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    Ribonucleoside cyclic acetal derivatives for the treatment of RNA-dependent RNA viral infection
    32.
    发明授权
    Ribonucleoside cyclic acetal derivatives for the treatment of RNA-dependent RNA viral infection 失效
    用于治疗RNA依赖性RNA病毒感染的核糖核苷环缩醛衍生物

    公开(公告)号：US07632821B2

    公开(公告)日：2009-12-15

    申请号：US11990051

    申请日：2006-08-04

    申请人： Gabor Butora ,  Kenneth Alan Koeplinger ,  Malcolm MacCoss ,  Daniel R. McMasters ,  David B. Olsen ,  Lihu Yang

    发明人： Gabor Butora ,  Kenneth Alan Koeplinger ,  Malcolm MacCoss ,  Daniel R. McMasters ,  David B. Olsen ,  Lihu Yang

    IPC分类号： A01N43/04 ,  A61K31/70

    CPC分类号： C07H19/06 ,  C07H19/16

    摘要： The present invention provides ribonucleoside 2′,3′-cyclic acetals of structural formula I which are precursors or prodrugs of inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors of inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors or prodrugs of inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors or prodrugs of inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such ribonucleoside 2′,3′-cyclic acetals alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the ribonucleoside 2′,3′-cyclic acetals of the present invention.

    摘要翻译： 本发明提供结构式I的核糖核苷2'，3'-环状缩醛，其为RNA依赖性RNA病毒聚合酶抑制剂的前体或前药。 这些化合物是RNA依赖性RNA病毒复制的抑制剂的前体，可用于治疗RNA依赖性RNA病毒感染。 它们特别可用作丙型肝炎病毒（HCV）NS5B聚合酶抑制剂的前体或前药，作为HCV复制抑制剂的前体或前药，和/或用于治疗丙型肝炎感染。 本发明还描述了含有这种核糖核苷2'，3'-环状缩醛单独或与其它对RNA依赖性RNA病毒感染，特别是HCV感染有活性的试剂组合的药物组合物。 还公开了本发明的核糖核苷2'，3'-环状缩醛的抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。

    Ribonucleoside Cyclic Acetal Derivatives for the Treatment of RNA-Dependent RNA Viral Infection
    33.
    发明申请
    Ribonucleoside Cyclic Acetal Derivatives for the Treatment of RNA-Dependent RNA Viral Infection 失效
    用于治疗RNA依赖性RNA病毒感染的核糖核苷环形缩醛衍生物

    公开(公告)号：US20090099126A1

    公开(公告)日：2009-04-16

    申请号：US11990051

    申请日：2006-08-04

    申请人： Gabor Butora ,  Kenneth Alan Koeplinger ,  Malcolm MacCoss ,  Daniel R. McMasters ,  David B. Olsen ,  Lihu Yang

    发明人： Gabor Butora ,  Kenneth Alan Koeplinger ,  Malcolm MacCoss ,  Daniel R. McMasters ,  David B. Olsen ,  Lihu Yang

    IPC分类号： A61K31/7076 ,  C07H19/16 ,  A61K31/7064 ,  A61P31/12 ,  C07H19/06

    CPC分类号： C07H19/06 ,  C07H19/16

    摘要： The present invention provides ribonucleoside 2′,3′-cyclic acetals of structural formula I which are precursors or prodrugs of inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors of inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as pre-cursors or prodrugs of inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors or prodrugs of inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such ribonucleoside 2′,3′-cyclic acetals alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the ribonucleoside 2′,3′-cyclic acetals of the present invention.

    摘要翻译： 本发明提供结构式I的核糖核苷2'，3'-环状缩醛，其为RNA依赖性RNA病毒聚合酶抑制剂的前体或前药。 这些化合物是RNA依赖性RNA病毒复制的抑制剂的前体，可用于治疗RNA依赖性RNA病毒感染。 它们特别可用作丙型肝炎病毒（HCV）NS5B聚合酶的抑制剂的前体或前药，作为HCV复制抑制剂的前体或前药，和/或用于治疗丙型肝炎感染。 本发明还描述了含有这种核糖核苷2'，3'-环状缩醛单独或与其它对RNA依赖性RNA病毒感染，特别是HCV感染有活性的试剂组合的药物组合物。 还公开了本发明的核糖核苷2'，3'-环状缩醛的抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。

    Rapid method to determine inhibitor sensitivity of NS3/4A protease sequences cloned from clinical samples
    40.
    发明申请
    Rapid method to determine inhibitor sensitivity of NS3/4A protease sequences cloned from clinical samples 审中-公开
    确定从临床样品克隆的NS3 / 4A蛋白酶序列的抑制剂敏感性的快速方法

    公开(公告)号：US20090203008A1

    公开(公告)日：2009-08-13

    申请号：US12308010

    申请日：2007-06-04

    申请人： Steven W. Ludmerer ,  Donald J. Graham ,  David B. Olsen

    发明人： Steven W. Ludmerer ,  Donald J. Graham ,  David B. Olsen

    IPC分类号： C12Q1/68

    CPC分类号： C12N9/506

    摘要： A method for measuring HCV NS3/4A activity from a HCV NS3/4A sequence, comprising obtaining and cloning the sequence into a mammalian expression vector, transiently transfecting a mammalian cell with the vector, which includes a reporter construct encoding a HCV NS3/4A cleavage site fused to a detectable label, measuring signal production from the label resulting from cleavage at the cleavage site, and measuring effects on signal production by addition of a test compound.

    摘要翻译： 一种从HCV NS3 / 4A序列测量HCV NS3 / 4A活性的方法，包括获得并将该序列克隆到哺乳动物表达载体中，该载体用载体瞬时转染哺乳动物细胞，其包括编码HCV NS3 / 4A切割的报道构建体 与可检测标记融合的位点，测量从切割位点处切割得到的标记物的信号产生，以及通过添加测试化合物测量对信号产生的影响。