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: WestwellA@cf.ac.uk.

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.

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