In vitro biotransformations of the prostaglandin D2 (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 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).
Nicoll-Griffith
Deborah A
DA
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Que., Canada H9R 4P8. deborah_nicoll-griffith@merck.com
Seto
Carmai
C
Aubin
Yves
Y
Lévesque
Jean François
JF
Chauret
Nathalie
N
Day
Stephen
S
Silva
José M
JM
Trimble
Laird A
LA
Truchon
Jean-François
JF
Berthelette
Carl
C
Lachance
Nicolas
N
Wang
Zhaoyin
Z
Sturino
Claudio
C
Braun
Matt
M
Zamboni
Robert
R
Young
Robert N
RN
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
D007211:Indoles; C518174:MK-0524; D015230:Prostaglandin D2