DERIVATIVES OF 1-(3-AMINOPHENYL)-6,8-DIMETHYL-5-(4-IODO-2-FLUORO-PHENYLAMINO)-3-CYCLOPROPYL-1H,6H-PYRIDO[4,3-d]PYRIMIDINE-2,4,7-TRIONE AS MEK1/2 INHIBITORS Russian patent published in 2016 - IPC C07D487/04 A61K31/519 A61K35/00 

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of 1-(3-aminophenyl)-6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-1H, 6H-pyrido[4,3-d]pyrimidine-2,4,7-trione, having effect on kinase MEK1 and can be used for treating and preventing cancer, in particular malignant melanoma. Said derivatives are selected from following group of compounds: N-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminoacetamide hydrochloride (1.1), N-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminopropionamide hydrochloride (1.4), N-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminobutyramide hydrochloride (1.7), (R)-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminopropionamide hydrochloride (1.10), {3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-amide(R)-1-methylpyrrolidine-2-carboxylic acid hydrochloride (1.14). Invention also relates to a method of producing said compounds.

EFFECT: method consists in that compound of formula 2 or salt thereof: , where R² is a hydrogen atom, reacts with corresponding organic acid or an activated derivative thereof, with subsequent treatment of obtained product with hydrogen chloride solution.

11 cl, 1 tbl, 7 ex