Design, Synthesis and ex vivo Study of the Vasorelaxant Activity Induced by Isosteric Derivatives of Dihydropyridines (NH→O)

Background: Hypertension is a complex and multifactorial disorder that is an important cause of morbidity and mortality in all around the world; and the rationalized structural modification of drugs represents an important strategy for to develop new antihypertensive drugs. Objective: To determine the vasorelaxant effect of 4H-pyranes and 2-pyridones derivatives designed from nifedipine and milrinone as pharmacophoric scaffolds. Methods: The vasorelaxant effect of all designed and synthesized compounds were carried out on the contraction induced by noradrenaline 0.1 μM in isolated rat aorta rings. Results: Compounds 4a—j, 6a-c and 8a-c showed a concentration– dependent and endothelium-independent relaxation on contraction induced by noradrenaline in isolated rat aorta rings. Compounds 6a, 8a, 8b, and 8c were the most potent compounds of entire series evaluated; however, were less potent than nifedipine and carbachol used as positive controls. Conclusions: Some compounds were designed and synthesized with significant vasorelaxant effect which can be used for the development of new antihypertensive drugs.