Synthesis and β-adrenergic blocking activity of oxime ether hybrids derived from a natural isochroman-4-one

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, β 1 -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 β 1 -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.