Abstract: AIM:In a search for new cardiovascular drug candidates,a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized.METHOD:Compounds 3 and 6,derived from the natural antihypertensive compound 7,8-dihydroxy-3-methyl-isochroman-4-one(XJP),were designed and synthesized.Subsequently,a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime.Furthermore,β1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria.RESULTS:Twenty target compounds were obtained,and the preliminary structure-activity relationships were deduced.The most promising compound Ic exhibited β1-adrenoceptor blocking activity(inhibition:52.2%) at 10-7 mol·L-1,which was superior to that of propranolol(inhibition:49.7%).CONCLUSION:The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.