Synthesis and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methyl purine nucleosides as inhibitors of hepatitis C virus RNA replication

Jeremy L Clark; J Christian Mason; Laurent Hollecker; Lieven J Stuyver; Phillip M Tharnish; Tamara R McBrayer; Michael J Otto; Phillip A Furman; Raymond F Schinazi; Kyoichi A Watanabe

doi:10.1016/j.bmcl.2005.12.002

Synthesis and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methyl purine nucleosides as inhibitors of hepatitis C virus RNA replication

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1712-5. doi: 10.1016/j.bmcl.2005.12.002. Epub 2005 Dec 20.

Authors

Jeremy L Clark¹, J Christian Mason, Laurent Hollecker, Lieven J Stuyver, Phillip M Tharnish, Tamara R McBrayer, Michael J Otto, Phillip A Furman, Raymond F Schinazi, Kyoichi A Watanabe

Affiliation

¹ Pharmasset Inc., 1860 Montreal Road, Tucker, GA 30084, USA. [email protected]

PMID: 16368235
DOI: 10.1016/j.bmcl.2005.12.002

Abstract

A series of purine nucleosides containing the 2'-deoxy-2'-fluoro-2'-C-methylribofuranosyl moiety were synthesized and evaluated as potential inhibitors of the hepatitis C virus in vitro. Of the nucleosides that were synthesized, only those possessing a 2-amino group on the purine base reduced the levels of HCV RNA in a subgenomic replicon assay.

MeSH terms

Antiviral Agents* / chemical synthesis
Antiviral Agents* / pharmacology
Cell Survival / drug effects
Cells, Cultured
Hepacivirus / drug effects*
Hepacivirus / genetics
Molecular Structure
Purine Nucleosides* / chemical synthesis
Purine Nucleosides* / pharmacology
RNA, Viral* / drug effects
RNA, Viral* / genetics
Replicon / drug effects
Structure-Activity Relationship
Virus Replication / drug effects*

Substances

Antiviral Agents
Purine Nucleosides
RNA, Viral