Base-functionalized carbocyclic nucleosides: design, synthesis, and mechanism of antiviral activity

Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):408-23. doi: 10.1080/15257770903044465.

Abstract

New carbocyclic ribonucleosides with unsaturated groups at the C-2 position of the nucleobase were designed as potential RNA antiviral compounds. The design was based on the expectation that the monophosphates of these compounds would be inhibitors of the enzyme, IMPDH. Appropriate methodologies were developed to achieve the target molecules. Results from the initial in vitro antiviral studies are mentioned. The IMPDH-associated mechanism of the antiviral activity of the most active compound is supported by enzyme inhibition studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Escherichia coli / enzymology
  • IMP Dehydrogenase / antagonists & inhibitors*
  • IMP Dehydrogenase / metabolism
  • Microbial Sensitivity Tests
  • RNA Virus Infections / drug therapy
  • RNA Viruses / drug effects*
  • Ribonucleosides / chemical synthesis
  • Ribonucleosides / chemistry*
  • Ribonucleosides / pharmacology*

Substances

  • Antiviral Agents
  • Ribonucleosides
  • IMP Dehydrogenase