title: Synthesis of unlabelled and stable-isotope-labelled glucuronide metabolites of dapagliflozin and synthesis of stable-isotope-labelled dapagliflozin.
abstract: Two regioisomeric glucuronide metabolites of dapagliflozin (BMS-512148) were synthesized and used to elucidate the structures of dapagliflozin metabolites observed in human urine samples. The structures of the synthetic metabolites were assigned by heteronuclear multiple-bond correlation, ROESY, and total correlation spectroscopy experiments. Analogues of these metabolites containing carbon-13 as a stable label were also prepared for use as internal standards for the analysis of urine samples obtained from patients participating in clinical studies.
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Cao
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Brailsford
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Caceres-Cortes
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Espina
authors.affiliation: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Bonacorsi
mesh_terms: D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism*; D007553:Isotope Labeling; D013237:Stereoisomerism
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D020719:Glucuronides; C529054:dapagliflozin
keywords: SGLT2; dapagliflozin; glucuronide metabolites; stable-isotope label