Title of article
Design, synthesis, and antiviral properties of 4′-substituted ribonucleosides as inhibitors of hepatitis C virus replication: The discovery of R1479
Author/Authors
David B. Smith ، نويسنده , , Joseph A. Martin، نويسنده , , Klaus Klumpp، نويسنده , , Stewart J. Baker، نويسنده , , Peter A. Blomgren، نويسنده , , René Devos، نويسنده , , Caroline Granycome، نويسنده , , Julie Hang، نويسنده , , Christopher J. Hobbs، نويسنده , , Wenrong Jiang، نويسنده , , Carl Laxton، نويسنده , , Sophie Le Pogam، نويسنده , , Vincent Leveque، نويسنده , , Han Ma، نويسنده , , Graham Maile، نويسنده , , John H. Merrett، نويسنده , , Arkadius Pichota، نويسنده , , Keshab Sarma، نويسنده , , Mark Smith، نويسنده , , Steven Swallow، نويسنده , , et al.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2007
Pages
7
From page
2570
To page
2576
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 IC50 of 1.28 μM in the HCV replicon system. The triphosphate of compound 28 was prepared and shown to be an inhibitor of RNA synthesis mediated by NS5B (IC50 = 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.
Keywords
Hepatitis C , HCV , R1479 , antiviral , nucleoside , Ribonucleoside , Replicon , NS5B
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2007
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
798084
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