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.

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