title: 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.
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.
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Brad D
authors.initials: BD
authors.lastname: Maxwell
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Tran
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lago
authors.affiliation: Discovery Chemistry, 311 Pennington-Rocky Hill Road, Pennington, NJ, 08534, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Bonacorsi
mesh_terms: D000327:Adsorption; D002250:Carbon Radioisotopes / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007553:Isotope Labeling; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: C000624964:BMS-823778; D002250:Carbon Radioisotopes; D011725:Pyridines; D014230:Triazoles
keywords: 11β-HSD1; carbon-14; human ADME; stable-isotope labeled metabolite synthesis; type 2 diabetes