Ivashchenko Aleksandr Vasilevich,Иващенко Александр Васильевич,Ignatev Vasilij Gennadevich,Игнатьев Василий Геннадьевич,Repik Aleksej Evgenevich,Репик Алексей Евгеньевич,Shafeev Mikhail Ajratovich,Шаф
申请号：
RU2015149668
公开号：
RU0002606949C9
申请日:
2015.11.19
申请国别(地区):
RU
年份:
2018
代理人:
摘要：
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 1R1 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 exИзобретение относится к новым замещенным N-{3-[4-(1-метил-1Н-индол-3-ил)пиримидин-2-иламино]-4-метоксифенил}-амидам общей формулы 1 и их фармацевтически приемлемым солям, обладающим свойствами модуляторов EGFR и пригодным для л
