作为丙型肝炎病毒复制抑制剂的4'-取代核糖核苷的设计、合成及抗病毒特性：R1479的发现
Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479.
作者信息
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
机构信息
Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.
出版信息
Bioorg Med Chem Lett. 2007 May 1;17(9):2570-6. doi: 10.1016/j.bmcl.2007.02.004. Epub 2007 Feb 4.
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.
已制备了一系列4'-取代的核糖核苷衍生物，并在细胞培养中评估了它们对丙型肝炎病毒（HCV）RNA复制的抑制作用。最有效且无细胞毒性毒性是化合物28（4'-叠氮胞苷，R1479），在HCV复制子系统中的IC(50)为1.28 microM。制备了化合物28的三磷酸酯，并证明它是由HCV编码的RNA聚合酶NS5B介导的RNA合成的抑制剂（IC(50)=320 nM）。有关相关类似物的数据已用于生成该系列核苷活性的一些初步要求。
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