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 ,
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
