Synthesis, QSAR and calcium channel antagonist activity of new 1,4-dihydropyridine derivatives containing 1-methyl-4,5-dichloroimidazolyl substituents

A group of dialkyl and diarylester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 was replaced by a 1-methyl-4,5-dichloroimidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K, concentration of guinea-pig ileum longitudinal smooth muscle. The structure of all compounds was confirmed by IR, (HNMR)-H-1, and mass spectra. The calcium-channel antagonist activity of compounds 10a-f demonstrated that compound 10b was the most active and 10f the least active one. With unsymmetrical diesters 12a-k, the most active compound was the ethyl, phenethyl derivative. Structural parameters on the calcium-channel antagonist activity were evaluated by QSAR analysis and a linear correlation was found between the -log IC50 values of these compounds and their constitutional and topological properties.