Synthesis and evaluation of 1,5-diaryl-substituted tetrazoles as novel selective cyclooxygenase-2 (COX-2) inhibitors

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]