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Synthesis of carbon-14 and stable isotope labeled Avagacestat: a novel gamma secretase inhibitor for the treatment of Alzheimer's disease.
- Source :
-
Journal of Labelled Compounds & Radiopharmaceuticals . Aug2014, Vol. 57 Issue 10, p600-605. 6p. - Publication Year :
- 2014
-
Abstract
- Bristol-Myers Squibb and others are developing drugs that target novel mechanisms to combat Alzheimer's disease. γ-Secretase inhibitors are one class of potential therapies that have received considerable attention. ( R)-2-(4-Chloro- N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide (Avagacestat) is a γ-secretase-inhibiting drug that has been investigated by Bristol-Myers Squibb in preclinical and clinical studies. An important step in the development process was the synthesis of a carbon-14-labeled analog for use in a human absorption, distribution, metabolism, and excretion study and a stable isotope labeled analog for use as a standard in bioanalytical assays to accurately quantify the concentration of the drug in biological samples. Carbon-14 labeled Avagacestat was synthesized in seven steps in a 33% overall yield from carbon-14 labeled potassium cyanide. A total of 5.95 mCi was prepared with a specific activity of 0.81 μCi/mg and a radiochemical purity of 99.9%. 13C6-Labeled Avagacestat was synthesized in three steps in a 15% overall yield from 4-chloro[13C6]aniline. A total of 585 mg was prepared with a ultraviolet purity of 99.9%. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03624803
- Volume :
- 57
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Journal of Labelled Compounds & Radiopharmaceuticals
- Publication Type :
- Academic Journal
- Accession number :
- 98488304
- Full Text :
- https://doi.org/10.1002/jlcr.3224