New n - hexamethylene imino alkyl acetates and n - (n - hexamethylene imino alkyl) - acetamides

摘要

1384022 Hexamethyleneimines INNOTHERA 19 March 1973 [30 March 1972] 13161/73 Heading C2C Novel hexamethyleneimines of the general formula wherein R is a hydrogen atom or methyl or ethyl group, n is 0, 1, 2 or 3 and A is or R 1 R 2 CHCONH-, in which each of R 1 and R 2 is a straight or branched chain saturated C 1-6 aliphatic, allyl, cyclopentyl, cyclohexyl, cyclohexenyl, benzyl, halobenzyl, phenyl, halophenyl, methylphenyl, ethylphenyl, heterocyclyl or heterocyclylmethyl group, provided that when A is R 1 R 2 CHCOO- and one of R 1 and R 2 is a 3-thienyl group, the other is not a cyclopentyl, cyclohexyl, phenyl, halophenyl, methylphenyl or ethylphenyl group, including racemates and optical isomers, and quaternary ammonium pharmaceutically acceptable acid addition salts and derivatives thereof are prepared by condensing an acid of the general formula R 1 R 2 CHCOOH or a reactive functional derivative thereof with a hexamethyleneimine of the general formula wherein B is a halogen atom or hydroxyl or amino group. Acids of the second general formula above are prepared (a) by condensing mandelic acid, which may be substituted, with an appropriate benzene derivative in the presence of stannic chloride, (b) by condensing (by a malonic synthesis), optionally substituted ethyl phenylmalonate with benzyl chloride, which may be substituted, 2-chloromethylfuran or 2- or 3- chloromethyl-thiophene, followed by saponification and decarboxylation of the resulting malonic acid ester and (c) by reducing a glycollic acid of the general formula R 1 R 2 C(OH)COOH, obtained by condensing an appropriate glyoxylic acid with a Grignard reagent. Pharmaceutical compositions having spasmolytic and vasodilating activity comprise, as active ingredient, a hexamethyleneimine of the first general formula above or a pharmaceutically acceptable acid addition salt or quartenary ammonium derivative thereof, in association with a pharmaceutically acceptable carrier.