Characterization of two cyclic metabolites of sitagliptin.
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.
Liu
David Q
DQ
Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.
Arison
Byron H
BH
Stearns
Ralph A
RA
Kim
Dooseop
D
Vincent
Stella H
SH
D000818:Animals; D001711:Biotransformation; D003500:Cyclization; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D007004:Hypoglycemic Agents / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011719:Pyrazines / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D000068900:Sitagliptin Phosphate; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate