The syntheses of [(14) C]BMS-823778 for use in a human ADME clinical study and of [(13) CD3 (13) CD2 ]BMT-094817, a stable-isotope labeled standard of a newly detected human metabolite

  • J Labelled Comp Radiopharm. 2016 May 30;59(6):255-9. doi: 10.1002/jlcr.3383.
Brad D Maxwell  1 ,  Scott B Tran  1 ,  Michael Lago  1 ,  Jun Li  2 ,  Samuel J Bonacorsi Jr  1
Affiliations
  • 1. Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA.
  • 2. Discovery Chemistry, 311 Pennington-Rocky Hill Road, Pennington, NJ, 08534, USA.
PMID: 27169762 DOI: 10.1002/jlcr.3383
Abstract

Type 2 diabetes is a significant worldwide health problem. To support the development of BMS-823778 as an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 for type 2 diabetes, the synthesis of carbon-14-labeled material was required for use in a human adsorption, distribution, metabolism, and excretion (ADME) study. The HCl salt form of [(14) C]BMS-823778 was synthesized in two steps from commercially available [2-(14) C]acetone. The radiochemical purity of the synthesized [(14) C]BMS-823778 after dilution with unlabeled clinical-grade BMS-823778 was 99.5% having a specific activity of 7.379 μCi/mg. One result of the human ADME study was the detection of a new human metabolite, BMT-094817. To support the quantification of BMT-094817 in clinical samples, it was necessary to synthesize [(13) CD3 (13) CD2 ]BMT-094817 for use as a liquid chromatography/mass spectrometry standard. [(13) CD3 (13) CD2 ]BMT-094817 was prepared in five labeled steps from [(13) CD3 ]iodomethane.

Keywords
11β-HSD1; carbon-14; human ADME; stable-isotope labeled metabolite synthesis; type 2 diabetes.
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