2. Academic Validation
  3. Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479

Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479

  • Bioorg Med Chem Lett. 2007 May 1;17(9):2570-6. doi: 10.1016/j.bmcl.2007.02.004.
David B Smith 1,  Joseph A Martin,  Klaus Klumpp,  Stewart J Baker,  Peter A Blomgren,  Rene Devos,  Caroline Granycome,  Julie Hang,  Christopher J Hobbs,  Wen-Rong Jiang,  Carl Laxton,  Sophie Le Pogam,  Vincent Leveque,  Han Ma,  Graham Maile,  John H Merrett,  Arkadius Pichota,  Keshab Sarma,  Mark Smith,  Steven Swallow,  Julian Symons,  David Vesey,  Isabel Najera,  Nick Cammack
Affiliations

Affiliation

  • 1 Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. Dave.Smith@Roche.com
PMID: 17317178 DOI: 10.1016/j.bmcl.2007.02.004
Abstract

A series of 4'-substituted ribonucleoside derivatives has been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in Cell Culture. The most potent and non-cytotoxic derivative was compound 28 (4'-azidocytidine, R1479) with an IC(50) of 1.28 microM in the HCV replicon system. The triphosphate of compound 28 was prepared and shown to be an inhibitor of RNA synthesis mediated by NS5B (IC(50)=320 nM), the RNA polymerase encoded by HCV. Data on related analogues have been used to generate some preliminary requirements for activity within this series of nucleosides.

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