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

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 8.1 mM for COX-1 and 2.0 to 200 μM for COX-2. Most potent compound 3c (IC50 (COX-2) = 2.0 μM) was further used in molecular modeling docking studies.

Graphical abstractA series of 1,5-diaryl-substituted tetrazole derivatives was synthesized. All compounds were evaluated in in vitro cyclooxygenase (COX) assays to determine COX-1 and COX-2 inhibitory potency and selectivity.Figure optionsDownload full-size imageDownload as PowerPoint slide