Cardiotonic agents. 10. Cardiovascular evaluation of dihydropyridazinone ring open analogues of imazodan

Abstract Several series of 4,5-dihydropyridazinone ring (A-ring) open analogues of imazodan (CI-914) were prepared and evaluated for inotropic activity in an anesthetized dog model. Although the overall cardiovascular profile of the acylhydrazone series was similar to the corresponding cyclic analogues, the inotropic potency was significantly reduced. The guanylhydrazone series demonstrated enhanced inotropic potency that was comparable to 4,5-dihydropyridazinones (DHPZ). Although these acyclic analogues qualitatively fit a 5-point model developed for several cyclic inotropes, at least partly, the inotropic mechanism of the guanylhydrazones seems to be different from the corresponding acylhydrazones and cyclic 4,5-dihydropyridazinones.