Pyrimidine base modulators and their use

Abstract

Compounds such as those of formula (I), formula (I-A), formula (I-B) or pharmaceutically acceptable salts of any one of them, which are useful for modulating KRAS GD12 and / or other G12 mutants, are provided herein. In certain embodiments, the disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I) and a pharmaceutically acceptable additive. In certain embodiments, the disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I-A) and a pharmaceutically acceptable additive. In certain embodiments, the disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I-B) and a pharmaceutically acceptable additive. TIFF2025522309000693.tif3353

Description

Technical Field

[0001] Cross-reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 345,794, filed May 25, 2022, U.S. Provisional Patent Application No. 63 / 380,544, filed Oct. 21, 2022, and U.S. Provisional Patent Application No. 63 / 486,934, filed Feb. 24, 2023, the entire contents of each of which are hereby incorporated by reference.

Background Art

[0002] Background of the Invention The low molecular weight GTPase protein Kirsten rat sarcoma 2 virus oncogene homolog (KRAS) is a member of the Ras family of cell signaling switches and regulates the growth and survival of normal and cancer cells (see, for example, Cully, M. and J. Downward, SnapShot: Ras Signaling. Cell, 2008. 133(7): p. 1292-1292 e1). KRAS mutations drive approximately 25% of human cancers through dysregulation of the mitogen-activated protein kinase (MAPK) signaling cascade and other effector pathways (see, for example, Stephen, A.G., et al., Dragging ras back in the ring. Cancer Cell, 2014. 25(3): p. 272-81). Ras has been recognized as a target in cancer for approximately 40 years, but Ras-driven cancers remain the most difficult to treat because they are insensitive to available targeted therapies. Ras, encoded by the three major genes KRAS, NRAS, and HRAS, has the most frequent mutations of any cancer gene. All oncogenic Ras mutations drive the switch to result in the accumulation in the active GTP-bound state. The most common Ras mutation found across human tumor types is KRAS G12D (see, for example, The AACR Project GENIE Consortium. Cancer Discovery, 2017. 7(8): p. 818-831. Dataset Version 4). Activating mutations at codon 12 impair the ability of these low molecular weight GTPases to perform their role of hydrolyzing GTP. This regulatory dysfunction is the basis for initiating and maintaining tumor progression.

[0003] Despite great efforts, small molecules that block effector binding or restore sensitivity to GTPase-activating protein (GAP) have not been identified, although several TESs that activate Ras at the plasma membrane exist. The most common KRAS G12C mutation 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. The KRAS G12D mutation results in an intrinsic rate of GTP hydrolysis that is significantly slower than that of G12C, leading to further constitutive activation. Therefore, pharmacological targeting of the inactive state is likely to achieve similar results for G12D, despite the presence of a similar binding pocket in the GDP state. Furthermore, the cysteine present at the site of the activating mutation provides the cysteine itself for covalent chemistry, while aspartic acid does not provide typical medicinal chemistry approaches for selective covalent modification.

[0004] To potentially exploit the accumulation of KRAS G12D and other mutant variants in the GTP-bound state as a vulnerability while preserving normal Ras function to achieve selective inhibition of cancer cells, it is attractive for small molecule inhibitors to selectively bind to the GTP state and stabilize a conformation that cannot interact with effector proteins and oncogenic signaling. Furthermore, it has been shown that only the constitutive activation of Raf, MEK, and ERK kinases in the MAPK cascade downstream of Ras can bypass the requirement for Ras proteins in proliferative signaling (see, for example, 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-promoting action of Ras in cancer, so selective inhibition of KRAS mutants in this pathway is considered an important functional lead-out for potential clinical benefits of new therapeutic approaches. Therefore, it is necessary to develop a novel inhibitor against KRAS-driven cancers that demonstrates inhibition of MAPK signaling through a mechanism selective for binding to the active GTP-bound state rather than the inactive GDP-bound state. Incorporation by reference All publications, patents, and patent applications cited herein are hereby incorporated by reference in the same manner as if each individual publication, patent, or patent application had been specifically and individually indicated to be incorporated by reference.

Prior art documents

Non-patent literature

[0005]

Non-patent literature 1

[0006] Summary of the Invention In certain embodiments, the present disclosure provides a compound represented by the structure of formula (I): [Chemical Formula] or a pharmaceutically acceptable salt thereof, wherein B is selected from 7- to 15-membered heterocycles and C7-C 15 carbocycles, and the 7- to 15-membered heterocycles and C7-C 15 carbocycles are halogen, -CN, -NO2, =O, -N(R 21 )2, -B(OR 21 )2, -OR 21 , -SR 21 , -S(O)2(R 21 ), -S(O)2N(R 21)2, -NR 21 S(O)2R 21 , -C(O)N(R 21 )2, -C(O)NR 21 OR 21 , -N(R 21 )C(O)R 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(O)OR 21 , -C(O)R 21 , C(O)OR 21 , -OC(O)R 21 , -OC(O)N(R 21 )2, 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 alkenyl, C 2~6 alkynyl, C3 - C 12 each optionally substituted with one or more substituents independently selected from carbocycles and 5 - to 12 - membered heterocycles, R 1 is selected from hydrogen and 5 - to 15 - membered heterocycles, and the 5 - to 15 - membered heterocycle is 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 1~6 alkyl(=NOR 20 ), -C(O)NR 20 OR20 , -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 alkoxyalkyl, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C3-C 12 is optionally substituted by one or more substituents independently selected from carbocycles and 5- to 12-membered heterocycles, and C3-C 12 carbocycles and 5- to 12-membered heterocycles are each optionally, independently substituted by one or more R 1* s, and R 1* s are each 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 OR20 ,-N(R 20 )C(O)R 20 ,-N(R 20 )C(O)N(R 20 )2,-N(R 20 )C(O)OR 20 ,-N(R 20 )2,-C(O)R 20 ,-C(O)OR 20 ,-OC(O)R 20 ,-OC(O)N(R 20 )2,-NO2,=O,=N(R 20 )、=NO(R 20 )、-CN、-NHCN、C 1~6 alkyl-N(R 20 )2、C 1~6 aminoalkyl、C 1~6 alkoxy、C 1~6 hydroxyalkyl、C 1~6 cyanoalkyl、C 1~6 haloalkyl、C 1~6 alkyl、C 2~6 alkenyl、C 2~6 alkynyl、and C3 - C 12 are independently selected from carbon rings, Y is selected from a bond, -O-, -S- and -N(R 5 )-, R 2 is a heterocyclic ring, aryl, C1 - C6 alkyl, -L-heterocyclic ring, -L-N(R 23 )2, -L-OR 23 , -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH2, -L-C(O)N(R 23 )2, -L-C1 - C6 haloalkyl, -L-OR 23 , -L-NR 23 C(O)-aryl, -L-COOH, -L-NR 23 S(O)2(R 23 ), -L-S(O)2N(R 23 )2, -L-N(R 23 )C(O)(OR 23 ), -L-OC(O)N(R 23)2 and -L-C(=O)OC1-C6 alkyl, the heterocyclic ring, the heterocyclic ring moiety of -L-heterocyclic ring and the cycloalkyl moiety of -L-cycloalkyl are each optionally substituted by one or more R 6 ; aryl, -L-NR 23 C(O)-aryl aryl moiety, -L-NR 23 C(O)-aryl aryl moiety, -L-aryl aryl and -L-heteroaryl heteroaryl are each optionally substituted by one or more R 7 ; R 3 is hydrogen, halogen, -CN, -NO2, -N(R 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, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -OC(O)N(R 20 )2, 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 alkenyl, C 2~6 alkynyl, C3-C 12Selected from a carbon ring and a 5- to 12-membered heterocyclic ring, R 4 each represents halogen, -NO2, =O, =S, -CN, C 1~6 alkyl, C 2~6 alkynyl, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 cyanoalkyl, C 1~6 hydroxyalkyl and C 1~6 haloalkyl, independently selected from n is selected from 0, 1, 2, 3, and 4, R 5 each represents hydrogen and C1-C6 alkyl, independently selected from R 6 each represents 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、-C1-C3 alkyl-N(R 5 )2、-C(O)N(R 5 )2、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, -OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl(C1-C3 alkyl)N(CH3)2, -OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl, -OC(O)heterocyclic ring, -O-C1-C3 alkyl, -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 and independently selected from -CH2 heterocyclic ring, the phenyl of -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C1-C3 alkyl)phenyl is optionally substituted by one or more substituents selected from -C(O)H and OH, the alkyl of -O-C1-C3 alkyl is optionally substituted by a substituent selected from heterocyclic ring, oxo and hydroxy, the heterocyclic ring of -CH2 heterocyclyl is optionally substituted by oxo, Each Q is independently selected from a bond, S and O, R 7 Each is independently selected from halogen, hydroxy, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, -C1-C3 alkyl-N(R 5 )2, -C(O)N(R 5 )2 and -N(R 5 )2, Each L is independently selected from a C1-C4 alkylene optionally substituted by one or more substituents independently selected from halogen, hydroxy, C 1~6 alkoxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbocyclic ring and 3-8 membered heterocyclic ring, and the C3-C6 carbocyclic ring and 3-8 membered heterocyclic ring are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 optionally substituted by one or more substituents independently selected from haloalkyl, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or a 3- to 8-membered heterocyclic ring, and the C3-C6 carbocyclic ring and the 3- to 8-membered heterocyclic ring are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl and C 1~6 optionally substituted by one or more substituents independently selected from haloalkyl, R 20 each is hydrogen; and C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~12 independently selected from carbocyclic rings and 3- to 12-membered heterocyclic rings, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 optionally substituted by one or more substituents independently selected from carbocyclic rings and 3- to 12-membered heterocyclic rings, R 21 each is hydrogen; and C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~12 independently selected from carbocyclic rings and 3- to 12-membered heterocyclic rings, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12Optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocyclic ring, R 23 each represents hydrogen; and C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~12 independently selected from a carbon ring and a 3- to 12-membered heterocyclic ring, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocyclic ring).

[0007] In an aspect, the present disclosure provides a compound of formula (I-A)

Chemical formula

[0008] In certain embodiments, formula (I-A) is formula (I-B)

Chemical formula

Chemical formula

[0009] In certain embodiments, the present disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I) and a pharmaceutically acceptable additive. In certain embodiments, the present disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I-A) and a pharmaceutically acceptable additive. In certain embodiments, the present disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I-B) and a pharmaceutically acceptable additive.

[0010] In certain embodiments, the present disclosure provides a method of treating a disease or disorder using a compound or salt of formula (I). In certain embodiments, the present disclosure provides a method of treating a disease or disorder using a compound or salt of formula (I) and a pharmaceutically acceptable additive. In certain embodiments, the present disclosure provides a method of treating a disease or disorder using a pharmaceutical composition comprising a compound or salt of formula (I).

[0011] In certain embodiments, the present disclosure provides methods of treating a disease or disorder using a compound or salt of formula (I-A). In certain embodiments, the present disclosure provides methods of treating a disease or disorder using a compound or salt of formula (I-A) and a pharmaceutically acceptable additive. In certain embodiments, the present disclosure provides methods of treating a disease or disorder using a pharmaceutical composition comprising a compound or salt of formula (I-A).

[0012] In certain embodiments, the present disclosure provides methods of inhibiting KRas G12D and / or other G12 mutants using a compound or salt of formula (I). In certain embodiments, the present disclosure provides methods of inhibiting KRas G12D and / or other G12 mutants using a compound or salt of formula (I) and a pharmaceutically acceptable additive. In certain embodiments, the present disclosure provides methods of inhibiting KRas G12D and / or other G12 mutants using a pharmaceutical composition comprising a compound or salt of formula (I) and a pharmaceutically acceptable additive.

[0013] In certain embodiments, the present disclosure provides methods of inhibiting KRas G12D and / or other G12 mutants using a compound or salt of formula (I-A). In certain embodiments, the present disclosure provides methods of inhibiting KRas G12D and / or other G12 mutants using a compound or salt of formula (I-A) and a pharmaceutically acceptable additive. In certain embodiments, the present disclosure provides methods of inhibiting KRas G12D and / or other G12 mutants using a pharmaceutical composition comprising a compound or salt of formula (I-A) and a pharmaceutically acceptable additive. DETAILED DESCRIPTION OF THE INVENTION

[0014] Detailed Description of the Invention Preferred embodiments of the present invention are shown and described herein, but it will be apparent to those skilled in the art that such embodiments are presented by way of example only. Without departing from the present invention, numerous variations, modifications, and substitutions will now occur to those skilled in the art. It should be understood that various alternatives to the embodiments of the invention described herein may be used in practicing the invention. The following claims are intended to define the scope of the present invention, and the methods and structures within the scope of these claims and their equivalents are intended to be covered thereby. Definition

[0015] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications mentioned herein are incorporated by reference.

[0016] As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0017] The term "C x~y ", when used in conjunction with a chemical moiety such as alkyl, alkenyl, or alkynyl, is intended to include groups containing x to y carbons in the chain. For example, the term "C 1~6 alkyl" refers to saturated hydrocarbon groups including straight-chain alkyl groups and branched-chain alkyl groups containing 1 to 6 carbons. For example, -C 1~6 alkyl- can be selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl, any one of which may be optionally substituted. The term -C x~y alkylene- refers to a substituted or unsubstituted alkylene chain containing x to y carbons in the alkylene chain. For example, -C 1~6 alkylene- can be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which may be optionally substituted.

[0018] As used herein, "alkyl" consists only of carbon and hydrogen atoms, contains no unsaturation, and preferably has 1 to 15 carbon atoms, and is a linear or branched hydrocarbon chain radical (i.e., C1-C 15 alkyl). In certain embodiments, alkyl contains 1 to 13 carbon atoms (i.e., C1-C 13 alkyl). In certain embodiments, alkyl contains 1 to 8 carbon atoms (i.e., C1-C8 alkyl). In other embodiments, alkyl contains 1 to 5 carbon atoms (i.e., C1-C5 alkyl). In other embodiments, alkyl contains 1 to 4 carbon atoms (i.e., C1-C4 alkyl). In other embodiments, alkyl contains 1 to 3 carbon atoms (i.e., C1-C3 alkyl). In other embodiments, alkyl contains 1 to 2 carbon atoms (i.e., C1-C2 alkyl). In other embodiments, alkyl contains 1 carbon atom (i.e., C1 alkyl). In other embodiments, alkyl contains 5 to 15 carbon atoms (i.e., C5-C 15 alkyl). In other embodiments, alkyl contains 5 to 8 carbon atoms (i.e., C5-C8 alkyl). In other embodiments, alkyl contains 2 to 5 carbon atoms (i.e., C2-C5 alkyl). In other embodiments, alkyl contains 3 to 5 carbon atoms (i.e., C3-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), 1-pentyl (n-pentyl). Alkyl is attached to the remainder of the molecule by a single bond.

[0019] As used herein, "alkenyl" consists only of carbon and hydrogen atoms, contains at least one carbon-carbon double bond, and preferably has 2 to 12 carbon atoms, and is a linear or branched hydrocarbon chain radical group (i.e., C2-C12 refers to "(alkenyl)". In certain embodiments, alkenyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkenyl). In certain embodiments, alkenyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, alkenyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkenyl). The alkenyl is bonded to the rest of the molecule by a single bond and examples include ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like.

[0020] As used herein, "alkynyl" refers to a linear or branched hydrocarbon chain radical group consisting of only carbon atoms and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms (i.e., C2-C 12 alkynyl). In certain embodiments, alkynyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, alkynyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, alkynyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkynyl). The alkynyl is bonded to the rest of the molecule by a single bond and examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0021] The term "C x~y alkenyl" and "C x~y alkynyl", as used herein, are similar to the alkyl described above in terms of length and possible substitutions, but each refers to a substituted or unsubstituted unsaturated aliphatic group containing at least one double bond or triple bond. The term -C x~y alkenylene- refers to a substituted or unsubstituted alkenylene chain containing x to y carbons in the alkenylene chain. For example, -C 2~6Alkenylene- can be selected from ethenylene, propenylene, butenylene, pentenylene and hexenylene, and any one of these can be optionally substituted. The alkenylene chain may have one double bond, or more than one double bond, in the alkenylene chain. The term -C x~y Alkynylene- refers to a substituted or unsubstituted alkynylene chain containing x to y carbons in the alkenylene chain. For example, -C 2~6 Alkynylene- can be selected from ethynylene, propynylene, butynylene, pentynylene and hexynylene, and any one of these can be optionally substituted. The alkynylene chain may have one triple bond, or more than one triple bond, in the alkynylene chain.

[0022] "Alkylene" refers to a linear divalent hydrocarbon chain that connects the remainder of the molecule to a radical group, consisting only of carbon and hydrogen, containing no unsaturation, and preferably having 1 to 12 carbon atoms, such as methylene, ethylene, propylene, butylene, etc. The alkylene chain is bonded to the remainder of the molecule and to the radical group via single bonds. The points of attachment of the alkylene chain to the remainder of the molecule and to the radical group are each via a terminal carbon. In other embodiments, alkylene contains 1 to 5 carbon atoms (i.e., C1-C5 alkylene). In other embodiments, alkylene contains 1 to 4 carbon atoms (i.e., C1-C4 alkylene). In other embodiments, alkylene contains 1 to 3 carbon atoms (i.e., C1-C3 alkylene). In other embodiments, alkylene contains 1 to 2 carbon atoms (i.e., C1-C2 alkylene). In other embodiments, alkylene contains 1 carbon atom (i.e., C1 alkylene). In other embodiments, alkylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkylene). In other embodiments, alkylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkylene). In other embodiments, alkylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkylene). Unless specifically specified otherwise herein, the alkylene chain is optionally substituted by one or more substituents such as those described herein.

[0023] "Alkenylene" refers to a linear divalent hydrocarbon chain that links the remainder of the 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 a single bond and to the radical group via a single bond. The points of attachment of the alkenylene chain to the remainder of the molecule and to the radical group are each via a terminal carbon. In other embodiments, alkenylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkenylene). In other embodiments, alkenylene contains 2 to 4 carbon atoms (i.e., C2-C4 alkenylene). In other embodiments, alkenylene contains 2 to 3 carbon atoms (i.e., C2-C3 alkenylene). In other embodiments, alkenylene contains 2 carbon atoms (i.e., C2 alkenylene). In other embodiments, alkenylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkenylene). In other embodiments, alkenylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkenylene). Unless specifically specified otherwise herein, the alkenylene chain is optionally substituted by one or more substituents such as those described herein.

[0024] "Alkynylene" refers to a linear divalent hydrocarbon chain that connects the remainder of the 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 a single bond and to the radical group via a single bond. The points of attachment of the alkynylene chain to the remainder of the molecule and to the radical group are each via a terminal carbon. In other embodiments, alkynylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, alkynylene contains 2 to 4 carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, alkynylene contains 2 to 3 carbon atoms (i.e., C2-C3 alkynylene). In other embodiments, alkynylene contains 2 carbon atoms (i.e., C2 alkynylene). In other embodiments, alkynylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, alkynylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkynylene). Unless specifically stated otherwise herein, the alkynylene chain is optionally substituted by one or more substituents such as those described herein.

[0025] "Halo" or "halogen", as used herein, refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents.

[0026] "Haloalkyl", as used herein, refers to an alkyl radical as defined above that is substituted by one or more halogen radicals, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. Examples of haloalkanes include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), dihalomethanes and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, and any other suitable combination of an alkane (or substituted alkane) and a halogen. When an alkyl group is substituted by more than one halogen radical, each halogen may be independently selected, for example, 1-chloro,2-bromoethane.

[0027] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above.

[0028] "Fluoroalkyl" refers to an alkyl radical as defined above that is substituted by one or more fluoro radicals, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like.

[0029] "Aminoalkyl" refers to an alkyl radical as defined above that is substituted by one or more amine radicals, for example, propane-2-amine, butane-1,2-diamine, pentane-1,2,4-triamine, and the like.

[0030] "Hydroxyalkyl" refers to an alkyl radical as defined above that is substituted by one or more hydroxy radicals, for example, propane-1-ol, butane-1,4-diol, pentane-1,2,4-triol, and the like.

[0031] "Alkoxyalkyl" refers to an alkyl radical as defined above substituted by one or more alkoxy radicals, for example, methoxymethane, 1,3-dimethoxybutane, 1-methoxypropane, 2-ethoxypentane, and the like.

[0032] "Cyanoalkyl", as used herein, refers to an alkyl radical as defined above substituted by one or more cyano radicals, for example, acetonitrile, 2-ethyl-3-methylsuccinonitrile, butyronitrile, and the like.

[0033] The term "carbocyclic ring", as used herein, refers to a saturated, unsaturated or aromatic ring in which each atom of the ring is a carbon atom. Carbocyclic rings include monocyclic rings of 3 to 10 members, bicyclic rings of 6 to 12 members and bridged rings of 6 to 12 members. Each ring of a bicyclic carbocyclic ring can be selected from saturated, unsaturated and aromatic rings. In an exemplary embodiment, an aromatic ring, such as phenyl, may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane or cyclohexene. Bicyclic carbocyclic rings include bicyclic rings of any combination of saturated, unsaturated and aromatic groups permitted by valence. Bicyclic carbocyclic rings 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. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl and naphthyl. Bicyclic carbocyclic rings may be fused ring systems, bridged ring systems or spiro ring systems. In some cases, the carbocyclic ring of a spiro ring has at least two molecular rings having only one shared atom.

[0034] As used herein, "aryl" refers to a radical derived from an aromatic monocyclic hydrocarbon ring system or an aromatic polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic polycyclic hydrocarbon ring system contains only hydrogen and carbon (5 to 18 carbon atoms), and at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic delocalized (4n + 2)π electron system that follows Hückel's theory. The ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene.

[0035] The term "unsaturated carbocyclic" refers to a carbocyclic ring having at least one degree of unsaturation and excluding aromatic carbocyclic rings. Examples of unsaturated carbocyclic rings include cyclohexadiene, cyclohexene, and cyclopentene.

[0036] "Cycloalkyl" refers to a fully saturated monocyclic or polycyclic hydrocarbon radical consisting only of carbon atoms and hydrogen atoms, which radical includes fused ring systems or bridged ring systems and preferably has 3 to 12 carbon atoms. In certain embodiments, cycloalkyl contains 3 to 10 carbon atoms. In other embodiments, cycloalkyl contains 5 to 7 carbon atoms. Cycloalkyl may be attached to the remainder of the molecule by a single bond. Examples of monocyclic cycloalkyl 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), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like.

[0037] The term "C x~y carbocyclic" is intended to include groups containing x to y carbons in the ring. For example, the term "C 3~6 carbocyclic" refers to a saturated, unsaturated, or aromatic ring containing 3 to 6 carbons. For example, -C 3~6The carbocyclene can be selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl, and any one of these may be optionally substituted.

[0038] The term "carbocyclene" refers to a divalent ring consisting only of carbon atoms and hydrogen atoms that connects the remainder of the molecule to a radical group. The carbocyclene is bonded to the remainder of the molecule via a single bond and to the radical group via a single bond. The bonding points of the carbocyclene are each for the remainder of the molecule and the radical group, and are by any two carbon atoms. The carbocyclene includes arylene and cycloalkylene. Thus, this term distinguishes the carbocyclene from a heterocyclene in which the divalent ring contains at least one atom different from a carbon atom. The heterocyclene is bonded to the remainder of the molecule via a single bond and to the radical group via a single bond. The bonding points of the heterocyclene are each for the remainder of the molecule and the radical group via any two atoms allowed by the valence. The heterocyclene includes heteroarylene and heterocycloalkylene. The carbocyclene and the heterocyclene may each be optionally substituted by one or more substituents such as those described herein.

[0039] As used herein, the term "heterocyclic ring" 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 heterocyclic ring may be attached to the remainder of the molecule via any atom of the heterocyclic ring, such as a carbon atom or a nitrogen atom of the heterocyclic ring, as permitted by its valence. The heterocyclic rings include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings and 6- to 12-membered bridged rings. The bicyclic heterocyclic rings include any combination of saturated, unsaturated and aromatic bicyclic rings as permitted by their valence. In an exemplary embodiment, an aromatic ring, such as pyridyl, may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, morpholine, piperidine or cyclohexene. The bicyclic heterocyclic rings 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. The bicyclic heterocyclic ring may be a fused ring system, a bridged ring system or a spiro ring system. The spiro-ring system may be referred to as a "spiroheterocycle", "spiro heterocycle" or "spiro-heterocycle". In some cases, a spiro-heterocycle, spiro heterocycle or spiroheterocycle has at least two molecular rings having only one shared atom. The spiro-heterocycle, spiro heterocycle or spiroheterocycle contains one or more heteroatoms.

[0040] "Heteroaryl" or "aromatic heterocycle" refers to a radical derived from a heteroaromatic ring containing 1 to 11 carbon atoms and at least one heteroatom, where each heteroatom can be selected from N, O, and S. As used herein, a heteroaryl ring may be selected from monocyclic or bicyclic ring systems, and fused or bridged ring systems of rings, with at least one of the rings in the ring system being aromatic, i.e., it contains a cyclic delocalized (4n + 2)π electron system that follows Hückel's theory. The heteroatom(s) in the heteroaryl radical may optionally be oxidized. One or more nitrogen atoms, if present, may optionally be quaternized. Heteroaryl may be attached to the remainder of the molecule via any atom of the heteroaryl, such as a carbon atom or nitrogen atom of the heteroaryl, as permitted by its valence. Examples of heteroaryl include, but are not limited to, pyridine, pyrimidine, oxazole, furan, thiophene, benzthiazole, and imdazopyridine.

[0041] "X-membered heteroaryl" refers to the number of atoms in the ring, i.e., X in the ring. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 ring atoms, such as triazole, oxazole, thiophene, etc.

[0042] 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 optionally be substituted by one or more substituents, such as those described herein.

[0043] "Replaced" means that the moiety has a substituent that replaces a hydrogen on one or more carbons of the compound or on a replaceable heteroatom, such as on NH or NH2. "Substituted" or "substituted by" is understood to imply that such substitution follows the allowed valences of the atoms being substituted and the substituents, and that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo conversions such as rearrangement, cyclization, elimination, etc. In certain embodiments, "replaced" means that the moiety has a substituent that replaces two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon by an oxo, imino, or thioxo group. As used herein, the term "substituted" is intended to include all allowed substituents of organic compounds. In a broad aspect, allowed substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. Allowed substituents can be one or more and can be the same or different for a given organic compound.

[0044] As used herein, the terms "optional" or "optionally" mean that the event or circumstance described thereafter may or may not occur, and the description includes the cases where the event or circumstance occurs and where they do not occur. For example, "optionally substituted aryl" means that the aryl group may or may not be substituted, and the description includes both substituted aryl groups and aryl groups having no substitution.

[0045] As used herein, the term "electrophile" or "electrophilic moiety" refers to any moiety capable of reacting with a nucleophile (e.g., a lone pair of electrons, a negative charge, a partial negative charge, and / or an excess of electrons, e.g., a moiety having a -SH group). Electrophiles are typically electron-deficient or contain an electron-deficient atom. In certain embodiments, the electrophile contains a positive charge or a partial positive charge, has a resonance structure containing a positive charge or a partial positive charge, or is a moiety in which one or more atoms containing a positive charge or a partial positive charge are brought about by delocalization or polarization of electrons. In some embodiments, the electrophile includes a conjugated double bond, e.g., an α,β-unsaturated carbonyl compound or an α,β-unsaturated thiocarbonyl compound.

[0046] In some embodiments, the substituent is any substituent described herein, e.g., halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=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 -O-R 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) tR a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2); and can include alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl, any of which can be alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO2), imino(=N-H), oxime(=N-OH), hydrazine(=N-NH2), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -O-R c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (where t is 1 or 2), -Rb -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2) and -R b -S(O) t N(R a )2 (t is 1 or 2) may be optionally substituted, R a each is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl, R a each is, valence permitting, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO2), imino(=N-H), oxime(=N-OH), hydrazine(=N-NH2), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -O-R 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 OR a (t is 1 or 2) and -R b -S(O) t N(R a )2 (t is 1 or 2) may be optionally substituted, and R b are each independently selected from a direct bond or a linear or branched alkylene, alkenylene or alkynylene chain, and R c are each a linear or branched alkylene, alkenylene or alkynylene chain. It will be understood by those skilled in the art that the substituents may themselves be substituted where appropriate.

[0047] The phrase "pharmaceutically acceptable" as used herein refers to compounds, substances, compositions and / or dosage forms that are suitable for use in contact with the tissues of humans and animals within the scope of sound medical judgment, without excessive toxicity, irritation, allergic response or other problems or complications, and commensurate with a reasonable benefit / risk ratio.

[0048] The terms "pharmaceutically acceptable additive" or "pharmaceutically acceptable carrier", as used herein, mean pharmaceutically acceptable substances, compositions or vehicles such as liquid or solid fillers, diluents, excipients, solvents or encapsulating materials. A carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of substances that can serve as pharmaceutically acceptable carriers include: (1) sugars such as lactose, glucose and sucrose; (2) starches such as corn starch and potato starch; (3) cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository waxes; (9) oils such as peanut oil, cottonseed oil, sesame oil, coconut oil, olive oil, corn oil and soybean oil; (10) glycols such as propylene glycol; (11) polyols such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances used in pharmaceutical formulations.

[0049] 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, cows, ungulates, rabbits, etc.). In various embodiments, the subject can be a human (e.g., adult male, adult female, young male, young female, male child, female child) under the care of a physician or other healthcare provider in a foreign patient or other clinical setting. In certain embodiments, the subject may not be under the care or prescription of a physician or other healthcare provider.

[0050] As used herein, the phrase "subject in need thereof" refers to a subject described below that has, or is at risk of having, a pathology that is prophylactically or therapeutically treated by a compound or salt described herein.

[0051] 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, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal or intraperitoneal routes of administration. In certain embodiments, an oral route of administering the composition can be used. It should be understood that "administer", "administered" compound, "administers" compound and "administering" compound mean supplying the compound of the invention or a prodrug of the compound of the invention to an individual in need thereof.

[0052] The term "effective amount" or "therapeutically effective amount" refers to an amount of a compound or salt described herein sufficient to provide a desired use, including but not limited to the disease treatment defined below. A therapeutically effective amount can vary depending on the desired use (in vitro or in vivo), or the subject and disease state being treated, such as the subject's weight and age, the severity of the disease state, the method of administration, etc., which can be readily determined by one of ordinary skill in the art. This term can also apply to a dosage that can induce a specific response in a target cell, such as a decrease in the proliferation of a target protein, or a downregulation of its activity. Specific dosages can vary depending on the particular compound selected, the dosing 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 by which the compound is carried.

[0053] As used herein, "treatment" or "treating" refers to a procedure for obtaining a beneficial or desired result, including therapeutic and / or prophylactic benefits, with respect to a disease, disorder or medical condition, without being limited to the following. In certain embodiments, treatment or treating includes administering a compound or composition disclosed herein to a subject. Therapeutic benefits can include eradication or amelioration of the underlying disorder being treated. Similarly, therapeutic benefits can be achieved by eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such as when improvement is observed in the subject even though the subject may still be suffering from the underlying disorder. In certain embodiments, for prophylactic benefit, the composition is administered to a subject at risk of developing a particular disease or a subject who has reported one or more of the physiological symptoms of such a disease even if the disease has not been diagnosed. Treating can include, for example, reducing, delaying or alleviating the severity of one or more symptoms of a disease or condition, or treating can include reducing the frequency of symptoms such as diseases, defects, disorders or adverse conditions experienced by a patient. Treating can be used herein to refer to a method that provides a certain level of treatment or improvement of a disease or condition, and can contemplate a range of end results including, but not limited to, complete prevention of the condition.

[0054] In certain embodiments, the term "prevent" or "preventing" associated with a disease or disorder can refer to a compound that reduces the occurrence of a disorder or condition in a treated sample compared to an untreated control sample, or delays the occurrence of a disorder or condition or reduces the severity of one or more of their symptoms in a treated sample compared to an untreated control sample, in a statistical sample.

[0055] "Therapeutic effect", as the term is used herein, encompasses the above-described therapeutic and / or prophylactic benefits. Prophylactic effects include delaying or eliminating the onset of a disease or condition, delaying or eliminating the occurrence of symptoms of a disease or condition, slowing, stopping or reversing the progression of a disease or condition, or any combination thereof.

[0056] As used herein, "sum frequency generation" (SFG) is a non-linear optical technique by which light at one frequency (Ω1) is mixed with light at another frequency (Ω2) to produce a response at the sum frequency (Ω1+Ω2) (Shen, 1984, 1989). For example, SFG is particularly useful for detecting molecules on a surface by their vibrational transitions, in which case it is essentially surface selective infrared spectroscopy by Ω1 and Ω2 at visible and infrared frequencies. When the terms "SHG" or "second harmonic generation" are used herein, it is understood that SFG and "sum frequency generation" can be substituted and used in place of SHG by methods well known to those skilled in the art.

[0057] "Second harmonic active moiety" or "second harmonic active moiety", as used herein, refers to a non-linear active moiety, particle or molecule that can be attached (covalently or non-covalently) to a molecule (e.g., a protein such as an enzyme), particle or phase (e.g., a lipid bilayer) to render it non-linearly optically active.

[0058] "Non-linear active moiety", as used herein, refers to a substance having a hyperpolarizability.

[0059] "Hyperpolarizability" or "non-linear susceptibility", as used herein, refers to the property of a molecule, particle, interface or phase that is capable of generating non-linear light. The terms "hyperpolarizability", "second-order non-linear polarizability" and "non-linear susceptibility" are sometimes used interchangeably.

[0060] As used herein, the terms "allosteric", "allosteric modulator" or "allosteric candidate" refer to a molecule, moiety or substance that binds primarily to a site other than the active site, causes a conformational change that can be determined by SHG or SFG, and thus exerts its effect by an allosteric mechanism.

[0061] As used herein, the terms "inhibit", "selectively inhibit" or "selectively inhibits" when referring to a bioactive agent, refer to the ability of an agent to preferentially reduce target signaling activity relative to off-target signaling activity, either directly or through interaction with the target.

[0062] As used herein, the terms "targeting agent" or "targeted therapy" refer to a treatment method that uses a specific drug to target a specific gene, protein or active site involved in the development, survival and proliferation of cancer cells.

[0063] It is intended that every numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were all expressly written herein. Every numerical limitation given throughout this specification includes every higher numerical limitation, as if such higher numerical limitations were all expressly written herein. Every numerical range given throughout this specification includes every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

[0064] The headings of the items used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. Compound

[0065] In certain embodiments, the disclosure relates to a structure of formula (I):

Chemical Formula

[0066] In some embodiments of the compound or salt of formula (I), B is a 7- to 15-membered fused heterocycle optionally substituted and a C7-C 15 selected from fused carbocycles. In some cases, and a C7-C 15 fused carbocycle. In some cases, B is a 7- to 15-membered fused heterocycle optionally substituted. In some cases, B is an optionally substituted 7- to 15-membered unsaturated fused heterocycle. In some cases, B is an optionally substituted 7- to 15-membered fused heteroaryl. In some cases, B is selected from an optionally substituted 7- to 15-membered fused heteroaryl and an optionally substituted C7-C 15 selected from fused aryls. In some cases, B is an optionally substituted unsaturated C7-C15 It is a condensed carbon ring. In some cases, B is a 7- to 15-membered condensed heterocyclic ring which is optionally substituted, and the condensed heterocyclic ring is partially unsaturated. In some cases, B is a 7- to 15-membered condensed heterocyclic ring which is optionally substituted, and the condensed heterocyclic ring is partially saturated.

[0067] In some embodiments of the compound or salt of formula (I), B is an 8- to 15-membered condensed heterocyclic ring which is optionally substituted and C8-C which is optionally substituted 15 Selected from condensed carbon rings. In some cases, and C8-C which is optionally substituted 15 Condensed carbon ring. In some cases, B is an 8- to 15-membered condensed heterocyclic ring which is optionally substituted. In some cases, B is an 8- to 15-membered unsaturated condensed heterocyclic ring which is optionally substituted. In some cases, B is an 8- to 15-membered condensed heteroaryl which is optionally substituted. In some cases, B is an 8- to 15-membered condensed heteroaryl which is optionally substituted and C8-C which is optionally substituted 15 Selected from condensed aryls. In some cases, B is unsaturated C8-C which is optionally substituted 15 It is a condensed carbon ring. In some cases, B is an 8- to 15-membered condensed heterocyclic ring which is optionally substituted, and the condensed heterocyclic ring is partially unsaturated. In some cases, B is an 8- to 15-membered condensed heterocyclic ring which is optionally substituted, and the condensed heterocyclic ring is partially saturated.

[0068] In some embodiments of the compound or salt of formula (I), B is selected from 8- to 15-membered condensed heterocyclic rings which are optionally substituted, and the condensed heterocyclic ring is formed by three rings joining together (for example, tricyclic). In some cases, B is selected from 8- to 15-membered condensed heterocyclic rings which are optionally substituted, and the condensed heterocyclic ring is formed by two rings joining together (for example, bicyclic). In some cases, with respect to B, 8- to 15-membered condensed heterocyclic rings which are optionally substituted and C8-C which is optionally substituted 15The fused carbon rings are each independently bicyclic or tricyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic ring is bicyclic. In some cases, for B, the optionally substituted 8- to 15-membered fused heterocyclic ring is tricyclic.

[0069] In some embodiments of the compound or salt of formula (I), the heterocyclic or carbon ring of B is bicyclic. In some cases, the heterocyclic or carbon ring of B is tricyclic. In some cases, the tricyclic heterocyclic ring contains three interconnected rings of atoms.

[0070] In some embodiments of the compound or salt of formula (I), for B, the heterocyclic ring and the carbon ring are each independently selected from bicyclic and tricyclic. In some cases, for B, the heterocyclic ring and the carbon ring are each independently tricyclic. In some cases, for B, the heterocyclic ring and the carbon ring are each independently bicyclic.

[0071] In some embodiments of the compound or salt of formula (I), for B, the optionally substituted 8- to 15-membered fused heterocyclic ring and the optionally substituted C8-C 15 The fused carbon ring is

Chem.

Chem.

Chem.

Chemical formula

Chemical formula

[0072] In some embodiments of the compound or salt of formula (I), B is

Chemical formula

Chemical formula

[0073] In some embodiments of the compound or salt of formula (I), for B, the optional substituents of the heterocyclic ring and the carbocyclic ring are halogen, -CN, -NO2, =O, -N(R 21 )2, -B(OR 21 )2, -OR 21 , -SR 21 , 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 alkenyl, C 2~6 alkynyl, C3-C 12It is independently selected from a carbon ring and a 5- to 12-membered heterocyclic ring. In some cases, the optionally substituted groups of the heterocyclic ring and the carbon ring are halogen, -CN, -NO2, =O, -N(R 21 )2, -B(OR 21 )2, -OH, -SR 21 , 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 alkenyl and C 2~6 alkynyl are each independently selected. In some cases, for B, one or more optionally substituted groups of the heterocyclic ring and the carbon ring are 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 alkynyl are each independently selected for each occurrence. In some cases, the optionally substituted groups of the heterocyclic ring and the carbon ring are halogen, -CN, =O, -NH2, -N(C 1~6 alkyl)H N(C 1~6 alkyl)2, -OH, 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 alkenyl and C 2~6 alkynyl are each independently selected. In some cases, one or more optionally substituted groups of the heterocyclic ring and the carbon ring are oxo, -NH2, halogen, C1-C3 alkyl, each independently selected. In some cases, for B, an optionally substituted 8- to 15-membered fused heterocyclic ring and an optionally substituted C8-C 15 fused carbon ring are [Chem.] selected from. In some cases, B is [Chem.] selected from. In some cases, B is [Chem.] [Chem.] selected from. In some cases, B is [Chem.] selected from.

[0074] In some embodiments of the compound or salt of formula (I), B is a 7- to 12-membered fused heterocycle optionally substituted and a C 9~10 selected from fused carbocycles. In some cases, the heterocycle of B has at least one sulfur atom. In some cases, the heterocycle of B has one or more sulfur atoms. In some cases, the heterocycle of B has at least one nitrogen atom. In some cases, B is [Chem.] selected from, each of which is optionally substituted. In some cases, one or more optional substituents of B are 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 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl, C 1~6 haloalkyl, C 2~6 alkenyl and C 2~6Independently selected each time it appears from alkynyl. In some cases, one or more optional substituents of B are independently selected each time it appears from halogen, C1-C3 alkyl, -OH, -NH2, =O and -CN. In some cases, B is

Chemical formula

[0075] In some embodiments relating to the compound or salt of formula (I), B is selected from optionally substituted 8- to 10-membered fused heterocycles having at least one sulfur atom. In some cases, B is

Chemical formula

Chemical formula

Chemical formula

[0076] In some embodiments of the compounds or salts of formula (I), B is a 7- to 11-membered fused heterocyclic ring optionally substituted. In some cases, B is an 8- to 10-membered fused heterocyclic ring optionally substituted. In some cases, B is a 7-membered fused heterocyclic ring optionally substituted. In some cases, B is an 8-membered fused heterocyclic ring optionally substituted. In some cases, B is a 9-membered fused heterocyclic ring optionally substituted. In some cases, B is a 10-membered fused heterocyclic ring optionally substituted. In some cases, the heterocyclic ring of B is an unsaturated heterocyclic ring. In some cases, the heterocyclic ring of B is a non-aromatic heterocyclic ring. In some cases, B has at least one sulfur atom. In some cases, B has two sulfur atoms. In some cases, B has at least one sulfur atom and at least one nitrogen atom. In some cases, B has at least one sulfur atom and at least one oxygen atom. In some cases, B has only one heteroatom. In some cases, B has at least two heteroatoms. In some cases, B is [Chemical formula] selected from, each of which is optionally substituted. In some cases, B is [Chemical formula] [Chemical formula] selected from, each of which is optionally substituted. In some cases, B is [Chemical formula] selected from, each of which is optionally substituted. In some cases, one or more optional substituents of B are halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -O-C1-C3 haloalkyl, -C(O)NH2, -NH2, =O, -CN, C1~6 alkoxy, C 1~6 hydroxyalkyl and C 2~6 are each independently selected at each occurrence from alkynyl. In some cases, one or more optional substituents of B are each independently selected at each occurrence from halogen, C1-C3 alkyl, -NH2 and -CN. In some cases, B is substituted with at least 3 substituents. In some cases, B is substituted with at least 2 substituents. In some cases, B is substituted with at least 1 substituent. In some cases, B is substituted with at least 1 substituent selected from halogen, C1-C3 alkyl, -NH2 and -CN. In some cases, B is substituted with at least 1 substituent selected from halogen. In some cases, B is substituted with at least 1 substituent selected from -NH2. In some cases, B is substituted with at least 1 substituent selected from -CN. In some cases, B is

Chemical formula

[0077] In some embodiments relating to the compound or salt of formula (I), R 3 is hydrogen, halogen, -CN, -NO2, -N(R 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 , -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -OC(O)N(R 20 )2, C 1~6Aminoalkyl, 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 Alkenyl, C 2~6 selected from alkynyl. In some cases, R 3 is hydrogen, halogen, -CN, -NO2, -N(R 20 )2, -OR 20 , -SR 20 , -C(O)N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , 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 Alkenyl, C 2~6 selected from alkynyl. In some cases, R 3 is hydrogen, halogen, -CN, -NO2, -NH2, -N(C 1~6 alkyl)H N(C 1~6 alkyl)2, -OH, -C(O)N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , 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 Alkenyl and C 2~6 selected from alkynyl. In some cases, R 3 is hydrogen, -CN, -C(O)R 20 , C1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Alkoxyalkyl, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl and C 1~6 is selected from alkyl. In some cases, R 3 is hydrogen, -CN, -C(O)R 20 , C 1~6 Hydroxyalkyl and C 1~6 is selected from alkyl. In some cases, R 3 is hydrogen, -CN, -C(O)H, C1 hydroxyalkyl and C 1~6 is selected from alkyl. In some cases, R 3 is selected from hydrogen, fluorine and -CN. In some cases, R 3 is selected from fluorine. In some cases, R 3 is selected from hydrogen. In some cases, R 3 is selected from -CN.

[0078] In some embodiments of the compound or salt of formula (I), Y is -O-. In some cases, Y is a bond. In some cases, Y is -S-. In some cases, Y is -N(R 5 ).

[0079] In some embodiments of the compound or salt of formula (I), L is selected from C1-C4 alkylene. In some cases, L is selected from unsubstituted C1-C4 alkylene. In some cases, L is selected from unsubstituted C1 alkylene. In some cases, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or a 3- to 8-membered heterocyclic ring, and the C3-C6 carbocyclic ring and the 3- to 8-membered heterocyclic ring are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6It is each optionally substituted by one or more substituents independently selected from haloalkyl. In some cases, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or a 3- to 8-membered heterocyclic ring. In some cases, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring. In some embodiments of the compound or salt of formula (I), L is selected from C1-C4 alkylene. In some cases, L is selected from unsubstituted C1-C4 alkylene. In some cases, each L is independently selected from optionally substituted C1-C4 alkylene, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or a 3- to 8-membered heterocyclic ring, and the C3-C6 carbocyclic ring and the 3- to 8-membered heterocyclic ring are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 It is each optionally substituted by one or more substituents selected from haloalkyl. In some cases, the optional substituents of L are selected from C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbocyclic ring, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or a 3- to 8-membered heterocyclic ring, and the C3-C6 carbocyclic ring and the 3- to 8-membered heterocyclic ring are halogen and C 1~6 It is optionally substituted by one or more substituents selected from haloalkyl. In some cases, L is

Chemical formula

Chemical formula

Chem.

Chem.

Chem.

Chem.

[0080] In some embodiments of the compound or salt of formula (I), each L is independently selected from unsubstituted C1-C4 alkylene. In some cases, L is,

Chem.

Chem.

[0081] In some embodiments relating to the compound or salt of formula (I), R 2 is a heterocyclic ring, C1-C6 alkyl, -L-heterocyclic ring, -L-N(R 23 )2, -L-OR 23 , -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-N(R 23 )2, -L-NHC(=NH)NH2, -L-C(O)N(R 23 )2, -L-C1-C6 haloalkyl, -L-OR 23 , -L-NR 23 C(O)-aryl, -L-COOH, -L-NR 23 S(O)2(R 23 ), -L-S(O)2N(R 23 )2, -L-N(R 23 )C(O)(OR 23 ), -L-OC(O)N(R 23 )2 and -L-C(=O)OC1-C6 alkyl, and the heterocyclic ring, the heterocyclic ring moiety of -L-heterocyclic ring and the cycloalkyl moiety of -L-cycloalkyl are each optionally substituted by one or more R 6 , and the aryl moiety of -L-NR 23 C(O)-aryl, the aryl moiety of -L-NR 23 C(O)-aryl, the aryl of -L-aryl and the heteroaryl of -L-heteroaryl are each optionally substituted by one or more R 7 .

[0082] In some embodiments relating to the compound or salt of formula (I), R 2 is selected from a heterocyclic ring, -L-heterocyclic ring, -L-aryl, -L-heteroaryl and -L-N(R 23 )2, and the heterocyclic ring, the heterocyclic ring moiety of -L-heterocyclic ring is each optionally substituted by one or more R 6 , and the aryl of -L-aryl and the heteroaryl of -L-heteroaryl are each optionally substituted by one or more R 7 .

[0083] In some embodiments related to the compound or salt of formula (I), R 2 is -L-heterocyclic, and the heterocyclic moiety is optionally substituted. In some cases, R 2 is -L-heterocyclic, and the heterocyclic moiety is a bicyclic heterocycle. In some cases, R 2 is -L-heterocyclic, and the heterocyclic moiety is a monocyclic heterocycle. In some cases, R 2 is -L-heterocyclic, and the heterocyclic moiety is a saturated heterocycle. In some cases, R 2 is selected from -L-5- to 10-membered heterocycles. In some cases, R 2 is selected from -(C1-C2 alkylene)-5- to 10-membered heterocycles. In some cases, R 2 is selected from -L-5- to 8-membered heterocycles. In some cases, R 2 is selected from -L-5- to 8-membered saturated heterocycles. In some cases, R 2 is -L-5-membered heterocycle. In some cases, R 2 is -L-8-membered heterocycle. In some cases, the heterocycle contains at least one nitrogen atom. In some cases, the heterocycle contains at most one nitrogen atom. In some cases, the heterocycle contains one nitrogen atom. In some cases, the bicyclic heterocycle contains at least one nitrogen atom. In some cases, the bicyclic heterocycle contains at most one nitrogen atom. In some cases, the bicyclic heterocycle contains one nitrogen atom. In some cases, Y-R 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0084] In some embodiments of the compound or salt of formula (I), R 2 is selected from -L-heterocycles which are optionally substituted. 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, Y-R 2 is [Chemical] selected from, and the heterocyclic moiety is optionally substituted. In some cases, Y-R 2 is [Chemical] selected from, and the heterocyclic moiety is optionally substituted. In some cases, Y-R 2 is [Chemical] selected from, and the heterocyclic moiety is optionally substituted. In some cases, Y-R 2 is [Chemical] selected from, and the heterocyclic moiety is optionally substituted. In some cases, the heterocyclic ring is optionally substituted by one or more substituents selected from halogen, hydroxy, 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)heterocyclic ring, -CH2heterocyclic ring, -CH2OC(O)N(R 5 )2 and -O-C1-C3 alkyl, and the alkyl of -O-C1-C3 alkyl is optionally substituted by a substituent selected from heterocyclic ring, oxo and hydroxy. In some cases, the heterocyclic ring is substituted by at least one halogen. In some cases, the heterocyclic ring is substituted by at least one =CH2. In some cases, Y-R 2 is [Chemical] [Chemical] selected from. In some cases, Y-R 2 is [Chemical] is selected from. In some cases, Y-R 2 is [Chemical formula] [Chemical formula] is selected from. In some cases, Y-R 2 is [Chemical formula] is selected from. In some cases, Y-R 2 is [Chemical formula] is selected from.

[0085] In some embodiments of the compound or salt of formula (I), R 2 is -L-heteroaryl, and the heteroaryl moiety is optionally substituted by one or more R 7 In some cases, heteroaryl is selected from 5- to 6-membered heteroaryl, and the heteroaryl moiety is optionally substituted by one or more R 7 In some cases, heteroaryl is selected from 5-membered heteroaryl, and the heteroaryl moiety is optionally substituted by one or more R 7 In some cases, heteroaryl has at least one nitrogen atom. In some cases, heteroaryl has two nitrogen atoms. In some cases, heteroaryl has three nitrogen atoms. In some cases, heteroaryl is [Chemical formula] is selected from, which is optionally substituted. In some cases, heteroaryl is [Chemical formula] and this is optionally substituted. In some cases, Y-R 2 is [Chem.] selected from, and the heteroaryl moiety is optionally substituted by one or more R 7 . In some cases, R 7 is independently selected from C1-C4 alkyl, halogen and C1-C4 haloalkyl respectively. In some cases, Y-R 2 is [Chem.] selected from. In some cases, Y-R 2 is [Chem.] selected from. In some cases, Y-R 2 is [Chem.] selected from.

[0086] In some embodiments of the compound or salt of formula (I), R 2 is -L-aryl optionally substituted by one or more R 7 . In some cases, Y-R 2 is [Chem.] selected from, and the heterocyclic moiety is optionally substituted by one or more R 7 . In some cases, Y-R 2 is [Chem.] selected from.

[0087] In some embodiments of the compound or salt of formula (I), R 2 is -L-N(R23 ) It is 2. In some cases, Y-R 2 is

Chem.

Chem.

Chem.

Chem.

[0088] In some embodiments of the compound or salt of formula (I), R 2 is a heterocyclic ring, -L-heterocyclic ring (the heterocyclic ring parts of the heterocyclic ring and -L-heterocyclic ring are each optionally substituted by one or more R 6 ), -L-aryl and -L-heteroaryl (the aryl of -L-aryl and the heteroaryl of -L-heteroaryl are each optionally substituted by one or more R 7 ), and -L-N(R 23 )2 selected from. In some cases, the heterocyclic ring of R 2 is

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

[0089] In some embodiments of the compound or salt of formula (I), L is independently selected from C1-C4 alkylene optionally substituted with one or more substituents independently selected from hydroxy, C1-C4 hydroxyalkyl, and C1-C4 alkyl. In some cases, L is independently selected from C1-C4 alkylene optionally substituted with one or more substituents independently selected from C1-C4 alkyl. In some cases, L is selected from C1-C4 alkylene. In some cases, L is selected from C1-C2 alkylene. In some cases, L is

Chemical formula

Chemical formula

[0090] In some embodiments of the compound or salt of formula (I), each L is independently selected from C1-C4 alkylene optionally substituted, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring, and the C3-C6 carbocyclic ring is halogen, -OH, -NO2, =O, =S, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 haloalkyl, and is optionally substituted with one or more substituents selected therefrom. In some cases, the optional substituents of L are selected from C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbocyclic ring, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or a 3- to 8-membered heterocyclic ring, and the C3-C6 carbocyclic ring and the 3- to 8-membered heterocyclic ring are halogen and C 1~6 haloalkyl, and is optionally substituted with one or more substituents selected therefrom.

[0091] In some embodiments regarding the compound or salt of formula (I), each L is independently selected from substituted C1-C4 alkylene, and two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring. In some cases, the C3-C6 carbocyclic ring is optionally substituted with one or more substituents selected from halogen, -OH, -NO2, =O, =S, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 haloalkyl.

[0092] In some embodiments regarding the compound or salt of formula (I), each L is independently selected from substituted C1-C4 alkylene, and two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring. In some cases, each L is independently selected from substituted C3 alkylene, and two substituents on the same carbon atom of L together form a C3 carbocyclic ring. In some cases, each L is

Chemical formula

[0093] In some embodiments regarding the compound or salt of formula (I), R 2 is selected from -L-heterocyclic ring, and the heterocyclic ring moiety of the -L-heterocyclic ring is optionally substituted with one or more R 6 . In some cases, the heterocyclic ring is a saturated heterocyclic ring. In some cases, the heterocyclic ring has at least one nitrogen atom and at least one sulfur atom. In some cases, the heterocyclic ring has at least one nitrogen atom. In some cases, the heterocyclic ring has at least one sulfur atom.

[0094] In some embodiments regarding the compound or salt of formula (I), R 2 is

Chemical formula

[0095] In some embodiments of the compound or salt of formula (I), Y-R 2 is

Chemical formula

[0096] In some embodiments of the compound or salt of formula (I), Y-R 2 is

Chemical formula

[0097] In some embodiments of the compound or salt of formula (I), Y-R 2 is

Chemical formula

[0098] In some embodiments of the compound or salt of formula (I), R 2 is selected from -L-saturated heterocycles, and the saturated heterocyclic moiety of the -L-saturated heterocycle is substituted by one or more R 6 as necessary and contains one nitrogen atom and one sulfur atom. In some cases, Y-R 2 is

Chemical formula

[0099] In some embodiments of the compound or salt of formula (I), Y is a bond. In some cases, R 2 is selected from heteroaryl optionally substituted and aryl optionally substituted. In some cases, R 2 is selected from heteroaryl optionally substituted. In some cases, the heteroaryl has at least one nitrogen atom. In some cases, the heteroaryl has at least two nitrogen atoms. In some cases, the heteroaryl contains only nitrogen atom(s). In some cases, the heteroaryl is a 6-membered heteroaryl. In some cases, the heteroaryl is a 5-membered heteroaryl. In some cases, the heteroaryl is [Chemical] selected from, each of which is optionally substituted. In some cases, the heteroaryl is [Chemical] selected from, each of which is optionally substituted. In some cases, R 2 is selected from aryl optionally substituted. In some cases, the aryl is phenyl. In some cases, the heteroaryl is optionally substituted with one or more R 6 and R6 is each independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, -CH2 heterocycle, -C1-C3 alkyl-N(R 5 )2 and -C(O)N(R 5 )2. In some cases, R 6 is selected from C1-C3 alkyl, -CH2 heterocycle and -C(O)N(R 5 )2. In some cases, aryl is optionally substituted by one or more R 7 . In some cases, Y-R 2 is selected from

Chemical formula

Chemical formula

[0100] In some embodiments of the compound or salt of formula (I), Y is -O-, and R 2 is selected from L-5-membered heteroaryl. In some cases, heteroaryl has at least one nitrogen atom. In some cases, heteroaryl has at least two nitrogen atoms. In some cases, heteroaryl has three nitrogen atoms. In some cases, L is selected from optionally substituted C1-C4 alkylene. In some cases, L is independently selected from optionally substituted C1-C4 alkylene, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocycle or a 3- to 8-membered heterocycle, and the C3-C6 carbocycle and the 3- to 8-membered heterocycle are each optionally substituted by one or more substituents selected from halogen, -OH, -NO2, =O, =S, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 haloalkyl. In some cases, L is [Chemical formula] [Chemical formula] selected from. In some cases, L is [Chemical formula] selected from. In some cases, heteroaryl is substituted, if necessary, by one or more R 7 . In some cases, each R 7 is independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkyl. In some cases, Y-R 2 is [Chemical formula] selected from.

[0101] In some embodiments of the compound or salt of formula (I), each R 6 is independently 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-C3 alkyl)O(C1-C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl(C1-C3 alkyl)N(CH3)2, -OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl, -OC(O)heterocycle and -CH2 heterocycle are independently selected, and the phenyl of -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C1-C3 alkyl)phenyl is optionally substituted by -C(O)H and OH respectively, and the heterocycle of -CH2 heterocyclyl is optionally substituted by oxo.

[0102] In some embodiments of the compound or salt of formula (I), R 6 are each independently selected from halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN and C1-C3 aminoalkyl. In some cases, R 6 are each independently selected from halogen, C1-C3 alkyl and C1-C3 haloalkyl.

[0103] In some embodiments of the compound or salt of formula (I), R 6 are each independently selected from halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -N(R 5 )2 and oxo. In some cases, R 6 are each independently selected from -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 aminoalkyl, C1-C3 alkoxy and -N(R 5 )2. In some cases, R 6 are each independently selected from C1-C3 alkyl, C1-C3 alkoxy and -N(R 5 )2. In some cases, R 6 are each independently selected from halogen, hydroxy, C1-C3 alkyl, C1-C3 haloalkyl, -N(R 5 )S(O)2(R 5)、 -OC(O)N(R 5 )2, =CH2, oxo, =NO-C1-C3 alkyl, -CH2OC(O)heterocyclic ring, -CH2heterocyclic ring, -CH2OC(O)N(R 5 )2 and -O-C1-C3 alkyl are independently selected, and the alkyl of -O-C1-C3 alkyl is optionally substituted by a substituent selected from a heterocyclic ring, oxo and hydroxy, and R 7 is each independently selected from C1-C3 alkyl, halogen and C1-C3 haloalkyl.

[0104] In some embodiments of the compound or salt of formula (I), R 6 is selected from halogen, -OH, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, -CN and C1-C3 aminoalkyl. In some cases, R 6 is selected from halogen and C1-C3 alkyl. In some cases, R 6 is halogen. In some cases, R 6 is C1-C3 alkyl. In some cases, R 6 is selected from halogen and C1-C3 alkyl. In some cases, R 6 is selected from methyl and fluorine.

[0105] In some embodiments of the compound or salt of formula (I), R 2 is

Chemical formula

[0106] In some embodiments of the compound or salt of formula (I), Y-R 2 is

Chemical formula

[0107] In some embodiments of the compound or salt of formula (I), Y-R 2 is [Chemical formula] selected from

[0108] In some embodiments of the compound or salt of formula (I), Y-R 2 is [Chemical formula] as follows.

[0109] In some embodiments of the compound or salt of formula (I), L is selected from unsubstituted C1-C4 alkylene.

[0110] In some embodiments of the compound or salt of formula (I), Y-R 2 is [Chemical formula] selected from, and the heterocyclic moiety is optionally substituted by one or more R 6 as required.

[0111] In some embodiments of the compound or salt of formula (I), R 2 of R 6 is independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano and C1-C3 aminoalkyl each time it appears.

[0112] In some embodiments of the compound or salt of formula (I), R 2 of R 6 is independently selected from C1-C3 alkyl and halogen each time it appears.

[0113] In some embodiments of the compound or salt of formula (I), Y-R 2 is [Chemical formula] selected from

[0114] In some embodiments relating to the compound or salt of formula (I), R 1 is selected from 5- to 12-membered heterocycles optionally substituted. In some cases, the heterocycle of R 1 is selected from 5- to 12-membered heterocycles, 6- to 12-membered heterocycles, 7- to 12-membered heterocycles and 8- to 12-membered heterocycles. In some cases, the heterocycle of R 1 is selected from 5- to 11-membered heterocycles, 5- to 10-membered heterocycles, 5- to 9-membered heterocycles and 5- to 8-membered heterocycles. In some cases, the heterocycle of R 1 is selected from 6- to 11-membered heterocycles, 6- to 10-membered heterocycles, 6- to 9-membered heterocycles and 6- to 8-membered heterocycles. In some cases, the heterocycle of R 1 is selected from 7- to 11-membered heterocycles, 7- to 10-membered heterocycles, 7- to 9-membered heterocycles and 7- to 8-membered heterocycles. In some cases, the heterocycle of R 1 is selected from 5- to 6-membered heterocycles and 5- to 9-membered heterocycles. In some cases, the heterocycle of R 1 is selected from 8- to 9-membered heterocycles. In some cases, R 1 is selected from 5- to 7-membered heterocycles optionally substituted. In some cases, R 1 is selected from 6- to 7-membered heterocycles optionally substituted. In some cases, R 1 is selected from 7-membered heterocycles optionally substituted. In some cases, the 5- to 12-membered heterocycle of R 1 is a bridged heterocycle. In some cases, the 5- to 12-membered heterocycle of R 1 is not a bridged heterocycle. In some cases, the heterocycle of R 1 is saturated. In some cases, the heterocycle of R 1 is unsaturated. In some cases, the heterocycle of R 1 is a non-bridged heterocycle. The heterocycle of R 1 is optionally substituted as described elsewhere in this specification.

[0115] In some embodiments relating to the compound or salt of formula (I), R 1 's heterocycle contains at most one nitrogen atom. In some embodiments, R1 The complex ring contains at most one heteroatom. In some cases, the heteroatom is selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 's complex ring contains at most two heteroatoms. In some cases, R 1 's complex ring contains one nitrogen atom. In some cases, R 1 's complex ring contains only one nitrogen atom. In some cases, R 1 's complex ring contains only one nitrogen atom and no other heteroatoms.

[0116] In some embodiments regarding the compound or salt of formula (I), R 1 is selected from 5- to 12-membered complex rings, and the 5- to 12-membered complex ring is optionally substituted by one or more substituents independently selected from halogen, -OH, -N(R 20 )2, -NO2, =O, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, and C 1~6 haloalkyl. In some cases, the 5- to 12-membered complex ring of R 1 is an unsaturated complex ring. In some cases, the 5- to 12-membered complex ring of R 1 is selected from saturated and unsaturated complex rings. In some cases, the 5- to 12-membered complex ring of R 1 is a saturated complex ring. In some cases, the 5- to 12-membered complex ring of R 1 is an unsaturated complex ring.

[0117] In some embodiments regarding the compound or salt of formula (I), R 1 is selected from 5- to 15-membered complex rings, and the 5- to 15-membered complex ring is optionally substituted. In some cases, R 1 is selected from optionally substituted 6- to 15-membered complex rings. In some cases, the complex ring is a spiro complex ring. In some cases, the complex ring is a fused complex ring. In some cases, the complex ring is a bridged complex ring. In some cases, the complex ring is an unsaturated complex ring.

[0118] In some embodiments of the compound or salt of formula (I), R 1 is a 6- to 12-membered fused heterocyclic ring, optionally substituted.

[0119] In some embodiments of the compound or salt of formula (I), R 1 is a 6- to 12-membered spiro heterocyclic ring, optionally substituted. In some cases, R 1 is selected from 7- to 8-membered spiro heterocyclic rings, optionally substituted.

[0120] In some embodiments of the compound or salt of formula (I), R 1 's heterocyclic ring is a 5- to 12-membered heterocyclic ring, a 6- to 12-membered heterocyclic ring, a 7- to 12-membered heterocyclic ring or an 8- to 12-membered heterocyclic ring. In some cases, R 1 's heterocyclic ring is a 5- to 11-membered heterocyclic ring, a 5- to 10-membered heterocyclic ring, a 5- to 9-membered heterocyclic ring or a 5- to 8-membered heterocyclic ring. In some cases, R 1 's heterocyclic ring is a 6- to 11-membered heterocyclic ring, a 6- to 10-membered heterocyclic ring, a 6- to 9-membered heterocyclic ring or a 6- to 8-membered heterocyclic ring. In some cases, R 1 's heterocyclic ring is a 7- to 11-membered heterocyclic ring, a 7- to 10-membered heterocyclic ring, a 7- to 9-membered heterocyclic ring or a 7- to 8-membered heterocyclic ring. In some cases, R 1 's heterocyclic ring is a 5- to 6-membered heterocyclic ring or a 5- to 9-membered heterocyclic ring. In some cases, R 1 's heterocyclic ring is an 8- to 9-membered heterocyclic ring. In some cases, R 1 's heterocyclic ring is saturated. The heterocyclic ring is optionally substituted as described elsewhere in this specification.

[0121] In some embodiments of the compound or salt of formula (I), R 1 is a 5- to 12-membered monocyclic heterocyclic ring. In some cases, R 1 's heterocyclic ring is a 5- to 12-membered monocyclic heterocyclic ring, a 6- to 12-membered monocyclic heterocyclic ring, a 7- to 12-membered monocyclic heterocyclic ring or an 8- to 12-membered monocyclic heterocyclic ring. In some cases, R 1 's heterocyclic ring is a 5- to 11-membered monocyclic heterocyclic ring, a 5- to 10-membered monocyclic heterocyclic ring, a 5- to 9-membered monocyclic heterocyclic ring or a 5- to 8-membered monocyclic heterocyclic ring. In some cases, R1 The heterocyclic ring is a 6- to 11-membered monocyclic heterocyclic ring, a 6- to 10-membered monocyclic heterocyclic ring, a 6- to 9-membered monocyclic heterocyclic ring, or a 6- to 8-membered monocyclic heterocyclic ring. In some cases, R 1 The heterocyclic ring is a 7- to 11-membered monocyclic heterocyclic ring, a 7- to 10-membered monocyclic heterocyclic ring, a 7- to 9-membered monocyclic heterocyclic ring, or a 7- to 8-membered monocyclic heterocyclic ring. In some cases, R 1 The heterocyclic ring is a 5- to 6-membered monocyclic heterocyclic ring or a 5- to 9-membered monocyclic heterocyclic ring. In some cases, R 1 The heterocyclic ring is an 8- to 9-membered monocyclic heterocyclic ring. In some cases, R 1 The heterocyclic ring is saturated. The monocyclic heterocyclic ring is optionally substituted as described elsewhere in this specification.

[0122] In some embodiments of the compound or salt of formula (I), R 1 is a bridged heterocyclic ring. In some cases, R 1 The heterocyclic ring is a 5- to 12-membered bridged heterocyclic ring, a 6- to 12-membered bridged heterocyclic ring, a 7- to 12-membered bridged heterocyclic ring, or an 8- to 12-membered bridged heterocyclic ring. In some cases, R 1 The heterocyclic ring is a 5- to 11-membered bridged heterocyclic ring, a 5- to 10-membered bridged heterocyclic ring, a 5- to 9-membered bridged heterocyclic ring, or a 5- to 8-membered bridged heterocyclic ring. In some cases, R 1 The heterocyclic ring is a 6- to 11-membered bridged heterocyclic ring, a 6- to 10-membered bridged heterocyclic ring, a 6- to 9-membered bridged heterocyclic ring, or a 6- to 8-membered bridged heterocyclic ring. In some cases, R 1 The heterocyclic ring is a 7- to 11-membered bridged heterocyclic ring, a 7- to 10-membered bridged heterocyclic ring, a 7- to 9-membered bridged heterocyclic ring, or a 7- to 8-membered bridged heterocyclic ring. In some cases, R 1 The heterocyclic ring is a 5- to 6-membered bridged heterocyclic ring or a 5- to 9-membered bridged heterocyclic ring. In some cases, R 1 The heterocyclic ring is an 8- to 9-membered bridged heterocyclic ring. In some cases, R 1 The heterocyclic ring is saturated. In some cases, the bridged heterocyclic ring is

Chemical formula

Chemical formula

[0123] In some embodiments of the compound or salt of formula (I), R 1 is a spiro heterocycle. R 1 's spiro heterocycle is a 7- to 12-membered spiro heterocycle, a 7- to 12-membered spiro heterocycle or an 8- to 12-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle is a 7- to 11-membered spiro heterocycle, a 7- to 10-membered spiro heterocycle, a 7- to 9-membered spiro heterocycle or a 7- to 8-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle is a 7- to 11-membered spiro heterocycle, a 7- to 10-membered spiro heterocycle, a 7- to 9-membered spiro heterocycle or a 7- to 8-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle is a 7- to 11-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle is a 7-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle is an 8-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle is a 9-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle is a 10-membered spiro heterocycle. In some cases, R 1 's spiro heterocycle contains at most one nitrogen atom. In some cases, R 1 's spiro heterocycle contains only one nitrogen atom. In some cases, R 1 's spiro heterocycle contains at most two heteroatoms. In some cases, R 1 's spiro heterocycle contains at least two heteroatoms. In some cases, R 1 's spiro heterocycle contains at least three heteroatoms. In some cases, the heteroatoms are selected from nitrogen, oxygen and sulfur. In some cases, R 1 's spiro heterocycle is attached to the formula via a nitrogen atom. In some embodiments, R 1 's spiro heterocycle is

Chemical formula

Chemical formula

[0124] In some embodiments of the compound or salt of formula (I), R 1 is a fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 6- to 12-membered fused heterocyclic ring, a 6- to 12-membered fused heterocyclic ring, a 7- to 12-membered fused heterocyclic ring, or an 8- to 12-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 6- to 11-membered fused heterocyclic ring, a 6- to 10-membered fused heterocyclic ring, a 6- to 9-membered fused heterocyclic ring, or a 6- to 8-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 7- to 11-membered fused heterocyclic ring, a 7- to 10-membered fused heterocyclic ring, a 7- to 9-membered fused heterocyclic ring, or a 7- to 8-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is an 8- to 11-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 9-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 10-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is an 11-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 6-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 7-membered fused heterocyclic ring. In some cases, R 1 's fused heterocyclic ring is a 10-membered fused heterocyclic ring. In some cases, the fused heterocyclic ring is

Chemical formula

[0125] In some embodiments of the compound or salt of formula (I), R 1is selected from 8- to 10-membered fused heterocyclic rings which are optionally substituted. In some cases, the 8- to 10-membered fused heterocyclic ring is a bicyclic heterocyclic ring. In some cases, the 8- to 10-membered fused heterocyclic ring is a saturated heterocyclic ring. In some cases, the 8- to 10-membered fused heterocyclic ring is an unsaturated heterocyclic ring. In some cases, the 8- to 10-membered heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, R 1 is selected from 9-membered fused heterocyclic rings which are optionally substituted. In some cases, R 1 is selected from 10-membered fused heterocyclic rings which are optionally substituted. In some cases, the 10-membered fused heterocyclic ring is a bicyclic heterocyclic ring. In some cases, the 10-membered fused heterocyclic ring is a saturated heterocyclic ring. In some cases, the 9-membered heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, the 10-membered heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, the fused heterocyclic ring has one saturated ring and one aromatic ring. In some cases, the fused heterocyclic ring has one saturated ring and one unsaturated ring. In some cases, the fused heterocyclic ring has two saturated rings. In some cases, the 10-membered heterocyclic ring contains at least one nitrogen atom. In some cases, the 10-membered heterocyclic ring contains at least two nitrogen atoms. In some cases, the 10-membered heterocyclic ring contains at least three nitrogen atoms. In some cases, the 9-membered heterocyclic ring contains at least one nitrogen atom. In some cases, the 9-membered heterocyclic ring contains at least two nitrogen atoms. In some cases, the 9-membered heterocyclic ring contains at least three nitrogen atoms. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0126] In some embodiments relating to the compound or salt of formula (I), R 1 is [Chemical formula] selected from, [Chemical formula] is selected from 5- to 12-membered heterocycles, the 5- to 12-membered heterocycles are independently optionally substituted with one or more R 1* , R B is selected from hydrogen, halogen, C 1~6 alkyl, C 1~6 haloalkyl, C 2~6 alkynyl and -CN. In some cases, R B is selected from hydrogen and halogen. In some cases, R B is chlorine. In some cases, R B is hydrogen. In some cases, [Chemical formula] has at least 1, 2, 3 or 4 heteroatoms. In some cases, [Chemical formula] has at least 1, 2, 3 or 4 nitrogen atoms. In some cases,

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chemical formula

Chemical formula

[0127] In some embodiments relating to the compound or salt of formula (I), R 1 when substituted by -C(O)R 20 then R 20 is selected from 5- to 12-membered heterocycles which are optionally substituted. In some cases, R 1 is substituted by -C(O)R 20 In some cases, R 20 is selected from 5- to 12-membered unsubstituted heterocycles. In some cases, R 20 is selected from 5- to 6-membered heterocycles which are optionally substituted. In some cases, the heterocycle has at least 1 nitrogen atom. In some cases, the heterocycle has at least 1 sulfur atom. In some cases, the heterocycle has at least 1 oxygen atom. In some cases, the heterocycle has 2 heteroatoms. In some cases, the heterocycle of R 20 is

Chemical formula

Chemical formula

[0128] In some embodiments relating to the compound or salt of formula (I), each of R 20 is independently hydrogen; and C 1~6 alkyl, C 3~12 carbocycle and 3- to 12-membered heterocycle, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10Optionally substituted by one or more substituents independently selected from alkyl, oxo and =NH. In some cases, R 20 is each independently hydrogen; and unsubstituted C 1~6 alkyl and a 3- to 12-membered heterocyclic ring, which 3- to 12-membered heterocyclic ring is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, optionally substituted by one or more substituents independently selected from oxo and =NH.

[0129] In some embodiments of the compound or salt of formula (I), R 21 is each independently hydrogen; and C 1~6 alkyl, a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 3~12 alkyl)2, C 1~6 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, optionally substituted by one or more substituents independently selected from oxo and =NH. In some cases, R 1~10 is each independently hydrogen; and unsubstituted C 21 alkyl and a 3- to 12-membered heterocyclic ring, which 3- to 12-membered heterocyclic ring is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~6 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, optionally substituted by one or more substituents independently selected from oxo and =NH. 1~10 is each independently hydrogen; and C

[0130] In some embodiments of the compound or salt of formula (I), R 20 is each independently hydrogen; and C 1~6 alkyl, C 3~12Independently selected from a carbon ring and a 3- to 12-membered heterocyclic ring, each of which is independently substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo and =NH as required. In some cases, R 20 is each hydrogen; and unsubstituted C 1~6 alkyl and a 3- to 12-membered heterocyclic ring independently selected, which are independently substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo and =NH as required.

[0131] In some embodiments of the compound or salt of formula (I), R 23 is each hydrogen; and C 1~6 alkyl, C 3~12 carbon ring and a 3- to 12-membered heterocyclic ring independently selected, each of which is independently substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo and =NH as required. In some cases, R 20 is each hydrogen; and unsubstituted C 1~6 alkyl and a 3- to 12-membered heterocyclic ring independently selected, which are independently substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo and =NH as required.

[0132] In some embodiments of the compound or salt of formula (I), R 1 is selected from 5- to 12-membered heterocycles, which are optionally substituted with one or more substituents. In some cases, one or more optional substituents are halogen, -CN, -NO2, =O, -N(R 20 )2, -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 , -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -OC(O)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 alkenyl, and C 2~6 alkynyl, independently selected. In some cases, one or more optional substituents are halogen, -OH, -N(R 20 )2, -NO2, =O, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl and C 1~6 haloalkyl, independently selected. In some cases, one or more optional substituents are halogen, -OH, -N(R 20 )2, -NO2, C1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl and C 1~6 is independently selected from haloalkyl. In some cases, R 20 is selected from hydrogen and C 1~3 alkyl.

[0133] In some embodiments of the compound or salt of formula (I), R 1 is selected from 5- to 12-membered saturated heterocycles, which are optionally substituted with one or more substituents. In some cases, the 5- to 12-membered heterocycle of R 1 is bridged. In some cases, the 5- to 12-membered heterocycle of R 1 is not bridged. In some cases, the 5- to 12-membered heterocycle is

Chemical formula

[0134] In some embodiments of the compound or salt of formula (I), R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0135] In some embodiments of the compound or salt of formula (I), R 1 is selected from optionally substituted 5- to 12-membered unsaturated heterocycles, the heterocycle having 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.

[0136] In some embodiments of the compound or salt of formula (I), R 1 's heterocycle contains only one nitrogen atom and, optionally, one or more heteroatoms selected from oxygen and sulfur. In some cases, the heterocycle is a fused heterocycle or a bridged heterocycle. In some cases, the heterocycle is a monocyclic heterocycle or a bridged heterocycle. In some cases, the heterocycle is a monocyclic heterocycle. In some cases, the heterocycle is a bridged heterocycle. In some cases, the heterocycle is

Chemical formula

[0137] In some embodiments of the compound or salt of formula (I), R 1 's heterocycle has at most one nitrogen atom. In some cases, R 1The heterocyclic ring has only one nitrogen atom and, optionally, one or more other heteroatoms selected from oxygen and sulfur. In some cases, R 1 The heterocyclic ring has only one nitrogen atom and no other heteroatoms.

[0138] In some embodiments of the compound or salt of formula (I), R 1 is selected from optionally substituted 5- to 12-membered saturated heterocyclic rings, the heterocyclic ring having at most one nitrogen atom. In some cases, the 5- to 12-membered unsaturated heterocyclic ring has at least one nitrogen atom. In some cases, the 5- to 12-membered unsaturated heterocyclic ring has only one nitrogen atom and has 0 to 2 other heteroatoms selected from nitrogen, oxygen, and sulfur. In some cases, the 5- to 12-membered unsaturated heterocyclic ring has only one nitrogen atom and no further heteroatoms. In some cases, the 5- to 12-membered unsaturated heterocyclic ring has three nitrogen atoms and no further heteroatoms.

[0139] In some embodiments of the compound or salt of formula (I), R 1 is selected from optionally substituted 5- to 12-membered unsaturated heterocyclic rings, the heterocyclic ring having at most one nitrogen atom. In some cases, the 5- to 12-membered unsaturated heterocyclic ring has at least one nitrogen atom. In some cases, the 5- to 12-membered unsaturated heterocyclic ring has only one nitrogen atom and no further heteroatoms.

[0140] In some embodiments of the compound or salt of formula (I), R 1 is selected from 6- to 7-membered heterocyclic rings. In some cases, R 1 is selected from 7-membered heterocyclic rings. In some cases, R 1is selected from 6-membered heterocycles. In some cases, the 6- to 7-membered heterocycle contains only one nitrogen atom and, optionally, one or more additional heteroatoms selected from oxygen and sulfur. In some cases, the one or more additional heteroatoms, when present, are selected from sulfur. In some cases, the one or more additional heteroatoms, when present, are selected from oxygen. In some cases, the 6- to 7-membered heterocycle contains only one nitrogen atom and no additional heteroatoms. In some cases, the 6- to 7-membered heterocycle is a 6- to 7-membered non-aromatic heterocycle. In some cases, R 1 's 6- to 7-membered heterocycle is attached to formula (I) through only one nitrogen atom. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0141] In some embodiments of the compound or salt of formula (I), R 1 is [Chemical formula] is selected from, each of which is optionally substituted with one or more substituents. In some cases, one or more of the optional substituents are halogen, -OH, -N(R 20 )2, -B(OH)2, -C(O)N(R 20 )2, -NHCN, -NO2, C 1~6 alkoxy, =O, -CN, C 1~6 alkyl, C 2~6 alkenyl, C 1~6 aminoalkyl, C 1~6 hydroxyalkyl and C 1~6 haloalkyl, independently selected. In some cases, R 1 is [Chemical formula] [Chemical formula] [Chemical formula] [Chemical formula] is selected from

[0142] In some embodiments of the compound or salt of formula (I), R 1 is selected from a 6- to 8-membered unsaturated heterocyclic ring optionally substituted. In some cases, R 1 is selected from a 6-membered unsaturated heterocyclic ring optionally substituted. In some cases, R 1is selected from 7-membered unsaturated heterocyclic rings which are optionally substituted. In some cases, the heterocyclic ring has one or two double bonds. In some cases, the heterocyclic ring has only one double bond. In some cases, the heterocyclic ring has only two double bonds. In some cases, R 1 is

Chem.

Chem.

Chem.

Chem.

[0143] In some embodiments relating to the compound or salt of formula (I), R 1 is selected from a 6- to 7-membered unsaturated heterocyclic ring, and the 6- to 7-membered unsaturated heterocyclic ring is substituted by one or more substituents selected from halogen. In some cases, the 6- to 7-membered unsaturated heterocyclic ring is substituted by at least one halogen. In some cases, the 6- to 7-membered unsaturated heterocyclic ring is substituted by only one halogen. In some cases, the 7-membered unsaturated heterocyclic ring is substituted by one fluorine. In some cases, R 1 is selected from a 6-membered unsaturated heterocyclic ring substituted by at least one halogen. In some cases, R 1 is selected from a 7-membered unsaturated heterocyclic ring substituted by at least one halogen. In some cases, R 1 is [Chemical formula] is selected from. In some cases, R 1 is [Chemical formula] is selected from. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0144] In some embodiments of the compound or salt of formula (I), R 1 is selected from a 6- to 8-membered unsaturated heterocyclic ring which is optionally substituted. In some cases, R 1 is selected from a 7-membered unsaturated heterocyclic ring which is optionally substituted. In some cases, R 1 is

Chemical formula

Chemical formula

[0145] In some embodiments relating to the compound or salt of formula (I), R 1 is selected from optionally substituted 6-membered heterocycles. In some cases, the 6-membered heterocycle contains only one nitrogen atom. In some cases, the 6-membered heterocycle of R 1 is attached to formula (I) via only one nitrogen atom. In some cases, R 1 is

Chemical formula

[0146] is selected from unsaturated 6-membered heterocycles and saturated 6-membered heterocycles which are optionally substituted 1 In some embodiments of the compound or salt of formula (I), R

[0147] is selected from 1 and is optionally substituted by one or more substituents independently selected from halogen, -OH, -NH2, -NO2, C [Chem.] aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 haloalkyl and C 1~6 alkyl 1~6 In some embodiments of the compound or salt of formula (I), R

[0148] is selected from 1 and is optionally substituted by one or more substituents independently selected from halogen and C [Chem.] haloalkyl 1~6 In some embodiments of the compound or salt of formula (I), R

[0149] is selected from 1 In some embodiments of the compound or salt of formula (I), R [Chem.] In some embodiments of the compound or salt of formula (I), R

[0150] is selected from 1 In some embodiments of the compound or salt of formula (I), R [Chemical formula] 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 optionally substituted by two substituents independently selected from alkyl.

[0151] In some embodiments of the compound or salt of formula (I), R 1 is [Chemical formula] selected from, respectively, halogen and C 1~6 haloalkyl, and is optionally substituted by two substituents independently selected therefrom. In some cases, R 1 is [Chemical formula] is.

[0152] In some embodiments of the compound or salt of formula (I), R 1 is selected from optionally substituted 6- to 10-membered heterocycles. In some cases, the 6- to 10-membered heterocycle contains at least one nitrogen atom. In some cases, R 1 is [Chemical formula] selected from, each of which is halogen, =O, -OH, -CN, -NHCN, -C(O)N(R 20 )2, C 1~6 aminoalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl and C 1~6 alkyl, and is optionally substituted by one or more substituents independently selected therefrom. In some cases, R 20are each hydrogen; and C 1~6 alkyl, C 3~12 independently selected from carbocyclic rings and 3- to 12-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 independently selected from carbocyclic rings and 3- to 12-membered heterocyclic rings. In some cases, R 1 is

Chemical formula

[0153] In some embodiments of the compound or salt of formula (I), R 1 is selected from 6- to 7-membered heterocyclic rings. In some cases, R 1 is selected from 7-membered heterocyclic rings. In some cases, R 1 is selected from 6-membered heterocyclic rings. In some cases, the 6- to 7-membered heterocyclic ring contains only one nitrogen atom and optionally contains one or more additional heteroatoms selected from oxygen and sulfur. In some cases, the one or more additional heteroatoms, if any, are selected from sulfur. In some cases, the one or more additional heteroatoms, if any, are selected from oxygen. In some cases, the 6- to 7-membered heterocyclic ring contains only one nitrogen atom and no additional heteroatoms. In some cases, the 6- to 7-membered heterocyclic ring is a 6- to 7-membered non-aromatic heterocyclic ring. In some cases, the 6- to 7-membered heterocyclic ring of R 1 is attached to formula (I) via only one nitrogen atom. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

[0154] In some embodiments of the compound or salt of formula (I), the 5- to 12-membered heterocyclic ring of R 1 is an unsaturated bridged heterocyclic ring. In some cases, R 1 is selected from 7- to 8-membered unsaturated bridged heterocyclic rings which are optionally substituted. In some cases, R 1 is selected from

Chem.

[0155] In some embodiments of the compound or salt of formula (I), R 1is selected from 5- to 10-membered heterocycles, 7-, 8-, 10-, 11-membered spiro heterocycles and 6-, 9-, 10-, 11- and 12-membered fused heterocycles, each optionally substituted with one or more substituents independently selected from 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 aminoalkyl. In some cases, R 1 is

Chem.

Chem.

Chem.

[0156] In some embodiments of the compound or salt of formula (I), R 1 is selected from a 10-membered heterocycle which is optionally substituted. In some cases, the 10-membered heterocycle is a bicyclic heterocycle. In some cases, the 10-membered heterocycle is a spiro heterocycle. In some cases, the 10-membered heterocycle is a fused heterocycle. In some cases, the 10-membered heterocycle is a saturated heterocycle. In some cases, the 10-membered heterocycle is a non-aromatic heterocycle. In some cases, the 10-membered heterocycle contains at least 1 nitrogen atom. In some cases, the 10-membered heterocycle contains at least 2 nitrogen atoms. In some cases, the 10-membered heterocycle contains at least 3 nitrogen atoms. In some cases, the 10-membered heterocycle contains at least 1 sulfur atom. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0157] In some embodiments of the compound or salt of formula (I), R 1 is selected from a 9- to 11-membered unsaturated heterocyclic ring, optionally substituted. In some cases, R 1 is selected from a 10-membered unsaturated heterocyclic ring, optionally substituted. In some cases, R 1 is selected from a 10-membered unsaturated fused heterocyclic ring, optionally substituted. In some cases, R 1 is [Chemical formula] and is optionally substituted. In some cases, one or more optional substituents are halogen, -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 1~6Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 1~6 Alkyl and C 2~6 selected from alkynyl. 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 optionally substituted by one or more substituents selected from alkynyl

Chemical formula

[0158] In some embodiments of the compound or salt of formula (I), R 1 is selected from 7- to 11-membered spiro heterocycles. In some cases, R 1 is selected from 10-membered spiro heterocycles. In some cases, the spiro heterocycle has at least 3 nitrogen atoms. In some cases, the spiro heterocycle has at least 1 sulfur atom. In some cases, R 1 is

Chemical formula

Chem.

Chem.

Chem.

[0159] In some embodiments of the compound or salt of formula (I), R 1 is selected from optionally substituted 8- to 10-membered fused heterocycles. In some cases, the 8- to 10-membered fused heterocycle is a bicyclic heterocycle. In some cases, the 8- to 10-membered fused heterocycle is a saturated heterocycle. In some cases, the 8- to 10-membered fused heterocycle is an unsaturated heterocycle. In some cases, the 8- to 10-membered heterocycle is a non-aromatic heterocycle. In some cases, R 1is selected from 10-membered fused heterocyclic rings which are optionally substituted. In some cases, the 10-membered fused heterocyclic ring is a bicyclic heterocyclic ring. In some cases, the 10-membered fused heterocyclic ring is a saturated heterocyclic ring. In some cases, the 10-membered heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, the fused heterocyclic ring has one saturated ring and one aromatic ring. In some cases, the fused heterocyclic ring has one saturated ring and one unsaturated ring. In some cases, the fused heterocyclic ring has two saturated rings. In some cases, the 10-membered heterocyclic ring contains at least one nitrogen atom. In some cases, the 10-membered heterocyclic ring contains at least two nitrogen atoms. In some cases, the 10-membered heterocyclic ring contains at least three nitrogen atoms. In some cases, R 1 is [Chemical Structure] selected from, each of which is optionally substituted by one or more substituents. In some cases, R 1 is [Chemical Structure] selected from, each of which is optionally substituted by one or more substituents. In some cases, R 1 is [Chemical Structure] and is optionally substituted by one or more substituents. In some cases, one or more optional substituents of R 1 are 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)R 20 , -NO2, =O, -CN, C 1~6 alkyl-N(R 20 )2, C​​​1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Hydroxyalkyl, C 1~6 Cyanoalkyl, C 1~6 Haloalkyl, C 1~6 Alkyl and C 2~6 are independently selected from alkynyl. In some cases, one or more optional substituents 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 OR 20 , C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl and C 1~6 are independently selected from alkyl. In some cases, one or more optional substituents are halogen, =O, C 1~6 alkyl-N(R 20 )2, -S(O)2(R 20 ), -S(O)N(R 20 )2, -S(O)R 20 (=NR 20 ), -C(O)R 20 , -C(O)N(R 20 )2 and -C(O)NR 20 OR 20 are independently selected from. In some cases, one or more optional substituents are halogen, =O, -S(O)2(R 20 ), -S(O)N(R 20 )2, -S(O)R 20 (=NR 20 ), -C(O)R 20 , -C(O)N(R 20 )2 and -C(O)NR 20 OR 20is independently selected from. In some cases, one or more substituents as required are -C(O)R 20 , -C(O)N(R 20 )2 and -C(O)NR 20 OR 20 is independently selected from. In some cases, one or more substituents as required are -S(O)2(R 20 ), -S(O)2N(R 20 )2, -S(O)N(R 20 )2, -S(O)R 20 (=NR 20 ) is independently selected from. In some cases, one or more substituents as required are -S(O)N(R 20 )2 is independently selected from. In some cases, one or more substituents as required are S(O)2(R 20 ) is independently selected from. In some cases, one or more substituents as required are S(O)R 20 (=NR 20 ) is independently selected from. In some cases, one or more substituents as required are -C(O)R 20 is independently selected from. In some cases, one or more substituents as required are -C(O)N(R 20 )2 is independently selected from. In some cases, one or more substituents as required are -C(O)NR 20 OR 20 is independently selected from. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

[0160] In some embodiments regarding the compound or salt of formula (I), when R 1 is substituted by -C(O)R 20 , R 20 is selected from 5- to 12-membered heterocyclic rings.

[0161] In some embodiments related to the compound or salt of formula (I), formula (II) or formula (III), R 1 is

Chemical formula

Chemical formula

Chemical formula

[0162] In some embodiments relating to the compounds or salts of formula (I), formula (II) or formula (III), one or more optional substituents of R 1 Are independently selected from -C(=NR 20 )N(R 20 )2 and a 5- to 12-membered heterocyclic ring optionally substituted. In some cases, one or more optional substituents of R 1 Are independently selected from a 5- to 12-membered heterocyclic ring optionally substituted. In some cases, the heterocyclic ring is [Chemical formula] selected from, each of which is one or more R 1* is optionally substituted by 1* . In some cases, one or more optional substituents of R 1 are selected from

Chemical Formula

[0163] In some embodiments relating to the compounds or salts of formula (I), formula (II) or formula (III), each R 1* is independently selected from halogen, -OR 20 , -S(O)2(R 20 ), -S(O)2N(R 20 )2, -S(O)N(R 20 )2, -S(O)R 20 (=NR 20 ), -NR 20 S(O)2R 20 , -C(O)N(R 20 )2, -C(O)NR 20 OR 20 , -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -OC(O)N(R 20 )2, -NO2, =O, =N(R 20 ), =NO(R 20 ), -CN, -NHCN, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl, C 1~6 haloalkyl, and C 1~6 alkyl. In some cases, each R 1* is independently selected from halogen, -OR20 ,-S(O)2(R 20 ),-S(O)2N(R 20 )2,-S(O)N(R 20 )2,-S(O)R 20 (=NR 20 ),-NR 20 S(O)2R 20 ,-C(O)N(R 20 )2,-C(O)NR 20 OR 20 ,-N(R 20 )C(O)R 20 ,-N(R 20 )C(O)N(R 20 )2,-N(R 20 )C(O)OR 20 ,-N(R 20 )2,-C(O)R 20 ,-C(O)OR 20 ,-OC(O)R 20 ,-OC(O)N(R 20 )2,-NO2,=O,=N(R 20 ),=NO(R 20 ),-CN,-NHCN,C 1~6 alkyl-N(R 20 )2,C 1~6 aminoalkyl,C 1~6 alkoxy,C 1~6 hydroxyalkyl,C 1~6 cyanoalkyl,C 1~6 haloalkyl,and C 1~6 alkyl are independently selected. In some cases, R 1* are each independently selected from halogen, C 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 alkyl. In some cases, R 1* are each independently selected from halogen, C 1~6 haloalkyl and C 1~6 alkyl. In some cases, R 1* are each independently selected from halogen and C 1~6is independently selected from alkyl. In some cases, R 1* is each independently selected from halogen. In some cases, R 1* is each independently selected from C 1~6 alkyl.

[0164] In some embodiments relating to the compound or salt of formula (I), R 1 is selected from 5- to 15-membered heterocycles (preferably 8- to 10-membered heterocycles or preferably 10-membered heterocycles), each of which is halogen, oxo, -C(O)N(R 20 )2, -C(O)NR 20 OR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -SO2R 20 , -NHCN, C 1~6 cyanoalkyl, C 1~6 alkyl, C 1~6 alkyl-N(R 20 )2, C 2~6 alkynyl and one or more substituents independently selected from 5- to 12-membered heterocycles (preferably 5- to 9-membered heterocycles), the 5- to 12-membered heterocycles are each independently optionally substituted by one or more R 1* , and R 1* is each independently selected from halogen, C 1~6 haloalkyl and C 1~6 alkyl. In some cases, the 8- to 10-membered heterocycle is bicyclic. In some cases, the 10-membered heterocycle is substituted. In some cases, R 1 is the selected

Chemical formula

Chemical formula

[0165] In some embodiments relating to the compound or salt of formula (I), R 1 is selected from 5- to 15-membered heterocycles (preferably 8- to 10-membered heterocycles or preferably 10-membered heterocycles or preferably 8-membered heterocycles), each of which is halogen, -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 alkynyl and 5- to 12-membered heterocycles (preferably 5- to 6-membered heterocycles) optionally substituted by one or more substituents independently selected therefrom, and the 5- to 12-membered heterocycles are each optionally independently substituted by one or more R 1* and R1* is independently selected from halogen, C 1~6 haloalkyl and C 1~6 alkyl. In some cases, the 8- to 10-membered heterocyclic ring is bicyclic. In some cases, the 10-membered heterocyclic ring is substituted. In some cases, R 1 is the selected [Chemical formula] and these are each optionally substituted. In some cases, R 1 is the selected [Chemical formula] and this is optionally substituted. In some cases, R 1 is the selected [Chemical formula] In some cases, R 1 is the selected [Chemical formula] In some embodiments relating to the compound or salt of formula (I), R

[0166] is selected from 1 [Chemical formula] In some embodiments relating to the compound or salt of formula (I), R

[0167] is selected from a 7- to 10-membered spiro heterocyclic ring optionally substituted and a 7- to 10-membered fused heterocyclic ring optionally substituted. In some cases, the heterocyclic ring of R 1 has at least one nitrogen atom. In some cases, at least one nitrogen of the heterocyclic ring of R 1 is bonded to formula (I). In some cases, R 1 of the heterocyclic ring is bonded to formula (I). In some cases, R 1 ​is selected from a 10-membered spiro heterocyclic ring optionally substituted and a 10-membered fused heterocyclic ring optionally substituted. In some cases, R 1 of one or more optional substituents are 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, independently selected from 5- to 12-membered heterocyclic rings, and the 5- to 12-membered heterocyclic rings are optionally substituted by one or more substituents selected from halogen and C 1~6 alkyl. In some cases, R 1 is [Chemical formula] selected from, which 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, is substituted by one or more substituents independently selected from 5- to 12-membered heterocycles, and the 5- to 12-membered heterocycle is optionally substituted by one or more substituents selected from halogen and C 1~6 alkyl. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

[0168] In some embodiments of the compound or salt of formula (I), R 1 is selected from optionally substituted 6- to 11-membered heterocycles, and the 6- to 11-membered heterocycle has at least one nitrogen atom. In some cases, one or more optional substituents of R 1 are halogen, -OR 20 , -C(O)N(R 20 )2, -C(O)R 20 , -S(O)2R 20 , =O, -C 1~6 alkyl(=NOR 20 ), =NO(R 20 ), -CN, -NHCN, C 1~6Selected from alkyl and 5- to 12-membered heterocycles, the 5- to 12-membered heterocycle is independently substituted, if necessary, by one or more Rs 1* and is independently selected, in each case, from halogen and C 1* alkyl. In some embodiments, R 1~6 is selected from 1

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0169] In some embodiments relating to the compound or salt of formula (I), R 1 is selected from hydrogen and a 5- to 15-membered heterocycle which is optionally substituted. In some cases, R 1 is

Chemical formula

Chemical formula

[0170] In some embodiments of the compound or salt of formula (I), R 1 is selected from hydrogen and an optionally substituted 7- to 10-membered heterocyclic ring. In some cases, R 1 is hydrogen, [Chemical formula] is selected from, and each of these is optionally substituted. In some cases, one or more optional substituents of R 1 are independently selected from halogen, -NH2, -S(O)2(R 20 ), -C(O)R 20 , -C(O)N(R 20 )2, =O, =NO(R 20 ), -CN, -NHCN, C 1~6 alkyl and a 5- to 12-membered heterocyclic ring, and the 5- to 12-membered heterocyclic ring is optionally independently substituted by one or more R 1* , and each R 1* is independently selected from halogen and C 1~6 alkyl. In some cases, R 1 is hydrogen, [Chemical formula] is selected from.

[0171] In some embodiments of the compound or salt of formula (I), R 1 is selected from an optionally substituted 8- to 10-membered heterocyclic ring. In some cases, the heterocyclic ring is bicyclic. In some cases, the heterocyclic ring has at least one nitrogen atom. In some cases, the heterocyclic ring has at least two nitrogen atoms. In some cases, [Chemical formula] is, and each of these is optionally substituted. In some cases, R 1One or more substituents as required are halogen,

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

[0172] In some embodiments of the compound or salt of formula (I), R 1 is selected from an 8- to 9-membered bridged heterocyclic ring optionally substituted. In some cases, the heterocyclic ring of R 1 is

Chem.

[0173] In some embodiments of the compound or salt of formula (I), R 1 is selected from an 8-membered bridged heterocyclic ring optionally substituted, the heterocyclic ring containing a heteroatom selected from nitrogen. In some cases, one or more substituents of R 1 are selected from C 1~6 alkyl, -N(R 20 )2 and C 1~6 aminoalkyl. In some cases, the heterocyclic ring of R 1 is [Chemical formula] selected from, each of which is optionally substituted. In some cases, R 1 is selected [Chemical formula] and is as follows. In some cases, R 1 is [Chemical formula] and is as follows. In some cases, R 1 is [Chemical formula] and is as follows.

[0174] In some embodiments of the compound or salt of formula (I), R 1 is hydrogen.

[0175] In some embodiments of the compound or salt of formula (I), R 1 is a 12- to 15-membered heterocyclic ring optionally substituted. In some cases, R 1 is a 12-membered heterocyclic ring optionally substituted. In some cases, R 1is a 13-membered heterocyclic ring which is optionally substituted. In some cases, R 1 is a 14-membered heterocyclic ring which is optionally substituted. In some cases, R 1 is a 15-membered heterocyclic ring which is optionally substituted. In some cases, R 1 The heterocyclic ring is tricyclic. In some cases, R 1 The heterocyclic ring contains a fused heterocyclic ring. In some cases, R 1 The heterocyclic ring contains a spiro heterocyclic ring. In some cases, R 1 The heterocyclic ring contains a fused spiro heterocyclic ring. In some cases, R 1 The heterocyclic ring is an unsaturated heterocyclic ring. In some cases, R 1 The heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, R 1 The heterocyclic ring has at least one double bond. In some cases, R 1 The heterocyclic ring has at least two double bonds. In some cases, R 1 The heterocyclic ring has at least two heteroatoms. In some cases, R 1 The heterocyclic ring has at least three heteroatoms. In some cases, R 1 The heterocyclic ring has at least four heteroatoms. In some cases, R 1 The heterocyclic ring has at least five heteroatoms. In some cases, R 1 The heterocyclic ring has at least six heteroatoms. In some cases, R 1 The heterocyclic ring has at least seven heteroatoms. In some cases, the heteroatoms are selected from oxygen, nitrogen and sulfur. In some cases, R 1 The heterocyclic ring has at least three, four or five nitrogen atoms and at least one sulfur atom. In some cases, R 1 The heterocyclic ring has at least three, four or five nitrogen atoms and at least one oxygen atom. In some cases, R 1 The heterocyclic ring has at least three, four or five nitrogen atoms. In some cases, R 1The complex ring 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 is [Chemical formula] selected from, each of which is optionally substituted with one or more substituents. In some cases, R 1 is [Chemical formula] selected from, each of which is optionally substituted with one or more substituents. In some cases, one or more optional substituents of R 1 are 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, =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 alkynyl, independently selected. In some cases, one or more optional substituents of R 1 are 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)NHOR20 , -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 alkynyl, independently selected. In some cases, one or more optional substituents of R 1 are independently selected from halogen, -OH, C 1~6 alkyl and -C(O)N(R 20 )2. In some cases, R 1 is

Chemical formula

Chemical formula

[0176] In some embodiments of the compound or salt of formula (I), R 1 is an optionally substituted 12- to 15-membered heterocyclic ring. In some cases, R 1 is

Chemical formula

Chemical formula

[0177] In some embodiments of the compound or salt of formula (I), R 1 is selected from 5- to 12-membered bridged heterocycles, which are optionally substituted by one or more substituents. In some cases, R 1is selected from an 8-membered crosslinked heterocyclic ring, which is optionally substituted with one or more substituents. In some cases, the crosslinked heterocyclic ring has at least one heteroatom. In some cases, the crosslinked heterocyclic ring has at least two heteroatoms. In some cases, the crosslinked heterocyclic ring has at least one nitrogen atom. In some cases, the crosslinked heterocyclic ring has at least two nitrogen atoms. In some cases, the crosslinked heterocyclic ring has two nitrogen atoms. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

[0178] In some embodiments of the compound or salt of formula (I), R 1 is selected from a 5- to 12-membered unsaturated heterocyclic ring, which is optionally substituted with one or more substituents. In some cases, the 5- to 12-membered unsaturated heterocyclic ring is

Chemical formula

[0179] In some embodiments of the compound or salt of formula (I), the 5- to 12-membered heterocyclic ring of R 1 is an unsaturated crosslinked heterocyclic ring. In some cases, R 1 is selected from an optionally substituted 7- to 8-membered unsaturated crosslinked heterocyclic ring. In some cases, R 1 is

Chemical formula

[0180] In some embodiments of the compound or salt of formula (I), R 1 is selected from a 10-membered heterocyclic ring which is optionally substituted. In some cases, the 10-membered heterocyclic ring is a bicyclic heterocyclic ring. In some cases, the 10-membered heterocyclic ring is a spiro heterocyclic ring. In some cases, the 10-membered heterocyclic ring is a fused heterocyclic ring. In some cases, the 10-membered heterocyclic ring is a saturated heterocyclic ring. In some cases, the 10-membered heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, the 10-membered heterocyclic ring contains at least one nitrogen atom. In some cases, the 10-membered heterocyclic ring contains at least two nitrogen atoms. In some cases, the 10-membered heterocyclic ring contains at least three nitrogen atoms. In some cases, the 10-membered heterocyclic ring contains at least one sulfur atom. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0181] In some embodiments of the compound or salt of formula (I), R 1 is selected from an optionally substituted 8- to 10-membered fused heterocyclic ring. In some cases, the 8- to 10-membered fused heterocyclic ring is a bicyclic heterocyclic ring. In some cases, the 8- to 10-membered fused heterocyclic ring is a saturated heterocyclic ring. In some cases, the 8- to 10-membered heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, R 1is selected from 10-membered fused heterocyclic rings which are optionally substituted. In some cases, the 10-membered fused heterocyclic ring is a bicyclic heterocyclic ring. In some cases, the 10-membered fused heterocyclic ring is a saturated heterocyclic ring. In some cases, the 10-membered heterocyclic ring is a non-aromatic heterocyclic ring. In some cases, the fused heterocyclic ring has one saturated ring and one aromatic ring. In some cases, the fused heterocyclic ring has one saturated ring and one unsaturated ring. In some cases, the fused heterocyclic ring has two saturated rings. In some cases, the 10-membered heterocyclic ring contains at least one nitrogen atom. In some cases, the 10-membered heterocyclic ring contains at least two nitrogen atoms. In some cases, the 10-membered heterocyclic ring contains at least three nitrogen atoms. In some cases, R 1 is [Chemical formula] selected from, each of which is optionally substituted by one or more substituents. In some cases, R 1 is [Chemical formula] wherein, which is optionally substituted by one or more substituents. In some cases, the one or more optional substituents are halogen, =O, -OH, -CN, -NHCN, -C(O)R 20 , -C(O)N(R 20 )2, -C(O)NR 20 OR 20 , C 1~6 aminoalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl and C 1~6 alkyl, independently selected. In some cases, the one or more optional substituents are halogen, =O, -C(O)R 20 , -C(O)N(R 20 )2 and -C(O)NR 20 OR 20 , independently selected. In some cases, the one or more optional substituents are -C(O)R 20 , -C(O)N(R 20 )2 and -C(O)NR20 OR 20 is independently selected from. In some cases, one or more optional substituents are -C(O)R 20 is independently selected from. In some cases, one or more optional substituents are -C(O)N(R 20 )2 is independently selected from. In some cases, one or more optional substituents are -C(O)NR 20 OR 20 is independently selected from. In some cases, R 20 are each hydrogen; and C 1~6 alkyl, C 3~12 carbocyclic ring and 3- to 12-membered heterocyclic ring are independently selected from. In some cases, R 20 are each hydrogen; and C 1~6 alkyl and 3- to 12-membered heterocyclic ring are independently selected from. In some cases, R 20 are each hydrogen; and C 1~6 alkyl and 3- to 12-membered saturated heterocyclic ring are independently selected from. In some cases, one or more optional substituents of R 1 are

Chemical formula

Chemical formula

Chemical formula

[0182] In some embodiments relating to the compound or salt of formula (I), R 1 is selected from a 6- to 7-membered saturated heterocyclic ring optionally substituted. In some cases, R 1 is selected from a 6-membered saturated heterocyclic ring optionally substituted. In some cases, R 1 is

Chemical formula

Chemical formula

Chemical formula

[0183] In some embodiments regarding the compound or salt of formula (I), R 3 is -CN, and R 1 is

Chemical formula

Chemical formula

[0184] In some embodiments of the compound or salt of formula (I), B is an 8- to 10-membered fused carbocyclic ring which is optionally substituted. In some cases, B is a substituted 8- to 10-membered fused carbocyclic ring. In some cases, B is an 8- to 10-membered fused carbocyclic ring which is optionally substituted. In some cases, B is a substituted 9-membered fused carbocyclic ring. In some cases, B is [Chemical formula] which is optionally substituted by one or more substituents. In some cases, B is [Chemical formula] which is substituted by one or more substituents. In some cases, for B, one or more substituents are independently selected from halogen, oxo, -NH2, C1-C3 alkyl, -B(OH)2, -OH, -C(O)NH2, -NH2, =O, -CN, C 1~6 alkoxy, C 1~6 hydroxyalkyl and C 2~6 alkynyl. In some cases, B is substituted by at least one halogen. In some cases, B is substituted by at least one chlorine. In some cases, B is substituted by at least one fluorine. In some cases, B is [Chemical] selected from. In some cases, B is [Chemical] and is substituted with one or more substituents selected from halogen and C 1~6 haloalkyl. In some cases, B is [Chemical] and is substituted with one or more substituents selected from halogen. In some cases, B is [Chemical] selected from. In some cases, B is [Chemical] and is substituted with one or more substituents selected from fluorine. In some cases, B is [Chemical] selected from. In some cases, B is [Chemical] and is substituted with one or more substituents selected from chlorine. In some cases, B is [Chemical] selected from.

[0185] In some embodiments of the compound or salt of formula (I), R 1 is selected from optionally substituted 10-membered unsaturated fused heterocycles. In some cases, R 1 is [Chemical] and this is optionally substituted. In some cases, R 1 one or more optional substituents of 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 OR 20 , C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl and C 1~6 alkyl are independently selected. In some cases, B is an optionally substituted 8- to 10-membered fused heterocycle containing one sulfur atom. In some cases, B is

Chemical Formula

Chemical Formula

[0186] In some embodiments of the compound or salt of formula (I), R 1 is selected from an optionally substituted 11-membered fused heterocyclic ring. In some cases, R 1 is selected from an optionally substituted 11-membered unsaturated fused heterocyclic ring. In some cases, the heterocyclic ring contains at least one sulfur atom. In some cases, the heterocyclic ring contains at least one nitrogen atom. In some cases, the heterocyclic ring contains three heteroatoms. In some cases, the heterocyclic ring is

Chemical formula

Chemical formula

[0187] In some embodiments of the compound or salt of formula (I), one or more optional substituents of R 1 are halogen, -CN, -NO2, =O, -N(R 20 )2, -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 1~6 Aminoalkyl, C 1~6 Alkoxy, C1~6 alkoxyalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl, C 1~6 haloalkyl, C 1~6 alkyl, C 2~6 alkenyl and C 2~6 alkynyl are each independently selected. In some cases, one or more optional substituents are halogen, -OH, -N(R 20 )2, -NO2, =O, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl and C 1~6 haloalkyl are independently selected. In some cases, the optional substituents of R 1 are halogen, -OH, -N(R 20 )2, -NO2, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl and C 1~6 haloalkyl are each independently selected. In some cases, the optional substituents of R 1 are halogen, -CN, -OH, -NH2, C 1~6 aminoalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl and C 1~6 haloalkyl are each independently selected. In some cases, the optional substituents of R 1 are each independently selected from -OH and -NH2. In some cases, R 20 is selected from hydrogen and C 1~3 alkyl.

[0188] In some embodiments of the compound or salt of formula (I), n is selected from 0 to 4. In some cases, n is selected from 0 to 3. In some cases, n is selected from 0 to 2. In some cases, n is selected from 0 and 1. In some cases, n is 0. In some cases, n is 1. In some cases, n is 2.

[0189] In some embodiments of the compound or salt of formula (I), R 4 is each independently selected from halogen, -NO2, =O, =S, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 2~6 alkynyl, C 1~6 cyanoalkyl and C 1~6 haloalkyl. In some cases, R 4 is independently selected from halogen, =O, -CN, C 1~6 cyanoalkyl, C 2~6 alkynyl, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl and C 1~6 haloalkyl. In some cases, R 4 is independently selected from halogen, =O, -CN, C 1~6 cyanoalkyl, C 2~6 alkynyl and C 1~6 haloalkyl. In some cases, R 4 is -CN, C 1~6 cyanoalkyl and C 2~6 alkynyl. In some cases, R 4 is each independently selected from halogen, -NO2, =O, =S, -CN, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 cyanoalkyl, C 1~6 hydroxyalkyl and C 1~6 haloalkyl.

[0190] In some embodiments of the compound or salt of formula (I), Q is a bond. In some cases, Q is S. In some cases, Q is O.

[0191] In some embodiments of the compound or salt of formula (I), R 7 is each independently halogen, hydroxy, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl and -N(R5 ) are independently selected from 2. In some cases, R 7 are each independently selected from halogen, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl and C1-C4 hydroxyalkyl.

[0192] In some embodiments of the compound or salt of formula (I), R 20 are each hydrogen; and C 1~6 alkyl, C 3~12 are independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 are independently selected from carbocycles and 3- to 12-membered heterocycles and are optionally substituted by one or more substituents selected therefrom. In some cases, R 20 are each independently selected from hydrogen and C 1~6 alkyl. In some cases, R 20 are each independently selected from C 1~6 alkyl.

[0193] In some embodiments of the compound or salt of formula (I), R 21 are each hydrogen; and C 1~6 alkyl, C 3~12 are independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 are independently selected from carbocycles and 3- to 12-membered heterocycles and are optionally substituted by one or more substituents selected therefrom. In some cases, R 21 are each independently selected from hydrogen and C 1~6 alkyl. In some cases, R21 is each independently selected from C 1~6 alkyls.

[0194] In some embodiments of the compound or salt of formula (I), R 20 is each independently hydrogen; and C 1~6 alkyl, C 3~12 carbocyclic ring, and 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 carbocyclic ring, and 3- to 12-membered heterocyclic ring. In some cases, R 20 is each independently selected from hydrogen and C 1~6 alkyl. In some cases, R 20 is each independently selected from C 1~6 alkyls.

[0195] In some embodiments of the compound or salt of formula (I), R 23 is each independently hydrogen; and C 1~6 alkyl, C 3~12 carbocyclic ring, and 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 carbocyclic ring, and 3- to 12-membered heterocyclic ring. In some cases, R 23 is each independently selected from hydrogen and C 1~6 alkyl. In some cases, R 23 is each independently selected from C 1~6 alkyls.

[0196] In one aspect, the present disclosure provides a compound of formula (I-A) [Chemical formula] or a pharmaceutically acceptable salt thereof (wherein R 1 is selected from 8- to 10-membered heterocycles, and the 8- to 10-membered heterocycle is halogen, -OR 20 , -S(O)2(R 20 ), -C(O)N(R 20 )2, -C 1~6 alkyl(=NOR 20 ), -C(O)R 20 , =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 1~6 alkyl-SO2R 20 , C 1~6 alkoxyalkyl, C 1~6 alkyl, C 2~6 alkynyl and one or more substituents independently selected from 5- to 12-membered heterocycles, and the 5- to 12-membered heterocycle is optionally substituted by one or more R 1* each independently as needed, R 1* each is 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 OR 20 , -N(R 20 )C(O)R20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -OC(O)N(R 20 )2, -NO2, =O, =N(R 20 ) =NO(R 20 ), -CN, -NHCN, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl, C 1~6 haloalkyl, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, and C3 - C 12 are independently selected from carbocycles, B is selected from 7 - to 15 - membered heterocycles and C7 - C 15 carbocycles, and the 7 - to 15 - membered heterocycles and C7 - C 15 carbocycles are halogen, -CN, -NO2, =O, -N(R 21 )2, -B(OR 21 )2, -OR 21 , -SR 21 , -S(O)2(R 21 ), -S(O)2N(R 21 )2, -NR 21 S(O)2R 21 , -C(O)N(R 21 )2, -C(O)NR 21 OR 21 , -N(R 21 )C(O)R 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )C(O)OR 21 , -C(O)R 21 , C(O)OR 21 , -OC(O)R 21, -OC(O)N(R 21 )2, 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 alkenyl, C 2~6 alkynyl, C3 - C 12 optionally substituted by one or more substituents independently selected from carbocycles and 5 - to 12 - membered heterocycles, Y is selected from a bond, -O-, -S- and -N(R 5 )-, R 2 is selected from heterocycles, aryl, C1 - C6 alkyl, -L - heterocycle, -L - N(R 23 )2, -L - OR 23 , -L - aryl, -L - heteroaryl, -L - cycloalkyl, -L - NHC(=NH)NH2, -L - C(O)N(R 23 )2, -L - C1 - C6 haloalkyl, -L - OR 23 , -L - NR 23 C(O)-aryl, -L - COOH, -L - NR 23 S(O)2(R 23 ), -L - S(O)2N(R 23 )2, -L - N(R 23 )C(O)(OR 23 ), -L - OC(O)N(R 23 )2 and -L - C(=O)OC1 - C6 alkyl, and the heterocyclic ring, the heterocyclic ring moiety of -L - heterocycle and the cycloalkyl moiety of -L - cycloalkyl are each optionally substituted by one or more R 6 ; the aryl, the aryl moiety of -L - NR 23 C(O)-aryl, the aryl moiety of -L - NR 23 C(O)-aryl, the aryl of -L - aryl and the heteroaryl of -L - heteroaryl are each optionally substituted by one or more R 7which is replaced as needed, respectively, R 3 is hydrogen, halogen, -CN, -NO2, -N(R 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, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -OC(O)N(R 20 )2, 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 alkenyl, C 2~6 alkynyl, C3-C 12 selected from carbocycles and 5- to 12-membered heterocycles, R 4 is each halogen, -NO2, =O, =S, -CN, C 1~6 alkyl, C 2~6 alkynyl, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6 cyanoalkyl, C 1~6 hydroxyalkyl and C 1~6independently selected from haloalkyl, n is selected from 0, 1, 2, 3 and 4, R 5 each is independently selected from hydrogen and C1-C6 alkyl, R 6 each is 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, -C1-C3 alkyl-N(R 5 )2, -C(O)N(R 5 )2, tert-butyldimethylsilyloxy CH2-, -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-C3 alkyl)O(C1-C3 alkyl), -OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl(C1-C3 alkyl)N(CH3)2, -OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl, -OC(O)heterocycle, -O-C1-C3 alkyl, -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 20and independently selected from -CH2 heterocycles, the phenyl of -NHC(O)phenyl and -OC(O)NH(C1-C3 alkyl)(C1-C3 alkyl)phenyl is optionally substituted by one or more substituents selected from -C(O)H and OH, the alkyl of -O-C1-C3 alkyl is optionally substituted by substituents selected from heterocycles, oxo and hydroxy, the heterocycle of -CH2 heterocyclyl is optionally substituted by oxo, Each Q is independently selected from a bond, S and O, R 7 is independently selected from halogen, hydroxy, HC(=O)-, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, -C1-C3 alkyl-N(R 5 )2, -C(O)N(R 5 )2 and -N(R 5 )2, Each L is independently selected from halogen, hydroxy, C 1~6 alkoxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C1-C4 alkylene optionally substituted by one or more substituents independently selected from C3-C6 carbocycles and 3-8 membered heterocycles, and the C3-C6 carbocycles and 3-8 membered heterocycles are halogen, -OH, -NO2, =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 haloalkyl, each optionally substituted by one or more substituents independently selected therefrom, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocycle or 3-8 membered heterocycle, and the C3-C6 carbocycles and 3-8 membered heterocycles are halogen, -OH, -NO2, =O, =S, -CN, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxy, C 1~6Hydroxyalkyl and C 1~6 Each is optionally substituted by one or more substituents independently selected from haloalkyl, R 20 each is hydrogen; and C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~12 independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is optionally substituted by one or more substituents, R 21 each is hydrogen; and C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~12 independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C 3~12 independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is optionally substituted by one or more substituents, R 23 each is hydrogen; and C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~12 independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is halogen, -OH, -CN, -NO2, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl, oxo, C3~12 (optionally substituted by one or more substituents independently selected from a carbon ring and a 3- to 12-membered heterocyclic ring).

[0197] In some embodiments, formula (I) or formula (I-A) is formula (I-B) [Chemical formula] or a pharmaceutically acceptable salt thereof, wherein R 1 is [Chemical formula] selected from, each of which is halogen, -S(O)2(R 20 ), -C(O)N(R 20 )2, -C 1~6 alkyl(=NOR 20 ), -C(O)R 20 , =O and optionally substituted by one or more substituents independently selected from a 5- to 12-membered heterocyclic ring, and the 5- to 12-membered heterocyclic ring is optionally independently substituted by one or more R 1* respectively, R 1* are each halogen, -OR 20 , -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 alkyl independently selected from, Y is -O-, R 2 is selected from -L-heterocyclic ring, -L-N(R 23 )2, and the heterocyclic ring portion of the -L-heterocyclic ring is one or more R 6is replaced as necessary, B is selected from 7- to 15-membered heterocycles, the 7- to 15-membered heterocycles being halogen, -CN, =O, -N(R 21 )2, -OR 21 , 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 alkynyl, independently selected from one or more substituents, and is replaced as necessary, R 3 is hydrogen, halogen, -CN, -N(R 20 )2, -OR 20 , -C(O)R 20 , 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 and C 1~6 alkyl, and is selected from, R 20 each is hydrogen; and C 1~6 alkyl and C 3~12 carbocycles, independently selected from these, each of which is halogen, -OH, -CN, -NH2, -N(C 1~6 alkyl)2, C 1~10 alkyl, -C 1~10 haloalkyl, -O-C 1~10 alkyl and oxo, and is replaced as necessary by one or more substituents selected independently.)

[0198] In some embodiments, in the case of a compound or salt of formula (I), formula (I-A) or formula (I-B), R 1 is, [Chemistry] selected from [Chemistry] is optionally substituted with one or more substituents independently selected from halogen, -S(O)2(R 20 ), -C(O)N(R 20 )2, -C 1~6 alkyl(=NOR 20 ), -C(O)R 20 ), =O and a 5- to 9-membered heterocyclic ring, and the 5- to -membered heterocyclic ring is optionally independently substituted with one or more R 1* s, R 1* s are each independently selected from halogen, C 1~6 haloalkyl and C 1~6 alkyl.

[0199] In some embodiments, for a compound or salt of formula (I), formula (I-A) or formula (I-B), Y is -O-.

[0200] In some embodiments, for a compound or salt of formula (I), formula (I-A) or formula (I-B), R 2 is selected from an optionally substituted -L-heterocyclic ring and -L-N(R 23 )2. In some cases, R 2 is selected from an optionally substituted -L-5- to 8-membered heterocyclic ring and -L-N(R 23 )2. In some cases, R 2 is selected from an optionally substituted -L-heterocyclic ring. In some cases, R 2 is -L-N(R 23) is selected from 2. In some cases, the heterocyclic ring contains at least one nitrogen atom. In some cases, the heterocyclic ring contains at least one sulfur atom. In some cases, the heterocyclic ring contains at least one oxygen atom. In some cases, the heterocyclic ring is heteroaryl. In some cases, the heterocyclic ring is a saturated heterocyclic ring. In some cases, R 6 are each 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, C1-C3 alkyl-substituted pyrazolyl, -C1-C3 alkyl-N(R 5 )2, -C(O)N(R 5 )2, -N(R 5 )2, (C1-C3 alkoxy)C1-C3 alkyl-, (C1-C3 alkyl)C(=O), oxo, -O-C1-C3 alkyl. In some cases, R 6 are each independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, =CH2 and -O-C1-C3 alkyl. In some cases, when R 2 is heteroaryl, R 6 is selected from halogen and C1-C3 haloalkyl, C1-C3 alkyl. In some cases, when R 2 is heteroaryl, R 6 is selected from halogen. In some cases, R 23 is selected from hydrogen and C1-C3 alkyl. In some cases, R 23 are each independently selected from C1-C3 alkyl. In some cases, R 23are each selected from methyl. In some cases, each L is independently selected from C1-C4 alkylene optionally substituted with one or more substituents independently selected from halogen and C1-C4 alkyl, and optionally, two substituents on the same carbon atom of L together form a C3-C6 carbocyclic ring or a 4-6 membered heterocyclic ring, and the C3-C6 carbocyclic ring and the 3-6 membered heterocyclic ring are each optionally substituted with one or more substituents independently selected from halogen. In some cases, each L is

Chemical formula

Chemical formula

Chemical formula

[0201] In some embodiments, in the case of a compound or salt of formula (I), formula (I-A) or formula (I-B), Y-R 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0202] In some embodiments, in the case of a compound or salt of formula (I), formula (I-A) or formula (I-B), B is selected from 8- to 10-membered heterocycles, and the 8- to 10-membered heterocycle is optionally substituted by one or more substituents independently selected from halogen, -CN, -NH2 and C 1~6 alkyl. In some cases, the heterocycle of B is [Chemical formula] selected from. In some cases, B is [Chemical formula] selected from, each of which is optionally substituted by one or more substituents independently selected from halogen, -CN, -NH2 and C 1~6 alkyl. In some cases, B is [Chemical formula] selected from.

[0203] In some embodiments, for a compound or salt of formula (I), formula (I-A) or formula (I-B), R 3 is -CN. In some cases, R 3 is hydrogen. In some cases, R 3 is halogen. In some cases, R 3 is fluorine.

[0204] In some embodiments, for a compound or salt of formula (I), formula (I-A) or formula (I-B), R 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0205] In some embodiments, the compound or salt of formula (I), formula (I-A) or formula (I-B) does not contain an electrophilic moiety.

[0206] In some embodiments of the compound or salt of formula (I), formula (I-A) or formula (I-B), one or more optional substituents of R 1 are not electrophiles.

[0207] In some embodiments of the compound or salt of formula (I), R 1is selected from the compounds in the examples. In some cases, B is selected from the compounds in the examples. In some cases, Y is selected from the compounds in the examples. In some cases, R 2 is selected from the compounds in the examples. In some cases, R 3 is selected from the compounds in the examples.

[0208] In some embodiments of the compound or salt of formula (I), R 20 are each independently selected from hydrogen and C 1~3 alkyl. In some cases, R 20 are each independently selected from hydrogen and C1 alkyl.

[0209] In an aspect, the present disclosure provides a compound of formula (II):

Chemical formula

[0210] In some embodiments of the compound or salt of formula (II), A is selected from a C5-C7 carbocyclic ring optionally substituted. In some cases, A is selected from an unsaturated C5-C7 carbocyclic ring optionally substituted. In some cases, A is selected from a C5 carbocyclic ring optionally substituted. In some cases, A is selected from a C6 carbocyclic ring optionally substituted. In some cases, A is selected from a C7 carbocyclic ring optionally substituted. In some cases, the C7 carbocyclic ring of A is monocyclic. In some cases, the C7 carbocyclic ring of A is bicyclic. In some cases, A is

Chemical formula

Chemical formula

[0211] In some embodiments, formula (II) is represented by formula (II-A)

Chemical formula

[0212] In some embodiments, formula (II) is represented by formula (II-B)

Chemical formula

[0213] In some embodiments, formula (II) is represented by formula (II-C)

Chemical formula

[0214] In some embodiments of the compound or salt of formula (II), A is a fused C6-C7 carbocycle optionally substituted. In some cases, A is selected from fused C6-C7 unsaturated carbocycles optionally substituted. In some cases, A is

Chemical formula

Chemical formula

[0215] In some embodiments, formula (II) is formula (II-D)

Chemical formula

[0216] In some embodiments of the compound or salt of formula (II), formula (II-A), formula (II-B), formula (II-C) or formula (II-D), R 91 is halogen, -CN, -NO2, -N(R 21 )2, -OR 21 , -C(O)R 21 , C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxyalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl, C 1~6 haloalkyl, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C3-C 12 carbocycles and 5- to 12-membered heterocycles. In some cases, R 91 is selected from -CN.

[0217] In some embodiments relating to a compound or salt of formula (II), formula (II-A), formula (II-B), formula (II-C) or formula (II-D), R 92 is hydrogen, halogen, -CN, -NO2, -N(R 21 )2, -OR 21 , -SR 21 , -C(O)R 21 , -C(O)OR 21 , -OC(O)R 21 , 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 alkenyl, C 2~6 alkynyl, selected from C3-C 12 carbocycles and 5- to 12-membered heterocycles. In some cases, R 92 is selected from hydrogen, halogen, -CN and -N(R 21 )2. In some cases, R 92 is a selected -N(R 21 )2. In some cases, R 92 is selected from -NH2. In some cases, R 92 is -N(R 21 )C(O)R 21 . In some cases, R 92 is -N(H)C(O)C 1~6 alkyl. In some cases, R 92 is -N(H)C(O)tert-butyl.

[0218] In some embodiments relating to a compound or salt of formula (II), formula (II-A), formula (II-B), formula (II-C) or formula (II-D), R 93 is selected from hydrogen. In some cases, R 93 is selected from -C(O)OR 21 . In some cases, R 93 is hydrogen and -C(O)OR21 is selected from. In some cases, R 93 is selected from -C(O)O-tert-butyl. In some cases, R 93 is -C(O)OC 1~6 alkyl.

[0219] In some embodiments relating to a compound or salt of formula (II-A), formula (II-B), formula (II-C) or formula (II-D), R 94 are each halogen, -CN, -NO2, =O, -N(R 21 )2, -B(OR 21 )2, -OR 21 , 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 alkenyl, C 2~6 alkynyl, C3-C 12 carbocyclic and 5- to 12-membered heterocyclic rings, independently selected. In some cases, R 94 are each halogen, C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxyalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl, C 1~6 haloalkyl and C 1~6 alkyl, independently selected. In some cases, R 94 are each independently selected from C 1~6 alkyl. In some cases, R 94 are each independently selected from methyl.

[0220] In one aspect, the disclosure provides a process for preparing a compound or salt of formula (II).

[0221] In one aspect, the present disclosure provides a compound of formula (III):

Chemical formula

[0222] In some embodiments of the compound of formula (III) or a salt thereof, B is selected from 5- to 7-membered heterocycles which may be optionally substituted. In some cases, B is selected from 5- to 7-membered unsaturated heterocycles which may be optionally substituted. In some cases, B is selected from 5-membered heterocycles which may be optionally substituted. In some cases, the heterocycle of B has at least one sulfur atom. In some cases, the heterocycle of B has one sulfur atom.

[0223] In some embodiments, formula (III) is formula (III-A)

Chemical formula

[0224] In some embodiments of the compound or salt of formula (III) and formula (III-A), R 91 is halogen, -CN, -NO2, -N(R 21 )2, -OR 21 , -C(O)R 21 , C 1~6 alkyl-N(R 20 )2, C 1~6 aminoalkyl, C 1~6 alkoxyalkyl, C 1~6 hydroxyalkyl, C 1~6 cyanoalkyl, C 1~6 haloalkyl, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C3-C 12 carbocycles and 5- to 12-membered heterocycles. In some cases, R 91 is selected from -CN.

[0225] In some embodiments of the compound or salt of formula (III) and formula (III-A), R 92 is hydrogen, halogen, -CN, -NO2, -N(R 21 )2, -OR 21 , -SR 21 , -C(O)R 21 , -C(O)OR 21, -OC(O)R 21 , 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 alkenyl, C 2~6 alkynyl, C3-C 12 is selected from carbocyclic rings and 5- to 12-membered heterocyclic rings. In some cases, R 92 is selected from hydrogen, halogen, -CN, and -N(R 21 )2. In some cases, R 92 is selected from -N(R 21 )2. In some cases, R 92 is -NH2. In some cases, R 92 is -N(R 21 )C(O)R 21 . In some cases, R 92 is -N(H)C(O)C 1~6 alkyl. In some cases, R 92 is -N(H)C(O)tert-butyl.

[0226] In some embodiments of the compounds or salts of formula (III) and formula (III-A), R 93 is selected from hydrogen. In some cases, R 93 is selected from -C(O)OR 21 . In some cases, R 93 is selected from hydrogen and -C(O)OR 21 . In some cases, R 93 is selected from -C(O)O-tert-butyl. In some cases, R 93 is selected from -C(O)OC 1~6 alkyl.

[0227] In an aspect, the disclosure provides a process for preparing any one compound or salt of formula (III).

[0228] Preferred embodiments of the present invention are shown and described herein, but it will be apparent to those skilled in the art that such embodiments are presented by way of example only. Without departing from the present invention, numerous variations, modifications, and substitutions will now occur to those skilled in the art. It should be understood that various alternatives to the embodiments of the invention described herein can be used in practicing the invention. The following claims are intended to define the scope of the present invention, and the methods and structures within the scope of these claims and their equivalents are intended to be covered thereby.

[0229] A chemical entity having a carbon-carbon double bond or a carbon-nitrogen double bond may exist as the Z-isomer or the E-isomer (or the cis-isomer or the trans-isomer). Further, some chemical entities may exist as various tautomers. Unless otherwise specified, the compounds or salts of formula (I) are also intended to include all of the Z-isomers, E-isomers, and tautomers.

[0230] "Isomers" are different compounds that have the same molecular formula. "Stereoisomers" are isomers that differ only in the spatial arrangement of atoms. "Enantiomers" are pairs of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. The term "(±)" is used, where appropriate, to represent a racemic mixture. "Diastereoisomers" or "diastereomers" are stereoisomers that have at least two chiral atoms but are not mirror images of each other. Absolute stereochemistry is assigned according to the Cahn-Ingold-Prelog R-S system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be assigned as either R or S. A resolved compound of unknown absolute configuration can be designated as (+) or (-) according to the direction (dextrorotatory or levorotatory) in which the compound rotates plane-polarized light at the wavelength of the sodium D line. Certain compounds described herein contain one or more chiral centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomers, and those chiral centers can be defined as (R)- or (S)- with respect to absolute stereochemistry. The chemical entities, pharmaceutical compositions, and methods are intended to include all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers, and mixtures of intermediates. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or can be resolved using conventional techniques. The optical activity of a compound can be analyzed by any suitable method, including but not limited to chiral chromatography and polarimetry, and the degree of preference of one stereoisomer over the other can be determined.

[0231] The compounds or salts of formula (I) herein may, in some cases, exist as diastereomers, enantiomers or other stereoisomers. The compounds presented herein include all of the diastereomeric forms, enantiomers and epimers, as well as their racemates, mixtures of diastereomers and other mixtures, to the extent that they can be carried out by one of ordinary skill in the art by conventional experiments. Separation of stereoisomers can be carried out by chromatography, or by forming diastereomers and separating them by recrystallization or chromatography, or by any combination thereof (Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions", John Wiley And Sons, Inc., 1981, which is incorporated herein by reference for the purposes of this disclosure). Stereoisomers can also be obtained by stereoselective synthesis. Further, by recrystallization and / or trituration, a mixture of two enantiomers enriched in one of the two enantiomers can be purified to obtain a major enantiomer in a more optically enriched form.

[0232] "Tautomers" refer to molecules in which a proton shift from one atom of a molecule to another atom of the same molecule is possible. In certain embodiments, the compounds or salts of formula (I) exist as tautomers. In situations where tautomerism is possible, there may be a chemical equilibrium of tautomers. The exact ratio of tautomers depends on several factors, including physical state, temperature, solvent and pH. Some non-limiting examples of tautomeric equilibria include the following:

Chem.

Chem.

[0233] The compounds disclosed herein, in some embodiments, for example, 2 H, 3 H,11 C, 13 C and / or 14 is used in various enriched isotope forms that are rich in the content of C. In a specific embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, and thus increase the duration of action of the drug.

[0234] Unless otherwise specified, the compounds described herein are intended to include compounds that differ only in that one or more isotope-enriched atoms are present. For example, replacement of hydrogen with deuterium or tritium, or 13 C or 14 compounds having this structure are within the scope of the present disclosure, except for replacement of carbon with carbon enriched in

[0235] The compounds of the present disclosure optionally contain atomic isotopes in non-natural ratios in one or more atoms that make up such compounds. For example, the compound may be labeled with isotopes such as, for example, deuterium ( 2 H), tritium ( 3 H), iodine-125 ( 125 I), or carbon-14 ( 14 C). 2 H, 11 C, 13 C, 14 C, 15 C, 12 N, 13 N, 15 N, 16 N, 16 O, 17 O, 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S,36 S, 35 Cl, 37 Cl, 79 Br, 81 Br and 125 all isotope substitutions with I are contemplated. All isotopic variants of the compounds of the invention are included within the scope of the invention, whether or not radioactive.

[0236] In certain embodiments, the compounds disclosed herein are 1 partially or fully replaced by 2 H atoms with H atoms. Methods for synthesizing deuterium-containing compounds are known in the art and include, for example only, the following synthetic methods.

[0237] Deuterium-substituted compounds are synthesized using a variety of methods, such as those described in Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0238] The deuterated starting materials are readily available and, when subjected to the synthetic methods described herein, result in the synthesis of deuterium-containing compounds. A number of deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0239] The compounds of the present invention also include crystalline and amorphous forms of such compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, non-solvated polymorphs (including anhydrates), conformational polymorphs and amorphous forms, and mixtures thereof, as well as pharmaceutically acceptable salts and active metabolites of these compounds.

[0240] The compounds described herein may, in some cases, exist as diastereomers, enantiomers or other stereoisomers. Where the absolute stereochemistry is not specified, the compounds presented herein include all of the diastereomeric, enantiomeric and epimeric forms, and suitable mixtures thereof. Separation of stereoisomers can be effected by chromatography, or by forming diastereomers and separating them by recrystallization or chromatography, or by any combination thereof (Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions", John Wiley And Sons, Inc., 1981, which is incorporated herein by reference for the purposes of this disclosure). Stereoisomers can also be obtained by stereoselective synthesis.

[0241] The methods and compositions described herein include the use of amorphous and crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. Similarly, in some embodiments, active metabolites of these compounds having the same type of activity are included within the scope of the present disclosure. Further, the compounds described herein can exist in unsolvated forms, as well as solvated forms with pharmaceutically acceptable solvents such as water and ethanol. Solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0242] In certain embodiments, the compound or a salt of the compound may be a prodrug. For example, a hydroxyl in the parent compound may be provided as an ester or a carbonate ester, or a carboxylic acid present in the parent compound may be provided as an ester. The term "prodrug" is intended to encompass compounds that are converted to the pharmaceutical agents of the present disclosure under physiological conditions. One method for making a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to give rise to the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of the host animal, such as specific target cells in the host animal. For example, esters or carbonate esters (e.g., esters or carbonate esters of alcohols or carboxylic acids, and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0243] Prodrug forms of the compounds described herein that are metabolized in vivo to produce the compounds described herein are included within the scope of the claims. In some cases, some of the compounds described herein may serve as prodrugs for another derivative or active compound.

[0244] In some situations, prodrugs can be more easily administered than the parent drug, and thus are often useful. For example, a prodrug may be bioavailable by oral administration while its parent is not. A prodrug may also help increase the cellular permeability of a compound compared to the parent drug. A prodrug may also have improved solubility in a pharmaceutical composition compared to the parent drug. A prodrug may be designed as a reversible drug derivative for use as a modifier to enhance drug delivery to a site-specific tissue or to increase drug retention within cells.

[0245] In some embodiments, the prodrug design increases the lipophilicity of the pharmaceutical agent. In some embodiments, the prodrug design increases the effective aqueous solubility. See, for example, Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, all of which are hereby incorporated by reference for the purposes of such disclosure. According to another embodiment, the present disclosure provides a method of generating the compounds defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0246] Synthetic chemical transformations and methods useful in the synthesis of the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995). Pharmaceutical formulation

[0247] In certain embodiments, compositions are provided herein that comprise a therapeutically effective amount of a compound or salt of any of formula (I), formula (I-A) or formula (I-B) (also referred to herein as a "pharmaceutical agent").

[0248] The pharmaceutical composition can be formulated using one or more physiologically acceptable carriers, including additives and adjuvants, which facilitate the processing of the pharmaceutical agent into a pharmaceutically useful preparation. The appropriate formulation depends on the route of administration chosen. Summaries of pharmaceutical compositions are found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa., Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins, 1999).

[0249] The compositions and methods of the present disclosure can be utilized to treat an individual in need thereof. In certain embodiments, the individual is a mammal, such as a human or non-human mammal. When administered to an animal such as a human, the composition or pharmaceutical agent is preferably administered as a pharmaceutical composition comprising, for example, a pharmaceutical agent and a pharmaceutically acceptable carrier or additive. Pharmaceutically acceptable carriers are well known in the art and include, for example, aqueous solutions such as water or physiologically buffered saline, or oils such as glycols, glycerol, olive oil, or other solvents or vehicles such as injectable organic esters. In preferred embodiments, when such a pharmaceutical composition is for human administration, particularly for invasive routes of administration, such as injection or implantation that avoid transport or diffusion through an epithelial barrier, the aqueous solution is free of, or substantially free of, pyrogens. Additives can be selected, for example, to effect delayed release of the agent or to selectively target one or more cells, tissues, or organs. The pharmaceutical composition can be in dosage unit forms such as tablets, capsules, granules, reconstitutable lyophilized products, powders, solutions, syrups, suppositories, injections, etc. The composition can also be present in a transdermal delivery system, such as a skin patch. The composition can also be present in a solution suitable for topical administration, such as an eye drop.

[0250] Pharmaceutically acceptable additives can contain physiologically acceptable agents that act, for example, to stabilize a compound such as a pharmaceutical agent, increase its solubility, or increase its absorption. Such physiologically acceptable agents include, for example, carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, or other stabilizers or excipients. The selection of pharmaceutically acceptable additives, including physiologically acceptable agents, depends, for example, on the route of administration of the composition. The preparation or pharmaceutical composition can be a self-emulsifying drug delivery system or a self-microemulsifying drug delivery system. The pharmaceutical composition (preparation) can also be, for example, a liposome or other polymeric matrix that can incorporate the compounds of the present invention. For example, liposomes containing phospholipids or other lipids are carriers that are relatively simple to prepare and administer, non-toxic, physiologically acceptable, and metabolizable.

[0251] The pharmaceutical composition (preparation) can be administered to a subject by any of several routes of administration, for example, orally, such as a hydropharmaceutical, tablet, sprinkle capsule and capsule including gelatin capsule, bolus, powder, granule, paste for application to the tongue; absorption through the oral mucosa, for example, sublingually; intrarectally, rectally or vaginally, for example, as a pessary, cream or foam; parenterally, including intramuscularly, intravenously, subcutaneously or intrathecally, for example, as a sterile solution or suspension; intranasally; intraperitoneally; subcutaneously; transdermally, for example, as a patch applied to the skin; and topically, for example, as a cream, ointment or spray applied to the skin or as an eye drop. The present compound can also be formulated for inhalation. In certain embodiments, the compound can simply be dissolved or suspended in sterile water.

[0252] The pharmaceutical composition may be a sterile aqueous or non-aqueous solution, suspension or emulsion, such as a microemulsion. The additives described herein are examples and are in no way limiting. An effective amount or therapeutically effective amount refers to the amount of one or more pharmaceutical agents administered to a subject, either as a single dose or as part of a series of doses, effective to produce the desired therapeutic effect.

[0253] The subject may generally be monitored for therapeutic efficacy using assays and methods suitable for the condition being treated, which assays are familiar to those skilled in the art and are described herein. The pharmacokinetics of the pharmaceutical agent or one or more of its metabolites administered to the subject may be monitored by determining the level of the pharmaceutical agent or metabolite in a biological fluid derived from the subject, such as blood, a blood fraction, such as serum and / or urine, and / or other biological samples or tissues. The level of the pharmaceutical agent or metabolite may be measured during the course of treatment using any method practiced in the art and described herein for detecting the agent.

[0254] The dosage of the pharmaceutical agent described herein for treating a disease or disorder may depend on the condition of the subject, i.e., the stage of the disease, the severity of the symptoms caused by the disease, the general health status, as well as age, gender and weight, and other factors apparent to those skilled in the medical art. The pharmaceutical composition may be administered in a manner appropriate for the disease to be treated, as determined by those skilled in the medical art. In addition to the factors described herein and above related to the use of a pharmaceutical agent for treating a disease or disorder, the preferred period and frequency of administration of the pharmaceutical agent may also be determined or adjusted by factors such as the condition of the patient, the type and severity of the patient's disease, the specific form of the active ingredient, and the method of administration. The optimal dosage of the agent can generally be determined using experimental models and / or clinical trials. The optimal dosage may depend on the physique, weight or blood volume of the subject. The use of the minimum dosage sufficient to achieve an effective treatment is usually preferred. The design and conduct of preclinical and clinical trials for the pharmaceutical agents described herein, including when administered for prophylactic benefit, are well within the skill of those of ordinary skill in the relevant art. When two or more pharmaceutical agents are administered to treat a disease or disorder, the optimal dosage of each agent may be different, such as less than when any of the pharmaceutical agents are administered alone as monotherapy. In certain specific embodiments, combining two pharmaceutical agents may act synergistically or additively, and one agent may be used in a lesser amount than when administered alone. The amount of the pharmaceutical agent that may be administered per day can be, for example, between about 0.01 mg and 100 mg per kg of body weight, such as between about 0.1 and 1 mg per kg, between about 1 and 10 mg per kg, between about 10 and 50 mg per kg, between about 50 and 100 mg per kg. In other embodiments, the amount of the pharmaceutical agent that may be administered per day is between about 0.01 mg and 1000 mg per kg of body weight, between about 100 and 500 mg per kg, or between about 500 and 1000 mg per kg. The optimal dosage per day or per course of treatment may vary for the disease or disorder being treated and may vary with the route of administration and treatment regimen.

[0255] A pharmaceutical composition containing a pharmaceutical agent can be formulated in a manner appropriate for the delivery method by using techniques commonly practiced in the art. The composition may be in solid form, such as tablets, capsules, semi-solid, such as gels, liquid, or gas, such as aerosols. In other embodiments, the pharmaceutical composition is administered as a bolus injection.

[0256] Pharmaceutically acceptable additives are well known in the pharmaceutical field, for example, Rowe et al., Handbook of Pharmaceutical Excipients: A Comprehensive Guide to Uses, Properties, and Safety, 5 th Ed., 2006, and Remington: The Science and Practice of Pharmacy (Gennaro, 21 stIt is described in (Ed. Mack Pub. Co., Easton, PA (2005)). Exemplary pharmaceutically acceptable additives include sterile saline and phosphate buffered saline at physiological pH. Preservatives, stabilizers, dyes, buffers, etc. may be provided in the pharmaceutical composition. Additionally, antioxidants and suspending agents may also be used. Generally, the type of additive is selected based on the mode of administration and the chemical composition of the active ingredient(s). Alternatively, the compositions described herein may be formulated as lyophilized products. The compositions described herein may be lyophilized or, if not, formulated as a lyophilized product using one or more suitable additive solutions for dissolving and / or diluting the pharmaceutical agent(s) of the composition at the time of administration. In other embodiments, the pharmaceutical agent may be encapsulated within liposomes using techniques known and practiced in the art. In certain specific embodiments, the pharmaceutical agent is not formulated within liposomes for application to a stent that is used, although not exclusively, for treating highly occluded arteries. The pharmaceutical composition may be formulated for any suitable mode of administration described herein and in the art.

[0257] For example, pharmaceutical compositions for oral administration, or for injection, infusion, subcutaneous delivery, intramuscular delivery, intraperitoneal delivery, or other methods, may be in liquid form. Liquid pharmaceutical compositions may include, for example, one or more of the following: water, aqueous saline solutions, preferably saline, Ringer's solution, isotonic sodium chloride, non-volatile oils that can act as solvents or suspension media, polyethylene glycol, glycerin, propylene glycol, or other solvents, such as sterile diluents; antibacterial agents; antioxidants; chelating agents; buffers, and agents that adjust tonicity, such as sodium chloride or dextrose. Parenteral compositions can be enclosed in glass or plastic ampoules, disposable syringes or multi-dose vials. The use of saline is preferred, and pharmaceutical compositions for injection are preferably sterilized. In another embodiment, for the treatment of ophthalmological conditions or diseases, the liquid pharmaceutical composition may be applied to the eye in the form of eye drops. The liquid pharmaceutical composition may be delivered orally.

[0258] For oral formulations, at least one of the pharmaceutical agents described herein can be used alone or in combination with additives suitable for making tablets, powders, granules or capsules, and, optionally, diluents, buffering agents, humectants, preservatives, coloring agents and flavoring agents. The pharmaceutical agent may be formulated using a buffering agent that provides protection of the compound from the low pH of the gastric environment and / or an enteric coating. The pharmaceutical agent included in the pharmaceutical composition may be formulated for oral delivery, for example, using a flavoring agent in a liquid, solid or semi-solid formulation and / or using an enteric coating.

[0259] A pharmaceutical composition comprising any one of the pharmaceutical agents described herein may be formulated for sustained or slow release, also referred to as timed or controlled release. Such compositions can generally be prepared using well-known techniques and may be administered, for example, orally, rectally, intradermally or subcutaneously implanted, or by implantation at the desired target site. Sustained release formulations may contain a compound dispersed in a carrier matrix and / or a compound enclosed within a reservoir surrounded by a rate control membrane. Additives for use in such formulations are biocompatible and may also be biodegradable, and preferably, the formulation achieves a relatively constant level of release of the active ingredient. The amount of the pharmaceutical agent contained in the sustained release formulation depends on the implantation site, the rate of release and the predicted duration, as well as the nature of the condition, disease or disorder being treated or prevented.

[0260] In certain embodiments, a pharmaceutical composition comprising a pharmaceutical agent is formulated for transdermal, intradermal or topical administration. The composition can be administered as a powder / talc or other solid, liquid, spray, aerosol, ointment, foam, cream, gel, paste, using a syringe, dressing, transdermal patch, insert or syringe-like applicator. This is preferably in the form of a controlled release or sustained release formulation that is topically administered or injected directly, for example intradermally or subcutaneously, into the skin adjacent to or within the area to be treated. The active composition can also be delivered by iontophoresis. Preservatives can be used to prevent the growth of fungi and other microorganisms. Suitable preservatives include, but are not limited to, benzoic acid, butyl paraben, ethyl paraben, methyl paraben, propyl paraben, sodium benzoate, sodium propionate, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, thimerosal and combinations thereof.

[0261] A pharmaceutical composition containing a medicament can be formulated as an emulsion for topical application. An emulsion contains one kind of liquid dispersed in a large amount of a second liquid. The emulsion may be an oil-in-water emulsion or a water-in-oil emulsion. One or both of the oil phase and the water phase may contain one or more of a surfactant, an emulsifier, an emulsion stabilizer, a buffer, and other additives. The oil phase may contain other pharmaceutically approved oily additives. Suitable surfactants include, but are not limited to, anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants. The composition for topical application may also contain at least one suitable suspending agent, antioxidant, chelating agent, emollient, or humectant.

[0262] Ointments and creams may be formulated using an aqueous base or an oily base, for example, with the addition of a suitable thickening agent and / or gelling agent. Lotions may be formulated using an aqueous base or an oily base and generally also contain one or more of an emulsifier, a stabilizer, a dispersant, a suspending agent, a thickening agent, or a coloring agent. Liquid sprays may be delivered from a pressurized pack, for example, via a specially shaped closure. Oil-in-water emulsions can also be used in compositions, patches, dressings, and articles. These systems are semi-solid emulsion, microemulsion, or foam emulsion systems.

[0263] In some embodiments, the pharmaceutical agents described herein can be formulated as inhalants. The inhalation method can directly deliver the pharmaceuticals to the airway. The pharmaceutical agents can be formulated as aerosols, microspheres, liposomes, or nanoparticles. The pharmaceutical agents can be formulated using solvents, gases, nitrates, or any combination thereof. The compositions described herein are formulated to be delivered as liquid aerosols or inhalable dry powders, as needed. The liquid aerosol formulations are preferably atomized into particle sizes that can be delivered mainly to the terminal bronchioles and respiratory bronchioles, as needed. The liquid aerosols and inhalable dry powder formulations are preferably delivered throughout the bronchial tree to the terminal bronchioles and ultimately to the parenchyma.

[0264] The aerosol formulations described herein are preferably delivered, as needed, using an aerosol-forming device, such as an injection, vibrating porous plate, or ultrasonic nebulizer, that is preferably selected to enable the formation of aerosol particles having a mass median aerodynamic diameter mainly between 1 and 5 μm. Further, the formulation preferably has an equilibrium osmolality, ionic strength, and chloride concentration, and the minimum aerosolizable amount capable of delivering an effective dose of the pharmaceutical agent. Further, the aerosol formulation preferably does not negatively affect the function of the airway and does not cause undesirable side effects.

[0265] Examples of aerosolization devices suitable for administration of the aerosol formulations described herein include, for example, jet, vibrating porous plate, ultrasonic nebulizers, and energy applied dry powder inhalers that can atomize the formulation mainly into aerosol particle sizes in the range of 1 to 5 μm. By mainly in this application is meant at least 70% of all the aerosol particles generated, but preferably more than 90% are within the range of 1 to 5 μm. Jet nebulizers operate by air pressure to break up a liquid solution into aerosol droplets. Vibrating porous plate nebulizers operate by using the acoustic vacuum generated by a rapidly vibrating porous plate to extrude solvent droplets from the porous plate. Ultrasonic nebulizers operate by piezoelectric crystals that shear the liquid into small aerosol droplets. Various suitable devices are available, including, for example, the AeroNeb™ and AeroDose™ vibrating porous plate nebulizers (AeroGen, Inc., Sunnyvale, California), the Sidestream® nebulizer (Medic-Aid Ltd., West Sussex, England), the Pari LC® and Pari LC Star® jet nebulizers (Pari Respiratory Equipment, Inc., Richmond, Virginia), and the Aerosonic™ (DeVilbiss Medizinische Produkte (Deutschland) GmbH, Heiden, Germany) and UltraAire® (Omron Healthcare, Inc., Vernon Hills, Illinois) ultrasonic nebulizers.

[0266] In some embodiments, the medicament(s) can be formulated using an oily base or an ointment to form a semi-solid composition having a desired shape. These semi-solid compositions can contain, in addition to the medicament, dissolved and / or suspended bactericides, preservatives, and / or buffer systems. The petrolatum component that may be included can be any paraffin having a viscosity ranging from mineral oil incorporating isobutylene, colloidal silica, or stearate to paraffin wax. The absorbent base can be used together with an oily system. Additives can include cholesterol, lanolin (lanolin derivatives, beeswax, fatty alcohols, wool wax alcohol, emulsifiers with low HLB (hydrophobic-lipophilic balance), and various ionic and non-ionic surfactants, either alone or in combination.

[0267] Controlled-release or sustained-release transdermal or topical formulations can be achieved by the addition of time-release additives such as polymer structures, matrices, etc. that are available in the art. For example, the composition may be administered by the use of hot melt extrusion articles such as bioadhesive hot melt extrusion films. The formulation can include a cross-linked polycarboxylic acid polymer formulation. The cross-linking agent can be present in an amount that provides an appropriate adhesive force such that the system can maintain its attachment to the target epithelial or endothelial cell surface for a time sufficient to allow for the desired release of the compound.

[0268] Inserts, transdermal patches, dressings, or articles can include a mixture or coating of polymers that provide for the release of the medicament at a constant rate over a long period of time. In some embodiments, the article, transdermal patch, or insert can include a water-soluble pore-forming agent such as polyethylene glycol (PEG) that can be mixed with a water-insoluble polymer to increase the durability of the insert and extend the release of the active ingredient.

[0269] Transdermal devices (inserts, patches, bandages) may also contain water-insoluble polymers. Rate-controlling polymers may be useful for administration to sites where release can be effected using pH changes. These rate-controlling polymers can be applied using a continuous coating film during the processes of spraying and drying with the active compound. In one embodiment, the coating formulation is used to coat pellets containing the active ingredient, which are compressed to form solid biodegradable inserts.

[0270] Polymeric formulations can also be utilized to achieve controlled or sustained release. Biodegradable polymers described in the art may be used. By way of example, sustained-release gels and compounds may be incorporated into a polymeric matrix such as a hydrophobic polymer matrix. Examples of polymeric matrices include microparticles. The microparticles can be microspheres and the core may be of a material different from the polymeric shell. Alternatively, the polymer may be cast as a thin slab or film, a powder produced by milling or other standard techniques, or a gel such as a hydrogel. The polymer can also be in the form of a coating or part of a device such as a bandage, stent, catheter, vascular graft, or other device that facilitates the delivery of a medicament. The matrix can be formed by solvent evaporation, spray drying, solvent extraction and other methods known to those skilled in the art.

[0271] Kits are provided that contain one or more unit doses of one or more of the agents described herein, usually in oral or injectable doses. Such kits can include a container housing the unit dose, a package insert with information explaining the use of the drug and attendant benefits in the treatment of a disease, and, optionally, an instrument or device for delivering the composition. Methods of treatment

[0272] In one aspect, the present disclosure provides compounds that inhibit KRas G12 mutants. In some cases, the method can inhibit the activity of the KRas G12 mutant in cells. In some cases, inhibiting the activity of the KRas G12 mutant in cells involves contacting a cell in which inhibition of the activity of the KRas G12 mutant is desired with an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing a compound or salt of formula (I), formula (I-A) or formula (I-B) and a pharmaceutically acceptable additive. In some cases, the contacting is in vitro. In some cases, the contacting is in vivo. As used herein, the term "contacting" refers to bringing the indicated moieties together in an in vitro system or an in vivo system. For example, "contacting" a KRas G12D and / or other G12 mutants with a compound provided herein refers to administration of the compound provided herein to an individual or patient, such as a human, having a KRas G12D and / or other G12 mutants, and introduction of the compound provided herein, for example, into a sample containing a cell preparation or purified preparation containing a KRas G12D and / or other G12 mutants. In some cases, a cell in which inhibition of the activity of a KRas G12D and / or other G12 mutant is desired is contacted with an effective amount of a compound or salt of formula (I) or a pharmaceutical composition thereof to negatively modulate the activity of the KRas G12D and / or other G12 mutants. In some cases, by negatively modulating the activity of the KRas G12D and / or other G12 mutants, the methods described herein are designed to inhibit unwanted cell proliferation resulting from enhanced activity of the KRas G12D and / or other G12 mutants within the cell. The cells can be contacted in a single dose or multiple doses according to a specific treatment regimen that results in the desired negative modulation of the KRas G12D and / or other G12 mutants. The ability of a compound to bind to a KRas G12D and / or other G12 mutants can be monitored in vitro using well-known methods.

[0273] In some embodiments, the inhibitory activity of exemplary compounds in cells can be monitored, for example, by measuring the inhibition of the activity of KRas G12D and / or other G12 mutants in the amount of phosphorylated ERK.

[0274] In another aspect, there is provided a method of treating cancer in a patient in need thereof, the method comprising administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt of any one thereof, or the compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable additive. The compositions and methods provided herein can be used for the treatment of KRas G12D and / or other G12 mutant-related cancers in a patient in need thereof, which comprises administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt of any one thereof, or the compound or a pharmaceutically acceptable salt of any one thereof. In some cases, the KRas G12D and / or other G12 mutant-related cancer is lung cancer. The compositions and methods provided herein can be used for the treatment of a wide range of cancers including tumors such as lung, prostate, breast, brain, skin, uterine cancer, testicular cancer, etc. More specifically, the cancers that can be treated by the compositions and methods of the present invention include, but are not limited to, tumors of astrocyte, breast, cervical, colorectal, endometrial, esophageal, gastric, head and neck, hepatocyte, pharyngeal, lung, oral, ovarian, prostate and thyroid cancers and sarcomas. More specifically, these compounds are as follows: Heart: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchioloalveolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondroma, mesothelioma; Gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, bipoma), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyosarcoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyosarcoma);Urogenital tract: kidneys (adenocarcinoma, Wilms tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumor, lipoma); liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; bile duct: gallbladder carcinoma, papillary carcinoma, cholangiocarcinoma; bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondroma (osteochronfroma) (cartilaginous exostosis), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumor; nervous system: skull (osteoma, hemangioma, granuloma, xanthoma, Paget's disease), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, intracranial endodermal cell tumor (pinealoma), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumor), spinal nerve fibroma, meningioma, glioma, sarcoma); gynecology: uterus (endometrial carcinoma), cervix (cervical carcinoma, pre-tumor cervical dysplasia), ovary (ovarian carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa cell tumor, Sertoli-Leydig cell tumor, undifferentiated embryonal cell tumor, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, sarcoma botryoides (fetal rhabdomyosarcoma), fallopian tube (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 sarcoma, dysplastic nevus, lipoma, hemangioma, dermatofibroma, keloid, psoriasis;And the adrenal gland: It can be used to treat neuroblastoma. In some cases, the cancer is non-small cell lung cancer, small cell lung cancer, colorectal cancer, rectal cancer or pancreatic cancer. In some cases, the cancer is non-small cell lung cancer. In some cases, the concentration and the route of administration to the patient vary depending on the cancer being treated. The present compound, its pharmaceutically acceptable salts, and pharmaceutical compositions containing such compounds and salts may also be co-administered with other anti-neoplastic compounds, such as chemotherapeutic agents, or used in combination with other treatments such as radiation or surgical intervention, either as an adjunct before or after surgery.;

[0275] Similarly, provided herein are compounds of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt of any one of them, or a pharmaceutical composition of any one of them for use in therapy.

[0276] Similarly, provided herein are compounds of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt of any one of them, or a pharmaceutical composition of any one of them for use in the treatment of cancer.

[0277] Similarly, provided herein are compounds of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt of any one of them, or a pharmaceutical composition of any one of them for use in the inhibition of KRas G12D and / or other G12 mutants.

[0278] Similarly, provided herein are a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the treatment of a KRas G12D and / or other G12 mutant-related disease or disorder.

[0279] Similarly, provided herein is the use of a compound of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for treating cancer.

[0280] Similarly, provided herein is the use of a compound of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt of any one thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for inhibiting the activity of KRas G12D and / or other G12 mutants.

[0281] Similarly, provided herein is the use of a compound of formula (I), formula (I-A) or formula (I-B), or a pharmaceutically acceptable salt of any one thereof, or a pharmaceutical composition of any one thereof, in the manufacture of a medicament for treating a KRas G12D and / or other G12 mutant-related disease or disorder.

[0282] In another aspect, the present disclosure provides a method for treating cancer in a patient in need thereof, comprising: (a) determining that the cancer is associated with a KRas G12D mutation and / or other G12 mutants (e.g., a KRas G12D and / or other G12 mutant-related cancer), e.g., determined using an assay or kit approved by a regulatory authority, e.g., approved by the FDA; and (b) administering to the patient a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0283] The compounds described herein can be used in the preparation of a medicament for the prevention or treatment of a disease or condition. Further, a method for treating any of the diseases or conditions described herein in a subject in need of such treatment comprises administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising at least one compound described herein, or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable prodrug or a pharmaceutically acceptable solvate.

[0284] Compositions containing the compound(s) described herein can be administered for prophylactic and / or therapeutic treatment. In therapeutic use, the composition is administered to a patient already suffering from a disease or condition in an amount sufficient to cure or at least partially arrest the symptoms of the disease or condition. The effective amount for this use depends on the severity and course of the disease or condition, previous treatment, the health status, weight and response of the patient to the drug, and the judgment of the treating physician.

[0285] In prophylactic use, the composition containing the compounds described herein is administered to patients susceptible to a particular disease, disorder or condition, or otherwise at risk thereof. Such an amount is defined as a "prophylactically effective amount or dose". In this use, the exact amount also depends on the health status, weight, etc. of the patient. When used in patients, the effective amount for this use depends on the severity and course of the disease, disorder or condition, previous treatment, the health status of the patient and response to the drug, and the judgment of the treating physician.

[0286] In the discretion of the physician, if the patient's condition does not improve, the administration of the compound may be carried out over a long period, i.e., over a long period including the entire lifetime of the patient, in order to improve the symptoms of the patient's disease or condition or to control or limit them in other ways.

[0287] Once improvement of the patient's condition occurs, a maintenance dose is administered if necessary. Subsequently, the dosage or dosing frequency, or both, can be reduced, depending on the symptoms, to a level at which improvement of the disease, disorder or condition is maintained. However, the patient may require intermittent treatment based on a long term basis upon any recurrence of symptoms.

[0288] The amount of a given agent corresponding to such amounts will vary depending on factors such as the specific compound, disease or condition and its severity, the identity (e.g., weight) of the subject or host in need of treatment, etc., but nevertheless can be determined in a manner recognized in the art according to the specific circumstances surrounding the case, including, for example, the particular agent being administered, the route of administration, the condition being treated, and the subject or host being treated. However, generally, the dosage used for adult human treatment will usually range from about 0.02 to about 5000 mg per day, and in some embodiments, from about 1 to about 1500 mg per day. The desired dosage may conveniently be supplied as a single dose, or as divided doses administered simultaneously (or over a short period of time) or at appropriate intervals, for example, as two, three, four or more sub-doses per day.

[0289] The pharmaceutical compositions described herein may be in unit dosage forms suitable for single administration of precise dosages. In unit dosage forms, the formulation is divided into unit doses containing appropriate amounts of one or more compounds. The unit dosage may be in the form of a package containing discrete amounts of the formulation. Non-limiting examples are packaged tablets or capsules, and powders in vials or ampoules. An aqueous suspension composition can be packaged in a non-resealable container for single use. Alternatively, a container that can be resealed for multiple uses can be used, in which case it is common to include a preservative in the composition. By way of mere example, a parenteral injectable formulation may be supplied in unit dosage form including, but not limited to, an ampoule, or in a multi-dose container with a preservative added.

[0290] The toxicity and therapeutic efficacy of such treatment regimens can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, including, but not limited to, determination of LD 50 (the dose lethal to 50% of the population) and ED 50 (the dose therapeutically effective in 50% of the population). The dose ratio between the toxic and therapeutic effects is the therapeutic index, which is LD 50 versus ED 50It can be expressed as a ratio to. Compounds showing a high therapeutic index are preferred. When formulating the dosage range for use in humans, data obtained from cell culture assays and animal studies can be used. The dosage of such a compound preferably has an ED 50 within the range of circulating concentrations including. The dosage may vary within this range depending on the dosage form used and the route of administration utilized.

[0291] In certain embodiments, the present invention provides a method of treating or preventing a disease, condition or state in a patient in need thereof, the method comprising administering to the patient an effective amount of a compound of any one of the embodiments of the present invention or a pharmaceutically acceptable salt thereof. The disease, condition or state can be selected from the groups described elsewhere in this specification. Bifunctional compound

[0292] In some embodiments, the compounds herein can be employed to selectively eliminate the over-activated KRas signaling induced by KRas mutations by directly binding to the mutant KRas protein, either by stabilizing its GDP-bound form (inactive form) or by blocking the interaction between the GTP-bound form and its downstream target proteins. In some embodiments, another approach is a bifunctional molecule called a proteolysis-targeting chimera (PROTAC) that can bind to both the mutant KRas protein and an E3 ligase, creating an interaction between these two proteins and inducing KRas degradation (Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A, Dhe-Paganon S, Bradner JE. DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science. 2015 Jun 19; 348 (6241): 1376-81), hijacking the proteolytic machinery in cells and leveraging the substrate specificity of an E3 ligase (such as VHL, CRBN, or IAP).

[0293] Disclosed herein are bifunctional compounds composed of a target protein (i.e., KRAS G12D)-binding moiety and an E3 ubiquitin ligase-binding moiety, which can induce proteasome-mediated degradation of a selected protein. In some embodiments, the bifunctional compound comprises a target protein (i.e., KRAS G12D)-binding moiety and an E3 ubiquitin ligase-binding moiety known in the art. In some embodiments, the use of the compounds disclosed herein in the preparation of degradable target protein compounds by using chemical modifications of the compounds disclosed herein is disclosed herein. In some cases, the target protein-binding moiety is derived from a compound of formula (I), formula (I-A), or formula (I-B). Preparation of Compounds

[0294] The compounds of the present disclosure can generally be prepared by several methods well-known to those skilled in organic synthesis. By way of example, the compounds of the present disclosure can be synthesized using the methods described herein, along with synthetic methods known in the field of synthetic organic chemistry or variants thereof recognized by those skilled in the art.

[0295] The compounds of the present disclosure can be prepared as described in the schemes and examples described elsewhere in this specification.

Examples

[0296] The following examples further illustrate the invention, but of course should not be construed as in any way limiting its scope.

[0297] The following synthetic schemes are presented for illustrative purposes only, not by way of limitation. The following examples illustrate various methods for making the compounds described herein. It is understood that those skilled in the art may be able to make these compounds by similar methods or by combining other methods known to those skilled in the art. It is also understood that those skilled in the art can make them by similar methods described below by using appropriate starting materials and, if necessary, modifying the synthetic route. Generally, starting materials and reagents can be obtained from commercial suppliers, or synthesized according to information sources known to those skilled in the art, or prepared as described herein.

[0298] The present disclosure provides a process for preparing the compounds described herein (described in more detail below). Certain compounds with tables herein can be prepared using appropriate reagents in the schemes described herein. Synthesis of Intermediates Synthesis of Intermediate 1. 3-Chloro-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide.

Chemical formula

[0299] Step 1. Synthesis of 2-nitro-prop-2-ynyl-benzenesulfonamide (Int-1a). A solution of prop-2-yl-1-amine (1.87 mL, 29.1 mmol) and N,N-diisopropylethylamine (10.15 mL, 58.3 mmol) in DCM (100 mL) was cooled to 0 °C. 2-Nitrobenzenesulfonyl chloride (6.46 g, 29.15 mmol) was added in portions. Next, the solution was warmed to room temperature and stirred for an additional 1 hour. The mixture was washed with water and brine, dried over Na2SO4 and concentrated. Purification of the crude product by silica gel chromatography (eluting with 20% - 50% EtOAc in petroleum ether) gave 2-nitro-prop-2-ynyl-benzenesulfonamide (Int-1a, 5.98 g, 24.9 mmol, 85.4% yield) as a yellow solid. LCMS C9H9N2O4S(M+H) + Calculated value of m / z = 241.0, measured value: 241.0.

[0300] Step 2. Synthesis of (3-chloropropyl)-2-nitro-prop-2-ynyl-benzenesulfonamide (Int-1b). To a solution of 2-nitro-prop-2-ynyl-benzenesulfonamide (Int-1a, 1.0 g, 4.16 mmol) and cesium carbonate (6.764 g, 20.81 mmol) in acetone (30 mL) was added neat 1-bromo-3-chloro-propane (6.05 mL, 61.19 mmol) dropwise. After the addition was complete, the reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated, then washed with water and brine, dried over Na2SO4 and concentrated. The crude product was purified by silica gel chromatography (eluting with 20% - 50% EtOAc in petroleum ether). (3-chloropropyl)-2-nitro-prop-2-ynyl-benzenesulfonamide (Int-1b, 2.43 g, 7.67 mmol, 92.1% yield) was obtained as a yellow oil. LCMS C 12 H 14 ClN2O4S(M+H) + Calculated m / z = 317.0, found: 317.0.

[0301] Step 3. Synthesis of ethyl 5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1c). To a solution of (3-chloropropyl)-2-nitro-prop-2-ynyl-benzenesulfonamide (Int-1b, 10.0 g, 31.6 mmol) and ethyl 2-diazoacetate (5.4 g, 47.3 mmol) in chlorobenzene (80 mL) was added N,N-diisopropylethylamine (5.5 mL, 31.57 mmol). Next, the mixture was heated at 140 °C for 1.5 h. Then, cesium carbonate (12.3 g, 37.9 mmol) was added and the mixture was heated at 140 °C for 30 min. The solvent was concentrated and the mixture was extracted with EtOAc, washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by silica gel chromatography (eluting with 20% - 90% EtOAc in petroleum ether) and then triturated in EtOAc to give ethyl 5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1c, 5.80 g, 14.7 mmol, 46.6% yield) as a yellow solid. LCMS C 16 H 19 N4O6S(M+H) + Calcd for m / z = 395.1, Found: 395.0.

[0302] Step 4. Synthesis of ethyl 5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1d). To a solution of ethyl 5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1c, 12.6 g, 31.95 mmol) in THF (100 mL) and methanol (25 mL) was added 1 M LiOH (128 mL, 128 mmol) at 25 °C. The mixture was stirred at 55 °C for 2 h. The mixture was acidified to pH = 6 with HCl (1 mol / L in H2O), and the crude product was triturated in water and filtered. 5-(2-Nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylic acid (Int-1d, 11.5 g, 31.1 mmol, 97.3% yield) was obtained as a yellow solid. LCMS C 14 H 14 N4O6S(M+H) + Calculated m / z = 367.1, found: 367.0.

[0303] Step 5. Synthesis of N,N-dimethyl-5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Int-1e). To a solution of 5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylic acid (Int-1d, 9.6 mg, 26.2 mmol), DIEA (18.3 mL, 104.8 mmol) and HATU (14.95 g, 39.3 mmol) in DMF (90 mL) was added 2M methylmethanamine in THF (20 mL, 39.3 mmol) at 30 °C. The mixture was stirred at 30 °C for 2 h. The mixture was diluted with DCM (300 × 2 mL), washed with water (400 mL) and brine (400 × 2 mL), dried over Na2SO4 and concentrated to give the crude product N,N-dimethyl-5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Int-1e, 10.1 g, 24.4 mmol, 93.1% yield) as a yellow oil. LCMS C 16 H 20 N4O3S(M+H) + Calculated m / z = 394.1, found: 394.2.

[0304] Step 6. Synthesis of 3-chloro-N,N-dimethyl-5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Int-1f). To a solution of N,N-dimethyl-5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Int-1e, 10 g, 25.67 mmol) in DMF (100 mL) was added chlorosuccinimide (3.428 g, 25.67 mmol) at 0 °C under argon. The mixture was stirred at 45 °C for 1 h. The mixture was concentrated to give a crude product. The crude product was triturated in water and filtered to give 3-chloro-N,N-dimethyl-5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Int-1f, 10.2 g, 23.4 mmol, 91.0% yield) as a crude yellow solid. LCMS C 16 H 17 ClN4O6S(M+H) + Calculated m / z = 428.1, found: 428.0.

[0305] Step 7. Synthesis of 3-chloro-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Intermediate 1). To a solution of 3-chloro-N,N-dimethyl-5-(2-nitrophenyl)sulfonyl-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Int-1f, 10.2 g, 23.84 mmol), 4-methoxybenzenethiol (8.8 mL, 71.52 mmol) and Cs2CO3 (31067.73 mg, 95.36 mmol) in acetonitrile (100 mL). The mixture was stirred at 25 °C for 2 h. The mixture was concentrated and the crude product was purified by silica gel chromatography (eluting with 3% - 10% MeOH in DCM) to give 3-chloro-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide (Intermediate 1, 3.2 g, 13.2 mmol, 55.3% yield) as a yellow solid. LCMS C 10 H 15 ClN4O(M+H) + Calculated m / z = 243.1, found: 243.0 Alternative synthesis of Intermediate 1. Synthesis of 3-chloro-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide.

Chemical Structure

[0306] Step 1. Synthesis of diethyl 4-chloro-1H-pyrazole-3,5-dicarboxylate (Int-1g). To a solution of diethyl 1H-pyrazole-3,5-dicarboxylate (20 g, 94.25 mmol) in acetic acid (360 mL) was added dropwise NaClO (264 mL, 1980 mmol). After stirring at 25 °C for 3 h, the residual mixture was diluted with water and the mixture was extracted with ethyl acetate. Concentration of the combined organic layers gave a yellow solid which was dissolved in petroleum ether (160 mL) and EtOAc (20 mL), and then filtered to collect the solid, giving diethyl 4-chloro-1H-pyrazole-3,5-dicarboxylate (Int-1g, 15.20 g, 61.6 mmol, 65.38% yield) as a white solid and a mother liquor (7 g). LCMS C9H 12 ClN2O4(M+H) + Calculated m / z = 247.6, found: 247. 1 H NMR (400 MHz, CD3OD) δ 4.44 - 4.36 (m, 4H), 1.39 (t, J = 7.1 Hz, 6H).

[0307] Step 2. Synthesis of diethyl 1-[3-(tert-butoxycarbonylamino)propyl]-4-chloro-pyrazole-3,5-dicarboxylate (Int-1h). To a solution of diethyl 1-[3-(tert-butoxycarbonylamino)propyl]-4-chloro-pyrazole-3,5-dicarboxylate (Int-1g, 24.7 g, 24.46 mmol, 39.70% yield) in DMF (150 mL) were added tert-butyl N-(3-bromopropyl)carbamate (16141.77 mg, 67.79 mmol), potassium iodide (204.6 mg, 1.23 mmol), and Cs2CO3 (40157.83 mg, 123.25 mmol). Next, the mixture was stirred at room temperature for 16 h. The reaction was quenched with water, and the mixture was extracted three times with EtOAc. The combined organic phases were washed three times with water, dried, filtered, and the filtrate was collected and concentrated to give diethyl 1-[3-(tert-butoxycarbonylamino)propyl]-4-chloro-pyrazole-3,5-dicarboxylate (Int-1h, 24.70 g, 24.5 mmol, 39.70% yield) as a reddish-brown oil. LCMS C 17 H 27 ClN3O6(M+H) + Calculated m / z = 404.8; Found: 304.1 (M+H - Boc).

[0308] Step 3. Synthesis of diethyl 1-(3-aminopropyl)-4-chloro-pyrazole-3,5-dicarboxylate; hydrochloride (Int-1i). To a solution of diethyl 1-(3-aminopropyl)-4-chloro-pyrazole-3,5-dicarboxylate; hydrochloride (Int-1h, 25.5 g, 23.99 mmol, 98.05% yield) in 1,4-dioxane (50 mL) was added HCl / dioxane (150 mL, 600 mmol). Next, the mixture was stirred at 25 °C for 1 h. The reaction was concentrated to give diethyl 1-(3-aminopropyl)-4-chloro-pyrazole-3,5-dicarboxylate; hydrochloride (Int-1i, 25.50 g, 24.0 mmol, 98.05% yield) as a yellow oil for the next step. LCMS C 12 H 19ClN3O4(M+H) + Calculated value m / z = 304.1; Measured value: 304.3.

[0309] Step 4. Synthesis of ethyl 3-chloro-4-oxo-5,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1j). To a solution of diethyl 1-(3-aminopropyl)-4-chloro-pyrazole-3,5-dicarboxylate; hydrochloride (Int-1i, 25.5 g, 23.99 mmol) in methanol (500 mL) was added Et3N (16.74 mL, 119.93 mmol), and the mixture was stirred at 80 °C overnight. The reaction was concentrated to 20 mL, the resulting white solid was filtered, then diluted with MeOH and stirred for 10 minutes and filtered. Next, the solid was washed three times with water and extracted three times with DCM to obtain ethyl 3-chloro-4-oxo-5,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1j, 4.80 g, 18.6 mmol, 77.66% yield). LCMS C 10 H 13 ClN3O3(M+H) + Calculated value m / z = 258.67; Measured value: 258.1.

[0310] Step 5. Synthesis of ethyl 3-chloro-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1k). To a solution of ethyl 3-chloro-4-oxo-5,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1j, 4.8 g, 18.63 mmol) in THF (60 mL) was added borane-methyl sulfide complex (27.94 mL, 55.89 mmol) under N2. The reaction was stirred at room temperature for 2 hours and then at 45 °C for 32 hours. MeOH was added to quench the reaction at 0 °C, and then the mixture was concentrated to obtain ethyl 3-chloro-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1k, 4.50 g, 18.5 mmol). LCMS C10 H 15 ClN3O2(M+H) + Calculated value of m / z = 244.7; measured value: 244.3.

[0311] Step 6. Synthesis of O5-tert-butyl O2-ethyl 3-chloro-4,6,7,8-tetrahydropyrazolo[1,5-a][1,4]diazepine-2,5-dicarboxylate (Int-1l). To a solution of ethyl 3-chloro-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxylate (Int-1k, 4.5 g, 18.47 mmol) in DCM (60 mL) were added Et3N (7.73 mL, 55.4 mmol) and DMAP (225.6 mg, 1.85 mmol). Next, the mixture was stirred at room temperature for 10 minutes, then Boc2O (8...

Claims

1. A compound of formula (I): 【Chemical 521】 or a pharmaceutically acceptable salt thereof [wherein, B is a 7- to 15-membered heterocycle and C ７ ~C １５ carbocycle, said 7-15 membered heterocycle and C ７ ~C １５ Carbocycles include halogens, -CN, -NO ２ , =O, -N(R ２１ ) ２ , -B(OR ２１ ) ２ , -OR ２１ , -SR ２１ , -S(O) ２ (R ２１ ), -S(O) ２ N (R ２１ ) ２ , -NR ２１ S (O) ２ R ２１ , -C(O)N(R ２１ ) ２ , -C(O)NR ２１ OR ２１ , -N(R ２１ ) C(O)R ２１ , -N(R ２１ ) C(O)N(R ２１ ) ２ , -N(R ２１ ) C(O)OR ２１ , -C(O)R ２１ , C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ) ２ , 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 Alkenyl, C ２～６ Alkynyl, C ３ ~C １２ each optionally substituted with one or more substituents independently selected from carbocycle and 5- to 12-membered heterocycle; R １ is selected from hydrogen and a 5- to 15-membered heterocycle, said 5- to 15-membered heterocycle being selected from 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 １～６ Alkyl (=NOR ２０ ), -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 alkoxyalkyl, C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３ ~C １２ is optionally substituted by one or more substituents independently selected from carbocycles and 5- to 12-membered heterocycles, and said C ３ ~C １２ carbocycles and 5- to 12-membered heterocycles are each optionally independently substituted by one or more R １＊ ; 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)R ２ (=NR ２０ ), -NR ２ S(O) ２０ R ２０ ), -C(O)N(R ２０ ), -C(O)NR ２ OR ２０ ), -N(R ２０ C(O)R ２ ), -N(R ２０ C(O)N(R ２０ ), -N(R ２０ 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 ２ ), =NO(R ２０ ), -CN, -NHCN, C ２０ alkyl-N(R ２０ ), C ２０ aminoalkyl, C ２ alkoxy, C ２ hydroxyalkyl, C ２０ cyanoalkyl, C ２０ haloalkyl, C １～６ alkyl, C ２０ ), C ２ alkenyl, C １～６ alkynyl, and C １～６ are each independently selected from a 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 a C ３ -C １２ carbocyclic ring, and are independently selected Y is selected from bonding, -O-, -S- and -N(R ５ )-, R ２ is a complex ring, aryl, C １ ~C ６ alkyl, -L-complex ring, -L-N(R ２３ ) ２ , -L-OR ２３ , -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH ２ , -L-C(O)N(R ２３ ) ２ , -L-C １ ~C ６ haloalkyl, -L-OR ２３ , -L-NR ２３ C(O)-aryl, -L-COOH, -L-NR ２３ S(O) ２ (R ２３ ), -L-S(O) ２ N(R ２３ ) ２ , -L-N(R ２３ )C(O)(OR ２３ ), -L-OC(O)N(R ２３ ) ２ and -L-C(=O)OC １ ~C ６ alkyl, wherein the complex ring, the complex ring moiety of -L-complex ring and the cycloalkyl moiety of -L-cycloalkyl are each optionally substituted by one or more R ６ , and the aryl, the aryl moiety of -L-NR ２３ C(O)-aryl, the aryl moiety of -L-NR ２３ C(O)-aryl, the aryl of -L-aryl and the heteroaryl of -L-heteroaryl are each optionally substituted by one or more R ７ , R ３ is hydrogen, halogen, -CN, -NO ２ , -N(R 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 ), -NRS(O) ２ R, -C(O)N(R ２０ ), -N(R ２０ )C(O)R ２０ , -N(R ２ )C(O)N(R ２０ ), -N(R ２０ )C(O)OR ２ , -C(O)R ２０ , -C(O)OR ２０ , -OC(O)R ２０ , -OC(O)N(R ２０ ), C ２ alkyl-N(R ２０ ), C ２０ aminoalkyl, C ２０ alkoxy, C ２０ alkoxyalkyl, C ２０ hydroxyalkyl, C ２０ cyanoalkyl, C ２ haloalkyl, C １～６ alkyl, C ２０ ), C ２ alkenyl, C １～６ alkynyl, C １～６ -C １～６ carbon ring and 5-12 membered heterocyclic ring selected from １～６ ~C １～６ ~C １～６ ~C １～６ ~C ２～６ ~C ２～６ ~C ３ ~C １２ and is selected from carbon rings and 5-12 membered heterocyclic rings, R ４ each represents halogen, -NO ２ , =O, =S, -CN, C １～６ alkyl, C ２～６ alkynyl, C １～６ alkyl-N(R ２０ ), ２ C １～６ aminoalkyl, C １～６ alkoxy, C １～６ cyanoalkyl, C １～６ hydroxyalkyl and C １～６ is independently selected from haloalkyl, n is selected from 0, 1, 2, 3, and 4, R ５ are each independently selected from hydrogen and C １ -C ６ -C alkyls, R ６ is each halogen, hydroxy, C １ to C ３ hydroxyalkyl, C １ to C ３ alkyl, oxo, C １ to C ３ haloalkyl, C １ to C ３ alkoxy, cyano, =CH ２ =NO-C １ to C ３ alkyl, C １ to 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 to C ３ alkyl-substituted pyrazolyl, -C １ to C ３ alkyl-N(R ５ ) ２ 、-C(O)N(R ５ ) ２ 、-C １ to C ３ alkyl-N(R ５ ) ２ 、-C(O)N(R ５ ) ２ 、tert-butyldimethylsilyloxyCH ２ -、-N(R ５ ) ２ 、(C １ to C ３ alkoxy)C １ to C ３ alkyl-、(C １ to C ３ alkyl)C(=O)、oxo、(C １ to C ３ haloalkyl)C(=O)-、-SO ２ F、(C １ to C ３ alkoxy)C １ to C ３ alkoxy、-CH ２ OC(O)N(R ５ ) ２ , -CH ２ NH C(O) OC １ ~C ６ alkyl, -CH ２ NH C(O) N(R ５ ) ２ , -CH ２ NH C(O) C １ ~C ６ alkyl, -CH ２ (pyrazolyl), -CH ２ NHSO ２ C １ ~C ６ alkyl, -CH ２ OC(O) heterocycle, -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, -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 and -CH ２ independently selected from heterocycles, -NH C(O) phenyl and -OC(O) NH(C １ ~C ３ alkyl)(C １ ~C ３ The phenyl of (alkyl)phenyl is optionally substituted by one or more substituents selected from -C(O)H and OH, -O-C １ ~C ３ The alkyl of alkyl is optionally substituted by substituents selected from heterocyclic ring, oxo and hydroxy, -CH ２ The heterocyclic ring of heterocyclyl is optionally substituted by oxo, each Q is independently selected from a bond, S, and O, R ７ is each independently selected from halogen, hydroxy, HC(=O)-, C １ ~C ４ alkyl, C １ ~C ４ alkoxy, C １ ~C ４ haloalkyl, C １ ~C ４ hydroxyalkyl, -C １ ~C ３ alkyl-N(R ５ ) ２ , -C(O)N(R ５ ) ２ and -N(R ５ ) ２ and is independently selected from L is each independently selected from halogen, hydroxy, C １～６ alkoxy, C １ to C ４ hydroxyalkyl, C １ to C ４ alkyl, C ３ to C ６ and is optionally substituted by one or more substituents independently selected from carbocyclic rings and 3- to 8-membered heterocyclic rings, the C １ to C ４ alkylene is independently selected, and the C ３ to C ６ carbocyclic ring and 3- to 8-membered heterocyclic ring are each optionally substituted by one or more substituents independently selected from halogen, -OH, -NO 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 haloalkyl, and optionally, two substituents on the same carbon atom of L together form a C ３ to C ６ carbocyclic ring or 3- to 8-membered heterocyclic ring, and the C ３ to C ６ carbocyclic ring and 3- to 8-membered heterocyclic ring are each optionally substituted by one or more substituents independently selected from halogen, -OH, -NO ２ , =O, =S, -CN, C １～６ alkyl-N(R ２０ ) ２ , C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl and C １～６ haloalkyl, and are each optionally substituted as needed, R ２０ is each independently hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ is independently selected from carbocyclic and 3- to 12-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from halogen, -OH, -CN, -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 is independently selected from carbocyclic and 3- to 12-membered heterocyclic rings and is optionally substituted by one or more substituents R ２１ is each hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ is independently selected from carbocycles and 3- to 12-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -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 is independently selected from carbocycles and 3- to 12-membered heterocycles and is optionally substituted with one or more substituents R ２３ is each, hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ selected independently from carbocycles and 3- to 12-membered heterocycles, each of which is optionally substituted with one or more substituents selected independently from halogen, -OH, -CN, -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 selected independently from carbocycles and 3- to 12-membered heterocycles and optionally substituted with one or more substituents].

2. B is an 8- to 15-membered fused heterocyclic ring which may be optionally substituted and C which may be optionally substituted ８ -C １５ The compound or salt according to claim 1, which is selected from a fused carbon ring

3. The compound or salt according to claim 1 or 2, wherein B is an 8- to 15-membered fused heterocyclic ring which is optionally substituted.

4. B is C which is optionally substituted ８ ~C １５ The compound or salt according to claim 1 or 2, which is a condensed carbon ring

5. Regarding B, the 8- to 15-membered condensed heterocyclic ring optionally substituted and C optionally substituted ８ -C １５ The compound or salt according to any one of claims 1 to 3, wherein the condensed carbon rings are each independently bicyclic or tricyclic.

6. The compound or salt according to any one of claims 1 to 5, wherein the heterocyclic or carbocyclic ring of B is bicyclic.

7. The compound or salt according to any one of claims 1 to 5, wherein the heterocyclic or carbocyclic ring of B is tricyclic.

8. Regarding B, the 8- to 15-membered condensed heterocyclic ring optionally substituted and the optionally substituted C ８ ~C １５ The condensed carbon ring is 【Chemical 522】 selected from, each of which is optionally substituted by one or more substituents, the compound or salt according to any one of claims 1 to 7.

9. Regarding B, the 8- to 15-membered condensed heterocyclic ring optionally substituted and optionally substituted C ８ -C １５ The condensed carbon ring is 【Chemical 523】 selected from, each of which is optionally substituted by one or more substituents, the compound or salt according to claim 8.

10. Regarding B, the one or more optional substituents of the heterocyclic ring and the carbocyclic ring are oxo, -NH ２ , halogen and C １ ~C ３ alkyl, respectively independently selected, the compound or salt according to any one of claims 1 to 9.

11. Regarding B, the 8- to 15-membered condensed heterocyclic ring optionally substituted and the optionally substituted C ８ -C １５ The condensed carbon ring is 【Chemical 524】 selected from, the compound or salt according to any one of claims 1 to 10.

12. B is a 5- to 15-membered heterocyclic ring which may be optionally substituted and C which may be optionally substituted ３ to C １５ The compound or salt according to any one of claims 1 to 7, which is selected from a carbon ring

13. B is an 8- to 15-membered fused heterocyclic ring which may be optionally substituted and C which may be optionally substituted ８ ~C １５ The compound or salt according to claim 12, which is selected from a fused carbon ring.

14. The compound or salt according to claim 13, wherein B is an 8- to 15-membered fused heterocyclic ring which is optionally substituted.

15. B is an unsaturated C which is optionally substituted ８ -C １５ The compound or salt according to claim 13, which is a condensed carbon ring

16. The compound or salt according to any one of claims 12 to 15, wherein the heterocyclic and carbocyclic rings of B are each independently bicyclic or tricyclic.

17. The compound or salt according to claim 16, wherein the heterocyclic and carbocyclic rings of B are each independently bicyclic.

18. The compound or salt according to claim 16, wherein the heterocyclic and carbocyclic rings of B are each independently tricyclic.

19. B is 【Chemical 525】 【Chemical 526】 selected from, each of which is optionally substituted by one or more substituents, the compound or salt according to any one of claims 12 to 18.

20. B is 【Chemical 527】 selected from, each of which is optionally substituted by one or more substituents, the compound or salt according to claim 19.

21. B is 【Chemical 528】 selected from, each of which is optionally substituted by one or more substituents, the compound or salt according to claim 20.

22. Regarding B, the one or more optional substituents are oxo, -NH ２ , halogen, C １ ~C ３ The compound or salt according to any one of claims 12 to 21, independently selected from alkyl.

23. B is 【Chemical 529】 selected from, the compound or salt according to claim 22.

24. Regarding B, the one or more optional substituents of the heterocyclic ring and the carbocyclic ring are halogen, C １ to 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 alkynyl, each independently selected at each occurrence, a compound or salt according to any one of claims 1 to 21.

25. Regarding B, the one or more optional substituents of the heterocyclic ring and the carbocyclic 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 alkynyl, each independently selected each time it occurs, the compound or salt according to claim 24.

26. B is 【Chemical 530】 【Chemical 531】 The compound or salt according to claim 24 or 25, selected from

27. The compound or salt according to any one of claims 1 to 7, wherein B is a 7- to 12-membered condensed heterocyclic ring which may be optionally substituted.

28. The compound or salt according to any one of claims 1 to 7, wherein B is a 7- to 11-membered condensed heterocyclic ring which may be optionally substituted.

29. The compound or salt according to claim 27 or 28, wherein B is an 8- to 10-membered condensed heterocyclic ring which may be optionally substituted.

30. The compound or salt according to claim 29, wherein B is an 8- to 9-membered condensed heterocyclic ring which may be optionally substituted.

31. The compound or salt according to claim 27 or 28, wherein the heterocyclic ring is an unsaturated heterocyclic ring.

32. The compound or salt according to any one of claims 27 to 31, wherein B has at least one sulfur atom.

33. The compound or salt according to any one of claims 27 to 32, wherein B has at least one sulfur atom and at least one nitrogen atom.

34. The compound or salt according to any one of claims 27 to 32, wherein B has at least one sulfur atom and at least one oxygen atom.

35. The compound or salt according to any one of claims 27 to 32, wherein B has two sulfur atoms.

36. B is 【Chemical 532】 selected from, each of which may be optionally substituted, the compound or salt according to any one of claims 27 to 35.

37. B is 【Chemical 533】 selected from, each of which may be optionally substituted, the compound or salt according to claim 36.

38. B is 【Chemical 534】 selected from, each of which may be optionally substituted, the compound or salt according to claim 37.

39. The one or more optional substituents of B 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 alkynyl, each independently selected each time it appears, a compound or salt according to any one of claims 27 to 38.

40. Said one or more optional substituents of B are halogen, C １ -C ３ alkyl, -NH ２ and -CN, each independently selected at each occurrence, a compound or salt according to claim 39.

41. B is 【Chemical 535】 selected from, the compound or salt according to any one of claims 27 to 37.

42. B is a 7- to 12-membered fused heterocyclic ring which is optionally substituted and C which is optionally substituted ９～１０ The compound or salt according to any one of claims 1 to 7, which is selected from a fused carbon ring.

43. The compound or salt according to claim 42, wherein the heterocyclic ring of B has at least one sulfur atom.

44. The compound or salt according to claim 42 or 43, wherein the heterocyclic ring of B has one or more sulfur atoms.

45. The compound or salt according to claim 44, wherein the heterocyclic ring of B has at least one nitrogen atom.

46. B is 【Chemical 536】 The compound or salt according to any one of claims 42 to 45, selected from and each of these being optionally substituted.

47. The one or more optional substituents of B are 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 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 alkynyl, each independently selected each occurrence, a compound or salt according to any one of claims 42 to 46.

48. The one or more optional substituents of B are each independently selected from halogen, C １ to C ３ alkyl, -OH, -NH ２ , =O and -CN, a compound or salt according to any one of claims 42 to 46.

49. B is 【Chemical 537】 The compound or salt according to claim 47, selected from.

50. The compound or salt according to any one of claims 1 to 7, wherein B is selected from 8- to 10-membered condensed heterocycles having at least one sulfur atom and being optionally substituted.

51. B is 【Chemical 538】 The compound or salt according to claim 50, selected from and each of these being optionally substituted.

52. The one or more optional substituents of B are halogen, C １ ~C ３ Alkyl, -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 52. The compound or salt of claim 50 or 51, independently selected at each occurrence from alkynyl.

53. Said one or more optional substituents of B are halogen, C １ to C ３ alkyl, -NH ２ and -CN, each independently selected at each occurrence, a compound or salt according to claim 52.

54. The compound or salt according to any one of claims 50 to 53, wherein B is substituted.

55. B is at least one -NH ２ The compound or salt according to any one of claims 50 to 53, wherein is substituted by.

56. B is 【Chemical 539】 The compound or salt according to any one of claims X to Y, selected from.

57. B is at least one -NH ２ The compound or salt according to any one of claims 50 to 55, wherein at least one -CN is substituted.

58. B is 【Chemical 540】 The compound or salt according to claim 57, selected from.

59. R ３ is hydrogen, halogen, -CN, -C(O)R ２２ , C １～６ aminoalkyl, C １～６ alkoxy, C １～６ alkoxyalkyl, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl and C １～６ alkyl, a compound or salt according to any one of claims 1 to 58.

60. R ３ is hydrogen, fluorine, -CN, -C(O)H, C １ hydroxyalkyl and C １～６ alkyl, the compound or salt according to claim 59.

61. R ３ The compound or salt according to claim 59 or 60, wherein R is selected from hydrogen, fluorine and -CN.

62. R ３ The compound or salt according to claim 61, wherein R is selected from fluorine.

63. R ３ The compound or salt according to claim 61, wherein R is selected from hydrogen.

64. R ３ The compound or salt according to claim 61, wherein R is selected from -CN.

65. The compound or salt according to any one of claims 1 to 64, wherein Y is -O-.

66. L is C １ ~C ４ The compound or salt according to any one of claims 1 to 65, selected from alkylene

67. L is unsubstituted C １ ~C ４ The compound or salt according to claim 66, which is selected from alkylene

68. L is each independently selected from C, optionally substituted １ to C ４ alkylene, and optionally, two substituents on the same carbon atom of L together form a C ３ to C ６ carbocyclic ring or a 3- to 8-membered heterocyclic ring, and the C ３ to C ６ carbocyclic ring and the 3- to 8-membered heterocyclic ring are each optionally substituted with one or more substituents selected from halogen, -OH, -NO ２ , =O, =S, -CN, C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl, C １～６ haloalkyl, or a salt thereof, according to claim 66.

69. The optional substituent of L is C １ to C ４ hydroxyalkyl, C １ to C ４ alkyl, C ３ to C ６ selected from a carbocyclic ring, and optionally, two substituents on the same carbon atom of L are taken together to form a C ３ to C ６ carbocyclic ring or a 3- to 8-membered heterocyclic ring, and the C ３ to C ６ carbocyclic ring and the 3- to 8-membered heterocyclic ring are optionally substituted by one or more substituents selected from halogen and C １～６ haloalkyl, the compound or salt according to claim 68.

70. L is 【Chemical Formula 541】 The compound or salt according to any one of claims 65 to 69, selected from.

71. L is 【Chemical Formula 542】 The compound or salt according to claim 70, selected from.

72. L is each independently selected from substituted C １ ~C ４ ~C ３ ~C ６ The compound or salt according to claim 68 or 69, wherein two substituents on the same carbon atom of L together form a 3- to 5-membered carbocyclic or heterocyclic ring.

73. L is each independently selected from substituted C ２～３ alkylene, and two substituents on the same carbon atom of L together form a C ３ carbocyclic ring or a 4-membered heterocyclic ring, and the C ３ carbocyclic ring is optionally substituted by one or more substituents selected from halogen, the compound or salt according to claim 72.

74. Each L is 【Chemical Formula 543】 The compound or salt according to claim 73, independently selected from.

75. Each L is 【Chemical 544】 The compound or salt according to claim 74, independently selected from.

76. Each L is 【Chemical 545】 The compound or salt according to claim 75, independently selected from.

77. L is each independently selected from halogen and C １ ~C ４ alkyl optionally substituted with one or more substituents independently selected from C １ ~C ４ alkylene, a compound or salt according to claim 66.

78. L is 【Chemical 546】 The compound or salt according to claim 77, selected from.

79. L is each independently selected from unsubstituted C １ ~C ４ The compound or salt according to claim 66, which is independently selected from alkylene.

80. L is 【Chemical 547】 The compound or salt according to claim 79, selected from.

81. L is 【Chemical 548】 The compound or salt according to claim 80, selected from.

82. R ２ is selected from a heterocyclic ring, -L-heterocyclic ring, -L-aryl, -L-heteroaryl and -L-N(R ２３ ), ２ wherein the heterocyclic ring moiety of the heterocyclic ring and -L-heterocyclic ring is each optionally substituted by one or more R ６ s, and the aryl of the -L-aryl and the heteroaryl of the -L-heteroaryl are each optionally substituted by one or more R ７ s, a compound or a salt according to any one of claims 1 to 81.

83. R ２ is an -L-heterocyclic ring, and the heterocyclic ring moiety of R ２ is a heterocyclic ring which is optionally substituted, the compound or salt according to claim 82.

84. R ２ is an -L-heterocyclic ring optionally substituted by one or more R ６ The compound or salt according to claim 82 or 83, wherein

85. Y - R ２ is 【Chemical 549】 selected from, wherein the heterocyclic moiety is substituted by one or more R ６ as required, the compound or salt according to any one of claims 1 to 84.

86. R ２ in which the heterocyclic ring moiety is optionally substituted by one or more substituents selected from halogen, hydroxy, -CN, C １ to C ３ hydroxyalkyl, C １ to C ３ alkyl, C １ to C ３ haloalkyl, C １ to C ３ alkoxy and C １ to C ３ aminoalkyl, or a salt thereof, which is a compound according to any one of claims 82 to 85

87. R ２ wherein the heterocyclic moiety of １ is a heterocyclic ring optionally substituted with one or more substituents selected from C ３ -alkyl and halogen, the compound or salt according to claim 86.

88. Y - R ２ is 【Chemical Formula 550】 The compound or salt according to any one of claims 1 to 88, selected from.

89. Y - R ２ is 【Chemical 551】 selected from, wherein the heterocyclic moiety is one or more R ６ optionally substituted by, a compound or salt according to any one of claims 1 to 85.

90. R ２ The R ６ is independently selected each time it appears from halogen, hydroxy, C １ to C ３ hydroxyalkyl, C １ to C ３ alkyl, C １ to C ３ haloalkyl, C １ to C ３ alkoxy, cyano and C １ to C ３ aminoalkyl, the compound or salt according to claim 89.

91. R ２ The R of ６ is C １ to C ３ The compound or salt according to claim 90, wherein R is independently selected each time from alkyl and halogen.

92. Y - R ２ is 【Chemical 552】 The compound or salt according to claim 91, selected from.

93. Y - R ２ is 【Chemical Formula 553】 【Chemical 554】 selected from, wherein the heterocyclic ring moiety is optionally substituted by one or more R ６ The compound or salt according to any one of claims 1 to 82, which is substituted as necessary.

94. Y - R ２ is 【Chemical Formula 555】 The compound or salt according to claim 93, selected from

95. Y - R ２ is 【Chemical Formula 556】 The compound or salt according to claim 94, selected from and the heterocyclic ring is optionally substituted

96. wherein the heterocyclic ring is optionally substituted with one or more substituents selected from halogen, hydroxy, 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)heterocyclic ring, -CH ２ heterocyclic ring, -CH ２ OC(O)N(R ５ ), ２ and -O-C １ -C ３ -alkyl, and the alkyl of -O-C １ -C ３ -alkyl is optionally substituted with a substituent selected from a heterocyclic ring, oxo and hydroxy; the compound or salt according to claim 95.

97. Y - R ２ is 【Chemical Formula 557】 【Chemical Formula 558】 The compound or salt according to claim 1 or claims 95 to 96, selected from

98. R ２ is -L-heteroaryl, wherein the heteroaryl moiety is optionally substituted by one or more R ７ The compound or salt according to claim 82, wherein the compound or salt is selected from the group consisting of:

99. R ７ is each independently selected from halogen and C １ -C ４ -C haloalkyl, the compound or salt according to claim 98.

100. Y - R ２ is 【Chemical 559】 The compound or salt according to claim 99, selected from

101. R ２ is replaced, if necessary, by one or more R ７ -aryl, the compound or salt according to claim 82.

102. Y - R ２ is 【Chemical Formula 560】 selected from, wherein the heterocyclic moiety is optionally substituted by one or more R ７ The compound or salt according to claim 101, which is substituted as necessary by

103. Y - R ２ is 【Chemical Formula 561】 The compound or salt according to claim 102, selected from

104. R ２ is replaced, if necessary, by one or more R ７ -L-heteroaryl, the compound or salt according to claim 82.

105. Y - R ２ is 【Chemical 562】 selected from, wherein said heteroaryl moiety is optionally substituted by one or more R ７ The compound or salt according to claim 104, which is substituted as required by.

106. Y - R ２ is 【Chemical Formula 563】 The compound or salt according to claim 104 or 105, selected from

107. R ２ is -L-N(R ２３ ) ２ is a compound or salt according to claim 82.

108. Y - R ２ is 【Chemical 564】 The compound or salt according to claim 107, selected from

109. R ２ is a heterocyclic ring optionally substituted by one or more R ６ The compound or salt according to claim 108, wherein:

110. Y - R ２ is 【Chemical Formula 565】 The compound or salt according to claim 109, which is

111. Y - R ２ is 【Chemical 566】 The compound or salt according to claim 82, which is

112. R ２ is selected from a heterocyclic ring, -L-heterocyclic ring, -L-aryl and -L-heteroaryl, and -L-N(R ２３ ), ２ wherein the heterocyclic ring moieties of the heterocyclic ring and -L-heterocyclic ring are each optionally substituted by one or more R ６ s, and the aryl of the -L-aryl and the heteroaryl of the -L-heteroaryl are each optionally substituted by one or more R ７ s, the compound or salt according to any one of claims 1 to 81.

113. R ２ wherein the complex ring of 【Chemical 567】 selected from, R ２ wherein said heterocyclic ring of R ６ is optionally substituted by one or more R ２ wherein said aryl and heteroaryl of R 【Chemical 568】 selected from, said aryl and said heteroaryl being one or more R ７ ; and 【Chemical 569】 The compound or salt according to claim 112, each optionally substituted by

114. R ２ wherein said complex ring of 【Chemical 570】 selected from, said heterocyclic ring being optionally substituted by one or more R ６ and said aryl and heteroaryl of R ２ being optionally substituted by 【Chemical 571】 selected from, wherein said aryl and said heteroaryl are one or more R ７ ; and 【Chemical Formula 572】 The compound or salt according to claim 113, each optionally substituted by

115. R ６ is each independently selected from halogen, hydroxy, C １ ~C ３ alkyl, C １ ~C ３ haloalkyl, -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)heterocyclic ring, -CH ２ heterocyclic ring, -CH ２ OC(O)N(R ５ ) ２ and -O-C １ ~C ３ alkyl, wherein the alkyl of -O-C １ ~C ３ alkyl is optionally substituted by a substituent selected from heterocyclic ring, oxo and hydroxy, and R ７ is each independently selected from C １ ~C ３ alkyl, halogen and C １ ~C ３ haloalkyl, a compound or salt according to any one of claims 112 to 114.

116. R ２ of the complex ring, R ２ of the aryl and heteroaryl, and R ２ of -N(R ２０ ) ２ is 【Chemical 573】 【Chemical 574】 The compound or salt according to any one of claims 112 to 115, selected from

117. Y - R ２ is 【Chemical 575】 [In the formula, the heterocyclic ring and the heterocyclic ring moiety of -L-heterocyclic ring are each optionally substituted by one or more Rs] ６ ​ 【Chemical 576】 【Chemical 577】 [wherein the aryl of -L-aryl and the heteroaryl of -L-heteroaryl are each optionally substituted by one or more R ７ ; and] 【Chemical 578】 The compound or salt according to any one of claims 1 to 116, selected from

118. Y - R ２ is 【Chemical 579】 【Chemical 580】 The compound or salt according to any one of claims 112 to 117, selected from

119. Y - R ２ is 【Chemical 581】 The compound or salt according to any one of claims 1 to 118, selected from

120. Y is -O-, and R ２ is selected from L-5-membered heteroaryl, and L is optionally substituted C １ to C ４ alkylene, and the heteroaryl is optionally substituted by one or more R ７ s, and each R ７ is preferably selected from halogen, C １ to C ４ alkyl and C １ to C ４ haloalkyl, the compound or salt according to any one of claims 1.

121. Y - R ２ is 【Chemical Formula 582】 The compound or salt according to any one of claim 120, selected from

122. R １ is selected from a 5- to 12-membered heterocycle, the 5- to 12-membered heterocycle being selected from halogen, —OH, —N(R ２０ ) ２ , -NO ２ , =O, -CN, C １～６ Aminoalkyl, C １～６ Alkoxy, C １～６ Hydroxyalkyl and C １～６ 120. The compound or salt of any one of claims 1 to 119, optionally substituted with one or more substituents independently selected from haloalkyl.

123. R １ is selected from 5- to 12-membered heterocycles, and the 5- to 12-membered heterocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -N(R ２０ ), -NO ２ , -NO ２ , C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl and C １～６ haloalkyl, the compound or salt according to claim 120.

124. R １ The compound or salt according to any one of claims 1 to 122, wherein R is a 5- to 12-membered heterocyclic ring which is optionally substituted.

125. R １ The compound or salt according to claim 124, wherein the 5- to 12-membered heterocyclic ring of R is unsaturated.

126. R １ The compound or salt according to claim 124, wherein the 5- to 12-membered heterocyclic ring of R is saturated.

127. R １ The compound or salt according to claim 124, wherein the 5- to 12-membered heterocyclic ring of R is crosslinked.

128. R １ The compound or salt according to claim 124, wherein the 5- to 12-membered heterocyclic ring of R is a spiro heterocyclic ring.

129. R １ The compound or salt according to claim 124, wherein the 5- to 12-membered heterocyclic ring of R is non-aromatic.

130. R １ is 【Chemical 583】 The compound or salt according to any one of claims 1 to 129, selected from and these are each optionally substituted

131. One or more of the optional substituents are independently selected from halogen, -OH, -N(R ２０ ), -NO ２ , C ２ aminoalkyl, C １～６ alkoxy, =O, -CN, C １～６ hydroxyalkyl and C １～６ haloalkyl, respectively, and the compound or salt according to claim 130. １～６ ​

132. R １ is 【Chemical 584】 selected from, each of which is halogen, -OH, -N(R ２０ ), -NO ２ , -NO ２ , C １～６ aminoalkyl, C １～６ alkoxy, =O, -CN, C １～６ hydroxyalkyl and C １～６ haloalkyl, optionally substituted by one or more substituents independently selected from, a compound or salt according to claim 131.

133. R １ is 【Chemical 585】 【Chemical 586】 【Chemical 587】 【Chemical Formula 588】 【Chemical Formula 589】 【Chemical 590】 The compound or salt according to claim 1, selected from

134. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 6- to 8-membered heterocyclic rings which are optionally substituted.

135. R １ The compound or salt according to claim 134, wherein R is selected from a 7-membered saturated complex ring, an 8-membered crosslinked complex ring, and a 6- to 7-membered unsaturated complex ring, each of which is optionally substituted.

136. R １ is 【Chemical Formula 591】 The compound or salt according to claim 135, selected from and these are each optionally substituted

137. The one or more optional substituents are selected independently from -OH, -CN, oxo, C １～６ The compound or salt according to claim 136, wherein the one or more optional substituents are selected independently from cyanoalkyl.

138. R １ is 【Chemical Formula 592】 The compound or salt according to claim 136 or 137, selected from

139. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 6- to 7-membered heterocyclic rings which are optionally substituted.

140. The compound or salt according to claim 139, wherein the 6- to 7-membered heterocyclic ring contains only one nitrogen atom and the 6- to 7-membered heterocyclic ring is optionally substituted.

141. R １ The compound or salt of 140, wherein the 6- or 7-membered heterocyclic ring of R is bonded to formula (I) via only the one nitrogen atom.

142. R １ The compound or salt according to any one of claims 139 to 141, wherein R is selected from 6-membered unsaturated heterocyclic rings which are optionally substituted.

143. R １ The compound or salt according to any one of claims 139 to 142, wherein R is selected from 7-membered unsaturated heterocyclic rings which are optionally substituted.

144. R １ is 【Chemical Formula 593】 Selected from, each of which is optionally substituted, the compound or salt according to any one of claims 139 to 143.

145. R １ is 【Chemical Formula 594】 Selected from, each of which is optionally substituted, the compound or salt according to any one of claims 139.

146. R １ wherein said one or more optional substituents of R are each independently selected from halogen, -OR ２０ , -N(R ２０ ), =O, -CN, C ２ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ alkyl, -NHCN and C １～６ alkynyl, and the compound or salt according to any one of claims 139 to 145 ２～６ ​

147. each being optionally substituted by one or more substituents independently selected from halogen, -OH, -NH ２ , -NO ２ , C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl, C １～６ haloalkyl and C １～６ alkyl, or a salt thereof, of any one of claims 139 to 146.

148. R １ The compound or salt according to any one of claims 139 to 147, wherein the one or more optional substituents of R are each independently selected from halogen.

149. R １ is 【Chemical 595】 Selected from, the compound or salt according to any one of claims 139 to 148.

150. R １ is 【Chemical Formula 596】 selected from, each being halogen, -OH, -NH ２ , -NO ２ , C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl, C １～６ haloalkyl and C １～６ The compound or salt according to any one of claims 139 to 145, optionally substituted by one or more substituents independently selected from alkyl.

151. R １ is 【Chemical 597】 selected from, each being halogen, -OH, -NH ２ , -NO ２ , C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl, C １～６ haloalkyl and C １～６ The compound or salt according to claim 150, optionally substituted by one or more substituents independently selected from alkyl.

152. R １ is 【Chemical 598】 selected from, each being optionally substituted by one or more substituents independently selected from halogen and C １～６ The compound or salt according to claim 151, which is optionally substituted by one or more substituents independently selected from haloalkyl.

153. R １ is 【Chemical 599】 Selected from, the compound or salt according to claim 152.

154. R １ is 【Chemical 600】 selected from, which is halogen, -OH, -NH ２ , -NO ２ , C １～６ cyanoalkyl, C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl, C １～６ haloalkyl and C １～６ The compound or salt according to claim 145, optionally substituted by one or more substituents independently selected from alkyl.

155. R １ is 【Chemical 601】 Selected from, which is optionally substituted by one or more substituents independently selected from halogens, the compound or salt according to claim 154.

156. R １ is 【Chemical Formula 602】 Selected from, the compound or salt according to claim 155.

157. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 6- to 7-membered heterocyclic rings which are optionally substituted.

158. The compound or salt according to claim 157, wherein the 6- to 7-membered heterocyclic ring contains only one nitrogen atom and optionally contains one or more additional heteroatoms selected from oxygen and sulfur.

159. The compound or salt according to claim 158, wherein the one or more additional heteroatoms optionally present are selected from sulfur.

160. The compound or salt according to any one of claims 157 to 159, wherein the 6- to 7-membered heterocyclic ring contains only one nitrogen atom and does not contain any additional heteroatoms.

161. The compound or salt according to any one of claims 157 to 160, wherein the 6- to 7-membered heterocyclic ring is a 6- to 7-membered non-aromatic heterocyclic ring.

162. R １ The compound or salt according to any one of claims 157 to 161, wherein the 6- or 7-membered heterocyclic ring of R is bonded to formula (I) via only the one nitrogen atom.

163. R １ is 【Chemical Formula 603】 Selected from, each of which is optionally substituted, the compound or salt according to any one of claims 157 to 162.

164. R １ wherein said one or more optional substituents are halogen, -OH, -CN, C １～６ cyanoalkyl, -NHCN, C １～６ alkyl, oxo and C ２～６ alkynyl, respectively independently selected, a compound or a salt according to any one of claims 157 to 163.

165. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 6- to 10-membered heterocyclic rings which are optionally substituted.

166. R １ is 【Chemical Formula 604】 Selected from, each of which is optionally substituted, the compound or salt according to claim 165.

167. The one or more optional substituents are halogen, =O, -OH, -C(O)N(R ２０ ) ２ , C ２～６ alkynyl, -NHCN, -CN, C １～６ aminoalkyl, C １～６ hydroxyalkyl, C １～６ cyanoalkyl and C １～６ alkyl, the compound or salt according to claim 166, which is independently selected from

168. R １ is 【Chemical Formula 605】 The compound or salt according to claim 166 or 167, selected from

169. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 7- to 11-membered spiro heterocyclic rings.

170. R １ The compound or salt according to claim 169, wherein R is selected from 10-membered spiro heterocycles.

171. The compound or salt according to claim 169 or 170, wherein the spiro heterocyclic ring has at least 3 nitrogen atoms.

172. R １ is 【Chemical Formula 606】 The compound or salt according to claim 171, selected from and each of them is optionally substituted.

173. R １ is 【Chemical Formula 607】 each of which is selected from halogen, —OH, —N(R 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 ２～６ 173. The compound or salt of claim 172, optionally substituted with one or more substituents independently selected from alkynyl.

174. R １ is 【Chemical Formula 608】 The compound or salt according to claim 173, selected from

175. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 9- to 11-membered unsaturated heterocyclic rings which are optionally substituted.

176. R １ The compound or salt according to claim 175, wherein R is selected from 10-membered unsaturated heterocyclic rings which are optionally substituted.

177. R １ is 【Chemical 609】 The compound or salt according to claim 175 or 176, selected from and this is optionally substituted.

178. R １ is 【Chemical Formula 610】 and this is halogen, -OH, -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 alkynyl, optionally substituted by one or more substituents selected from, a compound or salt according to claim 177.

179. R １ is 【Chemical Formula 611】 each of which is selected from 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 １～６ Alkyl and C ２～６ 179. The compound or salt of claim 178, further optionally substituted with one or more substituents selected from alkynyl.

180. R １ wherein said one or more 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(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 and C ２～６ 178. The compound or salt of any one of claims 175 to 177, independently selected from alkynyl.

181. R １ is 【Chemical 612】 The compound or salt according to claim 177 or 180, selected from and each of them is optionally substituted.

182. R １ is 【Chemical Formula 613】 【Chemical 614】 The compound or salt according to claim 181, selected from

183. R １ wherein said one or more optional substituents of R are independently selected from halogen, -OH, -N(R ２０ ), =O, -CN, C ２ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl, -C(O)N(R １～６ ), C ２０ alkyl and C ２ alkynyl, and the compound or salt according to claim 177. １～６ alkyl and C ２～６ alkynyl, and the compound or salt according to claim 177.

184. R １ wherein said one or more optional substituents are independently selected from halogen and -C(O)N(R ２０ ) ２ ), a compound or salt according to claim 183.

185. R １ is 【Chemical 615】 The compound or salt according to claim 184, selected from

186. R １ is 【Chemical 616】 The compound or salt according to claim 185, which is

187. R １ is 【Chemical Formula 617】 The compound or salt according to claim 185, which is

188. R １ wherein said one or more optional substituents are independently selected from halogen, C １～６ alkyl, C １～６ alkyl-N(R ２０ ), -C(O)NR ２ OR ２０ OR ２０ -C(O)N(R ２０ ), ２ and -C(O)R ２０ ; a compound or salt according to claim 177.

189. R １ wherein said one or more optional substituents are chlorine, 【Chemical Formula 618】 The compound or salt according to claim 188, selected from

190. R １ is 【Chemical Formula 619】 【Chemical 620】 The compound or salt according to claim 189, selected from

191. R １ wherein said one or more optional substituents are halogen, —N(R ２０ ) ２ , -C.N., 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 a 5- to 10-membered heterocycle, said 5- to 10-membered heterocycle being independently selected from one or more R １＊ and R is optionally independently substituted with １＊ are halogen, -OR ２０ and C １～６ 178. The compound or salt of any one of claims 175 to 177, wherein each is independently selected from alkyl.

192. R １ wherein said one or more optional substituents are chlorine, -NH ２ , -CN, C １ alkyl, C ２ alkenyl, 【Chemical Formula 621】 The compound or salt according to claim 177 or 191, selected from

193. R １ is 【Chemical Formula 622】 【Chemical Formula 623】 The compound or salt according to claim 192, selected from

194. R １ is selected from 6- to 11-membered heterocyclic rings which are optionally substituted, and the 6- to 11-membered heterocyclic ring has at least one nitrogen atom, the compound or salt according to any one of claims 1 to 129.

195. R １ wherein said one or more optional substituents are halogen, —OR ２０ , -C(O)N(R ２０ ) ２ , -C(O)R ２０ , -S(O) ２ R ２０ , =O, -C １～６ Alkyl (=NOR ２０ ), = NO (R ２０ ), -CN, -NHCN, C １～６ alkyl and a 5- to 12-membered heterocycle, said 5- to 12-membered heterocycle being selected from one or more R １＊ and R is optionally independently substituted with １＊ are halogen and C １～６ 200. The compound or salt of claim 194, wherein each is independently selected from alkyl.

196. R １ is 【Chemical 624】 【Chemical Formula 625】 The compound or salt according to claim 194, selected from

197. R １ is hydrogen, 【Chemical 626】 【Chemical Formula 627】 The compound or salt according to claim 1, selected from

198. R １ is hydrogen, 【Chemical 628】 【Chemical 629】 The compound or salt according to claim 1, selected from

199. R １ is a compound or salt according to any one of claims 1 to 129, selected from hydrogen and a 5- to 15-membered heterocyclic ring which may be substituted as required.

200. R １ is 【Chemical 630】 The compound or salt according to claim 199, selected from and each of them is optionally substituted.

201. R １ wherein said one or more optional substituents of R are selected from -OH, =NO(R ２０ ), -NHCN and C １～６ alkyl; the compound or salt according to claim 200.

202. R １ is hydrogen, 【Chemical 631】 【Chemical Formula 632】 The compound or salt according to any one of claims 199 to 201, selected from

203. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from hydrogen and a 7- to 10-membered heterocyclic ring which may be substituted as required.

204. R １ is hydrogen, 【Chemical 633】 The compound or salt according to claim 203, selected from and each of them is optionally substituted.

205. R １ wherein said one or more optional substituents of R are independently selected from halogen, -NH ２ , -S(O) ２ (R ２０ ), -C(O)R ２０ , -C(O)N(R ２０ ) ２ , =O, =NO(R ２０ ), -CN, -NHCN, C １～６ alkyl and 5- to 12-membered heterocycles, wherein said 5- to 12-membered heterocycles are independently optionally substituted by one or more R １＊ s, and each R １＊ is independently selected from halogen and C １～６ alkyl; a compound or salt according to claim 203 or 204.

206. R １ is hydrogen, 【Chemical 634】 【Chemical 635】 The compound or salt according to any one of claims 203 to 205, selected from

207. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 8- to 10-membered heterocyclic rings which are optionally substituted.

208. The compound or salt according to claim 207, wherein the heterocyclic ring is bicyclic.

209. The compound or salt according to claim 207 or 208, wherein the heterocyclic ring has at least one nitrogen atom.

210. The compound or salt according to claim 207 or 208, wherein the heterocyclic ring has at least two nitrogen atoms.

211. 【Chemical Formula 636】 The compound or salt according to any one of claims 207 to 210, which are each optionally substituted.

212. R １ wherein said one or more optional substituents of R are halogen, 【Chemical 637】 , oxo, 【Chemical Formula 638】 【Chemical Formula 639】 and independently selected from 5- to 9-membered heteroaryl, said 5- to 9-membered heteroaryl being substituted by at least one R １＊ wherein said R １＊ is selected from halogen and C １～６ alkyl, a compound or salt according to any one of claims 207 or 211.

213. R １ wherein the one or more optional substituents of R are chlorine, 【Chemical 640】 , oxo, 【Chemical 641】 The compound or salt according to any one of claims 207 or 212, independently selected from

214. 【Chemical Formula 642】 The compound or salt according to any one of claims 207 or 213, which is

215. R １ The compound or salt according to any one of claims 1 to 129, wherein R is a 12- to 15-membered heterocyclic ring which is optionally substituted.

216. R １ The compound or salt according to claim 215, wherein R is a 12-membered heterocyclic ring which is optionally substituted.

217. R １ The compound or salt according to claim 216, wherein R is a 13-membered heterocyclic ring which is optionally substituted.

218. R １ The compound or salt according to claim 217, wherein R is a 14-membered heterocyclic ring which is optionally substituted.

219. R １ The compound or salt according to claim 218, wherein R is a 15-membered heterocyclic ring which is optionally substituted.

220. R １ The compound or salt according to any one of claims 215 to 219, wherein the heterocyclic ring of

221. R １ The compound or salt according to any one of claims 215 to 220, wherein the heterocyclic ring of R contains a condensed heterocyclic ring.

222. R １ The compound or salt according to any one of claims 215 to 221, wherein the heterocyclic ring of R contains a spiro heterocyclic ring.

223. R １ The compound or salt according to any one of claims 215 to 222, wherein the heterocyclic ring of R contains a condensed spiro heterocyclic ring.

224. R １ The compound or salt according to any one of claims 215 to 223, wherein the heterocyclic ring of R is an unsaturated heterocyclic ring.

225. R １ The compound or salt according to any one of claims 215 to 223, wherein the heterocyclic ring of R is a non-aromatic heterocyclic ring.

226. R １ The compound or salt according to any one of claims 215 to 225, wherein the heterocyclic ring of R has at least one double bond.

227. R １ The compound or salt according to any one of claims 215 to 226, wherein the complex ring of R has at least two double bonds.

228. R １ The compound or salt according to any one of claims 215 to 227, wherein the complex ring of R has two double bonds.

229. R １ is 【Chemical Formula 643】 【Chemical Formula 644】 The compound or salt according to any one of claims 215 to 228, selected from, each of which is optionally substituted by one or more substituents.

230. One or more of the optional substituents are halogen, -OH, -NHCN, -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 alkynyl, the compound or salt according to claim 229

231. One or more of the optional substituents are halogen, -OH, C １～６ alkyl and -C(O)N(R ２０ ) ２ The compound or salt according to claim 230, selected from

232. R １ is 【Chemical 645】 【Chemical 646】 The compound or salt according to any one of claims 215 to 231, selected from

233. R １ is selected from 6- to 7-membered heterocyclic rings which are substituted, said 6- to 7-membered heterocyclic ring being substituted by at least one -NHCN, and one or more C １～６ alkyl, and optionally further substituted, a compound or a salt according to any one of claims 1 to 129.

234. R １ is 【Chemical 647】 The compound or salt according to claim 233, selected from

235. R １ The compound or salt according to any one of claims 1 to 129, wherein R is selected from 8- to 9-membered crosslinked heterocyclic rings which are optionally substituted.

236. R １ wherein the complex ring of 【Chemical Formula 648】 The compound or salt according to claim 235, selected from, each of which is optionally substituted.

237. R １ wherein said one or more substituents are halogen, C １～６ alkyl, -N(R ２０ ) ２ and C １～６ aminoalkyl, and the compound or salt according to claim 235 or 236

238. R １ is 【Chemical Formula 649】 The compound or salt according to any one of claims 235 to 237, selected from

239. R １ is selected from 8-membered bridged heterocyclic rings which are optionally substituted, said heterocyclic ring containing a heteroatom selected from nitrogen, the compound or salt according to claim 235.

240. R １ wherein said one or more substituents are C １～６ alkyl, -N(R ２０ ), ２ and C １～６ aminoalkyl, a compound or salt according to claim 239.

241. R １ wherein said complex ring of 【Chemical Formula 650】 The compound or salt according to claim 240, selected from, each of which is optionally substituted.

242. R １ is 【Chemical 651】 The compound or salt according to any one of claims 239 to 241, selected from

243. R １ is 【Chemical Formula 652】 The compound or salt according to claims 1 to 129 or 242, selected from

244. R １ The compound or salt according to any one of claims 1 to 124, wherein R is hydrogen.

245. The compound or salt according to any one of claims 1 to 244, wherein n is 0.

246. The compound of formula (I-A) 【Chemical Formula 653】 or a pharmaceutically acceptable salt thereof [wherein, R １ is selected from 8- to 10-membered heterocycles, and the 8- to 10-membered heterocycle is halogen, -OR ２０ , -S(O) ２ (R ２０ ), -C(O)N(R ２０ ) ２ , -C １～６ alkyl(=NOR ２０ ), -C(O)R ２０ , =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 １～６ alkyl-SO ２ R ２０ , C １～６ alkoxyalkyl, C １～６ alkyl, C ２～６ alkynyl, and is optionally substituted by one or more substituents independently selected from 5- to 12-membered heterocycles, where the 5- to 12-membered heterocycle is optionally independently substituted by one or more R １＊ s, 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 ２ alkenyl, C １～６ alkynyl, and C １～６ are independently selected from carbon rings, １～６ and １～６ each is independently selected from the group consisting of C １～６ haloalkyl, C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, and C ３ -C １２ carbon rings, B is a 7- to 15-membered heterocyclic ring and C ７ to C １５ selected from carbocyclic rings, and the 7- to 15-membered heterocyclic ring and C ７ to C １５ carbocyclic rings are each optionally substituted by one or more substituents independently selected from halogen, -CN, -NO ２ , =O, -N(R ２１ ), -B(OR ２ ), -OR ２１ ), -SR ２ ), -S(O) ２１ ), -S(O) ２１ N(R ２ ), -NR ２１ S(O) ２ R ２１ ), -C(O)N(R ２ ), -C(O)NRO ２１ R ２ ), -N(R ２１ C(O)R ２１ ), -N(R ２ C(O)NR ２１ R ２１ ), -N(R ２１ C(O)OR ２１ ), -C(O)R ２１ ), C(O)OR ２１ ), -OC(O)R ２ ), -OC(O)N(R ２１ ), C ２１ alkyl-N(R ２１ ), C ２１ aminoalkyl, C ２１ alkoxy, C ２１ alkoxyalkyl, C ２ hydroxyalkyl, C １～６ cyanoalkyl, C ２０ haloalkyl, C ２ alkyl, C １～６ alkenyl, C １～６ alkynyl, C １～６ to C １～６ carbocyclic rings and 5- to 12-membered heterocyclic rings, each optionally substituted by one or more substituents independently selected therefrom, １～６ and C １～６ to C １～６ carbocyclic rings are each optionally substituted by one or more substituents independently selected from halogen, -CN, -NO ２～６ , =O, -N(R ２～６ ), -B(OR ３ ), -OR １２ carbocyclic rings and 5- to 12-membered heterocyclic rings, each optionally substituted by one or more substituents independently selected therefrom, Y is selected from a bond and -O-, R ２ is a complex ring, aryl, C １ to C ６ alkyl, -L-complex ring, -L-N(R ２３ ) ２ , -L-OR ２３ , -L-aryl, -L-heteroaryl, -L-cycloalkyl, -L-NHC(=NH)NH ２ , -L-C(O)N(R ２３ ) ２ , -L-C １ to C ６ haloalkyl, -L-OR ２３ , -L-NR ２３ C(O)-aryl, -L-COOH, -L-NR ２３ S(O) ２ (R ２３ ), -L-S(O) ２ N(R ２３ ) ２ , -L-N(R ２３ )C(O)(OR ２３ ), -L-OC(O)N(R ２３ ) ２ and -L-C(=O)OC １ to C ６ alkyl, wherein the complex ring, the complex ring part of -L-complex ring and the cycloalkyl part of -L-cycloalkyl are each optionally substituted by one or more R ６ , and the aryl, the aryl part of -L-NR ２３ C(O)-aryl, the aryl part of -L-NR ２３ C(O)-aryl, the aryl of -L-aryl and the heteroaryl of -L-heteroaryl are each optionally substituted by one or more R ７ , R ３ is hydrogen, halogen, -CN, -NO ２ , -N(R 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 ), -N(R ２ )C(O)R ２０ , -N(R ２０ )C(O)N(R ２ ), -N(R ２０ )C(O)OR ２０ , -C(O)R ２０ , -C(O)OR ２０ , -OC(O)R ２ , -OC(O)N(R ２０ ), -C ２０ alkyl-N(R ２０ ), -C ２０ aminoalkyl, -C ２０ alkoxy, -C ２０ alkoxyalkyl, -C ２ hydroxyalkyl, -C １～６ cyanoalkyl, -C ２０ haloalkyl, -C ２ alkyl, -C １～６ alkenyl, -C １～６ alkynyl, -C １～６ -C １～６ to -C １～６ carbon ring and a 5- to 12-membered heterocyclic ring, and is selected from １～６ １～６ ２～６ ２～６ ３ １２ ​​​​​​ R ４ each represents halogen, -NO ２ , =O, =S, -CN, C １～６ alkyl, C ２～６ alkynyl, C １～６ alkyl-N(R ２０ ), ２ C １～６ aminoalkyl, C １～６ alkoxy, C １～６ cyanoalkyl, C １～６ hydroxyalkyl and C １～６ is independently selected from haloalkyl, n is selected from 0, 1, 2, 3, and 4, R ５ each is independently selected from hydrogen and C １ to C ６ alkyl, R ６ is each a halogen, hydroxy, C 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, -C １ -C ３ alkyl-N(R ５ ) ２ , -C(O)N(R ５ ) ２ tert-butyldimethylsilyloxyCH 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 , -CH ２ NHOC(O)OC １ -C ６ alkyl, -CH ２ NHOC(O)N(R ５ ), ２ , -CH ２ NH C(O)C １ ~C ６ alkyl, -CH ２ (pyrazolyl), -CH ２ NHSO ２ C １ ~C ６ alkyl, -CH ２ OC(O)heterocycle, -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, -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 and -CH ２ heterocycle are independently selected, and the phenyl of -NHC(O)phenyl and -OC(O)NH(C １ ~C ３ alkyl)(C １ ~C ３ alkyl)phenyl is optionally substituted by one or more substituents selected from -C(O)H and OH, -O-C １ ~C ３ The alkyl of the alkyl is optionally substituted with a substituent selected from a heterocyclic ring, oxo and hydroxy, and -CH ２ The heterocyclic ring of the heterocyclyl is optionally substituted with oxo, each Q is selected from a bond, S, and O, R ７ each represents halogen, hydroxy, HC(=O)-, C １ to C ４ alkyl, C １ to C ４ alkoxy, C １ to C ４ haloalkyl, C １ to C ４ hydroxyalkyl, -C １ to C ３ alkyl-N(R ５ ) ２ , -C(O)N(R ５ ) ２ and -N(R ５ ) ２ is independently selected from, L is each independently selected from halogen, hydroxy, C １～６ alkoxy, C １ to C ４ hydroxyalkyl, C １ to C ４ alkyl, C ３ to C ６ optionally substituted by one or more substituents independently selected from carbocycles and 3- to 8-membered heterocycles, C １ to C ４ alkylene, independently selected, said C ３ to C ６ carbocycles and 3- to 8-membered heterocycles are each optionally substituted by one or more substituents independently selected from halogen, -OH, -NO 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 haloalkyl, and are each optionally substituted by one or more substituents independently selected, and optionally, two substituents on the same carbon atom of L together form a C ３ to C ６ carbocycle or 3- to 8-membered heterocycle, said C ３ to C ６ carbocycles and 3- to 8-membered heterocycles are each optionally substituted by one or more substituents independently selected from halogen, -OH, -NO ２ , =O, =S, -CN, C １～６ alkyl-N(R ２０ ) ２ , C １～６ aminoalkyl, C １～６ alkoxy, C １～６ hydroxyalkyl and C １～６ haloalkyl, and are each optionally substituted by one or more substituents independently selected, and R ２０ is each, hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ carbocyclic and 3- to 12-membered heterocyclic rings independently selected therefrom, each of which is halogen, -OH, -CN, -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 carbocyclic and 3- to 12-membered heterocyclic rings optionally substituted by one or more substituents independently selected therefrom, R ２１ is each, hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ selected independently from carbocycles and 3- to 12-membered heterocycles, each of which is optionally substituted by one or more substituents selected independently from halogen, -OH, -CN, -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 selected independently from carbocycles and 3- to 12-membered heterocycles and optionally substituted by one or more substituents R ２３ is each, hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ carbocyclic ring and a 3- to 12-membered heterocyclic ring, independently selected therefrom, each of which is halogen, -OH, -CN, -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 carbocyclic ring and a 3- to 12-membered heterocyclic ring, optionally substituted by one or more substituents independently selected therefrom].

247. The compound or salt according to claim 246, wherein formula (I-A) is formula (I-B) 【Chemical 654】 or a pharmaceutically acceptable salt thereof [wherein, R １ is 【Chemical Formula 655】 selected from, each of which is halogen, -S(O) ２ (R ２０ ), -C(O)N(R ２０ ) ２ , -C １～６ alkyl(=NOR ２０ ), -C(O)R ２０ , =O and one or more substituents independently selected from 5- to 12-membered heterocycles, optionally substituted, said 5- to 12-membered heterocycle being optionally independently substituted by one or more R １＊ respectively R １＊ each independently represents halogen, -OR ２０ , -N(R ２０ ), -NO ２ , =O, =N(R ２ ), =NO(R ２０ ), -CN, -NHCN, C ２０ alkyl-N(R １～６ ), C ２０ aminoalkyl, C ２ alkoxy, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl and C １～６ alkyl, and is independently selected from １～６ ; １～６ ​ Y is -O-, R ２ is selected from -L-heterocyclic rings and -L-N(R ２３ ) ２ and the heterocyclic ring moiety of the -L-heterocyclic ring is optionally substituted by one or more R ６ ; B is selected from 7- to 15-membered heterocyclic rings, and the 7- to 15-membered heterocyclic ring is optionally substituted with one or more substituents independently selected from halogen, -CN, =O, -N(R ２１ ), -OR ２ , C ２１ alkyl-N(R １～６ ), C ２０ aminoalkyl, C ２ alkoxy, C １～６ alkoxyalkyl, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl, C １～６ alkyl and C １～６ alkynyl; １～６ and is optionally substituted by one or more substituents independently selected from ２～６ alkyl and C R ３ is selected from hydrogen, halogen, -CN, -N(R ２０ ) ２ , -OR ２０ , -C(O)R ２０ , 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 and C １～６ alkyl, R ２０ is each, hydrogen; and C １～６ alkyl and C ３～１２ independently selected from carbocycles, each of which is optionally substituted by one or more substituents independently selected from halogen, -OH, -CN, -NH ２ , -N(C １～６ alkyl) ２ , C １～１０ alkyl, -C １～１０ haloalkyl, -O-C １～１０ alkyl and oxo].

248. R １ is 【Chemical Formula 656】 selected from 【Chemical 657】 is optionally substituted by one or more substituents independently selected from halogen, -S(O) ２ (R ２０ ), -C(O)N(R ２０ ) ２ , -C １～６ alkyl(=NOR ２０ ), -C(O)R ２０ , =O and one or more substituents independently selected from 5- to 9-membered heterocycles, and said 5- to 9-membered heterocycles are each optionally independently substituted by one or more R １＊ ; R １＊ is each independently selected from halogen, C １～６ haloalkyl and C １～６ alkyl, a compound or salt according to claim 246 or 247.

249. The compound or salt according to any one of claims 246 to 248, wherein Y is -O-.

250. L is each independently selected from halogen and C １ ~C ４ alkyl, and is optionally substituted by one or more substituents independently selected therefrom, and C １ ~C ４ alkylene, and optionally, two substituents on the same carbon atom of L are taken together to form a C ３ ~C ６ carbocyclic ring or a 4- to 6-membered heterocyclic ring, and the C ３ ~C ６ carbocyclic ring and the 3- to 6-membered heterocyclic ring are each optionally substituted by one or more substituents independently selected from halogen, the compound or salt according to any one of claims 246 to 249.

251. each L is 【Chemical Formula 658】 【Chemical Formula 659】 selected from, the compound or salt according to any one of claims 246 to 250. In some cases, L is 【Chemical Formula 660】 is selected from. In some cases, R ２ is 【Chemical Formula 661】 selected from

252. Y - R ２ is 【Chemical 662】 selected from, the compound or salt according to any one of claims 246 to 251.

253. The compound or salt according to any one of claims 246 to 252, wherein B is selected from an 8- to 10-membered heterocyclic ring which is optionally substituted.

254. The 8- to 10-membered heterocyclic ring is optionally substituted by one or more substituents independently selected from halogen, -CN, -NH ２ and C １～６ The compound or salt according to claim 253, which is optionally substituted by one or more substituents independently selected from alkyl.

255. The heterocyclic ring of B is 【Chemical 663】 selected from, the compound or salt according to any one of claims 246 to 254.

256. 【Fig. 664】 and each of these is halogen, -CN, -NH ２ and C １～６ The compound or salt according to any one of claims 246 to 255, optionally substituted by one or more substituents independently selected from alkyl.

257. B is 【Chemical 665】 selected from, the compound or salt according to any one of claims 246 to 256.

258. R ３ The compound or salt according to any one of claims 246 to 257, wherein R is -CN.

259. R １ is 【Chemical 666】 and this is optionally substituted with one or more substituents, the compound or salt according to any one of claims 246 to 258.

260. R １ is 【Chemical 667】 is, the compound or salt according to any one of claims 246 to 258.

261. R １ is 【Chemical Formula 668】 is, the compound or salt according to any one of claims 246 to 258.

262. R １ is 【Chemical 669】 is, the compound or salt according to any one of claims 246 to 258.

263. R １ wherein said one or more optional substituents are independently selected from halogen, -S(O) ２ (R ２０ ), -C(O)N(R ２０ ), ２ , -C １～６ alkyl(=NOR ２０ ), -C(O)R ２０ =O and 5- to 9-membered heterocycles, and said 5- to 9-membered heterocycles are each independently optionally substituted by one or more R １＊ ; a compound or salt according to any one of claims 246 to 262.

264. R １ wherein said one or more optional substituents are independently selected from halogen, -S(O) ２ (R ２０ )-, -C(O)N(R ２０ ) ２ , -C １～６ alkyl(=NOR ２０ ), -C(O)R ２０ =O and a 5- to 9-membered heterocyclic ring, and said 5- to 9-membered heterocyclic ring is optionally independently substituted by one or more R １＊ ; a compound or salt according to any one of claims 246 to 262.

265. R １ wherein said one or more optional substituents are halogen, —C(O)N(R ２０ ) ２ , -C １～６ Alkyl (=NOR ２０ ), -C(O)R ２０ and a 5- to 9-membered heterocycle, said 5- to 9-membered heterocycle being independently selected from one or more R １＊ 263. The compound or salt of any one of claims 246-262, each optionally independently substituted by:

266. R １＊ is each independently selected from halogen, C １～６ haloalkyl and C １～６ alkyl, the compound or salt according to claim 265.

267. R １ is 【Chemical Formula 670】 and this is substituted with at least one substituent, the compound or salt according to any one of claims 246 to 259.

268. R １ is 【Chemical 671】 【Chemical 672】 is, the compound or salt according to any one of claims 246 to 259.

269. R １ is 【Chemical 673】 is, the compound or salt according to any one of claims 246 to 259.

270. A pharmaceutical composition comprising the compound according to any one of claims 1 to 269 and a pharmaceutically acceptable additive.

271. A method for treating a disease or disorder, which comprises using the compound or salt according to any one of claims 1 to 269 or the pharmaceutical composition according to claim 270.

272. A method for inhibiting KRas G12D and / or other G12 mutants, which comprises using the compound or salt according to any one of claims 1 to 269 or the pharmaceutical composition according to claim 270.

273. A method for inhibiting KRas G12D and / or other G12 mutants, which comprises using the compound or salt according to any one of claims 1 to 269 or the pharmaceutical composition according to claim 270.

274. A method for inhibiting KRas G12D and / or other G12 alleles, which comprises using the compound or salt according to any one of claims 1 to 269 or the pharmaceutical composition according to claim 270.

275. A method for inhibiting KRas G12D and / or other alleles, which comprises using the compound or salt according to any one of claims 1 to 269 or the pharmaceutical composition according to claim 270.

276. Use of the compound according to any one of claims 1 to 269 in the preparation of a target proteolytic compound by using chemical modification of the compound according to any one of claims 1 to 269.

277. A bifunctional compound composed of a target protein binding moiety and an E3 ubiquitin ligase binding moiety, wherein the target protein binding moiety is derived from the compound according to any one of claims 1 to 269.

278. The compound of formula (II): 【Chemical 674】 or a pharmaceutically acceptable salt thereof [wherein, A is C ５ ~C ８ selected from carbocyclic rings, said C ５ ~C ８ The carbocyclic ring is optionally substituted by one or more substituents independently selected from R ９４ and is optionally substituted by one or more substituents independently selected therefrom, R ９１ is halogen, -CN, -NO ２ , =O, -N(R ２１ ), ２ , -B(OR ２１ ), ２ , -OR ２１ , -SR ２１ , -S(O) ２ (R ２１ ), -S(O) ２ N(R ２１ ), ２ , -NR ２１ S(O) ２ R ２１ , -C(O)N(R ２１ ), ２ , -C(O)NR ２１ OR ２１ , -N(R ２１ ),C(O)R ２１ , -N(R ２１ ),C(O)N(R ２１ ), ２ , -N(R ２１ ),C(O)OR ２１ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ), ２ , 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 alkenyl, C ２～６ alkynyl, C ３ ~C １２ selected from carbocyclic rings and 5- to 12-membered heterocyclic rings, R ９２ is hydrogen, halogen, -CN, -NO ２ , =O, -N(R ２１ ), ２ , -B(OR ２１ ), ２ , -OR ２１ , -SR ２１ , -S(O) ２ (R ２１ ), -S(O) ２ N(R ２１ ), ２ , -NR ２１ S(O) ２ R ２１ , -C(O)N(R ２１ ), ２ , -C(O)NR ２１ OR ２１ , -N(R ２１ )C(O)R ２１ , -N(R ２１ )C(O)N(R ２１ ), ２ , -N(R ２１ )C(O)OR ２１ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ), ２ , 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 alkenyl, C ２～６ alkynyl, C ３ ~C １２ selected from carbocyclic rings and 5- to 12-membered heterocyclic rings, R ９３ is selected from hydrogen, -C(O)OR ２１ , -C(O)R ２１ and -SO ２ R ２１ and is selected from R ９４ is each independently halogen, -CN, -NO ２ , =O, -N(R ２１ ), ２ , -B(OR ２１ ), ２ , -OR ２１ , -SR ２１ , -S(O) ２ (R ２１ ), -S(O) ２ N(R ２１ ), ２ , -NR ２１ S(O) ２ R ２１ , -C(O)N(R ２１ ), ２ , -C(O)NR ２１ OR ２１ , -N(R ２１ )C(O)R ２１ , -N(R ２１ )C(O)N(R ２１ ), ２ , -N(R ２１ )C(O)OR ２１ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ), ２ , 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 alkenyl, C ２～６ alkynyl, C ３ ~C １２ independently selected from carbocycles and 5- to 12-membered heterocycles, R ２１ is each, hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ is independently selected from carbocyclic rings and 3- to 12-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from halogen, -OH, -CN, -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 is independently selected from carbocyclic rings and 3- to 12-membered heterocyclic rings and is optionally substituted by one or more substituents as required].

279. A is C which is optionally substituted ５ ~C ７ The compound or salt according to claim 278, which is selected from carbocyclic rings

280. A is an unsaturated C which is optionally substituted ５ ~C ７ The compound or salt according to claim 279, selected from a carbocyclic ring

281. A is C which is optionally substituted ５ A compound or salt according to any one of claims 278 to 280, selected from a carbocyclic ring

282. A is C which is optionally substituted ６ A compound or salt according to any one of claims 278 to 280, selected from a carbocyclic ring

283. A is C which is optionally substituted ７ The compound or salt according to any one of claims 278 to 280, selected from a carbocyclic ring

284. Said C of A ７ The compound or salt according to any one of claims 278 to 280, wherein the carbocyclic ring is monocyclic.

285. Said C of A ７ The compound or salt according to any one of claims 278 to 280, wherein the carbocyclic ring is bicyclic.

286. A is 【Chemical 675】 selected from, the compound or salt according to any one of claims 278 to 280.

287. A is 【Chemical Formula 676】 selected from, the compound or salt according to any one of claims 278 to 280.

288. Formula (II) is formula (II-A) 【Chemical Formula 677】 or represented by a pharmaceutically acceptable salt, wherein n is selected from 0, 1 and 2, the compound or salt according to any one of claims 278 to 287.

289. Formula (II) is formula (II-B) 【Chemical 678】 A compound or salt according to any one of claims 278 to 287, represented by or a pharmaceutically acceptable salt, wherein n is selected from 0, 1 and 2.

290. Formula (II) is formula (II-C) 【Chemical Formula 679】 A compound or salt according to any one of claims 278 to 287, represented by or a pharmaceutically acceptable salt, wherein n is selected from 0, 1 and 2.

291. A is a condensed C which is optionally substituted ６ ~C ７ The compound or salt according to any one of claims 278 to 262, which is a carbocyclic ring.

292. A is a condensed C which is optionally substituted ６ -C ７ The compound or salt according to any one of claims 278 to 260, selected from an unsaturated carbocyclic ring

293. A is 【Chemical Formula 680】 A compound or salt according to claim 292, selected from

294. A is 【Chemical Formula 681】 A compound or salt according to claim 293, selected from

295. Formula (II) is formula (II-D) 【Chemical Formula 682】 A compound or salt according to claim 293 or 294, represented by or a pharmaceutically acceptable salt, wherein n is selected from 0, 1 and 2.

296. R ９１ is halogen, -CN, -NO ２ , -N(R ２１ ), ２ , -OR ２１ , -C(O)R ２１ , C １～６ alkyl-N(R ２０ ), ２ , C １～６ aminoalkyl, C １～６ alkoxyalkyl, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl, C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３ ~C １２ a carbon ring and a 5- to 12-membered heterocyclic ring, the compound or salt according to any one of claims 278 to 295

297. R ９１ The compound or salt according to claim 296, wherein R is selected from -CN.

298. R ９２ is hydrogen, halogen, -CN, -NO ２ , -N(R ２１ ), ２ , -OR ２１ , -SR ２１ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , 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 alkenyl, C ２～６ alkynyl, C ３ ~C １２ a carbon ring and a 5- to 12-membered heterocyclic ring, the compound or salt according to any one of claims 278 to 297.

299. R ９２ is hydrogen, halogen, -CN and -N(R ２１ ) ２ selected from, the compound or salt according to claim 298.

300. R ９２ is selected -N(R ２１ ) ２ is, the compound or salt according to claim 299.

301. R ９３ The compound or salt according to any one of claims 278 to 300, wherein R is selected from hydrogen.

302. A process for preparing a compound or salt according to any one of claims 278 to 301.

303. A compound of formula (III): 【Chemical Formula 683】 [[B]] is selected from 5- to 8-membered heterocyclic rings, and the 5- to 8-membered heterocyclic ring is halogen, -CN, -NO ２ , =O, -N(R ２１ ), ２ , -B(OR ２１ ), ２ , -OR ２１ , -SR ２１ , -S(O) ２ (R ２１ ), -S(O) ２ N(R ２１ ), ２ , -NR ２１ S(O) ２ R ２１ , -C(O)N(R ２１ ), ２ , -C(O)NR ２１ OR ２１ , -N(R ２１ )C(O)R ２１ , -N(R ２１ )C(O)N(R ２１ ), ２ , -N(R ２１ )C(O)OR ２１ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ), ２ , 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 alkenyl, C ２～６ alkynyl, C ３ to C １２ optionally substituted by one or more substituents independently selected from carbocyclic rings and 5- to 12-membered heterocyclic rings, R ９１ is fluorine, iodine, -CN, -NO ２ , =O, -N(R ２１ ), ２ , -B(OR ２１ ), ２ , -OR ２１ , -SR ２１ , -S(O) ２ (R ２１ ), -S(O) ２ N(R ２１ ), ２ , -NR ２１ S(O) ２ R ２１ , -C(O)N(R ２１ ), ２ , -C(O)NR ２１ OR ２１ , -N(R ２１ ),C(O)R ２１ , -N(R ２１ ),C(O)N(R ２１ ), ２ , -N(R ２１ ),C(O)OR ２１ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , -OC(O)N(R ２１ ), ２ , 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 alkenyl, C ２～６ alkynyl, C ３ ~C １２ selected from carbocyclic rings and 5- to 12-membered heterocyclic rings, R ９２ is hydrogen, halogen, -CN, -NO ２ , =O, -N(R ２１ ), -B(OR ２ ), -OR ２１ ), -SR ２ ), -S(O) ２１ (R ２１ ), -S(O) ２ (R ２１ ), -NR ２ (R ２１ ), -NR ２ S(O) ２１ R ２ ), -C(O)N(R ２１ ), -C(O)NR ２１ OR ２ ), -N(R ２１ )C(O)R ２１ ), -N(R ２１ )C(O)N(R ２１ )C(O)R ２１ ), -N(R ２１ )C(O)OR ２ ), -C(O)R ２１ ), -C(O)OR ２１ ), -OC(O)R ２１ ), -OC(O)N(R ２１ )C(O)R ２１ ), -OC(O)N(R ２１ )C(O)R ２ ), C １～６ alkyl-N(R ２０ )C(O)R 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 alkenyl, C ２～６ alkynyl, C ３ ~C １２ is selected from carbocyclic rings and 5- to 12-membered heterocyclic rings, R ９３ is selected from hydrogen, -C(O)OR ２１ , -C(O)R ２１ and -SO ２ R ２１ and is selected from R ２１ is each, hydrogen; and C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３～１２ selected independently from carbocyclic rings and 3- to 12-membered heterocyclic rings, each of which is optionally substituted with one or more substituents selected independently from halogen, -OH, -CN, -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 selected independently from carbocyclic rings and 3- to 12-membered heterocyclic rings and optionally substituted with one or more substituents].

304. A compound or salt according to claim 303, wherein B is selected from optionally substituted 5- to 7-membered heterocycles.

305. A compound or salt according to claim 304, wherein B is selected from optionally substituted 5- to 7-membered unsaturated heterocycles.

306. A compound or salt according to claim 280, wherein B is selected from optionally substituted 5-membered heterocycles.

307. The compound or salt according to any one of claims 303 to 306, wherein the heterocycle of B has at least one sulfur atom.

308. Formula (III) is formula (III-A) 【Chemical 684】 A compound or salt according to claim 307, represented by or a pharmaceutically acceptable salt.

309. R ９１ is halogen, -CN, -NO ２ , -N(R ２１ ), ２ , -OR ２１ , -C(O)R ２１ , C １～６ alkyl-N(R ２０ ), ２ , C １～６ aminoalkyl, C １～６ alkoxyalkyl, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl, C １～６ alkyl, C ２～６ alkenyl, C ２～６ alkynyl, C ３ ~C １２ a carbon ring and a 5- to 12-membered heterocyclic ring, the compound or salt according to any one of claims 303 to 308.

310. R ９１ The compound or salt according to any one of claims 303 to 309, wherein R is selected from -CN.

311. R ９２ is hydrogen, halogen, -CN, -NO ２ , -N(R ２１ ), -OR ２ , -SR ２１ , -C(O)R ２１ , -C(O)OR ２１ , -OC(O)R ２１ , C ２１ alkyl-N(R １～６ ), C ２０ aminoalkyl, C ２ alkoxy, C １～６ alkoxyalkyl, C １～６ hydroxyalkyl, C １～６ cyanoalkyl, C １～６ haloalkyl, C １～６ alkyl, C １～６ alkenyl, C １～６ alkynyl, C ２～６ -C ２～６ -C ３ -C １２ a carbocyclic ring and a 5- to 12-membered heterocyclic ring, the compound or salt according to any one of claims 303 to 310.

312. R ９２ is hydrogen, halogen, -CN, and -N(R ２１ ) ２ selected from, the compound or salt according to claim 311.

313. R ９２ is selected -N(R ２１ ) ２ is a compound or salt according to claim 312.

314. R ９３ The compound or salt according to claim 313, wherein R is selected from hydrogen.

315. A process for preparing a compound or salt according to any one of claims 303 to 314.

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