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.
Keywords: Antihypertensive activity; Hybrids; Isochroman-4-one derivatives; Oxime ethers; β-Adrenergic blocking activity.
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