公开(公告)号：US08148349B2

公开(公告)日：2012-04-03

申请号：US12519038

申请日：2007-12-14

申请人： Malte Meppen ,  Frank Narjes ,  Barbara Pacini ,  Cristina Gardelli ,  Philippe L. Durette

发明人： Malte Meppen ,  Frank Narjes ,  Barbara Pacini ,  Cristina Gardelli ,  Philippe L. Durette

IPC分类号： A61K31/70 ,  C07H19/11

CPC分类号： C07H19/06

摘要： The present invention provides nucleoside cyclic phosphoramidates of formula (I), pharmaceutical compositions comprising the compounds of formula (I) and methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection using the compounds of formula (I).

摘要翻译： 本发明提供式（I）的核苷环状氨基磷酸酯，包含式（I）化合物的药物组合物和抑制RNA依赖性RNA聚合酶的方法，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒 使用式（I）化合物的感染。

公开(公告)号：US20100022468A1

公开(公告)日：2010-01-28

申请号：US12519038

申请日：2007-12-14

申请人： Malte Meppen ,  Frank Narjes ,  Barbara Pacini ,  Cristina Gardelli ,  Philippe L. Durette

发明人： Malte Meppen ,  Frank Narjes ,  Barbara Pacini ,  Cristina Gardelli ,  Philippe L. Durette

IPC分类号： A61K31/7068 ,  C07H19/06 ,  A61P31/12

CPC分类号： C07H19/06

摘要： The present invention provides nucleoside cyclic 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 pre-cursors 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 cyclic 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 cyclic phosphoramidates of the present invention.

摘要翻译： 本发明提供了作为RNA依赖性RNA病毒聚合酶抑制剂前体的结构式（I）核苷环状氨基磷酸酯。 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。 它们作为丙型肝炎病毒（HCV）NS5B聚合酶抑制剂作为HCV复制抑制剂前体和/或用于治疗丙型肝炎感染的前体特别有用。 本发明还描述了含有这种核苷环状氨基磷酸酯的药物组合物，或者与其它对RNA依赖性RNA病毒感染，特别是HCV感染有活性的试剂组合。 还公开了本发明的核苷环状氨基磷酸酯抑制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。

公开(公告)号：US20100152128A1

公开(公告)日：2010-06-17

申请号：US12601002

申请日：2008-05-19

申请人： Barbara Attenni ,  Monica Donghi ,  Cristina Gardelli ,  Malte Meppen ,  Frank Narjes ,  Barbara Pacini

发明人： Barbara Attenni ,  Monica Donghi ,  Cristina Gardelli ,  Malte Meppen ,  Frank Narjes ,  Barbara Pacini

IPC分类号： A61K31/7068 ,  C07H19/10 ,  C07H19/14 ,  A61P31/12 ,  A61P31/14

CPC分类号： C07H19/10 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7076 ,  C07H19/04 ,  C07H19/20

摘要： A compound of formula (I) and pharmaceutically acceptable salts thereof; compositions containing it and its use in medicine, particularly for the treatment or inhibition of HCV infections, and processes for making it are disclosed.

摘要翻译： 式（I）化合物及其药学上可接受的盐; 公开了含有它的组合物及其在药物中的用途，特别是用于治疗或抑制HCV感染的药物及其制备方法。

公开(公告)号：US20100234316A1

公开(公告)日：2010-09-16

申请号：US12223940

申请日：2007-02-12

申请人： Malcolm MacCoss ,  David B. Olsen ,  Monica Donghi ,  Cristina Gardelli ,  Steven Harper ,  Malte Meppen ,  Frank Narjes ,  Barbara Pacini

发明人： Malcolm MacCoss ,  David B. Olsen ,  Monica Donghi ,  Cristina Gardelli ,  Steven Harper ,  Malte Meppen ,  Frank Narjes ,  Barbara Pacini

IPC分类号： A61K31/7068 ,  C07H19/10 ,  A61P31/14

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。

公开(公告)号：US07879815B2

公开(公告)日：2011-02-01

申请号：US12223940

申请日：2007-02-12

申请人： Malcolm MacCoss ,  David B. Olsen ,  Monica Donghi ,  Cristina Gardelli ,  Steven Harper ,  Malte Meppen ,  Frank Narjes ,  Barbara Pacini

发明人： Malcolm MacCoss ,  David B. Olsen ,  Monica Donghi ,  Cristina Gardelli ,  Steven Harper ,  Malte Meppen ,  Frank Narjes ,  Barbara Pacini

IPC分类号： A01N43/04 ,  A61K31/70

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。

公开(公告)号：US20100035835A1

公开(公告)日：2010-02-11

申请号：US12520738

申请日：2007-12-28

申请人： Frank Narjes ,  Cristina Gardelli ,  Monica Donghi ,  Barbara Attenni ,  Philippe L. Durette

发明人： Frank Narjes ,  Cristina Gardelli ,  Monica Donghi ,  Barbara Attenni ,  Philippe L. Durette

IPC分类号： A61K31/7068 ,  C07H19/10 ,  A61P31/00

CPC分类号： C07H19/04 ,  C07H19/048 ,  C07H19/10 ,  C07H19/20

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。

公开(公告)号：US08071568B2

公开(公告)日：2011-12-06

申请号：US12520738

申请日：2007-12-28

申请人： Frank Narjes ,  Cristina Gardelli ,  Monica Donghi ,  Barbara Attenni ,  Philippe L. Durette

发明人： Frank Narjes ,  Cristina Gardelli ,  Monica Donghi ,  Barbara Attenni ,  Philippe L. Durette

IPC分类号： A61K31/70 ,  C07H19/10

CPC分类号： C07H19/04 ,  C07H19/048 ,  C07H19/10 ,  C07H19/20

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. (I)

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。 （一世）

公开(公告)号：US07091209B2

公开(公告)日：2006-08-15

申请号：US10333431

申请日：2001-07-11

申请人： Cristina Gardelli ,  Claudio Giuliano ,  Steven Harper ,  Uwe Koch ,  Frank Narjes ,  Jesus Maria Ontoria Ontoria ,  Marco Poma ,  Simona Ponzi ,  Ian Stansfield ,  Vincenzo Summa

发明人： Cristina Gardelli ,  Claudio Giuliano ,  Steven Harper ,  Uwe Koch ,  Frank Narjes ,  Jesus Maria Ontoria Ontoria ,  Marco Poma ,  Simona Ponzi ,  Ian Stansfield ,  Vincenzo Summa

IPC分类号： C07D239/557 ,  C07D409/04 ,  C07D409/12 ,  C07D417/14 ,  C07D401/12

CPC分类号： C07D239/557 ,  C07D401/12 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

摘要： A class of 2-aryl-4,5-dihydroxy-6-carboxypyrimidines of formula (I): wherein Ar is an optionally substituted aryl or heterocyclicgroup; as well as compounds of formula (I) which are derivatized at one or more of the 4-hydroxy, 5-hydroxy or 6-carboxy groups; and tautomers thereof, and pharmaceutically acceptable salts or esters thereof; and inhibitors of viral polymerases, especially the hepatitis C virus (HCV) polymerase enzyme

摘要翻译： 一类式（I）的2-芳基-4,5-二羟基-6-羧基嘧啶：其中Ar是任选取代的芳基或杂环基; 以及在一个或多个4-羟基，5-羟基或6-羧基衍生化的式（I）化合物; 及其互变异构体及其药学上可接受的盐或酯; 和病毒聚合酶抑制剂，特别是丙型肝炎病毒（HCV）聚合酶

公开(公告)号：US07119073B2

公开(公告)日：2006-10-10

申请号：US10473443

申请日：2002-03-26

申请人： Stefania Colarusso ,  Cristina Gardelli ,  Benjamin Gerlach ,  Steven Harper ,  Uwe Koch ,  Victor Giulio Matassa ,  Ester Muraglia ,  Frank Narjes ,  Jesus Maria Ontoria Ontoria ,  Alessia Petrocchi ,  Simona Ponzi ,  Ian Stansfield ,  Vicenzo Summa

发明人： Stefania Colarusso ,  Cristina Gardelli ,  Benjamin Gerlach ,  Steven Harper ,  Uwe Koch ,  Victor Giulio Matassa ,  Ester Muraglia ,  Frank Narjes ,  Jesus Maria Ontoria Ontoria ,  Alessia Petrocchi ,  Simona Ponzi ,  Ian Stansfield ,  Vicenzo Summa

IPC分类号： A61K38/06 ,  A61K38/07 ,  C07K5/08 ,  C07K5/10 ,  C07K7/04 ,  A61K38/00 ,  C07K2/00

CPC分类号： C07K5/0808 ,  A61K38/00 ,  C07K5/021 ,  C07K5/0819 ,  C07K5/0827 ,  C07K5/1021 ,  C07K5/1027 ,  C07K7/02

摘要： Compounds of formula (I), and pharmaceutically acceptable salts and esters thereof: (I); wherein Q, R2, X, Y and Z are as defined herein; are inhibitors of the hepatitis C virus (HCV) NS3 protease

摘要翻译： 式（I）化合物及其药学上可接受的盐和酯：（I）; 其中Q，R2，X，Y和Z如本文所定义; 是丙型肝炎病毒（HCV）NS3蛋白酶的抑制剂

公开(公告)号：US20090136449A1

公开(公告)日：2009-05-28

申请号：US12084846

申请日：2006-11-09

申请人： Marcello Di Filippo ,  Steven Harper ,  Frank Narjes ,  Barbara Pacini ,  Alessia Petrocchi ,  Michael Rowley ,  Ian Stansfield

发明人： Marcello Di Filippo ,  Steven Harper ,  Frank Narjes ,  Barbara Pacini ,  Alessia Petrocchi ,  Michael Rowley ,  Ian Stansfield

IPC分类号： A61K38/21 ,  C07D487/04 ,  A61K31/407 ,  C07D498/04

CPC分类号： C07D487/04

摘要： The present invention relates to tetracyclic indole derivatives of formula (I); wherein Ar, D1, D2, D3, D4, W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.

摘要翻译： 本发明涉及式（I）的四环吲哚衍生物; 其中Ar，D1，D2，D3，D4，W，X，Y和Z如本文所定义，及其药学上可接受的盐，包含它们的药物组合物及其用于治疗或预防丙型肝炎病毒感染的用途。