Synthesis and positive inotropic evaluation of 1-(benzylamino)-3-(4,5-di-hydro 1,2,4trizaolo4,3-aquinolin-7-yloxy)propan-2-ol derivatives

摘要

In an attempt to search for more potent positive inotropic agents,a series of 1-(benzylamino)-3-(4,5-dihydro[1,2,4]trizaolo[4,3-a]quinolin-7-yloxy)propan-2-ol derivatives was synthesized in four steps using 6-hydroxy-3,4-dihydro-2(1H)-quinolinone as a starting material,and their positive inotropic activities were evaluated by measuring the coronary blood flow(CBF)and the left ventricular pressure(LVP)followed by calculating the rate of pressure development(dp/dtmx values)in the preparation of rat Langendorff's heart.Three compounds(5d,5g,5j)showed favorable activities,among which 5g was shown the most potent with dp/dtmax value of 9.7% and CBF value of 17.8% at a concentration of 1×10-5 mol/L in our in vitro study.