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    RIBONUCLEOSIDE CYCLIC ACETAL DERIVATIVES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION
    1.
    发明公开
    RIBONUCLEOSIDE CYCLIC ACETAL DERIVATIVES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION 审中-公开
    核糖核苷的环状缩醛FOR RNA-依赖性RNA病毒感染的治疗

    公开(公告)号：EP1915054A2

    公开(公告)日：2008-04-30

    申请号：EP06789454.3

    申请日：2006-08-04

    申请人： Merck & Co., Inc.

    发明人： BUTORA, Gabor ,  KOEPLINGER, Kenneth, Alan ,  MACCOSS, Malcolm ,  MCMASTERS, Daniel, R. ,  OLSEN, David, B. ,  YANG, Lihu

    IPC分类号： A01N43/04 ,  A01N57/00 ,  A61K31/519

    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.

    DNA POLYMERASE EXTENSION ASSAY
    2.
    发明公开
    DNA POLYMERASE EXTENSION ASSAY 失效
    DNA聚合酶VERLÄNGUNGS测定法

    公开(公告)号：EP0833945A1

    公开(公告)日：1998-04-08

    申请号：EP96920611.0

    申请日：1996-06-03

    申请人： MERCK & CO., INC.

    发明人： COLE, James, L. ,  KUO, Lawrence, C. ,  OLSEN, David, B.

    IPC分类号： C12Q1

    CPC分类号： C12Q1/6813 ,  C12Q2533/101 ,  C12Q2521/307 ,  C12Q2521/337

    摘要： An assay for enzymes which act on substrates to produce a single-stranded oligonucleotide product has been developed which involves the DNA polymerase-catalyzed extension of the oligonucleotide cleavage product using labeled nucleotides and a DNA template containing a 3' region complementary to the oligonucleotide product joined to a 5' region consisting of repeated nucleotide residues. The DNA polymerase extension assay does not involve gel electrophoretic separation and is amenable to high volume screening of potential inhibitors. Other key features of the assay are that it monitors the substrate cleavage reaction only at the correct position in the sequence, thereby discriminating against nonspecific cleavage products, and that it is sensitive enough to detect 200 attomoles of product.

    FLUORINATED PYRROLOÝ2,3-D¨PYRIMIDINE NUCLEOSIDES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION
    4.
    发明公开
    FLUORINATED PYRROLOÝ2,3-D¨PYRIMIDINE NUCLEOSIDES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION 审中-公开
    氟化吡咯并[2,3-d]嘧啶核苷FOR RNA依赖性RNA病毒感染的治疗

    公开(公告)号：EP1804812A2

    公开(公告)日：2007-07-11

    申请号：EP05851224.5

    申请日：2005-10-17

    申请人： Merck & Co., Inc.

    发明人： MACCOSS, Malcolm ,  OLSEN, David, B. ,  LEONE, Joseph ,  DURETTE, Philippe, L.

    IPC分类号： A61K31/7052 ,  A61K31/7042 ,  C07H19/14

    CPC分类号： C07H19/14

    摘要： The present invention provides fluorinated pyrrolo[2,3,d]pyrimidine nucleoside compounds which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are 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 to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaeutical compositions containing such fluorinated pyrrolo[2,3-d]pyrimidine nucleoside 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 fluorinated pyrrolo[2,3-d]pyrimidine nucleoside of the present invention.

    NUCLEOSIDE ARYL PHOSPHORAMIDATES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION
    5.
    发明公开
    NUCLEOSIDE ARYL PHOSPHORAMIDATES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION 有权
    核苷芳基磷酸酯FOR RNA依赖性RNA病毒感染的治疗

    公开(公告)号：EP1773355A2

    公开(公告)日：2007-04-18

    申请号：EP05789867.8

    申请日：2005-06-20

    申请人： Merck & Co., Inc.

    发明人： MACCOSS, Malcolm ,  OLSEN, David, B.

    IPC分类号： A61K31/70 ,  C07H19/00

    CPC分类号： C07H19/20 ,  C07H19/14 ,  C07H19/16

    摘要： The present invention provides nucleoside aryl phosphoramidates which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to 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 to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates 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 nucleoside aryl phosphoramidates of the present invention.