Synthesis and Pharmacological Evaluation of N-(6-Functionalized-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidines as Antihypertensive Agents

Abstract

A series of amino acid conjugates of N-(6-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 potassium channel-opening and antihypertensive activities, but with undesirable changes of the urinary balance of electrolytes. Howere, alanine and histidine congeners (9, 19) reduced this undesirable side effect of 4 through improved pharmacokinetics without loss of antihypertensive activity. They also provided additional information on the structural requirements for pinacidil-type potassium channel openers.