Synthesis and calcium channel antagonist activity of 4-[[halobenzyl] imidazolyl] dihydropyridines

ABSTRACT

Seven analogues of nifedipine [in which the ortho nitrophenyl group at position 4] were replaced by 2-alkylthio-1-[halobenzyl-5-imidazolyl substituent] were synthesized and evaluated as calcium antagonists using the high K[+] contraction of rat ileal longitudinal smooth muscle. These analogues of nifedipine decreased the various contractile responses of the longitudinal smooth muscle of the isolated rat ileum in a dose-dependent manner. However, their potencies for inhibition of contraction varied significantly from each other. All tested compounds [except compound 5f], were stronger than nifedipine with IC50 1.16 x 10[-13]M. Compound 5a with IC[50] 6.73 x 10[-15]M was the most active compound tested