SUBSTITUTED N-{3-[4-(1-METHYL-1H-INDOL-3-YL)PYRIMIDIN-2-YLAMINO]-4-METHOXYPHENYL}-AMIDES AS MODULATORS OF EGFR, APPLICABLE FOR TREATING CANCER Russian patent published in 2017 - IPC C07D403/04 A61K31/506 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted N-{3-[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-ylamino]-4-methoxyphenyl}-amides of general formula 1 and pharmaceutically acceptable salts thereof, having properties of modulators of EGFR and suitable for treating cancer, for example small cell lung cancer. In general formula 1

R¹ represents CH₂=C(R³)-, R³CH=CH-; R² is (2-dimethylaminoethyl)-methylamino, 3-dimethylaminopiperidin-1-yl; R³ is fluorine, trifluoromethyl, dimethylcarbamoyl; or R² is 3-dimethylaminopiperidin-1-yl; R³ is H; or mesylate compound 1, where R¹ is C(CH3)≡C-, R² is (2-dimethylaminoethyl)-methylamino. Preferable compounds are N-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-2-fluoro-acrylamide (1.2); N-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-4,4,4-trifluorobut-2-enamide (1.6); (E)-3-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenylcarbamoyl}-N,N-dimethylacrylamide (1.8); N-{2-(3-dimethylaminopiperidin-1-yl)-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-acrylamide (1.11); mesylate N-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-2-butynamide (1.14⋅CH₃SO₃H) or mesylate N-{2-(3-dimethylaminopiperidin-1-yl)-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-acrylamide (1.11⋅CH₃SO₃H). Invention also relates to a method of producing compounds of formula 1.

EFFECT: method involves reacting a compound of formula 2 or its salt with activated derivative of corresponding organic acid, such as an acid, ester or organic acid anhydride.

15 cl, 2 tbl, 14 ex