Synthesis and calcium channel antagonist activity of nifedipine analogues with methylthioimidazole substituent.

Various diester analogues of nifedipine, in which the orthonitrophenyl group at position 4 is replaced by 1-methyl-2-methylthio-5-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonists on guinea-pig ileal smooth muscle. Nifedipine was used as standard. Comparison of the activities of symmetrical esters (3a-e) indicate that increasing the length of alkyl chain in C3 and C5 ester substituents increases the antagonist activity and the n-propyl ester being preferred (IC50= 2.66 x 10(-9) M). In asymmetrical series (6a-g), compound 6g having ethyl and n-butyl ester at C3 and C5 positions of basic dihydropyridine structure was found to be the most active (IC50= 1.32 x 10(-9) M).