Synthesis and biological evaluation of several 3-(coumarin-4-yl)tetrahydroisoxazole and 3-(coumarin-4-yl)dihydropyrazole derivatives

A series of novel 3-(coumarin-4-yl)tetrahydroisoxazoles 5a,b, 7, 9 and 3-(coumarin-4-yl)dihydropyrazoles 13a-d, 14, 15a,b were synthesized from coumarin-4-carboxaldehyde 1 via the intermediate N-methyl nitrone 3 and N-phenyl or N-methyl hydrazones 11a,b, These coumarin derivatives were isolated, characterized and evaluated in vitro for their ability to inhibit trypsin, P-glucuronidase, soybean lipoxygenase and to interact with the stable radical 1,1-diphenyl-2-picrylhydrazyl. The compounds were tested in vivo as antiinflammatory agents in the rat carrageenin paw edema assay. Compound 15a seems to be a lead molecule to be modified in order to improve the lipoxygenase inhibition. The results are discussed in terms of structural characteristics.