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. Epub 2011 May 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Floxuridine / analogs & derivatives*
  • Floxuridine / chemical synthesis
  • Floxuridine / chemistry
  • Floxuridine / pharmacology
  • Hepacivirus / drug effects*
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Phosphoric Acids / chemical synthesis
  • Phosphoric Acids / chemistry
  • Phosphoric Acids / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Amides
  • Antineoplastic Agents
  • Antiviral Agents
  • Phosphoric Acids
  • Floxuridine
  • phosphoramidic acid