In vitro biotransformations of the prostaglandin D2 (DP) antagonist MK-0524 and synthesis of metabolites

Bioorg Med Chem Lett. 2007 Jan 15;17(2):301-4. doi: 10.1016/j.bmcl.2006.10.055. Epub 2006 Oct 25.

Abstract

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 1H 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).

MeSH terms

  • Animals
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Dogs
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Macaca mulatta
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microsomes, Liver / metabolism
  • Oxidation-Reduction
  • Prostaglandin D2 / antagonists & inhibitors*
  • Rabbits
  • Rats
  • Saimiri
  • Sheep
  • Spectrophotometry, Ultraviolet

Substances

  • Indoles
  • MK-0524
  • Prostaglandin D2