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Abstract: A series of novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors was prepared via treatment of various diaryl amides with tetrachlorosilane/sodium azide. All compounds were tested in cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Tetrazoles contained a methylsulfonyl or sulfonamide group as COX-2 pharmacophore displayed only low inhibitory potency towards COX-2. Most potent compounds showed IC50 values of 6 and 7μM for COX-2. All compounds showed IC50 values greater 100μM for COX-1 inhibition. [Copyright &y& Elsevier]

Abstract: A series of 1,5-diaryl-substituted tetrazole derivatives was synthesized via conversion of readily available diaryl amides into corresponding imidoylchlorides followed by reaction with sodium azide. All compounds were evaluated by cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Tetrazoles 3a–e showed IC50 values ranging from 0.42 to 8.1mM for COX-1 and 2.0 to 200μM for COX-2. Most potent compound 3c (IC50 (COX-2)=2.0μM) was further used in molecular modeling docking studies. [Copyright &y& Elsevier]