Characterization of the in vitro oxidative metabolites of the COX-2 selective inhibitor L-766,112

L-766,112 (1), a potent and selective inhibitor of human COX-2, was incubated with rat and rhesus monkey hepatic microsomal fractions under oxidative conditions to generate a metabolite identified as the thiophene S-oxide. This oxide was trapped with glutathione to give a conjugate in which GSH added to the 3 position. The metabolites, also identified in rat hepatocyte incubations, were characterized by UV, NMR, and CF-LSIMS.