Synthesis of carbon‐14 and stable isotope labeled Censavudine. (10th February 2022)

• Record Type: Journal Article
• Authors: Burrell, Richard C.; Bonacorsi, Samuel J.; Ortiz, Adrian; Benkovics, Tamas; Shi, Zhongping
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 65:Number 4(2022)
• Page Start: 112
• Page End: 122
• Publication Date: 2022-02-10
• Subjects: carbon‐14 labeling -- Censavudine -- human immunodeficiency virus‐1 (HIV‐1) -- nucleoside reverse transcriptase inhibitors (NRTIs) -- stable isotope labeling; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3964
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : 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%. Abstract : 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.