SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF INO-3-PYRIDYL)-N'-BICYCLOALKYL-N''-CYANOGUANIDINES AS ANTIHYPERTENSIVE AGENTS

A series of amino acid conjugates of amino-3-pyridyl)-N'[exo-bicyclo[2 .2.1]hept-2-yl]-N ''-cyanoguanidine (4) were prepared and evaluated as antihypertensive agents. The parent compound 4 showed potent potassiu m channel-opening and antihypertensive activities, but with undesirabl e changes of the urinary balance of electrolytes. However, alanine and histidine congeners (9,19) reduced this undesirable side effect of 4 through improved pharmacokinetics without loss of antihypertensive act ivity. They also provided additional information on the structural req uirements for pinacidil-type potassium channel openers.