Synthesis of carbon-14 and stable isotope labeled Censavudine

J Labelled Comp Radiopharm. 2022 Apr;65(4):112-122. doi: 10.1002/jlcr.3964. Epub 2022 Feb 10.


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%.

Keywords: Censavudine; carbon-14 labeling; human immunodeficiency virus-1 (HIV-1); nucleoside reverse transcriptase inhibitors (NRTIs); stable isotope labeling.

MeSH terms

  • Carbon Radioisotopes
  • Humans
  • Radiochemistry
  • Radiopharmaceuticals*
  • Reverse Transcriptase Inhibitors*


  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • Reverse Transcriptase Inhibitors
  • Carbon-14