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

作者：Rendon Vallejo Priscila; Estrada Soto Samuel^*; Vazquez Miguel A^*; Hernandez Borja Fernando; Villalobos Molina Rafael; Ibarra Barajas Maximiliano

来源：Letters in Drug Design and Discovery, 2016, 13(5): 353-359.

DOI：10.2174/1570180812666151003002501

• 4H-pyrans
• 2-pyridones
• antihypertensive
• drug design
• hypertension
• vasorelaxant

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 mu M 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.

• 出版日期2016