2-Aminoalkyl-1,4-di:hydro-pyridine derivs. - with broad spectrum of effects on the heart and circulation, e.g. lowering blood pressure and spasmolytic effect

摘要

Dihydropyridines of formula (I) and their pharmaceutically acceptable acid addn. salts are new: In (I), R1 is H, alkyl, alkoxyalkyl or aralkyl, opt. substd. in the alkyl or aryl fragments; A is opt. branched alkylene; Y and Z are each COOR2,COR2,CN or SO(n)R3; R2 is alkyl (opt. substd. by alkoxy OH, NH2, or alkylamino)alkenyl, alkynyl, alkylaminoaralkyl or aralkyl, opt. substd. as in R1; R3 is alkyl (opt. substd. by alkoxy, NH2 or alkylamino) alkenyl, aryl, or aralkyl, opt. substd. as in R1; n is 0-2. R4 is H, alkyl (opt. interrupted by O), or -ANH2; X is aryl. opt. substd. by 1-3 of phenyl, alkyl, alkenyl, alkynyl alkoxy, alkynyloxy, acyloxy, halo, CF3, CF3O,OH,NO2,CN N3,NH2 (opt. substd. by alkyl or acyl), carbalkoxy, carboxamido, sulphamido or SO(n)alkyl; or X is quinolyl, pyridyl, pyrimidyl, thienyl, furyl or pyrryl (opt. substd. by alkyl, alkylamino, NO2 or halo), or opt. substd. aralkyl cycloalkyl, cycloalkenyl or styryl. (I) have circulatory activity. The main effects are (i) powerful and sustained dilation of cardiac blood vessels reinforced by a nitrate-like effect on the heart and modification of cardiac metabolism to save energy; (ii) redn. of blood pressure in normal and hypertonic subjects; (iii) antifibrillatory effect; (iv) spasmolytic effect on smooth muscles of the vascular system, stomach, intestines, urogenital tract and respiratory system; (v) effect on blood lipid and cholesterol levels.