Synthesis and in vitro activity of D- and L-enantiomers of 5-(trifluoromethyl)uracil nucleoside derivatives

Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):1123-5. doi: 10.1081/NCN-100002502.

Abstract

Recently, beta-L-nucleoside analogues have emerged as a new class of sugar modified nucleosides with potential antiviral and/or antitumoral activity. As a part of our ongoing research on this topic, we decided to synthesize 5-CF3-beta-L-dUrd (7), the hitherto unknown L-enantiomer of Trifluridine, an antiherpetic drug approved by FDA but only used in topical applications due to concomitant cytotoxicity. 5-CF3-beta-L-dUrd (7) as well as some other related L-nucleoside derivatives were stereospecifically prepared and tested in vitro against viral (HSV-1 and HSV-2) and human thymidine kinases (TK).

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / enzymology
  • Herpesvirus 2, Human / drug effects
  • Herpesvirus 2, Human / enzymology
  • Humans
  • Pyrimidine Nucleotides / chemical synthesis*
  • Pyrimidine Nucleotides / pharmacology
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology
  • Stereoisomerism
  • Thymidine Kinase / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Pyrimidine Nucleotides
  • Pyrimidines
  • trifluoromethyluracil
  • Thymidine Kinase