In Vitro Biotransformations Of The Prostaglandin D-2 (Dp) Antagonist Mk-0524 And Synthesis Of Metabolites

Metabolites of the potent DP antagonist, MK-0524, were generated using in vitro systems including hepatic microsomes and hepatocytes. Four metabolites (two hydroxylated diastereomers, a ketone and an acyl glucuronide) were characterized by LC-MS/MS and H-1 NMR. Larger quantities of these metabolites were prepared by either organic synthesis or biosynthetically to be used as standards in other studies. The propensity for covalent binding was assessed and was found to be acceptable (< 50 pmol-equiv/mg protein). (c) 2006 Elsevier Ltd. All rights reserved.