Selective COX-2 inhibitors. Part 1: Synthesis and biological evaluation of phenylazobenzenesulfonamides

A series of phenylazobenzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB) and an enzymatic assay using purified ovine enzymes. Extensive structure–activity relationships (SAR) were studied within this series, and several of selective COX-2 inhibitors have been identified. Among them, compound 8, 4-(4-amino-2-methylsulfanyl-phenylazo)benzenesulfonamide, showed a potent inhibitory activity to the cyclooxygenase enzymes (IC50’s for COX-1: 23.28 μM; COX-2: 2.04 μM), being active but less COX-2 selective than celecoxib.

Graphical abstractThe synthesis, evaluation, and structure–activity relationships of a series of phenylazobenzenesulfonamides as potent and selective COX-2 inhibitors are described.Figure optionsDownload full-size imageDownload as PowerPoint slide