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Tricyclic 2'-C-modified nucleosides as potential anti-HCV therapeutics. 2010
Orrette R Wauchope, and
Matthew J Tomney, and
Joseph L Pepper, and
Brent E Korba, and
Katherine L Seley-Radtke
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
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.
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