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

• Published in: Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (6), p.1823-1826
• Main Authors: Al-Hourani, Baker Jawabrah, Sharma, Sai Kiran, Mane, Jonathan Y., Tuszynski, Jack, Baracos, Vickie, Kniess, Torsten, Suresh, Mavanur, Pietzsch, Jens, Wuest, Frank
• Format: Article
• Language: English
• Subjects: 1,5-Diaryl-tetrazoles; amides; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; COX-2 inhibitors; Cyclooxygenase; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacology; Drug Evaluation, Preclinical; Hydrogen Bonding; in vitro studies; inhibitory concentration 50; Medical sciences; Models, Molecular; Pharmacology. Drug treatments; prostaglandin synthase; sodium azide; Tetrazoles - chemical synthesis; Tetrazoles - chemistry; Tetrazoles - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.01.057

A 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. 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 IC 50 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 (IC 50 (COX-2) = 2.0 μM) was further used in molecular modeling docking studies.