respectively. 1~6 It is independently selected from alkyl groups and 3- to 12-membered heterocycles. In some cases, R 20 These are hydrogen and C, respectively. 1~6 A alkyl group and a saturated heterocycle with 3 to 12 members are independently selected. In some cases, R 1 One or more substituents as needed are [ka] It is selected independently of R. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 teeth, [ka] [ka] Selected from. In some cases, R 1 teeth, [ka] That is the case.

[0384] In some embodiments relating to compounds or salts of formula (I), R 1 It is selected from saturated hetero rings of 6-7 members, which are substituted as needed. In some cases, R 1 It is selected from a 6-member saturated hetero ring, which is substituted as needed. In some cases, R 1 teeth, [ka] Selected from these, which are substituted as needed. In some cases, one or more substituents as needed are halogen, -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed may be -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed may be -CN, -NHCN, C 1~6 Cyanoalkyl and C 1~6 Selected independently of alkyl. In some cases, one or more substituents as needed are -NHCN and C1~6 Selected independently of alkyl. In some cases, R 1 teeth, [ka] Selected from, this is -NHCN and C 1~6 It is substituted with one or more substituents selected from alkyl groups. In some cases, R 1 teeth, [ka] Selected from.

[0385] In some embodiments relating to compounds or salts of formula (I), R 1 The 6-membered saturated heterocycle is selected from the substituted 6-membered saturated heterocycles, the 6-membered saturated heterocycle being at least one -NHCN and optionally one or more C 1~6 It is substituted with alkyl, and B is an 8-15 member fused heterocycle which is substituted as needed, and C8-C which is substituted as needed. 15 Selected from condensed carbocyclic rings, these are halogen, oxo, -NH2, C1-C3 alkyl, -OH, -C(O)NH2, -NH2, =O, -CN, and C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 2~6 The ring A is optionally substituted with one or more substituents independently selected from the alkynyl ring, where Y is O and R is optionally substituted from a heterocycle. 2 The heterocyclic portion is selected from -L-heterocycles, and the heterocyclic portion is halogen, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl or -N(R 5 ) is optionally substituted by one or more substituents independently selected from 2, where L is selected from C1-C4 alkylenes. In some cases, R 1 teeth, [ka] Selected from. In some cases, B is [ka] Selected from. In some cases, B is [ka] Selected from. In some cases, B is [ka] That is the case.

[0386] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), B is an optionally substituted 8- to 10-membered condensed carbon ring. In some cases, B is a substituted 8- to 10-membered condensed carbon ring. In some cases, B is an unsubstituted 8- to 10-membered condensed carbon ring. In some cases, B is an optionally substituted 9-membered condensed carbon ring. In some cases, B is, [ka] This is substituted as needed by one or more substituents. In some cases, B is [ka] This is substituted by one or more substituents. In some cases, with respect to B, the one or more substituents are 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 Selected independently of alkynyl. 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 [ka] Selected from. In some cases, B is [ka] This is because halogen and C 1~6 It is substituted with one or more substituents selected from haloalkyl groups. In some cases, B is [ka] This is substituted by one or more substituents selected from halogens. In some cases, B is [ka] Selected from. In some cases, B is [ka] This is substituted with one or more substituents selected from fluorine. In some cases, B is [ka] Selected from. In some cases, B is [ka] This is substituted with one or more substituents selected from chlorine. In some cases, B is [ka] Selected from the following. In some cases, B is a substituted 10-membered condensed carbon ring. In some cases with respect to the 10-membered condensed carbon ring of B, one or more substituents are halogen, -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 It is selected independently of alkinyl. In some cases, B is [ka] Selected from. In some cases, the 10-membered condensed carbocyclic ring of B is substituted with at least one halogen. In some cases, B is [ka] Selected from. In some cases, B is an unsubstituted 9-10 member condensed carbon ring. In some cases, B is selected. [ka] These are all non-substitutive. In some cases, B is [ka] In some cases, B is [ka] That is the case.

[0387] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 One or more substituents as needed may be halogen, -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, C1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 1~6 Alkyl, C 2~6 Alkynnyls are independently selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens and C 1~6 They are optionally substituted with one or more substituents selected from alkyl groups.

[0388] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 teeth, [ka] And R 1 One or more substituents as needed may be halogen, -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 An alkynyl and optionally substituted 5- to 12-membered heteroring is independently selected. In some cases, R 1 One or more substituents as needed may be halogen, -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 An alkynyl and optionally substituted 5- to 12-membered heteroring is independently selected. In some cases, R 1 One or more substituents as needed may be halogen, -CN, C 2~6 Alkinyl, -C(=NR) 20 )N(R 20 )2 and 5- to 12-membered heterorings are independently selected as needed. In some cases, R 1 One or more substituents as needed may be halogens, -C(=NR 20 )N(R 20 )2 and 5- to 12-membered heterorings are independently selected as needed. In some cases, R 1 One or more substituents as needed are -C(=NR 20 )N(R 20 )2 and 5- to 12-membered heterorings are independently selected as needed. In some cases, R 1 One or more optional substituents are independently selected from 5- to 12-membered heterocycles, which are substituted as needed. In some cases, R 1 One or more optional substituents are independently selected from 5-membered heterocycles and 9-membered heterocycles, each of which has one or more R 1*It is replaced independently as needed. In some cases, R 1 It is substituted with at least one halogen atom, -CN,C 2~6 Alkinyl, -C(=NR) 20 )N(R 20 ) optionally substituted with one or more substituents independently selected from 2 and 5-12 membered heterocycles, the 5-12 membered heterocycle being one or more R 1* Substitutions are made independently as needed. 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 1 The heterocycle of one or more optional substituents is [ka] These are selected from, and each of them is one or more R 1* It is replaced as needed by R. 1 The heterocycle of one or more optional substituents is [ka] Selected from, this is one or more R 1* It is replaced as needed by R. 1* These are halogen and -OR respectively. 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 Ure 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 and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and -OR respectively. 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 Ure 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 and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 alkyl-N(R 20 )2, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 Haloalkyl and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 Selected independently of alkyl. In some cases, R 1* Each is selected independently of the halogen. In some cases, R 1* These are C 1~6 Selected independently of alkyl. In some cases, R 1* These are -OR respectively. 20 It is selected independently of R. In some cases, R 1* Each is selected independently of -OH. In some cases, R 1* Each is selected independently of -OMe. In some cases, R 1 The heterocycle of one or more optional substituents is [ka] Selected from.

[0389] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 One or more substituents as needed are -C(=NR 20)N(R 20 )2 and 5- to 12-membered heterorings are independently selected as needed. In some cases, R 1 One or more optional substituents are independently selected from the 5- to 12-membered heterocycles which are substituted as needed. In some cases, the heterocycle is [ka] These are selected from, and each of them is one or more R 1* It is replaced as needed by R. 1 One or more substituents as needed are [ka] Selected from.

[0390] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1* These are halogen and -OR respectively. 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 Ure 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 1~6alkyl-N(R 20 )2, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and -OR respectively. 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 Ure 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 and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 alkyl-N(R 20 )2, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C1~6 Cyanoalkyl, C 1~6 Haloalkyl and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 Haloalkyl and C 1~6 Selected independently of alkyl. In some cases, R 1* These are halogen and C, respectively. 1~6 Selected independently of alkyl. In some cases, R 1* Each is selected independently of the halogen. In some cases, R 1* These are C 1~6 It is selected independently of alkyl.

[0391] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 These are selected from 5-15 member heterocycles (preferably 8-10 member heterocycles or preferably 10 member heterocycles), and these are halogens, oxos, and -C(O)N(R) 20 )2, -C(O)NR 20 Ure 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 2~6 The alkynyl and one or more substituents optionally selected independently from a 5- to 12-membered heterocycle (preferably a 5- to 9-membered heterocycle), wherein the 5- to 12-membered heterocycle is substituted with one or more R 1* Each is substituted independently as needed, R 1* These are halogen and C, respectively. 1~6 Haloalkyl and C 1~6 Selected independently of alkyl groups. In some cases, the 8- to 10-membered heterocycles are bicyclic. In some cases, the 10-membered heterocycles are substituted. In some cases, R 1 is selected [ka] These are, and each is substituted as needed. In some cases, R 1 is selected [ka] And this is replaced as needed. In some cases, R 1 is selected [ka] [ka] In some cases, R 1 is selected [ka] In some cases, R 1 teeth, [ka] That is the case.

[0392] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 These are selected from 5-15 member heterocycles (preferably 8-10 member heterocycles or preferably 10 member heterocycles), and these are halogens, -C(O)N(R) 20 )2, -C(O)NR 20 Ure 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 The alkynyl and one or more substituents optionally selected independently from a 5- to 12-membered heterocycle (preferably a 5- to 6-membered heterocycle), wherein the 5- to 12-membered heterocycle is substituted with one or more R substituents. 1*Each is substituted independently as needed, R 1* These are halogen and C, respectively. 1~6 Haloalkyl and C 1~6 Selected independently of alkyl groups. In some cases, the 8- to 10-membered heterocycles are bicyclic. In some cases, the 10-membered heterocycles are substituted. In some cases, R 1 is selected [ka] These are, and each is substituted as needed. In some cases, R 1 is selected [ka] And this is replaced as needed. In some cases, R 1 is selected [ka] [ka] In some cases, R 1 is selected [ka] In some cases, M is selected from O and NMe. In some cases, M is O. In some cases, M is NMe. In some cases, R 2 is -LN(R 21 )2, and one or more R 6 Selected from the -L-heterogenes which are substituted as needed. In some cases, YR 2 teeth, [ka] Selected from. In some cases, B is selected from a carbon ring that is substituted as needed. In some cases, B is [ka] They are selected from, and each is replaced as necessary. In some cases, B is [ka] Selected from. In some cases, B is [ka] In some cases, B is [ka] In some cases, n is 0.

[0393] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 Y is 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 B is selected from the compounds in 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 necessary substituents on the heterocycle are selected from the compounds in the section of Examples.

[0394] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 2 is -LN(R 21 )2. In some cases, R 2 is -L-OR 21 In some cases, R 2 It is a complex algebra. In some cases, R 2 These are C1-C6 alkyl groups. In some cases, R 2 It is an L-complex algebra. In some cases, R 2 is an -L-aryl. In some cases, R 2 It is a -L-heteroaryl. In some cases, R 2 It is a -L-cycloalkyl. In some cases, R 2is -LN(R 21 )2. In some cases, R 2 It is -L-NHC(=NH)NH2. In some cases, R 2 is -LC(O)N(R 21 )2. In some cases, R 2 It is a -L-C1~C6 haloalkyl. In some cases, R 2 is -L-OR 21 In some cases, R 2 is -L-NR 21 It is a C(O)-aryl compound. In some cases, R 2 It is -L-COOH. In some cases, R 2 is -L-NR 21 S(O)2(R 21 ) is the case. In some cases, R 2 is -LS(O)2N(R 21 )2. In some cases, R 2 is -LN(R 21 )C(O)(OR 21 ) is the case. In some cases, R 2 is -L-OC(O)N(R 21 )2. In some cases, R 2 These are -LC(=O)OC1~C6 alkyl groups. In some cases, they are heterocyclic, -L-NR groups. 21 The aryl portion of C(O)-aryl, the heterocyclic portion of -L-heterocyclic, and the cycloalkyl portion of -L-cycloalkyl are one or more R 6 Each is substituted as needed, and the aryl portion of -L-aryl and the heteroaryl portion of -L-heteroaryl are replaced by one or more R 7 Each is substituted as needed. In some cases, Y is a bond, O or S, R 2 It is further selected from hydrogen.

[0395] In some embodiments, formula (I) or formula (II) is used instead of formula (II * ): [ka] or represented by a pharmaceutically acceptable salt thereof (in the formula, M is O and NR 3 Selected from, R 3 is hydrogen, C 1~6 Alkyl and C 1~6 Selected from cyanoalkyl groups, R 1 It is selected from 7- to 10-membered heterocycles, and these 7- to 10-membered heterocycles include 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 Ure 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 Alkenil, C 2~6The alkynyl group is optionally substituted with one or more substituents independently selected from a 5- to 12-membered heterocycle, wherein the 5- to 12-membered heterocycle has one or more R substituents. 1* It is replaced independently as needed. R 1* These are halogen, -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 Ure 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 Alkenil, C 2~6 Alkinyl, and C3~C 12 Selected independently from the carbon ring, B is C6~C 15 Selected from the carbon ring, C6~C 15The carbon ring is a halogen, C1-C3 alkyl, -B(OR 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 It is optionally substituted with one or more substituents independently selected from the alkynyl, R 2 is selected from the -L-heterogenetic rings, and the heterogenetic rings of the -L-heterogenetic rings are one or more R 6 It is replaced as needed, L is independently selected from C1-C4 alkylenes, and the C1-C4 alkylenes are optionally substituted with one or more substituents selected from hydroxy, C1-C4 hydroxyalkyl, and C1-C4 alkyl, and optionally two substituents on the same carbon atom of L combine to form a C3-C6 carbon ring. R 20 These are hydrogen, respectively; and halogens, -OH, -CN, -NO2, -NH2, -N(C) 1~6 Alkyl)2, C 1~10 Alkyl, -C 1~10 Haloalkyl, -OC 1~10 Alkyl, oxo, =NH, C 3~12 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. 1~6 Alkyl, C 3~6 (Independently selected from carbon rings and 3- to 6-membered heterocycles).

[0396] Formula (II * In some embodiments relating to compounds or salts of ), 1These are selected from 7-10 member spiroheterocycles and 7-10 member fused heterocycles, which are substituted as needed. In some cases, R 1 The heterocycle has at least one nitrogen atom. In some cases, R 1 At least one nitrogen in the heterocycle of is given by equation (II * It is coupled to R. In some cases, 1 This is selected from 10-membered spiroheterocycles and 10-membered fused heterocycles, which are substituted as needed. In some cases, R 1 One or more substituents as needed may be halogen, -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 Alkynnyls are independently selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens and C 1~6 It is optionally substituted with one or more substituents selected from alkyl groups. In some cases, R 1 teeth, [ka] Selected from, this is halogen, -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 Alkynyl, substituted with one or more substituents independently selected from a 5-12 membered heterocycle, wherein the 5-12 membered heterocycle is a halogen and C 1~6 It is optionally substituted with one or more substituents selected from alkyl groups. In some cases, R 1 teeth, [ka] Selected from. In some cases, R 1 is selected [ka] [ka] In some cases, R 1 teeth, [ka] In some cases, M is selected from O. In some cases, M is NCH2CH3. In some cases, M is NMe. In some cases, R 2The complex algebra of is a saturated complex algebra. In some cases, R 2 R 6 Each of the following is independently selected from halogen, =CH2, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and C1-C3 aminoalkyl. In some cases, R 2 L is C1-C4 alkylene and [ka] Selected from. In some cases, R 2 teeth, [ka] Selected from. In some cases, B is replaced by C9~C as needed. 10 Selected from condensed carbocyclic rings. In some cases, B is [ka] They are selected from these, and each is substituted as needed. In some cases, B is halogen, oxo, -NH2, C1~C3 alkyl, -B(OH)2, -OH, -O-C1~C3 haloalkyl, -C(O)NH2, -NH2, =O, -CN, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 2~6 It is optionally substituted with one or more substituents independently selected from the alkynyl. In some cases, B is optionally substituted with one or more substituents independently selected from the halogen. In some cases, B is [ka] In some cases, B is [ka] In some cases, B is unsubstituted. In other cases, B is substituted.

[0397] Formula (II* In some embodiments relating to compounds or salts of ), 1 These are selected from 7-10 member spiroheterocycles and 7-10 member fused heterocycles, which are substituted as needed. In some cases, R 1 This is selected from 10-membered spiroheterocycles and 10-membered fused heterocycles, which are substituted as needed. In some cases, R 1 It is selected from 10-membered spiroheterocycles, which are substituted as needed. In some cases, R 1 It is selected from 10-membered condensed heterorings, which are substituted as needed. In some cases, R 1 The heterocycle of has at least three heteroatoms. In some cases, R 1 One or more substituents as needed may be halogen, -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 Alkynnyls are independently selected from 5- to 12-membered heterocycles, and these 5- to 12-membered heterocycles include halogens and C 1~6 It is optionally substituted with one or more substituents selected from alkyl groups. In some cases, R 1teeth, [ka] Selected from, this is halogen, -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 Alkynyl, substituted with one or more substituents independently selected from a 5-12 membered heterocycle, wherein the 5-12 membered heterocycle consists of halogens and C 1~6 It is optionally substituted with one or more substituents selected from alkyl groups. In some cases, R 1 teeth, [ka] [ka] [ka] Selected from. In some cases, R 1 teeth, [ka] Selected from. In some cases, R1 teeth, [ka] In some cases, M is selected from O. In some cases, M is NMe. In some cases, R 2 The complex algebra of is a saturated complex algebra. In some cases, R 2 R 6 Each of the following is independently selected from halogen, =CH2, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and C1-C3 aminoalkyl. In some cases, R 2 L is C1-C4 alkylene and [ka] Selected from. In some cases, R 2 teeth, [ka] Selected from. In some cases, B is replaced by C9~C as needed. 10 Selected from condensed carbocyclic rings. In some cases, B is [ka] They are selected from these, and each is substituted as needed. In some cases, B is halogen, oxo, -NH2, C1~C3 alkyl, -B(OH)2, -OH, -O-C1~C3 haloalkyl, -C(O)NH2, -NH2, =O, -CN, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl and C 2~6 It is optionally substituted with one or more substituents independently selected from the alkynyl. In some cases, B is optionally substituted with one or more substituents independently selected from the halogen. In some cases, B is [ka] In some cases, B is [ka] In some cases, B is unsubstituted. In other cases, B is substituted.

[0398] Formula (I), Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III), R 1 The heterocycle or carbon ring of C 1~6 Not substituted with cyanoalkyl. In some embodiments relating to compounds or salts of formula (I), R 1 The heterocycle or carbon ring of C 1~6 Not substituted with a cyanoalkyl group. In some embodiments relating to the compound or salt of formula (II), R 1 The heterocycle or carbon ring of C 1~6 Not substituted with cyanoalkyl. In some embodiments relating to compounds or salts of formula (III), R 1 The heterocycle or carbon ring of C 1~6 It is not substituted with cyanoalkyl.

[0399] Formula (I), Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III), R 20 These are hydrogen and C, respectively. 1~6 It is selected independently of alkyl.

[0400] Formula (I), Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III), C 1~6 It is not substituted with cyanoalkyl.

[0401] In some embodiments relating to compounds or salts of formula (I), formula (II), or formula (III), R 1 It is not piperazine. In some cases, R 1 It is not a substituted piperazine.

[0402] In some embodiments relating to the compound of formula (I), the compound is not a Michael acceptor.

[0403] In some embodiments relating to the compound of formula (I), the compound or salt does not contain an electrophilic substituent.

[0404] Formula (I), Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III) or formula (III), the electrophilic moiety is absent.

[0405] Formula (I), Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III) or formula (III), the covalent modifier is not included.

[0406] Formula (I), Formula (II), Formula (II * In some embodiments relating to compounds or salts of formula (III), R 1 One or more of the optional substituents are not electrophiles.

[0407] In some embodiments, the compounds of formula (I), (II), (III), or subformula used in this method include trifluoroacetates of the above compounds.

[0408] In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of approximately 5 mg to approximately 500 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of approximately 10 mg to approximately 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of approximately 10 mg to approximately 125 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of approximately 10 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of approximately 25 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of approximately 50 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of approximately 5 mg to approximately 75 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in amounts 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 or salt of formula (II) is administered to the subject in amounts of 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 in amounts of about 15 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 30 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 45 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 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 or older and 18 years of age or younger. 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 or salt of formula (II) is administered once daily. In some embodiments, the compound or salt of formula (II) is administered twice daily. In some embodiments, the compound or salt of formula (II) is administered three times daily. In some embodiments, the compound or salt of formula (II) is administered once weekly. In some embodiments, the compound or salt of formula (II) is administered every other day. In some embodiments, the compound or salt of formula (II) is administered every three days.

[0410] 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 in 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 in 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 in doses of 15 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of 30 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject in doses of 45 mg. In some embodiments, the compound or salt of formula (II) 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 years or older and 18 years or younger. In some embodiments, the subject is an adult. In some embodiments, the subject is 18 years of age or older.

[0411] In some embodiments, the compound or salt of formula (II) is administered to the subject daily at a dose of approximately 10 mg to approximately 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at a dose of approximately 10 mg to approximately 125 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at a dose of approximately 10 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at a dose of approximately 25 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at a dose of approximately 50 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at a dose of approximately 5 mg to approximately 75 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at approximately 10 mg, approximately 15 mg, approximately 20 mg, approximately 25 mg, approximately 30 mg, approximately 35 mg, approximately 40 mg, approximately 45 mg, approximately 50 mg, approximately 55 mg, approximately 60 mg, approximately 65 mg, approximately 70 mg, approximately 75 mg, approximately 80 mg, approximately 85 mg, approximately 90 mg, approximately 100 mg, approximately 105 mg, approximately 110 mg, approximately 115 mg, approximately 120 mg, approximately 125 mg, approximately 130 mg, approximately 135 mg, approximately 140 mg, approximately 145 mg, or approximately 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at approximately 15 mg, approximately 30 mg, approximately 45 mg, or approximately 60 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject daily at approximately 15 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 30 mg daily. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 45 mg daily. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 60 mg daily. In some embodiments, the compound or salt of formula (II) 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 years of age or older and 18 years of age or younger. In some embodiments, the subject is an adult. In some embodiments, the subject is 18 years of age or older.

[0412] In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at a dose of approximately 10 mg to approximately 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at a dose of approximately 10 mg to approximately 125 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at a dose of approximately 10 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at a dose of approximately 25 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at a dose of approximately 50 mg to approximately 100 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at a dose of approximately 5 mg to approximately 75 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at doses of approximately 10 mg, approximately 15 mg, approximately 20 mg, approximately 25 mg, approximately 30 mg, approximately 35 mg, approximately 40 mg, approximately 45 mg, approximately 50 mg, approximately 55 mg, approximately 60 mg, approximately 65 mg, approximately 70 mg, approximately 75 mg, approximately 80 mg, approximately 85 mg, approximately 90 mg, approximately 100 mg, approximately 105 mg, approximately 110 mg, approximately 115 mg, approximately 120 mg, approximately 125 mg, approximately 130 mg, approximately 135 mg, approximately 140 mg, approximately 145 mg, or approximately 150 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at doses of approximately 15 mg, approximately 30 mg, approximately 45 mg, or approximately 60 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject twice daily at doses of approximately 15 mg. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 30 mg twice daily. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 45 mg twice daily. In some embodiments, the compound or salt of formula (II) is administered to the subject at approximately 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 years of age or older and 18 years of age or younger. In some embodiments, the subject is an adult. In some embodiments, the subject is 18 years of age or older.

[0413] In some embodiments, the compound of formula (II) is administered as a capsule for a certain period of time. In some cases, the tablet or capsule formulation of the compound of formula (II) is available in doses of approximately 10 mg to approximately 100 mg (e.g., approximately 10 mg to approximately 95 mg, approximately 10 mg to approximately 90 mg, approximately 10 mg to approximately 85 mg, approximately 10 mg to approximately 80 mg, approximately 10 mg to approximately 75 mg, approximately 10 mg to approximately 70 mg, approximately 10 mg to approximately 65 mg, approximately 10 mg to approximately 60 mg, approximately 10 mg to approximately 55 mg, approximately 10 mg to approximately 50 mg, approximately 10 mg to approximately 45 mg, approximately 10 mg to approximately 40 mg, approximately 10 mg to approximately 35 mg, approximately 10 mg to approximately 30 mg, approximately 10 mg to approximately 25 mg, approximately 10 mg to approximately 20 mg). g, approx. 10 mg to approx. 15 mg, approx. 15 mg to approx. 100 mg, approx. 15 mg to approx. 95 mg, approx. 15 mg to approx. 90 mg, approx. 15 mg to approx. 85 mg, approx. 0mg, about 15mg to about 55mg, about 15mg to about 50mg, about 15mg to about 45mg, about 15mg to about 40mg, about 15mg to about 35mg, about 15mg to about 30mg, about 15mg to about 25mg, about 15mg to about 20mg, about 20mg to about 100mg, about 20mg Approx. 95 mg, approx. 20 mg ~ approx. 90 mg, approx. 20 mg ~ approx. 85 mg, approx. 20 mg ~ approx. 80 mg, approx. 20 mg ~ approx. 75 mg, approx. 20 mg ~ approx. 70 mg, approx. ~45mg, 20mg~40mg, 20mg~35mg, 20mg~30mg, 20mg~25mg, 25mg~100mg, 25mg~95mg, 25mg~90mg, 25mg~85mg, 25mg~80mg, 25 mg ~ about 75mg, about 25mg - about 70mg, about 25mg - about 65mg, about 25mg - about 60mg, about 25mg - about 55mg, about 25mg - about 50mg, about 25mg - about 45mg, about 25mg - about 40mg, about 25mg - about 35mg, about 25mg - about 30mg, about 3 0mg to about 100mg, about 30mg to about 95mg, about 30mg to about 90mg, about 30mg to about 85mg, about 30mg to about 80mg, about 30mg to about 75mg, about 30mg to about 70mg, about 30mg to about 65mg, about 30mg to about 60mg, about 30mg to about 55mg,Approximately 30mg~50mg, approximately 30mg~45mg, approximately 30mg~40mg, approximately 30mg~35mg, approximately 35mg~100mg, approximately 35mg~95mg, approximately 35mg~90mg, approximately 35mg~85mg, approximately 35mg~80mg, approximately 35mg~75mg, approximately 35mg~70mg, approximately 35mg~65mg, approximately 35mg~60mg, approximately 35mg~55mg, approximately 35mg~50mg, approximately 35mg~45mg, approximately 35mg~40mg, approximately 40mg~100mg, approximately 40mg~95mg, approximately 40mg~90mg, approximately 40mg~ Approximately 85mg, approximately 40mg~80mg, approximately 40mg~75mg, approximately 40mg~70mg, approximately 40mg~65mg, approximately 40mg~60mg, approximately 40mg~55mg, approximately 40mg~50mg, approximately 40mg~45mg, approximately 45mg~100mg, approximately 45mg~95mg, approximately 45mg~90mg, approximately 45mg~85mg, approximately 45mg~80mg, approximately 45mg~75mg, approximately 45mg~70mg, approximately 45mg~65mg, approximately 45mg~60mg, approximately 45mg~55mg, approximately 45mg~50mg, approximately 50mg~100mg Approximately 50mg~95mg, approximately 50mg~90mg, approximately 50mg~85mg, approximately 50mg~80mg, approximately 50mg~75mg, approximately 50mg~70mg, approximately 50mg~65mg, approximately 50mg~60mg, approximately 50mg~55mg, approximately 55mg~100mg, approximately 55mg~95mg, approximately 55mg~90mg, approximately 55mg~85mg, approximately 55mg~80mg, approximately 55mg~75mg, approximately 55mg~70mg, approximately 55mg~65mg, approximately 55mg~60mg, approximately 60mg~100mg, approximately 60mg~95mg, approximately 60mg~ Approximately 90mg, approximately 60mg~approximately 85mg, approximately 60mg~approximately 80mg, approximately 60mg~approximately 75mg, approximately 60mg~approximately 70mg, approximately 60mg~approximately 65mg, approximately 65mg~approximately 100mg, approximately 65mg~approximately 95mg, approximately 65mg~approximately 90mg, approximately 65mg~approximately 85mg, approximately 65mg~approximately 80mg, approximately 65mg~approximately 75mg, approximately 65mg~approximately 70mg, approximately 70mg~approximately 100mg, approximately 75mg~approximately 95mg, approximately 70mg~approximately 90mg, approximately 70mg~approximately 85mg, approximately 70mg~approximately 75mg, approximately 75mg~approximately 100mg, approximately 75mg~approximately 95mgApproximately 75mg to approximately 90mg, approximately 75mg to approximately 85mg, approximately 75mg to approximately 80mg, approximately 80mg to approximately 100mg, approximately 80mg to approximately 95mg, approximately 80mg to approximately 90mg, approximatel...

Claims

1. A method for treating cancer in a subject requiring it, wherein the subject is given an RTK-MAPK pathway inhibitor and a compound of formula (II): 【Chemical 460】 A method comprising the step of administering a therapeutically effective amount of a combination of the salt or a pharmaceutically acceptable salt thereof [in the formula, M is O, S, SO, SO ２ and NR ３ Selected from, R １ is selected from C ３ to C １２ carbon rings and 5- to 15-membered heterocyclic rings, each of which is halogen, -B(OR ２０ ), -OR ２ , -SR ２０ , -S(O) ２０ (R ２ ), -S(O) ２０ N(R ２ ), -S(O)N(R ２０ ), -S(O)R ２ (=NR ２０ ), -NR ２ S(O) ２０ R ２０ , -C(O)N(R ２０ ), -C(=NR ２ )(R ２０ ), -C(O)NR ２０ OR ２ , -N(R ２０ )(R ２０ ), -N(R ２ )(R ２０ ), -N(R ２０ )(R ２０ ), -N(R ２０ )(R ２０ ), -N(R ２０ ), -C(O)R ２ , -C(O)OR ２０ , -OC(O)R ２０ , -OC(O)N(R ２０ ), -NO ２ , =O, =N(R<s ２０ ), =NO(R ２０ ), -CN, -NHCN, C ２０ alkyl-N(R ２０ ), C ２ aminoalkyl, C ２ alkoxy, C ２０ hydroxyalkyl, C ２０ cyanoalkyl, C １～６ haloalkyl, C ２０ alkyl-SO [[ID=)00]] ２ １～６ <0000))50> １～６ １～６ １～６ １～６ ２ ２０ １～６ ２～６ ２～６ ３ [[ID=10)) １２ alkyl-SO ３ R ２０ , C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３ ~C １２ The carbon ring is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle. ３ ~C １２ Carbon rings and 5-12 membered heterocycles have one or more R １＊ Each is replaced independently as needed. R １＊ each represents halogen, -B(OR ２０ ), -OR ２ , -SR ２０ , -S(O) ２０ (R ２ ), -S(O) ２０ N(R ２ ) ２０ , -S(O)N(R ２ ) ２０ , -S(O)R ２ (=NR ２０ ), -NR ２０ S(O) ２０ R<00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ Y is bond, O, S and NR ５ Selected from, R ２ is -L-N(R ２１ ) ２ , -L-OR ２１ , complex algebras, C １ ~C ６ Alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH ２ , -LC(O)N(R ２１ ) ２ , -L-C １ ~C ６ Haloalkyl, -L-NR ２１ C(O)-aryl, -L-COOH, -L-NR ２１ S(O) ２ (R ２１ ), -L-S(O) ２ N(R) ２１ ) ２ , -L-N(R ２１ )C(O)(OR ２１ ), -L-OC(O)N(R ２１ ) ２ and -LC(=O)OC １ ~C ６ Selected from alkyl groups, the heterocycle, -L-NR ２１ The aryl portion of C(O)-aryl, the heterocyclic portion of -L-heterocyclic, and the cycloalkyl portion of -L-cycloalkyl are one or more R ６ Each is substituted as necessary, and the aryl portion of the -L-aryl and the heteroaryl portion of the -L-heteroaryl are one or more R ７ Each is substituted as necessary, and if Y is a bond, O, or S, then R ２ It is further selected from hydrogen, L stands for hydroxy, C １ ~C ４ Hydroxyalkyl, C １ ~C ４ Alkyl, C ３ ~C ６ C is optionally substituted with one or more substituents selected from a carbon ring or a 3- to 8-membered heterocycle. １ ~C ４ Selected independently from alkylene, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ ,=O,=S,-CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L are together C ３ ~C ６ Forming a carbon ring or a 3- to 8-membered heterocycle, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ ,=O,=S,-CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. R ３ is hydrogen, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, 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 Selected from carbon rings and 3- to 12-membered heterocycles, C ３～１２ Carbon rings and 3- to 12-membered heterocycles include halogens, -OH, -CN, and -NO. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. n is selected from 0 to 2. R ４ These are C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkynyl, oxo, hydroxyl, halogen, C ３～１２ A carbon ring and a 3- to 12-membered heterocycle are independently selected, and the C １ ~C ６ Alkyl, C ３～１２ Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR ５ and -N(R ５ ) ２ Each of these is optionally substituted by one or more substituents selected independently of the original, R ５ These are hydrogen or C, respectively. １ ~C ６ Selected independently of alkyl, R ６ These are halogen, hydroxyl, and C, respectively. １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, oxo, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, =CH ２ , = NO-C １ ~C ３ Alkyl, C １ ~C ３ Aminoalkyl, -N(R) ５ ) S(O) ２ (R ５ ), -Q-phenyl, -Q-phenylSO ２ F,-NHC(O)phenyl,-NHC(O)phenylSO ２ F, C １ ~C ３ Alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxy CH ２ -, -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) C １ ~C ３ Alkyl-, (C １ ~C ３ Alkyl) C (= O), oxo, (C １ ~C ３ Haloalkyl)C(=O)-, -SO ２ F, (C １ ~C ３ Alkoxy) C １ ~C ３ Alkoxy, -CH ２ OC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)OC １ ~C ６ Alkyl, -CH ２ NHC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)C １ ~C ６ Alkyl, -CH ２ (Pyrazolyl), -CH ２ NHSO ２ C １ ~C ６ Alkyl, -CH ２ OC(O) heteroalgebra, -OC(O)N(R ５ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl), -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl (C １ ~C ３ Alkyl)N(CH ３ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl, -OC(O) heterocycle, -O-C １ ~C ３ Alkyl and -CH ２ Independently selected from heterocycles, -NHC(O)phenyl and -OC(O)NH(C) １ ~C ３ (Alkyl) (C １ ~C ３ The phenyl in alkyl(phenyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, respectively, -O-C １ ~C ３ The alkyl group of the alkyl group is optionally substituted with substituents selected from heterocyclic, oxo, and hydroxyl groups, -CH ２ The heterocyclic ring is substituted with an oxo as needed. Q is selected independently from the combination, S, and O, R ７ These are halogen, hydroxyl, HC(=O)-, and C, respectively. １ ~C ４ Alkyl, C １ ~C ４ Alkoxy, C １ ~C ４ Haloalkyl, C １ ~C ４ Hydroxyalkyl or -N(R) ５ ) ２ Selected independently from, R ２０ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, =NH, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, R ２１ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, B is selected from heterocycles and carbocycles, and the heterocycles and carbocycles are halogen, cyano, hydroxy, =O, -NO ２ , C ｌ ~C ４ Alkyl, C １～６ Aminoalkyl, -S-C ｌ ~C ３ Alkyl, C ２ ~C ４ Alkenil, C ２ ~C ４ Alkinyl, C ２ ~C ４ Hydroxyalkynyl, C １ ~C ３ Cyanoalkyl, triazolyl, C ｌ ~C ３ Haloalkyl, -O-C ｌ ~C ３ Haloalkyl, -S-C ｌ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, C ｌ ~C ３ Hydroxyalkyl, -CH ２ C(=O)N(R) ５ ) ２ , -C ３ ~C ４ Alkinyl (NR) ５ ) ２ , -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) Halo C ｌ ~C ３ Alkyl-, C １～６ Alkyl-N(R) ２０ ) ２ , C ３ ~C １２ Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle, C ３ ~C １２ Carbon rings and 5- to 12-membered heterocycles include halogens, -OH, and -NO. ２ , -NH ２ ,=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 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups.

2. The method according to 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 and the compound or salt of formula (II) results in, in the subject, an increase in overall survival, an increase in progression-free survival, an increase in tumor growth regression, an increase in tumor growth inhibition, and an increase in the period of disease stabilization, compared 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) of the combination is between approximately 0.01 and 100 mg / kg per day.

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

6. The method according to any one of claims 1 to 5, wherein the therapeutically effective dose of the RTK-MAPK pathway inhibitor in the combination is between approximately 0.01 and 100 mg / kg per day.

7. The method according to any one of claims 1 to 6, wherein the therapeutically effective dose of the RTK-MAPK pathway inhibitor in the combination is between approximately 0.1 and 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 days.

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

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 the group consisting of afatinib, dacomitinib, poziotinib, erlotinib, gefitinib, sapitinib, 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-methylpiperidine-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]decane-8-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazine-2-yl)methanol), RMC-4360, or TNO155 (Novartis).

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

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

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

22. The method according to 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 according to 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 aforementioned cancers are as follows: Heart: Sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyomas, fibromas, lipomas, and teratomas; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, cartilaginous hamartoma, mesothelioma; Gastrointestinal tract: Esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, chorioadenoma, hamartoma, leiomyoma); Urogenital tract: kidney (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testes (seminocarcinoma, teratoma, fetal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); Liver: Hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Bile duct: gallbladder cancer, papillary cancer, cholangiocellular carcinoma; Bone: Osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondroma (chondrodystostoma), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; Nervous system: Skull (osteoma, hemangioma, granuloma, xanthomas, degenerative osteitis), meninges (meningioma, meningiosarcoma, glioma), brain (astrocytoma, medulloblastoma, glioma, ependymoma, intracranial germ cell tumor (pineal glandoma), glioblastoma pleomorphic, oligodendroglioma, Schwann cell tumor, retinoblastoma, congenital tumor), spinal neurofibroma, meningioma, glioma, sarcoma); Gynecology: Uterus (endometrial cancer), cervix (cervical cancer, preneoplastic cervical malformation), ovaries (ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassifiable cancer), granulosacytic cell tumor, Sertley-Leydig cell tumor, undifferentiated germ cell tumor, malignant teratoma), vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, staphyloid sarcoma (embryonic rhabdomyosarcoma), fallopian tubes (carcinoma); Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes), Hodgkin's disease, non-Hodgkin lymphoma (malignant lymphoma); Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus moles, lipomas, hemangiomas, dermatofibromas, keloids, psoriasis; and Adrenal gland: Neuroblastoma The method according to any one of claims 1 to 25, selected from the following.

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 KRas mutant-associated cancers.

35. The method according to any one of claims 1 to 26, wherein the cancer is selected from KRas wild-type associated 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-related 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 associated 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. M is NR ３ And Y is O, R １ If the piperazine is a piperazine, then the piperazine is one tera R ９ It is replaced by R ９ These are halogen and -B (OR ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -NR ２０ S(O) ２ R 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 , -NO ２ , = O, = NO (R ２０ ), -CN, -NHCN, C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, and C １～６ The method according to claim 1, independently selected from haloalkyl groups.

42. The aforementioned compound or salt 【Chemistry 461】 【Chemistry 462】 【Chemical 463】 【Chemical 464】 【Chemical 465】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

43. The aforementioned compound, 【Chemical 466】 【Chemistry 467】 【Chemical Formula 468】 【Chemistry 469】 【Chemical 470】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

44. The aforementioned compound, 【Chemistry 471】 【Chemistry 472】 【Chemistry 473】 【Chemistry 474】 The method according to any one of claims 1 to 42, or selected from any one of those salts.

45. The aforementioned compound, 【Chemistry 475】 【Chemistry 476】 【Chemistry 477】 The method according to any one of claims 1 to 43, or selected from any one of those salts.

46. The aforementioned compound, 【Chemistry 478】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

47. The aforementioned compound, 【Chemistry 479】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

48. The aforementioned compound, 【Chemical 480】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

49. The aforementioned compound, 【Chemistry 481】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

50. The aforementioned compound, 【Chemistry 482】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

51. The aforementioned compound, 【Chemistry 483】 The method according to any one of claims 1 to 41, or selected from any one of those salts.

52. The aforementioned compound, 【Chemical 484】 The method according to any one of claims 1 to 41, or selected from any one of those 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 according to claim 52, wherein M is O.

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

56. The method according to claim 54, wherein M is selected from NH and NMee.

57. The method according to claim 55, wherein M is NMe.

58. B is a 5- to 15-membered heterocycle which is substituted as needed, and C is substituted as needed. ３ ~C １５ The method according to any one of claims 1 to 56, selected from a carbocyclic ring.

59. B is an 8- to 15-member fused heterocycle which is substituted as needed, and C which is substituted as needed. ８ ~C １５ The method according to claim 57, selected from condensed carbocyclic rings.

60. The method according to claim 59, wherein B is an 8- to 15-member fused heteroring which is substituted as needed.

61. B is an unsaturated C which is substituted as needed. ８ ~C １５ The method according to claim 60, wherein the condensed carbon ring is used.

62. Regarding B, the 8-15 member fused heterocycles that are substituted as necessary and C that are substituted as necessary ８ ~C １５ The method according to any one of claims 59 to 61, wherein each condensed carbon ring is independently bicyclic or tricyclic.

63. The method according to claim 62, wherein, with respect to B, the heterocycle and the carbon ring are each independently bicyclic.

64. The method according to claim 62, wherein, with respect to B, the heterocycle and the carbon ring are each independently tricyclic.

65. B, 【Chemistry 485】 The method according to any one of claims 59 to 64, wherein selected from, each of which is optionally substituted with one or more substituents.

66. B, 【Chemical 486】 The method according to claim 65, wherein selected from, each of which is optionally substituted with one or more substituents.

67. B, 【Chemistry 487】 The method according to claim 66, wherein selected from, each of which is optionally substituted with one or more substituents.

68. With respect to B, the one or more substituents as needed are oxo, -NH ２ , halogen, C １ ~C ３ The method according to any one of claims 58 to 67, independently selected from alkyl.

69. B, 【Chemical 488】 The method according to any one of claims 1 to 68, selected from the following.

70. Regarding B, the one or more optional substituents of the heterocycle and carbon ring are halogens, C １ ~C ３ Alkyl, -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 The method according to any one of claims 58 to 67, wherein each occurrence is independently selected from alkynyl.

71. With respect to B, the one or more optional substituents of the heterocycle and carbon ring are halogen, oxo, -NH ２ , C １ ~C ３ Alkyl, -B(OH) ２ -OH, -O-C １ ~C ３ Haloalkyl, -C(O)NH ２ , -NH ２ , = O, -CN, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C ２～６ The method according to any one of claims 58 to 67, wherein each occurrence is independently selected from alkynyl.

72. B, 【Chemistry 489】 【Chemistry 490】 The method according to any one of claims 58 to 71, selected from the above.

73. R ４ Each of these is C １～６ Alkyl, C ２～６ Alkenil, C ２～６ The method according to any one of claims 1 to 72, independently selected from alkynyl, oxo, hydroxyl, and halogen.

74. R ４ Each of these is C １～６ The method according to claim 73, independently selected from 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. R １ The method according to any one of claims 1 to 76, wherein the 5- to 12-membered heteroring is selected as necessary.

78. R １ However, a heterocycle with 5 to 12 members is selected, and the heterocycle with 5 to 12 members is a halogen, -OH, -N(R) ２０ ) ２ , -NO ２ , = O, -CN, C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C １～６ The method according to claim 77, wherein the substituents are optionally substituted with one or more substituents independently selected from the haloalkyl group.

79. R １ However, a heterocycle with 5 to 12 members is selected, and the heterocycle with 5 to 12 members is a halogen, -OH, -N(R) ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C １～６ The method according to claim 78, wherein the substituents are optionally substituted with one or more substituents independently selected from the haloalkyl group.

80. R ２０ However, hydrogen and C １～３ The method according to claim 78 or 79, selected from alkyl groups.

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

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

83. R １ The method according to any one of claims 77 to 79, wherein the 5 to 12-membered heteroring is a bridging heteroring.

84. R １ but, 【Chemistry 491】 The method according to any one of claims 77 to 83, wherein selected from and each of which is replaced as necessary.

85. The one or more substituents as needed may be halogen, -OH, -N(R) ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, =O, -CN,C １～６ Hydroxyalkyl and C １～６ The method according to claim 84, wherein each is independently selected from haloalkyl groups.

86. R １ but, 【Chemistry 492】 These are selected from halogen, -OH, and -N(R) respectively. ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, =O, -CN,C １～６ Hydroxyalkyl and C １～６ The method according to claim 84, wherein the substituent is optionally substituted with one or more substituents independently selected from the haloalkyl group.

87. R １ but, 【Chemistry 493】 The method according to claim 86, selected from the following.

88. R １ The method according to any one of claims 77 to 83, wherein the 6- to 8-membered heteroring is selected as necessary.

89. R １ The method according to claim 88, wherein the member is selected from a 7-membered saturated heterocycle, an 8-membered bridging heterocycle, and a 6- to 7-membered unsaturated heterocycle, and each of these is substituted as necessary.

90. R １ but, 【Chem.494】 The method according to claim 89, wherein selected from and each of which is substituted as necessary.

91. The one or more substituents as needed are -OH, -CN, oxo, C １～６ The method according to claim 90, independently selected from cyanoalkyl.

92. R １ but, 【Chemical 495】 The method according to claim 90 or 91, selected from the above.

93. R １ The method according to any one of claims 1 to 76, wherein the 6- to 7-membered heteroring is selected as necessary.

94. The method according to claim 93, wherein the 6- to 7-membered heterocycle contains only one nitrogen atom, and the 6- to 7-membered heterocycle is substituted as necessary.

95. R １ The method according to claim 94, wherein the 6- to 7-membered heterocycle is bonded to formula (II) via the single nitrogen atom.

96. R １ The method according to any one of claims 93 to 95, wherein the six-membered unsaturated hetero ring is selected as necessary.

97. R １ The method according to any one of claims 93 to 95, wherein the seven-membered unsaturated hetero ring is selected as necessary.

98. R １ but, 【Chemistry 496】 The method according to any one of claims 93 to 97, wherein selected from and any of these are substituted as necessary.

99. R １ but, 【Chemistry 497】 The method according to any one of claims 93 to 98, wherein selected from and any of these are substituted as necessary.

100. R １ The one or more substituents as needed are 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 The method according to any one of claims 93 to 99, each independently selected from alkynyl.

101. Each is a halogen, -OH, and -NH. ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Haloalkyl and CC １～６ The method according to any one of claims 93 to 100, wherein the alkyl group is optionally substituted with one or more substituents independently selected from the alkyl group.

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

103. R １ but, 【Chem.498】 The method according to any one of claims 93 to 102, selected from the following.

104. R １ but, 【Chem.499】 Selected from, each is halogen, -OH, -NH ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Haloalkyl and CC １～６ The method according to any one of claims 93 to 101, wherein the alkyl group is optionally substituted with one or more substituents independently selected from the alkyl group.

105. R １ but, [500] Selected from, each is halogen, -OH, -NH ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Haloalkyl and CC １～６ The method according to claim 104, wherein the alkyl group is optionally substituted with one or more substituents independently selected from the alkyl group.

106. R １ but, 【Chemical 501】 Selected from, each is halogen and C １～６ The method according to claim 105, wherein the substituent is optionally substituted with one or more substituents independently selected from the haloalkyl group.

107. R １ but, 【Chemical 502】 The method according to claim 106, selected from the following.

108. R １ but, 【Chemical 503】 Selected from, this is halogen, -OH, -NH ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Haloalkyl and CC １～６ The method according to any one of claims 93 to 101, wherein the alkyl group is optionally substituted with one or more substituents independently selected from the alkyl group.

109. R １ but, 【Chemical 504】 The method according to claim 108, wherein a halogen is selected from which a halogen is optionally substituted by one or more substituents selected independently of the halogen.

110. R １ but, 【Chemical 505】 The method according to claim 109, selected from the following.

111. R １ The method according to claim 93, wherein the ring is selected from a 6- to 7-membered heteroring.

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

113. The method according to claim 112, wherein one or more additional heteroatoms as needed are selected from sulfur.

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

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

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

117. R １ but, 【Chemical 506】 The method according to any one of claims 111 to 116, wherein selected from and each of which is substituted as necessary.

118. R １ The one or more substituents as needed are halogen, -OH, -CN, C １～６ Cyanoalkyl, -NHCN, C １～６ Alkyl, oxo, and C ２～６ The method according to claim 117, wherein each is independently selected from alkynyl.

119. R １ The method according to claim 113, wherein the 6- to 10-membered heteroring is selected as necessary.

120. R １ but, 【Chemical 507】 The method according to claim 119, wherein selected from and each of which is substituted as necessary.

121. The one or more substituents as needed are halogen, =O, -OH, -C(O)N(R) ２０ ) ２ , C ２～６ Alkinyl, -NHCN, -CN, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Cyanoalkyl and C １～６ The method according to claim 120, independently selected from alkyl.

122. R １ but, 【Chemical 508】 The method according to claim 121, selected from the following.

123. R １ The method according to claim 77, wherein the member is selected from a spiroheterocycle with 7 to 11 members.

124. R １ The method according to claim 123, wherein the material is selected from a 10-membered spiroheterocyclic ring.

125. The method according to claim 123 or 124, wherein the spiroheterocyclic ring has at least three nitrogen atoms.

126. R １ but, 【Chemical 509】 The method according to claim 125, wherein selected from and each of which is substituted as necessary.

127. R １ but, 【Chemical 510】 These are selected from halogen, -OH, and -N(R) respectively. ２０ ) ２ , -NO 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 １～６ Alkyl, C ２～６ Alkenyl and C ２～６ The method according to claim 126, wherein the alkynyl is optionally substituted with one or more substituents independently selected.

128. R １ but, 【Chemical 511】 Selected from, preferably, 【Chemical 512】 The method according to claim 127.

129. R １ The method according to claim 77, wherein the ring is selected from 9 to 11-membered unsaturated hetero rings, which are substituted as needed.

130. R １ The method according to claim 129, wherein the selected ring is a 10-membered unsaturated hetero ring that is substituted as needed.

131. R １ but, 【Chemical 513】 The method according to claim 130, wherein this is replaced as necessary.

132. R １ but, 【Chemical 514】 And this is halogen, -OH, -C(O)N(R) ２０ ) ２ , -C(O)OR ２０ , -C(O)NHOR ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -NO 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 The method according to claim 131, wherein the substituents are optionally substituted with one or more substituents selected from alkynyls.

133. R １ but, ​ These are selected from halogen, -OH, and -N(R) respectively. 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 The compound or salt according to claim 132, which is optionally substituted with one or more substituents selected from alkynyls.

134. R １ The method according to claim 77, wherein the ring is selected from 9 to 11-membered unsaturated hetero rings, which are substituted as needed.

135. R １ The method according to claim 134, wherein the selected ring is a 10-membered unsaturated hetero ring that is substituted as needed.

136. R １ but, 【Chemical 516】 The method according to claim 135, wherein this is replaced as necessary.

137. R １ The one or more of the above-mentioned optional substituents are halogen, -OH, -S(O) ２ (R ２０ ), -S(O) ２ N(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 , -NO ２ , = 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 Alkynyl, independently selected from a 5- to 12-membered heterocycle, wherein the 5- to 12-membered heterocycle is a halogen, -OR ２０ and C １～６ The method according to claim 136, wherein the substituents are optionally substituted with one or more substituents selected from alkyl groups.

138. R １ but, 【Chemical 517】 The method according to any one of claims 134 to 137, wherein selected from and each of which is replaced as necessary.

139. R １ but, 【Chemical 518】 【Chemical 519】 The method according to any one of claims 134 to 138, selected from the following.

140. R １ The one or more substituents as needed are halogen, -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 The method according to any one of claims 134 to 137, independently selected from alkynyl.

141. R １ The one or more optional substituents of the above are halogens and -C(O)N(R ２０ ) ２ The method according to claim 140, which is independently selected from the above.

142. R １ but, 【Chemical 520】 The method according to claim 141, selected from the following.

143. R １ The one or more substituents as needed are 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 independently selected from 5- to 10-membered hetero rings, wherein the 5- to 10-membered hetero rings are one or more R １＊ It is substituted independently as needed by R １＊ These are halogen, -OR respectively ２０ and C １～６ The method according to any one of claims 134 to 137, independently selected from alkyl.

144. R １ The one or more substituents as needed are chlorine, -NH ２ ,-CN,C １ Alkyl, C ２ Alkenil, 【Chem.521】 The method according to claim 143, selected from the following.

145. R １ but, 【Chemical 522】 【Chemical 523】 【Chemical 524】 The method according to claim 144, selected from the following.

146. R １ The method according to any one of claims 1 to 76, wherein the hetero ring is a 12- to 15-member ring that is substituted as necessary.

147. R １ The method according to claim 146, wherein the 12-membered hetero ring is substituted as necessary.

148. R １ The method according to claim 146, wherein the 13-membered hetero ring is substituted as necessary.

149. R １ The method according to claim 146, wherein the 14-membered hetero ring is substituted as necessary.

150. R １ The method according to claim 146, wherein the 15-membered hetero ring is substituted as necessary.

151. R １ The method according to any one of claims 146 to 150, wherein the aforementioned complex ring is a triring ring.

152. R １ The method according to any one of claims 146 to 151, wherein the heterocycle includes a fused heterocycle.

153. R １ The method according to any one of claims 146 to 152, wherein the heterocycle contains a spiroheterocycle.

154. R １ The method according to any one of claims 146 to 153, wherein the heterocycle contains a fused spiroheterocycle.

155. R １ The method according to any one of claims 146 to 154, wherein the aforementioned hetero ring is an unsaturated hetero ring.

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

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

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

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

160. R １ but, 【Chemical Formula 525】 The method according to any one of claims 146 to 159, wherein selected from, each of which is optionally substituted with one or more substituents.

161. The one or more substituents as needed may be halogen, -OH, -NHCN, or -S(O). ２ (R ２０ ), -S(O) ２ N(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 , -NO 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 The method according to claim 160, selected from alkynyl.

162. The one or more substituents as needed may be halogen, -OH, C １～６ Alkyl and -C(O)N(R) ２０ ) ２ The method according to claim 161, selected from the following.

163. R １ but, 【Chemical 526】 【Chemical 527】 The method according to any one of claims 146 to 162, selected from the following.

164. R １ However, it is selected from substituted 6- to 7-membered heterorings, and the 6- to 7-membered heteroring is substituted with at least one -NHCN, and one or more C １～６ The method according to claim 93, further optionally substituted with alkyl.

165. R １ but, 【Chemical 528】 The method according to claim 164, selected from the following.

166. R １ However, these are selected from 8- to 10-membered heterocycles, and these are respectively 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 The alkynyl and the 5-12 membered heterocycle (preferably a 5-6 membered heterocycle) are optionally substituted with one or more substituents independently selected from the alkynyl and 5-12 membered heterocycles, wherein the 5-12 membered heterocycle is substituted with one or more R １＊ Each is substituted independently as needed, R １＊ These are halogen and C, respectively. １～６ Haloalkyl and CC １～６ The method according to any one of claims 1 to 75, independently selected from alkyl.

167. R １ However, 【Chemical 529】 The method according to claim 166, wherein each of these is substituted as necessary.

168. R １ However, 【Chemical 530】 The method according to claim 167, wherein this is replaced as necessary.

169. R １ but, 【Chemistry 531】 The method according to claim 168, selected from the following.

170. R １ However, 【Chemical 532】 The method according to claim 167.

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

172. R ２ However, 1 or more R ６ The method according to any one of claims 1 to 171, wherein the -L-heterogene is substituted as necessary by the method.

173. L is C １ ~C ４ The method according to claim 172, wherein the alkylene is selected from the alkylene.

174. L is unsubstituted C １ ~C ４ The method according to claim 173, wherein the alkylene is selected from the alkylene.

175. Each L is replaced as needed in C １ ~C ４ Independently selected from alkylenes, and if necessary, two substituents on the same carbon atom of L, together as C ３ ~C ６ Forming a carbon ring, the C ３ ~C ６ The carbon ring is a halogen, -OH, -NO ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ The method according to claim 173, which is optionally substituted with one or more substituents selected from haloalkyls.

176. The substituents of L as needed are C １ ~C ４ Hydroxyalkyl, C １ ~C ４ Alkyl, C ３ ~C ６ Selected from the carbon ring, and if necessary, two substituents on the same carbon atom of L, together, C ３ ~C ６ Forming a carbon ring or a 3- to 8-membered heterocycle, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles are halogens and C １～６ The method according to claim 175, which is optionally substituted with one or more substituents selected from haloalkyl groups.

177. Y-R ２ but, 【Chemical Formula 533】 Selected from, the complex ring portion is one or more R ６ The method according to claims 1 to 176, which is replaced as necessary by the method described above.

178. R ２ R ６ However, halogens, hydroxy, C １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, and C １ ~C ３ The method according to claim 177, wherein each aminoalkyl is independently selected from the appearances.

179. R ２ R ６ However, C １ ~C ３ The method according to claim 178, wherein each alkyl and halogen is independently selected.

180. Y-R ２ but, 【Chemistry 534】 The method according to claims 177 to 179, selected from among them.

181. Y-R ２ but, 【Chemical 535】 Selected from, the complex ring portion is one or more R ６ The method according to any one of claims 171 to 175, which is replaced as necessary by the method described herein.

182. R ６ However, halogen, -OH, C １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, C １ ~C ３ Haloalkyl, oxo, C １ ~C ３ Alkoxy, -CN, and C １ ~C ３ The method according to claim 181, selected from aminoalkyls.

183. R ６ However, halogens and C １ ~C ３ The method according to claim 182, selected from alkyl groups.

184. Y-R ２ but, 【Chemical 536】 The method according to claim 183, selected from the following.

185. Y-R ２ but, 【Chemical 537】 The method according to claim 181, selected from the following.

186. R ２ However, selected from the -L-heterogenetic rings, the aforementioned heterogenetic ring portion of the -L-heterogenetic ring is one or more R ６ The method according to claims 1 to 171, wherein substitutions are made as necessary.

187. L is a substitution C １ ~C ４ Independently selected from alkylene, two substituents on the same carbon atom of L combine to form C ３ ~C ６ Forming a carbon ring, the C ３ ~C ６ The carbon ring is a halogen, -OH, -NO ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ The method according to claim 186, which is optionally substituted with one or more substituents selected from haloalkyl groups.

188. L is a substitution C １ ~C ４ Independently selected from alkylene, two substituents on the same carbon atom of L combine to form C ３ ~C ６ The method according to claim 187, which forms a carbon ring.

189. L is a substitution C ３ Independently selected from alkylene, two substituents on the same carbon atom of L combine to form C ３ The method according to claim 188, wherein a carbon ring is formed.

190. Each L is, 【Chemical 538】 The method according to claim 189, which is independently selected from the above.

191. Y-R ２ but, 【Chemical 539】 The method according to claim 190.

192. Y-R ２ but, 【Chemical 540】 The method according to claims 1 to 176, wherein the heterocycle is selected from and the heterocycle is substituted as necessary.

193. The aforementioned heterocycle is a halogen, hydroxyl, C １ ~C ３ Alkyl, -N(R ５ ) S(O) ２ (R ５ ), -OC(O)N(R ５ ) ２ ❖ = CH ２ , oxo, = NO-C １ ~C ３ Alkyl, -CH ２ OC(O) heteroalgebra, -CH ２ Heterogeneous ring, -CH ２ OC(O)N(R) ５ ) ２ and -O-C １ ~C ３ They are optionally substituted with one or more substituents selected from alkyl groups, -O-C １ ~C ３ The method according to claim 192, wherein the alkyl group of the alkyl is optionally substituted with substituents selected from heterocyclic, oxo, and hydroxyl groups.

194. Y-R ２ but, 【Chemistry 541】 The method according to claim 193, selected from the following.

195. R ２ However, -L-N(R ２１ ) ２ The method according to any one of claims 1 to 176 or 186 to 190, selected from among them.

196. L is substituted C １ ~C ４ Independently selected from alkylene, two substituents on the same carbon atom of L combine to form C ３ ~C ６ Forming a carbon ring, the C ３ ~C ６ The method according to claim 195, wherein the carbon ring is optionally substituted with one or more substituents selected from halogens.

197. L, 【Chemistry 542】 The method according to claim 1, 195, or 196.

198. R ２ but, 【Chemistry 543】 The method according to any one of claims 1 or 195 to 197.

199. Y-R ２ but, 【Chemical 544】 The method according to any one of claims 1 or 195 to 197.

200. The aforementioned compound is as follows: 【Chemical 545】 【Chemical 546】 【Chemistry 547】 【Chemical 548】 【Chemistry 549】 The method according to claim 1, or selected from any one of the pharmaceutically acceptable salts thereof.

201. A method for treating cancer in a subject requiring it, wherein the subject is given an RTK-MAPK pathway inhibitor and a compound of formula (III): 【Chemical 550】 A method comprising the step of administering a therapeutically effective amount of a combination of the salt or a pharmaceutically acceptable salt thereof [in the formula, R １ is selected from C ３ to C １２ carbocyclic rings and 5- to 15-membered heterocyclic rings, each of which is halogen, -B(OR ２０ ), -OR ２ , -SR ２０ , -S(O) ２０ (R ２ ), -S(O) ２０ N(R ２ ), -S(O)N(R ２０ ), -S(O)R ２ (=NR ２０ ), -NR ２ S(O) ２０ R ２０ , -C(O)N(R ２０ ), -C(=NR ２ N(R ２０ ), -C(O)NR ２０ OR ２ , -N(R ２０ )C(O)R ２０ , -N(R I ２ )C(O)N(R ２０ )OR ２０ , -N(R ２０ )C(O)R ２０ , -N(R ２０ )C(O)N(R ２０ ), -N(R ２ )C(O)OR ２０ , -N(R ２０ ), -C(O)R ２０ , -C(O)OR ２ , -OC(O)R ２０ , -OC(O)N(R ２０ ), -NO ２０ , =O, =N(R ２０ ), =NO(R ２ ), -CN, -NHCN, C ２ alkyl-N(R ２０ ), C ２０ aminoalkyl, C １～６ alkoxy, C ２０ hydroxyalkyl, C ２ cyanoalkyl, C １～６ haloalkyl, C １～６ alkyl, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl, C １～６ alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３ ~C １２ The carbon ring is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle. ３ ~C １２ Carbon rings and 5-12 membered heterocycles have one or more R １＊ Each is replaced independently as needed. R １＊ each represents halogen, -B(OR ２０ ), -OR ２ , -SR ２０ , -S(O) ２０ (R ２ ), -S(O) ２０ N(R ２ ), -S(O)N(R ２０ ), -S(O)N(R ２ ), -S(O)R ２０ (=NR ２ ), -NR ２０ S(O) ２０ R ２０ ), -C(O)N(R ２ ), -C(O)NR ２０ OR ２０ ), -N(R ２ C(O)R ２０ ), -N(R ２０ C(O)N(R ２０ ), -N(R ２０ C(O)OR ２０ ), -N(R ２０ ), -C(O)R ２ ), -C(O)OR ２０ ), -OC(O)R ２０ ), -OC(O)N(R ２０ ), -NO ２ ), =O, =N(R ２０ ), =NO(R ２０ ), -CN, -NHCN, C ２０ alkyl-N(R ２０ ), C ２ aminoalkyl, C ２ alkoxy, C ２０ hydroxyalkyl, C ２０ cyanoalkyl, C １～６ haloalkyl, C ２０ alkyl, C[[ID=8l]] ２ alkenyl, C １～６ alkynyl, and C １～６ are each independently selected from 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 C ３ -C １２ carbocycles, and are independently selected, R ２ is -L-NR ２１ S(O) ２ (R ２１ ), -L-S(O) ２ N(R) ２１ ) ２ , -L-N(R ２１ ) C(O)(OR ２１ ), -L-OC(O)N(R ２１ ) ２ and selected from L-bicyclic heterocycles, the bicyclic heterocycle being one or more R ６ It is replaced as needed, L stands for hydroxy, C １ ~C ４ Hydroxyalkyl, C １ ~C ４ Alkyl, C ３ ~C ６ C is optionally substituted with one or more substituents selected from a carbon ring or a 3- to 8-membered heterocycle. １ ~C ４ Selected independently from alkylene, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L are together C ３ ~C ６ Forming a carbon ring or a 3- to 8-membered heterocycle, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. n is selected from 0 to 3. R ４ These are C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkynyl, oxo, hydroxyl, halogen, C ３～１２ A carbon ring and a 3- to 12-membered heterocycle are independently selected, and the C １ ~C ６ Alkyl, C ３～１２ Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR ５ and -N(R ５ ) ２ Each of these is optionally substituted by one or more substituents selected independently of the original, B is selected from heterocycles and carbocycles, and the heterocycle or carbocycle is halogen, cyano, hydroxy, =O, -NO ２ , C ｌ ~C ４ Alkyl, C １～６ Aminoalkyl, -S-C ｌ ~C ３ Alkyl, C ２ ~C ４ Alkenil, C ２ ~C ４ Alkinyl, C ２ ~C ４ Hydroxyalkynyl, C １ ~C ３ Cyanoalkyl, triazolyl, C ｌ ~C ３ Haloalkyl, -O-C ｌ ~C ３ Haloalkyl, -S-C ｌ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, C ｌ ~C ３ Hydroxyalkyl, -CH ２ C(=O)N(R) ５ ) ２ , -C ３ ~C ４ Alkinyl (NR) ５ ) ２ , -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) Halo C ｌ ~C ３ Alkyl-, C １～６ Alkyl-N(R) ２０ ) ２ , C ３ ~C １２ It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle, C ３ ~C １２ Carbon rings and 5- to 12-membered heterocycles include halogens, -OH, and -NO. ２ , -NH ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. Y is bond, O, S and NR ５ Selected from, R ６ These are halogen, hydroxyl, and C, respectively. １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, oxo, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, =CH ２ , = NO-C １ ~C ３ Alkyl, C １ ~C ３ Aminoalkyl, -N(R) ５ ) S(O) ２ (R ５ ), -Q-phenyl, -Q-phenylSO ２ F,-NHC(O)phenyl,-NHC(O)phenylSO ２ F, C １ ~C ３ Alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxy CH ２ -, -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) C １ ~C ３ Alkyl-, (C １ ~C ３ Alkyl) C (= O), oxo, (C １ ~C ３ Haloalkyl)C(=O)-, -SO ２ F, (C １ ~C ３ Alkoxy) C １ ~C ３ Alkoxy, -CH ２ OC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)OC １ ~C ６ Alkyl, -CH ２ NHC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)C １ ~C ６ Alkyl, -CH ２ (Pyrazolyl), -CH ２ NHSO ２ C １ ~C ６ Alkyl, -CH ２ OC(O) heteroalgebra, -OC(O)N(R ５ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl), -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl (C １ ~C ３ Alkyl)N(CH ３ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl, -OC(O) heterocycle, -O-C １ ~C ３ Alkyl and -CH ２ Independently selected from heterocycles, -NHC(O)phenyl and -OC(O)NH(C) １ ~C ３ (Alkyl) (C １ ~C ３ The phenyl in alkyl(phenyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, -O-C １ ~C ３ The alkyl group of the alkyl group is optionally substituted with substituents selected from heterocyclic, oxo, and hydroxyl groups, -CH ２ The heterocyclic ring is substituted with an oxo as needed. Q is selected independently from the combination, S, and O, R ２０ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, R ２１ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, R ５ These are hydrogen or C, respectively. １ ~C ６ [Selected independently of alkyl groups].

202. R ２ However, selected from L-pyrrolidine, the pyrrolidine is one or more R ６ The method according to claim 201, wherein substitutions are made as necessary.

203. B is a 5- to 15-membered heterocycle which is substituted as needed, and C is substituted as needed. ３ ~C １５ The method according to any one of claims 201 to 202, selected from a carbocyclic ring.

204. B is an 8- to 15-member fused heterocycle which is substituted as needed, and C which is substituted as needed. ８ ~C １５ The method according to claim 203, selected from condensed carbocyclic rings.

205. The method according to claim 204, wherein B is selected from 8- to 15-membered fused heterorings which are substituted as needed.

206. B is an unsaturated C which is substituted as needed. ８ ~C １５ The method according to claim 204, selected from condensed carbocyclic rings.

207. Regarding B, the 8-15 member fused heterocycles that are substituted as necessary and C that are substituted as necessary ８ ~C １５ The method according to any one of claims 203 to 206, wherein the condensed carbon rings are bicyclic and tricyclic, respectively.

208. The method according to claim 207, wherein, with respect to B, the heterocycle and the carbon ring are each independently bicyclic.

209. The method according to claim 207, wherein, with respect to B, the heterocycle and the carbon ring are each independently tricyclic.

210. B, 【Chemistry 551】 The method according to any one of claims 201 to 209, wherein selected from, each of which is optionally substituted with one or more substituents.

211. B, 【Chemical 552】 The method according to claim 210, wherein selected from, each of which is optionally substituted with one or more substituents.

212. B, 【Chemical 553】 The method according to claim 211, wherein selected from, each of which is optionally substituted with one or more substituents.

213. With respect to B, the one or more optional substituents of the heterocycle and carbon ring are oxo, -NH ２ , halogen, C １ ~C ３ A method according to any one of claims 201 to 212, independently selected from alkyl.

214. B, 【Chemical 554】 The method according to any one of claims 201 to 213, selected from the following.

215. Regarding B, the one or more optional substituents of the heterocycle and carbon ring are halogens, C １ ~C ３ Alkyl, -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 The method according to any one of claims 201 to 212, wherein each occurrence is independently selected from alkynyl.

216. With respect to B, the one or more optional substituents of the heterocycle and carbon ring are halogen, oxo, -NH ２ , C １ ~C ３ Alkyl, -B(OH) ２ , -OH, -C(O)NH ２ , -NH ２ , = O, -CN, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C ２～６ The method according to claim 205, wherein each instance is independently selected from alkynyl.

217. B, 【Chemical 555】 【Chemical 556】 The method according to any one of claims 215 to 216, selected from the above.

218. R ４ Each of these is C １～６ Alkyl, C ２～６ Alkenil, C ２～６ The method according to any one of claims 201 to 217, independently selected from alkynyl, oxo, hydroxyl, and halogen.

219. R ４ Each of these is C １～６ The method according to claim 218, independently selected from 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. R １ The method according to any one of claims 201 to 212, wherein the 5- to 12-membered heteroring is selected as necessary.

224. R １ However, a heterocycle with 5 to 12 members is selected, and the heterocycle with 5 to 12 members is a halogen, -OH, -N(R) ２０ ) ２ , -NO ２ , = O, -CN, C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C １～６ The method according to claim 223, wherein the substituent is optionally substituted with one or more substituents independently selected from the haloalkyl group.

225. R １ However, a heterocycle with 5 to 12 members is selected, and the heterocycle with 5 to 12 members is a halogen, -OH, -N(R) ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C １～６ The method according to claim 224, wherein the substituent is optionally substituted with one or more substituents independently selected from the haloalkyl group.

226. R ２０ However, hydrogen and C １～３ The method according to claim 224 or 225, selected from alkyl groups.

227. R １ The method according to claims 201 to 226, wherein the 5- to 12-membered heterocycle is unsaturated.

228. R １ The method according to claims 201 to 226, wherein the 5- to 12-membered heterocycle is saturated.

229. R １ The method according to claims 201 to 226, wherein the 5 to 12 member hetero rings are bridged.

230. R １ The method according to claims 201 to 226, wherein the 5 to 12-membered heterocycle is a spiroheterocycle.

231. R １ but, 【Chemical 557】 These are selected from halogen, -OH, and -N(R) respectively. ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, =O, -CN,C １～６ Hydroxyalkyl and C １～６ The method according to claims 201 to 230, wherein the haloalkyl group is optionally substituted with one or more substituents independently selected from the haloalkyl group.

232. R １ but, 【Chemical 558】 These are selected from halogen, -OH, and -N(R) respectively. ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, =O, -CN,C １～６ Hydroxyalkyl and C １～６ The method according to claim 231, wherein the substituent is optionally substituted with one or more substituents independently selected from the haloalkyl group.

233. R １ but, 【Chemical 559】 The method according to claim 232, selected from the following.

234. R ２ However, 1 or more R ６ The method according to claims 201 to 233, wherein the -L-heterocycle is substituted as necessary by the method.

235. L is C １ ~C ４ The method according to claim 234, selected from alkylenes.

236. L is unsubstituted C １ ~C ４ The method according to claim 235, selected from alkylenes.

237. Y-R ２ but, 【Chemical 560】 Selected from, the complex ring portion is one or more R ６ The method according to any one of claims 234 to 236, which is replaced as necessary by the method described herein.

238. R ２ R ６ However, halogens, hydroxy, C １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, and C １ ~C ３ The method according to claim 237, wherein each aminoalkyl is independently selected from the appearances.

239. R ２ R ６ However, C １ ~C ３ The method according to claim 238, wherein each alkyl and halogen is independently selected.

240. Y-R ２ but, 【Chemical 561】 The method according to claim 239, selected from the following.

241. A method for treating cancer in a subject requiring it, wherein the subject is given an RTK-MAPK pathway inhibitor and a compound of formula (I): 【Chemical 562】 A method comprising the step of administering a therapeutically effective amount of a combination of the salt or a pharmaceutically acceptable salt thereof [in the formula, R １ C ３ ~C １２ Selected from carbon rings and 5- to 15-membered heterocycles, these are halogens, -B (OR ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ Alkinyl, C ３ ~C １２ The carbon ring is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle. ３ ~C １２ Carbon rings and 5-12 membered heterocycles have one or more R １＊ Each is replaced independently as needed. R １＊ These are halogen and -B (OR) respectively. ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ Alkinyl and C ３ ~C １２ Selected independently from the carbon ring, Y is bond, O, S and NR ５ Selected from, R ２ is hydrogen, -N(R ２１ ) ２ , -L-N(R ２１ ) ２ , -L-OR ２１ , complex algebras, C １ ~C ６ Alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-N(R) ２１ ) ２ , -L-NHC(=NH)NH ２ , -LC(O)N(R ２１ ) ２ , -L-C １ ~C ６ Haloalkyl, -L-OR ２１ , -L-NR ２１ C(O)-aryl, -L-COOH, -L-NR ２１ S(O) ２ (R ２１ ), -L-S(O) ２ N(R) ２１ ) ２ , -L-N(R ２１ ) C(O)(OR ２１ ), -L-OC(O)N(R ２１ ) ２ and -LC(=O)OC １ ~C ６ Selected from alkyl groups, the heterocycle and -L-NR ５ The aryl portion of C(O)-aryl, the heterocyclic portion of -L-heterocyclic, and the cycloalkyl portion of -L-cycloalkyl are one or more R ６ The aryl or heteroaryl in the -L-aryl and the -L-heteroaryl may be substituted as needed, and one or more R ７ This may be replaced as needed. L stands for hydroxy, C １ ~C ４ Hydroxyalkyl, C １ ~C ４ Alkyl, C ３ ~C ６ C is optionally substituted with one or more substituents selected from a carbon ring or a 3- to 8-membered heterocycle. １ ~C ４ Selected independently from alkylene, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L are together C ３ ~C ６ Forming a carbon ring or a 3- to 8-membered heterocycle, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ It is optionally substituted with one or more substituents selected from haloalkyl groups. R ４ These are C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Cyanoalkyl, C １～６ Haloalkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, C ３～１２ Carbon rings and 3- to 12-membered heterocycles include halogens, -OH, -CN, and -NO. ２ , -NH ２ ,-NH(C １～６ Alkyl), -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. R ５ These are hydrogen or C, respectively. １ ~C ６ Selected independently of alkyl, R ６ These are halogen, hydroxyl, and C, respectively. １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, oxo, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, =CH ２ , = NO-C １ ~C ３ Alkyl, C １ ~C ３ Aminoalkyl, -N(R) ５ ) S(O) ２ (R ５ ), -Q-phenyl, -Q-phenylSO ２ F,-NHC(O)phenyl,-NHC(O)phenylSO ２ F, C １ ~C ３ Alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxy CH ２ -, -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) C １ ~C ３ Alkyl-, (C １ ~C ３ Alkyl) C (= O), oxo, (C １ ~C ３ Haloalkyl)C(=O)-, -SO ２ F, (C １ ~C ３ Alkoxy) C １ ~C ３ Alkoxy, -CH ２ OC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)OC １ ~C ６ Alkyl, -CH ２ NHC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)C １ ~C ６ Alkyl, -CH ２ (Pyrazolyl), -CH ２ NHSO ２ C １ ~C ６ Alkyl, -CH ２ OC(O) heteroalgebra, -OC(O)N(R ５ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl), -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl (C １ ~C ３ Alkyl)N(CH ３ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl, -OC(O) heterocycle, -O-C １ ~C ３ Alkyl and -CH ２ Independently selected from heterocycles, -NHC(O)phenyl and -OC(O)NH(C) １ ~C ３ (Alkyl) (C １ ~C ３ The phenyl in alkyl(phenyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, -O-C １ ~C ３ The alkyl group of the alkyl group is optionally substituted with substituents selected from heterocyclic, oxo, and hydroxyl groups, -CH ２ The heterocyclic ring is substituted with an oxo as needed. R ７ These are halogen, hydroxyl, HC(=O)-, and C, respectively. １ ~C ４ Alkyl, C １ ~C ４ Alkoxy, C １ ~C ４ Haloalkyl, C １ ~C ４ Hydroxyalkyl or -N(R) ５ ) ２ Selected independently from, R ２０ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, =NH, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, R ２１ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, Q is selected independently from the combination, S, and O, B is selected from heterocycles and carbocycles, and the heterocycles and carbocycles are halogen, cyano, hydroxy, =O, -NO ２ , C ｌ ~C ４ Alkyl, C １～６ Aminoalkyl, -S-C ｌ ~C ３ Alkyl, C ２ ~C ４ Alkenil, C ２ ~C ４ Alkinyl, C ２ ~C ４ Hydroxyalkynyl, C １ ~C ３ Cyanoalkyl, triazolyl, C ｌ ~C ３ Haloalkyl, -O-C ｌ ~C ３ Haloalkyl, -S-C ｌ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, C ｌ ~C ３ Hydroxyalkyl, -CH ２ C(=O)N(R) ５ ) ２ , -C ３ ~C ４ Alkinyl (NR) ５ ) ２ , -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) Halo C ｌ ~C ３ Alkyl-, C １～６ Alkyl-N(R) ２０ ) ２ , C ３ ~C １２ It is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle, C ３ ~C １２ Carbon rings and 5- to 12-membered heterocycles include halogens, -OH, and -NO. ２ , -NH ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Each is optionally substituted with one or more substituents selected from haloalkyl groups, and B forms a spiro ring with ring A. Ring A is selected from heterocycles and carbocycles, and the heterocycle or carbocycle is R ４ [Optionally substituted with one or more substituents selected from the following.]

242. B is a 5- to 15-membered heterocycle which is substituted as needed, and C is substituted as needed. ３ ~C １５ The method according to claim 241, selected from a carbocyclic ring.

243. B is an 8- to 15-member fused heterocycle which is substituted as needed, and C which is substituted as needed. ８ ~C １５ The method according to claim 242, selected from condensed carbocyclic rings.

244. The method according to claim 243, wherein B is an 8- to 15-member fused heteroring which is substituted as needed.

245. B is an unsaturated C which is substituted as needed. ８ ~C １５ The method according to claim 243, wherein the condensed carbon ring is used.

246. Regarding B, the 8-15 member fused heterocycles that are substituted as necessary and C that are substituted as necessary ８ ~C １５ The method according to any one of claims 241 to 245, wherein each condensed carbon ring is independently bicyclic or tricyclic.

247. The method according to claim 246, wherein, with respect to B, the heterocycle and the carbon ring are each independently bicyclic.

248. The method according to claim 246, wherein, with respect to B, the heterocycle and the carbon ring are each independently tricyclic.

249. B, 【Chemical 563】 The method according to any one of claims 241 to 248, wherein selected from, each of which is optionally substituted with one or more substituents.

250. B, 【Chemical 564】 The method according to claim 249, wherein selected from, each of which is optionally substituted with one or more substituents.

251. B, 【Chemical 565】 The method according to claim 250, wherein selected from, each of which is optionally substituted with one or more substituents.

252. With respect to B, the one or more optional substituents of the heterocycle or carbon ring are oxo, -NH ２ , halogen, C １ ~C ３ The method according to any one of claims 241 to 251, independently selected from alkyl.

253. B, 【Chemical 566】 The method according to any one of claims 241 to 252, selected from the following.

254. R ４ Each of these is C １～６ Alkyl, C ２～６ Alkenil, C ２～６ The method according to any one of claims 241 to 253, independently selected from alkynyl, oxo, hydroxyl, and halogen.

255. R ４ Each of these is C １～６ The method according to claim 254, independently selected from alkyl, oxo, and halogen.

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

257. R １ However, these are 5-5 member complex rings that are substituted as needed. The method according to any one of claims 241 to 256, selected from the following.

258. R １ However, a heterocycle with 5 to 12 members is selected, and the heterocycle with 5 to 12 members is a halogen, -OH, -N(R) ２０ ) ２ , -NO ２ , = O, -CN, C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C １～６ The method according to claim 257, wherein the substituents are optionally substituted with one or more substituents independently selected from the haloalkyl group.

259. R １ However, a heterocycle with 5 to 12 members is selected, and the heterocycle with 5 to 12 members is a halogen, -OH, -N(R) ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C １～６ The method according to claim 258, wherein the substituents are optionally substituted with one or more substituents independently selected from the haloalkyl group.

260. R ２０ However, hydrogen and C １～３ The method according to claims 258 to 259, selected from alkyl groups.

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

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

263. R １ The method according to any one of claims 241 to 260, wherein the 5 to 12 member hetero rings are bridged.

264. R １ but, 【Chemical 567】 These are selected from halogen, -OH, and -N(R) respectively. ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, =O, -CN,C １～６ Hydroxyalkyl and C １～６ The method according to any one of claims 245 to 260, wherein the substituent is optionally substituted with one or more substituents independently selected from the haloalkyl group.

265. R １ but, 【Chemical 568】 These are selected from halogen, -OH, and -N(R) respectively. ２０ ) ２ , -NO ２ , C １～６ Aminoalkyl, C １～６ Alkoxy, =O, -CN,C １～６ Hydroxyalkyl and C １～６ The method according to claim 264, wherein the substituents are optionally substituted with one or more substituents independently selected from the haloalkyl group.

266. R １ but, 【Chemical 569】 The method according to claim 265, selected from the following.

267. R ２ However, 1 or more R ６ The method according to any one of claims 241 to 266, wherein the -L-heterogene is substituted as necessary by the method.

268. L is C １ ~C ４ The method according to any one of claims 241 to 267, selected from alkylenes.

269. L is unsubstituted C １ ~C ４ The method according to claim 267 or 268, wherein the alkylene is selected from the following:

270. Y-R ２ but, 【Chemical 570】 Selected from, the complex ring portion is one or more R ６ The method according to any one of claims 231 to 259, which is replaced as necessary by the method described herein.

271. R ２ R ６ However, halogens, hydroxy, C １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, and C １ ~C ３ The method according to claim 270, wherein each aminoalkyl is independently selected from the appearances thereof.

272. R ２ R ６ However, C １ ~C ３ The method according to claim 271, wherein each alkyl and halogen is independently selected.

273. Y-R ２ but, 【Chemistry 571】 The method according to claim 272, selected from the following.

274. A method for treating cancer in a subject requiring it, wherein the subject is given an RTK-MAPK pathway inhibitor and formula (II ＊ Compounds of: 【Chemistry 572】 A method comprising the step of administering a therapeutically effective amount of a combination of the salt or a pharmaceutically acceptable salt thereof [in the formula, M is O and NR ３ Selected from, R ３ is hydrogen, C １～６ Alkyl and C １～６ Selected from cyanoalkyl groups, R １ The 7-10 member heterocycle is selected from a 7- to 10 member heterocycle, and the 7- to 10 member heterocycle is a halogen, -B (OR ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ The alkynyl group is optionally substituted with one or more substituents independently selected from a 5- to 12-membered heterocycle, wherein the 5- to 12-membered heterocycle is one or more R １＊ It is replaced independently as needed. R １＊ These are halogen and -B (OR) respectively. ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ Alkinyl and C ３ ~C １２ Selected independently from the carbon ring, B is C ６ ~C １５ Selected from the carbon ring, the C ６ ~C １５ The carbon ring is a halogen, C １ ~C ３ Alkyl, -B (OR 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 It is optionally substituted with one or more substituents independently selected from the alkynyl, R ２ is selected from the -L-heterogenetic rings, and the heterogenetic rings of the -L-heterogenetic rings are one or more R ６ It is replaced as needed, L is C １ ~C ４ Selected independently from alkylene, the C １ ~C ４ Alkylenes are hydroxy, C １ ~C ４ Hydroxyalkyl, C １ ~C ４ It is optionally substituted with one or more substituents selected from alkyl groups, and optionally, two substituents on the same carbon atom of L are together, C ３ ~C ６ Forming a carbon ring, R ２０ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, =NH, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～６ [Independently selected from carbon rings and 3- to 6-membered heterocycles.]

275. R １ The method according to claim 274, wherein the 7-10 member spiroheterocycles are selected as necessary from substituted 7-10 member fused heterocycles and substituted 7-10 member fused heterocycles.

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

277. R １ The at least one nitrogen in the heterocycle of the above is given by formula (II ＊ The method according to claim 276, wherein the member is coupled to the member.

278. R １ The method according to any one of claims 275 to 277, wherein the selected material is a 10-membered spiroheterocycle that is substituted as necessary and a 10-membered fused heterocycle that is substituted as necessary.

279. R １ The one or more substituents as needed are halogen, -OH, -S(O) ２ (R ２０ ), -S(O) ２ N(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 , -NO ２ , = 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 Alkynyl, independently selected from 5- to 12-membered heterocycles, wherein the 5- to 12-membered heterocycle is a halogen and C １～６ The method according to any one of claims 275 to 278, wherein the substituents are optionally substituted with one or more substituents selected from alkyl groups.

280. R １ The one or more substituents as needed are halogen, -OH, -S(O) ２ (R ２０ ), -S(O) ２ N(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 , -NO ２ , = 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 An alkyl group is independently selected from a 5- to 12-membered heterocycle, wherein the 5- to 12-membered heterocycle is a halogen and C １～６ The method according to any one of claims 275 to 279, wherein the substituents are optionally substituted with one or more substituents selected from alkyl groups.

281. R １ but, 【Chemistry 573】 The method according to any one of claims 275 to 280, wherein a selected and replaced thereof.

282. R １ However, halogen, -OH, -S(O) ２ (R ２０ ), -S(O) ２ N(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 , -NO ２ , = 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 ring is substituted with one or more substituents independently selected from a 5- to 12-membered heterocycle. 【Chemistry 574】 Selected from, the 5-12 member heterocycle is a halogen and C １～６ The method according to any one of claims 275 to 281, wherein the substituents are optionally substituted with one or more substituents selected from alkyl groups.

283. R １ but, 【Chemical 575】 【Chemical 576】 The method according to any one of claims 275 to 281, selected from the following.

284. R １ However, 【Chemical 577】 The method according to any one of claims 275 to 282.

285. R １ but, 【Chemical 578】 The method according to claim 278.

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

287. M is NCH ３ and NCH ２ CH ３ The method according to claim 274, selected from the following.

288. The method according to claim 287, wherein M is NMee.

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

290. R ２ The method according to claim 289, wherein the aforementioned hetero ring is a saturated hetero ring.

291. R ２ R ６ However, halogen, =CH ２ , hydroxy, C １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, and C １ ~C ３ The method according to claim 290, wherein each aminoalkyl is independently selected from the appearances thereof.

292. R ２ L is C １ ~C ４ Alkylene and 【Chemistry 579】 The method according to claim 291, selected from the following.

293. R ２ but, 【Chemical 580】 A method according to any one of claims 274 to 292, selected from the following.

294. B is replaced by C as needed. ９ ~C １０ The method according to any one of claims 274 to 293, selected from condensed carbon rings.

295. B, 【Chemistry 581】 The method according to any one of claims 274 to 294, wherein selected from and each of which is replaced as necessary.

296. B is halogen, oxo, -NH ２ , C １ ~C ３ Alkyl, -B(OH) ２ -OH, -O-C １ ~C ３ Haloalkyl, -C(O)NH ２ , -NH ２ , = O, -CN, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C ２～６ The method according to any one of claims 274 to 295, wherein the alkynyl is optionally substituted with one or more substituents independently selected.

297. The method according to claim 296, wherein B is optionally substituted with one or more substituents independently selected from the halogen.

298. B, 【Chemical Formula 582】 The method according to claim 296, selected from the following.

299. B, 【Chemical 583】 The method according to claim 298.

300. B, 【Chemical 584】 The method according to claim 298.

301. The method according to claim 274, wherein B is unsubstituted.

302. The method according to claim 274, wherein B is substituted.

303. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a therapeutically effective combination of an RTK-MAPK pathway inhibitor and a compound of formula (II), wherein the compound is compound 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 A method selected from 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 any one of their pharmaceutically acceptable salts.

304. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a therapeutically effective combination of a RAF-MEK-ERK pathway inhibitor and a compound of formula (II), wherein the compound is compound 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 A method selected from 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 any one of their pharmaceutically acceptable salts.

305. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a therapeutically effective combination of an ERBB family inhibitor and a compound of formula (II), wherein the compound is compound 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, A method selected from 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 any one of their pharmaceutically acceptable salts.

306. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a therapeutically effective combination of an EGFR inhibitor and a compound of formula (II), wherein the compound is compound 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 A method selected from 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 any one of their pharmaceutically acceptable salts.

307. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a therapeutically effective combination of an SHP-2 inhibitor and a compound of formula (II), wherein the compound is compound 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 A method selected from 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 any one of their pharmaceutically acceptable salts.

308. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a therapeutically effective combination of an SOS1 inhibitor and a compound of formula (II), wherein the compound is compound 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 A method selected from 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 any one of their pharmaceutically acceptable salts.

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 any one thereof as a pharmaceutically acceptable salt.

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 and 309 to 315, wherein the inhibitor is selected from the group consisting of afatinib, dacomitinib, poziotinib, erlotinib, gefitinib, sapitinib, 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 for treating cancer in a subject requiring it, wherein the subject is given an RTK-MAPK pathway inhibitor and formula (II ＊ Compounds of: 【Chemical 585】 A method comprising the step of administering a therapeutically effective amount of a combination of the salt or a pharmaceutically acceptable salt thereof [in the formula, M is O and NR ３ Selected from, R ３ is hydrogen, C １～６ Alkyl and C １～６ Selected from cyanoalkyl groups, R １ The 7-10 member heterocycle is selected from a 7- to 10 member heterocycle, and the 7- to 10 member heterocycle is a halogen, -B (OR ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ The alkynyl group is optionally substituted with one or more substituents independently selected from a 5- to 12-membered heterocycle, wherein the 5- to 12-membered heterocycle is one or more R １＊ It is replaced independently as needed. R １＊ These are halogen and -B (OR) respectively. ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ Alkinyl and C ３ ~C １２ Selected independently from the carbon ring, B is C ６ ~C １５ Selected from the carbon ring, the C ６ ~C １５ The carbon ring is a halogen, C １ ~C ３ Alkyl, -B (OR 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 It is optionally substituted with one or more substituents independently selected from the alkynyl, R ２ is selected from the -L-heterogenetic rings, and the heterogenetic rings of the -L-heterogenetic rings are one or more R ６ It is replaced as needed, L is C １ ~C ４ Selected independently from alkylene, the C １ ~C ４ Alkylenes are hydroxy, C １ ~C ４ Hydroxyalkyl, C １ ~C ４ It is optionally substituted with one or more substituents selected from alkyl groups, and optionally, two substituents on the same carbon atom of L are together, C ３ ~C ６ Forming a carbon ring, R ２０ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, =NH, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～６ [Independently selected from carbon rings and 3- to 6-membered heterocycles.]

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

321. The method according to claim 303 or 319, wherein the therapeutically effective amount of the combination of the inhibitor and the compound or salt results in, in the subject, an increase in overall survival, an increase in progression-free survival, an increase in tumor growth regression, an increase in tumor growth inhibition, and an increase in the period of disease stabilization, compared to treatment with the compound or salt or any combination thereof alone.

322. The method according to any one of claims 303 to 321, wherein the therapeutically effective amount of the compound or salt of the combination is between approximately 0.01 and 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 between approximately 0.1 and 50 mg / kg per day.

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

325. The method according to any one of claims 303 to 324, wherein the therapeutically effective dose of the inhibitor in the combination is between approximately 0.1 and 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 days.

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

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

331. The method according to 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 the group consisting of afatinib, dacomitinib, poziotinib, erlotinib, gefitinib, sapitinib, tarloxotinib, and cetuximab.

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

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

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

336. The method according to claim 335, wherein the SHP-2 inhibitor is SHP-099 (6-(4-amino-4-methylpiperidine-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]decane-8-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazine-2-yl)methanol), RMC-4360, or TNO155 (Novartis).

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

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

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

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

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

342. The method according to 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 aforementioned cancers are as follows: Heart: Sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyomas, fibromas, lipomas, and teratomas; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, cartilaginous hamartoma, mesothelioma; Gastrointestinal tract: Esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, chorioadenoma, hamartoma, leiomyoma); Urogenital tract: kidney (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testes (seminocarcinoma, teratoma, fetal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); Liver: Hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Bile duct: gallbladder cancer, papillary cancer, cholangiocellular carcinoma; Bone: Osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondroma (chondrodystostoma), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; Nervous system: Skull (osteoma, hemangioma, granuloma, xanthomas, degenerative osteitis), meninges (meningioma, meningiosarcoma, glioma), brain (astrocytoma, medulloblastoma, glioma, ependymoma, intracranial germ cell tumor (pineal glandoma), glioblastoma pleomorphic, oligodendroglioma, Schwann cell tumor, retinoblastoma, congenital tumor), spinal neurofibroma, meningioma, glioma, sarcoma); Gynecology: Uterus (endometrial cancer), cervix (cervical cancer, preneoplastic cervical malformation), ovaries (ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassifiable cancer), granulosacytic cell tumor, Sertley-Leydig cell tumor, undifferentiated germ cell tumor, malignant teratoma), vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, staphyloid sarcoma (embryonic rhabdomyosarcoma), fallopian tubes (carcinoma); Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes), Hodgkin's disease, non-Hodgkin lymphoma (malignant lymphoma); Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus moles, lipomas, hemangiomas, dermatofibromas, keloids, psoriasis; and Adrenal gland: Neuroblastoma The method according to any one of claims 303 to 343, selected from the following.

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 carcinoma.

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

353. The method according to any one of claims 303 to 351, wherein the cancer is selected from KRas wild-type associated 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-related 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 associated 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 aforementioned compound, 【Chemical 586】 【Chemical Formula 587】 【Chemical 588】 【Chemical 589】 【Chemical 590】 The method according to any one of claims 1 to 40, or selected from pharmaceutically acceptable salts thereof.

360. A method for treating cancer in a subject requiring it, wherein the subject is given an RTK-MAPK pathway inhibitor and a compound of formula (II): 【Chemistry 591】 A method comprising the step of administering a combination thereof with a pharmaceutically acceptable salt [in the formula, M is O, S, SO, SO ２ and NR ３ Selected from, R １ C ３ ~C １２ Selected from carbon rings and 5- to 15-membered heterocycles, these are halogens, -B (OR ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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-SO ２ R ２０ , C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３ ~C １２ The carbon ring is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle. ３ ~C １２ Carbon rings and 5-12 membered heterocycles have one or more R １＊ Each is replaced independently as needed. R １＊ These are halogen and -B (OR) respectively. ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ Alkinyl and C ３ ~C １２ Selected independently from the carbon ring, Y is bond, O, S and NR ５ Selected from, R ２ is -L-N(R ２１ ) ２ , -L-OR ２１ , complex algebras, C １ ~C ６ Alkyl, -L-heterocyclic, -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH ２ , -LC(O)N(R ２１ ) ２ , -L-C １ ~C ６ Haloalkyl, -L-NR ２１ C(O)-aryl, -L-COOH, -L-NR ２１ S(O) ２ (R ２１ ), -L-S(O) ２ N(R) ２１ ) ２ , -L-N(R ２１ ) C(O)(OR ２１ ), -L-OC(O)N(R ２１ ) ２ and -LC(=O)OC １ ~C ６ Selected from alkyl groups, the heterocycle, -L-NR ２１ The aryl portion of C(O)-aryl, the heterocyclic portion of -L-heterocyclic, and the cycloalkyl portion of -L-cycloalkyl are one or more R ６ Each is replaced as needed, and the aryl portion of the -L-aryl and the heteroaryl portion of the -L-heteroaryl are one or more R ７ Each is substituted as necessary, and if Y is a bond, O, or S, then R ２ It is further selected from hydrogen, L stands for hydroxy, C １ ~C ４ Hydroxyalkyl, C １ ~C ４ Alkyl, C ３ ~C ６ C is optionally substituted with one or more substituents selected from a carbon ring or a 3- to 8-membered heterocycle. １ ~C ４ Selected independently from alkylene, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ It is optionally substituted with one or more substituents selected from haloalkyl groups, and optionally, two substituents on the same carbon atom of L are together C ３ ~C ６ Forming a carbon ring or a 3- to 8-membered heterocycle, the C ３ ~C ６ Carbon rings and 3- to 8-membered heterocycles include halogens, -OH, and -NO. ２ , =O, =S, -CN,C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl, C １～６ Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups. R ３ is hydrogen, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, 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 Selected from carbon rings and 3- to 12-membered heterocycles, C ３～１２ Carbon rings and 3- to 12-membered heterocycles include halogens, -OH, -CN, and -NO. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. n is selected from 0 to 2. R ４ These are C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkynyl, oxo, hydroxyl, halogen, C ３～１２ A carbon ring and a 3- to 12-membered heterocycle are independently selected, and the C １ ~C ６ Alkyl, C ３～１２ Carbon rings and 3- to 12-membered heterocycles are cyano, halogen, -OR ５ and -N(R ５ ) ２ Each of these is optionally substituted by one or more substituents selected independently of the original, R ５ These are hydrogen or C, respectively. １ ~C ６ Selected independently of alkyl, R ６ These are halogen, hydroxyl, and C, respectively. １ ~C ３ Hydroxyalkyl, C １ ~C ３ Alkyl, oxo, C １ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, cyano, =CH ２ , = NO-C １ ~C ３ Alkyl, C １ ~C ３ Aminoalkyl, -N(R) ５ ) S(O) ２ (R ５ ), -Q-phenyl, -Q-phenylSO ２ F,-NHC(O)phenyl,-NHC(O)phenylSO ２ F, C １ ~C ３ Alkyl-substituted pyrazolyl, tert-butyldimethylsilyloxy CH ２ -, -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) C １ ~C ３ Alkyl-, (C １ ~C ３ Alkyl) C (= O), oxo, (C １ ~C ３ Haloalkyl)C(=O)-, -SO ２ F, (C １ ~C ３ Alkoxy) C １ ~C ３ Alkoxy, -CH ２ OC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)OC １ ~C ６ Alkyl, -CH ２ NHC(O)N(R) ５ ) ２ ien-CH ２ NHC(O)C １ ~C ６ Alkyl, -CH ２ (Pyrazolyl), -CH ２ NHSO ２ C １ ~C ６ Alkyl, -CH ２ OC(O) heteroalgebra, -OC(O)N(R ５ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl), -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl (C １ ~C ３ Alkyl)N(CH ３ ) ２ , -OC(O)NH(C １ ~C ３ Alkyl)O(C １ ~C ３ Alkyl)phenyl, -OC(O) heterocycle, -O-C １ ~C ３ Alkyl and -CH ２ Independently selected from heterocycles, -NHC(O)phenyl and -OC(O)NH(C) １ ~C ３ (Alkyl) (C １ ~C ３ The phenyl in alkyl(phenyl)phenyl is optionally substituted with one or more substituents selected from -C(O)H and OH, respectively, -O-C １ ~C ３ The alkyl group of the alkyl group is optionally substituted with substituents selected from heterocyclic, oxo, and hydroxyl groups, -CH ２ The heterocyclic ring is substituted with an oxo as needed. Q is selected independently from the combination, S, and O, R ７ These are halogen, hydroxyl, HC(=O)-, and C, respectively. １ ~C ４ Alkyl, C １ ~C ４ Alkoxy, C １ ~C ４ Haloalkyl, C １ ~C ４ Hydroxyalkyl or -N(R) ５ ) ２ Selected independently from, R ２０ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, =NH, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, R ２１ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～１２ Independently selected from carbon rings and 3- to 12-membered heterocycles, B is selected from heterocycles and carbocycles, and the heterocycles and carbocycles are halogen, cyano, hydroxy, =O, -NO ２ , C ｌ ~C ４ Alkyl, C １～６ Aminoalkyl, -S-C ｌ ~C ３ Alkyl, C ２ ~C ４ Alkenil, C ２ ~C ４ Alkinyl, C ２ ~C ４ Hydroxyalkynyl, C １ ~C ３ Cyanoalkyl, triazolyl, C ｌ ~C ３ Haloalkyl, -O-C ｌ ~C ３ Haloalkyl, -S-C ｌ ~C ３ Haloalkyl, C １ ~C ３ Alkoxy, C ｌ ~C ３ Hydroxyalkyl, -CH ２ C(=O)N(R) ５ ) ２ , -C ３ ~C ４ Alkinyl (NR) ５ ) ２ , -N(R ５ ) ２ , (C １ ~C ３ Alkoxy) Halo C ｌ ~C ３ Alkyl-, C １～６ Alkyl-N(R) ２０ ) ２ , C ３ ~C １２ Each is optionally substituted with one or more substituents independently selected from a carbon ring and a 5- to 12-membered heterocycle, C ３ ~C １２ Carbon rings and 5- to 12-membered heterocycles include halogens, -OH, and -NO. ２ , -NH ２ , =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 Each substituent is optionally substituted with one or more substituents selected from haloalkyl groups.

361. A method for treating cancer in a subject requiring it, wherein the subject is given an RTK-MAPK pathway inhibitor and formula (II ＊ Compounds of: 【Chemical 592】 A method comprising the step of administering a combination thereof with a pharmaceutically acceptable salt [in the formula, M is O and NR ３ Selected from, R ３ is hydrogen, C １～６ Alkyl and C １～６ Selected from cyanoalkyl groups, R １ The 7-10 member heterocycle is selected from a 7- to 10 member heterocycle, and the 7- to 10 member heterocycle is a halogen, -B (OR ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ The alkynyl group is optionally substituted with one or more substituents independently selected from a 5- to 12-membered heterocycle, wherein the 5- to 12-membered heterocycle is one or more R １＊ It is replaced independently as needed. R １＊ These are halogen and -B (OR) respectively. ２０ ) ２ , -OR ２０ , -SR ２０ , -S(O) ２ (R ２０ ), -S(O) ２ N(R) ２０ ) ２ , -S(O)N(R ２０ ) ２ , -S(O)R ２０ (=NR ２０ ), -NR ２０ S(O) ２ R 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 , -NO ２ , = 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 Alkenil, C ２～６ Alkinyl and C ３ ~C １２ Selected independently from the carbon ring, B is C ６ ~C １５ Selected from the carbon ring, the C ６ ~C １５ The carbon ring is a halogen, C １ ~C ３ Alkyl, -B (OR 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 It is optionally substituted with one or more substituents independently selected from the alkynyl, R ２ is selected from the -L-heterogenetic rings, and the heterogenetic rings of the -L-heterogenetic rings are one or more R ６ It is replaced as needed, L is C １ ~C ４ Selected independently from alkylene, the C １ ~C ４ Alkylenes are hydroxy, C １ ~C ４ Hydroxyalkyl, C １ ~C ４ It is optionally substituted with one or more substituents selected from alkyl groups, and optionally, two substituents on the same carbon atom of L are together, C ３ ~C ６ Forming a carbon ring, R ２０ These are hydrogen, respectively; and halogens, -OH, -CN, and -NO, respectively. ２ , -NH ２ , -N(C １～６ Alkyl) ２ , C １～１０ Alkyl, -C １～１０ Haloalkyl, -O-C １～１０ Alkyl, oxo, =NH, C ３～１２ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocycle. １～６ Alkyl, C ３～６ [Independently selected from carbon rings and 3- to 6-membered heterocycles.]

362. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a combination of an RTK-MAPK pathway inhibitor and a compound of formula (II), wherein the compound is compound 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, A method selected from 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 any one of their pharmaceutically acceptable salts.

363. A method for treating cancer in a subject requiring such treatment, comprising the step of administering to the subject a combination of an EGFR inhibitor and a compound of formula (II), wherein the compound is compound 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, A method selected from 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 any one of their pharmaceutically acceptable salts.

364. A method for treating cancer in a subject requiring such treatment, comprising the step of 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 any one thereof as a pharmaceutically acceptable salt.

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

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

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

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

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

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

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

372. The aforementioned cancers are as follows: Heart: Sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyomas, fibromas, lipomas, and teratomas; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, cartilaginous hamartoma, mesothelioma; Gastrointestinal tract: Esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vipoma), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, chorioadenoma, hamartoma, leiomyoma); Urogenital tract: kidney (adenocarcinoma, Wilms' tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testes (seminocarcinoma, teratoma, fetal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); Liver: Hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Bile duct: gallbladder cancer, papillary cancer, cholangiocellular carcinoma; Bone: Osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticular cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondroma (chondrodystostoma), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; Nervous system: Skull (osteoma, hemangioma, granuloma, xanthomas, degenerative osteitis), meninges (meningioma, meningiosarcoma, glioma), brain (astrocytoma, medulloblastoma, glioma, ependymoma, intracranial germ cell tumor (pineal glandoma), glioblastoma pleomorphic, oligodendroglioma, Schwann cell tumor, retinoblastoma, congenital tumor), spinal neurofibroma, meningioma, glioma, sarcoma); Gynecology: Uterus (endometrial cancer), cervix (cervical cancer, preneoplastic cervical malformation), ovaries (ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassifiable cancer), granulosacytic cell tumor, Sertley-Leydig cell tumor, undifferentiated germ cell tumor, malignant teratoma), vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, staphyloid sarcoma (embryonic rhabdomyosarcoma), fallopian tubes (carcinoma); Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes), Hodgkin's disease, non-Hodgkin lymphoma (malignant lymphoma); Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus moles, lipomas, hemangiomas, dermatofibromas, keloids, psoriasis; and Adrenal gland: Neuroblastoma The method according to any one of claims 360 to 371, selected from the following.

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 carcinoma.

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

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

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

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

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

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