Structural effects on the phosphorylation of 3-substituted 1-beta-D-ribofuranosyl-1,2,4-triazoles by human adenosine kinase

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3203-7. doi: 10.1016/j.bmcl.2007.03.018. Epub 2007 Mar 12.

Abstract

The conversion of ribavirin to the monophosphate by adenosine kinase is the rate-limiting step in activation of this broad spectrum antiviral drug. Variation of the 3-substituents in a series of bioisosteric and homologated 1-beta-D-ribofuranosyl-1,2,4-triazoles has marked effects on activity with the human adenosine kinase, and analysis of computational descriptors and binding models offers insight for the design of novel substrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Kinase / metabolism*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / metabolism*
  • Computers
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Phosphorylation
  • Ribavirin / analogs & derivatives*
  • Stereoisomerism
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / metabolism*

Substances

  • Antiviral Agents
  • Triazoles
  • Ribavirin
  • Adenosine Kinase