Synthesis and calcium antagonist activity of 1,4-dihydropyridines containing phenylaminoimidazolyl substituents.

Alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by 2-methylthio-1-phenylamino-5-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 esters showed that in the series of alkyl esters increasing the length of methylene chain in C-3 and C-5 ester substituents for more than two methylene units decreases activity. In the phenylalkyl ester series increasing the length of methylene chain also decreases activity. The results demonstrate that most of the compounds had similar activity to the reference drug nifedipine. In addition, two compounds, 5b and 5f were more active than the nifedipine.