Spiro-heterocyclic inhibitors of KRAS G12C mutant protein and their use

Abstract

This disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising such compounds, and methods for treating specific disorders such as cancers including but not limited to lung cancer, pancreatic cancer, colorectal cancer, and solid tumors. In particular, this disclosure provides compounds of formula (II): We provide TIFF2026515933000856.tif57170 and its pharmaceutically acceptable salts (wherein substituents are as described).

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 464102, filed on 4 May 2023, and to U.S. Provisional Patent Application No. 63 / 632098, filed on 10 April 2024, each of which is incorporated herein by reference in whole for all purposes as if described herein in its entirety.

[0002] This disclosure generally relates to compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions containing such compounds, and their use and methods for treating disorders including but not limited to cancers such as lung cancer, pancreatic cancer, and colorectal cancer. [Background technology]

[0003] KRAS oncoproteins are G proteins that link extracellular pro-mitotic signaling to intracellular pro-proliferative responses. KRAS functions as a molecular "on / off" switch, alternating between an inactive GDP-bound state and an active GTP-bound state. The transition between these states is facilitated by guanine nucleotide exchange factors. Mitogen stimulation can induce GTP binding, which results in a conformational change that allows KRAS to interact with downstream effector proteins, leading to cell proliferation. In normal cells, pro-proliferative signaling is regulated by the action of GTPase-activated proteins (GAPs), which return KRAS to its GDP-bound non-proliferative state. Mutations in KRAS disrupt this regulated cycling of KRAS between these GDP-bound and GTP-bound states, leading to the accumulation of the GTP-bound active state and a dysfunction of cell proliferation. See Simanshu et al., Cell 2017, 170, 17-33.

[0004] Attempts to develop inhibitors of mutated KRAS protein have historically been hampered by the picomolar affinity of KRAS to GDP and GTP, as well as the absence of a drug pocket on the protein surface. See Cox et al., Nat. Rev. Drug Discov. 2014, 13, 828-851. The G12C mutant of KRAS, "KRAS G12C Covalent inhibitors of GDP-KRAS have been identified. These inhibitors are GDP-KRAS G12C It may bind to the previously unrecognized allosteric pocket above and prevent its subsequent activation. See O'Bryan, JP Pharmacol. Res. 2019, 139, 503-511 and Ostrem et al., Nature 2013, 503, 548-551. This finding represents a significant new development in KRAS inhibitor research and has recently led to the entry of KRAS inhibitors into human clinical trials. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Simanshu et al.,Cell 2017,170,17-33 [Non-Patent Document 2] Cox et al.,Nat.Rev.Drug Discov.2014,13,828-851 [Non-Patent Document 3] O'Bryan,JPPharmacol.Res.2019,139,503-511 [Non-Patent Document 4] Ostrem et al.,Nature 2013,503,548-551 [Overview of the project] [Means for solving the problem]

[0006] One aspect of this disclosure is a compound of formula (II): [ka] or a pharmaceutically acceptable salt thereof is provided (wherein: m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; q is 0, 1, or 2; r is 0 or 1; A is N, CH, C-halo, C-CN, C-C 1~3 alkyl, C-C 1~3 haloalkyl, C-C 0~3 alkylene OH or C-C 0~3 alkylene-C 1~4 alkoxy; W 1 and W 2 each of which is independently N, CH, C-halo, C-CN, C-C 1~3 alkyl, C-C 2~3 alkenyl, C-C 2~3 alkynyl, C-C 1~3 haloalkyl, C-C 0~3 alkylene OH or C-C 0~3 alkylene-C 1~4 alkoxy, wherein each of said alkenyl and alkynyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently halo, C 1~3 haloalkyl, C 0~3 alkylene OH or C 0~3 alkylene C 1~4 alkoxy; X is N or C-R 5a ; Y’ is C 3~7 cycloalkyl, C 4~7 cycloalkenyl, heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; R 1a 、R1b , and R 2 Each of these is independently H, D, Halo, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, C 0~2 Alkylene-N(R) N1 )C having 2, 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. 1~2 It is either alkylene-heterocycloalkyl, or R 1b and R 2 Along with the carbon atoms to which they are bonded, [ka] Forming, Each R 3 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, [ka] , C 0~3 Alkylene CN, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 3 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7Forming a cycloalkenyl, a condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R A1 and R A2 Each of these is independently H, C 1~3 Alkyl, C 1~3 Haloalkyl, or C 3~5 It is a cycloalkyl; Each R 4 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~3 Alkylene CN, C 1~3 Alkylene OH, C 1~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 A cycloalkyl or spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R 5a H, CN, Haro, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, or C 3~5 It is a cycloalkyl; R 5b Hello, C 1~3 Haloalkyl, C 1~6 Alkyl, C 2~4 Alkenil, C 2~4 Alkinyl, C 1~3 Alkoxy, C 1~3 Thioalkyl, C 3~7 Cycloalkyl, C 5~7Cycloalkenyl, heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or R 5a and R 5b together with the atom to which they are attached form a C 3~7 cycloalkyl; wherein each of the above C 1~6 alkyl, C 2~4 alkenyl, C 2~4 alkynyl, C 3~7 cycloalkyl, C 5~7 cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl is independently unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently C 1~3 haloalkyl, C 0~6 alkylene-OH, C 0~6 alkylene-C 1~3 alkoxy, C 3~7 cycloalkyl, C 5~7 cycloalkenyl, heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or phenyl; each R 6 is independently halo, CN, C 1~3 alkyl, C 2~3 alkenyl, C 1~3 haloalkyl, C 0~3 alkylene-OH, C 0~3 alkylene-C 1~3 alkoxy, deuterated C 0~3 alkylene-C 1~3 alkoxy, C 1~4 alkylene-N(R N1 )2, oxo, =CH2, C 3~7 cycloalkyl, C 4~7Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is alkylene CN; Each R 7 Independently, Halo, C 0~3 Alkylene-CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, oxo, =CH2, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkilen heteroaryl; Spiro-C 3~7 It is a cycloalkyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or it is a spiro-heterocycloalkyl having 2 vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensed heterocycloalkyl having 3-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S, condensed-C 6~10 They form aryl or condensed heteroaryls having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 Alkyl and Each R N1 H or C 1~4 (It is alkyl.)

[0007] Further aspects of this disclosure provide compounds listed in Table A, Table B, Table C, or Table D, or pharmaceutically acceptable salts of any of the above.

[0008] Another aspect of this disclosure provides a pharmaceutical composition comprising the compounds disclosed herein (compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, Table B, Table C, or Table D, or pharmaceutically acceptable salts of any of the above) and pharmaceutically acceptable excipients.

[0009] A further aspect of this disclosure provides a method for treating a cancer in a subject requiring treatment, comprising administering to the subject a therapeutically effective amount of a compound described herein (such as compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, Table B, Table C, or Table D, or pharmaceutically acceptable salts of any of the above) or a pharmaceutical composition described herein.

[0010] Further aspects of this disclosure provide compounds described herein (compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, Table B, Table C, or Table D, or pharmaceutically acceptable salts of any of the above) or pharmaceutical compositions described herein for use as pharmaceuticals.

[0011] Another aspect of this disclosure provides compounds disclosed herein (compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, Table B, Table C, or Table D, or pharmaceutically acceptable salts of any of the above) or pharmaceutical compositions disclosed herein for use in the treatment of cancer. Yet another aspect of this disclosure provides compounds disclosed herein (compounds of formula (I), formula (IA), formula (IB), formula (II), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, Table B, Table C, or Table D, or pharmaceutically acceptable salts of any of the above) or pharmaceutical compositions disclosed herein for the manufacture of pharmaceuticals for the treatment of cancer. In some cases, any of the above cancers may be non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed-type cancer of unknown primary origin, pancreatic cancer, hepatobiliary tract cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, solid tumor, or any combination of the above.

[0012] Another aspect of this disclosure relates to a compound of formula (B): [ka] Alternatively, provide nitrogen-protected analogues or pharmaceutically acceptable salts of any of the above (wherein formula: o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; Each R 6 , Haro, CN, C 1~3 Alkyl, C 2~3 Alkenil, C 1~3 Haloalkyl, C 0~3 Alkylene-OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3 Alkylene-C 1~3 Alkoxy, C 1~4 Alkylene-N(R) N1 )2, oxo, =CH2, C3~7 Cycloalkyl, C 4~7 Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is alkylene CN; Each R 7 Independently, Halo, C 0~3 Alkylene-CN, C 1~3 Alkyl, C 1~3Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, oxo, =CH2, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkilen heteroaryl; Spiro-C 3~7 It is a cycloalkyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or it is a spiro-heterocycloalkyl having 2 vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensed heterocycloalkyl having 3-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S, condensed-C 6~10 They form aryl or condensed heteroaryls having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 Alkyl and Each R N1 H or C 1~4 (It is alkyl.)

[0013] A further aspect of the present disclosure is a method for preparing the compounds or salts of the present disclosure (such as compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, Table B, Table C, or Table D, or any pharmaceutically acceptable salt thereof), wherein the compound of formula (B): [ka] compound: [ka] Then, when mixed under conditions that form carbon-nitrogen bonds, [ka] The present invention provides a method for forming a (wherein PG is a protecting group) compound.

[0014] A further aspect of this disclosure is a method for preparing the compounds or salts of the disclosure (compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, Table B, Table C, or Table D, or any pharmaceutically acceptable salt thereof), which include the compounds listed in Table E, Table F, Table G, 3-001.1, 3-001.2, 3-002.1, 3-002.2, 3-003.1, 3-003.2, 3-020.1, 3-020.2, 3-021.1, 3-021.2, 3-04 6.1, 3.046.2, 3-050.1, 3-050.2, 3-051.1, 3-051.2, 3-051.3, 3-051.4, 3-051.5, 3-052.1, 3-052.2, 3-052.3, 3-052.4, 3-052.5, 3-053.1, 3-053.2, 3-053.3, 3-053.4, 3-053.5, 3-054-1, 3-054-2, 3-055.1, 3-055.2, 3-055.3, 3-055.4, 3-055.5, 3-057.1, 3-057.2, 3-057.3, 3-058. 1, 3-058.2-1, 3-058.2.2, 3-058.3, 3-059.1, 3-060.1, 3-060.2, 3-060.3, 3-060.4, 3-060.5, 3-060.6, 3-060.7, 3-060.8, 3-060.9, 3-061.1, 3-061.2, 3-061.3, 3-061.4, 3-061.5, 3-062.1-1, 3-062.1-2, 3-062.1-1, 3-062.2, 3-063.1, 3-063.2, 3-065.1, 3-065.2, 3-065.3, 3-065. The present invention provides a method comprising converting a compound selected from the group consisting of 4, 3-065.5, 3-067-1, 3-067-2, 3-069.1, 3-069.2, 3-073.1, 3-073.2, 3-073.3, 3-073.4, 3-073.5, 3-074.1, 3-074.2, 3-074.3, 3-074.4, 3-075.1, 3-075.2, 3-075.3, 3-076.1, and 3-076.2, a protected analog of any of the above, or a pharmaceutically acceptable salt of any of the above, into a compound of the present disclosure.

[0015] Further aspects and advantages will become apparent to those skilled in the art by examining the following detailed description. The following description includes specific examples, embodiments, and examples, with the understanding that this disclosure is illustrative and not intended to limit embodiments of this disclosure to the specific examples, embodiments, and examples described herein. [Modes for carrying out the invention]

[0016] Compounds having activity as inhibitors of the G12C-mutated KRAS protein, pharmaceutical compositions containing such compounds, and methods of using the compounds and pharmaceutical compositions described herein to treat disorders such as cancer are disclosed herein.

[0017] Compound of formula (II) Compound of formula (II): [ka] Or a pharmaceutically acceptable salt thereof is provided herein. (In the formula, m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; q is 0, 1, or 2; r is either 0 or 1; A stands for N, CH, C-Hello, C-CN, CC. 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy; W 1 and W 2 Each of these is independently N, CH, C-HALO, C-CN, CC 1~3 Alkyl, CC 2~3 Alkenil, CC 2~3 Alkinil, CC 1~3 Haloalkyl, CC 0~3Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy, where each of the alkenyl and alkynyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently a halo, C 1~3 Haloalkyl, C 0~3 Alkylene OH or C 0~3 Alkilen C 1~4 It is an alkoxy; X is N or CR 5a ; Y' is C 3~7 Cycloalkyl, C 4~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; R 1a , R 1b , and R 2 Each of these is independently H, D, Halo, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, C 0~2 Alkylene-N(R) N1 )C having 2, 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. 1~2 It is either alkylene-heterocycloalkyl, or R 1b and R 2 Along with the carbon atoms to which they are bonded, [ka] Forming, Each R 3 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, [ka] , C 0~3 Alkylene CN, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 3 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R A1 and R A2 Each of these is independently H, C 1~3 Alkyl, C 1~3 Haloalkyl, or C 3~5 It is a cycloalkyl; Each R 4 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~3 Alkylene CN, C 1~3 Alkylene OH, C 1~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 A cycloalkyl or spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R 5a H, CN, Haro, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, or C 3~5 It is a cycloalkyl; R 5b Hello, C 1~3 Haloalkyl, C 1~6 Alkyl, C 2~4 Alkenil, C 2~4 Alkinyl, C 1~3 Alkoxy, C 1~3 Thioalkyl, C 3~7 Cycloalkyl, C 5~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or R 5a and R 5b C 3~7 Forms a cycloalkyl group; Here, C 1~6 Alkyl, C 2~4 Alkenil, C 2~4 Alkinyl, C 3~7 Cycloalkyl, C 5~7 Each of the cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl compounds is independently unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently C 1~3 Haloalkyl, C 0~6 Alkylene-OH, C 0~6 Alkylene-C 1~3 Alkoxy, C 3~7 Cycloalkyl, C 5~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a phenyl; Each R 6 They are independently: Hello, CN, C 1~3Alkyl, C 2~3 Alkenil, C 1~3 Haloalkyl, C 0~3 Alkylene-OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3 Alkylene-C 1~3 Alkoxy, C 1~4 Alkylene-N(R) N1 )2, oxo, =CH2, C 3~7 Cycloalkyl, C 4~7 Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C 1~3Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is alkylene CN; Each R 7 Independently, Halo, C 0~3 Alkylene-CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, oxo, =CH2, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkilen heteroaryl; Spiro-C 3~7 It is a cycloalkyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or it is a spiro-heterocycloalkyl having 2 vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensed heterocycloalkyl having 3-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S, condensed-C 6~10 They form aryl or condensed heteroaryls having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 Alkyl and Each R N1H or C 1~4 (It is alkyl.)

[0018] In some cases, the compound of formula (II) is a free base. In some cases, the compound of formula (II) is a pharmaceutically acceptable salt.

[0019] In some cases, R 1a is H or D. In some cases, R 1a H is H. In some cases, R 1a It is D. In some cases, R 1b is H or D. In some cases, R 1b H is H. In some cases, R 1b It is D. In some cases, R 2 is H or D. In some cases, R 2 H is H. In some cases, R 2 It is D. In some cases, R 1a , R 1b , and R 2 At least one of them is H or D. In some cases, R 1a , R 1b , and R 2 At least one of them is H. In some cases, R 1a , R 1b , and R 2 At least one of them is D. In some cases, R 1a , R 1b , and R 2 At least two of them are, independently, H or D. In some cases, R 1a , R 1b , and R 2 At least two of them are H. In some cases, R 1a , R 1b , and R 2 At least two of them are D. In some cases, R 1a , R 1b , and R 2 Each of them is independently either H or D. In some cases, R1a , R 1b , and R 2 Two of them are H, and R 1a , R 1b , and R 2 One of them is Halo, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, C 0~2 Alkylene-N(R) N1 )C having 2, or 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S 1~2 It is alkylene-heterocycloalkyl. In some cases, R 1a , R 1b , and R 2 Each of them is H. In some cases, R 1a , R 1b , and R 2 Each of them is D. In some cases, R 1a , R 1b , and R 2 At least one of them is a halo. In some cases, R 1a , R 1b and R 2 One of them is a halo. In some cases, R 1a is a halo, R 1b and R 2 Each of them is H. In some cases, R 1a , R 1b and R 2 At least one of them is Br, Cl, or F. In some cases, R 1a , R 1b and R 2 One of them is Br, Cl, or F. In some cases, R 1a is Br, Cl, or F, and R 1b and R 2 Each of them is H. In some cases, R1a , R 1b and R 2 At least one of them is Br or Cl. In some cases, R 1a , R 1b and R 2 One of them is Br or Cl. In some cases, R 1a is Br or Cl, and R 1b and R 2 Each of them is H. In some cases, R 1a , R 1b and R 2 At least one of them is C 1~4 Alkyl or C 1~4 It is a haloalkyl. In some cases, R 1a , R 1b and R 2 One of them is C 1~4 Alkyl or C 1~4 It is a haloalkyl. In some cases, R 1a , R 1b , and R 2 At least one of them is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 One of these is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 At least one of them is CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 One of them is CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 At least one of them is C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, or C 0~2 Alkylene-N(R) N1 )2, and each R N1 H or C 1~4 It is alkyl. In some cases, each R N1 These are independently H or CH3. In some cases, each R N1 H is independent of R. In some cases, R 1a , R 1b , and R 2 At least one of them is CH2OH, OCH3, CH2OCH3, OCF3, CH2OCF3, CN, CH2CN, NH2, N(CH3)2, CH2NH2, or CH2N(CH3)2. In some cases, R 1a , R 1b , and R 2 One of these is CH2OH, OCH3, CH2OCH3, OCF3, CH2OCF3, CN, CH2CN, NH2, N(CH3)2, CH2NH2, or CH2N(CH3)2. In some cases, R 1a , R 1b , and R 2 At least one of them is C 1~2 Alkylene-heterocycloalkyl, where the heterocycloalkyl contains 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. In some cases, the heterocycloalkyl is azilidinyl, oxylanil, azetidinyl, oxetanil, pyrrolidinyl, tetrahydrofuranil, imidazolidinyl, pyrazolidinyl, oxathiolidinyl, isoxathiodinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, diazinyl, or morpholinyl. In some cases, the heterocycloalkyl is azilidinyl, azetidinyl, pyrrolidinyl, piperidinyl, or morpholinyl. In some cases, R 1a , R 1b , and R2 At least one of these is aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl. In some cases, R 1a , R 1b , and R 2 One of these is aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl. In some cases, R 1a , R 1b , and R 2 One of these is Br, Cl, F, CH3, CH2F, CHF2, CF3, CH2OH, OCH3, CH2OCH3, OCF3, CH2OCF3, CN, CH2CN, NH2, N(CH3)2, CH2NH2, CH2N(CH3)2, aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl. In some cases, R 1b and R 2 Along with the carbon atoms to which they are bonded, [ka] It forms R 1a H is H. In some cases, R 1b and R 2 Along with the carbon atoms to which they are bonded [ka] To form (from). In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0020] In some cases, m is 0, [ka] teeth [ka] In some cases, m is 1. In some cases, m is 2. In some cases, m is 3. In some cases, m is 4. In some cases, [ka] It is deuterated. In some cases, [ka] It is completely deuterated, structure: [ka] It has. In some cases, at least one R 3 C 1~3 Alkyl or C 1~3It is a haloalkyl. In some cases, at least one R 3 is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, at least one R 3 is CH3, CH2CH3, CF3, CHF2, or CH2F. In some cases, at least one R 3 It is CH3. In some cases, m is 1 or 2, and each R 3 It is CH3. In some cases, m is 1 and R 3 is CF3, CHF2, or CH2F. In some cases, at least one R 3 teeth, [ka] And R A1 and R A2 Each of these is independently H, C 1~3 Alkyl, C 1~3 Haloalkyl, or C 3~5 It is a cycloalkyl. In some cases, m is 1 and R 3 teeth [ka] In some cases, R A1 and R A2 Each of these is independently H, CH3, CH2F, CHF2, CF3, CH2CH3, CH2CH2CH3, CH(CH3)2, cyclopropyl, or cyclobutyl. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, at least one R 3 teeth [ka] In some cases, at least one R 3 teeth [ka] In some cases, at least one R 3 C 0~3 It is alkylene CN. In some cases, at least one R 3 is CN, CH2CN, or CH2CH2CN. In some cases, at least one R 3 is CN or CH2CN. In some cases m is 1 and R 3 is CN or CH2CN. In some cases, at least one R 3 C 0~3 Alkylene OH or C 0~3 Alkylene-C 1~3 It is an alkoxy. In some cases, at least one R 3 is OH, CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3. In some cases, m is 1 and R 3 is OH, CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3. In some cases, at least one R 3 is oxo (=O). In some cases, there is at least one R 3 Spiro-C 3~7A spiro-heterocycloalkyl having a cycloalkyl group or 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. In some cases, at least one R 3 is spiro-cyclopropyl, spiro-cyclobutyl, or spiro-cyclopentyl. In some cases, at least one R 3 These are spiro-azetidinil, spiro-oxetanil, spiro-pyrrolidinil, spiro-imidazolidinil, spiro-pyrazolidinil, or spiro-tetrahydrofuranil. In some cases, at least one R 3 These are spiro-cyclopropyl, spiro-cyclobutyl, spiro-cyclopentyl, spiro-azetidinil, spiro-oxetanil, spiro-pyrrolidinil, spiro-imidazolidinil, spiro-pyrazolidinil, or spiro-tetrahydrofuranil. In some cases, at least one R 3 These are spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanil, or spiro-tetrahydrofuranil. In some cases, at least one R 3 Spiro-C 4~7 A cycloalkenyl or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. In some cases, two vicinal R atoms. 3 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 It forms a cycloalkyl or a condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. In some cases, two vicinal R 3 These, along with the atoms to which they are bonded, form condensed-cyclopropyl, condensed-cyclobutyl, condensed-cyclopentyl, or condensed-cyclohexyl. In some cases, two vicinal R 3 These, along with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl. In some cases, two vicinal R 3 These atoms, along with the atoms to which they are bonded, undergo condensation -C4~7 It forms a cycloalkenyl or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. In some cases, each R 3 These are independently CH3, CH2CH3, CF3, CHF2, CH2F, [ka] ,CN,CH2CN,OH,CH2OH,CH2CH2OH,OCH3,CH2OCH3,CH2CH2OCH3,oxo,spiro-cyclopropyl,spiro-cyclobutyl,spiro-oxetanyl, or spiro-tetrahydrofuranyl; or two vicinal R 3 These, along with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl. In some cases, each R 3 These are independently CH3, CH2CH3, CH2F, CHF2, CF3, CN, CH2CN, OH, CH2OH, CH2CH2OH, OCH3, CH2OCH3, CH2CH2OCH3, oxo, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranyl; or two vicinal R 3 These, along with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl. In some cases, m is 0; or m is 1, R 3 is CH3, CH2F, CHF2, CF3, CN, CH2CN, CH2OH, CH2OCH3, or spiro-oxetanyl. In some cases m is 0; or m is 1, R 3 It is CH3. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0021] In some cases, A is N. In some cases, A is CH, C-HALO, C-CN, CC 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy. In some cases, A is CH. In some cases, A is CF, C-Cl, or C-CN. In some cases, A is C-halo or C-CN. In some cases, A is CF or C-Cl. In some cases, A is CF. In some cases, A is C-CN. In some cases, A is CC 1~3It is alkyl. In some cases, A is C-CH3, C-CH2CH3, C-CH2CH2CH3, or C-CH(CH3)2. In some cases, A is C-CH3. In some cases, A is CC 1~3 It is a haloalkyl group. In some cases, A is C-CF3, C-CHF2, or C-CH2F. In some cases, A is C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, or C-CH2F. In some cases, A is C-CH3, C-CH2F, C-CHF2, or C-CF3. In some cases, A is CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy. In some cases, A is C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, A is C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, A is CH, CF, C-Cl, C-CN, C-CH3, C-CH2F, C-CHF2, C-CF3, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, A is N, CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, C-CH2F, C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, A is N, CH, CF, C-Cl, C-CN, C-CH3, C-CF3, C-CHF2, C-CH2F, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, A is N, CH, or C-CH3. In some cases, n is 0. In some cases, n is 1. In some cases, n is 2. In some cases, at least one R 4 C 1~3 Alkyl or C 1~3 It is a haloalkyl. In some cases, at least one R4 is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, at least one R 4 It is CH3. In some cases, one R 4 is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, n is 2, and each R 4 These are independently CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, n is 1, and R 4 is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, n is 1, and R 4 It is CH3. In some cases, at least one R 4 is C 0~3 It is alkylene CN. In some cases, at least one R 4 is CN or CH2CN. In some cases n is 1 and R 4 is CN or CH2CN. In some cases, at least one R 4 C 1~3 Alkylene OH or C 1~3 Alkylene-C 1~3 It is an alkoxy. In some cases, at least one R 4 is CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3. In some cases, n is 1, and R 4 is CH2OH, CH2CH2OH, CH2OCH3, or CH2CH2OCH3. In some cases, at least one R 4 It is an oxo. In some cases, at least one R 4 is C 3~7It is a spirocycloalkyl. In some cases, the spirocycloalkyl is spirocyclopropyl, spirocyclobutyl, or spirocyclopentyl. In some cases, the spirocycloalkyl is spirocyclopropyl or spirocyclobutyl. In some cases, it is at least one R 4 It is a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. In some cases, the spiro-heterocycloalkyl is spiro-oxetanyl or spiro-tetrahydrofuranyl. In some cases, the spiro-heterocycloalkyl is spiro-oxetanyl. In some cases, at least one R 4 These are spiro-cyclopropyl, spiro-cyclobutyl, or spiro-oxetanil. In some cases, each R 4 These are independently CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, CH2F, CN, CH2CN, CH2OH, CH2CH2OH, CH2OCH3, CH2CH2OCH3, oxo, spirocyclopropyl, spirocyclobutyl, or spirooxetanyl. In some cases, each R 4 These are independently CH3, CH2CH3, CH2CH2CH3, CH2F, CN, CH2CN, CH2OH, CH2CH2OH, CH2OCH3, or spirocyclopropyl. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0022] In some cases, W 1 It is N. In some cases, W 1 is CH. In some cases, W 1 This is C-halo or C-CN. In some cases, W 1 These are CF, C-Cl, or C-Br. In some cases, W 1 These are CF, C-Cl, or C-CN. In some cases, W 1 CC 1~3 Alkyl or CC 1~3 It is a haloalkyl. In some cases, W 1 These are C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, or C-CH2F. In some cases, W 1 These are C-CH3, C-CH2CH3, C-CH2F, C-CHF2, or C-CF3. In some cases, W 1 This is C-CH3 or C-CH2CH3. In some cases, W 1 CC 2~3 Alkenil or CC 2~3The molecule is an alkynyl, where each alkenyl and alkynyl is either unsubstituted or substituted with one or more substituents. In some cases, each alkenyl and alkynyl is unsubstituted. In some cases, each alkenyl and alkynyl is substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, each alkenyl and alkynyl is substituted with 1 substituent. In some cases, each alkenyl and alkynyl is substituted with 2 substituents. In some cases, each alkenyl and alkynyl is substituted with 3 substituents. In some cases, each substituent of the alkenyl and alkynyl is independently a halo, C 1~3 Haloalkyl, C 0~3 Alkylene OH, or C 0~3 Alkilen C 1~4 It is an alkoxy. In some cases, W 1 These are C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), or C-CCH. In some cases, W 1 CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy. In some cases, W 1 These are C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, W 1 These are C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, W 1 These are CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, C-CH2F, C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, W 1These are CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, W 1 These are CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2F, C-CHF2, C-CF3, C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), C-CCH, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, W 2 It is N. In some cases, W 2 is CH. In some cases, W 2 This is C-halo or C-CN. In some cases, W 2 These are CF, C-Cl, or C-Br. In some cases, W 2 These are CF, C-Cl, or C-CN. In some cases, W 2 CC 1~3 Alkyl or CC 1~3 It is a haloalkyl. In some cases, W 2 These are C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, or C-CH2F. In some cases, W 2 These are C-CH3, C-CH2CH3, C-CH2F, C-CHF2, or C-CF3. In some cases, W 2 This is C-CH3 or C-CH2CH3. In some cases, W 2 CC 2~3 Alkenil or CC 2~3The molecule is an alkynyl, where each alkenyl and alkynyl is either unsubstituted or substituted with one or more substituents. In some cases, each alkenyl and alkynyl is unsubstituted. In some cases, each alkenyl and alkynyl is substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, each alkenyl and alkynyl is substituted with 1 substituent. In some cases, each alkenyl and alkynyl is substituted with 2 substituents. In some cases, each alkenyl and alkynyl is substituted with 3 substituents. In some cases, each substituent is independently a halo, C 1~3 Haloalkyl, C 0~3 Alkylene OH, or C 0~3 Alkilen C 1~4 It is an alkoxy. In some cases, W 2 These are C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), or C-CCH. In some cases, W 2 CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy. In some cases, W 2 These are C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, W 2 These are C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, W 2 These are CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, C-CH2F, C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, W 2These are CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, W 2 These are CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2F, C-CHF2, C-CF3, C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), C-CCH, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, W 1 and W 2 Each of these is independently N, CH, or C-CH3. In some cases, W 1 CH is W 2 It is N, CH, or C-CH3. In some cases, W 2 is N and W 1 It is N, CH, or C-CH3. In some cases, W 1 CH is W 2 is N. In some cases X is N. In some cases W 1 CH is and X is N. In some cases, W 2 X is N, and X is N. In some cases, W 1 CH is W 2 X is N, and X is N. In some cases, X is CR 5a In some cases, W 1 CH is CH, and X is CR 5a In some cases, W 2 is N, and X is CR 5a In some cases, W 1 CH is W 2 is N, and X is CR 5a In some cases, W 1 CH, C-Hello, C-CN, CC 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy; W 2is N; X is N or CR 5a In some cases, R 5a H is H. In some cases, R 5a is CN. In some cases, R 5a is Br, Cl, or F. In some cases, R 5a C 1~3 Alkyl or C 1~3 It is a haloalkyl. In some cases, R 5a is CH3, CH2CH3, CF3, CHF2, or CH2F. In some cases, R 5a It is CH3. In some cases, R 5a C 2~6 Alkenyl or C 2~6 It is alkinyl. In some cases, R 5a C 2~3 Alkenyl or C 2~3 It is alkinyl. In some cases, R 5a teeth, [ka] In some cases, R 5a teeth, [ka] In some cases, R 5a C 0~3 Alkylene OH or C 0~3 Alkylene-C 1~3 It is an alkoxy. In some cases, R 5a is OH, CH2OH, OCH3, or CH2OCH3. In some cases, R 5a is C 3~5 It is a cycloalkyl. In some cases, R 5a is OH, CH2OH, OCH3, CH2OCH3, or [ka] In some cases, R 5a teeth, [ka] In some cases, R 5a are H, CN, Br, Cl, F, CH3, CH2CH3, CF3, CHF2, CH2F, [ka] OH, CH2OH, OCH3, CH2OCH3, or [ka] In some cases, R 5a is H, CN, or CH3. In some cases, R 5a is CN or CH3. In some cases, X is N, C-CH3, or C-CN. In some cases, W 1 is CH;W 2 is N; X is N, C-CH3, or C-CN.

[0023] In some cases, R 5b is a halo. In some cases, R 5b is Br, Cl, or F. In some cases, R 5b is C 1~3 It is a haloalkyl. In some cases, R 5b These are CF3, CF2H, CFH2, or CF2CH3. In some cases, R 5b This is CF3 or CF2H. In some cases, R 5b It is CF3. In some cases, R 5b is CF2H. In some cases, R 5b It is CHF2. In some cases, R 5b C 1~3 Alkoxy or C 1~3 It is a thioalkyl group. In some cases, R 5b is OCH3, OCH2CH3, SCH3, or SCH2CH3. In some cases, R 5b It is OCH3 or SCH3. In some cases, R 5b C1~6 Alkyl, C 2~4 Alkenyl, or C 2~4 It is an alkynyl, each of which is unsubstituted or substituted with one or more substituents. In some cases, C 1~6 Alkyl groups are CH3, CH2CH3, CH2CH2CH3, or CH(CH3)2, where each of the above is either unsubstituted or substituted with one or more substituents. In some cases, C 2~4 Alkenyls are CH=CH2 or CH=CHCH3, where each of the above is either unsubstituted or substituted with one or more substituents. In some cases, C 2~4 Alkinil is [ka] Here, each of the above is either unsubstituted or substituted with one or more substituents. In some cases, C 1~6 Alkyl, C 2~4 Alkenyl and C 2~4 Alkinyl is unsubstituted. In some cases, R 5b is CH3, CH2CH3, CH2CH2CH3, or CH(CH3)2. In some cases, C 1~6 Alkyl, C 2~4 Alkenyl and C 2~4 Alkynnyl is substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, C 1~6 Alkyl, C 2~4 Alkenyl and C 2~4 Each alkynyl is substituted with a single substituent. In some cases, C 1~6 Alkyl, C 2~4 Alkenyl and C 2~4 Each alkynyl is substituted with two substituents. In some cases, C 1~6 Alkyl, C 2~4 Alkenyl and C 2~4Each alkynyl is substituted with three substituents. In some cases, each substituent of the alkyl, alkenyl, and alkynyl is independently C 1~3 Haloalkyl, C 0~6 Alkylene (OH), C 0~6 Alkylene-C 1~3 Alkoxy, C 3~7 Cycloalkyl, C 5~7 The substituents are cycloalkenyls, heterocycloalkyls having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, heterocycloalkenyls having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or phenyl. In some cases, each substituent is independently CH3, CF3, CF2H, CFH2, OH, OCH3, OCF3, CH2OH, CH2OCH3, cyclopropyl, cyclobutyl, or phenyl. In some cases, R 5b is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, [ka] In some cases, R 5b C 3~7 Cycloalkyl, C 5~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, the cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl are each substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, each substituent of the cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl is independently a halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~6Alkylene (OH), or C 0~6 Alkylene-C 1~3 It is an alkoxy. In some cases, C 3~7 Cycloalkyls are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, where each of the above is unsubstituted or substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, C 5~7 Cycloalkenyl is cyclopentenyl or cyclohexenyl, where each of the above is unsubstituted or substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, heterocycloalkyls having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S are azilidinyl, oxyranyl, thyranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothipyranyl, dithianyl, morpholinyl, or thiomorpholinyl, where each of the above is unsubstituted or substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, heterocycloalkenyls having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S are dihydropyrrolyl, dihydrofuranyl, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridinyl, dihydropyranyl, or dihydrothipyranyl, where each of the above is unsubstituted or substituted with 1 to 3 substituents (e.g., 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, or 3 substituents). In some cases, R 5bThese are cyclopropyl, cyclobutyl, cyclopentenyl, oxetanyl, or tetrahydrofuranil. In some cases, R 5b are CH3, CF3, CF2H, CFH2, CH2CH3, CH2CH2CH3, CH(CH3)2, [ka] In some cases, R 5b are Br, Cl, F, OCH3, SCH3, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, [ka] In some cases, [ka] teeth [ka] And X is N, C-CH3, or C-CN; R b It is CF3 or CF2H. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0024] In some cases, q is 0. In some cases, q is 1. In some cases, q is 2. In some cases, r is 0. In some cases, r is 1. In some cases, both q and r are 0. In some cases, q is 0 and r is 1. In some cases, q is 1 and r is 0. In some cases, q is 1 and r is 1. In some cases, q is 2 and r is 0. In some cases, q is 2 and r is 1. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, the compound of formula (II) is of formula (IIA): [ka] Equation (IIB) [ka] , formula (IIC) [ka] It has the structure of . In some cases, the compound is the compound of formula (IIA) or a pharmaceutically acceptable salt thereof. In some cases, the compound is W 1 However, CH, C-Haro, C-CN, CC 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy; W 2X is N and X is N or CR 5a The compound is of formula (IIA) or a pharmaceutically acceptable salt thereof. In some cases, the compound is of formula (IIB) or a pharmaceutically acceptable salt thereof. In some cases, the compound is of formula (IIC) or a pharmaceutically acceptable salt thereof.

[0025] In some cases, o is 0. In some cases, o is 1. In some cases, o is 2. In some cases, o is 3. In some cases, o is 4. In some cases, at least one R 6 is a halo or CN. In some cases, there is at least one R 6 is Br, Cl, F, or CN. In some cases, at least one R 6 is F. In some cases, o is 1 or 2, and each R 6 F is independent of F. In some cases, at least one R 6 C 1~3 Alkyl or C 1~3 It is a haloalkyl. In some cases, at least one R 6 is CH3, CH2F, CHF2, or CF3. In some cases, o is 1 or 2, and each R 6 These are independently CH3. In some cases, at least one R 6 C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3 Alkylene-C 1~3 Alkoxy, or C 1~4 Alkylene-N(R) N1 )2, and each R N1 These are independently H or CH3. In some cases, each R N1 H is independent of R. In some cases, at least one R is 6 is OH, CH2OH, CH2CH2OH, OCH3, OCD3, CH2OCH3, or CH2CH2OCH3. In some cases, at least one R 6is CH2N(CH3)2, CH2NH(CH3), or CH2NH2. In some cases, at least one R 6 is OH, CH2OH, OCH3, OCD3, CH2OCH3, or CH2N(CH3)2. In some cases, o is 1 and R 6 is OH, CH2OH, OCH3, or CH2OCH3. In some cases, at least one R 6 is oxo or =CH2. In some cases, at least one R 6 C 3~7 Cycloalkyl, C 4~7 A cycloalkenyl, a heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 6 is cyclopropyl, cyclobutyl, oxetanyl, or tetrahydrofuranyl; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 6 It is cyclopropyl. In some cases, at least one R 6 Spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 6 Spiro-C 3~7A spiro-heterocycloalkyl having a cycloalkyl group or 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 6 is spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranil, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 6 is a spirocyclopropyl that is unsubstituted or substituted with one or more substituents. In some cases, at least one R 6 It is spiro-cyclopropyl. In some cases, two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming cycloalkenyls, condensed heterocycloalkyls having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or condensed heterocycloalkenyls having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, condensed-C 3~7 The cycloalkyl groups are condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, two vicinal R groups are present. 6 These, together with the atoms to which they are bonded, form condensed-cyclopropyl, condensed-cyclobutyl, condensed-cyclopentyl, condensed-oxetanyl, or condensed-tetrahydrofuranyl, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, two vicinal R 6These, together with the atoms to which they are bonded, form condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, condensed-heterocycloalkenyl is unsubstituted. In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, condensed-heterocycloalkenyl is substituted with one or more substituents. In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, or condensed-heterocycloalkenyl is substituted with 1 to 4 substituents (e.g., 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, 3 substituents, or 4 substituents). In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, or condensed-heterocycloalkenyl is substituted with 1 or 2 substituents.In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, condensed-heterocycloalkenyl are substituted with one substituent. In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, condensed-heterocycloalkenyl are substituted with two substituents. In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, condensed-heterocycloalkenyl are substituted with three substituents. In some cases, any of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spiro-cycloalkyl, spiro-cycloalkenyl, spiro-heterocycloalkyl, spiro-heterocycloalkenyl, condensed-cycloalkyl, condensed-cycloalkenyl, condensed-heterocycloalkyl, condensed-heterocycloalkenyl are substituted with four substituents. In some cases, each substituent is independently halo, C. 1~3 Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is an alkylene CN. In some cases, each substituent is independently a halo, OH, C 1~3It is an alkoxy or CN. In some cases, each substituent is independently F, Cl, OH, OCH3, OCH2CH3, or CN. In some cases, two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 It forms a thioether crosslink. In some cases, two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridged, or C 1~3 Forms an ether bridge. In some cases, two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking or aC 2~3 It forms an alkenylene bridge. In some cases, two non-adjacent R 6 They combine together, C 1~3 Ether crosslinking or aC 1~3 It forms a thioether crosslink. In some cases, two non-adjacent R 6 They bond together, forming a C1 alkylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They bond together, forming a C2 alkylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They bond together, forming a C3 alkylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They bond together, forming a C2 alkenylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They bond together, forming a C3 alkenylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They combine together, C 1~3 Ether crosslinking (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They combine together, C 1~3 Thioether crosslinking (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They combine to form -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2-CH=CH-, or -CH2OCH2-. In some cases, at least one R 6 is Br, Cl, F, CN, CH3, CH2F, CHF2, CF3, OH, CH2OH, OCH3, OCD3, CH2OCH3, CH2N(CH3)2, oxo, =CH2, or cyclopropyl, or two vicinal R 6 These, together with the atoms to which they are bonded, form condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl, or two adjacent R 6 They are bonded together to form -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2-CH=CH- or -CH2OCH2-; where each of the above cycloalkyl groups is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being F, Cl, OH, OCH3, OCH2CH3, or CN. In some cases o is 0; or o is 1, R 6 is H, CH3, or cyclopropyl. In some cases, o is 0; or o is 1, R6 It is CH3. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0026] In some cases, Y' is C 3~7 Cycloalkyl or C 4~7It is a cycloalkenyl. In some cases, Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl. In some cases, Y' is cyclopropyl, cyclobutyl, cyclopentyl, or cyclopentenyl. In some cases, Y' is cyclopropyl or cyclobutyl. In some cases, Y' is a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. In some cases, Y' is azilidinyl, oxylanil, thiranil, azetidinyl, oxetanil, thietanil, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydrothiophenyl, dioxolanil, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranil, dioxanil, tetrahydrothiopyranil, dithianil, morpholinil, or thiomorpholinil. In some cases, Y' is oxetanil, thietanil, tetrahydrofuranil, dioxolanil, oxazolidinyl, tetrahydropyranil, tetrahydrothiopyranil, or morpholinil. In some cases, Y' is oxetanyl, pyrrolidinyl, tetrahydrofuranyl, dioxolanyl, oxazolidinyl, isoxazolidinyl, or tetrahydropyranyl. In some cases, Y' is tetrahydrofuranyl, tetrahydropyranyl, or morpholinyl. In some cases, Y' is tetrahydrofuranyl or tetrahydropyranyl. In some cases, Y' is a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. In some cases, Y' is dihydropyrrolyl, dihydrofuranyl, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridinyl, dihydropyranyl, or dihydrochipyranyl. In some cases, Y' is dihydropyrrolyl, dihydrofuranyl, or dihydropyranyl. In some cases, Y' is dihydrofuranyl or dihydropyranyl.In some cases, Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azilidinyl, oxylanil, thyranil, azetidinyl, oxetanil, thietanil, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydrothiophenyl, dioxolanil, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranil, dioxanil, tetrahydrothiopyranil, dithianil, morpholinil, thiomorpholinil, dihydropyrrolyl, dihydrofuranil, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridinyl, dihydropyranil, or dihydrochipyranil. In some cases, Y' is oxetanyl, thietanyl, tetrahydrofuranil, dioxolanil, oxazolidinil, tetrahydropyranil, tetrahydrothiopyranil, morpholinil, dihydrofuranil, or dihydropyranil. In some cases, Y' is tetrahydrofuranil, tetrahydropyranil, morpholinil, dihydrofuranil, or dihydropyranil. In some cases, Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, oxetanyl, pyrrolidinil, tetrahydrofuranil, dioxolanil, oxazolidinil, isoxazolidinil, tetrahydropyranil, dihydropyrrolyl, dihydrofuranil, or dihydropyranil. In some cases, p is 0. In some cases, p is 1. In some cases, p is 2. In some cases, p is 3. In some cases, p is 4. In some cases, p is 5. In some cases, at least one R. 7 is F, Cl, Br, CN, or CH2CN. In some cases, at least one R 7 is F, Cl, or Br. In some cases, at least one R 7 is CN or CH2CN. In some cases, at least one R 7 is F or CH2CN. In some cases, at least one R 7 C1~3 Alkyl, C 1~3 Haloalkyl, or C 2~3 It is an alkenyl. In some cases, at least one R 7 is CH3, CH2CH3, CH2F, CHF2, or CF3. In some cases, at least one R 7 is CH3, CH2F, or CHF2. In some cases, at least one R 7 C 0~3 Alkylene OH or C 0~3 Alkylene-C 1~3 It is an alkoxy. In some cases, at least one R 7 is OH, OCH3, OCH2CH3, CH2OH, CH2OCH3, or CH2CH2OCH3. In some cases, at least one R 7 is OH or CH2OCH3. In some cases, at least one R 7 is C(=O)OC 1~3 It is alkyl. In some cases, at least one R 7 is C(=O)OCH3. In some cases, there is at least one R 7 is oxo or =CH2. In some cases, at least one R 7 C 0~4 Alkylene-C 3~7 Cycloalkyl; C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 Aryl; or C having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 They are alkylene heteroaryl compounds; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 7 C 0~4 Alkylene-cyclopropyl, C 0~4 Alkylene-cyclobutyl, C 0~4 Alkylene-cyclopentyl, C 0~4Alkylene-oxetanyl, C 0~4 Alkylene-pyrrolidinil, C 0~4 Alkylene-phenyl, or C 0~4 Alkylene-oxadiazolyl; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 7 It is cyclopropyl. In some cases, at least one R 7 Spiro-C 3~7 A spiro-heterocycloalkyl ring having a cycloalkyl or 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 7 is spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, spiro-tetrahydrofuranil, or spiro-tetrahydropyranil, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, at least one R 7 The compounds are spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, spiro-tetrahydrofuranil, or spiro-tetrahydropyranil, where each of the above is unsubstituted or substituted with one or more substituents. In some cases, two vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Forms a cycloalkyl or condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, two vicinal R 7 These, along with the atoms to which they are bonded, form condensed-cyclopropyl, condensed-cyclobutyl, condensed-oxetanyl, or condensed-tetrahydrofuranyl. In some cases, two vicinal R 7 These, along with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl. In some cases, two vicinal R7 These, along with the atoms to which they are bonded, form a condensed tetrahydrofuranyl. In some cases, two vicinal R atoms 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 6~10 Forms a condensed heteroaryl having an aryl or 5-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, two vicinal R 7 These, together with the atoms to which they are bonded, form condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, condensed-pyridyl, condensed-pyridazinyl, condensed-pyridazinyl, or condensed-pyrimidinyl; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, two vicinal R 7 These, together with the atoms to which they are bonded, form condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, condensed-pyridyl, condensed-pyridazinyl, or condensed-pyrazinyl; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, two vicinal R 7These, together with the atoms to which they are bonded, form condensed-pyrazolyl, condensed-pyridyl, condensed-pyridazinyl, or condensed-pyrimidinyl; where each of the above is unsubstituted or substituted with one or more substituents. In some cases, each of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed-aryl, and condensed-heteroaryl is unsubstituted or substituted with 1 to 4 substituents. In some cases, each of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed-aryl, and condensed-heteroaryl is unsubstituted. In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed-aryl, and condensed-heteroaryl are substituted with 1 to 4 substituents (e.g., 1 to 4 substituents, 1 to 3 substituents, 1 to 2 substituents, 1 substituent, 2 substituents, 3 substituents, or 4 substituents). In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed -aryl and condensed-heteroaryl are substituted with one or two substituents. In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed-aryl, and condensed-heteroaryl are substituted with one substituent. In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed-aryl, and condensed-heteroaryl are substituted with two substituents. In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed-aryl, and condensed-heteroaryl are substituted with three substituents. In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, heteroaryl, spiro-cycloalkyl, spiro-heterocycloalkyl, condensed-cycloalkyl, condensed-heterocycloalkyl, condensed-aryl, and condensed-heteroaryl are substituted with four substituents. In some cases, each of the above substituents is independently halo, CN, oxo, or C 1~3 It is alkyl. In some cases, each substituent is independently F, Cl, Br, CN, oxo, or CH3. In some cases, each R 7 Independently, these are F, Cl, Br, CN, CH2CN, CH3, CH2CH3, CH2F, CHF2, CF3, OH, OCH3, OCH2CH3, CH2OH, CH2OCH3, CH2CH2OCH3, C(=O)OCH3, oxo, =CH2, cyclopropyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, spiro-tetrahydrofuranyl, spiro-tetrahydropyranyl; or two R 7These, together with the atoms to which they are bonded, form condensed-cyclopropyl, condensed-cyclobutyl, condensed-oxetanyl, condensed-tetrahydrofuranyl, condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, condensed-pyridyl, condensed-pyridazinyl, condensed-pyridazinyl, or condensed-pyrimidinyl; where each of pyrazolyl, pyridyl, pyridazinyl, and pyrimidinyl is either unsubstituted or substituted with CH3. In some cases, each substituent is independently F, Cl, Br, CN, oxo, or CH3. In some cases, each R 7 These are independently F, Cl, Br, CN, CH2CN, CH3, CH2CH3, CH2F, CHF2, CF3, OH, OCH3, OCH2CH3, CH2OH, CH2OCH3, CH2CH2OCH3, C(=O)OCH3, oxo, =CH2, cyclopropyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranyl; or two R 7 These, together with the atoms to which they are bonded, form condensed-cyclopropyl, condensed-cyclobutyl, condensed-oxetanyl, condensed-tetrahydrofuranyl, condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, condensed-pyridyl, condensed-pyridazinyl, or condensed-pyrazinyl; where pyrazolyl, pyridyl, and pyridazinyl are each substituted with CH3. In some cases, Y' is F, CH2CN, CH3, CH2F, CHF2, OH, CH2OCH3, oxo, [ka] ; or it is substituted with any combination of the above. In some cases, Y' is F, CH2CN, CH3, CH2F, CHF2, OH, CH2OCH3, oxo, [ka] ; or replaced by any combination of the above. In some cases, [ka] teeth, [ka] [ka] [ka] [ka] In some cases, [ka] teeth, [ka] [ka] [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] In some cases, [ka] teeth [ka] That is the case.

[0027] In some cases, [ka] teeth [ka] and; [ka] teeth [ka] and; [ka] teeth [ka] and; [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] [ka] [ka] [ka] That is the case. In some cases, [ka] teeth [ka] [ka] [ka] In some cases, [ka] teeth [ka] That is the case.

[0028] In some cases, equation (II) [ka] teeth [ka] That is the case. In some cases, [ka] Its stereochemical configuration is as follows: [ka] This indicates that, [ka] teeth [ka] In some cases, [ka] Its stereochemical configuration is as follows: [ka] This shows that in some cases, R 6 It is CH3.

[0029] It is understood that the selection of each variable element value leads to the formation of stable or chemically feasible compounds.

[0030] Compound of formula (I) Compound of formula (I): [ka] and pharmaceutically acceptable salts thereof are further provided (in the formula, m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; A stands for N, CH, C-Hello, C-CN, CC. 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy; W stands for CH, C-Hallo, C-CN, CC 1~3 Alkyl, CC 1~3Haloalkyl, C-C 0~3 Alkylene OH or C-C 0~3 Alkylene-C 1~4 Is alkoxy; X is N or C-R 5a And: Y’ is cycloalkyl having 3 to 7 total ring atoms, cycloalkenyl having 4 to 7 total ring atoms, heterocycloalkyl having 3 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S, or heterocycloalkenyl having 5 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S; R 1a 、R 1b 、And R 2 Each of is independently H, D, halo, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, C 0~2 Alkylene-N(R N1 )2, C having 3 to 6 total ring atoms and 1 or 2 heteroatoms selected from N, O, and S 1~2 Alkylene-heterocycloalkyl, or R 1b And R 2 Together with the carbon atom to which they are attached

Chemical formula

Chemical formula

[0031] In some cases, the compound of formula (I) is a free base. In some cases, the compound of formula (I) is a pharmaceutically acceptable salt.

[0032] In some cases, R 1a is H or D. In some cases, R 1a H is H. In some cases, R 1a It is D. In some cases, R 1b is H or D. In some cases, R 1b H is H. In some cases, R 1b It is D. In some cases, R 2 is H or D. In some cases, R 2 H is H. In some cases, R 2 It is D. In some cases, R 1a , R 1b , and R 2 At least one of them is H or D. In some cases, R 1a , R 1b , and R 2 At least one of them is H. In some cases, R 1a , R 1b , and R 2 At least one of them is D. In some cases, R 1a , R 1b , and R 2 At least two of them are independently H or D. In some cases, R 1a , R 1b , and R 2 At least two of them are H. In some cases, R 1a , R 1b , and R 2 At least two of them are D. In some cases, R 1a , R 1b , and R 2 Each of them is independently either H or D. In some cases, R 1a , R 1b , and R 2Each of them is independently H. In some cases, R 1a , R 1b , and R 2 Each of them is independently D. In some cases, R 1a , R 1b , and R 2 At least one of them is a halo (e.g., Br, Cl, or F). In some cases, R 1a , R 1b and R 2 One of them is a halo. In some cases, R 1a is a halo, R 1b and R 2 Each of them is H. In some cases, R 1a , R 1b and R 2 At least one of them is Br, Cl, or F. In some cases, R 1a , R 1b and R 2 One of them is Br, Cl, or F. In some cases, R 1a is Br, Cl, or F, and R 1b and R 2 Each of them is H. In some cases, R 1a , R 1b and R 2 At least one of them is Br or Cl. In some cases, R 1a , R 1b and R 2 One of them is Br or Cl. In some cases, R 1a is Br or Cl, and R 1b and R 2 Each of them is H. In some cases, R 1a , R 1b and R 2 At least one of them is C 1~4 Alkyl or C 1~4 It is a haloalkyl. In some cases, R 1a , R 1b and R 2 One of them is C 1~4 Alkyl or C 1~4It is a haloalkyl. In some cases, R 1a , R 1b , and R 2 At least one of them is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 One of these is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 At least one of them is CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 One of them is CH3, CH2F, CHF2, or CF3. In some cases, R 1a , R 1b , and R 2 At least one of them is C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, or C 0~2 Alkylene-N(R) N1 )2, and each R N1 H or C 1~4 It is alkyl. In some cases, each R N1 These are independently H or CH3. In some cases, each R N1 H is independent of R. In some cases, R 1a , R 1b , and R 2 At least one of them is CH2OH, OCH3, CH2OCH3, OCF3, CH2OCF3, CN, CH2CN, NH2, N(CH3)2, CH2NH2, or CH2N(CH3)2. In some cases, R 1a , R 1b , and R2 One of these is CH2OH, OCH3, CH2OCH3, OCF3, CH2OCF3, CN, CH2CN, NH2, N(CH3)2, CH2NH2, or CH2N(CH3)2. In some cases, R 1a , R 1b and R 2 At least one of them is C 1~2 The heterocycloalkyl group is an alkylene-heterocycloalkyl group, where the heterocycloalkyl group contains 3 to 6 total ring atoms and 1 or 2 heteroatoms selected from N, O, and S. In some cases, the heterocycloalkyl group is azilidinyl, oxylanil, azetidinyl, oxetanil, pyrrolidinyl, tetrahydrofuranil, imidazolidinyl, pyrazolidinyl, oxathiolidinyl, isoxusthiodinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, diazinyl, or morpholinyl. In some cases, the heterocycloalkyl group is azilidinyl, azetidinyl, pyrrolidinyl, piperidinyl, or morpholinyl. In some cases, R 1a , R 1b and R 2 At least one of these is aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl. In some cases, R 1a , R 1b and R 2 One of these is aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl. In some cases, R 1b and R 2 Along with the carbon atoms to which they are bonded, [ka] It forms R 1a H is H. In some cases, R 1b and R 2 Along with the carbon atoms to which they are bonded, [ka] It forms. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0033] In some cases, m is 0, [ka] teeth [ka] In some cases, m is 1. In some cases, m is 2. In some cases, m is 3. In some cases, m is 4. In some cases, [ka] It is deuterated. In some cases, [ka] It is completely deuterated. In some cases, [ka] teeth [ka] In some cases, at least one R 3 C 1~3 Alkyl or C 1~3 It is a haloalkyl. In some cases, at least one R 3 is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, at least one R 3 is CH3, CH2CH3, CF3, CHF2, or CH2F. In some cases, m is 1 or 2, and each R 3 It is CH3. In some cases m is 1 and R 3 is CF3, CHF2, or CH2F. In some cases, at least one R 3 teeth, [ka] And R A1 and R A2 Each of these is independently H, C 1~3 Alkyl, C 1~3 It is a haloalkyl or a cycloalkyl having 3 to 5 total ring atoms. In some cases, m is 1 and R 3 teeth, [ka] In some cases, R A1 and R A2 Each of these is independently H, CH3, CH2F, CHF2, CF3, CH2CH3, CH2CH2CH3, CH(CH3)2, cyclopropyl, or cyclobutyl. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, at least one R 3 teeth [ka] In some cases, at least one R 3 teeth [ka] In some cases, at least one R 3 is C 0~3 It is alkylene CN. In some cases, at least one R 3 is CN, CH2CN, or CH2CH2CN. In some cases, at least one R 3 is CN or CH2CN. In some cases m is 1 and R 3 is CN or CH2CN. In some cases, at least one R 3 C 0~3 Alkylene OH or C 0~3 Alkylene-C 1~3 It is an alkoxy. In some cases, at least one R 3 is OH, CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3. In some cases, m is 1 and R 3These are OH, CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3. In some cases, there are two geminal R 3 It forms an oxo group (=O). In some cases, two geminal R 3 These, together with the atoms to which they are bonded, form a spiro-cycloalkyl ring having 3 to 7 total ring atoms or a spiro-heterocycloalkyl ring having 3 to 7 total ring atoms and 1 or 2 heteroatoms selected from N, O, and S. In some cases, the spiro-cycloalkyl ring is spiro-cyclopropyl, spiro-cyclobutyl, or spiro-cyclopentyl. In some cases, the spiro-heterocycloalkyl ring is spiro-azetidinyl, spiro-oxetanyl, spiro-pyrrolidinyl, spiro-imidazolidinyl, spiro-pyrazolidinyl, or spiro-tetrahydrofuranil. In some cases, two geminal R 3 These, together with the atoms to which they are bonded, form spiro-cyclopropyl, spiro-cyclobutyl, spiro-cyclopentyl, spiro-azetidinyl, spiro-oxetanyl, spiro-pyrrolidinyl, spiro-imidazolidinyl, spiro-pyrazolidinyl, or spiro-tetrahydrofuranil. In some cases, two adjacent R 3 These, along with the atoms to which they are bonded, form a condensed cycloalkyl ring having 3 to 7 total ring atoms. In some cases, two adjacent R atoms 3 These, along with the atoms to which they are bonded, form a condensed cyclopropyl ring, a condensed cyclobutyl ring, a condensed cyclopentyl ring, or a condensed cyclohexyl ring. In some cases, two adjacent R 3 These, together with the atoms to which they are bonded, form a condensed-cyclopropyl ring or a condensed-cyclobutyl ring. In some cases, each R 3 These are independently CH3, CH2CH3, CF3, CHF2, CH2F, [ka] , CN, CH2CN, OH, CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3; two geminal R 3 It forms an oxo group (=O); two geminal R 3 They form a spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranyl group with the atom to which they are bonded; or two adjacent R 3 These, along with the atoms to which they are bonded, form a condensed cyclopropyl ring or a condensed cyclobutyl ring. In some cases, m is 1, and R 3 These are CH3, CF3, CHF2, CH2F, CN, CH2CN, CH2OH, CH2OCH3, or spiro-oxetanyl. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0034] In some cases, A is N. In some cases, A is CH, C-HALO, C-CN, CC 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4It is an alkoxy. In some cases, A is CH. In some cases, A is C-halo or C-CN. In some cases, A is CF or C-Cl. In some cases, A is CF. In some cases, A is C-CN. In some cases, A is CC. 1~3 Alkyl or CC 1~3 It is a haloalkyl group. In some cases, A is C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, or C-CH2F. In some cases, A is C-CH3, C-CH2F, C-CHF2, or C-CF3. In some cases, A is CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy. In some cases, A is C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, A is C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, A is N, CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, C-CH2F, C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, A is N, CH, CF, C-Cl, C-CN, C-CH3, C-CF3, C-CHF2, C-CH2F, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, n is 0. In some cases, n is 1. In some cases, n is 2. In some cases, there is at least one R. 4 C 1~3 Alkyl or C 1~3 It is a haloalkyl. In some cases, at least one R 4 These are CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, one R 4is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, n is 2, and each R 4 These are independently CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, n is 1, and R 4 is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, or CH2F. In some cases, n is 1, and R 4 It is CH3. In some cases, at least one R 4 is C 0~3 It is alkylene CN. In some cases, at least one R 4 is CN or CH2CN. In some cases n is 1 and R 4 is CN or CH2CN. In some cases, at least one R 4 C 1~3 Alkylene OH or C 1~3 Alkylene-C 1~3 It is an alkoxy. In some cases, at least one R 4 is CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3. In some cases, n is 1, and R 4 The R is CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3. In some cases, there are two geminal Rs. 4 It forms an oxo group (=O). In some cases, two geminal R 4 These, together with the atoms to which they are bonded, form a spiro-cycloalkyl ring having a total of 3 to 7 ring atoms. In some cases, the spiro-cycloalkyl ring is spiro-cyclopropyl, spiro-cyclobutyl, or spiro-cyclopentyl. In some cases, the spiro-cycloalkyl ring is spiro-cyclopropyl or spiro-cyclobutyl. In some cases, two geminal R 4These, together with the atoms to which they are bonded, form a spiro-heterocycloalkyl ring having 4 to 7 total ring atoms and 1 or 2 heteroatoms selected from N, O, and S. In some cases, the spiro-heterocycloalkyl ring is spiro-oxetanyl or spiro-tetrahydrofuranyl. In some cases, the spiro-heterocycloalkyl ring is spiro-oxetanyl. In some cases, two geminal R 4 These, together with the atoms to which they are bonded, form spiro-cyclopropyl, spiro-cyclobutyl, or spiro-oxetanyl. In some cases, each R 4 These are independently CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, CH2F, CN, CH2CN, CH2OH, CH2CH2OH, OCH3, CH2OCH3, CH2CH2OCH3; or two geminal R 4 These, together with the atoms to which they are bonded, form an oxo group, spiro-cyclopropyl, spiro-cyclobutyl, or spiro-oxetanyl. In some cases, each R 4 These are independently CH3, CH2CH3, CH2CH2CH3, CH2F, CN, CH2CN, CH2OH, CH2CH2OH, CH2OCH3, or two geminal R 4 These, along with the atoms to which they are bonded, form a spirocyclopropyl group. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0035] In some cases, W is CH. In some cases, W is a C-halo (e.g., CF, C-Cl, or C-Br) or C-CN. In some cases, W is CF, C-Cl, or C-CN. In some cases, W is CC 1~3 Alkyl or CC 1~3It is a haloalkyl group. In some cases, W is C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, or C-CH2F. In some cases, W is C-CH3 or C-CH2CH3. In some cases, W is CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 It is an alkoxy. In some cases, W is C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, W is C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, W is CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2CH2CH3, C-CH(CH3)2, C-CF3, C-CHF2, C-CH2F, C-OH, C-CH2OH, C-CH2CH2OH, C-OCH3, C-CH2OCH3, or C-CH2CH2OCH3. In some cases, W is CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3. In some cases, X is N. In some cases, W is CH and X is N. In some cases, X is CR. 5a In some cases, W is CH and X is CR. 5a In some cases, R 5a H is H. In some cases, R 5a is CN. In some cases, R 5a is Br, Cl, or F. In some cases, R 5a C 1~3 Alkyl or C 1~3 It is a haloalkyl. In some cases, R 5a is CH3, CH2CH3, CF3, CHF2, or CH2F. In some cases, R 5a It is CH3. In some cases, R 5a C 2~6 Alkenyl or C 2~6 It is alkinyl. In some cases, R5a C 2~3 Alkenyl or C 2~3 It is alkinyl. In some cases, R 5a teeth [ka] In some cases, R 5a teeth [ka] In some cases, R 5a C 0~3 Alkylene OH or C 0~3 Alkylene-C 1~3 It is an alkoxy. In some cases, R 5a is OH, CH2OH, OCH3, or CH2OCH3. In some cases, R 5a It is a cycloalkyl having 3 to 5 total ring atoms. In some cases, R 5a teeth, [ka] In some cases, R 5a are H, CN, Br, Cl, F, CH3, CH2CH3, CF3, CHF2, CH2F, [ka] OH, CH2OH, OCH3, CH2OCH3, or [ka] In some cases, R 5a This is H, CN, or CH3.

[0036] In some cases, R 5b is C 1~3 It is a haloalkyl. In some cases, R 5b These are CF3, CF2H, CFH2, or CF2CH3. In some cases, R 5b It is CF3. In some cases, R5b is CF2H. In some cases, R 5b It is CHF2. In some cases, R 5b is a halo. In some cases, R 5b is Br, Cl, or F. In some cases, R 5b C 1~3 Alkoxy or C 1~3 It is a thioalkoxy. In some cases, R 5b is OCH3, OCH2CH3, SCH3, or SCH2CH3. In some cases, R 5b It is OCH3 or SCH3. In some cases, R 5b C 1~6 Alkyl (e.g., CH3, CH2CH3, CH2CH2CH3, CH(CH3)2), C 2~4 Alkenyls (e.g., CH=CH2, CH=CHCH3), or C 2~4 These are alkynyl groups (e.g., CCH, CCH3), each of which is either unsubstituted or substituted with one or more substituents. In some cases, C 1~6 Alkyl, C 2~4 Alkenyl, or C 2~4 Alkinyl is unsubstituted. In some cases, R 5b is CH3, CH2CH3, CH2CH2CH3, or CH(CH3)2. In some cases, C 1~6 Alkyl, C 2~4 Alkenyl, or C 2~4 Alkynnyl is substituted with one, two, or three substituents. In some cases, each of the one, two, or three substituents is independently C 1~3 Haloalkyl, C 0~6 Alkylene (OH), C 0~6 Alkylene-C 1~3The substituents are alkoxy, cycloalkyl with 3 to 7 total ring atoms, cycloalkenyl with 5 to 7 total ring atoms, heterocycloalkyl with 3 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S, heterocycloalkenyl with 3 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S, or phenyl. In some cases, each of the 1, 2, or 3 substituents is independently CH3, CF3, CF2H, CFH2, OH, OCH3, OCF3, CH2OH, CH2OCH3, cyclopropyl, cyclobutyl, or phenyl. In some cases, R 5b This refers to a cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) having 3 to 7 total ring atoms, a cycloalkenyl (e.g., cyclopentenyl or cyclohexenyl) having 5 to 7 total ring atoms, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S, or a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S, where each of the above is a halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~6 Alkylene (OH), or C 0~6 Alkylene-C 1~3The heterocycloalkyl group is optionally substituted with one, two, or three substituents independently selected from the alkoxy. In some cases, the heterocycloalkyl group is azilidinyl, oxyranil, thyranil, azetidinil, oxetanil, thietanil, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydrothiophenyl, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranil, dioxanil, tetrahydrotipiranil, dithianil, morpholinil, or thiomorpholinil. In some cases, the heterocycloalkenyl group is dihydropyrrolyl, dihydrofuranil, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridinyl, dihydropyranil, or dihydrotipiranil. In some cases, R 5b These are cyclopropyl, cyclobutyl, cyclopentenyl, oxetanyl, or tetrahydrofuranil. In some cases, R 5b are CF3, CF2H, CFH2, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, [ka] In some cases, R 5a and R 5b These, together with the atoms to which they are bonded, form a condensed cycloalkyl ring having a total of 3 to 7 ring atoms. In some cases, R 5a and R 5b These, along with the atoms to which they are bonded, form condensed cyclopropyl, condensed cyclobutyl, or condensed cyclopentyl. In some cases, W is CH; X is N; R 5b It is CF3 or CF2H. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, W is CH and X is CR. 5a And; R 5a is CN, Br, Cl, F, or CH3; R 5b These are CF3, CF2H, or CFH2. In some cases, [ka] teeth [ka] [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0037] In some cases, o is 0. In some cases, o is 1. In some cases, o is 2. In some cases, o is 3. In some cases, o is 4. In some cases, there is at least one R 6 is a halo or CN. In some cases, at least one R 6 is Br, Cl, F, or CN. In some cases, at least one R 6is F. In some cases, o is 1 or 2, and each R 6 F is independent of F. In some cases, at least one R 6 C 1~3 Alkyl or C 1~3 It is a haloalkyl. In some cases, at least one R 6 is CH3, CH2F, CHF2, or CF3. In some cases, o is 1 or 2, and each R 6 These are independently CH3. In some cases, at least one R 6 C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3 Alkylene-C 1~3 Alkoxy, or C 1~4 Alkylene-N(R) N1 )2, and each R N1 These are independently H or CH3. In some cases, each R N1 H is independent of R. In some cases, at least one R is 6 is OH, CH2OH, CH2CH2OH, OCH3, OCD3, CH2OCH3, or CH2CH2OCH3. In some cases, at least one R 6 is CH2N(CH3)2, CH2NH(CH3), or CH2NH2. In some cases, at least one R 6 is OH, CH2OH, OCH3, OCD3, CH2OCH3, or CH2N(CH3)2. In some cases, o is 1 and R 6 These are OH, CH2OH, OCH3, or CH2OCH3. In some cases, there are two geminal R 6 It forms an oxo group (=O). In some cases, two geminal R 6 These, together with the atoms to which they are bonded, form a spiro-cycloalkyl ring having 3 to 7 total ring atoms or a spiro-heterocycloalkyl ring having 4 to 7 total ring atoms and 1 or 2 heteroatoms selected from N, O, and S. In some cases, two geminal R 6These, together with the atoms to which they are bonded, form spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranil. In some cases, two geminal R 6 These, along with the atoms to which they are bonded, form a spirocyclopropyl group. In some cases, two adjacent R atoms 6 These, along with the atoms to which they are bonded, form a condensed cycloalkyl ring having 3 to 7 total ring atoms. In some cases, two adjacent R atoms 6 These, together with the atoms to which they are bonded, form a condensed-cyclopropyl ring, a condensed-cyclobutyl ring, or a condensed-cyclopentyl ring. In some cases, the spiro-cycloalkyl ring, spiro-heterocycloalkyl ring, and condensed-cycloalkyl ring are unsubstituted. In some cases, the spiro-cycloalkyl ring, spiro-heterocycloalkyl ring, and condensed-cycloalkyl ring are substituted with one or more substituents. In some cases, the spiro-cycloalkyl ring, spiro-heterocycloalkyl ring, and condensed-cycloalkyl ring are substituted with 1, 2, 3, or 4 substituents. In some cases, the spiro-cycloalkyl ring, spiro-heterocycloalkyl ring, and condensed-cycloalkyl ring are substituted with 1 or 2 substituents. In some cases, one or more substituents (e.g., 1, 2, or 3 substituents or 1 or 2 substituents) are independently halo, OH, and C. 1~3 It is an alkoxy (e.g., OCH3, OCH2CH3), or CN. In some cases, two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking or C 1~3 Forms an ether bridge. In some cases, two non-adjacent R 6 They bond together, forming a C1 alkylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They bond together, forming a C2 alkylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They bond together, forming a C3 alkylene bridge (for example, [ka] ) forms. In some cases, two non-adjacent R 6 They combine together, C 1~3 Ether crosslinking (for example, [ka] ) forms. In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0038] In some cases, Y' is a cycloalkyl having 3 to 7 total ring atoms or a cycloalkenyl having 4 to 7 total ring atoms. In some cases, Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl. In some cases, Y' is a heterocycloalkyl having 3 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S; or a heterocycloalkenyl having 5 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S. In some cases, Y' is azilidinyl, oxyranil, thyranil, azetidinyl, oxetanil, thietanil, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydrothiophenyl, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranil, dioxanil, tetrahydrotipiranil, dithianil, morpholinil, thiomorpholinil, dihydropyrrolyl, dihydrofuranil, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridinyl, dihydropyranil, or dihydrotipiranil. In some cases, Y' is azetidinil, oxetanil, thietanil, pyrrolidinil, imidazolidinil, tetrahydrofuranil, oxazolidinil, isoxazolidinil, tetrahydropyranil, dioxanil, morpholinil, dihydropyrrolyl, dihydrofuranil, dihydroisoxazolyl, or dihydropyranil. In some cases, Y' is oxetanil, pyrrolidinil, tetrahydrofuranil, dioxolanil, oxazolidinil, isoxazolidinil, tetrahydropyranil, or morpholinil. In some cases, Y' is pyrrolidinil, tetrahydrofuranil, tetrahydropyranil, morpholinil, dihydrofuranil, dihydroisoxazolyl, or dihydropyranil. In some cases, Y' is pyrrolidinil, tetrahydrofuranil, tetrahydropyranil, or dihydrofuranil. In some cases, Y' is pyrrolidinil. In some cases, Y' is tetrahydrofuranyl.In some cases, Y' is tetrahydropyranyl. In some cases, Y' is morpholinyl. In some cases, Y' is dihydrofuranyl. In some cases, Y' is dihydroisoxazolyl. In some cases, Y' is dihydropyranyl. In some cases, p is 0. In some cases, p is 1. In some cases, p is 2. In some cases, p is 3. In some cases, p is 4. In some cases, p is 5. In some cases, there is at least one R. 7 is F, Cl, Br, or CN. In some cases, at least one R 7 is F, Cl, Br, or CN. In some cases, at least one R 7 C 1~3 Alkyl, C 1~3 Haloalkyl, or C 2~3 It is an alkenyl. In some cases, at least one R 7 is CH3, CH2CH3, CH2CH2CH3, CH(CH3), CH2F, CHF2, or CF3. In some cases, at least one R 7 is CH3, CH2CH3, CH2F, CHF2, or CF3. In some cases, at least one R 7 It is CH3. In some cases, at least one R 7 is CF3, CHF2, or CH2F. In some cases, at least one R 7 C 0~3 Alkylene OH or C 0~3 Alkylene-C 1~3 It is an alkoxy. In some cases, at least one R 7 is OH, OCH3, OCH2CH3, CH2OH, CH2OCH3, or CH2CH2OCH3. In some cases, at least one R 7 is C(=O)OC 1~3 It is alkyl. In some cases, at least one R 7 is C(=O)OCH3. In some cases, there is at least one R 7C has 3 to 7 total ring atoms. 0~4 It is an alkylene-cycloalkyl group. In some cases, the cycloalkyl group is cyclopropyl, cyclobutyl, or cyclopentyl. In some cases, at least one R 7 is cyclopropyl, cyclobutyl, cyclopentyl, CH2-cyclopropyl, CH2-cyclobutyl, or CH2-cyclopentyl. In some cases, at least one R 7 This is a carbon atom having 3 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S. 0~4 It is an alkylene-heterocycloalkyl. In some cases, the heterocycloalkyl is azilidinyl, oxyranil, thyranil, azetidinyl, oxetanil, thietanil, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydrothiophenyl, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranil, dioxanil, tetrahydrochipyranil, dithianil, morpholinil, or thiomorpholinil. In some cases, the heterocycloalkyl is azetidinyl, oxetanil, pyrrolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydropyranil, or piperidinyl. In some cases, at least one R 7 These are oxetanil, pyrrolidinil, or CH2-pyrrolidinil. In some cases, at least one R 7 C has 6 to 10 total ring atoms. 0~4 It is an alkylene-aryl compound. In some cases, the aryl is a phenyl compound. In some cases, there is at least one R compound. 7 is phenyl or CH2-phenyl. In some cases, at least one R 7 This is a carbon atom having 5 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S. 0~4It is an alkylene heteroaryl. In some cases, the heteroaryl is pyrrolyl, furanil, thiophenyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, or triazinyl. In some cases, the heteroaryl is pyrrolyl, furanil, thiophenyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, or pyridyl. In some cases, the heteroaryl is thiophenyl. In some cases, the heteroaryl is pyrazolyl. In some cases, the heteroaryl is thiazolyl. In some cases, the heteroaryl is pyridyl. In some cases, at least one R 7 C 0~4 Alkylene-cyclopropyl, C 0~4 Alkylene-cyclobutyl, C 0~4 Alkylene-cyclopentyl, C 0~4 Alkylene-oxetanyl, C 0~4 Alkylene-pyrrolidinil, C 0~4 Alkylene-phenyl, or C 0~4 It is alkylene-oxadiazolyl. In some cases, it has two geminal R 7 This forms a CH2 or oxo group (=O). In some cases, two geminal R groups 7 These, together with the atoms to which they are bonded, form a spiro-cycloalkyl ring having 3 to 7 total ring atoms or a spiro-heterocycloalkyl ring having 4 to 7 total ring atoms and 1 or 2 heteroatoms selected from N, O, and S. In some cases, the spiro-cycloalkyl group is spiro-cyclopropyl, spiro-cyclobutyl, or spiro-cyclopentyl. In some cases, the spiro-heterocycloalkyl group is spiro-azetidinyl, spiro-oxetanyl, spiro-thietanyl, or spiro-tetrahydrofuranil. In some cases, two geminal R atoms are present. 7These, together with the atoms to which they are bonded, form spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranil. In some cases, two adjacent R 7 These, together with the atoms to which they are bonded, form a condensed cycloalkyl ring having 3 to 7 total ring atoms or a condensed heterocycloalkyl ring having 3 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S. In some cases, the condensed cycloalkyl ring is condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl. In some cases, two adjacent R 7 These, together with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl. In some cases, the condensed heterocycloalkyl ring is condensed-azetidinyl, condensed-oxetanyl, condensed-thietanyl, condensed-pyrrolidinyl, condensed-imidazolidinyl, condensed-pyrazolidinyl, condensed-tetrahydrofuranyl, or condensed-tetrahydrothiophenyl. In some cases, two adjacent R 7 These, along with the atoms to which they are bonded, form a condensed oxetanyl. In some cases, two adjacent R atoms 7 These, along with the atoms to which they are bonded, form a fused aryl ring with a total of six ring atoms. In some cases, two adjacent R atoms 7These, together with the atoms to which they are bonded, form a condensed heteroaryl ring having 5 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S. In some cases, the condensed heteroaryl is condensed-pyrrolyl, condensed-furanyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-imidazolyl, condensed-thiazolyl, condensed-isothiazolyl, condensed-oxazolyl, condensed-isoxazolyl, condensed-triazolyl, condensed-thiadiazolyl, condensed-oxadiazolyl, condensed-pyridyl, condensed-pyridazinyl, condensed-pyrimidinyl, condensed-pyrazinyl, or condensed-triazinyl. In some cases, the heteroaryl is condensed-pyrrolyl, condensed-furanyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-imidazolyl, condensed-thiazolyl, condensed-isothiazolyl, condensed-oxazolyl, condensed-isoxazolyl, or condensed-pyridyl. In some cases, the condensed-heteroaryl is condensed-thiazolyl, condensed-pyrazolyl, condensed-pyridyl, or condensed-pyridazinyl. In some cases, the condensed-heteroaryl is condensed-thiazolyl. In some cases, the condensed-heteroaryl is condensed-pyrazolyl. In some cases, the condensed-heteroaryl is condensed-pyridyl. In some cases, the condensed-heteroaryl is condensed-pyridazinyl. In some cases, two adjacent R 7 These, together with the atoms to which they are bonded, form condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, condensed-pyridyl, or condensed-pyridazinyl. In some cases, none of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings are substituted. In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings are substituted with one or more substituents. In some cases, any of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings are substituted with one, two, or three substituents. In some cases, each substituent is independently halo, CN, OH, C 1~3 Alkoxy, oxo, C 1~3 Alkyl, or C 1~3It is a haloalkyl. In some cases, each substituent is independently halo, CN, oxo, or C 1~3 It is an alkyl group, where each substituent is independently F, Cl, Br, CN, oxo, or CH3.

[0039] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] In some cases, [ka] teeth [ka] That is the case.

[0040] In some cases, equation (I) [ka] teeth [ka] and; [ka] teeth [ka] [ka] and; [ka] teeth [ka] and; [ka] teeth [ka] In some cases, equation (I) [ka] teeth [ka] In some cases, equation (I) [ka] teeth [ka] That is the case.

[0041] In some cases, the compound of formula (I) has the structure of formula (IA) or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) has the structure of formula (IB) or a pharmaceutically acceptable salt thereof. [ka]

[0042] In some cases, equation (I) [ka] teeth [ka] In some cases, [ka] It exhibits the following stereochemical configuration: [ka] In some cases, [ka] teeth [ka] In some cases, [ka] It exhibits the following stereochemical configuration: [ka] In some cases, R 6 It is CH3.

[0043] It is understood that the selection of each variable element value leads to the formation of stable or chemically feasible compounds.

[0044] Compounds of formulas (I) and (II) that are intended Specific compounds intended for formulas (I) and (II) include, but are not limited to, the compounds listed in the table below and their pharmaceutically acceptable salts.

[0045] In some cases, the compound of formula (I) or formula (II) is one of the compounds listed in Table A or a pharmaceutically acceptable salt thereof:

[0046] Table 1

[0047] Table 2

[0048] Table 3

[0049] Table 4

[0050] Table 5

[0051] Table 6

[0052] Table 7

[0053] Table 8

[0054] Table 9

[0055] Table 10

[0056] [Table 11]

[0057] [Table 12]

[0058] [Table 13]

[0059] [Table 14]

[0060] [Table 15]

[0061] [Table 16]

[0062] [Table 17]

[0063] In some cases, the compound of formula (I) or formula (II) is selected from the list of compounds in Table A.

[0064] In some cases, this disclosure is valid if Y' is C 3~7 Cycloalkyl or C 4~7 The present invention provides a cycloalkenyl compound of formula (I) or formula (II), or a pharmaceutically acceptable salt of either of the above. Examples of such compounds include: [ka] There are, but are not limited to, pharmaceutically acceptable salts thereof.

[0065] In some cases, the present disclosure provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, wherein Y' is oxetanyl or dioxanyl. Examples of such compounds include: [ka] There are, but are not limited to, pharmaceutically acceptable salts thereof.

[0066] In some cases, the present disclosure provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, where Y' is tetrahydrofuranyl and p is 0. Examples of such compounds include: [ka] Furthermore, there are, but are not limited to, any of the above-mentioned pharmaceutically acceptable salts.

[0067] In some cases, this disclosure is that Y' is tetrahydrofuranyl, and each p is CH2, oxo, halo, CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl, C 0~4 Alkylene-C 6~10 C having an aryl group, 5 to 7 total ring atoms, and 1, 2, or 3 heteroatoms selected from N, O, and S. 0~4 The present invention provides a compound of formula (I) or formula (II) that is alkylene-heteroaryl, or a pharmaceutically acceptable salt of either of the above. Examples of such compounds include: [ka] Furthermore, there are, but are not limited to, any of the above-mentioned pharmaceutically acceptable salts.

[0068] In some cases, this disclosure is that Y' is tetrahydrofuranyl and two vicinal R 7 However, along with the atoms to which they are bonded, condensed C atoms are optionally substituted. 3~7 Cycloalkyl or optionally substituted condensed-C 6~10 The present invention provides compounds of formula (I) or formula (II) that form an aryl group, or pharmaceutically acceptable salts of either of the above. In some cases, the cycloalkyl and aryl groups are unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 It is alkyl. Examples of such compounds include: [ka] There are, but are not limited to, pharmaceutically acceptable salts thereof.

[0069] In some cases, this disclosure is that Y' is tetrahydrofuranyl and two vicinal R 7 The present invention provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts of either of the above, which form optionally substituted condensed heteroaryls having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, together with the atoms to which they are bonded. In some cases, the heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 It is alkyl. Examples of such compounds include: [ka] [ka] There are, but are not limited to, pharmaceutically acceptable salts thereof.

[0070] In some cases, the present disclosure provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, where Y' is tetrahydropyranyl and p is 0. Examples of such compounds are: [ka] and its pharmaceutically acceptable salts.

[0071] In some cases, this disclosure is that Y' is tetrahydropyranyl and two vicinal R 7 The present invention provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, which, together with the atoms to which they are bonded, form a condensed thiazolyl ring, a condensed thiophenyl ring, or a condensed pyridyl ring. Examples of such compounds include: [ka] There are, but are not limited to, pharmaceutically acceptable salts thereof.

[0072] In some cases, this disclosure is that Y' is morpholinyl; p is 2 or 3; and 2 vicinal R 7 The present invention provides a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt of either of the above, which forms a condensed pyrazolyl with optionally substituted atoms, together with the atoms to which they are bonded. In some cases, the pyrazolyl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 It is alkyl. Examples of such compounds include: [ka] [ka] There are, but are not limited to, pharmaceutically acceptable salts thereof.

[0073] In some cases, this disclosure is that Y' is thiazolidinyl; p is 2, 3, or 4; and at least one R 7 The present invention provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, wherein the compound is an oxo. Examples of such compounds include: [ka] The above-mentioned pharmaceutically acceptable salts are, but are not limited to, those listed above.

[0074] In some cases, the present disclosure provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, wherein Y' is optionally substituted with a pyrrolidinyl (e.g., substituted with an oxo group to form a pyrrolidinone). Examples of such compounds include: [ka] The above-mentioned pharmaceutically acceptable salts are, but are not limited to, those listed above.

[0075] In some cases, the present disclosure provides compounds of formula (I) or formula (II) in which Y' is optionally substituted with dihyropyrrolyl, isoxazolyl, dihydrofuranyl, or dihydropyranyl, and pharmaceutically acceptable salts thereof. Examples of such compounds include: [ka] [ka] [ka] The above-mentioned pharmaceutically acceptable salts are, but are not limited to, those listed above.

[0076] In some cases, the compound of formula (I) or formula (II) is one of the compounds listed in Table B or a pharmaceutically acceptable salt thereof.

[0077] [Table 18]

[0078] [Table 19]

[0079] [Table 20]

[0080] In some cases, this disclosure provides compounds listed in Table C below. If the stereochemistry of a structure or part of a structure in Table C is not clearly indicated (e.g., by dashed or thick lines), the structure or part of a structure is understood to be either achiral or a possible stereoisomer of the structure or part of a structure. If the stereochemistry of a structure or part of a structure is clearly indicated in Table C, a single stereoisomer of the structure or part of a structure is shown, along with the understanding that the stereochemistry of the structure or part of a structure shown in Table C is arbitrarily assigned.

[0081] [Table 21]

[0082] [Table 22]

[0083] [Table 23]

[0084] [Table 24]

[0085] [Table 25]

[0086] Table 26

[0087] Table 27

[0088] Table 28

[0089] Table 29

[0090] Table 30

[0091] Table 31

[0092] Table 32

[0093] Table 33

[0094] Table 34

[0095] Table 35

[0096] [Table 36]

[0097] [Table 37]

[0098] [Table 38]

[0099] [Table 39]

[0100] [Table 40]

[0101] In some cases, the compound of formula (I) or formula (II) is selected from the list of compounds in Table C. In some cases, the compounds of formulas (I) and (II) are compounds selected from compounds 3-001 to 3-104 (as shown in Table C).

[0102] In some cases, this disclosure is valid if Y' is C 3~7 Cycloalkyl or C 4~7 The present invention provides a cycloalkenyl compound of formula (I) or formula (II), or a pharmaceutically acceptable salt of either of the above. In some cases, the compound of formula (I) or formula (II) is compound 3-022, 3-023, 3-036, 3-037, 3-038, 3-063, 3-073, 3-093, or 3-099, or a pharmaceutically acceptable salt of any of the above.

[0103] In some cases, the present disclosure provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, wherein Y' is oxetanyl or dioxanyl. In some cases, the compounds of formula (I) or (II) are compounds 3-019 or 3-024, or pharmaceutically acceptable salts thereof.

[0104] In some cases, the present disclosure provides a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt of either of the above, wherein Y' is tetrahydrofuranyl and p is 0. In some cases, the compound of formula (I) or (II) is compound 3-025, 3-026, 3-039, 3-062-1, 3-062-2, or 3-071, or a pharmaceutically acceptable salt of any of the above.

[0105] In some cases, this disclosure is that Y' is tetrahydrofuranyl, and each p is CH2, oxo, halo, CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl, C 0~4 Alkylene-C 6~10 C having an aryl group, 5 to 7 total ring atoms, and 1, 2, or 3 heteroatoms selected from N, O, and S. 0~4 The present invention provides a compound of formula (I) or formula (II) that is alkylene-heteroaryl, or a pharmaceutically acceptable salt of either of the above. In some cases, the compound of formula (I) or formula (II) is compound 3-029, 3-030, 3-031, 3-044, 3-045, 3-058, or 3-074, or a pharmaceutically acceptable salt of any of the above.

[0106] In some cases, this disclosure is that Y' is tetrahydrofuranyl and two vicinal R 7 However, along with the atoms to which they are bonded, condensed C atoms are optionally substituted. 3~7 Cycloalkyl or optionally substituted condensed-C 6~10 The present invention provides compounds of formula (I) or formula (II) that form an aryl group, or pharmaceutically acceptable salts of either of the above. In some cases, the cycloalkyl and aryl groups are unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 It is alkyl. In some cases, the compound of formula (I) or formula (II) is compound 3-015, 3-018, 3-027, 3-028, 3-040, 3-041, or 3-042, or a pharmaceutically acceptable salt of any of the above.

[0107] In some cases, this disclosure is that Y' is tetrahydrofuranyl and two vicinal R 7 The present invention provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts of either of the above, which form optionally substituted condensed heteroaryls having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, together with the atoms to which they are bonded. In some cases, the heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 It is alkyl. In some cases, the compound of formula (I) or formula (II) is compound 3-001, 3-043, 3-046, 3-047, 3-049, 3-079, 3-080, 3-086, 3-092, 3-095, 3-096, 3-102, 3-103, or 3-104, or a pharmaceutically acceptable salt of any of the above.

[0108] In some cases, the present disclosure provides a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof, wherein Y' is tetrahydropyranyl and p is 0. In some cases, the compound of formula (I) or formula (II) is compound 3-035 or a pharmaceutically acceptable salt thereof.

[0109] In some cases, this disclosure is that Y' is tetrahydropyranyl and two vicinal R 7 The present invention provides compounds of formula (I) or formula (II), or pharmaceutically acceptable salts thereof, which, together with the atoms to which they are bonded, form a condensed thiazolyl ring, a condensed thiophenyl ring, or a condensed pyridyl ring. In some cases, the compound of formula (I) or formula (II) is 3-002, 3-064, 3-069, 3-085, 3-091, 3-092, or 3-094, or any pharmaceutically acceptable salt thereof.

[0110] In some cases, this disclosure is that Y' is morpholinyl; p is 2 or 3; and 2 vicinal R 7 The present invention provides a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt of either of the above, which forms a condensed pyrazolyl with optionally substituted atoms, together with the atoms to which they are bonded. In some cases, the pyrazolyl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 It is alkyl. In some cases, the compound of formula (I) or formula (II) is compound 3-076, 3-077, 3-078, 3-081, 3-082, 3-083, 3-084, 3-087-1, 3-087-2, 3-088-1, 3-088-2, 3-089-1, 3-089-2, 3-090-1, 3-090-2, 3-097, 3-098, 3-100, or 3-101, or any pharmaceutically acceptable salt of any of the above.

[0111] In some cases, this disclosure is that Y' is thiazolidinyl; p is 2, 3, or 4; and at least one R 7The present invention provides a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt of either of the above, wherein the compound of formula (I) or formula (II) is compound 3-032, 3-033, or 3-034, or a pharmaceutically acceptable salt of either of the above.

[0112] In some cases, the present disclosure provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts of either of the above, wherein Y' is pyrrolidinyl. In some cases, the compounds of formula (I) or formula (II) are compounds 3-004, 3-013, 3-014, 3-016, 3-020, 3-048, or 3-075, or pharmaceutically acceptable salts of any of the above.

[0113] In some cases, the present disclosure provides compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof, wherein Y' is optionally substituted with dihydroxyrrolyl, isoxazolyl, dihydrofuranil, or dihydropyranil. In some cases, the compound of formula (I) or formula (II) is compound 3-003, 3-005, 3-006, 3-007, 3-008, 3-009, 3-010, 3-011, 3-012, 3-017, 3-021, 3-050, 3-051, 3-052, 3-053, 3-054-1, 3-054-2, 3-055, 3-057, 3-059, 3-060, 3-061, 3-065, 3-066, 3-067-1, 3-067-2, 3-068-1, 3-068-2, 3-070, or 3-072, or any pharmaceutically acceptable salt of any of the above.

[0114] In some cases, compounds of formula (I) or formula (II) are compounds 3-001, 3-002, 3-003, 3-004, 3-005, 3-008, 3-009, 3-010, 3-011, 3-014, 3-015, 3-016, 3-017, 3-046, 3-049, 3-050, 3-051, 3-052, 3-053, 3-054-1, 3-054-2, 3-057, 3-058, 3-059, 3-060, 3-061, 3-065, 3-066, Selected from the group consisting of 3-067-1, 3-067-2, 3-069, 3-074, 3-075, 3-076, 3-077, 3-078, 3-079, 3-080, 3-081, 3-082, 3-083, 3-084, 3-085, 3-087-1, 3-087-2, 3-088-1, 3-088-2, 3-089-1, 3-089-2, 3-090-1, 3-091-1, or 3-091-2, or any of the above pharmaceutically acceptable salts.

[0115] In some cases, compounds of formula (I) or formula (II) are compounds 3-001, 3-002, 3-004, 3-005, 3-008, 3-014, 3-046, 3-051, 3-052, 3-053, 3-054-1, 3-054-2, 3-057, 3-059, 3-060, 3-061, 3-074, 3-076, 3-077, Selected from the group consisting of 3-078, 3-079, 3-080, 3-081, 3-082, 3-083, 3-084, 3-085, 3-087-1, 3-087-2, 3-088-1, 3-088-2, 3-089-1, 3-089-2, 3-090-1, or 3-091-1, or any of the above pharmaceutically acceptable salts.

[0116] In some cases, the compound of formula (I) or formula (II) is selected from the group consisting of compounds 3-004, 3-005, 3-051, 3-052, 3-053, 3-054-1, 3-059, 3-061, 3-076, 3-077, 3-078, 3-079, 3-081, 3-082, 3-083, 3-084, 3-085, 3-087-1, 3-087-2, 3-088-1, 3-088-2, 3-089-1, 3-089-2, 3-090-1, or 3-091-1, or any pharmaceutically acceptable salt of any of the above.

[0117] In some cases, the compound of formula (I) or formula (II) is selected from the group consisting of compounds 3-076, 3-077, 3-078, 3-079, 3-081, 3-082, 3-083, 3-085, 3-087-1, 3-087-2, 3-088-2, 3-089-1, 3-089-2, or 3-091-1, or any pharmaceutically acceptable salt of any of the above.

[0118] In some cases, the compound of formula (I) or formula (II) is selected from the group consisting of compounds 3-092, 3-093, 3-094, 3-095, 3-096, 3-097, 3-098, 3-099, 3-100, 3-101, 3-102, 3-103, or 3-104, or any pharmaceutically acceptable salt of any of the above.

[0119] In some cases, the compound of formula (I) or formula (II) is selected from the list of compounds in Table D below. If the stereochemistry of a structure or part of a structure in Table D is not clearly indicated (e.g., by dashed or thick lines), the structure or part of a structure is understood to be either achiral or a possible stereoisomer of the structure or part of a structure. If the stereochemistry of a structure or part of a structure in Table D is clearly indicated, a single stereoisomer of the structure or part of a structure is shown, along with the understanding that the stereochemistry of the structure or part of a structure shown in Table D is arbitrarily assigned.

[0120] [Table 41]

[0121] [Table 42]

[0122] [Table 43]

[0123] In some cases, the compound of formula (I) or formula (II) is compound 3-001 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-002 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-052 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-076 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-077 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-078 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-079 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-085 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-089-1 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-090-1 or a pharmaceutically acceptable salt thereof. In some cases, the compound of formula (I) or formula (II) is compound 3-091-1 or a pharmaceutically acceptable salt thereof.

[0124] Unless otherwise specified, descriptions of substructures do not represent a specific orientation of that substructure. For example, [ka] of [ka] Compounds of formulas (I) and (II) having the following characteristics: [ka] The compound of formula (I) described as and [ka] It includes the compound of formula (II) as described.

[0125] stereoisomer The compounds of this disclosure may contain, for example, double bonds, one or more chiral carbon atoms, and rotationally hindered bonds, and therefore may exist as stereoisomers such as double bond isomers (i.e., geometric isomers (E / Z)), enantiomers, diastereomers, and atropisomers. Accordingly, it should be understood that the scope of this disclosure includes all possible stereoisomers of the exemplary compounds, including stereoisomerically pure forms (e.g., geometrically pure, enantiomerically pure, diastereoisomerically pure, and atropisomerically pure), as well as mixtures of stereoisomers of any chemical structure (all or part) disclosed herein (e.g., mixtures of geometric isomers, enantiomers, diastereomers, and atropisomers, or any of the aforementioned mixtures), unless the stereochemistry is specifically identified.

[0126] If the stereochemistry of a structure or part of a structure is not indicated by, for example, a thick line or a dashed line, then this structure or part of this structure should be interpreted as encompassing all of its stereoisomers. If the stereochemistry of a structure or part of a structure is indicated by, for example, a thick line or a dashed line, then this structure or part of this structure should be interpreted as encompassing only the specified stereoisomer, unless otherwise stated. For example, [ka] teeth, [ka] This represents (4R)-4-methoxy-5-methyl-4,5,6,7-tetrahydro-2H-isoindole, for example, represents (4R,5R)-4-methoxy-5-methyl-4,5,6,7-tetrahydro-2H-isoindole and (4R,5S)-4-methoxy-5-methyl-4,5,6,7-tetrahydro-2H-isoindole. In certain cases, a bond drawn with a wavy line may be used to indicate the presence of both stereoisomers. This should not be confused with a wavy line drawn perpendicular to the bond, which indicates the bond point to the rest of the molecule.

[0127] As used herein, the terms “stereoisomer” or “stereoisomerically pure” refer to a single stereoisomer of a compound that substantially does not contain any other stereoisomers of that compound (e.g., geometric isomers, enantiomers, diastereomers, and atropoisomers). For example, a stereoisomerically pure compound having one chiral center substantially does not contain any enantiomers of that compound, and a stereoisomerically pure compound having two chiral centers substantially does not contain any other enantiomers or diastereomers of that compound. A typical stereoisomerically pure compound contains more than 80% by weight of one stereoisomer of this compound and less than 20% by weight of other stereoisomers of this compound, or more than 90% by weight of one stereoisomer of this compound and less than 10% by weight of other stereoisomers of this compound, or more than 95% by weight of one stereoisomer of this compound and less than 5% by weight of other stereoisomers of this compound, or more than 97% by weight of one stereoisomer of this compound and less than 3% by weight of other stereoisomers of this compound.

[0128] This disclosure also includes pharmaceutical compositions containing stereoisomerically pure forms, and the use of stereoisomerically pure forms of any compound disclosed herein. Furthermore, this disclosure also includes pharmaceutical compositions containing mixtures of stereoisomers of any compound disclosed herein, and the use of such pharmaceutical compositions or mixtures of stereoisomers. These stereoisomers or mixtures thereof can be synthesized according to methods well known in the art and methods disclosed herein. Mixtures of stereoisomers can be resolved using standard techniques such as chiral columns or chiral resolving agents. For example, see Jacques et al., Enantiomers, Racemates and Resolutions (Wiley-Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725; Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions, page 268 (Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN, 1972).

[0129] Tautomers As is known to those skilled in the art, certain compounds disclosed herein may exist in one or more tautomerized forms. Since one chemical structure may be used to represent only one tautomerized form, for convenience it will be understood that a reference to a compound of a given structural formula includes other tautomers of that structural formula. For example, [ka] teeth [ka] Similarly, for example, the chemical name (4R,5R)-4-methoxy-5-methyl-4,5,6,7-tetrahydro-1H-indazole represents (4R,5R)-4-methoxy-5-methyl-4,5,6,7-tetrahydro-1H-indazole and (4R,5R)-4-methoxy-5-methyl-4,5,6,7-tetrahydro-2H-indazole. Therefore, the scope of this disclosure should be understood to encompass all tautomer forms of the compounds disclosed herein.

[0130] isotope labeled compounds Furthermore, the scope of this disclosure includes all pharmaceutically acceptable isotope-labeled compounds of the compounds disclosed herein, such as the compounds of formulas (I), (IA), (IB), (II), (IIA), (IIB), and (IIC), in which one or more atoms are replaced by atoms having the same atomic number but with atomic masses or mass numbers different from those normally found in nature. Examples of isotopes suitable for inclusion in the compounds disclosed herein include: 2 H and 3 Hydrogen such as H, 11 C, 13 C and 14 Carbon such as C, 36 Chlorine such as Cl, 18 Fluorine such as F 123 I and 125 Iodine, such as I 13 N and 15 Nitrogen such as N 15 O, 17 O and 18 Oxygen such as O, 32 Phosphorus such as P and 35 Examples include sulfur isotopes such as ₂S. Specific isotope-labeled compounds of formulas (I) and (II), for example, those incorporating radioactive isotopes, are useful in drug and / or substrate tissue distribution studies. Radioactive isotope tritium ( 3 H) and carbon-14 ( 14 C) is particularly useful for this purpose given the ease of their incorporation and the ease of detection. Deuterium ( 2Substitution with isotopes such as H or D can be advantageous in some situations because it may result in certain therapeutic benefits stemming from increased metabolic stability, such as an extended in vivo half-life or a reduction in the required dose. Therefore, the term "deuteration" refers to the substitution of one or more hydrogen atoms with one or more deuterium atoms on a particular structure or functional group. 11 C, 18 F, 15 O, and 13 Substitution with positron-emitting isotopes such as 1N may be useful, for example, in positron emission tomography (PET) tests to investigate target occupancy. The isotopically labeled compounds of the compounds disclosed herein can usually be prepared by conventional methods known to those skilled in the art or by processes similar to those described in the accompanying general synthesis procedures and examples, using appropriate isotopically labeled reagents instead of conventionally used unlabeled reagents.

[0131] biological activity In some cases, the compounds disclosed herein (e.g., compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), the compounds listed in Table A, the compounds listed in Table B, the compounds listed in Table C, and the compounds listed in Table D, and any pharmaceutically acceptable salts thereof) are acceptable in binding exchange assays described in Section 3: Biochemical and Cellular Assays at concentrations of less than 5 μM, less than 4 μM, or less than 3 μM. ICs that are full, or less than 2 μM, or less than 1 μM, or less than 0.9 μM, or less than 0.8 μM, or less than 0.7 μM, or less than 0.6 μM, or less than 0.5 μM, or less than 0.4 μM, or less than 0.3 μM, or less than 0.2 μM, or less than 0.1 μM, or less than 0.09 μM, or less than 0.08 μM, or less than 0.07 μM, or less than 0.06 μM, or less than 0.05 μM, or less than 0.04 μM, or less than 0.03 μM, or less than 0.02 μM, or less than 0.01 μM 50 It has a value. In some cases, the compounds and salts disclosed herein have an IC of less than 1 μM. 50 It has a value. In some cases, the compounds and salts disclosed herein have an IC of less than 0.5 μM.50 It has a value. In some cases, the compounds and salts disclosed herein have an IC of less than 0.3 μM. 50 It has a value. In some cases, the compounds and salts disclosed herein have an IC of less than 0.1 μM. 50 It has a value of less than 5 μM IC in a 2-hour binding exchange assay. 50 Compounds of the present disclosure having the above characteristics are also provided herein. IC50 is less than 3 μM in a 2-hour binding exchange assay. 50 Compounds of the present disclosure having the above characteristics are further provided herein. IC50 is less than 1 μM in a 2-hour binding exchange assay. 50 Compounds of the present disclosure having the following characteristics are further provided herein. IC50 is less than 0.5 μM in the 2-hour binding exchange assay described herein. 50 Compounds of the present disclosure having or pharmaceutically acceptable salts thereof are further provided herein. IC < 0.1 μM in the 2-hour bond exchange assay described herein. 50 Compounds of the present disclosure having or pharmaceutically acceptable salts thereof are also provided herein. IC < 0.05 μM in the 2-hour bond exchange assay described herein. 50 Compounds of the present disclosure having or pharmaceutically acceptable salts thereof are also provided herein. IC < 0.04 μM in the 2-hour bond exchange assay described herein. 50 Compounds of the present disclosure having or pharmaceutically acceptable salts thereof are also provided herein. IC < 0.03 μM in the 2-hour bond exchange assay described herein. 50 Compounds of the present disclosure having or pharmaceutically acceptable salts thereof are also provided herein. IC < 0.02 μM in the 2-hour bond exchange assay described herein. 50 Compounds of the present disclosure having or pharmaceutically acceptable salts thereof are also provided herein. IC < 0.01 μM in the 2-hour bond exchange assay described herein. 50 Compounds of the present disclosure having or pharmaceutically acceptable salts thereof are also provided herein.

[0132] The foregoing merely outlines certain aspects of the Disclosure and is not intended to, and should not be construed to, limit the Disclosure in any way.

[0133] Formulation and route of administration In the uses described herein, it may be possible to administer the compounds disclosed herein alone, but the compounds to be administered are usually present as active ingredients in a pharmaceutical composition. Therefore, pharmaceutical compositions are further provided herein that contain the compounds disclosed herein (e.g., compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), the compounds listed in Table A, the compounds listed in Table B, the compounds listed in Table C, and the compounds listed in Table D, and any pharmaceutically acceptable salt thereof) in combination with one or more pharmaceutically acceptable excipients and, if desired, other active ingredients. For example, see Remington: The Science and Practice of Pharmacy, Volume I and Volume II, 20-second edition, edited by Loyd V. Allen Jr., Philadelphia, PA, Pharmaceutical Press, 2012; Pharmaceutical Dosage Forms (Vol. 1-3), Liberman et al., Eds., Marcel Dekker, New York, NY, 1992; Handbook of Pharmaceutical Excipients (3rd Ed.), edited by Arthur H. Kibbe, American Pharmaceutical Association, Washington, 2000; Pharmaceutical Formulation: The Science and Technology of Dosage Forms (Drug Discovery), first edition, edited by GD Tovey, Royal Society of Chemistry, 2018. In some cases, the pharmaceutical compositions described herein contain a therapeutically effective amount of the compound disclosed herein or a pharmaceutically acceptable salt thereof.

[0134] The compounds disclosed herein may be administered by any preferred route in the form of a pharmaceutical composition adapted to such route and in a dose effective for the intended treatment. The compounds and compositions presented herein may be administered, for example, orally, mucosally, topically, transdermally, rectally, pulmonaryly, parenterally, intranasally, intravascularly, intravenously, intra-arterially, intraperitoneally, intrathecally, subcutaneously, sublingually, intramuscularly, intrasternally, or vaginally, in the form of a conventional pharmaceutically acceptable excipient, or by infusion techniques.

[0135] The pharmaceutical composition may be in the form of, for example, tablets, chewable tablets, minitablets, caplets, pills, beads, hard capsules, soft capsules, gelatin capsules, granules, powders, licks, patches, creams, gels, sachets, microneedle arrays, syrups, flavored syrups, juices, drops, injections, emulsions, microemulsions, ointments, aerosols, aqueous suspensions, or oily suspensions. In some cases, the pharmaceutical composition is prepared in the form of a dosage unit containing a specific amount of the active ingredient.

[0136] Accordingly, further embodiments of the present disclosure are pharmaceutical compositions comprising one or more compounds disclosed herein, or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients. Compounds of the present disclosure, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions described herein for use as pharmaceuticals are further provided herein.

[0137] How to use The compounds described herein are GDP-bound G12C-mutant KRAS proteins ("KRAS") G12C It can covalently bond to cysteine-12 of (). In some cases, the compounds described herein can permanently inactivate proteins, for example, KRAS G12CThey can act as potent inhibitors. While not intended to be bound by any particular theory, the compounds of this disclosure may, in some cases, inhibit the phosphorylation of extracellular signaling regulation ("ERK"), a key downstream effector of KRAS, leading to tumor regression. In addition to their usefulness in human therapy, the compounds provided herein may be useful in the veterinary treatment of companion animals, including mammals, rodents, exotic animals, and livestock. For example, animals including horses, dogs, and cats may be treated with the compounds provided herein.

[0138] Another aspect of this disclosure provides a method for treating disease conditions, including, but not limited to, conditions involving the KRAS G12C mutation (e.g., cancer), using the compounds disclosed herein, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions herein. See, for example, U.S. Patent No. 10,519,146B2 issued on 31 December 2019, which is incorporated herein by reference, specifically sections 198, line 1 to 201, line 36.

[0139] While we do not wish to be bound by any particular theory, please note the following: Sotrasib, like the compounds disclosed herein, is KRAS G12C It is a small molecule that specifically and irreversibly inhibits (Hong et al., N.Engl.J.Med. 2020,383,1207,at 1208). Hong et al. reported that "[p]Re-clinical studies have shown that [sotrasib] inhibits almost all detectable phosphorylation of extracellular signal-regulated kinase (ERK), a key downstream effector of KRAS, resulting in permanent complete tumor regression in mice harboring KRAS p.G12C tumors" (see also the section titled "Biological Evaluation" below, Canon et al., Nature 2019,575(7781),217; and Lanman et al., J.Med. Chem. 2020,63,52).

[0140] Sotrasib was evaluated in a phase 1 dose-escalation and expansion study involving 129 patients with histologically confirmed locally advanced or metastatic cancer with the KRAS G12C mutation, identified by local molecular testing of tumor tissue, including 59 patients with non-small cell lung cancer, 42 patients with colorectal cancer, and 28 patients with other tumor types (Hong et al., 2020, pp. 1208-1209). Hong et al. reported disease control rates (95% CI) of 88.1% for non-small cell lung cancer, 73.8% for colorectal cancer, and 75.0% for other tumor types (Hong et al., 2020, p. 1213, Table 3). The cancer types that showed either stable disease (SD) or partial reduction (PR), as reported by Hong et al., were non-small cell lung cancer, colorectal cancer, pancreatic cancer, appendiceal cancer, endometrial cancer, esophageal cancer, cancer of unknown primary origin, duodenal papilla cancer, gastric cancer, small intestine cancer, paranasal sinus cancer, bile duct cancer, or melanoma (Hong et al., 2020, p. 1212 (Figure A), and Appendix (p. 59 (Figure S5) and p. 63 (Figure S6)).

[0141] KRAS G12C mutations occur at the frequencies shown in the table below (Cerami et al., Cancer Discov. 2012, 2(5), 401; Gao et al., Science Signaling 2013, 6(269), p11). For example, the table shows that 11.6% of subjects with non-small cell lung cancer have cancer in which one or more cells express the KRAS G12C mutant protein. Therefore, KRAS is specifically and irreversibly affected. G12C The compounds provided herein that bind to (see Section 3: Biochemistry and Cellular Assays) are useful for the treatment of subjects with cancers, including but not limited to those listed in the table below.

[0142] [Table 44]

[0143] [Table 45]

[0144] Another aspect of this disclosure provides compounds disclosed herein (e.g., compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, compounds listed in Table B, compounds listed in Table C, or compounds listed in Table D, or any pharmaceutically acceptable salt thereof) or pharmaceutically acceptable salt thereof, or pharmaceutical compositions disclosed herein, for use in the treatment of cancer. Yet another aspect of this disclosure provides compounds disclosed herein, pharmaceutically acceptable salt thereof, or pharmaceutical compositions disclosed herein, for use in the treatment of cancer in which one or more cells express the KRAS G12C mutant protein.

[0145] Another aspect of this disclosure provides a compound disclosed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition disclosed herein, in the preparation of a pharmaceutical for treating cancer. Yet another aspect of this disclosure provides a compound disclosed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described herein, in the preparation of a pharmaceutical for treating cancer in which one or more cells express the KRAS G12C mutant protein.

[0146] A further aspect of the present disclosure is a method for treating cancer in a subject requiring cancer treatment, comprising administering to the subject a therapeutically effective amount of one of the compounds disclosed herein (e.g., compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, compounds listed in Table B, compounds listed in Table C, or compounds listed in Table D, or pharmaceutically acceptable salts of any of the above) or a pharmaceutical composition described herein. Another aspect of the present disclosure is a method for treating cancer in a subject requiring cancer treatment, comprising administering to the subject a therapeutically effective amount of one of the compounds disclosed herein or a pharmaceutically acceptable salt thereof or a pharmaceutical composition disclosed herein, wherein one or more cells express the KRAS G12C mutant protein. In some cases, the subject has cancer that has been determined to have one or more cells expressing the KRAS G12C mutant protein prior to administration of the compound or a pharmaceutically acceptable salt thereof.

[0147] In some cases, the cancer is metastatic. In some cases, the cancer is non-metastatic. In some cases, the cancers disclosed herein are non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed cancer of unknown primary origin, pancreatic cancer, hepatobiliary cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, or solid tumors. In some cases, the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, appendiceal cancer, endometrial cancer, esophageal cancer, cancer of unknown primary origin, duodenal papilla cancer, gastric cancer, small intestine cancer, paranasal sinus cancer, bile duct cancer, melanoma, or solid tumors. In some cases, the cancer is non-small cell lung cancer. In some cases, cancer is colorectal cancer. In some cases, cancer is pancreatic cancer. In some cases, cancer is a solid tumor.

[0148] Combination therapy The Disclosure also provides methods of combination therapy in which agents known to modulate other pathways, or other components of the same pathway, or even overlapping sets of target enzymes are used in combination with the compounds of the Disclosure (e.g., compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, compounds listed in Table B, compounds listed in Table C, or compounds listed in Table D, or pharmaceutically acceptable salts of any of the above). In one embodiment, such therapy includes, but is not limited to, a combination of one or more compounds of the Disclosure with a chemotherapeutic agent, a therapeutic antibody and / or radiotherapy to provide a synergistic or additive therapeutic effect. For example, see U.S. Patent No. 10,519,146B2 issued December 31, 2019, which is incorporated herein by reference (specifically, see sections 201 (line 37) to 212 (line 46) and 219 (line 64) to 220 (line 39)).

[0149] The compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of a second compound in any of the methods described herein. In some cases, the second compound is an ATR inhibitor, an Aurora kinase A inhibitor, an AKT inhibitor, an arginase inhibitor, a CDK2 inhibitor, a CDK4 / 6 inhibitor, an ErbB family inhibitor, an ERK inhibitor, a FAK inhibitor, an FGFR inhibitor, a glutaminase inhibitor, an IGF-1R inhibitor, a KIF18A inhibitor, a MAT2A inhibitor, a MCL-1 inhibitor, a MEK inhibitor, an mTOR inhibitor, a PARP inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PI3K inhibitor, a PRMT5 inhibitor, a Raf kinase inhibitor, a SHP2 inhibitor, a SOS1 inhibitor, a Src kinase inhibitor, or one or more chemotherapeutic agents. In some cases, the second compound is administered as a pharmaceutically acceptable salt. In some cases, the second compound is administered as a pharmaceutical composition comprising the second compound or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients.

[0150] ATR inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of an ATR inhibitor in any of the methods described herein. ATR inhibitors are compounds that target ataxia telangiectasia mutations and Rad3-related kinases. Exemplary ATR inhibitors for use in the methods provided herein include dactricib, VE-821 (3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide, 3-amino-6-[4-(methylsulfonyl)phenyl]-N-phenyl-2-pyrazinecarboxamide), thrin-2 (9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]-benzo[h]-1,6-naphthyridine-2(1H)-one), and ETP-46464 (α,α-dimethyl-4-[2-oxo-9-(3-quinolinyl)-2H-[1,3]oxazino[5,4132zetidinelin)-1(4H)-yl]-be This includes, but is not limited to, benzoacetamide (Benzenacetonitrile), CGK733 (α-phenyl-N-[2,2,2-trichloro-1-[[[(4-fluoro-3-nitrophenyl)amino]thioxomethyl]amino]ethyl]benzeneacetamide), AZ20 (4-[4-[(3R)-3-methyl-4-morpholinyl]-6-[1-(methylsulfonyl)cyclopropyl]-2-pyrimidinyl]-1H-indole), SKLB-197 ((R)-4-(2-(1H-indole-4-yl)-6-(1-methyl-1H-pyrazole-5-yl)quinazolin-4-yl)-3-methylmorpholine), elimusertib, galticertive, elimusertib hydrochloride, ceracertib, and cisandrin B.

[0151] Aurora kinase A inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of an aurora kinase A inhibitor in any of the methods described herein.Examples of Aurora kinase A inhibitors used in the methods provided herein include, but are not limited to, aricertib, senicertib, danucertib, tozacertib, LY3295668((2R,4R)-1-[(3-chloro-2-fluorophenyl)methyl]-4-[[3-fluoro-6-[(5-methyl-1H-pyrazole-3-yl)amino]pyridine-2-yl]methyl]-2-methylpiperidine-4-carboxylic acid), ENMD-2076(6-(4-methylpiperazine-1-yl)-N-(5-methyl (-1H-pyrazole-3-yl)-2-[(E)-2-phenylethenyl]pyrimidine-4-amine), TAK-901 (5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidine-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide), TT-00420 (4-[9-(2-chlorophenyl)-6-methyl-2,4,5,8,12-pentazatricyclo[8.4.0.03,7]tetradeca-1(14),3,6,8,10,12-hexaen-13-yl]morpholine), AMG 900(N-[4-[3-(2-aminopyrimidine-4-yl)pyridine-2-yl]oxyphenyl]-4-(4-methylthiophen-2-yl)phthalazine-1-amine), MLN 8054(4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepine-2-yl]amino]benzoic acid), PF-03814735(N-[2-[(1R,8S)-4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidine-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-to Lien-11-yl]-2-oxoethyl]acetamide), SNS-314 (1-(3-chlorophenyl)-3-[5-[2-(thieno[3,2-d]pyrimidine-4-ylamino)ethyl]-1,3-thiazole-2-yl]urea), CYC116 (4-methyl-5-[2-(4-morpholine-4-ylanilino)pyrimidine-4-yl]-1,3-thiazole-2-amine), TAS-119, BI 811283, and TTP607.

[0152] AKT inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of an AKT inhibitor. Examples of AKT inhibitors used in the methods provided herein include, but are not limited to, afrecertib, capivacertib, ipatasertib, uprosertib, BAY1125976 (2-[4-(1-aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-b]pyridazine-6-carboxamide), ARQ 092(3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridine-2-yl]pyridine-2-amine), MK2206(8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridine-3-one), SR13668(indro[2,3-b]carbazole-2,10-dicarboxylic acid,5,7-dihydro-6-methoxy-,2,10 -Diethyl ester), ONC201(11-benzyl-7-[2-methylphenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one), ARQ751(N-(3-aminopropyl)-N-[(1R)-1-(3-anilino-7-chloro-4-oxoquinazolin-2-yl)buta-3-inyl]-3-chloro-2-fluorobenzamide), RX-0201, and LY2780301.

[0153] Arginase inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of an arginase inhibitor. Exemplary arginase inhibitors used in the methods provided herein include, but are not limited to, numidaldistat and CB 280.

[0154] CDK2 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of a CDK2 inhibitor. As used herein, the term “CDK2” refers to cyclin-dependent kinase (”CDK”) 2, a member of the mammalian serine / threonine protein kinases. As used herein, the term “CDK2 inhibitor” refers to a compound that can negatively modulate or inhibit all or part of the enzymatic activity of CDK2. Exemplary CDK2 inhibitors for use in the methods provided herein include, but are not limited to, flavopyridol, roscovitin, dinacyclib, milcyclib, meriolin, variolin, AZD5438 (4-[2-methyl-1-(1-methylethyl)-1H-imidazole-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidineamine), roniciclib, and SNS-032 (N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide).

[0155] CDK4 / 6 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of a CDK4 / 6 inhibitor. The term "CDK4 / 6," as used herein, refers to cyclin-dependent kinases ("CDK") 4 and 6, which are members of mammalian serine / threonine protein kinases. The term "CDK4 / 6 inhibitor," as used herein, refers to compounds that can negatively modulate or inhibit all or part of the enzymatic activity of CDK4 and / or 6. Examples of CDK4 / 6 inhibitors used in the methods provided herein include, but are not limited to, abemaciclib, palbociclib, ribociclib, trilaciclib, and PF-06873600 ((pyrido[2,3-d]pyrimidine-7(8H)-one, 6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(methylsulfonyl)-4-piperidinyl]amino]). In some cases, the CDK4 / 6 inhibitor is palbociclib.

[0156] ErbB family inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of an ErbB family inhibitor. The term "ErbB family," as used herein, refers to members of the mammalian transmembrane protein tyrosine kinase family, including ErbB1 (EGFR HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4). The term "ErbB family inhibitor," as used herein, refers to a drug (e.g., a compound or antibody) that can negatively modulate or inhibit all or part of the activity of at least one member of the ErbB family. Modulation or inhibition of one or more ErbB tyrosine kinases may occur by modulating or inhibiting the kinase enzyme activity of one or more ErbB family members, or by blocking homodimerization or heterodimerization of ErbB family members. In some cases, ErbB family inhibitors are EGFR inhibitors, such as anti-EGFR antibodies. Examples of anti-EGFR antibodies used in the methods provided herein include, but are not limited to, saltumumab, nimotuzumab, matuzumab, nesitumumab, panitumumab, and cetuximab. In some cases, the anti-EGFR antibody is cetuximab. In some cases, the anti-EGFR antibody is panitumumab. In some cases, the ErbB family inhibitor is a HER2 inhibitor, such as an anti-HER2 antibody. Examples of anti-HER-2 antibodies used in the methods provided herein include, but are not limited to, pertuzumab, trastuzumab, and trastuzumab emtansine. In some cases, the ErbB family inhibitor is a HER3 inhibitor, such as an anti-HER3 antibody like HMBD-001 (Hummingbird Bioscience). In some cases, the ErbB family inhibitor is a combination of an anti-EGFR antibody and an anti-HER2 antibody. In some cases, the ErbB family inhibitor is an irreversible inhibitor.Examples of irreversible ErbB family inhibitors used in the methods provided herein include, but are not limited to, afatinib, dacomitinib, canertinib, poziotinib, AV 412 ((N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4-methyl-1-piperazinyl)-1-butin-1-yl]-6-quinazolinyl]-2-propenamide)), PF 6274484 (N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]-2-propenamide), and HKI 357 ((E)-N-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-3-cyano-7-ethoxyquinoline-6-yl]-4-(dimethylamino)buta-2-enamide). In some cases, the irreversible ErbB family inhibitor is afatinib. In some cases, the irreversible ErbB family inhibitor is dacomitinib. In some cases, the ErbB family inhibitor is a reversible inhibitor. Examples of reversible ErbB family inhibitors used in the methods provided herein include, but are not limited to, erlotinib, gefitinib, sapitinib, vallitinib, tarloxotinib, TAK-285 (N-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidine-5-yl)ethyl)-3-hydroxy-3-methylbutanamide), AEE788 ((S)-6-(4-((4-ethylpiperazine-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine), BMS 599626((3S)-3-morpholinylmethyl-[4-[[1-[(3-fluorophenyl)methyl]-1H-indazole-5-yl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-yl]carbamate), and GW 583340(N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazole-4-yl]quinazoline-4-amine).In some cases, the reversible ErbB family inhibitor is sapitinib. In one embodiment, the reversible ErbB family inhibitor is tarloxotinib.

[0157] ERK inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of an ERK inhibitor. Examples of ERK inhibitors used in the methods provided herein include, but are not limited to, urixerutinib, laboxerutinib, CC-90003 (N-[2-[[2-[(2-methoxy-5-methylpyridine-4-yl)amino]-5-(trifluoromethyl)pyrimidine-4-yl]amino]-5-methylphenyl]propaneamide), LY3214996 (6,6 -Dimethyl-2-[2-[(2-methylpyrazole-3-yl)amino]pyrimidine-4-yl]-5-(2-morpholine-4-ylethyl)thieno[2,3-c]pyrrole-4-one), KO-947(1,5,6,8-tetrahydro-6-(phenylmethyl)-3-(4-pyridinyl)-7H-pyrazolo[4,3-g]quinazolin-7-one), ASTX029, LTT462, and JSI-1187.

[0158] FAK inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of an FAK inhibitor in any of the methods described herein. Examples of FAK inhibitors used in the methods provided herein include, but are not limited to, GSK2256098 (2-[[5-chloro-2-[(5-methyl-2-propane-2-ylpyrazole-3-yl)amino]pyridine-4-yl]amino]-N-methoxybenzamide), PF-00562271 (N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindole-5-yl)amino]-5-(trifluoromethyl)pyrimidine-4-yl]amino]methyl]pyridine-2-yl]methanesulfonamide), VS-4718 (2-[[2-(2-methoxy-4-morpholine-4-ylanilino)-5-(trifluoromethyl)pyridine-4-yl]amino]-N-methylbenzamide), and APG-2449.

[0159] FGFR inhibitors In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of the FGFR inhibitor. Exemplary FGFR inhibitors for use in the methods provided herein include futibatinib, pemigatinib, ASP5878 (2-[4-[[5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]pyrimidine-2-yl]amino]pyrazole-1-yl]ethanol), AZD4547 (N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-3-yl]-4-[(3S,5R)-3,5-dimethylpiperazine-1-yl]benzamide), and debio1347 ([5-amino Examples include, but are not limited to, -1-(2-methyl-3H-benzimidazole-5-yl)pyrazole-4-yl]-(1H-indole-2-yl)methanone), INCB062079, H3B-6527(N-[2-[[6-[(2,6-dichloro-3,5-dimethoxyphenyl)carbamoyl-methylamino]pyrimidine-4-yl]amino]-5-(4-ethylpiperazine-1-yl)phenyl]propa-2-enamide), ICP-105, CPL304110, HMPL-453 and HGS1036.

[0160] Glutaminase inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of glutaminase inhibitor in any of the methods described herein. Exemplary glutaminase inhibitors used in the methods provided herein include, but are not limited to, teragrenastat, IPN60090, and OP 330.

[0161] IGF-1R inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of an IGF-1R inhibitor. Examples of IGF-1R inhibitors used in the methods provided herein include, but are not limited to, cyclopropyl-1H-pyrazole-3-ylamino(5- N-(6-fluoropyridine-3-yl)-2-methylpyrrolidine-2-carboxamide), KW-2450(N-[5-[[4-(2-hydroxyacetyl)piperazine-1-yl]methyl]-2-[(E)-2-(1H-indazole-3-yl)ethenyl]phenyl]-3-methylthiophene-2-carboxamide), PL225B, AVE1642, and BIIB022.

[0162] KIF18A inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of a KIF18A inhibitor. Examples of KIF18A inhibitors used in the methods provided herein include, but are not limited to, those disclosed in U.S. Patent Application Publication No. 2020 / 0239441, International Publication No. 2020 / 132649, International Publication No. 2020 / 132651, and International Publication No. 2020 / 132653 (each of which is incorporated herein by reference in whole). In some cases, the KIF18A inhibitor is sovilnesib (AMG 650).

[0163] MAT2A inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of a MAT2A inhibitor. A MAT2A inhibitor is a compound that inhibits methionine adenosyltransferase II alpha. An exemplary MAT2A inhibitor for use in the methods provided herein is AG270(3-(cyclohexa-1-en-1-yl)-6-(4-methoxyphenyl)-2-phenyl-136zetidindinin-2-ylamino)pyrazolo[1,5-a]pyrimidine-7(4H)-one).

[0164] MCL-1 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of an MCL-1 inhibitor. Examples of MCL-1 inhibitors used in the methods provided herein include, but are not limited to, murizatocrax, topotoclax, AZD 5991 ((3aR)-5-chloro-2,11,12,24,27,29-hexahydro-2,3,24,33-tetramethyl-22H-9,4,8-(metheniminomethino)-14,20:26,23-dimetheno-10H,20H-pyrazolo[4,3-l][2,15,22,18,19]benzoxaditiasiazacyclohexacosin-32-carboxylic acid), MIK 665((αR)-α-[[(5S)-5-[3-chloro-2-methyl-4-[2-(4-methyl-1-piperazinyl)ethoxy]phenyl]-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine-4-yl]oxy]-2-[[2-(2-methoxyphenyl)-4-pyrimidinyl]methoxy]benzenepropanoic acid), and ABBV-467. In some cases, the MCL-1 inhibitor is murizatocrax. In some cases, the MCL-1 inhibitor is tapotoclax.

[0165] MEK inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of a MEK inhibitor. Examples of MEK inhibitors used in the methods provided herein include, but are not limited to, trametinib, cobimetinib, selumetinib, pimacertib, refametinib, PD-325901 (N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide), AZD8330 (2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl- 6-Oxopyridine-3-carboxamide), GDC-0623(5-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide), RO4987655(3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(3-oxoxazinan-2-yl)methyl]benzamide), TAK-733(3-[(2R)-2,3-dihydroxypropyl]- 6-Fluoro-5-(2-Fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione), PD0325901(N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide), CI-1040(2-(2-chloro-4-iodophenylamino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide), PD318088(5-bromo-N-(2, 3-Dihydroxypropoxy)-3,4-Difluoro-2-(2-Fluoro-4-iodophenylamino)benzamide), PD98059 (2-(2-amino-3-methoxyphenyl)-4H-chromen-4-one), PD334581 (N-[5-[3,4-Difluoro-2-[(2-Fluoro-4-iodophenyl)amino]phenyl]-1,3,4-Oxadiazole-2-yl]-4-morpholineethanamine), FCN-159, CS3006, HL-085, SHR 7390, and WX-554. In some cases, the MEK inhibitor is trametinib.

[0166] mTOR inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of an mTOR inhibitor. Examples of mTOR inhibitors used in the methods provided herein include, but are not limited to, everolimus, rapamycin, zotarolimus (ABT-578), ridafololimus (defololimus, MK-8669), sapanicertib, buparulisib, pictilisib, vistocertib, dactricib, torin-1(1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)cyclohexyl)-9-(quinoline-3-yl)benzo[h][ [1,6]naphthyridine-2(1H)-one), GDC-0349((S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-7-(oxetan-3-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-2-yl)phenyl)urea), and VS-5584(SB2343, (5-(8-methyl-2-morpholin-4-yl-9-propan-2-ylpurine-6-yl)pyrimidine-2-amine). In some cases, the mTOR inhibitor is everolimus.

[0167] PARP inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of a PARP inhibitor. PARP inhibitors are compounds that target poly(adenosine diphosphate)-ribose polymerase. The term PARP inhibitor encompasses PARP1, PARP2, and PARP3 inhibitors. Exemplary PARP inhibitors for use in the methods provided herein include, but are not limited to, t137 zetidinrib, lucaparib, lucaparib cansylate, niraparib, niraparib tosylate, talazoparib, AG-1461, A-966492, PJ34 HCl, niraparib, UPF 1069, ME0328, benadaparib, AZD5305, DR2313, BYK204165, pamiparib, NMS-P118, and NU 1025.

[0168] PD-1 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of a PD-1 inhibitor in any of the methods described herein. Examples of PD-1 inhibitors used in the methods provided herein include, but are not limited to, pembrolizumab, nivolumab, semiprimab, spartalizumab (PDR001), camrelizumab (SHR1210), cintilimab (IBI308), tisrelizumab (BGB-A317), tripalimab (JS 001), dostallimab (TSR-042, WBP-285), INCMGA00012 (MGA012), AMP-224, AMP-514, and anti-PD-1 antibodies as described in U.S. Patent No. 10,640,504 B2 ("Anti-PD-1 Antibody A", paragraphs 66, 56-67, 24, and 67, 54-57), which are incorporated herein by reference. In some cases, the PD-1 inhibitor is pembrolizumab. In other cases, the PD-1 inhibitor is anti-PD-1 antibody A.

[0169] PD-L1 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of a PD-L1 inhibitor in any of the methods described herein. Examples of PD-L1 inhibitors used in the methods provided herein include, but are not limited to, atezolizumab, avelumab, durvalumab, ZKAB001, TG-1501, SHR-1316, MSB2311, MDX-1105, KN035, IMC-001, HLX20, FAZ053, CS1001, CK-301, CBT-502, BGB-A333, BCD-135, and A167. In some cases, the PD-L1 inhibitor is atezolizumab.

[0170] PI3K inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein in an effective amount of a PI3K inhibitor. Examples of PI3K inhibitors used in the methods provided herein include, but are not limited to, idelalisib, copanlisib, duvelisib, alpelisib, taselicib, perifosin, buparlisib, umbralicib, pictilisib, dactlicib, voxtalisib, sonolicib, tenalisib, ceravelicib, acalisib, CUDC-907(N-hydroxy-2-[[2-(6-methoxypyridine-3-yl)-4-mo (Morpholin-4-ylthieno[3,2-d]pyrimidine-6-yl]methyl-methylamino]pyrimidine-5-carboxamide), ME-401(N-[2-methyl-1-[2-(1-methylpiperidine-4-yl)phenyl]propan-2-yl]-4-(2-methylsulfonylbenzimidazole-1-yl)-6-morpholin-4-yl-1,3,5-triazine-2-amine), IPI-549(2-amino-N-[(1S)-1-[8-[ 2-(1-methylpyrazole-4-yl)ethinyl]-1-oxo-2-phenylisoquinoline-3-yl]ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide), SF1126(((2S)-2-[[(2S)-3-carboxy-2-[[2-[[(2S)-5-(diaminomethylideneamino)-2-[[4-oxo-4-[[4-(4-oxo-8-phenylchromen-2-yl)morpholine-4-ium-4-yl]methoxy [C]butanoyl]amino]pentanoyl]amino]acetyl]amino]propanoyl]amino]-3-hydroxypropanoate), XL147 (N-[3-(2,1,3-benzothiadiazole-5-ylamino)quinoxaline-2-yl]-4-methylbenzenesulfonamide), GSK1059615 ((5Z)-5-[(4-pyridine-4-ylquinoline-6-yl)methylidene]-1,3-thiazolidinedione-2,4-dione), and AMG 319 (N-[(1S)-1-(7-fluoro-2-pyridine-2-ylquinoline-3-yl)ethyl]-7H-purine-6-amine).

[0171] PRMT5 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of a PRMT5 inhibitor. PRMT5 inhibitors in compounds that inhibit protein arginine methyltransferase 5. The term "PRMT5 inhibitor" includes PRMT5 inhibitors that work in conjunction with MTA. Exemplary PRMT5 inhibitors for use in the methods provided herein include pemurametostat (6-[(1-acetylpiperidine-4-yl)amino]-N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]pyrimidine-4-carboxamide), GSK3203591 (2-(cyclobutylamino)-N-[(2S)-3-(3,4-dihydro-2(1H)-isoquinolinyl)-2-hydropropyl]-4-pyridinecarboxamide dihydrochloride), and LLY-283 ((R)-5'-phenyl-7-deazaadenosine). This includes, but is not limited to, 6-amino-9-[(R)-5'-phenyl(ribofuranosyl)]-7-deazapurine, (2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidine-7-yl)-5-((R)-hydroxy(phenyl)methyl)tetrahydrofuran-3,4-diol), PRT811, and MRTX1719 (2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazine-6-yl)-1-methyl-1H-pyrazole-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile).

[0172] Raf kinase inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially in any of the methods described herein, in an effective amount of a Raf kinase inhibitor. As used herein, the term "RAF kinase" refers to a member of the mammalian serine / threonine kinase, comprising three isoforms (C-Raf, B-Raf, and A-Raf), including homodimers of each isoform and heterodimers between isoforms (e.g., C-Raf / B-Raf heterodimer). As used herein, the term "Raf kinase inhibitor" refers to a compound that can negatively modulate or inhibit all or part of the enzymatic activity of one or more members of the Raf family kinases, or that can inhibit activity by interfering with the formation of Raf homodimers or heterodimers.In some cases, Raf kinase inhibitors include, but are not limited to, the following: encorafenib, sorafenib, rifilafenib, vemurafenib, dabrafenib, PLX-8394 (N-(3-(5-(2-cyclopropylpyrimidine-5-yl)-3a,7a-dihydro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)-3-fluoropyrrolidine-1-sulfonamide), Raf-709 (N-(2-methyl-5 -Molfolino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'-bipyridine]-5-yl)-3-(trifluoromethyl)benzamide), LXH254(N-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridine-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide), LY3009120(1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino )Pyrido[2,3-d]pyrimidine-6-yl)phenyl)urea), Tak-632(N-(7-cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamide)phenoxy)benzo[d]thiazole-2-yl)cyclopropanecarboxamide), CEP-32496(1-(3-((6,7-dimethoxyquinazoline-4-yl)oxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropane-2-yl)isoxazole- 3-yl)urea), CCT196969(1-(3-(tert-butyl)-1-phenyl-1H-pyrazole-5-yl)-3-(2-fluoro-4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazine-8-yl)oxy)phenyl)urea), and RO5126766(N-[3-fluoro-4-[[4-methyl-2-oxo-7-(2-pyrimidinyloxy)-2H-1-benzopyran-3-yl]methyl]-2-pyridinyl]-N'-methyl-sulfamide). In some cases, the Raf kinase inhibitor is encorafenib. In some cases, the Raf kinase inhibitor is sorafenib. In some cases, the Raf kinase inhibitor is rifilafenib.

[0173] SHP2 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of an SHP2 inhibitor in any of the methods described herein. Examples of SHP2 inhibitors used in the methods provided herein include, but are not limited to, SHP-099 (6-(4-amino-4-methylpiperidine-1-yl)-3-(2,3-dichlorophenyl)pyrazine-2-amine dihydrochloride), RMC-4550 ([3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decane-8-yl]-6-(2,3-dichlorophenyl)-5-methylpyrazine-2-yl]methanol), TNO155, (3S,4S)-8-[6-amino-5-(2-amino-3-chloropyridine-4-yl)sulfanylpyrazine-2-yl]-3-methyl-2-oxa-8-azaspiro[4.5]decane-4-amine), and RMC-4630 (Revolution Medicine; Bosiprotafib (RMC-4630; 6-[(2-amino-3-chloro-4-pyridinyl)thio]-3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-5-methyl-2-pyrazinemethanol)). In some cases, the SHP inhibitor for use in the manner provided herein is RMC-4630 (bosiprotafib, Revolution Medicine). In some cases, exemplary SHP2 inhibitors used in the methods provided herein include, but are not limited to, the following: 3-[(1R,3R)-1-amino-3-methoxy-8-azaspiro[4.5]deca-8-yl]-6-(2,3-dichlorophenyl)-5-methyl-2-pyrazinemethanol (CAS 2172651-08-8), 3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-6-[(2,3-dichlorophenyl)thio]-5-methyl-2-pyrazinemethanol (CAS 2172652-13-8), 3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-6-[[3-chloro-2-(3-hydroxy-1-azetidinyl)-4-pyridinyl]thio]-5-methyl-2-pyrazinemethanol (CAS 2172652-38-7), and 6-[(2-amino-3-chloro-4-pyridinyl)thio]-3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-5-methyl-2-pyrazinemethanol (CAS 2172652-48-9). In some cases, exemplary SHP2 inhibitors used in the methods provided herein include, but are not limited to, the following: 1-[5-(2,3-dichlorophenyl)-6-methylimidazo[1,5-a]pyrazine-8-yl]-4-methyl-4-piperidineamine (CAS 2240981-75-1), (1R)-8-[5-(2,3-dichlorophenyl)-6-methylimidazo[1,5-a]pyrazine-8-yl]-8-azaspiro[4.5]decane-1-amine (CAS 2240981-78-4), (3S,4S)-8-[7-(2,3-dichlorophenyl)-6-methylpyrazolo[1,5-a]pyrazine-4-yl]-3-methyl-2-oxa-8-azaspiro[4.5]decane-4-amine (CAS 2240982-45-8), (3S,4S)-8-[7-[(2-amino-3-chloro-4-pyridinyl)thio]pyrazolo[1,5-a]pyrazine-4-yl]-3-methyl-2-oxa-8-azaspiro[4.5]decane-4-amine (CAS 2240982-57-2), 4-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-7-(2,3-dichlorophenyl)-6-methyl-pyrazolo[1,5-a]pyrazine-2-methanol (CAS 2240982-69-6), 7-[(2-amino-3-chloro-4-pyridinyl)thio]-4-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-6-methyl-pyrazolo[1,5-a]pyrazine-2-methanol (CAS 2240982-73-2), and (3S,4S)-8-[7-[(2-amino-3-chloro-4-pyridinyl)thio]-6-methylpyrazolo[1,5-a]pyrazine-4-yl]-3-methyl-2-oxa-8-azaspiro[4.5]decane-4-amine (CAS 2240982-77-6). In some cases, the SHP inhibitor used in the methods provided herein is (1R)-8-[5-(2,3-dichlorophenyl)-6-methylimidazo[1,5-a]pyrazine-8-yl]-8-azaspiro[4.5]decane-1-amine (CAS 2240981-78-4). In some cases, exemplary SHP2 inhibitors for use in the methods provided herein are 3-[(1R)-1-amino-8-azaspiro[4.5]decane-8-yl]-6-(2,3-dichlorophenyl)-5-hydroxy-2-pyridinemethanol (CAS 2238840-54-3), 3-[(1R)-1-amino-8-azaspiro[4.5]decane-8-yl]-6-[(2,3-dichlorophenyl [(Nyl)thio]-5-hydroxy-2-pyridinemethanol (CAS 2238840-56-5), 5-[(1R)-1-amino-8-azaspiro[4.5]deca-8-yl]-2-(2,3-dichlorophenyl)-3-pyridinol (CAS 2238840-58-7), 3-[(1R)-1-amino-8-azaspiro[4.5]deca-8-yl]-6-(2,3-dichlorophenyl)-5-methyl-2-pyridine Methanol (CAS 2238840-60-1), (1R)-8-[6-(2,3-dichlorophenyl)-5-methyl-3-pyridinyl]-8-azaspiro[4.5]decane-1-amine (CAS 2238840-62-3), 3-[(1R)-1-amino-8-azaspiro[4.5]deca-8-yl]-6-[(2,3-dichlorophenyl)thio]-5-methyl-2-pyridinemethanol (CAS 2238840 -63-4), (1R)-8-[6-[(2,3-dichlorophenyl)thio]-5-methyl-3-pyridinyl]-8-azaspiro[4.5]decane-1-amine (CAS2238840-64-5), 5-(4-amino-4-methyl-1-piperidinyl)-2-[(2,3-dichlorophenyl)thio]-3-pyridinol (CAS2238840-65-6), 5-[(1R)-1-amino-8-azaspiro[4.5]deca-8-yl]-2-[(2,3-dichlorophenyl)thio]-3-pyridinol (CAS 2238840-66-7), 6-[(2-amino-3-chloro-4-pyridinyl)thio]-3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-5-hydroxy-2-pyridinemethanol (CAS 2238840-67-8), 3-(4-amino-4-methyl-1-piperidinyl)-6-(2,3-dichlorophenyl)-5-hydro Xy-2-pyridinemethanol (CAS 2238840-68-9), 3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-6-(2,3-dichlorophenyl)-5-methyl-2-pyridinemethanol (CAS 2238840-69-0), 6-[(2-amino-3-chloro-4-pyridinyl)thio]-3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-5-methyl-2- Pyridinemethanol (CAS 2238840-70-3), 3-(4-amino-4-methyl-1-piperidinyl)-6-(2,3-dichlorophenyl)-5-methyl-2-pyridinemethanol (CAS 2238840-71-4), 6-[(2-amino-3-chloro-4-pyridinyl)thio]-3-(4-amino-4-methyl-1-piperidinyl)-2-pyridinemethanol (CAS 2238840-72-5), 5-[(2-amino-3-chloro-4-pyridinyl)thio]-2-[(3S ,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-6-methyl-3-pyridinemethanol (CAS 2238840-73-6), 2-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]deca-8-yl]-5-(2,3-dichlorophenyl)-6-methyl-3-pyridinemethanol (CAS 2238840-74-7), 3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.Examples include, but are not limited to, 5]deca-8-yl]-6-(2,3-dichlorophenyl)-5-hydroxy-2-pyridinemethanol (CAS 2238840-75-8) and 2-[(2-amino-3-chloro-4-pyridyl)sulfanyl]-5-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-6-(hydroxymethyl)pyridine-3-ol. In some cases, the SHP inhibitor used in the methods provided herein is 3-[(1R)-1-amino-8-azaspiro[4.5]deca-8-yl]-6-[(2,3-dichlorophenyl)thio]-5-hydroxy-2-pyridinemethanol (CAS 2238840-56-5). In some cases, the SHP2 inhibitors for use in the methods provided herein are those disclosed in U.S. Patent No. 10,590,090B2, U.S. Patent Application Publication No. 2020 / 017517A1, U.S. Patent Application Publication No. 2020 / 017511A1, International Publication No. 2019 / 075265A1, or International Publication No. 2021 / 142026, each of which is incorporated herein by reference in its entirety.

[0174] SOS1 inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of an SOS1 inhibitor in any of the methods described herein. Exemplary SOS1 inhibitors for use in the methods provided herein include, but are not limited to, BI 3406 (N-[(1R)-1-[3-amino-5-(trifluoromethyl)phenyl]ethyl]-7-methoxy-2-methyl-6-[(3S)-oxolan-3-yl]oxyquinazoline-4-amine), BI 1701963, AST-NS2102, MRTX-0902 ((R)-2-methyl-3-(1-((4-methyl-7-morpholinopyrid[3,4-d]pyridazin-1-yl)amino)ethyl)benzonitrile), ERAS-9, RMC-5845, HM-99462, and GH-52.

[0175] Src kinase inhibitors. In some cases, the compounds of this disclosure may be administered simultaneously, separately, or sequentially with an effective amount of a Src kinase inhibitor in any of the methods described herein. The term "Src kinase," as used herein, refers to members of the mammalian nonreceptor tyrosine kinase family, including Src, Yes, Fyn, and Fgr (SrcA subfamily); Lck, Hck, Blk, and Lyn (SrcB subfamily), and the Frk subfamily. The term "Src kinase inhibitor," as used herein, refers to compounds that can negatively modulate or inhibit all or part of the enzymatic activity of one or more members of Src kinase. Examples of Src kinase inhibitors used in the methods provided herein include, but are not limited to, dasatinib, ponatinib, vandetanib, bosutinib, salakatinib, KX2-391 (N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridine-2-yl)acetamide), SU6656 ((Z)-N,N-dimethyl-2-oxo-3-((4,5,6,7-tetrahydro-1H-indole-2-yl)methylene)indoline-5-sulfonamide), PP 1(1-(tert-butyl)-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine), WH-4-023(2,6-dimethylphenyl(2,4-dimethoxyphenyl)(2-((4-(4-methylpiperazine-1-yl)phenyl)amino)pyrimidine-4-yl)carbamate), and KX-01(N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridine-2-yl)acetamide). In some cases, the Src kinase inhibitor is dasatinib. In some cases, the Src kinase inhibitor is salakatinib. In some cases, the Src kinase inhibitor is ponatinib. In some cases, the Src kinase inhibitor is vandetanib. In some cases, the Src kinase inhibitor is KX-01.

[0176] Chemotherapy agents. In some cases, the compounds of this disclosure may be administered in an effective amount of one or more chemotherapeutic agents simultaneously, separately, or sequentially in any of the methods described herein. Examples of chemotherapeutic agents used in the methods provided herein include, but are not limited to, leucovorin calcium (calcium folate), 5-fluorouracil, irinotecan, oxaliplatin, cisplatin, carboplatin, pemetrexed, docetaxel, paclitaxel, gemcitabine, vinorelbine, chlorambucil, cyclophosphamide, and methotrexate.

[0177] Definitions and general terms The following definitions are provided to facilitate understanding of the scope of this disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs.

[0178] Unless otherwise indicated, all figures used in this specification or in the claims, representing quantities of components, reaction conditions, etc., should be understood in all cases to be modified by the term “approximately.” Therefore, unless otherwise indicated, the numerical parameters shown in the following specification and the appended claims are approximations that may vary depending on the standard deviation observed in their respective test measurements.

[0179] As used herein, if any variable element appears multiple times in a chemical formula, its definition in each appearance is independent of its definition in any other appearance.

[0180] This section defines additional terms used to describe the compounds, compositions, and scope of use disclosed herein.

[0181] For the purposes of this disclosure, chemical elements are identified in accordance with the CAS Periodic Table of the Elements (CAS version) and Handbook of Chemistry and Physics, 75th Ed. Furthermore, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and March's Advanced Organic Chemistry, 5th Ed., Ed.: Smith, MB and March, J., John Wiley & Sons, New York: 2001 (their entire contents are incorporated herein by reference).

[0182] As described herein, the compounds described herein are optionally substituted with one or more substituents, as generally exemplified below, or as exemplified by the specific classes, subclasses, and species described herein. It will be recognized that the phrase “optionally substituted” is used interchangeably with the phrases “substituted or unsubstituted” and “unsubstituted or substituted.” In general, the term “substituted,” whether preceded by the term “optionally,” means replacing one or more hydrogen radicals in a given structure with radicals of a particular substituent. Unless otherwise indicated, an optionally substituted group may have substituents at each of its substitutable positions. If two or more positions in a given structure can be substituted with two or more substituents selected from a particular group, the substituents may be the same or different at each position. When the term “optionally substituted” precedes a list, the term refers to all subsequent substitutable groups in that list. If a substituent group or structure is not identified or defined as “optionally substituted,” the substituent group or structure is unsubstituted. In some cases, each substituent is independently deuterium, halo, oxo, carboxyl, CHO, NH2, amide, NO2, ester, thioester, C 0~3 Alkylene CN, C 1~6 Alkyl, C 1~6Haloalkyl, C 0~6 Alkylene-OH, C 0~3 Alkylene-C 1~4 Alkoxy, C 0~3 Alkylene-C 1~4 Haloalkoxy, C 0~3 Alkylene-C 1~4 Thioalkoxy, C 0~6 Alkylene-C 1~3 Alkoxy, deuterated C 0~6 Alkylene-OC 1~3 Alkoxy, amide, and C with 3 to 7 total ring atoms 0~2 Alkylene-cycloalkyl, C with 5-7 total ring atoms 0~2 Alkylene-cycloalkenyl, having 3 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S. 0~2 Alkylene-heterocycloalkyl, having 3 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S. 0~2 Alkylene-heterocycloalkenyl, and C 0~2 Alkylene-C 6~10 It is Ariel.

[0183] The compounds disclosed herein may be “deuterated” in which one or more hydrogen atoms (CH) bonded to a carbon atom are replaced by deuterium to form a carbon-deuterium bond (CD). In some cases, the compounds disclosed herein are deuterated by one deuterium atom. In some cases, the compounds disclosed herein are deuterated by two or three deuterium atoms. In some cases, the compounds disclosed herein are deuterated by four or more deuterium atoms. In some cases, each hydrogen atom of the CH bond within a particular functional group is replaced by deuterium. In some cases, the entire compound is deuterated.

[0184] The selection of substituents and substituent combinations contemplated herein results in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, means a compound that remains substantially unchanged when subjected to conditions that enable their generation, detection, specifically their recovery, purification, and use for one or more purposes disclosed herein. In some cases, a stable or chemically feasible compound is one that remains substantially unchanged when maintained at a temperature of 40°C or below for at least one week in the absence of moisture or other chemically reactive conditions. Only the selection and combination of substituents that result in stable structures are contemplated. Such selections and combinations are obvious to those skilled in the art and can be determined without excessive experimentation.

[0185] The term "halo" or "halogen" refers to fluoro(-F), chloro(-Cl), bromo(-Br), and / or iodine(-I).

[0186] The term "oxo" refers to a substituted oxygen atom connected to another atom by a double bond (e.g., =O). In some cases, a single R group can be an oxo group (e.g., R 7 But, hello, C 1~3 (If alkyl or oxo). In some cases, two geminal R groups, together with the atom to which they are bonded, can form an oxo group. Therefore, the phrase "two geminal R groups, together with the atom to which they are bonded, can form an oxo group" results in an O group bonded to a single atom.

[0187] The term "carbonyl" is, [ka] This refers to divalent C=O groups such as those mentioned above.

[0188] The term "heteroatom" refers to an atom that is neither carbon nor hydrogen, unless otherwise specified herein. Examples of heteroatoms include oxygen, sulfur, nitrogen, and phosphorus.

[0189] The term "ether" refers to an oxygen atom (ROR) bonded to two alkyl or aryl groups. The term "ether bridge" refers to an ether group that forms a bridge on a ring, and the bridge has the indicated number of carbon atoms. For example, a C1 ether bridge on a cyclohexylene ring ( [ka] ) is, for example, [ka] It can be described as follows.

[0190] The term "thioether" refers to a sulfur atom (RSR) bonded to two alkyl or aryl groups. The term "thioether bridge" refers to a thioether group that forms a bridge on a ring, and the bridge has the indicated number of carbon atoms. For example, a C1 thioether bridge on a cyclohexylene ring ( [ka] ) is, for example, [ka] It can be described as follows.

[0191] The term "geminal" refers to two atoms, a functional group, and / or substituents bonded to the same atom. Geminal R groups on chains and rings are: each, [ka] It can be described as follows.

[0192] The terms "vicinal" and "adjacent" are interchangeable and refer to two atoms, functional groups, and / or substituents bonded to adjacent atoms on a chain or ring. A vicinal or adjacent R group on a chain or ring is, respectively, [ka] It can be described as follows.

[0193] The terms “non-adjacent” or “non-adjacent” are interchangeable and refer to two atoms, functional groups, and / or substituents bonded to atoms on a chain or ring that are not adjacent to each other (e.g., not adjacent and not geminal). Non-adjacent or non-adjacent R groups on a chain and ring are, respectively, [ka] It can be described as follows.

[0194] The term "alkyl" refers to a saturated linear or saturated branched hydrocarbon containing the specified number of carbon atoms. For example, C3 alkyl means that the alkyl group has three carbon atoms. 1~6 Alkyl refers to an alkyl group having a number of carbon atoms that encompasses the entire range (e.g., 1, 2, 3, 4, 5, or 6 carbon atoms) and all subgroups (e.g., 1-2, 1-3, 1-4, 1-5, 1-6, 2-3, 2-4, 2-5, 2-6, 3-4, 3-5, 3-6, 4-5, 4-6, and 5-6 carbon atoms). Non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, and hexyl.

[0195] The term "alkylene" refers to a divalent saturated aliphatic radical containing the specified number of carbon atoms. For example, C3 alkylene means that the alkylene group has three carbon atoms. 1~6 Alkylene refers to an alkylene group having a number of carbon atoms that encompasses the entire range (e.g., 1, 2, 3, 4, 5, or 6 carbon atoms) and all subgroups (e.g., 1-2, 1-3, 1-4, 1-5, 1-6, 2-3, 2-4, 2-5, 2-6, 3-4, 3-5, 3-6, 4-5, 4-6, and 5-6 carbon atoms). When the number of carbon atoms in an alkylene group is indicated as "C0", there is no alkylene group, and the listed substituents are directly bonded to the rest of the compound. For example, C 0~6The term alkylene-OH refers to a compound in which the OH group is directly or C 1~6 This demonstrates that linkage can occur via alkylene linkers. Examples of alkylene groups include methylene (-CH2-), ethylene (-CH2CH2-), n-propylene (-CH2CH2CH2-), isopropylene (-CH(CH3)CH2-), 1-butylene (-CH2CH2CH2CH2-), 1-methylbutylene (-CH(CH3)CH2CH2-), 2-methylbutylene (-CH2CH(CH3)CH2-), and 3-methylbutylene (-CH2CH2CH2(CH3)-).

[0196] The term "alkylene bridge" refers to an alkylene group that forms a bridge on a ring having the specified number of carbon atoms. For example, a C1 alkylene bridge on a cyclohexylene ring ( [ka] ) is, for example, [ka] It can be described as: C2 alkylene bridge on a cyclohexylene ring ( [ka] ) is, for example, [ka] It can be described as: C3 alkylene bridge on the cyclohexylene ring ( [ka] ) is, for example, [ka] It can be described as follows.

[0197] The term "haloalkyl" refers to an alkyl group, as previously defined herein, in which one or more hydrogen atoms are replaced by a halogen. The halogen is independently selected in each occurrence. This term includes, for example, monohaloalkyls (e.g., CH2F, CH(CH2F)CH3), dihaloalkyls (e.g., CHF2, CH(CHF2)CH3), trihaloalkyls (e.g., CF3, CH(CF3)CH3), and polyhaloalkyls (e.g., CF(CF3)CH3). The term further includes totally fluorine-substituted alkyl groups such as CF3 and CF2CF3. For example, "C 1~4 The term "haloalkyl" is defined herein as C, where one or more hydrogen atoms are substituted with halogens. 1~4 Refers to alkyl. 1~4 Representative examples of haloalkyls include, but are not limited to, CH2F, CHF2, CF3, CHFCl, CH2CF3, CFHCF3, CF2CF3, CH(CF3)2, CF(CHF2)2, CH(CH2F)(CF3), CH2Cl, CHCl2, CCl3, CHFCl, CH2CCl3, CClHCCl3, CCl2CCl3, CH(CCl3)2, CCl(CHCl2)2, CH(CH2Cl)CCl3, and CH2CF(CH3)2.

[0198] The term "alkenyl" refers to a straight-chain or branched-chain hydrocarbon containing the specified number of carbon atoms and one or more double bonds. For example, C3 alkenyl means that the alkenyl group has three carbon atoms. 2~6 An alkenyl refers to an alkenyl group having a number of carbon atoms that encompasses the entire range (e.g., 2, 3, 4, 5, or 6 carbon atoms) and all subgroups (e.g., 2-3, 2-4, 2-5, 2-6, 3-4, 3-5, 3-6, 4-5, 4-6, and 5-6 carbon atoms). Non-restrictive examples of alkenyl groups include ethenyl(vinyl), 1-propenyl, 2-propenyl(allyl), isopropenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, and 5-hexenyl.

[0199] The term "alkynyl" refers to a straight-chain or branched-chain hydrocarbon containing the indicated number of carbon atoms and one or more triple bonds. For example, C3 alkynyl means that the alkynyl group has three carbon atoms. 2~6 Alkynyl refers to an alkynyl group having a number of carbon atoms that encompasses the entire range (e.g., 2, 3, 4, 5, and 6 carbon atoms) and all subgroups (e.g., 2-3, 2-4, 2-5, 2-6, 3-4, 3-5, 3-6, 4-5, 4-6, and 5-6 carbon atoms). Non-restrictive examples of alkynyl groups include ethynyl, 1-propynyl, 2-propynyl, butynyl (e.g., 1-butynyl, 2-butynyl, 3-butynyl), 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, and 5-hexynyl.

[0200] The term "hydroxy" or "hydroxyl" refers to the alcohol group (-OH).

[0201] The term "alkoxy" or "alkoxyl" refers to an alkyl group as previously defined herein, having the indicated number of carbon atoms bonded to a molecule via an oxygen atom (e.g., (-O-alkyl). For example, a C3 alkoxy group means that the alkoxy group has three carbon atoms (e.g., OCH2CH2CH3). 1~6 An alkoxy refers to an alkoxy group having a number of carbon atoms that encompasses the entire range (e.g., 2, 3, 4, 5, or 6 carbon atoms) and all subgroups (e.g., 2-3, 2-4, 2-5, 2-6, 3-4, 3-5, 3-6, 4-5, 4-6, and 5-6 carbon atoms). Non-restrictive examples of alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, and butoxy.

[0202] The terms "thioalkyl" and "thioalkoxy" are interchangeable and refer to alkyl groups (e.g., -S-alkyl) as defined herein, which are bonded to a molecule via a sulfur atom. For example, a C3 thioalkyl group or a C3 thioalkoxy group means that the thioalkyl or thioalkoxy group has three carbon atoms (e.g., SCH2CH2CH3). 1~6 Thioalkyl or C 1~6 A thioalkoxy refers to a thioalkyl or thioalkoxy group having a number of carbon atoms that encompasses the entire range (e.g., 2, 3, 4, 5, or 6 carbon atoms) and all subgroups (e.g., 2-3, 2-4, 2-5, 2-6, 3-4, 3-5, 3-6, 4-5, 4-6, and 5-6 carbon atoms). Non-limiting examples of thioalkyl / thioalkoxy groups include thiomethoxy, thioethoxy, thiopropoxy, thioisopropoxy, and butoxy. Additional examples of thioalkyl / thioalkoxy groups include methylthiyl, ethylthiyl, n-propylthiyl, isopropylthiyl, n-butylthiyl, isobutylthiyl, sec-butylthiyl, and -butylthiyl.

[0203] The terms “haloalkoxy” and “haloalkoxyl” are interchangeable and refer to an alkoxyl group as previously defined herein, in which one or more hydrogen atoms are replaced by halogens. The halogens are independently selected in each occurrence. This term includes monohaloalkoxys (e.g., OCH2F, OCH(CH2F)CH3), dihaloalkoxys (e.g., OCHF2, OCH(CHF2)CH3), trihaloalkoxys (e.g., OCF3, OCH(CF3)CH3), and polyhaloalkoxys (e.g., OCF(CF3)CH3). This term includes perfluorinated alkyl groups such as OCF3 and OCF2CF3. 1~4 Typical examples of haloalkoxys include, but are not limited to, OCH2F, OCHF2, OCF3, OCHFCl, OCH2CF3, OCFHCF3, OCF2CF3, OCH(CF3)2, OCF(CHF2)2, and OCH(CH2F)(CF3). 1~4Additional examples of haloalkoxys include OCH2Cl, OCHCl2, OCF3, OCHFCl, OCH2CCl3, OCClHCCl3, OCCl2CCl3, OCH(CCl3)2, OCCl(CHCl2)2, OCH(CH2Cl)CCl3, and OCH2CF(CH3)2.

[0204] The term "carbocyclic" or "carbocyclic" refers to a ring (saturated, unsaturated, or aromatic) that contains only carbon atoms. Non-exclusive examples of carbocyclic compounds include cyclopropyl, cyclobutyl, cyclopentyl, 2,3-dihydroindene, bicyclo[2.2.2]octanyl, adamantyl, spiro[4.4]nonanyl, and naphthalenyl.

[0205] The term "cycloalkyl" refers to an aliphatic cyclic hydrocarbon group that contains the number of carbon atoms indicated within its ring. For example, C5 cycloalkyl refers to a cycloalkyl group that has five carbon atoms in its ring. 3~7 A cycloalkyl group refers to a cycloalkyl group having a number of carbon atoms that encompasses the entire range (e.g., 3, 4, 5, 6, and 7 carbon atoms in the ring) and all subgroups (e.g., 3-4, 3-5, 3-6, 3-7, 4-5, 4-6, 4-7, 5-6, 5-7, and 6-7 carbon atoms in the ring). x~y The terms "cycloalkyl" and "cycloalkyl group having X to Y total ring atoms" are interchangeable. Non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "spiro-cycloalkyl" refers to a cycloalkyl group previously defined herein that is bonded to the compound via one common atom. For example, a methylpiperidine ring having a spiro-cyclopropyl group as a substituent is, [ka] It can be described as follows. The terms “condensed cycloalkyl ring” or “condensed-cycloalkyl” are interchangeable and refer to a cycloalkyl group as defined herein, which shares two adjacent atoms with the compound to which it is bonded (i.e., one covalent bond). For example, a methylpiperidine ring having a condensed cyclopropyl group as a substituent is [ka] It can be described as follows.

[0206] The term "cycloalkenyl" refers to a cyclic hydrocarbon group that contains the number of carbon atoms and one or more double bonds shown within its ring. For example, C5 cycloalkenyl refers to a cycloalkenyl group that has five carbon atoms in its ring. 5~7 A cycloalkenyl refers to a cycloalkenyl group having a number of carbon atoms that encompasses the entire range (e.g., 5, 6, and 7 carbon atoms in the ring) and all subgroups (e.g., 5-6, 5-7, and 6-7 carbon atoms in the ring). x~y The terms "cycloalkenyl" and "cycloalkenyl group having X to Y total ring atoms" are interchangeable. Non-limiting examples of cycloalkyl groups include cyclopentenyl and cyclohexenyl. The term "spiro-cycloalkenyl" refers to a cycloalkenyl group, as defined herein, bonded to a compound via one common atom. For example, a methylpiperidine ring having a spiro-cyclopentenyl group as a substituent is [ka] It can be described as follows. The terms “condensed cycloalkenyl ring” or “condensed-cycloalkenyl” are interchangeable and refer to a cycloalkenyl group as defined herein, which shares two adjacent atoms with the compound to which it is bonded (i.e., one covalent bond). For example, a methylpiperidine ring having a condensed cyclopentenyl group as a substituent is, [ka] It can be described as follows.

[0207] The term "heterocycloalkyl" refers to a saturated ring containing carbon atoms and one or more heteroatoms (e.g., N, O, and / or S), having the indicated number of total ring atoms (the sum of carbon atoms and heteroatoms in the ring). For example, a heterocycloalkyl group having 5 total atoms and 2 heteroatoms selected from N and S refers to a ring having 3 carbon atoms and 2 heteroatoms (where each heteroatom in the ring is independently N or S). As another example, a heterocycloalkyl group having 5 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S refers to a ring having a total number of ring atoms encompassing the indicated range (e.g., 5, 6, or 7 total atoms) and all subgroups (e.g., 5 to 6 or 6 to 7 total ring atoms) (where 1, 2, or 3 atoms in the ring are heteroatoms, and each heteroatom is independently selected from N, O, and S). Therefore, heterocycloalkyls having 5 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S include, for example, rings containing 4 carbon atoms and 1 heteroatom, 3 carbon atoms and 2 heteroatoms, 2 carbon atoms and 3 heteroatoms, 5 carbon atoms and 1 heteroatom, 4 carbon atoms and 2 heteroatoms, 3 carbon atoms and 3 heteroatoms, 6 carbon atoms and 1 heteroatom, 5 carbon atoms and 2 heteroatoms, and 4 carbon atoms and 3 heteroatoms, where each of the above heteroatoms is independently selected from N, O, and S. Non-exclusive examples of heterocycloalkyl groups include, but are not limited to, azilidinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, azepanyl, diazepanyl, triazepanyl, oxazepanyl, azokanyl, diazokanyl, triazokanyl, oxazokanyl, thiazepanyl, and thiazokanyl. The term “spiro-heterocycloalkyl” refers to a heterocycloalkyl group, as previously defined herein, bonded to a compound via a common atom.For example, methylpiperidine having a spiro-oxetanyl group as a substituent is... [ka] It can be described as follows. The term “condensed-heterocycloalkyl” refers to a heterocycloalkyl group as defined herein that shares two adjacent atoms (i.e., one covalent bond) with the compound to which it is bonded. For example, a methylpiperidine ring having a condensed-azetidinyl group as a substituent is [ka] It can be described as follows.

[0208] The term "heterocycloalkenyl" is defined similarly to "heterocycloalkyl," except that the ring contains one or more carbon-carbon double bonds. For example, a heterocycloalkenyl group having 5 total atoms and 2 heteroatoms selected from N and S refers to a ring having at least one double bond, 3 carbon atoms and 2 heteroatoms, where each heteroatom in the ring is independently N or S. As another example, a heterocycloalkenyl group having 5 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S refers to a ring having at least one double bond and a total number of ring atoms encompassing the indicated range (e.g., 5, 6, or 7 total atoms) and all subgroups (e.g., 5 to 6 or 6 to 7 total ring atoms) (where 1, 2, or 3 atoms in the ring are heteroatoms, and each heteroatom is independently selected from N, O, and S). Therefore, heterocycloalkenyls having 5 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S include at least one double bone and rings containing, for example, 4 carbon atoms and 1 heteroatom, 3 carbon atoms and 2 heteroatoms, 2 carbon atoms and 3 heteroatoms, 5 carbon atoms and 1 heteroatom, 4 carbon atoms and 2 heteroatoms, 3 carbon atoms and 3 heteroatoms, 6 carbon atoms and 1 heteroatom, 5 carbon atoms and 2 heteroatoms, and 4 carbon atoms and 3 heteroatoms (where each of the above heteroatoms is independently selected from N, O, and S). Non-limiting examples of heterocycloalkenyl groups include, but are not limited to, dihydropyrrolyl, dihydrofuranyl, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridyl, dihydropyranyl, and dihydrothiopyranyl. The term “spiro-heterocycloalkenyl” refers to a heterocycloalkenyl group, as defined herein, bonded to a compound via a common atom. For example, a methylpiperidine ring having a spirodihydropyrrolyl group as a substituent is [ka] It can be described as follows. The term “condensed-heterocycloalkenyl” refers to a heterocycloalkenyl group, as defined herein, that shares two adjacent atoms (i.e., one covalent bond) with the compound to which it is bonded. For example, a methylpiperidine ring having a condensed-dihydrofuranyl group as a substituent is [ka] It can be described as follows.

[0209] The term "aryl" refers to an aromatic carbon ring having the specified number of carbon ring atoms. For example, C6 aryl refers to an aryl group (e.g., phenyl) having 6 carbon atoms in the ring. 10 The term "aryl" refers to an aryl group having 10 carbon atoms in the ring (e.g., naphthyl). The aryl group can be isolated (e.g., phenyl) or fused to another aryl group (e.g., naphthyl or anthracenyl). The term "fused-aryl" refers to an aryl group, as defined herein, that shares two adjacent atoms (i.e., one covalent bond) with the compound to which it is bonded. For example, a methylpiperidine ring having a fused-phenyl group as a substituent is: [ka] It can be described as follows.

[0210] The term "heteroaryl" refers to an aromatic ring containing carbon and one or more heteroatoms, having the indicated number of total ring atoms (the sum of carbon atoms and heteroatoms in the ring). For example, a heteroaryl group having 5 total atoms and 2 heteroatoms selected from N and S refers to an aromatic ring having 3 carbon atoms and 2 heteroatoms, where each heteroatom in the ring is independently N or S. As another example, a heteroaryl having 5 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S refers to an aromatic ring having a total number of ring atoms encompassing the indicated range (e.g., 5, 6, or 7 total atoms) and all subgroups (e.g., 5 to 6 or 6 to 7 total ring atoms), where 1, 2, or 3 atoms in the ring are heteroatoms, each heteroatom independently selected from N, O, and S. Therefore, heteroaryls having 5 to 7 total ring atoms and 1 to 3 heteroatoms selected from N, O, and S include, for example, rings containing 4 carbon atoms and 1 heteroatom, 3 carbon atoms and 2 heteroatoms, 2 carbon atoms and 3 heteroatoms, 5 carbon atoms and 1 heteroatom, 4 carbon atoms and 2 heteroatoms, 3 carbon atoms and 3 heteroatoms, 6 carbon atoms and 1 heteroatom, 5 carbon atoms and 2 heteroatoms, and 4 carbon atoms and 3 heteroatoms, where each of the above heteroatoms is independently selected from N, O, and S.Non-exclusive examples of heteroaryl groups include furanil, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiadiazolyl, thiazolyl, thiophenyl, tetrazolyl, triazinyl, triazolyl, pyridyl, pyridadinyl, pyrazinyl, pyrimidinyl, benzofuranil, benzimidazolyl, benzoisoxazolyl, benzopyranil, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzothiophenyl, and Examples include, but are not limited to, ionzotriazolyl, benzoxazolyl, phlopyridyl, imidazopyridinyl, imidazothiazolyl, indolidinyl, indazolyl, isobenzofuranyl, isobenzothienyl, isoindolyl, isoquinolinyl, isothiazolyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl, pteridinyl, purinyl, pyridopyridyl, pyrrolopyridyl, quinolinyl, quinoxalinyl, quiazolinyl, thiadiazolopyrimidyl, and thienopyridyl. The term "condensed-heteroaryl" refers to a heteroaryl group, as defined herein, that shares two adjacent atoms (i.e., one covalent bond) with the compound to which it is bonded. For example, a methylpiperidine ring having a condensed-thiazolyl group as a substituent is... [ka] It can be described as follows.

[0211] The term "bicyclic ring" refers to a functional group containing two bonded rings. Unless otherwise specified, a bicyclic ring may be a spirocyclic ring in which two rings share a single atom (e.g., a quaternary carbon atom), a condensation in which two rings share two adjacent atoms (i.e., one covalent bond), or a bridge in which rings share three or more atoms and include a bridge having at least one atom.

[0212] As used herein, the terms “protecting group” and “protective group” are interchangeable and refer to agents used to temporarily block one or more desired functional groups in a compound having multiple reactive sites. In some cases, the protecting group has one or more, or specifically all, of the following characteristics: (a) it is selectively added to the functional group in good yield; (b) it provides a protecting group that is stable to reactions occurring at one or more other reactive sites; and (c) it is selectively removed in good yield by a reagent that does not attack the regenerated deprotected functional group. As will be understood by those skilled in the art, in some cases the reagent does not attack other reactive groups in the compound. In other cases the reagent may also react with other reactive groups in the compound. Examples of protecting groups are detailed in Greene, TW, Wuts, PG “Protective Groups in Organic Synthesis”, Third Edition, John Wiley & Sons, New York: 1999 (and other editions of the same book, such as Wuts, PGM and Greene, TW “Greene's Protective Groups in Organic Synthesis”, Fourth Edition, John Wiley & Sons, Hoboken: 2007) (the entire contents of each are incorporated herein by reference). As used herein, the term “nitrogen protecting group” refers to an agent used to temporarily block one or more desired nitrogen-reactive sites in a polyfunctional compound.Nitrogen protecting groups also possess the characteristics exemplified for the protecting groups described above, and specific exemplary nitrogen protecting groups are also described in detail in Chapter 7 of "Protective Groups in Organic Synthesis," Third Edition, John Wiley & Sons, New York: 1999 by Greene, TW, and Wuts, PG (and in other editions of the aforementioned book, such as Wuts, PGM and Greene, TW, "Greene's Protective Groups in Organic Synthesis," Fourth Edition, John Wiley & Sons, Hoboken: 2007) (the entire contents of each are incorporated herein by reference).

[0213] The terms "bond" and "absent" are used interchangeably to indicate the absence of a specified functional group.

[0214] As used herein, the term “pharmaceutically acceptable” generally refers to a composition or component of a composition that is safe, non-toxic, and not biologically or otherwise undesirable.

[0215] The term "pharmaceutically acceptable salt," as used herein, refers to a salt of a compound that is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound. Examples of such salts include: (1) acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; or acid addition salts formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, and methanesulfonic acid; or (2) salts formed when an acidic proton present in the parent compound is replaced with a metal ion, such as an alkali metal ion, an alkaline earth ion, or an aluminum ion; or salts formed when coordinated with an organic base such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, or dicyclohexylamine. Examples of such salt additions can be found in Berge et al., J. Pharm. Sci. 66(1):1-19 (1977). Stahl et al., Pharmaceutical Salts: Properties, Selection, and Use, 2 nd See also the Revised Edition (2011).

[0216] The term “pharmaceutically acceptable excipients,” as used herein, refers to a broad range of components that can be combined with the compounds or salts disclosed herein to prepare a pharmaceutical composition or formulation. Typically, excipients include, but are not limited to, diluents, colorants, vehicles, anti-tacks, flow enhancers, disintegrants, flavorings, coatings, binders, sweeteners, lubricants, adsorbents, and preservatives.

[0217] As used herein, the term "subject" refers to humans and animals, including but not limited to primates, cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In some cases, the subject is human.

[0218] The term "therapeutably effective amount," as used herein, means the amount of a compound disclosed herein that would elicit a biological or medical response to a tissue, system, or subject as sought by a researcher, veterinarian, physician, or other clinician.

[0219] The term "metastatic" refers to cancer that has spread from its original site to another part of the body. The term "non-metastatic" refers to cancer that has not spread from its original site to another part of the body.

[0220] As used herein, the terms “binding exchange assay” or “2-hour binding exchange assay” refer to the assays described in Section 3: Biochemical and Cellular Assays.

[0221] General synthesis procedure The compounds provided herein can be synthesized according to the procedures described in this section and the following sections. The synthetic methods described herein are illustrative only, and the compounds disclosed herein can also be synthesized by alternative routes using alternative synthetic strategies, as will be understood by those skilled in the art. The general synthetic procedures and specific examples provided herein are illustrative only and should not be construed as limiting the scope of this disclosure.

[0222] Generally, compounds of formulas (I) and (II) can be synthesized according to the following schemes. The variable elements used in the following schemes are those defined with respect to formulas (I) and (II), unless otherwise specified. All starting materials are commercially available from, for example, Merck Sigma-Aldrich Inc., Fluorochem Ltd., Enamine Ltd, Combi-Blocks, Astech, Oakwood, Thermal Fisher, LabNetwork, PharmBlock, BLD Pharm, Astatec, Inc., Apollo Scientific, AmBeed, Inc., eNovation Chemicals, and Aurum Pharmatech, or are known in the art and can be synthesized by using known procedures with ordinary skill. Starting materials can also be synthesized by procedures disclosed herein. Preferred reaction conditions (e.g., solvents, reaction temperatures, and reagents) for the schemes considered in this section can be found in the examples provided herein. The abbreviation PG refers to the protecting group as defined in the Definitions and General Terms section herein. In the following scheme, each PG may be the same as or different from another PG in the compound, as long as each protecting group can be selectively removed.

[0223] In general, compounds of formula (I) can be synthesized according to scheme 1A: Scheme 1A [ka]

[0224] The nitrogen-protected piperazine linker portion of formula (I): [ka] The desired nitrogen-protected 3-azetidinone can be synthesized by reacting the desired nitrogen-protected piperazine with a suitable reducing agent such as a borohydride reagent via a reductive amination reaction. The resulting nitrogen-protected piperazine linker moiety of formula (I) forms the desired halogenated pyrimidine or pyridine core: [ka] First, the nitrogen of azetidine is deprotected, and then a nucleophilic aromatic substitution reaction is carried out in the presence of a suitable base to protect the core-linker portion of formula (I). [ka] By forming this, coupling can be achieved.

[0225] Spirotail of equation (I) [ka] For example, it can be synthesized according to scheme A or scheme B. [ka]

[0226] In scheme A, a desired, optionally substituted, N-protected, piperidine-4-one compound: [ka] And the desired ZY-Z' compound undergoes a nucleophilic addition reaction, [ka] Each of the following can be formed, where Z is a functional group capable of nucleophilic addition of piperidine-4-one to the carbonyl (e.g., an alkyne in an alkynylation reaction or a halogen in a nucleophilic aromatic substitution reaction), Y is a precursor of the desired Y' spiro group, and Z' is a nucleophile that acts in the subsequent cyclization reaction (e.g., OH). In the next step, [ka] By subjecting it to cyclization and deprotection reactions, a spirotail (B) can be formed: [ka]

[0227] In scheme B, a boronic acid ester or acid derived from a substituted, N-protected piperidine-4-one compound (e.g., a piperidine-4-one compound derived from pinacolborane and N-protected) undergoes a Suzuki coupling reaction with the desired ZY-Z' group (where Z is a halogen or leaving group, Y is a precursor of the desired Y' spiro group, and Z' is a nucleophile (e.g., OH) that acts in the subsequent cyclization reaction). [ka] It is possible to form this. In the next step, [ka] Compound (B) undergoes iodine-mediated cyclization, reduction, and deprotection: [ka] This can form the desired substituents. If necessary, further reactions can be carried out to add the desired substituents to the spiro Y' group. The piperidine tail can be added to the core, for example, by carrying out a nucleophilic aromatic substitution reaction in the presence of a base (e.g., DIPEA). Alternatively, the CN bond can be formed, for example, by a palladium-catalyzed amination reaction. Finally, the Michael acceptor can be attached to the compound by deprotecting the nitrogen atom of the piperazine ring in the presence of an acid such as TFA, and reacting the deprotected piperazine ring with a desired halogenated α,β-unsaturated ketone such as acryloyl chloride to form the compound of formula (I).

[0228] Therefore, a method for preparing the compound of formula (I) and its pharmaceutically acceptable salt, wherein the compound of formula (B): [ka] The protected core-linker portion of equation (I): [ka] When mixed under conditions that form a carbon-nitrogen bond, an intermediate having the following structure is obtained: [ka] Methods comprising forming (wherein the formula, the variable elements are as previously defined herein) are further provided herein. In some cases, the carbon-nitrogen bond formation conditions involve carrying out a nucleophilic aromatic substitution reaction in the presence of a base such as a sterically hindered nitrogen base (e.g., DIPEA). In some cases, the carbon-nitrogen bond formation conditions involve a palladium-catalyzed amination reaction. In some cases, the method involves an intermediate: [ka] The piperazine is deprotected, and the resulting compound is [ka] (Here, the variable elements are as previously defined herein) and are mixed together in equation (I): [ka] of The specification further includes forming as previously described. In some cases, piperazine is deprotected under acidic conditions. In some cases, piperazine is deprotected in the presence of a strong acid such as trifluoroacetic acid (TFA). In some cases, the method is to prepare the compound of formula (B), where the compound: [ka] By making it a ring [ka] Form a compound, then deprotect the cyclized compound: [ka] The preparation further includes forming as described earlier in the specification. In some cases, the method is [ka] The process involves preparing, [ka] To couple ZY-Z' as previously described in the specification, and then the resulting [ka] The preparation further includes subjecting to a cyclization reaction. In some cases, the method is [ka] The process involves preparing, [ka] The following was coupled to ZY-Z' as previously described in the specification, and then the resulting [ka] The method further includes preparation by subjecting to a cyclization reaction. In some cases, Z is an alkyne and the coupling occurs by an alkynylation reaction. In some cases, Z is a halogen and Y is an aryl or heteroaryl group and the reaction is a nucleophilic aromatic substitution reaction. In some cases, the method involves the protected linker moiety of formula (I): [ka] The process involves preparing, [ka] Deprotect [ka] Forms a deprotected compound, [ka] The method further includes preparation by coupling in the presence of a suitable base via a nucleophilic aromatic substitution reaction. In some cases, the method involves the nitrogen-protected linker moiety of formula (I): [ka] The preparation involves further comprising mixing a desired nitrogen-protected 3-azetidinone with a desired nitrogen-protected piperazine in a reductive amination reaction in the presence of a suitable reducing agent such as a borohydride reagent.

[0229] The compound of formula (II) can be prepared in the same manner as the scheme and method described above for the compound of formula (I), as shown in scheme 1B: Scheme 1B [ka]

[0230] Therefore, a method for preparing the compound of formula (II) and its pharmaceutically acceptable salt, wherein the compound of formula (B'): [ka] The protected core-linker portion of equation (II): [ka] When mixed under conditions that form a carbon-nitrogen bond, an intermediate having the following structure is obtained: [ka] A method is further provided herein that includes forming (where the variable elements are as previously defined herein). A method for preparing a compound of formula (II) where q is 1 and r is 1, wherein the compound of formula (B): [ka] The protected core-linker portion of equation (II): [ka] When mixed under conditions that form a carbon-nitrogen bond, an intermediate having the following structure is obtained: [ka] Methods comprising forming (wherein the variable elements are as previously defined herein) are further provided herein. In some cases, the carbon-nitrogen bond formation conditions involve carrying out a nucleophilic aromatic substitution reaction in the presence of a base such as a sterically hindered nitrogen base (e.g., DIPEA). In some cases, the carbon-nitrogen bond formation conditions involve a palladium-catalyzed amination reaction. In some cases, the method involves the intermediate piperazine: [ka] Deprotect the compound, and the resulting compound [ka] (Here, the variable elements are as previously defined herein) are mixed with equation (II): [ka] The method further includes forming the as described earlier in the specification. In some cases, the piperazine is deprotected under acidic conditions. In some cases, the piperazine is deprotected in the presence of a strong acid such as trifluoroacetic acid (TFA). In some cases, the method further includes preparing the compound of formula (B') using the same method described for preparing the compound of formula (B). In some cases, the method includes forming the protected linker portion of formula (II): [ka] The process involves preparing, [ka] Deprotect [ka] Forms a deprotected compound, [ka] The method further includes preparation by coupling in the presence of a suitable base by a nucleophilic aromatic substitution reaction. In some cases, the method involves the nitrogen-protected linker moiety of formula (II): [ka] The preparation involves further comprising mixing a desired nitrogen-protected 3-azetidinone with a desired nitrogen-protected piperazine in a reductive amination reaction in the presence of a suitable reducing agent such as a borohydride reagent.

[0231] As will be understood by those skilled in the art, the above-described synthesis schemes and representative examples are not intended to be a comprehensive list of all means by which the compounds described and claimed in this application can be synthesized. Further methods will be obvious to those skilled in the art. In addition, the various synthesis steps described above can be carried out in alternative orders or sequences to obtain the desired compounds.

[0232] The methods for purifying the compounds described herein are known in the art and include, for example, crystallization, chromatography (e.g., liquid, gas, and supercritical fluid), extraction, distillation, polishing, and reverse-phase HPLC.

[0233] intermediate This disclosure further encompasses “intermediate” compounds, including structures generated from the described synthetic procedures before obtaining the final desired compound, whether isolated or generated in situ and not isolated. These intermediates are included within the scope of this disclosure.

[0234] Therefore, this disclosure relates to compounds of formula (B): [ka] The formula further provides nitrogen-protected analogues or pharmaceutically acceptable salts of any of the above (wherein, o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; Each R 6 , Haro, CN, C 1~3 Alkyl, C 2~3 Alkenil, C 1~3 Haloalkyl, C 0~3 Alkylene-OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3 Alkylene-C 1~3 Alkoxy, C 1~4 Alkylene-N(R) N1 )2, oxo, =CH2, C 3~7 Cycloalkyl, C 4~7 Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R 6 They combine together, C 1~3Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is alkylene CN; Each R 7 Independently, Halo, C 0~3 Alkylene-CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, oxo, =CH2, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkilen heteroaryl; Spiro-C 3~7 It is a cycloalkyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or it is a spiro-heterocycloalkyl having 2 vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensed heterocycloalkyl having 3-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S, condensed-C 6~10They form aryl or condensed heteroaryls having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 Alkyl and Each R N1 H or C 1~4 (It is alkyl.)

[0235] In some cases, the compound of formula (B) has a free base (for example, the nitrogen atom of piperidine is free): [ka] ) In some cases, the compound of formula (B) is a pharmaceutically acceptable salt (e.g., a TFA salt). In some cases, the compound of formula (B) is a nitrogen protecting group (PG): [ka] They are protected by (for example, a di-tert-butyldicarbonyl or "BOC" group). In some cases, the compound of formula (B) is selected from the compounds listed in Table E below, their free bases, their nitrogen-protected analogs, or any of the pharmaceutically acceptable salts described above.

[0236] [Table 46]

[0237] [Table 47]

[0238] [Table 48]

[0239] [Table 49]

[0240] [Table 50]

[0241] [Table 51]

[0242] In some cases, the compound of formula (B) is selected from intermediates B-1 to B-34, their free bases, their nitrogen-protected forms, or their pharmaceutically acceptable salts.

[0243] This disclosure relates to a piperazine linker intermediate having the following structure: [ka] The following further provides nitrogen- and / or oxygen-protected analogues thereof, or pharmaceutically acceptable salts of any of the above (where the variable elements are as previously described herein). In some cases, the piperazine linker intermediate is one of the compounds listed in Table F below, one of the nitrogen- and / or oxygen-protected analogues thereof, or a pharmaceutically acceptable salt of any of the above. In some cases, the nitrogen protecting group is BOC or Bn.

[0244] [Table 52]

[0245] [Table 53]

[0246] [Table 54]

[0247] [Table 55]

[0248] [Table 56]

[0249] [Table 57]

[0250] In some cases, the piperazine linker intermediate is selected from compounds D-1 to D-10-1, their nitrogen- and / or oxygen-protected analogues, their nitrogen- and / or oxygen-deprotected analogues, or any pharmaceutically acceptable salt of the above.

[0251] This disclosure relates to an intermediate having the following structure: [ka] The following further provides nitrogen- and / or oxygen-protected analogues thereof, or pharmaceutically acceptable salts of any of the above (where the variable elements are as previously described herein). In some cases, the piperazine linker intermediate is one of the compounds listed in Table G below, a nitrogen- and / or oxygen-protected analogue thereof, or a pharmaceutically acceptable salt of any of the above.

[0252] [Table 58]

[0253] [Table 59]

[0254] [Table 60]

[0255] [Table 61]

[0256] [Table 62]

[0257] [Table 63]

[0258] In some cases, the intermediate is selected from compound E-1 to E-8-1, its nitrogen- and / or oxygen-protected analogues, its nitrogen- and / or oxygen-deprotected analogues, or any pharmaceutically acceptable salt of the above.

[0259] This disclosure relates to intermediates 3-001.1, 3-001.2, 3-002.1, 3-002.2, 3-003.1, 3-003.2, 3-020.1, 3-020.2, 3-021.1, 3-021.2, 3-046.1, 3-046.2, 3-050.1, 3-050.2, 3-051.1, 3-051.2, 3-051.3, 3-051.4, 3-051.5, 3-052.1, described in Section 2: Synthesis of Example Compounds. 3-052.2, 3-052.3, 3-052.4, 3-052.5, 3-053.1, 3-053.2, 3-053.3, 3-053.4, 3-053.5, 3-054-1, 3-054-2, 3-055.1, 3-055.2, 3-055.3, 3-055.4, 3-055.5, 3-057.1, 3-057.2, 3-057.3, 3-058.1, 3-058.2-1, 3-058.2.2, 3-058.3, 3-0 59.1, 3-060.1, 3-060.2, 3-060.3, 3-060.4, 3-060.5, 3-060.6, 3-060.7, 3-060.8, 3-060.9, 3-061.1, 3-061.2, 3-061.3, 3-061.4, 3-061.5, 3-062.1-1, 3-062.1-2, 3-062.1-1, 3-062.2, 3-063.1, 3-063.2, 3-065.1, 3-065.2, 3-0 Further details are provided for 65.3, 3-065.4, 3-065.5, 3-067-1, 3-067-2, 3-069.1, 3-069.2, 3-073.1, 3-073.2, 3-073.3, 3-073.4, 3-073.5, 3-074.1, 3-074.2, 3-074.3, 3-074.4, 3-075.1, 3-075.2, 3-075.3, 3-076.1, and 3-076.2, as well as their pharmaceutically acceptable salts.

[0260] Another aspect of this disclosure is a process for preparing compounds or salts described herein (compounds of formula (I), formula (IA), formula (IB), formula (II), formula (IIA), formula (IIB), formula (IIC), compounds listed in Table A, compounds listed in Table B, compounds listed in Table C, or compounds listed in Table D, or any pharmaceutically acceptable salt thereof), wherein the intermediates described herein include, for example, the intermediate of formula (B), or the intermediates listed in Tables E, F, G, 3-001.1, 3-001.2, 3-0 02.1, 3-002.2, 3-003.1, 3-003.2, 3-020.1, 3-020.2, 3-021.1, 3-021.2, 3-046.1, 3.046.2, 3-050.1, 3-050.2, 3-051.1, 3-051.2, 3-051.3, 3-051.4, 3-051.5, 3-052.1, 3-052.2, 3-052.3, 3-052.4, 3-052.5, 3-053.1, 3-053.2, 3-053.3, 3-053.4, 3-053.5, 3-054-1, 3-054-2, 3-055.1, 3-055.2, 3-055.3, 3-055.4, 3-055.5, 3-057.1, 3-057.2, 3-057.3, 3-058.1, 3-058.2-1, 3-058.2.2, 3-058.3, 3-059.1, 3-060.1, 3-060.2, 3-060.3, 3-060.4, 3-060.5, 3-060.6, 3-060.7, 3-060.8, 3-060.9, 3-061.1, 3-061.2, 3-061.3, 3-061.4, 3-061.5, 3-062.1-1 3-062.1-2, 3-062.1-1, 3-062.2, 3-063.1, 3-063.2, 3-065.1, 3-065.2, 3-065.3, 3-065.4, 3-065.5, 3-067-1, 3-067-2, 3-069.1, 3-069.2, 3-073.1, 3-073.2, 3-073.3, 3-073.4, 3-073.5, 3-074.1, 3-074.2, 3-074.3, 3-074.4, 3-075.1, 3-075.2, 3-075.3, 3-076.1, and 3-076.The process involves converting an intermediate selected from the group consisting of 2, any protected analog of the above, or any pharmaceutically acceptable salt of the above, into a compound disclosed herein.

[0261] Further embodiments Embodiment B1 is a compound of formula (II): [ka] Or a pharmaceutically acceptable salt thereof is provided herein. (In the formula, m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; q is 0, 1, or 2; r is either 0 or 1; A stands for N, CH, C-Hello, C-CN, CC. 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy; W 1 and W 2 Each of these is independently N, CH, C-HALO, C-CN, CC 1~3 Alkyl, CC 2~3 Alkenil, CC 2~3 Alkinil, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy, where each of the alkenyl and alkynyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently a halo, C 1~3 Haloalkyl, C 0~3 Alkylene OH, or C 0~3 Alkilen C 1~4 It is an alkoxy; X is N or CR5a and; Y' is C 3~7 Cycloalkyl, C 4~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; R 1a , R 1b , and R 2 Each of these is independently H, D, Halo, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, C 0~2 Alkylene-N(R) N1 )C having 2, 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. 1~2 It is either alkylene-heterocycloalkyl, or R 1b and R 2 Along with the carbon atoms to which they are bonded, [ka] form; Each R 3 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, [ka] , C 0~3 Alkylene CN, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7A cycloalkenyl, a spiro-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 3 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R A1 and R A2 Each of these is independently H, C 1~3 Alkyl, C 1~3 Haloalkyl, or C 3~5 It is a cycloalkyl; Each R 4 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~3 Alkylene CN, C 1~3 Alkylene OH, C 1~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 A cycloalkyl or spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R 5a H, CN, Haro, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, or C 3~5 It is a cycloalkyl; R 5b Hello, C 1~3 Haloalkyl, C1~6 Alkyl, C 2~4 Alkenil, C 2~4 Alkinyl, C 1~3 Alkoxy, C 1~3 Thioalkyl, C 3~7 Cycloalkyl, C 5~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or R 5a and R 5b C 3~7 Forms a cycloalkyl group; Here, C 1~6 Alkyl, C 2~4 Alkenil, C 2~4 Alkinyl, C 3~7 Cycloalkyl, C 5~7 Each of the cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl compounds is independently unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently C 1~3 Haloalkyl, C 0~6 Alkylene-OH, C 0~6 Alkylene-C 1~3 Alkoxy, C 3~7 Cycloalkyl, C 5~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a phenyl; Each R 6 They are independently: Hello, CN, C 1~3 Alkyl, C 2~3 Alkenil, C 1~3 Haloalkyl, C 0~3 Alkylene-OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3 Alkylene-C 1~3 Alkoxy, C 1~4Alkylene-N(R) N1 )2, oxo, =CH2, C 3~7 Cycloalkyl, C 4~7 Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is alkylene CN; Each R 7 Independently, Halo, C 0~3Alkylene-CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, oxo, =CH2, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkilen heteroaryl; Spiro-C 3~7 It is a cycloalkyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or it is a spiro-heterocycloalkyl having 2 vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensed heterocycloalkyl having 3-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S, condensed-C 6~10 A condensed heteroaryl is formed having an aryl, or 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; where each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 Alkyl and Each R N1 H or C 1~4 (It is alkyl.)

[0262] As Embodiment B2, R 1a , R 1b , and R 2Compounds or salts of Embodiment B1 are provided herein, wherein at least one of them is H or D.

[0263] As embodiment B3, R 1a , R 1b , and R 2 Compounds or salts of Embodiment B1 or B2 are provided herein, each of which is independently H or D.

[0264] Embodiment B4 is R 1a , R 1b , and R 2 At least one of them is Halo, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, C 0~2 Alkylene-N(R) N1 )C having 2, 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. 1~2 It is either alkylene-heterocycloalkyl, or R 1b and R 2 However, along with the carbon atoms to which they are bonded, [ka] Forms (where each R N1 Compounds or salts of Embodiment B1 or B2 (wherein H or CH3 are independently provided herein).

[0265] Embodiment B5 is R 1a , R 1b , and R 2Compounds or salts of Embodiment B4 are provided herein, wherein at least one of the following is Br, Cl, F, CH3, CH2F, CHF2, CF3, CH2OH, OCH3, CH2OCH3, OCF3, CH2OCF3, CN, CH2CN, NH2, N(CH3)2, CH2NH2, CH2N(CH3)2, aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl.

[0266] Embodiment B6, [ka] but [ka] Compounds or salts of Embodiment B1 or B2 are provided herein.

[0267] Embodiment B7 is, [ka] but [ka] Compounds or salts of Embodiment B6 are provided herein.

[0268] Embodiment B8, [ka] but [ka] A compound or salt of Embodiment B7 is provided herein.

[0269] As Embodiment B9, a compound or salt from any one of Embodiments B1 to B8 is provided herein, wherein m is 0 or 1.

[0270] As Embodiment B10, a compound or salt from any one of Embodiments B1 to 8 is provided herein, wherein m is 2, 3, or 4.

[0271] Embodiment B11 includes at least one R 3 However, C 1~3 Alkyl or C 1~3 A compound or salt from any one of embodiments B1 to B10, which is a haloalkyl compound, is provided herein.

[0272] Embodiment B12 includes at least one R 3 However, compounds or salts of Embodiment B11, which are CH3, CH2CH3, CF3, CHF2, or CH2F, are provided herein.

[0273] Embodiment B13 includes at least one R 3 but, [ka] , C 0~3 Alkylene CN, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 A cycloalkyl, a spiro-heterocycloalkyl, or spiro-C having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. 4~7 A cycloalkenyl, a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; two vicinal R 3 However, along with the atoms to which they are bonded, condensation -C 3~7 Cycloalkyl, condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, condensed-C 4~7 Forming a cycloalkenyl, or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; where R A1 and R A2The following compounds or salts from any one of Embodiments B1 to 10 are provided herein, each of which is independently H, CH3, CH2F, CHF2, CF3, CH2CH3, CH2CH2CH3, CH(CH3)2, cyclopropyl, or cyclobutyl.

[0274] Embodiment B14 includes at least one R 3 but, [ka] ,CN,CH2CN,OH,CH2OH,CH2CH2OH,OCH3,CH2OCH3,CH2CH2OCH3,oxo,spiro-cyclopropyl,spiro-cyclobutyl,spiro-oxetanyl,spiro-tetrahydrofuranil, or two vicinal R 3 However, the compounds or salts of Embodiment B13 are provided herein, which, together with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl.

[0275] Embodiment B15, each R 3 However, independently, CH3, CH2CH3, CF3, CHF2, CH2F, [ka] ,CN,CH2CN,OH,CH2OH,CH2CH2OH,OCH3,CH2OCH3,CH2CH2OCH3,oxo,spiro-cyclopropyl,spiro-cyclobutyl,spiro-oxetanyl, or spiro-tetrahydrofuranyl; or two vicinal R 3 However, the following compounds or salts of any one of Embodiments B1 to 10 are provided herein, which, together with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl.

[0276] Embodiment B16 is such that m is 0; or m is 1, R 3The following compounds or salts of any one of Embodiments B1 to 8 are provided herein, wherein the compound is CH3, CH2F, CHF2, CF3, CN, CH2CN, CH2OH, CH2OCH3, or spiro-oxetanyl.

[0277] Embodiment B17 is such that m is 0; or m is 1, R 3 Compounds or salts of Embodiment B16, wherein CH3 is provided herein.

[0278] Embodiment B18, [ka] but [ka] One compound or salt from any of embodiments B1 to B8 is provided herein.

[0279] Embodiment B19 is, [ka] but [ka] A compound or salt of Embodiment B18 is provided herein.

[0280] As Embodiment B20, one compound or salt from any of Embodiments B1 to B19 is provided herein, wherein A is N.

[0281] Embodiment B21 is defined as CH, C-halo, C-CN, CC 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 One compound or salt from any of embodiments B1 to B19, which is an alkoxy, is provided herein.

[0282] As Embodiment B22, the compounds or salts of Embodiment B21 are provided herein, wherein A is CH, CF, C-Cl, C-CN, C-CH3, C-CH2F, C-CHF2, C-CF3, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3.

[0283] As Embodiment B23, one compound or salt from any of Embodiments B1 to B22 is provided herein, wherein n is 0 or 1.

[0284] Embodiment B24 includes at least one R 4 However, C 1~3 Alkyl or C 1~3 A compound or salt from any one of embodiments B1 to 23, which is a haloalkyl compound, is provided herein.

[0285] Embodiment B25 includes at least one R 4 However, compounds or salts of Embodiment B24 are provided herein, which are CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, or CF3.

[0286] Embodiment B26 includes at least one R 4 However, C 0~3 Alkylene CN, C 1~3 Alkylene OH, C 1~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 The following compounds or salts of any one of Embodiments B1 to 23 are provided herein, which are cycloalkyl or spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S.

[0287] Embodiment B27 includes at least one R 4 Compounds or salts of Embodiment B26 are provided herein, wherein the compound is CN, CH2CN, CH2OH, CH2CH2OH, CH2OCH3, CH2CH2OCH3, oxo, spiro-cyclopropyl, spiro-cyclobutyl, or spiro-oxetanyl.

[0288] Embodiment B28, each R 4 However, the following compounds or salts of any one of Embodiments B1 to 23 are provided herein, independently of CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, CH2F, CN, CH2CN, CH2OH, CH2CH2OH, CH2OCH3, CH2CH2OCH3, oxo, spiro-cyclopropyl, spiro-cyclobutyl, or spiro-oxetanyl.

[0289] Embodiment B29 is, [ka] but [ka] A compound or salt of Embodiment B28 is provided herein.

[0290] Embodiment B30 is, [ka] but [ka] Compounds or salts of Embodiment B29 are provided herein.

[0291] Embodiment B31 is W 1 The following compounds or salts of any one of Embodiments B1 to 30 are provided herein, wherein the compound is N, CH, CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2F, C-CHF2, C-CF3, C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), or C-CCH, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3.

[0292] As embodiment B32, W 1 Compounds or salts of Embodiment B31, wherein CH is provided herein.

[0293] Embodiment B33 is W 2 , N, CH, CF, C-Cl, C-CN, C-CH 3、 A compound or salt from any one of Embodiments B1 to 32 is provided herein, which is C-CH2CH3, C-CH2F, C-CHF2, C-CF3, C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), or C-CCH, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3.

[0294] Embodiment B34 is W 2 Compounds or salts of Embodiment B33, wherein N is provided herein.

[0295] Embodiment B35 is W 1 CH is W 2 A compound or salt from any one of the embodiments B1 to 30 is provided herein, wherein is N.

[0296] As Embodiment B36, one compound or salt from any of Embodiments B1 to B35 is provided herein, wherein X is N.

[0297] Embodiment B37 is CR 5a And R 5a But H, CN, Br, Cl, F, CH3, CH2CH3, CF3, CHF2, CH2F, [ka] OH, CH2OH, OCH3, CH2OCH3, or [ka] One of the compounds or salts from Embodiments B1 to 35 is provided herein.

[0298] Embodiment B38 is R 5a However, compounds or salts of Embodiment B37, which are CN or CH3, are provided herein.

[0299] As Embodiment B39, a compound or salt from any one of Embodiments B1 to B35 is provided herein, wherein X is N, C-CH3, or C-CN.

[0300] Embodiment B40 is W 1 CH is; W 2 A compound or salt from any one of the embodiments B1 to 30 is provided herein, wherein is N; and X is N, C-CH3, or C-CN.

[0301] Embodiment B42 is R 5b is Br, Cl, F, CF3, CF2H, CFH2, CF2CH3, OCH3, SCH3CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, [ka] One of the compounds or salts of Embodiments B1 to 40 is provided herein.

[0302] Embodiment B42 is R 5b However, compounds or salts of Embodiment B41, which are CF3 or CF2H, are provided herein.

[0303] Embodiment B43 is, [ka] but [ka] And X is N, C-CH3, or C-CN; R b However, one compound or salt of any of embodiments B1 to 30, which is CF3 or CF2H, is provided herein.

[0304] Embodiment B44 is, [ka] but, [ka] [ka] [ka] One of the compounds or salts of Embodiments B1 to 30 is provided herein.

[0305] Embodiment B45 is, [ka] but [ka] Compounds or salts of Embodiment B44 are provided herein.

[0306] As Embodiment B46, one compound or salt from any of Embodiments B1 to B45 is provided herein, wherein q is 0.

[0307] As Embodiment B47, one compound or salt from any of Embodiments B1 to B45 is provided herein, wherein q is 1.

[0308] As Embodiment B48, one compound or salt from any of Embodiments B1 to B45 is provided herein, wherein q is 2.

[0309] As Embodiment B49, one compound or salt from any of Embodiments B1 to B45 is provided herein, wherein r is 0.

[0310] As Embodiment B50, one compound or salt from any of Embodiments B1 to B45 is provided herein, wherein r is 1.

[0311] Embodiment B51 is: [ka] but [ka] One of the compounds or salts from Embodiments B1 to 45 is provided herein.

[0312] As Embodiment B52, one compound from any of Embodiments B1 to B51 is provided herein, wherein o is 0, 1, or 2.

[0313] As Embodiment B53, one compound from any of Embodiments B1 to B51 is provided herein, wherein o is 3 or 4.

[0314] Embodiment B54 includes at least one R 6 However, is Br, Cl, F, CN, CH3, CH2F, CHF2, CF3, OH, CH2OH, OCH3, OCD3, CH2OCH3, CH2N(CH3)2, oxo, =CH2, cyclopropyl, cyclobutyl, oxetanyl, tetrahydrofuranyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranyl; or two vicinal R 6 However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl; or two adjacent R 6 These are bonded together to form -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2-CH=CH- or -CH2OCH2-; where each of cyclopropyl, cyclobutyl, oxetanyl, tetrahydrofuranyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, spiro-tetrahydrofuranyl, condensed-cyclopropyl, condensed-cyclobutyl, and condensed-cyclopentyl is independently unsubstituted or substituted with 1 to 4 substituents, and each substituent is independently halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2One of the compounds from Embodiments B1 to 53, which is alkylene CN, is provided herein.

[0315] As Embodiment B55, the compounds or salts of Embodiment B54 are provided herein, wherein each substituent is independently F, Cl, OH, OCH3, OCH2CH3, or CN.

[0316] Embodiment B56 includes at least one R 6 However, it is either Br, Cl, F, CN, CH3, CH2F, CHF2, CF3, OH, CH2OH, OCH3, OCD3, CH2OCH3, CH2N(CH3)2, oxo, =CH2, cyclopropyl, or two vicinal R 6 However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl, or two adjacent R 6 The compounds or salts of 54 or 55 are provided herein, wherein each of the cycloalkyl groups is either unsubstituted or substituted with 1 to 4 substituents, each substituent independently being F, Cl, OH, OCH3, OCH2CH3, or CN.

[0317] Embodiment B57 is such that o is 0; or o is 1, R 6 However, it is either H, CH3, CH2OH, or two non-adjacent R 6 The following compounds or salts from any one of Embodiments B1 to 51 are provided herein, wherein the two groups combine to form -CH2CH2-.

[0318] Embodiment B58 is: [ka] but [ka] One of the compounds or salts from Embodiments B1 to B51 is provided herein.

[0319] Embodiment B59 is, [ka] but [ka] but [ka] A compound or salt of Embodiment B58 is provided herein.

[0320] Embodiment B60 is a compound of formula (IIA), formula (IIB), or formula (IIC): [ka] Alternatively, one compound or salt of any of the above embodiments B1 to 30 is provided herein.

[0321] Embodiment B61 is provided herein, which is any one compound or salt from Embodiments B1 to 60, wherein Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azilidinyl, oxyranil, thyranil, azetidinil, oxetanil, thietanil, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydrothiophenyl, dioxolanil, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranil, dioxanil, tetrahydrothiopyranil, dithianil, morpholinil, thiomorpholinil, dihydropyrrolyl, dihydrofuranil, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridinyl, dihydropyranil, or dihydrochipyranil.

[0322] As Embodiment B62, compounds or salts of Embodiment B61 are provided herein, wherein Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, oxetanyl, pyrrolidinyl, tetrahydrofuranil, dioxolanil, oxazolidinyl, isoxazolidinyl, tetrahydropyranil, dihydropyrrolyl, dihydrofuranil, or dihydropyranil.

[0323] As Embodiment B63, a compound or salt from any one of Embodiments B1 to B62 is provided herein, wherein p is 0 or 1.

[0324] As Embodiment B64, a compound or salt from any one of Embodiments B1 to B62 is provided herein, wherein p is 2, 3, or 4.

[0325] Embodiment B65, each R 7 However, independently, F, Cl, Br, CN, CH2CN, CH3, CH2CH3, CH2F, CHF2, CF3, OH, OCH3, OCH2CH3, CH2OH, CH2OCH3, CH2CH2OCH3, C(=O)OCH3, oxo, =CH2, cyclopropyl, [ka] , oxetanyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, spiro-tetrahydrofuranil, spiro-tetrahydropyranil; or two vicinal R 7 However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-cyclobutyl, condensed-oxetanyl, condensed-tetrahydrofuranyl, condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, condensed-pyridyl, condensed-pyridazinyl, condensed-pyridazinyl, and condensed-pyrimidinyl; where each of phenyl, pyrazolyl, pyridyl, pyridazinyl, and pyrimidinyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent independently forms halo, CN, oxo, or C 1~3 One of the compounds or salts from Embodiments B1 to 64, which is alkyl, is provided herein.

[0326] Embodiment B66, each R 7 However, independently, F, Cl, Br, CN, CH3, CH2CH3, CH2F, OH, CH2OH, CH2OCH3, CH2CH2OCH3, oxo, =CH2, [ka] , oxetanyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or two vicinal R 7 However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, and condensed-pyridyl; where each of phenyl, pyrazolyl, and pyridyl is unsubstituted or substituted with CH3, compounds or salts of Embodiment B65 are provided herein.

[0327] Embodiment B67 is, [ka] but [ka] [ka] [ka] [ka] One of the compounds or salts from Embodiments B1 to B59 is provided herein.

[0328] Embodiment B68 is, [ka] but [ka] [ka] [ka] One of the compounds or salts from Embodiments B1 to B59 is provided herein.

[0329] Embodiment B69 is, [ka] but [ka] Compounds or salts of Embodiment B68 are provided herein.

[0330] Embodiment B70 is, [ka] but [ka] and; [ka] but [ka] and; [ka] but [ka] and; [ka] but [ka] A compound or salt of Embodiment B1 is provided herein.

[0331] Embodiment B71, [ka] but [ka] A compound of Embodiment B70 is provided.

[0332] Embodiment B72, [ka] but [ka] Compounds or salts of Embodiment B70 or B71 are provided herein.

[0333] Embodiment B73 is such that q is 1; r is 1; W 1 However, CH, C-Haro, C-CN, CC 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy; W 2 X is N and X is N or CR 5a One of the compounds or salts of Embodiments B1 to 30 is provided herein.

[0334] As Embodiment B74, the compounds of Embodiment B1 are provided herein, which are the compounds listed in Table A, or pharmaceutically acceptable salts thereof.

[0335] Embodiment B75 is provided herein, which is the compound of Embodiment B1, or a pharmaceutically acceptable salt thereof, as listed in Table C.

[0336] Embodiment B76 is provided herein, which comprises a pharmaceutical composition comprising one compound or salt from any of Embodiments B1 to B75 and a pharmaceutically acceptable excipient.

[0337] Embodiment B77 is provided herein as a method for treating a target cancer requiring treatment, comprising administering to the target a therapeutically effective amount of any one compound or salt from Embodiments B1 to B76 or a composition of Embodiment B77.

[0338] Embodiment B78 is provided herein, which is the method of Embodiment B77, wherein one or more cancer cells express the KRAS G12C mutant protein.

[0339] Embodiment B79 provides herein the method of Embodiment B77 or B78, wherein the cancer is non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed-type cancer of unknown primary origin, pancreatic cancer, hepatobiliary tract cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, solid tumor, or any combination thereof.

[0340] Embodiment B80 is provided herein, wherein the method of Embodiment B79 is characterized in that the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, or a solid tumor.

[0341] Embodiment B81 is provided herein, which is a method according to any one of Embodiments B77 to B80, wherein the subject has cancer in which it has been confirmed that one or more cells expressing the KRAS G12C mutant protein are present prior to administration of the compound, salt, or pharmaceutical composition.

[0342] Embodiment B82 further comprises simultaneous, separate, or sequential administration of an effective amount of a second compound, wherein the second compound is an ATR inhibitor, an Aurora kinase A inhibitor, an AKT inhibitor, an arginase inhibitor, a CDK2 inhibitor, a CDK4 / 6 inhibitor, an ErbB family inhibitor, an ERK inhibitor, a FAK inhibitor, a FGFR inhibitor, a glutaminase inhibitor, an IGF-1R inhibitor, a KIF18A inhibitor, a MAT2A inhibitor, a MCL-1 inhibitor, a MEK inhibitor, an mTOR inhibitor, a PARP inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PI3K inhibitor, a PRMT5 inhibitor, a Raf kinase inhibitor, a SHP2 inhibitor, a SOS1 inhibitor, a Src kinase inhibitor, or one or more chemotherapeutic agents, and is provided herein according to any one of Embodiments B77 to B81.

[0343] Embodiment B83 is provided herein, which includes any one compound or salt from Embodiments B1 to B75 or a composition from Embodiment B76 for use as a pharmaceutical.

[0344] Embodiment B84 is provided herein, which includes any one compound or salt from Embodiments B1 to B75 or a composition from Embodiment B76 for use in the treatment of cancer.

[0345] Embodiment B85 provides herein a compound or salt from any one of Embodiments B1 to B75 or a pharmaceutical composition from Embodiment B76 for use in the treatment of cancer in which one or more cancer cells express the KRAS G12C mutant protein.

[0346] Embodiment B86 provides herein a compound or salt of Embodiment B84 or B85, wherein the cancer is non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed-type cancer of unknown primary origin, pancreatic cancer, hepatobiliary cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, or solid tumor.

[0347] Embodiment B87 provides herein a compound or salt of Embodiment B86, wherein the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, or a solid tumor.

[0348] Embodiment B88 provides herein the use of any one compound or salt from Embodiments B1 to B75 or the pharmaceutical composition of Embodiment B76 for the manufacture of a pharmaceutical for the treatment of cancer.

[0349] Embodiment B89 provides herein the use of any one compound or salt from Embodiments B1 to B75 or the pharmaceutical composition of Embodiment B76 in the preparation of a pharmaceutical for treating cancer in which one or more cancer cells express the KRASG12C mutant protein.

[0350] Embodiment B90 provides herein the use of Embodiment 88 or B89, wherein the cancer is non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed-type cancer of unknown primary origin, pancreatic cancer, hepatobiliary tract cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, solid tumor, or any combination thereof.

[0351] Embodiment B90 is provided herein, in which Embodiment B91, the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, or a solid tumor.

[0352] Embodiment B92 is a compound of formula (B): [ka] Alternatively, nitrogen-protected analogs or pharmaceutically acceptable salts of any of the above are provided herein (wherein, o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; Each R 6 , Haro, CN, C 1~3 Alkyl, C 2~3 Alkenil, C1~3 Haloalkyl, C 0~3 Alkylene-OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3 Alkylene-C 1~3 Alkoxy, C 1~4 Alkylene-N(R) N1 )2, oxo, =CH2, C 3~7 Cycloalkyl, C 4~7 Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, and each substituent independently forms a halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is alkylene CN; Each R 7 Independently, Halo, C 0~3 Alkylene-CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, oxo, =CH2, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkilen heteroaryl; Spiro-C 3~7 It is a cycloalkyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or it is a spiro-heterocycloalkyl having 2 vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensed heterocycloalkyl having 3-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S, condensed-C 6~10 A condensed heteroaryl is formed having an aryl, or 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; where each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 Alkyl and Each R N1 H or C 1~4 (It is alkyl.)

[0353] Embodiment B93 provides a method for preparing one of the compounds or salts from Embodiments B1 to 75, comprising converting the compound of Embodiment B92, any of the above protected analogues, or any of the above pharmaceutically acceptable salts to one of the compounds from Embodiments B1 to 75.

[0354] Additional Embodiments Embodiment A1 includes a compound of formula (II): [ka] Or a pharmaceutically acceptable salt thereof is provided herein. (In the formula, m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; q is 0, 1, or 2; r is either 0 or 1; A stands for N, CH, C-Hello, C-CN, CC. 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy; W 1 and W 2 Each of these is independently N, CH, C-HALO, C-CN, CC 1~3 Alkyl, CC 2~3 Alkenil, CC 2~3 Alkinil, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 It is an alkoxy, where each of the alkenyl and alkynyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently a halo, C 1~3 Haloalkyl, C 0~3Alkylene OH, or C 0~3 Alkilen C 1~4 It is an alkoxy; X is N or CR 5a and; Y' is C 3~7 Cycloalkyl, C 4~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; R 1a , R 1b , and R 2 Each of these is independently H, D, Halo, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, C 0~2 Alkylene-N(R) N1 )C having 2, 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. 1~2 It is either alkylene-heterocycloalkyl, or R 1b and R 2 Along with the carbon atoms to which they are bonded, [ka] form; Each R 3 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, [ka] , C 0~3 Alkylene CN, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 3 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R A1 and R A2 Each of these is independently H, C 1~3 Alkyl, C 1~3 Haloalkyl, or C 3~5 It is a cycloalkyl; Each R 4 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~3 Alkylene CN, C 1~3 Alkylene OH, C 1~3 Alkylene-C 1~3 Alkoxy, oxo, spiro-C 3~7 A cycloalkyl or spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R 5a H, CN, Haro, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, or C 3~5 It is a cycloalkyl; R5b Hello, C 1~3 Haloalkyl, C 1~6 Alkyl, C 2~4 Alkenil, C 2~4 Alkinyl, C 1~3 Alkoxy, C 1~3 Thioalkyl, C 3~7 Cycloalkyl, C 5~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or R 5a and R 5b C 3~7 Forms a cycloalkyl group; Here, C 1~6 Alkyl, C 2~4 Alkenil, C 2~4 Alkinyl, C 3~7 Cycloalkyl, C 5~7 Each of the cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl compounds is independently unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently C 1~3 Haloalkyl, C 0~6 Alkylene-OH, C 0~6 Alkylene-C 1~3 Alkoxy, C 3~7 Cycloalkyl, C 5~7 A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a phenyl; Each R 6 They are independently: Hello, CN, C 1~3 Alkyl, C 2~3 Alkenil, C 1~3 Haloalkyl, C 0~3 Alkylene-OH, C 0~3 Alkylene-C 1~3 Alkoxy, deuterated C 0~3Alkylene-C 1~3 Alkoxy, C 1~4 Alkylene-N(R) N1 )2, oxo, =CH2, C 3~7 Cycloalkyl, C 4~7 Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C 3~7 Cycloalkyl, Spiro-C 4~7 A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R 6 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensation-C 4~7 Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R 6 They combine together, C 1~3 Alkylene crosslinking, C 2~3 Alkenylene bridge, C 1~3 Ether crosslinking, or C 1~3 A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C 1~3 Alkyl, C 1~3 Haloalkyl, C 0~2 Alkylene OH, C 0~2 Alkilen C 1~3 Alkoxy, or C 0~2 It is alkylene CN; Each R7 Independently, Halo, C 0~3 Alkylene-CN, C 1~3 Alkyl, C 1~3 Haloalkyl, C 2~3 Alkenil, C 0~3 Alkylene OH, C 0~3 Alkylene-C 1~3 Alkoxy, C(=O)OC 1~3 Alkyl, oxo, =CH2, C 0~4 Alkylene-C 3~7 Cycloalkyl, C having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkylene-heterocycloalkyl; C 0~4 Alkylene-C 6~10 C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. 0~4 Alkilen heteroaryl; Spiro-C 3~7 It is a cycloalkyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or it is a spiro-heterocycloalkyl having 2 vicinal R 7 These atoms, along with the atoms to which they are bonded, undergo condensation -C 3~7 Cycloalkyl, condensed heterocycloalkyl having 3-7 total ring atoms and 1-3 heteroatoms independently selected from N, O, and S, condensed-C 6~10 A condensed heteroaryl is formed having an aryl, or 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; where each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C 1~3 Alkyl and Each R N1 H or C 1~4 (It is alkyl.)

[0355] As Embodiment A2, R 1a , R 1b , and R 2Compounds or salts of Embodiment A1 are provided herein, wherein at least one of them is H or D.

[0356] As Embodiment A3, R 1a , R 1b , and R 2 Compounds or salts of Embodiment A2 are provided herein, each of which is independently H or D.

[0357] Embodiment A4 is R 1a , R 1b , and R 2 Compounds or salts of Embodiment A3 are provided herein, wherein each of the elements is H.

[0358] As Embodiment A5, R 1a , R 1b , and R 2 Compounds or salts of Embodiment A3 are provided herein, each of which is D.

[0359] Embodiment A6 is R 1a , R 1b , and R 2 Compounds or salts of Embodiment A1 or A2 are provided herein, wherein at least one of them is a halo.

[0360] As Embodiment A7, R 1a That is Haro, R 1b and R 2 Compounds or salts of Embodiment A6 are provided herein, wherein each of the elements is H.

[0361] As Embodiment A8, compounds or salts of Embodiment A6 or A7 are provided herein, wherein each halo is independently Br, Cl, or F.

[0362] Embodiment A9 is R 1a , R 1b , and R 2 At least one of them is C 1~4 Alkyl or C 1~4Compounds or salts of Embodiment A1 or A2 that are haloalkyl are provided herein.

[0363] Embodiment A10 is R 1a , R 1b , and R 2 Compounds or salts of Embodiment A9 are provided herein, wherein at least one of them is CH3, CH2F, CHF2, or CF3.

[0364] Embodiment A11 is R 1a , R 1b , and R 2 At least one of them is C 1~2 Alkylene-OH, C 0~2 Alkylene-C 1~4 Alkoxy, C 0~2 Alkylene-C 1~4 Haloalkoxy, C 0~2 Alkylene-CN, or C 0~2 Alkylene-N(R) N1 Compounds or salts of Embodiment A1 or A2, which are )2, are provided herein.

[0365] Embodiment A12, each R N1 However, compounds or salts of Embodiment A11, which are independently H or CH3, are provided herein.

[0366] Embodiment A13, each R N1 Compounds or salts of Embodiment A12, wherein is H, are provided herein.

[0367] Embodiment A14 is R 1a , R 1b , and R 2 Compounds or salts of Embodiment A11 or A12 are provided herein, wherein at least one of the is CH2OH, OCH3, CH2OCH3, OCF3, CH2OCF3, CN, CH2CN, NH2, N(CH3)2, CH2NH2, or CH2N(CH3)2.

[0368] Embodiment A15 is R 1a , R1b , and R 2 At least one of them is a carbon atom having 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S. 1~2 Compounds or salts of Embodiment A1 or A2, which are alkylene-heterocycloalkyl, are provided herein.

[0369] Embodiment A16 provides herein a compound or salt of Embodiment A15 in which the heterocycloalkyl is azilidinyl, azetidinyl, pyrrolidinyl, piperidinyl, or morpholinyl.

[0370] Embodiment A17 is R 1a , R 1b , and R 2 Compounds or salts of Embodiment A15 or A17 are provided herein, wherein at least one of the is aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl.

[0371] Embodiment A18 is R 1b and R 2 However, along with the carbon atoms to which they are bonded, [ka] Compounds or salts of Embodiment A1 or A2 that form are provided herein.

[0372] Embodiment A19 is, [ka] but [ka] Compounds or salts of Embodiment A1 or A2 are provided herein.

[0373] Embodiment A20 is, [ka] but [ka] Compounds or salts of Embodiment A19 are provided herein.

[0374] Embodiment A21 is, [ka] but [ka] Compounds or salts of Embodiment A20 are provided herein.

[0375] As Embodiment A22, one compound or salt from any one of Embodiments A1 to A21 is provided herein, wherein m is 0.

[0376] As Embodiment A23, one compound or salt from any one of Embodiments A1 to A21 is provided herein, wherein m is 1.

[0377] As Embodiment A24, one compound or salt from any one of Embodiments A1 to A21 is provided herein, wherein m is 2.

[0378] As Embodiment A25, one compound or salt from any of Embodiments A1 to A21 is provided herein, wherein m is 3.

[0379] As Embodiment A26, one compound or salt from any of Embodiments A1 to A21 is provided herein, wherein m is 4.

[0380] Embodiment A27 is: [ka] A compound or salt from any one of embodiments A23 to A26, wherein the compound is deuterated, is provided herein.

[0381] Embodiment A28 is: [ka] but [ka] Compounds or salts of Embodiment A27 are provided herein.

[0382] Embodiment A29 includes at least one R 3 However, C 1~3 Alkyl or C 1~3 A compound or salt from any one of embodiments A23 to A26, which is a haloalkyl compound, is provided herein.

[0383] Embodiment A30 includes at least one R 3 However, compounds or salts of Embodiment A29, which are CH3, CH2CH3, CF3, CHF2, or CH2F, are provided herein.

[0384] Embodiment A31 includes at least one R 3 Compounds or salts of Embodiment A30, wherein the compound is CH3, are provided herein.

[0385] Embodiment A32 includes at least one R 3 but, [ka] One compound or salt from any of embodiments A23 to A26 is provided herein.

[0386] Embodiment A33 is R A1 and R A2 Compounds or salts of Embodiment A32 are provided herein, each of which is independently H, CH3, CH2F, CHF2, CF3, CH2CH3, CH2CH2CH3, CH(CH3)2, cyclopropyl, or cyclobutyl.

[0387] Embodiment A34 includes at least one R 3 but [ka] Compounds or salts of Embodiment A32 or A33 are provided herein.

[0388] Embodiment A35 includes at least one R 3 C 0~3 A compound or salt of any one of embodiments A23 to A26, which is alkylene CN, is provided herein.

[0389] Embodiment A36 includes at least one R 3 However, compounds or salts of Embodiment A35, which are CN or CH2CN, are provided herein.

[0390] Embodiment A37 includes at least one R 3 However, C 0~3 Alkylene OH or C 0~3 Alkylene-C 1~3 One compound or salt of any of embodiments A23 to A26, which is an alkoxy, is provided herein.

[0391] Embodiment A38 includes at least one R 3 The compounds or salts of Embodiment A37, wherein the compounds are OH, CH2OH, CH2CH2OH, OCH3, CH2OCH3, or CH2CH2OCH3, are provided herein.

[0392] Embodiment A39 includes at least one R 3 A compound or salt from any one of embodiments A23 to A26 is provided herein, wherein the compound is an oxo.

[0393] Embodiment A40 includes at least one R 3 However, Spiro-C 3~7A compound or salt of any one of embodiments A23 to A26 is provided herein, which is a cycloalkyl or a spiro-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S.

[0394] Embodiment A41 includes at least one R 3 The compounds or salts of Embodiment A40, which are spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanil, or spiro-tetrahydrofuranil, are provided herein.

[0395] Embodiment A42 includes at least one R 3 However, Spiro-C 4~7 The following compounds or salts of any one of embodiments A23 to A26 are provided herein, which are cycloalkenyls or spiro-heterocycloalkenyls having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S.

[0396] Embodiment A43 includes two vicinal R 3 However, along with the atoms to which they are bonded, condensation -C 3~7 The following compounds or salts of any one of embodiments A24 to A26 are provided herein, which form a cycloalkyl or a condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S.

[0397] Embodiment A44 includes two vicinal R 3 However, compounds or salts of Embodiment A43 are provided herein, which, together with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl.

[0398] Embodiment A45 includes two vicinal R 3 However, along with the atoms to which they are bonded, condensation -C 4~7The following compounds or salts of any one of embodiments A24 to A26 are provided herein, which form a cycloalkenyl or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S.

[0399] Embodiment A46, each R 3 However, independently, CH3, CH2CH3, CF3, CHF2, CH2F, [ka] ,CN,CH2CN,OH,CH2OH,CH2CH2OH,OCH3,CH2OCH3,CH2CH2OCH3,oxo,spiro-cyclopropyl,spiro-cyclobutyl,spiro-oxetanyl, or spiro-tetrahydrofuranyl; or two vicinal R 3 However, the following compounds or salts of any one of Embodiments A23 to A26 are provided herein, which, together with the atoms to which they are bonded, form condensed-cyclopropyl or condensed-cyclobutyl.

[0400] Embodiment A47 is such that m is 0; or m is 1, R 3 The following compounds or salts of any one of Embodiments A1 to A21 are provided herein, wherein the compound is CH3, CH2F, CHF2, CF3, CN, CH2CN, CH2OH, CH2OCH3, or spiro-oxetanyl.

[0401] Embodiment A48 is such that m is 0; or m is 1, R 3 Compounds or salts of Embodiment A47, wherein CH3 is provided herein.

[0402] Embodiment A49 is: [ka] but [ka] One compound or salt from any of embodiments A1 to A21 is provided herein.

[0403] Embodiment A50 is, [ka] but [ka] Compounds or salts of Embodiment A49 are provided herein.

[0404] Embodiment A51 is, [ka] but [ka] Compounds or salts of Embodiment A50 are provided herein.

[0405] As Embodiment A52, one compound or salt from any of Embodiments A1 to A51 is provided herein, wherein A is N.

[0406] Embodiment A53 is one in which A is CH, C-halo, C-CN, CC 1~3 Alkyl, CC 1~3 Haloalkyl, CC 0~3 Alkylene OH, or CC 0~3 Alkylene-C 1~4 One compound or salt from any of embodiments A1 to A51, which is an alkoxy, is provided herein.

[0407] As Embodiment A54, a compound or salt of Embodiment A53 is provided herein, wherein A is CH.

[0408] As Embodiment A55, a compound or salt of Embodiment A53 is provided herein, wherein A is CF, C-Cl, or C-CN.

[0409] Embodiment A56 is, 1~3 Compounds or salts of Embodiment A53, which are alkyl, are provided herein.

[0410] As Embodiment A57, a compound or salt of Embodiment A56 is provided herein, wherein A is C-CH3.

[0411] Embodiment A58 is CC 1~3 Compounds or salts of Embodiment A53, which are haloalkyl, are provided herein.

[0412] As Embodiment A59, a compound or salt of Embodiment A58 is provided herein, wherein A is C-CH2F, C-CHF2, or C-CF3.

[0413] Embodiment A60 is, 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 Compounds or salts of Embodiment A53 that are alkoxys are provided herein.

[0414] As Embodiment A61, a compound or salt of Embodiment A60 is provided herein, wherein A is C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3.

[0415] As Embodiment A62, the compounds or salts of Embodiment A53 are provided herein, wherein A is CH, CF, C-Cl, C-CN, C-CH3, C-CH2F, C-CHF2, C-CF3, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3.

[0416] As Embodiment A63, one compound or salt from any of Embodiments A1 to A62 is provided herein, wherein n is 0.

[0417] As Embodiment A64, one compound or salt from any of Embodiments A1 to A62 is provided herein, wherein n is 1.

[0418] Embodiment A65 is provided herein, which is one compound or salt from any of Embodiments A1 to A62, wherein n is 2.

[0419] Embodiment A66 includes at least one R 4 However, C 1~3 Alkyl or C 1~3 Compounds or salts of Embodiments A64 or A65 that are haloalkyl are provided herein.

[0420] Embodiment A67 includes at least one R 4 However, compounds or salts of Embodiment A66 are provided herein, which are CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, or CF3.

[0421] Embodiment A68 includes at least one R 4 Compounds or salts of Embodiment A67, wherein CH3 is provided herein.

[0422] Embodiment A69 includes at least one R 4 C 0~3 Compounds or salts of Embodiments A64 or A65, which are alkylene CN, are provided herein.

[0423] Embodiment A70 includes at least one R 4 However, compounds or salts of Embodiment A69, which are CN or CH2CN, are provided herein.

[0424] Embodiment A71 includes at least one R 4 However, C 1~3 Alkylene OH or C 1~3 Alkylene-C 1~3 Compounds or salts of Embodiments A64 or A65 that are alkoxys are provided herein.

[0425] Embodiment A72 includes at least one R 4However, compounds or salts of Embodiment A71, which are CH2OH, CH2CH2OH, CH2OCH3, or CH2CH2OCH3, are provided herein.

[0426] Embodiment A73 includes at least one R 4 Compounds or salts of Embodiments A64 or A65, wherein the compound is an oxo, are provided herein.

[0427] Embodiment A74 includes at least one R 4 However, Spiro-C 3~7 Compounds or salts of Embodiments A64 or A65 are provided herein, which are cycloalkyl or spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S.

[0428] Embodiment A75 includes at least one R 4 The compounds or salts of Embodiment A74, which are spiro-cyclopropyl, spiro-cyclobutyl, or spiro-oxetanil, are provided herein.

[0429] Embodiment A76, each R 4 Compounds or salts of Embodiment A64 or A65 are provided herein, independently of CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, CHF2, CH2F, CN, CH2CN, CH2OH, CH2CH2OH, CH2OCH3, CH2CH2OCH3, oxo, spiro-cyclopropyl, spiro-cyclobutyl, or spiro-oxetanyl.

[0430] Embodiment A77 is, [ka] but [ka] Compounds or salts of Embodiment A52 are provided herein.

[0431] Embodiment A78 is: [ka] but [ka] Compounds or salts of Embodiment A77 are provided herein.

[0432] Embodiment A79 is, [ka] but [ka] Compounds or salts of Embodiment A78 are provided herein.

[0433] Embodiment A80 is, [ka] but [ka] Compounds or salts of Embodiment A79 are provided herein.

[0434] Embodiment A81 is, [ka] but [ka] Compounds or salts of Embodiment A53 are provided herein.

[0435] Embodiment A82 is W 1 A compound or salt from any one of embodiments A1 to A81 is provided herein, wherein is N.

[0436] Embodiment A83 is W 1A compound or salt from any one of embodiments A1 to A81 is provided herein, wherein CH is present.

[0437] Embodiment A84 is W 1 However, one compound or salt of any one of embodiments A1 to A81 is provided herein, which is CF, C-Cl, or C-CN.

[0438] Embodiment A85 is W 1 However, CC 1~3 Alkyl or CC 1~3 A compound or salt from any one of embodiments A1 to A81, which is a haloalkyl compound, is provided herein.

[0439] Embodiment A86 is W 1 Compounds or salts of Embodiment A85, wherein the compound is C-CH3, C-CH2CH3, C-CH2F, C-CHF2, or C-CF3, are provided herein.

[0440] Embodiment A87 is W 1 However, CC 2~3 Alkenil or CC 2~3 It is an alkynyl, where each of the alkenyl and alkynyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently a halo, C 1~3 Haloalkyl, C 0~3 Alkylene OH, or C 0~3 Alkilen C 1~4 One compound or salt of any of embodiments A1 to A85, which is an alkoxy, is provided herein.

[0441] Embodiment A88 is W 1 However, compounds or salts of Embodiment A87 are provided herein, wherein the compounds are C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), or C-CCH.

[0442] Embodiment A89 is W 1 However, CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4A compound or salt from any one of embodiments A1 to A81, which is an alkoxy, is provided herein.

[0443] Embodiment A90 is W 1 Compounds or salts of Embodiment A89, wherein the compound is C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3, are provided herein.

[0444] Embodiment A91 is W 1 The following compounds or salts of any one of Embodiments A1 to A81 are provided herein, wherein the compound is CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2F, C-CHF2, C-CF3, C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), C-CCH, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3.

[0445] As embodiment A92, W 2 A compound or salt from any one of embodiments A1 to A91 is provided herein, wherein is N.

[0446] Embodiment A93 is W 2 A compound or salt from any one of embodiments A1 to A91 is provided herein, wherein CH is present.

[0447] Embodiment A94 is W 2 However, one compound or salt of any of Embodiments A1 to A91 is provided herein, which is CF, C-Cl, or C-CN.

[0448] Embodiment A95 is W 2 However, CC 1~3 Alkyl or CC 1~3 One compound or salt from any of Embodiments A1 to A91, which is a haloalkyl compound, is provided herein.

[0449] Embodiment A96 is W 2Compounds or salts of Embodiment A95, wherein the compound is C-CH3, C-CH2CH3, C-CH2F, C-CHF2, or C-CF3, are provided herein.

[0450] Embodiment A97 is W 2 However, CC 2~3 Alkenil or CC 2~3 It is an alkynyl, where each of the alkenyl and alkynyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently a halo, C 1~3 Haloalkyl, C 0~3 Alkylene OH, or C 0~3 Alkilen C 1~4 A compound or salt from any one of embodiments A1 to A91, which is an alkoxy, is provided herein.

[0451] Embodiment A98 is W 2 However, compounds or salts of Embodiment A97 are provided herein, wherein the compounds are C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), or C-CCH.

[0452] Embodiment A99 is W 2 However, CC 0~3 Alkylene OH or CC 0~3 Alkylene-C 1~4 A compound or salt from any one of embodiments A1 to A91, which is an alkoxy, is provided herein.

[0453] As embodiment A100, W 2 Compounds or salts of Embodiment A99, which are C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3, are provided herein.

[0454] Embodiment A101 is W 2The following compounds or salts of any one of Embodiments A1 to A91 are provided herein, wherein the compound is CF, C-Cl, C-CN, C-CH3, C-CH2CH3, C-CH2F, C-CHF2, C-CF3, C-CH=CH2, CC(OH)=CH2, C-CH=CH(OH), C-CCH, C-OH, C-CH2OH, C-OCH3, or C-CH2OCH3.

[0455] Embodiment A102 is W 1 and W 2 The following compounds or salts from any one of Embodiments A1 to A81 are provided herein, each of which is independently N, CH, or C-CH3.

[0456] Embodiment A103 is W 1 CH is W 2 Compounds or salts of Embodiment A102, wherein the compound is N, CH, or C-CH3, are provided herein.

[0457] Embodiment A104 is W 2 N is W 1 Compounds or salts of Embodiment A102, wherein the compound is N, CH, or C-CH3, are provided herein.

[0458] Embodiment A105 is W 1 CH is W 2 Compounds or salts of Embodiment A102, wherein is N, are provided here...

Claims

1. Compound of formula (II): 【Chemistry 1】 or a pharmaceutically acceptable salt thereof (In the formula, m is 0, 1, 2, 3, or 4; n is 0, 1, or 2; o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; q is 0, 1, or 2; r is either 0 or 1; A is N, CH, C-HALO, C-CN, C-C １～３ Alkyl, C-C １～３ Haloalkyl, C-C ０～３ Alkylene OH, or C-C ０～３ Alkylene-C １～４ It is an alkoxy; W １ and W ２ each of which is, independently, N, CH, C-halo, C-CN, C-C １～３ alkyl, C-C ２～３ alkenyl, C-C ２～３ alkynyl, C-C １～３ haloalkyl, C-C ０～３ alkylene OH, or C-C ０～３ alkylene-C １～４ alkoxy, where each of said alkenyl and alkynyl is unsubstituted or substituted by 1 to 3 substituents, and each substituent is, independently, halo, C １～３ haloalkyl, C ０～３ alkylene OH, or C ０～３ alkylene C １～４ alkoxy; X is N or C-R ５ａ And; Y' is C ３～７ Cycloalkyl, C ４～７ A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; R １ａ , R １ｂ , and R ２ Each of these is independently H, D, Halo, C １～４ Alkyl, C １～４ Haloalkyl, C １～２ Alkylene-OH, C ０～２ Alkylene-C １～４ Alkoxy, C ０～２ Alkylene-C １～４ Haloalkoxy, C ０～２ Alkylene-CN, C ０～２ Alkylene-N(R) Ｎ１ ) ２ , C having 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S １～２ It is either alkylene-heterocycloalkyl or R １ｂ and R ２ Along with the carbon atoms to which they are bonded, 【Chemistry 2】 form Each R ３ Independently, C １～３ Alkyl, C １～３ Haloalkyl, 【Transformation 3】 , C ０～３ Alkylene CN, C ０～３ Alkylene OH, C ０～３ Alkylene-C １～３ Alkoxy, oxo, spiro-C ３～７ Cycloalkyl, Spiro-C ４～７ A cycloalkenyl, a spiro-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R ３ These atoms, along with the atoms to which they are bonded, undergo condensation -C ３～７ Cycloalkyl, condensation-C ４～７ Forming a cycloalkenyl, a condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R Ａ１ and R Ａ２ Each of these independently corresponds to H and C １～３ Alkyl, C １～３ Haloalkyl, or C ３～５ It is a cycloalkyl; Each R ４ Independently, C １～３ Alkyl, C １～３ Haloalkyl, C ０～３ Alkylene CN, C １～３ Alkylene OH, C １～３ Alkylene-C １～３ Alkoxy, oxo, spiro-C ３～７ A cycloalkyl or spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; R ５ａ H, CN, Halo, C １～３ Alkyl, C １～３ Haloalkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ０～３ Alkylene OH, C ０～３ Alkylene-C １～３ Alkoxy, or C ３～５ It is a cycloalkyl; R ５ｂ Hello, C １～３ Haloalkyl, C １～６ Alkyl, C ２～４ Alkenil, C ２～４ Alkinyl, C １～３ Alkoxy, C １～３ Thioalkyl, C ３～７ Cycloalkyl, C ５～７ A cycloalkenyl, a heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, a heterocycloalkenyl having 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or R ５ａ and R ５ｂ C ３～７ Forms a cycloalkyl group; Here, the above C １～６ alkyl, C ２～４ alkenyl, C ２～４ alkynyl, C ３～７ cycloalkyl, C ５～７ cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl are each independently unsubstituted or substituted by 1 to 3 substituents, and each substituent is independently C １～３ haloalkyl, C ０～６ alkylene-OH, C ０～６ alkylene-C １～３ alkoxy, C ３～７ cycloalkyl, C ５～７ cycloalkenyl, heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or phenyl; Each R ６ is, independently, halo, CN, C １～３ alkyl, C ２～３ alkenyl, C １～３ haloalkyl, C ０～３ alkylene-OH, C ０～３ alkylene-C １～３ alkoxy, deuterated C ０～３ alkylene-C １～３ alkoxy, C １～４ alkylene-N(R Ｎ１ ) ２ , oxo, =CH ２ , C ３～７ cycloalkyl, C ４～７ cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C ３～７ cycloalkyl, spiro-C ４～７ cycloalkenyl, spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or, two vicinal R ６ together with the atoms to which they are attached form a fused-C ３～７ cycloalkyl, fused-C ４～７ cycloalkenyl, fused-heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or fused-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or, two non-adjacent R ６ are joined together to form a C １～３ alkylene bridge, C ２～３ alkenylene bridge, C １～３ ether bridge, or C １～３ A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C １～３ Alkyl, C １～３ Haloalkyl, C ０～２ Alkylene OH, C ０～２ Alkilen C １～３ Alkoxy, or C ０～２ It is alkylene CN; Each R ７ Independently, Halo, C ０～３ Alkylene-CN, C １～３ Alkyl, C １～３ Haloalkyl, C ２～３ Alkenil, C ０～３ Alkylene OH, C ０～３ Alkylene-C １～３ Alkoxy, C(=O)OC １～３ Alkyl, oxo, =CH ２ , C ０～４ Alkylene-C ３～７ C having cycloalkyl, 3 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. ０～４ Alkylene-heterocycloalkyl; C ０～４ Alkylene-C ６～１０ C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. ０～４ Alkylene heteroaryl; Spiro-C ３～７ A spiro-heterocycloalkyl having a cycloalkyl group, 4 to 7 total ring atoms, and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R atoms. ７ These atoms, along with the atoms to which they are bonded, undergo condensation -C ３～７ Cycloalkyl, condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, condensed-C ６～１０ A condensed heteroaryl is formed having an aryl, or 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C １～３ Alkyl; and Each R Ｎ１ H or C １～４ (It is alkyl.)

2. R １ａ , R １ｂ , and R ２ The compound or salt according to claim 1, wherein at least one of them is H or D.

3. R １ａ , R １ｂ , and R ２ The compound or salt according to claim 1 or 2, wherein each of them is independently H or D.

4. R １ａ , R １ｂ , and R ２ At least one of them is Halo, C １～４ Alkyl, C １～４ Haloalkyl, C １～２ Alkylene-OH, C ０～２ Alkylene-C １～４ Alkoxy, C ０～２ Alkylene-C １～４ Haloalkoxy, C ０～２ Alkylene-CN, C ０～２ Alkylene-N(R) Ｎ１ ) ２ , C having 3 to 6 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S １～２ It is either alkylene-heterocycloalkyl or R １ｂ and R ２ However, along with the carbon atoms to which they are bonded, 【Chemistry 4】 Forms, and here each R Ｎ１ However, independently, H or CH ３ The compound or salt according to claim 1 or 2.

5. R １ａ , R １ｂ , and R ２ At least one of them is Br, Cl, F, CH ３ ,CH ２ F, CHF ２ CF ３ ,CH ２ OH, OCH ３ ,CH ２ OCH ３ OCF ３ ,CH ２ OCF ３ , CN, CH ２ CN, NH ２ , N (CH ３ ) ２ ,CH ２ NH ２ ,CH ２ N(CH ３ ) ２ The compound or salt according to claim 4, which is aziridine-1-ylmethyl, azetidine-1-ylmethyl, pyrrolidine-1-ylmethyl, piperidine-1-ylmethyl, or morpholine-1-ylmethyl. 【Request Item 6】 【Chemistry 5】 but 【Transformation 6】 The compound or salt according to claim 1 or 2. 【Request Item 7】 【Chemistry 7】 but 【Transformation 8】 The compound or salt according to claim 6. [Request Item 8] [Chemistry 9] but 【Chemistry 10】 The compound or salt according to claim 7.

9. The compound or salt according to any one of claims 1 to 8, wherein m is 0 or 1.

10. The compound or salt according to any one of claims 1 to 8, wherein m is 2, 3, or 4.

11. at least one R ３ However, C １～３ Alkyl or C １～３ A compound or salt according to any one of claims 1 to 10, which is a haloalkyl compound.

12. at least one R ３ However, CH ３ ,CH ２ CH ３ CF ３ CHF ２ , or CH ２ The compound or salt according to claim 11, wherein F.

13. at least one R ３ but, 【Chemistry 11】 , C ０～３ Alkylene CN, C ０～３ Alkylene OH, C ０～３ Alkylene-C １～３ Alkoxy, oxo, spiro-C ３～７ A cycloalkyl, a spiro-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, and a spiro-C ４～７ A cycloalkenyl, a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; two vicinal R ３ However, along with the atoms to which they are bonded, condensation occurs -C ３～７ Cycloalkyl, condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, condensed-C ４～７ Forming a cycloalkenyl, or a condensed-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; where R Ａ１ and R Ａ２ Each of them independently produces H and CH ３ ,CH ２ F, CHF ２ CF ３ ,CH ２ CH ３ ,CH ２ CH ２ CH ３ , CH (CH ３ ) ２ The compound or salt according to any one of claims 1 to 10, which is cyclopropyl or cyclobutyl.

14. at least one R ３ but, 【Chemistry 12】 , CN, CH ２ CN, OH, CH ２ OH, CH ２ CH ２ OH, OCH ３ ,CH ２ OCH ３ ,CH ２ CH ２ OCH ３ , oxo, spirocyclopropyl, spirocyclobutyl, spirooxetanil, spirotetrahydrofuranil, or two vicinal R ３ The compound or salt according to claim 13, wherein, together with the atoms to which they are bonded, they form condensed-cyclopropyl or condensed-cyclobutyl.

15. Each R ３ However, independently, CH ３ ,CH ２ CH ３ CF ３ CHF ２ ,CH ２ F, 【Chemistry 13】 , CN, CH ２ CN, OH, CH ２ OH, CH ２ CH ２ OH, OCH ３ ,CH ２ OCH ３ ,CH ２ CH ２ OCH ３ , oxo, spirocyclopropyl, spirocyclobutyl, spirooxetanil, or spirotetrahydrofuranil; or two vicinal R ３ The compound or salt according to any one of claims 1 to 10, wherein they form condensed-cyclopropyl or condensed-cyclobutyl together with the atoms to which they are bonded.

16. m is 0; or m is 1, R ３ However, CH ３ ,CH ２ F, CHF ２ CF ３ , CN, CH ２ CN, CH ２ OH, CH ２ OCH ３ The compound or salt according to any one of claims 1 to 8, which is spiro-oxetanil.

17. m is 0; or m is 1, R ３ ga CH ３ The compound or salt according to claim 16. 【Request Item 18】 【Chemistry 14】 but 【Chemistry 15】 The compound or salt according to any one of claims 1 to 8. 【Request Item 19】 【Chemistry 16】 but 【Chemistry 17】 The compound or salt according to claim 18.

20. A compound or salt according to any one of claims 1 to 19, wherein A is N.

21. A is CH, C-Halo, C-CN, C-C １～３ Alkyl, C-C １～３ Haloalkyl, C-C ０～３ Alkylene OH, or C-C ０～３ Alkylene-C １～４ A compound or salt according to any one of claims 1 to 19, which is an alkoxy.

22. A is CH, C-F, C-Cl, C-CN, C-CH ３ C-CH ２ F, C-CHF ２ C-CF ３ , C-OH, C-CH ２ OH, C-OCH ３ , or C-CH ２ OCH ３ The compound or salt according to claim 21.

23. A compound or salt according to any one of claims 1 to 22, wherein n is 0 or 1.

24. at least one R ４ However, C １～３ Alkyl or C １～３ A compound or salt according to any one of claims 1 to 23, which is a haloalkyl compound.

25. at least one R ４ However, CH ３ ,CH ２ CH ３ ,CH ２ CH ２ CH ３ , CH (CH ３ ) ２ ,CH ２ F, CHF ２ , or CF ３ The compound or salt according to claim 24.

26. at least one R ４ However, C ０～３ Alkylene CN, C １～３ Alkylene OH, C １～３ Alkylene-C １～３ Alkoxy, oxo, spiro-C ３～７ The compound or salt according to any one of claims 1 to 23, which is a cycloalkyl or a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S.

27. at least one R ４ However, CN, CH ２ CN, CH ２ OH, CH ２ CH ２ OH, CH ２ OCH ３ ,CH ２ CH ２ OCH ３ The compound or salt according to claim 26, which is oxo, spirocyclopropyl, spirocyclobutyl, or spirooxetanil.

28. Each R ４ However, independently, CH ３ ,CH ２ CH ３ ,CH ２ CH ２ CH ３ , CH (CH ３ ) ２ CF ３ CHF ２ ,CH ２ F, CN, CH ２ CN, CH ２ OH, CH ２ CH ２ OH, CH ２ OCH ３ ,CH ２ CH ２ OCH ３ The compound or salt according to any one of claims 1 to 23, which is oxo, spirocyclopropyl, spirocyclobutyl, or spirooxetanil. 【Request Item 29】 【Chemistry 18】 but 【Chemistry 19】 The compound or salt according to claim 28. 【Request Item 30】 【Chemistry 20】 but 【Chemistry 21】 The compound or salt according to claim 29.

31. W １ is N, CH, C-F, C-Cl, C-CN, C-CH ３ C-CH ２ CH ３ C-CH ２ F, C-CHF ２ C-CF ３ C-CH=CH ２ , CC(OH)=CH ２ , C-CH=CH(OH), or C-CCH, C-OH, C-CH ２ OH, C-OCH ３ , or C-CH ２ OCH ３ The compound or salt according to any one of claims 1 to 30.

32. W １ The compound or salt according to claim 31, wherein is CH.

33. W ２ is N, CH, C-F, C-Cl, C-CN, C-CH ３、 C-CH ２ CH ３ C-CH ２ F, C-CHF ２ C-CF ３ C-CH=CH ２ , CC(OH)=CH ２ , C-CH=CH(OH), or C-CCH, C-OH, C-CH ２ OH, C-OCH ３ , or C-CH ２ OCH ３ The compound or salt according to any one of claims 1 to 32.

34. W ２ The compound or salt according to claim 33, wherein is N.

35. W １ CH is W ２ A compound or salt according to any one of claims 1 to 30, wherein is N.

36. A compound or salt according to any one of claims 1 to 35, wherein X is N.

37. X is CR ５ａ And R ５ａ However, H, CN, Br, Cl, F, CH ３ ,CH ２ CH ３ CF ３ CHF ２ ,CH ２ F, 【Chemistry 22】 、OH、EH ２ OH、OCH ３ ,H ２ OCH ３ 、 or 【Chemistry 23】 The compound or salt according to any one of claims 1 to 35.

38. R ５ａ However, CN or CH ３ The compound or salt according to claim 37.

39. X is N, C-CH ３ The compound or salt according to any one of claims 1 to 35, which is C-CN.

40. W １ CH is; W ２ N is N; X is N, C-CH ３ The compound or salt according to any one of claims 1 to 30, which is C-CN.

41. R ５ｂ が、Br、Cl、F、CF ３ 、CF ２ H、CFH ２ 、CF ２ CH ３ 、OCH ３ 、SCH ３ CH ３ 、CH ２ CH ３ 、CH ２ CH ２ CH ３ 、CH(CH ３ ) ２ 、 【Chemistry 24】 The compound or salt according to any one of claims 1 to 40.

42. R ５ｂ However, CF ３ or CF ２ The compound or salt according to claim 41, wherein H is present. 【Request Item 43】 【Chemistry 25】 but 【Chemistry 26】 And X is N, C-CH ３ , or C-CN; R ｂ However, CF ３ or CF ２ A compound or salt according to any one of claims 1 to 30, wherein H is present. 【Request Item 44】 【Chemistry 27】 but 【Chemistry 28】 【Chemistry 29】 The compound or salt according to any one of claims 1 to 30. 【Request Item 45】 【Chemistry 30】 but 【Chemistry 31】 The compound or salt according to claim 44.

46. A compound or salt according to any one of claims 1 to 45, wherein q is 0.

47. A compound or salt according to any one of claims 1 to 45, wherein q is 1.

48. A compound or salt according to any one of claims 1 to 45, wherein q is 2.

49. A compound or salt according to any one of claims 1 to 45, wherein r is 0.

50. A compound or salt according to any one of claims 1 to 45, wherein r is 1. 【Request Item 51】 【Chemistry 32】 but 【Transformation 33】 The compound or salt according to any one of claims 1 to 45.

52. The compound according to any one of claims 1 to 51, wherein o is 0, 1, or 2.

53. The compound according to any one of claims 1 to 51, wherein o is 3 or 4.

54. at least one R ６ However, Br, Cl, F, CN, CH ３ ,CH ２ F, CHF ２ CF ３ OH, CH ２ OH, OCH ３ OCD ３ ,CH ２ OCH ３ ,CH ２ N(CH ３ ) ２ , oxo, = CH ２ , cyclopropyl, cyclobutyl, oxetanyl, tetrahydrofuranyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, or spiro-tetrahydrofuranyl; or two vicinal R ６ However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl; or two adjacent R ６ They bond together, -CH ２ -ien-CH ２ CH ２ -ien-CH ２ CH ２ CH ２ -ien-CH ２ -CH=CH- or -CH ２ OCH ２ - forms; where each of the cyclopropyl, cyclobutyl, oxetanyl, tetrahydrofuranyl, spiro-cyclopropyl, spiro-cyclobutyl, spiro-oxetanyl, spiro-tetrahydrofuranyl, condensed-cyclopropyl, condensed-cyclobutyl, and condensed-cyclopentyl is independently unsubstituted or substituted with 1 to 4 substituents, and each substituent is independently halo, C １～３ Alkyl, C １～３ Haloalkyl, C ０～２ Alkylene OH, C ０～２ Alkilen C １～３ Alkoxy, or C ０～２ The compound according to any one of claims 1 to 53, wherein the compound is alkylene CN.

55. Each substituent independently corresponds to F, Cl, OH, OCH ３ , OCH ２ CH ３ The compound or salt according to claim 54, which is CN.

56. at least one R ６ However, Br, Cl, F, CN, CH ３ ,CH ２ F, CHF ２ CF ３ OH, CH ２ OH, OCH ３ OCD ３ ,CH ２ OCH ３ ,CH ２ N(CH ３ ) ２ , oxo, = CH ２ , cyclopropyl or two vicinal R ６ However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-cyclobutyl, or condensed-cyclopentyl, or two non-adjacent R ６ They bond together, -CH ２ -ien-CH ２ CH ２ -ien-CH ２ CH ２ CH ２ -ien-CH ２ -CH=CH- or -CH ２ OCH ２ - forms; where each of the above cycloalkyl groups is unsubstituted or substituted with 1 to 4 substituents, and each substituent independently is F, Cl, OH, OCH ３ , OCH ２ CH ３ The compound or salt according to claim 54 or 55, which is CN.

57. o is 0; or o is 1, R ６ However, H, CH ３ ,CH ２ It is either OH or two non-adjacent R ６ They bond together, -CH ２ CH ２ A compound or salt according to any one of claims 1 to 51 that forms -. 【Request Item 58】 【Chemistry 34】 but 【Chemistry 35】 The compound or salt according to any one of claims 1 to 51. 【Request Item 59】 【Chemistry 36】 but 【Chemistry 37】 but 【Transformation 38】 The compound or salt according to claim 58.

60. Compounds of formula (IIA), formula (IIB), or formula (IIC): 【Chemistry 39】 The compound or salt according to any one of claims 1 to 30, or a pharmaceutically acceptable salt of any of the above.

61. The compound or salt according to any one of claims 1 to 60, wherein Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azilidinyl, oxyranil, thyranil, azetidinil, oxetanil, thietanil, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuranil, tetrahydrothiophenyl, dioxolanil, oxazolidinyl, oxathiolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, tetrahydropyranil, dioxanil, tetrahydrothiopyranil, dithianil, morpholinil, thiomorpholinil, dihydropyrrolyl, dihydrofuranil, dihydrothiophenyl, dihydroisoxazolyl, tetrahydropyridinyl, dihydropyranil, or dihydrochipyranil.

62. The compound or salt according to claim 61, wherein Y' is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, oxetanyl, pyrrolidinyl, tetrahydrofuranil, dioxolanil, oxazolidinyl, isoxazolidinyl, tetrahydropyranil, dihydropyrrolyl, dihydrofuranil, or dihydropyranil.

63. A compound or salt according to any one of claims 1 to 62, wherein p is 0 or 1.

64. The compound or salt according to any one of claims 1 to 62, wherein p is 2, 3, or 4.

65. Each R ７ However, independently, F, Cl, Br, CN, CH ２ CN, CH ３ ,CH ２ CH ３ ,CH ２ F, CHF ２ CF ３ OH, OCH ３ , OCH ２ CH ３ ,CH ２ OH, CH ２ OCH ３ ,CH ２ CH ２ OCH ３ , C(=O)OCH ３ , oxo, = CH ２ cyclopropyl, 【Chemistry 40】 , oxetanil, spirocyclopropyl, spirocyclobutyl, spirooxetanil, spirotetrahydrofuranil, spirotetrahydropyranil; or two vicinal R ７ However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-cyclobutyl, condensed-oxetanyl, condensed-tetrahydrofuranyl, condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, condensed-pyridyl, condensed-pyridazinyl, condensed-pyridazinyl, and condensed-pyrimidinyl; where each of the phenyl, pyrazolyl, pyridyl, pyridazinyl, and pyrimidinyl is unsubstituted or substituted with 1 to 3 substituents, and each substituent is independently halo, CN, oxo, or C １～３ A compound or salt according to any one of claims 1 to 64, wherein the compound is alkyl.

66. Each R ７ However, independently, F, Cl, Br, CN, CH ３ ,CH ２ CH ３ ,CH ２ F, OH, CH ２ OH, CH ２ OCH ３ ,CH ２ CH ２ OCH ３ , oxo, = CH ２ , 【Chemistry 41】 , oxetanyl, spirocyclopropyl, spirocyclobutyl, spirooxetanyl, or two vicinal R ７ However, together with the atoms to which they are bonded, they form condensed-cyclopropyl, condensed-phenyl, condensed-thiophenyl, condensed-pyrazolyl, condensed-thiazolyl, and condensed-pyridyl; where each of the phenyl, pyrazolyl, and pyridyl is unsubstituted or CH ３ The compound or salt according to claim 65, which is substituted by... 【Request Item 67】 【Chemistry 42】 but 【Chemistry 43】 【Chemistry 44】 【Chemistry 45】 【Chemistry 46】 The compound or salt according to any one of claims 1 to 59. 【Request Item 68】 【Chemistry 47】 but 【Chemistry 48】 【Chemistry 49】 [Transformation 50] The compound or salt according to any one of claims 1 to 59. 【Request Item 69】 【Chemistry 51】 but 【Chemistry 52】 The compound or salt according to claim 68. 【Request Item 70】 【Chemistry 53】 but 【Chemistry 54】 And; 【Transformation 55】 but 【Transformation 56】 And; 【Chemistry 57】 but 【Chemistry 58】 And; 【Chemistry 59】 but 【Transformation 60】 The compound or salt according to claim 1. 【Request Item 71】 【Chemistry 61】 but 【Transformation 62】 The compound according to claim 70. 【Request Item 72】 【Chemistry 63】 but 【Chemistry 64】 The compound or salt according to claim 70 or 71.

73. q is 1; r is 1; W １ However, CH, C-Halo, C-CN, C-C １～３ Alkyl, C-C １～３ Haloalkyl, C-C ０～３ Alkylene OH, or C-C ０～３ Alkylene-C １～４ It is an alkoxy; W ２ is N; X is N or C-R ５ａ The compound or salt according to any one of claims 1 to 30.

74. The compound according to claim 1, which is one of the compounds listed in Table A, or a pharmaceutically acceptable salt thereof.

75. The compound according to claim 1, which is one of the compounds listed in Table C, or a pharmaceutically acceptable salt thereof.

76. A pharmaceutical composition comprising a compound or salt according to any one of claims 1 to 75 and a pharmaceutically acceptable excipient.

77. A method for treating a target cancer requiring treatment, comprising administering to the target a therapeutically effective amount of a compound or salt according to any one of claims 1 to 76 or a composition according to claim 77.

78. The method according to claim 77, wherein one or more cancer cells express the KRAS G12C mutant protein.

79. The method according to claim 77 or 78, wherein the cancer is non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed-type cancer of unknown primary origin, pancreatic cancer, hepatobiliary tract cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, solid tumor, or any combination of the above.

80. The method according to claim 79, wherein the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, or a solid tumor.

81. The method according to any one of claims 77 to 80, wherein the subject has cancer that has been determined to have one or more cells expressing the KRAS G12C mutant protein prior to administration of the compound, salt, or pharmaceutical composition.

82. The method according to any one of claims 77 to 81, further comprising simultaneous, separate, or sequential administration of an effective amount of a second compound, wherein the second compound is an ATR inhibitor, an Aurora kinase A inhibitor, an AKT inhibitor, an arginase inhibitor, a CDK2 inhibitor, a CDK4 / 6 inhibitor, an ErbB family inhibitor, an ERK inhibitor, a FAK inhibitor, an FGFR inhibitor, a glutaminase inhibitor, an IGF-1R inhibitor, a KIF18A inhibitor, a MAT2A inhibitor, an MCL-1 inhibitor, a MEK inhibitor, an mTOR inhibitor, a PARP inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PI3K inhibitor, a PRMT5 inhibitor, a Raf kinase inhibitor, a SHP2 inhibitor, a SOS1 inhibitor, a Src kinase inhibitor, or one or more chemotherapeutic agents.

83. A compound or salt according to any one of claims 1 to 75, or a composition according to claim 76, for use as a pharmaceutical.

84. A compound or salt according to any one of claims 1 to 75, or a composition according to claim 76, for use in the treatment of cancer.

85. A compound or salt according to any one of claims 1 to 75, or a pharmaceutical composition according to claim 76, for use in the treatment of cancer in which one or more cancer cells express the KRAS G12C mutant protein.

86. The compound or salt according to claim 84 or 85, wherein the cancer is non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed-type cancer of unknown primary origin, pancreatic cancer, hepatobiliary tract cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, or solid tumor.

87. The compound or salt according to claim 86, wherein the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, or a solid tumor.

88. Use of a compound or salt according to any one of claims 1 to 75 or a pharmaceutical composition according to claim 76 for manufacturing a pharmaceutical for treating cancer.

89. Use of a compound or salt according to any one of claims 1 to 75 or a pharmaceutical composition according to claim 76 in the preparation of a pharmaceutical for treating cancer in which one or more cancer cells express the KRAS G12C mutant protein.

90. The use according to claim 88 or 89, wherein the cancer is non-small cell lung cancer, small intestine cancer, appendiceal cancer, colorectal cancer, cancer of unknown primary origin, endometrial cancer, mixed-type cancer of unknown primary origin, pancreatic cancer, hepatobiliary tract cancer, small cell lung cancer, cervical cancer, germ cell cancer, ovarian cancer, gastrointestinal neuroendocrine cancer, bladder cancer, myelodysplastic / myeloproliferative neoplasm, head and neck cancer, esophagogastric junction cancer, soft tissue sarcoma, mesothelioma, thyroid cancer, leukemia, melanoma, solid tumor, or any combination of the above.

91. The use according to claim 90, wherein the cancer is non-small cell lung cancer, colorectal cancer, pancreatic cancer, or a solid tumor.

92. Compound of formula (B): 【Transformation 65】 or nitrogen-protected analogues or any of the above pharmaceutically acceptable salts (wherein, o is 0, 1, 2, 3, or 4; p is 0, 1, 2, 3, 4, or 5; Each R ６ Halo, CN, C １～３ Alkyl, C ２～３ Alkenil, C １～３ Haloalkyl, C ０～３ Alkylene-OH, C ０～３ Alkylene-C １～３ Alkoxy and deuterated C ０～３ Alkylene-C １～３ Alkoxy, C １～４ Alkylene-N(R) Ｎ１ ) ２ , oxo, = CH ２ , C ３～７ Cycloalkyl, C ４～７ Cycloalkenyl, heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, spiro-C ３～７ Cycloalkyl, Spiro-C ４～７ A cycloalkenyl, a spiro-heterocycloalkyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S, or a spiro-heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R ６ These atoms, along with the atoms to which they are bonded, undergo condensation -C ３～７ Cycloalkyl, condensation-C ４～７ Forming a cycloalkenyl, a condensed heterocycloalkyl having 4 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, or a condensed heterocycloalkenyl having 4 to 7 total ring atoms and 1 or 2 heteroatoms independently selected from N, O, and S; or two non-adjacent R ６ They combine together, C １～３ Alkylene bridged, C ２～３ Alkenylene bridge, C １～３ Ether crosslinking, or C １～３ A thioether crosslink is formed; where each of the above cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is unsubstituted or substituted with 1 to 4 substituents, each substituent independently being halo, C １～３ Alkyl, C １～３ Haloalkyl, C ０～２ Alkylene OH, C ０～２ Alkilen C １～３ Alkoxy, or C ０～２ It is alkylene CN; Each R ７ Independently, Halo, C ０～３ Alkylene-CN, C １～３ Alkyl, C １～３ Haloalkyl, C ２～３ Alkenil, C ０～３ Alkylene OH, C ０～３ Alkylene-C １～３ Alkoxy, C(=O)OC １～３ Alkyl, oxo, =CH ２ , C ０～４ Alkylene-C ３～７ C having cycloalkyl, 3 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. ０～４ Alkylene-heterocycloalkyl; C ０～４ Alkylene-C ６～１０ C having aryl atoms, 4 to 7 total ring atoms, and 1 to 3 heteroatoms independently selected from N, O, and S. ０～４ Alkylene heteroaryl; Spiro-C ３～７ A spiro-heterocycloalkyl having a cycloalkyl group, 4 to 7 total ring atoms, and 1 or 2 heteroatoms independently selected from N, O, and S; or two vicinal R atoms. ７ These atoms, along with the atoms to which they are bonded, undergo condensation -C ３～７ Cycloalkyl, condensed-heterocycloalkyl having 3 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S, condensed-C ６～１０ A condensed heteroaryl is formed having an aryl, or 5 to 7 total ring atoms and 1 to 3 heteroatoms independently selected from N, O, and S; each of the above cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1 to 3 substituents, each substituent independently being halo, CN, oxo, or C １～３ Alkyl; and Each R Ｎ１ H or C １～４ (It is alkyl.)

93. A method for preparing a compound or salt according to any one of claims 1 to 75, comprising converting the compound according to claim 92, any of the above protected analogues, or any of the above pharmaceutically acceptable salts to the compound according to any one of claims 1 to 75.

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