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-β-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.
Bibliographical noteFunding Information:
This work was supported by Department of Defense USAMRC Grant No. W81XWH-04-C-0055 (C.J.), and NIH INBRE RR016480 (J.A.).
- Adenosine kinase