Synthesis And Positive Inotropic Activity Of [1,2,4]triazolo[4,3-a]quinoline Derivatives Containing Substituted 1,4-Diazepane Moiety

Congestive heart failure (CHF)is a reason of cardiovascular diseases whose mortalitystands the first place in the world. Therefore, finding new treatment methods of CHF isstill one of the most important challenges in the cardiovascular field at current and in thenear future.As reported, PHR0007 is 2(1H)-quinoline derivative having favorable activity strongerthan Vesnarinone. Therefore, the author designed to optimize the structure of PHR0007,changing piperazine to 1,4-diazepane ring, and changing the substituents on thebenzene ring simultaneously, to find new compounds with stronger activity and toinvestigate the structure-activity relationship.In order to develop more effective positive inotropic agents having lower side effects,15 derivatives of 2-[4-(4-(substitutedbenzyloxy-3-methoxybenzyl)-1,4-diazepam-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4, 3-a]quinolin-7-yl)acetamide were designed andsynthesized in this paper and their structures were confirmed by 1H-NMR, 13C-NMR, IRand MS.The biological evaluation were carried out on the isolated rabbit heart preparationsand the results shows that three (PHR0704, PHR0705, PHR0706) out of seventeencompounds exhibited significant inotropic activities.