Synthesis and effects of novel dihydropyridines as dual calcium channel blocker and angiotensin antagonist on isolated rat aorta

Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors [AT1] and L-type calcium channels were investigated on isolated rat aorta. Aortic rings were pre-contracted with 1 microM Angiotensin II or 80 mM KC1 and relaxant effects of losartan, nifedipine, 5a and 5b were evaluated by cumulative addition of these drugs to the bath solution. The results showed that compounds 5a and 5b have both L-type calcium channel and AT1 receptor blocking activity. Their effects on AT1 receptors are 1000 and 100, 000 times more than losartan respectively. The activity of compound 5b on L-type calcium channel is significantly less than nifedipine but compound 5a has comparable effect with nifedipine. Finally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents