Design and synthesis of new potassium channel activators derived from the ring opening of diazoxide: study of their vasodilatory effect, stimulation of elastin synthesis and inhibitory effect on insulin release

Bioorganic & Medicinal Chemistry
Nafila BouiderSmail Khelili

Abstract

Benzenesulfonylureas and benzenesulfonylthioureas, as well as benzenecarbonylureas and benzenecarbonylthioureas, were prepared and evaluated as myorelaxants on 30mMKCl-precontracted rat aortic rings. The most active compounds were further examined as stimulators of elastin synthesis by vascular smooth muscle cells and as inhibitors of insulin release from pancreaticβ-cells. The drugs were also characterized for their effects on glycaemia in rats. Benzenesulfonylureas and benzenesulfonylthioureas did not display any myorelaxant activity on precontracted rat aortic rings. Such an effect could be attributed to their ionization at physiological pH. By contrast, almost all benzenecarbonylureas and benzenecarbonylthioureas displayed a myorelaxant activity, in particular the benzenecarbonylureas with an oxybenzyl group linked to the ortho position of the phenyl ring. The vasodilatory activity of the most active compounds was reduced when measured in the presence of 80mMKCl or in the presence of 30mM KCl and 10μM glibenclamide. Such results suggested the involvement, at least in part, of KATP channels. Preservation of a vasodilatory activity in rat aortic rings without endothelium indicated that the site of action of such molecules was...Continue Reading

Citations

Jan 12, 2017·Journal of Cellular Physiology·Sheng-Nan WuFeng-Shiun Shie
May 2, 2018·Current Medicinal Chemistry·Vivek K VyasManjunath Ghate
Apr 2, 2016·Journal of Cardiovascular Pharmacology·Xiaojing LiuQinglei Zhu
Oct 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ndze Denis JumbamSphumusa Mtwa
Apr 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Benjamin D DicksonMichael P Hay
Sep 8, 2019·Matrix Biology : Journal of the International Society for Matrix Biology·Wassim FhayliGilles Faury

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