|
|||||
|
|
Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479 |
|
| Authors: | Smith David B Martin Joseph A Klumpp Klaus Baker Stewart J Blomgren Peter A Devos Rene Granycome Caroline Hang Julie Hobbs Christopher J Jiang Wen-Rong Laxton Carl Le Pogam Sophie Leveque Vincent Ma Han Maile Graham Merrett John H Pichota Arkadius Sarma Keshab Smith Mark Swallow Steven Symons Julian Vesey David Najera Isabel Cammack Nick |
| Institution: | Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. Dave.Smith@Roche.com |
| 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. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |