title: In vitro biotransformations of the prostaglandin D2 (DP) antagonist MK-0524 and synthesis of metabolites.
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).
authors.affiliation: Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Que., Canada H9R 4P8. deborah_nicoll-griffith@merck.com
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nicoll-Griffith
authors.forename: Carmai
authors.initials: C
authors.lastname: Seto
authors.forename: Yves
authors.initials: Y
authors.lastname: Aubin
authors.forename: Jean François
authors.initials: JF
authors.lastname: Lévesque
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chauret
authors.forename: Stephen
authors.initials: S
authors.lastname: Day
authors.forename: José M
authors.initials: JM
authors.lastname: Silva
authors.forename: Laird A
authors.initials: LA
authors.lastname: Trimble
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Truchon
authors.forename: Carl
authors.initials: C
authors.lastname: Berthelette
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lachance
authors.forename: Zhaoyin
authors.initials: Z
authors.lastname: Wang
authors.forename: Claudio
authors.initials: C
authors.lastname: Sturino
authors.forename: Matt
authors.initials: M
authors.lastname: Braun
authors.forename: Robert
authors.initials: R
authors.lastname: Zamboni
authors.forename: Robert N
authors.initials: RN
authors.lastname: Young
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D012453:Saimiri; D012756:Sheep; D013056:Spectrophotometry, Ultraviolet
chemical_list: D007211:Indoles; C518174:MK-0524; D015230:Prostaglandin D2