COMPOUND HAVING INHIBITORY ACTIVITY ON KDM5, AND PHARMACEUTICAL USE THEREOF Russian patent published in 2025 - IPC C07D403/12 C07D403/14 C07D413/14 A61K31/4155 A61K31/4178 A61K31/422 A61K31/4245 A61P25/28 A61P35/00 

FIELD: chemistry.

SUBSTANCE: group of inventions relates to organic chemistry and includes a compound of formula (I), a pharmaceutically acceptable salt thereof, a pharmaceutical composition and use thereof, a method for preventing or treating a disease associated with KDM5, and [(1R,5S,6r)-6-(5,5-dimethyl-4,5-dihydro-1,2-oxazol-3-yl)-3-azabicyclo[3.1.0]hex-3-yl][1-(1-methylcyclopropyl)-1H-imidazol-4-yl]methanone. In formula (I), R¹ is Cyc1, -CO-Cyc2 or -CONR¹⁰R¹¹; Cyc1 is 5–9 membered aromatic hetero ring containing 2–4 heteroatoms selected from N and O, or 5-member non-aromatic hetero ring containing 2–3 heteroatoms selected from N and O, each of which can be substituted with 1–3 R¹²; R¹² is (1) C1-4 alkyl, (2) C3-7 cycloalkyl, (3) C1-4 haloalkyl, (4) C1-4 alkoxy, (5) phenyl, which may be substituted with 1 R¹⁷, (6) C1-4 alkyl substituted with phenyl, (7) dimethylamino, (8) pyridyl or (9) 1-(cyclopropylmethyl)pyrazol-3-yl; several R¹² can be identical or different; two R¹² together with the atom to which these R¹² are attached, can form C3-5 cycloalkane; R¹⁷ is C1-4 alkyl, C1-4 alkoxy or halogen; several R¹⁷ can be identical or different; Cyc2 is a C3 monocyclic carbocycle or 5–9-membered mono- or bicyclic heterocycle containing 1–2 heteroatoms selected from N and S, each of which can be substituted with 1–2 R¹³; R¹³ is C1-4 alkyl or C1-4 alkoxy; several R¹³ can be identical or different; R¹⁰ is , where R¹⁸ and R¹⁹ independently represent C1-4 alkyl; R¹⁸ and R¹⁹ together with the carbon atom to which R¹⁸ and R¹⁹ are bonded can form C3-5 cycloalkane; R²⁰ represents a hydrogen atom, C1-4 alkyl, C1-4 haloalkyl or nitrile; (in the group, the arrow indicates bonding with the nitrogen atom -CON<); R¹¹ is a hydrogen atom or C1-4 alkyl; R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ independently represent a hydrogen atom or C1-4 alkyl; R⁹ is imidazole, which can be substituted with 1 R¹⁴, or pyrazole, which may be substituted with 1 R¹⁵; R¹⁴ is (1) C1-8 alkyl, (2) C3-7 cycloalkyl, which may be substituted with C1-4 alkyl, (3) C1-8 haloalkyl, (4) C1-8 alkyl substituted with Cyc3 which may be substituted with 1 R¹⁶, or (5) C1-8 alkyl substituted with phenoxy; Cyc3 is phenyl, C3-7 cycloalkyl, pyridyl, thiazolyl or tetrahydropyranyl; R¹⁶ is cyano; R¹⁵ is (1) C1-8 alkyl, (2) C3-7 cycloalkyl, (3) C1-8 alkyl substituted with Cyc4; Cyc4 is C3-7 cycloalkyl. Provided that compounds ((1R,5S,6r)-6-(cyclopropanecarbonyl)-3-azabicyclo[3.1.0]hexan-3-yl)(5-isopropyl-1H-pyrazol-3-yl)methanone, (5-isopropyl-1H-pyrazol-3-yl)-[(1R,5S)-6-[(2R)-2-methylpyrrolidine-1-carbonyl]-3-azabicyclo[3.1.0]hexan-3-yl]methanone, (5-isopropyl-1H-pyrazol-3-yl)-[(1S,5R)-6-[(2S)-2-methylpyrrolidine-1-carbonyl]-3-azabicyclo[3.1.0]hexan-3-yl]methanone, [(1S,5R)-6-(2,2-dimethylpyrrolidine-1-carbonyl)-3-azabicyclo[3.1.0]hexane-3-yl]-(5-isopropyl-1H-pyrazol-3-yl)methanone and (5-isopropyl-1H-pyrazol-3-yl)-[(1S,5R)-6-(5-methyl-4-phenyl-isoxazol-3-yl)-3-azabicyclo[3.1.0]hexane-3-yl]methanone are excluded. (I).

EFFECT: compounds of formula (I), which are KDM5 inhibitors.

25 cl, 3 tbl, 151 ex