Novel 1,4-dihydropyridine calcium antagonists. II. Synthesis and antihypertensive activity of 3-[4-(substituted amino)phenylalkyl]ester derivatives

Novel 1,4-dihydropyridine derivatives bearing 3-[4-(substituted amino)phenylalkyl]ester side chains were prepared and tested for their antihypertensive activity in spontaneously hypertensive rats. Most compounds showed a more potent antihypertensive effect and a longer duration of action than nicardipine. The derivatives with a benzhydrylpiperazinyl and a benzhydrylpiperidinyl group were distinctive. 2-[4-(4-Benzhydryl-1-piperazinyl)phenyl]ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (4e), its 4-(4-cyano-2-pyridyl) analogue (4f), its 3-[4-(4-benzhydryl-1-piperazinyl)phenyl]propyl ester analogue (4h), its 2-[4-(4-benzhydryl-1-piperidinyl)phenyl]ethyl ester analogue (4j), and its 2-[4-(1-benzhydryl-4-piperidinyl)phenyl]ethyl ester analogue (4k) were selected as candidates for further pharmacological investigations.