1,5-NAPHTHRIDINE DERIVATIVES AND MELK INHIBITORS CONTAINING THEM Russian patent published in 2018 - IPC C07D471/04 A61K31/4375 A61K31/496 A61P35/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to a heterocyclic compound of the formula (I) or to a pharmaceutically acceptable salt thereof, wherein X¹ is selected from a direct bond or -NH^-; Q¹ is selected from the group consisting of C₅-C₇ cycloalkyl, phenyl, pyridyl, pyrazolyl, pyrimidinyl, piperidyl, (C₃-C₁₀ cycloalkyl)-C₁-C₆ alkyl and (3-10-membered non-aromatic heterocyclyl)-C₁-C₆ alkyl; where Q¹ is optionally substituted by one A¹; X² is selected from -CO- and -SO₂-; R¹¹ is selected from the group consisting of C₁-C₆ alkyl and C₃-C₆ cycloalkyl, which are optionally substituted by one hydroxyl group; R⁵ is selected from the group consisting of a halogen atom, C₆-C₁₀ aryl, 5-10-membered heteroaryl and 3-10-membered non-aromatic heterocyclyl; wherein aryl, heteroaryl and heterocyclyl are optionally substituted by 1 to 3 substituents A³; R², R³ and R⁴ represent a hydrogen atom; A¹ is selected from the group consisting of C₁-C₆ alkyl, -NR¹⁶R¹⁷, -OR¹⁸, 3-10-membered non-aromatic heterocyclyl and (CD₃)₂N-C₁-C₆ alkyl; where alkyl and heterocyclyl are optionally substituted by one A⁴ and where heterocyclyl is optionally substituted by one C₁-C₆ alkyl; A³ is independently selected from the group consisting of a halogen atom, cyano, C₁-C₆ alkyl and -OR¹⁸; R¹⁶ is independently selected from the group consisting of a hydrogen atom, C₁-C₆ alkyl and -COR²⁰; where alkyl is optionally substituted by one A⁴; R¹⁷ is selected from the group consisting of a hydrogen atom and C₁-C₆ alkyl, which is optionally substituted by one A⁴; or R¹⁸ is selected from the group consisting of a hydrogen atom and C₁-C₆ alkyl, where alkyl is optionally substituted by one or three A⁴; R²⁰ is selected from the group consisting of C₁-C₆ alkyl and 3-10-membered non-aromatic heterocyclyl; wherein alkyl and heterocyclyl are optionally substituted by one amino group; A⁴ are independently selected from the group consisting of a halogen atom, -NR²⁴R²⁵, hydroxy and 3-10-membered non-aromatic heterocyclyl; where heterocyclyl is optionally substituted by one A⁵; R²⁴ and R²⁵ are independently selected from the group consisting of a hydrogen atom and C₁-C₆ alkyl, where alkyl is optionally substituted by one hydroxy group; A⁵ is selected from the group consisting of a halogen atom, C₁-C₆ alkyl and hydroxy; where the 5-10 membered heteroaryl is selected from the group consisting of pyridyl, pyrazolyl, pyrimidinyl, benzoimidazolyl and pyrrolopyridinyl; the 3 to 10-membered non-aromatic heterocyclyl is selected from the group consisting of piperidyl, piperazinyl, pyrrolidinyl and morpholinyl. The invention also relates to a pharmaceutical composition, a MELK inhibitor, an agent based on a compound of formula (I), a method of treatment and/or prevention of the said disease, application of the compound of formula (I), a method for preparation of the compound of formula (I), an intermediate of formula (II).

EFFECT: new compounds are obtained that are useful for cancer treatment.

20 cl, 3 dwg, 3 tbl, 246 ex

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