Design, Synthesis, and Calcium Channel Antagonist Activity of New 1,4‐Dihydropyridines Containing 4‐(5)‐Chloro‐2‐ethyl‐5‐(4)‐imidazolyl Substituent

A series of dialkyl, dicycloalkyl, and diaryl ester analogues of nifedipine, in which the ortho ‐nitro phenyl group at position 4 is replaced by the 4‐(5)‐chloro‐2‐ethyl‐5‐(4)‐imidazolyl substituent, were synthesized and evaluated as calcium channel antagonists using the high K + contraction of guinea pig ileal longitudinal smooth muscle. The results for the symmetrical ester series showed that increasing the length of the chain in C 3 ‐ and C 5 ‐ester substituents increased the activity and the most active compound was the diphenylethyl ester derivative, so it was more active than the reference drug nifedipine. In unsymmetrical diester series, when R 1 is methyl or ethyl, increasing lipophilic properties in the R substituent, increased the activity. The most active compounds were methyl/phenethyl and ethyl/phenethyl ester derivatives, being slightly more active than nifedipine.