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

Baker Jawabrah Al-Hourani; Sai Kiran Sharma; Jonathan Y Mane; Jack Tuszynski; Vickie Baracos; Torsten Kniess; Mavanur Suresh; Jens Pietzsch; Frank Wuest

doi:10.1016/j.bmcl.2011.01.057

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

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1823-6. doi: 10.1016/j.bmcl.2011.01.057. Epub 2011 Jan 21.

Authors

Baker Jawabrah Al-Hourani¹, Sai Kiran Sharma, Jonathan Y Mane, Jack Tuszynski, Vickie Baracos, Torsten Kniess, Mavanur Suresh, Jens Pietzsch, Frank Wuest

Affiliation

¹ Department of Oncology, University of Alberta, Edmonton, Canada.

PMID: 21316237
DOI: 10.1016/j.bmcl.2011.01.057

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 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cyclooxygenase 2 Inhibitors / chemical synthesis*
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology*
Drug Evaluation, Preclinical
Hydrogen Bonding
Models, Molecular
Tetrazoles / chemical synthesis*
Tetrazoles / chemistry
Tetrazoles / pharmacology*

Substances

Cyclooxygenase 2 Inhibitors
Tetrazoles

Grants and funding

Canadian Institutes of Health Research/Canada