Characterization Of Two Cyclic Metabolites Of Sitagliptin
DRUG METABOLISM AND DISPOSITION(2007)
摘要
Two novel metabolites of the dipeptidyl peptidase inhibitor sitagliptin (MK-0431, (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[ 1,2,4] triazolo[4,3-a] pyrazin-7(8H)- yl]-1-(2,4,5-trifluorophenyl)butan-2- amine), were identified after purification from dog urine. The metabolites ( referred to as M2 and M5) were characterized by hydrogen/deuterium exchange tandem mass spectrometry and NMR spectroscopy nuclear Overhauser effect experiments as the cis and trans stereoisomers formed by cyclization of the primary amino group with the alpha carbon of the piperazine ring, following oxidative desaturation.
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