Details

Autor(en) / Beteiligte

• Clark, Jeremy L
• Hollecker, Laurent
• Mason, J. Christian
• Stuyver, Lieven J
• Tharnish, Phillip M
• Lostia, Stefania
• McBrayer, Tamara R
• Schinazi, Raymond F
• Watanabe, Kyoichi A
• Otto, Michael J
• Furman, Phillip A
• Stec, Wojciech J
• Patterson, Steven E
• Pankiewicz, Krzysztof W

Titel

Design, Synthesis, and Antiviral Activity of 2‘-Deoxy-2‘-fluoro-2‘-C-methylcytidine, a Potent Inhibitor of Hepatitis C Virus Replication

Ist Teil von

• Journal of medicinal chemistry, 2005-08, Vol.48 (17), p.5504-5508

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• The pyrimidine nucleoside beta-d-2‘-deoxy-2‘-fluoro-2‘-C-methylcytidine (1) was designed as a hepatitis C virus RNA-dependent RNA polymerase (HCV RdRp) inhibitor. The title compound was obtained by a DAST fluorination of N 4-benzoyl-1-(2-methyl-3,5-di-O-benzoyl-β-d-arabinofuranosyl]cytosine (6) to provide N 4-benzoyl-1-[2-fluoro-2-methyl-3,5-di-O-benzoyl-β-d-ribofuranosyl]cytosine (7a). The protected 2‘-C-methylcytidine (7c) was obtained as a byproduct from the DAST fluorination and allowed for the preparation of two biologically active compounds from a common precursor. Compound 1 and 2‘-C-methylcytidine were assayed in a subgenomic HCV replicon assay system and found to be potent and selective inhibitors of HCV replication. Compound 1 shows increased inhibitory activity in the HCV replicon assay compared to 2‘-C-methylcytidine and low cellular toxicity.