CONFORMATIONAL FEATURES OF CALCIUM-CHANNEL AGONIST AND ANTAGONIST ANALOGS OF NIFEDIPINE

Abstract

The crystal and molecular structures of methyl 2,6-dimethyl-5-nitro-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-2-carboxylate and ethyl 4-(2-difluoromethoxyphenyl)-1,4,5,7,-tetrahydro-2-methyl-5-oxofuro[3,4-b]pyridine-3-carboxylate, which are anlogs of the calcium channel antagonist nifedipine reported to have agonist activity, were determined. The conformations of these 2 agonists are compared with the conformational features shown by nifedipine and related 1,4-dihydropyridine calcium channel antagonists. Common conformational features shown by these agonists and antagonists allow both to the same plasma membrane receptor while subtle differences in hydrogen-bonding activity of the amino group, and ester group orientation and hydrophobic fit, may control the availability of channel open and closed states.