RMT5 INHIBITORS Russian patent published in 2024 - IPC C07D487/04 C07D519/00 A61K31/519 A61P35/00 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. In formula (I): X represents either CH₂ or O; Y represents either CH₂, NH or O; R¹ and R⁷ are taken together to form a five-membered carbon ring, optionally substituted with 1–3 halogens, or a five-membered heterocycloalkyl ring containing one O atom; R² represents either H, OH, CH₃, CHF₂ or F; R³ represents H, halogen, NH₂, NHCH ₃, OH, OCH_3, C_1-4 alkyl, optionally substituted with 1–3 halogens or OH, or C_3-5cycloalkyl, optionally substituted either with 1–3 halogens or OH; R⁵ is either H, NH₂ or NHR⁶; and R⁴ is either H, halogen, CH₃, CHF₂ or CF₃; or R⁴ and R⁵, taken together with the carbon atoms to which they are attached, combine to form a 5-membered heterocycloalkyl containing one N atom, the said heterocycloalkyl being optionally substituted with one to four substituents independently selected from halogen, CH₃, CF₃ and CF₂H; R⁶ when present is either CH₃, C₂H₅, CH₂CH₂CH₃, CH(CH₃)₂, CH₂CHF₂, CH₂CF₃ or CH₂-cyclopropyl; R⁸ represents H, halogen, C_1-4 alkyl, optionally substituted with 1–3 halogens, C_3-5 cycloalkyl, optionally substituted with 1–3 halogens, or phenyl, optionally substituted with 1–3 halogens; R¹⁰ represents H, C_1-6 alkyl, NH₂ or halogen. Also the following is proposed: a compound of formula Ia, a compound selected from a group of individual compounds, and a composition including the above compounds.

EFFECT: proposed compounds are PRMT5 inhibitors and can be used to treat cancer, sickle cell disease and mutations associated with hereditary persistence of fetal hemoglobin (HPFH).

18 cl, 26 tbl, 137 ex