6-Substituted 2,2-bis(fluoromethyl)-benzopyran-4-carboxamide K+ channel openers.

Abstract In the course of our study to find an ideal antihypertensive potassium channel opener (KCO), N -(2-cyanoethyl)-2,2-bis(fluoromethyl)-6-pentafluoroethyl-2 H -1-benzopyran-4-carboxamide ( 13f , KC-515) showed a highly potent, slow and long-lasting antihypertensive effect with reduced reflex tachycardia, together with the beneficial effects of KCO such as improvement in lipid metabolism. These profiles identify KC-515 as a potential candidate. In conscious spontaneously hypertensive rats (SHR), the onset of the hypotensive effect of KC-515 ( 13f ) was gradual and the maximum response was attained at around 6 h after dosing. The duration of action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks with 0.03–0.3 mg/kg po range in the antihypertensive doses in hypertensive rat models, KC-515 ( 13f ) significantly and dose-dependently reduced serum triglycerides to less than 70% of control without affecting total cholesterol.