NOVEL POTASSIUM-CHANNEL OPENERS - PREPARATION AND PHARMACOLOGICAL EVALUATION OF RACEMIC AND OPTICALLY-ACTIVE AMINO-3-PYRIDYL)-N'-BICYCLOALKYL-N'-CYANOGUANIDINE DERIVATIVES

The previous paper reported on the synthesis and pharmacological evalu ation of mino-3-pyridyl)-N'-bicycloalkyl-N''-cyanoguanidine derivative s, from among which three compounds were selected as potent potassium- channel openers. In the present study, selected compounds were tested for antagonism of potassium-induced contraction of rat aorta, hypotens ive activity in normotensive rats, and diuretic activity in spontaneou sly hypertensive rats. This led to further evaluation of compound (+/- )-10 and selection of 2R,4R)-bicyclo[2.2.1]hept-2-yl]-N''-cyanoguanidi ne ((+)-10) (AL0670) for development as an antihypertensive agent. Alt hough AL0670 is regarded as a pinacidil-type K+-channel opener, it sho wed different pharmacological and conformational profiles from pinacid il.