title: Synthesis, anti-HIV and cytostatic evaluation of 3'-deoxy-3'-fluorothymidine (FLT) pro-nucleotides.
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.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB Wales, UK.
authors.forename: Winnie
authors.initials: W
authors.lastname: Velanguparackel
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB Wales, UK.
authors.forename: Nadège
authors.initials: N
authors.lastname: Hamon
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB Wales, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
authors.affiliation: 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.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Westwell
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009711:Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D054697:Cytostatic Agents; D015224:Dideoxynucleosides; D009711:Nucleotides; C002854:alovudine
keywords: Anticancer; Antiviral; Nucleosides; Phosphoramidates; Pro-drugs; Pro-nucleotides