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11. 发明申请

WO2007095269A2 NUCLEOSIDE ARYL PHOSPHORAMIDATES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION 审中-公开
标题翻译：用于治疗RNA依赖性RNA病毒感染的核苷类ARYL磷酸酯
公开(公告)号：WO2007095269A2
公开(公告)日：2007-08-23
申请号：PCT/US2007003862
申请日：2007-02-12
申请人： MERCK & CO INC , ANGELETTI P IST RICHERCHE BIO , MACCOSS MALCOLM , OLSEN DAVID B , DONGHI MONICA , GARDELLI CRISTINA , HARPER STEVEN , MEPPEN MALTE , NARJES FRANK , PACINI BARBARA
发明人： MACCOSS MALCOLM , OLSEN DAVID B , DONGHI MONICA , GARDELLI CRISTINA , HARPER STEVEN , MEPPEN MALTE , NARJES FRANK , PACINI BARBARA
CPC分类号： C07H19/06
摘要： The present invention provides nucleoside aryl phosphoramidates of structural formula (I) 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.
摘要翻译：本发明提供结构式（I）的核苷芳基氨基磷酸酯，其是RNA依赖性RNA病毒聚合酶抑制剂的前体。这些化合物是RNA依赖性RNA病毒复制抑制剂的前体，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，作为HCV复制抑制剂的前体和/或治疗丙型肝炎感染。本发明还描述了单独或与其它对RNA依赖性RNA病毒感染，特别是HCV感染有活性的试剂组合的含有这种核苷芳基氨基磷酸酯的药物组合物。还公开了本发明的核苷芳基氨基磷酸酯抑制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。

12. 发明申请

WO2007022073A3 NOVEL 2'-C-METHYL AND 4'-C-METHYL NUCLEOSIDE DERIVATIVES 审中-公开
标题翻译：新型2'-C-甲基和4'-C-甲基核苷衍生物
公开(公告)号：WO2007022073A3
公开(公告)日：2007-11-15
申请号：PCT/US2006031614
申请日：2006-08-14
申请人： MERCK & CO INC , METABASIS THERAPEUTICS INC , ERION MARK D , REDDY K RAJA , MACCOSS MALCOLM , OLSEN DAVID B
发明人： ERION MARK D , REDDY K RAJA , MACCOSS MALCOLM , OLSEN DAVID B
IPC分类号： A01N43/00 , A61K31/70
CPC分类号： C07H19/10
摘要： Novel 2'-C-methyl nucleoside 5 '-monophosphate and 4'-C-methyl nucleoside 5'- monophosphate derivatives, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of hepatitis C viral infection are described.
摘要翻译：新型2'-C-甲基核苷5'-单磷酸酯和4'-C-甲基核苷5'-单磷酸酯衍生物，立体异构体及其药学上可接受的盐或前药，它们的制备及其治疗丙型肝炎病毒感染的用途被描述。

13. 发明申请

WO2006012078A2 NUCLEOSIDE ARYL PHOSPHORAMIDATES FOR THE TREATMENT OF RNA-DEPENDENT RNA VIRAL INFECTION 审中-公开
标题翻译：用于治疗RNA依赖性RNA病毒感染的核苷类ARYL磷酸酯
公开(公告)号：WO2006012078A2
公开(公告)日：2006-02-02
申请号：PCT/US2005021684
申请日：2005-06-20
申请人： MERCK & CO INC , MACCOSS MALCOLM , OLSEN DAVID B
发明人： MACCOSS MALCOLM , OLSEN DAVID B
IPC分类号： C12Q1/68
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.
摘要翻译：本发明提供核苷芳基氨基磷酸酯，其是RNA依赖性RNA病毒聚合酶抑制剂的前体。这些化合物是RNA依赖性RNA病毒复制抑制剂的前体，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，作为HCV复制抑制剂的前体和/或治疗丙型肝炎感染。本发明还描述了单独含有这种核苷芳基氨基磷酸酯或与其它对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苷芳基氨基磷酸酯抑制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。

14. 发明申请

WO2007145894A2 A RAPID METHOD TO DETERMINE INHIBITOR SENSITIVITY OF NS3/4A PROTEASE SEQUENCES CLONED FROM CLINICAL SAMPLES 审中-公开
标题翻译：确定从临床样品中克隆的NS3 / 4A蛋白酶序列的抑制敏感性的快速方法
公开(公告)号：WO2007145894A2
公开(公告)日：2007-12-21
申请号：PCT/US2007013154
申请日：2007-06-04
申请人： MERCK & CO INC , LUDMERER STEVEN W , GRAHAM DONALD J , OLSEN DAVID B
发明人： LUDMERER STEVEN W , GRAHAM DONALD J , OLSEN DAVID B
IPC分类号： C12Q1/70
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产生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。

15. 发明申请

WO2012142093A3 2'-CYANO SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES 审中-公开
标题翻译： 2'-氰基取代的核苷衍生物及其用于治疗病毒性疾病的方法
公开(公告)号：WO2012142093A3
公开(公告)日：2013-02-07
申请号：PCT/US2012033028
申请日：2012-04-11
申请人： MERCK SHARP & DOHME , GIRIJAVALLABHAN VINAY , NJOROGE F GEORGE , BOGEN STEPHANE , KEREKES ANGELA , BENNETT FRANK , HUANG YING , NAIR LATHA , PISSARNITSKI DMITRI , VERMA VISHAL , DANG QUN , DAVIES IAN , OLSEN DAVID B , STAMFORD ANDREW , VACCA JOSEPH P
发明人： GIRIJAVALLABHAN VINAY , NJOROGE F GEORGE , BOGEN STEPHANE , KEREKES ANGELA , BENNETT FRANK , HUANG YING , NAIR LATHA , PISSARNITSKI DMITRI , VERMA VISHAL , DANG QUN , DAVIES IAN , OLSEN DAVID B , STAMFORD ANDREW , VACCA JOSEPH P
IPC分类号： A01N43/04 , A61K31/70 , C07H19/00
CPC分类号： C07H19/16 , A61K31/7056 , A61K31/7068 , A61K31/7076 , A61K45/06 , C07H19/06 , C07H19/10 , C07H19/11 , C07H19/20 , C07H19/207 , C07H19/213
摘要： The present invention relates to 2'-Cyano Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2 and R3are as defined herein. The present invention also relates to compositions comprising at least one 2'-Cyano Substituted Nucleoside Derivative, and methods of using the 2'-Cyano Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.
摘要翻译：本发明涉及式（I）的2'-氰基取代的核苷衍生物及其药学上可接受的盐，其中B，X，R 1，R 2和R 3如本文所定义。本发明还涉及包含至少一种2'-氰基取代的核苷衍生物的组合物，以及使用2'-氰基取代的核苷衍生物治疗或预防患者HCV感染的方法。

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