Synthesis, anti-HIV and cytostatic evaluation of 3'-deoxy-3'-fluorothymidine (FLT) pro-nucleotides

  • Bioorg Med Chem Lett. 2014 May 15;24(10):2240-3. doi: 10.1016/j.bmcl.2014.03.092.
Winnie Velanguparackel  1 ,  Nadège Hamon  1 ,  Jan Balzarini  2 ,  Christopher McGuigan  1 ,  Andrew D Westwell  3
Affiliations
  • 1. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB Wales, UK.
  • 2. Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
  • 3. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB Wales, UK. Electronic address: [email protected].
PMID: 24751439 DOI: 10.1016/j.bmcl.2014.03.092
Abstract

A series of pro-nucleotide phosphoramidates and phosphorodiamidates of the Antiviral lead compound 3'-deoxy-3'-fluorothymidine (FLT) have been designed and synthesized. In vitro antiretroviral and cytostatic studies revealed potent (sub-micromolar) inhibition of HIV-1 and HIV-2 replication, with retention of activity in thymidine kinase-negative cell models, as predicted by the ProTide concept.

Keywords
Anticancer; Antiviral; Nucleosides; Phosphoramidates; Pro-drugs; Pro-nucleotides.