公开(公告)号：US08143394B2

公开(公告)日：2012-03-27

申请号：US12519496

申请日：2007-12-24

申请人： William John Watkins ,  Lee Shun Chong ,  Jennifer R. Zhang

发明人： William John Watkins ,  Lee Shun Chong ,  Jennifer R. Zhang

IPC分类号： C07D471/00 ,  C07D487/00

CPC分类号： C07D471/04

摘要： 2-amino-pyrido(3,2-d)pyrimidine derivatives with a specific substitution pattern on positions 4 and 6 of the core structure are useful in the treatment or prevention of an infection due to a virus from the Flaviviridae family, especially HCV, when administered to a patient in a therapeutically effective amount.

摘要翻译： 具有核心结构位置4和6上特定取代模式的2-氨基 - 吡啶并（3,2-d）嘧啶衍生物可用于治疗或预防由于来自黄病毒科的病毒感染，特别是HCV， 当以治疗有效量施用于患者时。

公开(公告)号：US10144736B2

公开(公告)日：2018-12-04

申请号：US12374457

申请日：2007-07-20

申请人： Piet AndréMaurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

发明人： Piet AndréMaurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

IPC分类号： C07D487/00 ,  C07D475/02 ,  C07D475/00 ,  C07D475/04 ,  C07D475/06 ,  C07D475/08

摘要： The invention provides 4,6-di- and 2,4,6-tri-substituted pteridine derivatives with a specific substitution pattern which exhibit a significant and selective activity against certain types of viral infections, in particular selectively inhibit replication of Flaviridae such as the hepatitis C virus, and are useful for the prevention and treatment of such viral infections.

公开(公告)号：US08673929B2

公开(公告)日：2014-03-18

申请号：US12374242

申请日：2007-07-20

申请人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

发明人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

IPC分类号： A01N43/54 ,  A61K31/517 ,  C07D239/72 ,  C07D401/00

CPC分类号： C07D403/04 ,  C07D239/90 ,  C07D239/95 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04

摘要： This invention provides the treatment of viral infections with a 4,6-disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R2 is selected from the group consisting of hydrogen, NR′R″ and C1-7 alkyl; —A is selected from the group consisting of a bond, O, S(O)n, C1-7 alkylene, C2-7 alkenylene and C2-7 alkynylene; R4 is selected from the group consisting of C1-7 alkyl, C2-7 alkenyl, C3-10cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted alkyl and cycloalkyl-alkyl; —Y is selected from the group consisting of a single bond, C1-7 alkylene, C2-7 alkenylene, and C2-7 alkynylene; n is 0, 1 or 2; and R6 is selected from the group consisting of halogen, heteroaryl and aryl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-Λ/-oxide, a solvate or a pro-drug thereof.

摘要翻译： 本发明提供用结构式[（I）]表示的4,6-二取代或2,4,6-三取代喹唑啉衍生物治疗病毒感染，其中：R2选自氢，NR'R “和C 1-7烷基; -A选自键，O，S（O）n，C 1-7亚烷基，C 2-7亚烯基和C 2-7亚炔基; R 4选自C 1-7烷基，C 2-7烯基，C 3-10环烷基，C 3-10环烯基，芳基，杂环，芳基烷基，杂环取代的烷基和环烷基 - 烷基; -Y选自单键，C1-7亚烷基，C2-7亚烯基和C2-7亚炔基; n为0,1或2; 并且R 6选自卤素，杂芳基和芳基; 药学上可接受的加成盐，立体异构体，单或二 - 二氧化物，其溶剂合物或前体药物。

公开(公告)号：US20090253696A1

公开(公告)日：2009-10-08

申请号：US12374223

申请日：2007-06-20

申请人： Piet Andre' Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong ,  Jennifer Zhang

发明人： Piet Andre' Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong ,  Jennifer Zhang

IPC分类号： A61K31/5377 ,  C07D471/04 ,  A61K31/519 ,  A61P31/12

CPC分类号： C07D471/04

摘要： This invention provides di-, tri- and tetra-substituted pyrido(3,2-d)pyrimidine derivatives with specific substituting patterns, their pharmaceutically acceptable salts, N-oxides, solvates, pro-drugs and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular being highly active antiviral agents. The invention also provides use of such derivatives in the treatment of viral infections and pathologic conditions associated therewith, including hepatitis C.

摘要翻译： 本发明提供了具有特定取代模式的二，三和四取代的吡啶并（3,2-d）嘧啶衍生物，其药学上可接受的盐，N-氧化物，溶剂合物，前药和对映异构体， 特别是高活性抗病毒剂。 本发明还提供了这样的衍生物在治疗与其相关的病毒感染和病理状况（包括丙型肝炎）中的用途。

公开(公告)号：US08338435B2

公开(公告)日：2012-12-25

申请号：US12374223

申请日：2007-06-20

申请人： Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong ,  Jennifer Zhang

发明人： Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong ,  Jennifer Zhang

IPC分类号： A61K31/517 ,  C07D471/00

CPC分类号： C07D471/04

摘要： This invention provides di-, tri- and tetra-substituted pyrido(3,2-d)pyrimidine derivatives with specific substituting patterns, their pharmaceutically acceptable salts, N-oxides, solvates, pro-drugs and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular being highly active antiviral agents. The invention also provides use of such derivatives in the treatment of viral infections and pathologic conditions associated therewith, including hepatitis C.

摘要翻译： 本发明提供了具有特定取代模式的二，三和四取代的吡啶并（3,2-d）嘧啶衍生物，其药学上可接受的盐，N-氧化物，溶剂合物，前药和对映异构体， 特别是高活性抗病毒剂。 本发明还提供了这样的衍生物在治疗与其相关的病毒感染和病理状况（包括丙型肝炎）中的用途。

公开(公告)号：US20100305117A1

公开(公告)日：2010-12-02

申请号：US12374457

申请日：2007-07-20

申请人： Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

发明人： Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

IPC分类号： A61K31/519 ,  C07D475/04 ,  A61K31/5377 ,  C07D475/08 ,  A61P31/14

CPC分类号： C07D475/02 ,  C07D475/00 ,  C07D475/04 ,  C07D475/06 ,  C07D475/08

摘要： The invention provides 4,6-di- and 2,4,6-tri-substituted pteridine derivatives with a specific substitution pattern which exhibit a significant and selective activity against certain types of viral infections, in particular selectively inhibit replication of Flaviridae such as the hepatitis C virus, and are useful for the prevention and treatment of such viral infections.

摘要翻译： 本发明提供具有特定取代模式的4,6-二 - 和2,4,6-三取代的蝶啶衍生物，其具有对某些类型的病毒感染的显着和选择性活性，特别是选择性抑制黄病毒科的复制， 丙型肝炎病毒，并且可用于预防和治疗这种病毒感染。

公开(公告)号：US09259426B2

公开(公告)日：2016-02-16

申请号：US12374433

申请日：2007-07-20

申请人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

发明人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

IPC分类号： A61K31/517 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  C07D239/72 ,  C07D239/78 ,  C07D239/88 ,  C07D239/94 ,  C07D239/95 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

CPC分类号： C07D413/04 ,  A61K31/517 ,  A61K31/5375 ,  A61K31/5377 ,  C07D239/72 ,  C07D239/78 ,  C07D239/86 ,  C07D239/88 ,  C07D239/94 ,  C07D239/95 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04

摘要： This invention provides quinazoline derivatives represented by the structural formula: (I); wherein: R2 is hydrogen, NR′R″, C1-7 alkyl, arylC1-7 alkyl or C3-10 cycloalkyl; R4 is amino, C1-7 alkyl, C2-7 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted C1-7 alkyl or C3-10 cycloalkyl-C1-7 alkyl; R5 is hydrogen or C1-7 alkyl, or R5 and R4 together with the nitrogen atom to which they are attached form a heterocyclic ring; Y is a single bond, C1-7 alkylene, C2-7 alkenylene or C2-7 alkynylene; R6 is halogen, heteroaryl or aryl; R′ and R″ are each independently hydrogen, C1-7 alkyl-carbonyl or C1-7 alkyl; provided that R4 is not phenyl substituted with morpholino when R2 is H and R5 is H, and provided that when NR4R5 is piperazinyl, said NR4R5 is either non-substituted or substituted with methyl or acetyl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-N-oxide, a solvate or a pro-drug thereof, for the treatment of viral infections.

摘要翻译： 本发明提供由结构式（I）表示的喹唑啉衍生物： 其中：R 2是氢，NR'R“，C 1-7烷基，芳基C 1-7烷基或C 3-10环烷基; R4是氨基，C1-7烷基，C2-7烯基，C3-10环烷基，C3-10环烯基，芳基，杂环，芳基烷基，杂环取代的C1-7烷基或C3-10环烷基C1-7烷基; R5是氢或C1-7烷基，或R5和R4与它们所连接的氮原子一起形成杂环; Y是单键，C1-7亚烷基，C2-7亚烯基或C2-7亚炔基; R6是卤素，杂芳基或芳基; R'和R“各自独立地为氢，C 1-7烷基 - 羰基或C 1-7烷基; 条件是当R 2为H且R 5为H时，R 4不为被吗啉代取代的苯基，并且条件是当NR 4 R 5为哌嗪基时，所述NR 4 R 5为未取代或被甲基或乙酰基取代的; 用于治疗病毒感染的药学上可接受的加成盐，立体异构体，单或二-N-氧化物，溶剂合物或前体药物。

公开(公告)号：US20100143299A1

公开(公告)日：2010-06-10

申请号：US12374242

申请日：2007-07-20

申请人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

发明人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

IPC分类号： A61K38/21 ,  C07D239/88 ,  A61K31/517 ,  C07D239/84 ,  C07D403/04 ,  C07D413/12 ,  A61K31/5377 ,  A61K31/7056 ,  A61P31/12

CPC分类号： C07D403/04 ,  C07D239/90 ,  C07D239/95 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04

摘要： This invention provides the treatment of viral infections with a 4,6-disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R2 is selected from the group consisting of hydrogen, NR′R″ and C1-7 alkyl; —A is selected from the group consisting of a bond, O, S(O)n, C1-7 alkylene, C2-7 alkenylene and C2-7 alkynylene; R4 is selected from the group consisting of C1-7 alkyl, C2-7 alkenyl, C3-10cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted alkyl and cycloalkyl-alkyl; —Y is selected from the group consisting of a single bond, C1-7 alkylene, C2-7 alkenylene, and C2-7 alkynylene; n is 0, 1 or 2; and R6 is selected from the group consisting of halogen, heteroaryl and aryl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-Λ/-oxide, a solvate or a pro-drug thereof.

摘要翻译： 本发明提供用结构式[（I）]表示的4,6-二取代或2,4,6-三取代喹唑啉衍生物治疗病毒感染，其中：R2选自氢，NR'R “和C 1-7烷基; -A选自键，O，S（O）n，C 1-7亚烷基，C 2-7亚烯基和C 2-7亚炔基; R 4选自C 1-7烷基，C 2-7烯基，C 3-10环烷基，C 3-10环烯基，芳基，杂环，芳基烷基，杂环取代的烷基和环烷基 - 烷基; -Y选自单键，C1-7亚烷基，C2-7亚烯基和C2-7亚炔基; n为0,1或2; 并且R 6选自卤素，杂芳基和芳基; 药学上可接受的加成盐，立体异构体，单 - 或二 - / - 氧化物，其溶剂合物或前体药物。

公开(公告)号：US20090285782A1

公开(公告)日：2009-11-19

申请号：US12374433

申请日：2007-07-20

申请人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

发明人： Ling-Jie Gao ,  Piet André Maurits Maria Herdewijn ,  Steven Cesar Alfons De Jonghe ,  William John Watkins ,  Lee Shun Chong

IPC分类号： A61K31/517 ,  A61K31/5377 ,  A61K31/506 ,  A61K38/21 ,  A61K31/708 ,  C07D239/95 ,  C07D403/04 ,  C07D413/04 ,  A61P31/12

CPC分类号： C07D413/04 ,  A61K31/517 ,  A61K31/5375 ,  A61K31/5377 ,  C07D239/72 ,  C07D239/78 ,  C07D239/86 ,  C07D239/88 ,  C07D239/94 ,  C07D239/95 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04

摘要： This invention provides quinazoline derivatives represented by the structural formula: (I); wherein: R2 is hydrogen, NR′R″, C1-7 alkyl, arylC1-7 alkyl or C3-10 cycloalkyl; R4 is amino, C1-7 alkyl, C2-7 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted C1-7 alkyl or C3-10 cycloalkyl-C1-7 alkyl; R5 is hydrogen or C1-7 alkyl, or R5 and R4 together with the nitrogen atom to which they are attached form a heterocyclic ring; Y is a single bond, C1-7alkylene, C2-7 alkenylene or C2-7 alkynylene; R6 is halogen, heteroaryl or aryl; R′ and R″ are each independently hydrogen, C1-7 alkyl-carbonyl or C1-7 alkyl; provided that R4 is not phenyl substituted with morpholino when R2 is H and R5 is H, and provided that when NR4R5 is piperazinyl, said NR4R5 is either non-substituted or substituted with methyl or acetyl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-N-oxide, a solvate or a pro-drug thereof, for the treatment of viral infections.

摘要翻译： 本发明提供由结构式（I）表示的喹唑啉衍生物： 其中：R 2是氢，NR'R“，C 1-7烷基，芳基C 1-7烷基或C 3-10环烷基; R4是氨基，C1-7烷基，C2-7烯基，C3-10环烷基，C3-10环烯基，芳基，杂环，芳基烷基，杂环取代的C1-7烷基或C3-10环烷基C1-7烷基; R5是氢或C1-7烷基，或R5和R4与它们所连接的氮原子一起形成杂环; Y是单键，C1-7亚烷基，C2-7亚烯基或C2-7亚炔基; R6是卤素，杂芳基或芳基; R'和R“各自独立地为氢，C 1-7烷基 - 羰基或C 1-7烷基; 条件是当R 2为H且R 5为H时，R 4不为被吗啉代取代的苯基，并且条件是当NR 4 R 5为哌嗪基时，所述NR 4 R 5为未取代或被甲基或乙酰基取代的; 用于治疗病毒感染的药学上可接受的加成盐，立体异构体，单或二-N-氧化物，溶剂合物或前体药物。