Journal
DRUG METABOLISM AND DISPOSITION
Volume 34, Issue 9, Pages 1502-1507Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.106.009282
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The glucuronidation of (1S, 2R, 3R, 5R)-3-(hydroxymethyl)-5-[7{[( 1R, 2S)-2-phenylcyclopropyl]amino}-5-(propylthio)-3H-[1,2,3] triazolo[ 4,5-d] pyrimidin-3-yl]cyclopentane-1,2-diol(AZ11939714) was studied in UDP-glucuronic acid (UDPGA)-supplemented hepatic microsomes from rat, dog, and human liver. The major biliary metabolite of this compound after intraduodenal administration to a beagle dog was also studied. The techniques of HPLC, HPLC-MS and HPLC-NMR were used to characterize the glucuronides. An analysis of the proton NMR chemical shift differences between parent and metabolites was sufficient to deduce the sites of glucuronidation, although these were confirmed by 2D ROESY experiments.
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