Novel Potassium-Channel Openers: Preparation and Pharmacological Evaluation of Racemic and Optically Active N-(6-Amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine Derivatives

Article abstract of DOI:10.1021/jm00039a011

The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, 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, hypotensive activity in normotensive rats, and diuretic activity in spontaneously hypertensive rats. This led to further evaluation of compound (+/-)-10 and selection of (+)-N-(6-amino-3-pyridyl)-N'-<(1S,2R,4R)-bicyclo<2.2.1>hept-2-yl>-N"-cyanoguanidine ((+)-10) (AL0670) for development as an antihypertensive agent. Although AL0670 is regarded as a pinacidil-type K⁺-channel opener, it showed different pharmacological and conformational profiles from pinacidil.