SYNTHESES AND BIOLOGICAL-ACTIVITIES OF POTENT POTASSIUM CHANNEL OPENERS DERIVED FROM (+ -)-2-OXO-1-PYRIDIN-3-YL-CYCLOHEXANECARBOTHIOIC ACIDMETHYLAMIDE - NEW POTASSIUM CHANNEL OPENERS/

The syntheses and biological activities of anomethylene)-1-pyridin-3-y lcyclohexanecarbothioic acid methylamide (6) and (cyanomethyl)-1-pyrid in-3-ylcyclohexanecarbothioic acid methylamide (14) derived from (+/-) -2-oxo-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (4) are r eported. Compounds were tested for antagonism of potassium-induced con traction of de-endothelialized rat aorta. The effects of modification of 6 and 14 on in vitro K+-channel opening activity are presented. The se new series of potassium channel openers so derived are best exempli fied by l)ethylidene]-1-pyridin-3-ylcyclohexanecarbothioic acid methyl amide (13d, RP 66266) and )amino]ethyl]-1-pyridin-3-ylcyclohexanecarbo thioic acid methylamide (25a, RP 66784), which have IC90 values of 3 a nd 0.3 nM, respectively. The potency of the most active compounds indi cates a possible interaction at an extra binding site. The compounds d escribed herein are potential antihypertensive and antianginal agents.