2-AMINOPYRASINE DERIVATIVES AS CSF-1R KINASE INHIBITORS Russian patent published in 2018 - IPC C07D241/20 C07D401/12 C07D401/14 C07D403/04 C07D403/10 C07D403/12 A61K31/4965 A61K31/497 A61P3/00 A61P9/00 A61P25/00 A61P29/00 A61P35/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to a compound that is an amino acid or ester of an amino acid of formula , or a pharmaceutically acceptable salt thereof, which has an inhibitory activity against CSF-1R kinase. In formula (I), ring A is a phenyl group; R¹ and R² independently represent a hydrogen atom, a halogen atom or an unsubstituted C_1-4 alkyl; n is 1; X is NH; V is -N=, W is -C(Z)=; Z represents a hydrogen atom, a fluorine atom, a chlorine atom or unsubstituted C_1-3 alkyl; ring B is a 1,4-phenylene, 1,3-phenylene or pyridinyl group; [Linker] is a -(CH₂)_m-X¹-(Alk¹)_x-Y¹ group, where m is 0, 1, 2 or 3; x is 0 or 1; Alk¹ is an unsubstituted C_1-3 alkylene group; X¹ and Y¹ independently represent a bond, -O-, -S-, -NR^7th-, -C(=O) - or -C(=O)NR⁵-, where R⁵ is a hydrogen atom or C_1-4 alkyl and R⁷ is a hydrogen atom, unsubstituted C_1-4 alkyl or -C(=O)CH₃; R is a group of formula or , in which R⁸ is a -COOH group or an ester group of the formula -(C=O)OR¹⁴, where R¹⁴ is R¹⁵R¹⁶R¹⁷C-, where any R¹⁵ represents a hydrogen atom or C_1-3alkyl-(Z¹)_a-[(C₁-C₃)alkyl]_b-, where a and b are independently 0 or 1, Z¹ is -O-, -S- or -NH-, R¹⁶ and R¹⁷ independently represent a hydrogen atom or C_1-3 alkyl- or R¹⁵ and R¹⁶, taken together with the carbon atom to which they are attached, form a 3-7-membered cycloalkyl ring; and R¹⁷ represents a hydrogen atom; where (i) R⁹ and R¹⁰ are side chains of natural amino acids, (ii) one of R⁹ and R¹⁰ represents a hydrogen atom or unsubstituted C_1-4 alkyl, and the other is an unsubstituted C_1-6 alkyl group or C_1-6 alkyl group substituted by a C_1-4 alkoxy group, or (iii) R⁹ and R¹⁰, taken together with the carbon atom to which they are attached, form a saturated spiro-cyclobutyl ring; R¹¹ represents a hydrogen atom or an unsubstituted C_1-2alkyl group; ring D is a 5- to 7-membered saturated heterocyclyl group with at least one nitrogen atom in the ring. The invention also relates to a pharmaceutical composition, a method of treatment or prevention of diseases or disorders mediated by CSF-1R kinase, as well as application of the said compounds for preparation of a medicament useful for treatment of such diseases.

EFFECT: increased application efficiency.

18 cl, 59 ex