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Bioorg Med Chem Lett. 2013 Jun 1;23(11):3354-7. doi: 10.1016/j.bmcl.2013.03.095. Epub 2013 Apr 2.

Evaluation of 2'-α-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase.

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  • 1Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA.


Ribonucleoside phosphonate analogues containing 2'-α-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase. The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1.9-2.1 μM, but only modest cell-based activity in the HCV replicon. Pro-drugs of the parent nucleoside phosphonates improved the cell-based activity.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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