Details

Autor(en) / Beteiligte

• Burrell, Richard C.
• Bonacorsi, Samuel J.
• Ortiz, Adrian
• Benkovics, Tamas
• Shi, Zhongping

Titel

Synthesis of carbon‐14 and stable isotope labeled Censavudine

Ist Teil von

• Journal of labelled compounds & radiopharmaceuticals, 2022-04, Vol.65 (4), p.112-122

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Censavudine is a nucleoside reverse transcriptase inhibitor (NRTI) explored clinically by Bristol Myers Squibb for the treatment of human immunodeficiency virus‐1 (HIV‐1). As part of the development process, a carbon‐14 labeled analog was synthesized for use in a human absorption, distribution, metabolism, and excretion (ADME) study. A stable isotope labeled analog was also synthesized for use as a mass spectrum internal standard in bioanalytical assays to accurately quantify the concentration of the drug in biological samples. Carbon‐14 labeled Censavudine was synthesized in 10 steps in a 9% overall yield from carbon‐14 labeled trimethylsilylacetylene. A total of 4.44 mCi of material was prepared with a specific activity of 0.25 μCi/mg. The radiochemical and UV purities were 99% and it met all of the specifications for use in a human clinical study. Deuterium labeled Censavudine was synthesized in two steps in a 68% overall yield from [D4]‐thymine. A total of 237 mg were prepared with a UV purity of 99%. Carbon‐14 labeled Censavudine was synthesized in ten steps in a 9% overall yield from carbon‐14 labeled trimethylsilylacetylene. A total of 4.44 mCi of material was prepared with a specific activity of 0.25 μCi/mg. The radiochemical and UV purities were 99% and it met all of the specifications for use in a human clinical study. Deuterium labeled Censavudine (237 mg) was synthesized in two steps in a 68% yield from [D4]‐thymine.