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, ß1-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 ß1-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.
Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Adrenergic beta-Antagonists/pharmacology , Benzopyrans/chemical synthesis , Benzopyrans/pharmacology , Drugs, Chinese Herbal/chemical synthesis , Drugs, Chinese Herbal/pharmacology , Hypertension/drug therapy , Oximes/chemistry , Adrenergic beta-Antagonists/chemistry , Animals , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/chemistry , Antihypertensive Agents/pharmacology , Benzopyrans/chemistry , Drugs, Chinese Herbal/chemistry , Humans , Hypertension/physiopathology , Male , Molecular Structure , Rats , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
Neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata, was synthesized through a key coupling reaction between a perbenzylated thiosugar and an appropriately protected perseitol triflate derived from D-mannose. This key step was found to be quite temperature dependent, and a simultaneous cyclization of the triflate leading to a characteristic 2,4,7-trioxabicyclo[4.2.1]nonane system was detected.