Synthesis And Positive Inotropic Activity Of The Benzyl Of Piperaquine Ketone Derivatives

Generally speaking, the mortality caused by angiocardiopathy is declining eveiy year, but the mortality caused by congestive heart failure (Cl-IF) is rising steadily and there is short of effective drugs for Cl-IF in clinic up till the present moment. Therefore, the great efforts for developing new positive inotropic agents are being made by scientists. In order to developing more effective positive inotropic agents having lower side effects, I-jun Piao et al reported the synthesis and the positive inotropic activities of 20 4-substitutedpiperazine- 1 -acetamido-3 ,4-dihydroquinolinon e derivatives using the principle of isosterism through investigating and analysing the structure and the activities of reported 3 ,4-dihydroquinolinone derivatives, among which the PHR9 600 12 has been screened and showed the moderate positive inotropic activity followed angiectatic effect and high selectivity (having few effects on the heart -3- rate). In this paper, a series of substituents on the benzene ring of the benzyl group on the PI-IiR9600 12 which was considered as a lead compound were investigated and the corresponding 14 compounds were synthesized. Their structures were confirmed by IR, 慖-INN4R and elemental analysis and the myocardial contraction forces were measured on the isolated cardiac muscles of guinea pigs using Milinone as a control. The biological tests showed that 8 compounds exhibited stronger activities compared to Milinone and compounds PI-1R9906 and PHR9903 showed the most significant positive inotropic activities among those compounds, which were of great value to be developed as new cardiotonics.