Synthesis And Positive Inotropic Activity Of Oxazinone's Derivates

At present, the mortality caused by cardiovascular disease are decreasing, but the mortality caused by congestive heart failure are still rising. According to the statistics of New York Cardiology Institute, the mortality of the cardiac failure patients is about 50%. Now, more and more experts and scholars are paying great attention to the treatment of cardiac failure.In a searching of more effective inotropic agents having less side effect, Huri Piao et al. designed and synthesized 20 derivates of 2-(4-substitutedpiperazin-1-yl)-N-(1,2,3,4-tetrahydro-2-oxoquinolin-6-yl)acetamide, in which PHR960012 and PHR96003 having moderate inotropic activity were screened out. In the attempt of optimizing the structure of PHR960012, the author designed to change piperidinone moiety to morpholinone, and to change the substituents on the piperazine simultaneously, to find new compounds with stronger activity and to investigate the structure-activity relationship.In order to develop more effective positive inotropic agents having lower side effects, 18 derivatives of 2-(4-substitutedpiperazine-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4] oxazin-7-yl)acetamide were designed and synthesized in this paper and their structures were confirmed by 1H-NMR, 13C-NMR, lR and MS.The biological evaluation were carried out on the isolated rabbit heart preparations and the results shows that three (PHRL0709, PHRL0711, PHRL0712) out of 17 compounds exhibited inotropic activities.