Synthesis of unlabelled and stable-isotope-labelled glucuronide metabolites of dapagliflozin and synthesis of stable-isotope-labelled dapagliflozin

J Labelled Comp Radiopharm. 2017 Mar;60(3):150-159. doi: 10.1002/jlcr.3484. Epub 2017 Feb 1.

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.

Keywords: SGLT2; dapagliflozin; glucuronide metabolites; stable-isotope label.

MeSH terms

  • Benzhydryl Compounds / chemical synthesis*
  • Benzhydryl Compounds / chemistry*
  • Benzhydryl Compounds / metabolism
  • Chemistry Techniques, Synthetic
  • Glucosides / chemical synthesis*
  • Glucosides / chemistry*
  • Glucosides / metabolism
  • Glucuronides / metabolism*
  • Isotope Labeling
  • Stereoisomerism

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Glucuronides
  • dapagliflozin