Design, synthesis and biological evaluation of 2'-deoxy-2',2'-difluoro-5-halouridine phosphoramidate ProTides

  • Bioorg Med Chem. 2011 Jul 15;19(14):4338-45. doi: 10.1016/j.bmc.2011.05.037.
Maurizio Quintiliani  1 ,  Leentje Persoons ,  Nicola Solaroli ,  Anna Karlsson ,  Graciela Andrei ,  Robert Snoeck ,  Jan Balzarini ,  Christopher McGuigan
Affiliations
  • 1. Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
PMID: 21696963 DOI: 10.1016/j.bmc.2011.05.037
Abstract

We report the synthesis of a series of novel 2'-deoxy-2',2'-difluoro-5-halouridines and their corresponding phosphoramidate ProTides. All compounds were evaluated for Antiviral activity and for cellular toxicity. Interestingly, 2'-deoxy-2',2'-difluoro-5-iodo- and -5-bromo-uridines showed selective activity against feline herpes virus replication in Cell Culture due to a specific recognition (activation) by the virus-encoded thymidine kinase.