Tricyclic 2'-C-modified nucleosides as potential anti-HCV therapeutics.
Promising biological activity in a number of therapeutic areas has been reported for both tricyclic nucleosides and 2'-modified nucleosides. In particular, disubstitution at the C-2' position of nucleosides has resulted in significant activity against the hepatitis C virus (HCV). Combining this with the observation that tricyclic nucleosides developed in our laboratory have been shown to inhibit the RNA-dependent RNA polymerase NS5B led to the design of a series of 2'-modified tricyclic nucleosides. Details of the synthesis, structural characterization, and preliminary biological results are reported.
Wauchope
Orrette R
OR
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
Tomney
Matthew J
MJ
Pepper
Joseph L
JL
Korba
Brent E
BE
Seley-Radtke
Katherine L
KL
D000998:Antiviral Agents / Q000138:chemical synthesis*; D016174:Hepacivirus / Q000187:drug effects*; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis*; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis*
D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D009705:Nucleosides