Selective COX-2 inhibitors. Part 2: Synthesis and biological evaluation of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamides

Two series of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB). Extensive structure–activity relationships (SAR) were studied within these series. Several compounds were found to be novel and selective COX-2 inhibitors. Among them, the most potent and selective was 4-(3-carboxy-4-hydroxy-benzylideneamino)benzenesulfonamide (20, LA2135), (IC50’s for COX-1: 85.13 μM; COX-2: 0.74 μM; SI: 114.5), being more active COX-2 selective than celecoxib.

The synthesis, evaluation, and structure–activity relationships of two series of benzenesulfonamides as potent and selective COX-2 inhibitors are described.Figure optionsDownload as PowerPoint slide