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The syntheses of [ 14 C]BMS‐823778 for use in a human ADME clinical study and of [ 13 CD 3 13 CD 2 ]BMT‐094817, a stable‐isotope labeled standard of a newly detected human metabolite
Author(s) -
Maxwell Brad D.,
Tran Scott B.,
Lago Michael,
Li Jun,
Bonacorsi Samuel J.
Publication year - 2016
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3383
Subject(s) - chemistry , adme , metabolite , mass spectrometry , radiochemistry , stereochemistry , chromatography , biochemistry , in vitro
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 CD 3 13 CD 2 ]BMT‐094817 for use as a liquid chromatography/mass spectrometry standard. [ 13 CD 3 13 CD 2 ]BMT‐094817 was prepared in five labeled steps from [ 13 CD 3 ]iodomethane.