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

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Abstract

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 abstract

The synthesis, evaluation, and structure–activity relationships of a series of phenylazobenzenesulfonamides as potent and selective COX-2 inhibitors are described.

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Acknowledgments

We gratefully thank the National Science Council of Republic of China Grants NSC-94-2320-B-077-005 (L.-M.Y.) and NSC-94-2320-B-038-030 (S.-J.L.), and National Research Institute of Chinese Medicine for research funding (Grant NRICM-95-DMC-007).

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