Synthesis and activity on rat aorta rings and rat pancreatic beta-cells of ring-opened analogues of benzopyran-type potassium channel activators

Ring-opened analogues of dihydrobenzopyran potassium channel openers (PCOs) were prepared and evaluated as putative PCOs on rat aorta rings (myorelaxant effect) and rat pancreatic beta-cells (inhibition of insulin secretion). These derivatives are characterized by the presence of a sulfonylurea, a urea or an amide function. Some compounds bearing an arylurea moiety provoked vasorelaxant effects and a marked inhibition of insulin release. Derivatives bearing a sulfonylurea or an amide function were, however, poorly active on both tissues. Structure-activity relationships and apparent tissue selectivity are discussed.