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

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 ex...

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Bibliographic Details
Published in:Journal of labelled compounds & radiopharmaceuticals 2016-05, Vol.59 (6), p.255-259
Main Authors: Maxwell, Brad D., Tran, Scott B., Lago, Michael, Li, Jun, Bonacorsi Jr, Samuel J.
Format: Article
Language:English
Subjects:
11β-HSD1
Adsorption
Carbon Radioisotopes - chemistry
carbon-14
Chemistry Techniques, Synthetic
human ADME
Humans
Isotope Labeling
Pyridines - chemical synthesis
Pyridines - chemistry
Pyridines - metabolism
stable-isotope labeled metabolite synthesis
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - metabolism
type 2 diabetes
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Summary: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 [14C]BMS‐823778 was synthesized in two steps from commercially available [2‐14C]acetone. The radiochemical purity of the synthesized [14C]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 [13CD3 13CD2]BMT‐094817 for use as a liquid chromatography/mass spectrometry standard. [13CD3 13CD2]BMT‐094817 was prepared in five labeled steps from [13CD3]iodomethane. To support the development of BMS‐823778 as an inhibitor of 11β‐hydroxysteroid dehydrogenase type 1 for type 2 diabetes, the synthesis of [14C]BMS‐823778 for use in a human adsorption, distribution, metabolism, and excretion (ADME) study was required. One result of the ADME study was the detection of a new human metabolite, BMT‐094817. [13CD3 13CD2]BMT‐094817 was then prepared for use as a liquid chromatography/mass spectrometry standard.
ISSN:0362-4803
1099-1344
DOI:10.1002/jlcr.3383