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

Denis Riendeau; Myriam Salem; Angela Styhler; Marc Ouellet; Joseph A Mancini; Chun Sing Li

doi:10.1016/j.bmcl.2003.12.047

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.

Authors

Denis Riendeau¹, Myriam Salem, Angela Styhler, Marc Ouellet, Joseph A Mancini, Chun Sing Li

Affiliation

¹ Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Quebec, Canada H9H 3L1. [email protected]

PMID: 14980665
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