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

摘要

Type 2 diabetes is a significant worldwide health problem. To support the development of BMS-823778 as an inhibitor of 11 beta-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 [C-14]BMS-823778 was synthesized in two steps from commercially available [2-C-14] acetone. The radiochemical purity of the synthesized [C-14] BMS-823778 after dilution with unlabeled clinical-grade BMS-823778 was 99.5% having a specific activity of 7.379 mu Ci/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 [(CD3)-C-13 (CD2)-C-13] BMT-094817 for use as a liquid chromatography/mass spectrometry standard. [(CD3)-C-13 (CD2)-C-13] BMT-094817 was prepared in five labeled steps from [(CD3)-C-13] iodomethane.