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.

Autor: Maxwell BD; Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA., Tran SB; Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA., Lago M; Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA., Li J; Discovery Chemistry, 311 Pennington-Rocky Hill Road, Pennington, NJ, 08534, USA., Bonacorsi SJ Jr; Discovery Chemistry Platforms-Radiochemistry, Research and Development, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ, 08540, USA.
Jazyk: angličtina
Zdroj: Journal of labelled compounds & radiopharmaceuticals [J Labelled Comp Radiopharm] 2016 May 30; Vol. 59 (6), pp. 255-9.
DOI: 10.1002/jlcr.3383
Abstrakt: 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.
(Copyright © 2016 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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