Abstract |
Type 2 diabetes is a significant worldwide health problem. To support the development of BMS-770767 as an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) for type 2 diabetes was required the synthesis of carbon-14-labelled material for use in metabolic profiling and for the human adsorption, distribution, metabolism and excretion (ADME) study. Initially, [phenyl-14 C(U)]BMS-770767 was synthesized in two steps from a late-stage intermediate and [14 C(U)]2- chlorophenol to give the desired final product in 18% yield. Later, the synthesis was completed for the human ADME clinical study using a combination of the discovery and process chemistry routes under cGMP to prepare [phenyl-14 C(U)]BMS-770767. The radiochemical purity of the synthesized [phenyl-14 C(U)]BMS-770767 after dilution with unlabelled clinical grade BMS-770767 was 99.1% having a specific activity of 1.61 μCi/mg. In addition, to support the quantification of BMS-770767 in LC/MS analyses, [13 C6 ]BMT-770767 was prepared in two steps from a late-stage intermediate and [13 C6 ]2- chlorophenol.
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Authors | Brad D Maxwell, Samuel J Bonacorsi Jr |
Journal | Journal of labelled compounds & radiopharmaceuticals
(J Labelled Comp Radiopharm)
Vol. 59
Issue 14
Pg. 657-664
(12 2016)
ISSN: 1099-1344 [Electronic] England |
PMID | 27460954
(Publication Type: Journal Article)
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Copyright | Copyright © 2016 John Wiley & Sons, Ltd. |
Chemical References |
- BMS-770767
- Carbon Radioisotopes
- Enzyme Inhibitors
- Pyridines
- Triazoles
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
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Topics |
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
(antagonists & inhibitors)
- Absorption, Physicochemical
- Biotransformation
- Carbon Radioisotopes
(chemistry)
- Chemistry Techniques, Synthetic
- Enzyme Inhibitors
(analysis, chemical synthesis, metabolism, pharmacology)
- Humans
- Pyridines
(analysis, chemical synthesis, metabolism, pharmacology)
- Radiochemistry
- Triazoles
(analysis, chemical synthesis, metabolism, pharmacology)
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