Synthesis and biological evaluation of 4,5-diphenyloxazolone derivatives on route towards selective COX-2 inhibitors

A series of 3-unsubstituted/substituted-4,5-diphenyl-2-oxo-3H-1,3-oxazole derivatives were prepared as selective cyclooxygenase-2 (COX-2) inhibitors. Among the synthesized compounds, 4-(4-phenyl-3-methyl-2-oxo-3H-1,3-oxazol-5-yl)benzensulfonamide (compound 6) showed selective COX-2 inhibition with a selectivity index of >50 (IC50COX-1 = >100 μm, IC50COX-2 = 2 μm) in purified enzyme (PE) assay. Compound 6 also exhibited selective COX-2 inhibition in human whole blood assay. Molecular docking studies showed that 6 can be docked into the COX-2 binding site thus providing the molecular basis for its activity.

Graphical abstractA series of 3-unsubstituted/substituted-4,5-diphenyl-2-oxo-3H-1,3-oxazole derivatives were prepared and evaluated for their inhibitory properties of cyclooxygenase-2 (COX-2).Figure optionsDownload full-size imageDownload as PowerPoint slide