Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1201-3. doi: 10.1016/j.bmcl.2003.12.047.

Abstract

Loxoprofen, its trans-alcohol and cis-alcohol metabolites were evaluated for selectivity of inhibition of COX-2 over COX-1. The (2S,1'R,2'S)-trans-alcohol derivative was found to be the most active metabolite and to be a potent and nonselective inhibitor of COX-2 and COX-1 in both enzyme and human whole blood assays.

MeSH terms

  • Alcohols / metabolism
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / metabolism*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Membrane Proteins
  • Phenylpropionates / chemistry
  • Phenylpropionates / metabolism*
  • Phenylpropionates / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / metabolism

Substances

  • Alcohols
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Phenylpropionates
  • loxoprofen
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases