1. Use of 2′-SpirocyclicEthers in HCV NucleosideDesign.
- Author
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Du, Jinfa, Chun, Byoung-Kwon, Mosley, Ralph T., Bansal, Shalini, Bao, Haiying, Espiritu, Christine, Lam, Angela M., Murakami, Eisuke, Niu, Congrong, Micolochick Steuer, Holly M., Furman, Phillip A., and Sofia, Michael J.
- Subjects
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HEPATITIS C virus , *NUCLEOSIDES , *CONFORMATIONAL analysis , *ANTIVIRAL agents , *PHOSPHORAMIDATES - Abstract
Conformationally restricted 2′-spironucleosidesand theirprodrugs were synthesized as potential anti-HCV agents. Although thereplicon activity of the new agents containing pyrimidine bases wasmodest, the triphosphate of a 2′-oxetane cytidine analoguedemonstrated potent intrinsic biochemical activity against the NS5Bpolymerase, with IC50= 8.48 μM. Activity againstNS5B bearing the S282T mutation was reduced. Phosphoramidate prodrugsof a 2′-oxetane 2-amino-6-O-methyl-purinenucleoside demonstrated potent anti-HCV activity in vitro, and thecorresponding triphosphate retained similar potent activity againstboth wild-type and S282T HCV NS5B polymerase. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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