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1. 发明授权

US07125855B2 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权
公开(公告)号：US07125855B2
公开(公告)日：2006-10-24
申请号：US10688691
申请日：2003-10-17
申请人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
发明人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
IPC分类号： A61K31/70 , C07H19/14
CPC分类号： C07H19/16 , A61K9/4858 , A61K31/7056 , A61K31/7064 , A61K31/7076 , A61K38/21 , A61K45/06 , C07D473/00 , C07D487/04 , C07H19/00 , C07H19/06 , C07H19/10 , C07H19/12 , C07H19/14 , C07H19/20 , Y02P20/582 , A61K2300/00
摘要： The present invention provides nucleoside compounds and certain derivatives thereof 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 inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds 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 compounds of the present invention.

2. 发明授权

US07105499B2 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权
标题翻译：核苷衍生物作为RNA依赖性RNA病毒聚合酶的抑制剂
公开(公告)号：US07105499B2
公开(公告)日：2006-09-12
申请号：US10250873
申请日：2002-01-18
申请人： Steven S. Carroll , David B. Olsen , Malcolm MacCoss , Balkrishen Bhat , Phillip Dan Cook , Anne B. Eldrup , Thazha P. Prakash
发明人： Steven S. Carroll , David B. Olsen , Malcolm MacCoss , Balkrishen Bhat , Phillip Dan Cook , Anne B. Eldrup , Thazha P. Prakash
IPC分类号： A61K31/7052 , A61K31/7042 , A61K31/7068 , C07H19/04 , C07H19/06
CPC分类号： A61K45/06 , A61K9/4858 , A61K31/7056 , A61K31/7064 , A61K31/7068 , A61K31/7076 , A61K38/212 , A61K38/2292 , C07H19/10 , C07H19/14 , C07H19/20 , Y02P20/582 , A61K2300/00
摘要： The present invention provides nucleoside derivatives 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 inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside derivatives 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 derivatives of the present invention.
摘要翻译：本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷衍生物。这些化合物是RNA依赖性RNA病毒复制的抑制剂，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，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。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药物组合物。还公开了本发明的核苷衍生物抑制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。

3. 发明授权

US06777395B2 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase of hepatitis C virus 有权
标题翻译：核苷衍生物作为丙型肝炎病毒RNA依赖性RNA病毒聚合酶的抑制剂
公开(公告)号：US06777395B2
公开(公告)日：2004-08-17
申请号：US10052318
申请日：2002-01-18
申请人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
发明人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
IPC分类号： A61K3170
CPC分类号： C07H19/16 , A61K9/4858 , A61K31/7056 , A61K31/7064 , A61K31/7076 , A61K38/21 , A61K45/06 , C07D473/00 , C07D487/04 , C07H19/00 , C07H19/06 , C07H19/10 , C07H19/12 , C07H19/14 , C07H19/20 , Y02P20/582 , A61K2300/00
摘要： The present invention provides nucleoside compounds and certain derivatives thereof 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 inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds 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 compounds of the present invention.
摘要翻译：本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷化合物及其某些衍生物。这些化合物是RNA依赖性RNA病毒复制的抑制剂，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，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。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药物组合物。还公开了本发明的核苷化合物抑制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。

4. 发明申请

US20120165515A1 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权
标题翻译：核苷衍生物作为RNA依赖性RNA病毒聚合酶的抑制剂
公开(公告)号：US20120165515A1
公开(公告)日：2012-06-28
申请号：US11701682
申请日：2007-02-02
申请人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
发明人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
IPC分类号： C07H19/20
CPC分类号： C07H19/10 , A61K9/4858 , C07D471/04 , C07D473/34 , C07D487/04 , C07H17/02 , C07H19/06 , C07H19/16 , C07H19/207 , Y02P20/582
摘要： The present invention provides nucleoside compounds and certain derivatives thereof 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 inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds 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 compounds of the present invention.
摘要翻译：本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷化合物及其某些衍生物。这些化合物是RNA依赖性RNA病毒复制的抑制剂，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，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。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药物组合物。还公开了本发明的核苷化合物抑制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。

5. 发明授权

US08481712B2 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权
公开(公告)号：US08481712B2
公开(公告)日：2013-07-09
申请号：US11701682
申请日：2007-02-02
申请人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
发明人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
IPC分类号： C07H19/10 , C07H19/20
CPC分类号： C07H19/10 , A61K9/4858 , C07D471/04 , C07D473/34 , C07D487/04 , C07H17/02 , C07H19/06 , C07H19/16 , C07H19/207 , Y02P20/582
摘要： The present invention provides nucleoside compounds and certain derivatives thereof 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 inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds 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 compounds of the present invention.

6. 发明授权

US07919612B2 2′-substituted oligomeric compounds and compositions for use in gene modulations 有权
标题翻译： 2'-取代的寡聚化合物和用于基因调节的组合物
公开(公告)号：US07919612B2
公开(公告)日：2011-04-05
申请号：US10701316
申请日：2003-11-04
申请人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
发明人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
IPC分类号： C07H21/04 , C07H21/02 , A61K48/00
CPC分类号： C12N15/113 , A61K38/00 , C07H21/00 , C12N9/22 , C12N15/1135 , C12N2310/311 , C12N2310/312 , C12N2310/314 , C12N2310/315 , C12N2310/316 , C12N2310/318 , C12N2310/3181 , C12N2310/321 , C12N2310/322 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , C12N2310/346 , Y02A50/395 , Y02P20/582 , C12N2310/3527 , C12N2310/3525 , C12N2310/3521
摘要： Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2′ substituent group on a sugar moiety that is not H or OH. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide of the oligomer has a modified sugar and/or backbone modification.
摘要翻译：提供包含第一和第二寡聚体的组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与选定的靶互补并能够与选定的靶核酸，并且第一或第二寡聚体中的至少一种包括修饰的糖和/或骨架修饰。在一些实施方案中，修饰是糖部分上不是H或OH的2'取代基。还提供低聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一个核苷酸低聚物具有修饰的糖和/或骨架修饰。

7. 发明授权

US07812149B2 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations 有权
标题翻译： 2'-氟取代低聚化合物和用于基因调控的组合物
公开(公告)号：US07812149B2
公开(公告)日：2010-10-12
申请号：US10700689
申请日：2003-11-04
申请人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
发明人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
IPC分类号： C07H21/04 , C07H21/02 , A61K48/00
CPC分类号： C12N15/111 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/346 , C12N2310/3521 , C12N2310/3533 , C12N2310/531 , C12N2320/51
摘要： Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2′-F substituent group on a sugar moiety. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleoside of the oligomer has a modified sugar and/or backbone modification.
摘要翻译：提供包含第一和第二寡聚体的组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与选定的靶互补并能够与选定的靶核酸，并且第一或第二寡聚体中的至少一种包括修饰的糖和/或骨架修饰。在一些实施方案中，修饰是糖部分上的2'-F取代基。还提供寡聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一种核苷低聚物具有修饰的糖和/或骨架修饰。

8. 发明申请

US20140309412A1 NUCLEOSIDE DERIVATIVES AS INHIBITORS OF RNA-DEPENDENT RNA VIRAL POLYMERASE 审中-公开
标题翻译：作为RNA依赖性RNA病毒聚合酶抑制剂的核苷衍生物
公开(公告)号：US20140309412A1
公开(公告)日：2014-10-16
申请号：US13916322
申请日：2013-06-12
申请人： Balkrishen Bhat , Anne B. El drup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
发明人： Balkrishen Bhat , Anne B. El drup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
IPC分类号： C07H17/02
CPC分类号： C07H19/10 , A61K9/4858 , C07D471/04 , C07D473/34 , C07D487/04 , C07H17/02 , C07H19/06 , C07H19/16 , C07H19/207 , Y02P20/582
摘要： The present invention provides nucleoside compounds and certain derivatives thereof 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 inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds 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 compounds of the present invention.
摘要翻译：本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷化合物及其某些衍生物。这些化合物是RNA依赖性RNA病毒复制的抑制剂，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，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。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药物组合物。还公开了本发明的核苷化合物抑制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。

9. 发明授权

US07534767B2 C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase 有权
标题翻译： C-嘌呤核苷类似物作为RNA依赖性RNA病毒聚合酶的抑制剂
公开(公告)号：US07534767B2
公开(公告)日：2009-05-19
申请号：US11628513
申请日：2005-06-10
申请人： Gabor Butora , Malcolm MacCoss , Balkrishen Bhat , Anne B. Eldrup
发明人： Gabor Butora , Malcolm MacCoss , Balkrishen Bhat , Anne B. Eldrup
IPC分类号： A01N43/04
CPC分类号： C07D491/04 , C07D487/04 , C07H19/16 , C07H19/20
摘要： The present invention provides C-purine nucleoside analogs and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such C-nucleoside compounds 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 C-nucleoside compounds of the present invention.
摘要翻译：本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的C-嘌呤核苷类似物及其某些衍生物。这些化合物是RNA依赖性RNA病毒复制的抑制剂，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，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。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C-核苷化合物的药物组合物。还公开了本发明的C-核苷化合物抑制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。

10. 发明授权

US07323449B2 Thionucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 失效
标题翻译：核苷衍生物作为RNA依赖性RNA病毒聚合酶的抑制剂
公开(公告)号：US07323449B2
公开(公告)日：2008-01-29
申请号：US10520925
申请日：2003-07-18
申请人： David B. Olsen , Balkrishen Bhat , Phillip Dan Cook
发明人： David B. Olsen , Balkrishen Bhat , Phillip Dan Cook
IPC分类号： C07D487/04 , A61K31/52 , A61K31/675 , C07F9/6561 , A61P31/14
CPC分类号： A61K45/06 , C07H19/14
摘要： The present invention provides thionucleoside compounds and certain derivatives thereof 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 inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such thionucleoside compounds 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 thionucleoside compounds of the present invention.
摘要翻译：本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷类化合物及其某些衍生物。这些化合物是RNA依赖性RNA病毒复制的抑制剂，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，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。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）有活性的试剂组合含有这样的硫代核苷化合物的药物组合物。还公开了用本发明的硫代核苷化合物抑制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。

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