The design and synthesis of new triazolo, pyrazolo-, and pyridazo-pyridazine derivatives as inhibitors of angiotensin converting enzyme

Abstract

Bicyclic mimetics of the antihypertensive, angiotensin converting enzyme (A.C.E.) inhibitor, captopril, have been designed with the aid of computer graphics. The synthesis and structure activity relationships of the three bicyclic systems tetrahydro[1,2,4]triazolo[1,2-a]-, hexahydropyrazoio[1,2-a]- and octahydropyridazo[1,2-a]-pyridazinediones are described. The compounds with the terminal carboxy group, the thiol, and the amide carbonyl function orientated most closely to correspond to the three-dimensional array of these groups in bound captopril are the most active inhibitors of angiotensin converting enzyme, in vitro.