ANTI-CANCER BENZOPYRAZINES ACTING THROUGH FGFR-KINASES INHIBITION Russian patent published in 2017 - IPC C07D241/42 C07D241/44 C07D401/04 C07D403/04 C07D407/04 C07D413/04 A61K31/498 A61K31/4985 A61K31/506 A61K31/5377 A61P35/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to benzopyrazine derivatives of the general formula (I)

,

including any stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof, wherein W is -N(R³)-; R² is C_1-4alkoxy; Y is -CR¹⁸=N-OR¹⁹ or -E-D; E is bond, C_2-4alkynediyl, -CO-(CR²²R²³)_s-, -NR²²-(CR²²R²³)_s-, -(CR²²R²³)_s-CO-NR²²-(CR²²R²³)_s- or -(CR²²R²³)_s-NR²²-CO-(CR²²R²³)_s-; D is phenyl, 3-6 membered cycloalkyl or 5-9 membered mono- or bicyclic saturated, partially saturated or aromatic heterocyclyl containing 1-4 heteroatoms selected from N, O or S, wherein the said phenyl, cycloalkyl and heterocyclyl can each optionally being substituted with 1-2 R¹-groups; with the exception of the compounds indicated in the formula; R¹ is halogen, cyano, C_1-6alkyl, C_1-6alkoxy, -C(=O)-O-C_1-6alkyl, hydroxyC_1-6alkyl, -NR⁴R⁵ , C_1-6alkyl substituted by -O-C(=O)-C_1-6alkyl, C_1-6alkyl substituted by -NR⁴R⁵, -C(=O)-NR⁴R⁵, R⁶, C_1-6alkyl substituted by R⁶, -C(=O)-R⁶; R³ is halogenC_1-6alkyl, optionally substituted by -O-C(=O)-C_1-6alkyl, hydroxyC_1-6alkyl, hydroxyhalogenC_1-6alkyl, C_1-6alkoxyC_1-6alkyl, where each C_1-6alkyl may optionally be substituted by one hydroxyl group or -O-C(=O)-C_1-6alkyl, C_1-6alkyl substituted by R⁹, C_2-6alkynyl substituted with R⁹, C_1-6alkyl substituted by -NR¹⁰R¹¹, C_1-6alkyl substituted by -O-C(=O)-NR¹⁰R¹¹; R⁴ and R⁵ are hydrogen, C_1-6alkyl, C_1-6alkyl substituted by -NR¹⁴R¹⁵, hydroxyC_1-6alkyl, C_1-6alkoxyC_1-6alkyl, where each C_1-6alkyl may optionally be substituted by one hydroxyl group, -C(=O)-NR¹⁴R¹⁵, -C(=O)-O-C_1-6alkyl, -C(=O)-R¹³; R⁶ is a 6-membered saturated or aromatic monocyclic heterocyclyl having 1 to 2 heteroatoms selected from N or O; the said heterocyclyl is optionally substituted by 1 substituent selected from C_1-6alkyl, halogen, C_1-6alkyl-O-C(=O)-; R⁹ is C₃cycloalkyl or 3-6 membered monocyclic saturated, partially saturated or aromatic heterocyclyl containing 1-2 heteroatoms selected from N or O, the said heterocyclyl is optionally substituted by 1 substituent selected from =O, hydroxyC_1-4alkyl, C_1-4alkyl-C(=O)-, C_1-4alkyl substituted by -NR¹⁴R¹⁵, C_1-4alkoxy; R¹⁰ and R¹¹ are hydrogen, C_1-6alkyl, halogen C_1-6alkyl, hydroxyC_1-6alkyl or C_1-6alkyl substituted by carboxyl; R¹³ is a saturated 6-membered monocyclic heterocyclyl containing 1-2 heteroatoms selected from N and O; R¹⁴ and R¹⁵ are hydrogen or C_1-4alkyl; R¹⁸ and R¹⁹ are C_1-6alkyl; R²² and R²³ are hydrogen; n=2; s=0, 1, 2, or 3. Invention also relates to a pharmaceutical composition and a product based thereon, the use of a compound of formula (I) and a method of prevention or treatment of conditions mediated by FGFR kinase.

EFFECT: new derivatives of benzopyrazine, useful for cancer treatment.

28 cl, 4 tbl, 54 ex