公开(公告)号：US08691824B2

公开(公告)日：2014-04-08

申请号：US13056919

申请日：2009-08-03

申请人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

发明人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

IPC分类号： A61K31/497

CPC分类号： A61K31/42 ,  Y02A50/401 ,  Y02A50/411 ,  Y02A50/465

摘要： Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

摘要翻译： 本文提供了某些化学实体。 还提供了包含至少一种化学实体和一种或多种药学上可接受的载体的药物组合物。 描述了治疗患有对KMO活性的抑制作用的某些疾病和病症的患者的方法，其包括给予这些患者一定量的至少一种有效减少疾病或病症的体征或症状的化学实​​体。 这些疾病包括神经变性疾病如亨廷顿氏病。 还描述了治疗方法，包括给予至少一种作为单一活性剂的化学实体或与一种或多种其它治疗剂组合施用至少一种化学实体。 还提供了用于筛选能够抑制KMO活性的化合物的方法。

公开(公告)号：US20130331370A1

公开(公告)日：2013-12-12

申请号：US13963822

申请日：2013-08-09

申请人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

发明人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

IPC分类号： C07D239/52 ,  C07D403/12 ,  C07D401/12 ,  C07D239/38 ,  C07D239/69

CPC分类号： C07D239/52 ,  A61K31/505 ,  A61K31/506 ,  C07D213/79 ,  C07D213/81 ,  C07D239/28 ,  C07D239/38 ,  C07D239/42 ,  C07D239/69 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  Y02A50/401 ,  Y02A50/411 ,  Y02A50/465

摘要： Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

公开(公告)号：US20120329812A1

公开(公告)日：2012-12-27

申请号：US13056919

申请日：2009-08-03

申请人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

发明人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

IPC分类号： A61K31/42 ,  C07D413/12 ,  A61K31/4439 ,  A61K31/506 ,  A61P25/08 ,  A61K31/437 ,  A61K31/422 ,  C07D413/06 ,  A61P25/28 ,  A61P25/16 ,  C07D261/04 ,  C07D471/04

CPC分类号： A61K31/42 ,  Y02A50/401 ,  Y02A50/411 ,  Y02A50/465

摘要： Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

摘要翻译： 本文提供了某些化学实体。 还提供了包含至少一种化学实体和一种或多种药学上可接受的载体的药物组合物。 描述了治疗患有对KMO活性的抑制作用的某些疾病和病症的患者的方法，其包括给予这些患者一定量的至少一种有效减少疾病或病症的体征或症状的化学实​​体。 这些疾病包括神经变性疾病如亨廷顿氏病。 还描述了治疗方法，包括给予至少一种作为单一活性剂的化学实体或与一种或多种其它治疗剂组合施用至少一种化学实体。 还提供了用于筛选能够抑制KMO活性的化合物的方法。

公开(公告)号：US09145373B2

公开(公告)日：2015-09-29

申请号：US13963822

申请日：2013-08-09

申请人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

发明人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

IPC分类号： A61K31/506 ,  C07D239/52 ,  C07D213/79 ,  C07D213/81 ,  C07D239/28 ,  C07D239/42 ,  C07D239/69 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D239/38 ,  C07D403/12 ,  A61K31/505

CPC分类号： C07D239/52 ,  A61K31/505 ,  A61K31/506 ,  C07D213/79 ,  C07D213/81 ,  C07D239/28 ,  C07D239/38 ,  C07D239/42 ,  C07D239/69 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  Y02A50/401 ,  Y02A50/411 ,  Y02A50/465

摘要： Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

摘要翻译： 本文提供了某些化学实体。 还提供了包含至少一种化学实体和一种或多种药学上可接受的载体的药物组合物。 描述了治疗患有对KMO活性的抑制作用的某些疾病和病症的患者的方法，其包括给予这些患者一定量的至少一种有效减少疾病或病症的体征或症状的化学实​​体。 这些疾病包括神经变性疾病如亨廷顿氏病。 还描述了治疗方法，包括给予至少一种作为单一活性剂的化学实体或与一种或多种其它治疗剂组合施用至少一种化学实体。 还提供了用于筛选能够抑制KMO活性的化合物的方法。

公开(公告)号：US08536186B2

公开(公告)日：2013-09-17

申请号：US13056305

申请日：2009-08-04

申请人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

发明人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

IPC分类号： A01N43/54 ,  C07D239/42 ,  C07D401/04

CPC分类号： C07D239/52 ,  A61K31/505 ,  A61K31/506 ,  C07D213/79 ,  C07D213/81 ,  C07D239/28 ,  C07D239/38 ,  C07D239/42 ,  C07D239/69 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  Y02A50/401 ,  Y02A50/411 ,  Y02A50/465

摘要： Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

公开(公告)号：US20110230428A1

公开(公告)日：2011-09-22

申请号：US13054931

申请日：2009-07-22

申请人： John Wityak ,  Leticia M. Toledo-sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

发明人： John Wityak ,  Leticia M. Toledo-sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

IPC分类号： A61K31/7024 ,  C07D271/06 ,  A61K31/4245 ,  C07D233/64 ,  A61K31/4164 ,  C07D257/04 ,  A61K31/41 ,  C07C251/38 ,  A61K31/15 ,  C07D207/50 ,  A61K31/40 ,  C07C255/64 ,  A61K31/277 ,  C07D471/04 ,  A61K31/437 ,  C07C311/05 ,  A61K31/18 ,  A61K31/192 ,  C07D295/13 ,  A61K31/5375 ,  C07H13/04 ,  A61P25/28 ,  A61P25/16 ,  A61P25/00 ,  A61P25/08

CPC分类号： C07C311/05 ,  C07C251/48 ,  C07C251/58 ,  C07C255/61 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D207/09 ,  C07D207/12 ,  C07D207/14 ,  C07D211/46 ,  C07D211/56 ,  C07D213/53 ,  C07D213/71 ,  C07D213/75 ,  C07D231/40 ,  C07D233/61 ,  C07D233/64 ,  C07D237/20 ,  C07D239/42 ,  C07D241/20 ,  C07D249/08 ,  C07D257/04 ,  C07D261/08 ,  C07D261/10 ,  C07D261/14 ,  C07D271/06 ,  C07D285/125 ,  C07D309/10 ,  C07D471/04 ,  C07H15/18

摘要： Certain chemical entities are provided herein. Pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

摘要翻译： 本文提供了某些化学实体。 包含至少一种化学实体和一种或多种药学上可接受的载体的药物组合物。 描述了治疗患有对KMO活性的抑制作用的某些疾病和病症的患者的方法，其包括给予这些患者一定量的至少一种有效减少疾病或病症的体征或症状的化学实​​体。 这些疾病包括神经变性疾病如亨廷顿氏病。 治疗方法包括给予至少一种化学实体作为单一活性剂或与一种或多种其它治疗剂组合施用至少一种化学实体。 还提供了用于筛选能够抑制KMO活性的化合物的方法。

公开(公告)号：US20110183957A1

公开(公告)日：2011-07-28

申请号：US13056305

申请日：2009-08-04

申请人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

发明人： John Wityak ,  Leticia M. Toledo-Sherman ,  Celia Dominguez ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Paula C. De Aguiar Pena ,  Andreas Scheel ,  Dirk Winkler

IPC分类号： A61K31/506 ,  C07D239/28 ,  C07D239/42 ,  C07D401/12 ,  C07D239/69 ,  C07D401/04 ,  C07D413/06 ,  C07D401/06 ,  C07D403/06 ,  C07D413/04 ,  C07D239/38 ,  C07D417/12 ,  C07D403/12 ,  C07D413/12 ,  C07D213/79 ,  A61K31/505 ,  A61K31/5377 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/444 ,  A61P25/28 ,  A61P25/00 ,  A61P25/16

CPC分类号： C07D239/52 ,  A61K31/505 ,  A61K31/506 ,  C07D213/79 ,  C07D213/81 ,  C07D239/28 ,  C07D239/38 ,  C07D239/42 ,  C07D239/69 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  Y02A50/401 ,  Y02A50/411 ,  Y02A50/465

摘要： Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

摘要翻译： 本文提供某些化学实体。 还提供了包含至少一种化学实体和一种或多种药学上可接受的载体的药物组合物。 描述了治疗患有对KMO活性的抑制作用的某些疾病和病症的患者的方法，其包括给予这些患者一定量的至少一种有效减少疾病或病症的体征或症状的化学实​​体。 这些疾病包括神经变性疾病如亨廷顿氏病。 还描述了治疗方法，包括给予至少一种作为单一活性剂的化学实体或与一种或多种其它治疗剂组合施用至少一种化学实体。 还提供了用于筛选能够抑制KMO活性的化合物的方法。

公开(公告)号：US20150232420A1

公开(公告)日：2015-08-20

申请号：US14429288

申请日：2013-09-19

申请人： Celia DOMINGUEZ ,  Michael PRIME ,  Richard MARSTON ,  Frederick A. BROOKFIELD ,  Stephen M. COURTNEY ,  Douglas MACDONALD ,  John WITYAK ,  Christopher John YARNOLD ,  Darshan VAIDYA

发明人： Celia Dominguez ,  Michael Prime ,  Richard Marston ,  Frederick A. Brookfield ,  Stephen M. Courtney ,  Douglas Macdonald ,  John Wityak ,  Christopher John Yarnold ,  Darshan Vaidya

IPC分类号： C07C271/22 ,  C07D207/06 ,  C07D213/74 ,  C07D205/04 ,  C07D211/08 ,  C07D295/185 ,  C07D223/04

CPC分类号： C07C271/22 ,  C07D205/04 ,  C07D207/06 ,  C07D207/16 ,  C07D211/08 ,  C07D211/16 ,  C07D213/72 ,  C07D213/74 ,  C07D223/04 ,  C07D277/42 ,  C07D295/18 ,  C07D295/185 ,  C07D309/08 ,  C07D401/12

摘要： Certain compounds and pharmaceutically acceptable salts are provided herein. Also provided are pharmaceutical compositions comprising at least one compound or pharmaceutically acceptable salt therein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain disease states responsive to the inhibition of transglutaminase TG2 activity are described. These disease states include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound or pharmaceutically acceptable salt thereof as a single active agent or administering at least one compound or pharmaceutically acceptable salt thereof in combination with one or more other therapeutic agents.

摘要翻译： 本文提供了某些化合物和药学上可接受的盐。 还提供了包含至少一种化合物或其药学上可接受的盐的药物组合物和一种或多种药学上可接受的载体。 描述了治疗患有某种疾病状态的患者对抑制转谷氨酰胺酶TG2活性有反应的方法。 这些疾病状态包括神经变性疾病如亨廷顿病。 还描述了治疗方法，包括给予至少一种化合物或其药学上可接受的盐作为单一活性剂，或者与一种或多种其它治疗剂组合施用至少一种化合物或其药学上可接受的盐。

公开(公告)号：US20110118258A1

公开(公告)日：2011-05-19

申请号：US12599116

申请日：2008-05-15

申请人： Stephen Martin Courtney ,  Mark Whittaker ,  Owen Clifford Mather ,  Christopher John Yarnold ,  Oliver Robin Barker ,  Christian Aldo Georges Napoleon Montalbetti ,  Thomas Hesterkamp ,  Mihaly Daniel Gardiner

发明人： Stephen Martin Courtney ,  Mark Whittaker ,  Owen Clifford Mather ,  Christopher John Yarnold ,  Oliver Robin Barker ,  Christian Aldo Georges Napoleon Montalbetti ,  Thomas Hesterkamp ,  Mihaly Daniel Gardiner

IPC分类号： A61K31/517 ,  C07D239/84 ,  C07D413/12 ,  C07D409/08 ,  C07D405/10 ,  C07D401/10 ,  C07D403/10 ,  C07D403/12 ,  A61K31/5377 ,  A61P35/00 ,  A61P29/00 ,  A61P31/12

CPC分类号： C07D239/84 ,  C07D401/04 ,  C07D403/10 ,  C07D405/04 ,  C07D409/04

摘要： Compounds of general formula (I); or a stereoisomers, tautomers, pharmaceutically acceptable salts, or prodrugs thereof, wherein R1, R2, R3, R4, R5, R6, R8 and R9 are as defined herein, are useful for the treatment of diseases and conditions which are mediated by excessive or inappropriate Hsp90 activity such as cancers, viral infection and inflammatory diseases or conditions.

摘要翻译： 通式（I）的化合物; 或其立体异构体，互变异构体，药学上可接受的盐或前药，其中R 1，R 2，R 3，R 4，R 5，R 6，R 8和R 9如本文所定义，可用于治疗疾病和病症， 不适当的Hsp90活动如癌症，病毒感染和炎性疾病或病症。

公开(公告)号：US20080194574A1

公开(公告)日：2008-08-14

申请号：US10596508

申请日：2004-12-16

申请人： Jan Eike Eikhoff ,  Mark Richard Ashton ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Maurizio Varrone ,  Pui Leng Loke ,  Thomas Herget ,  Wilfried Schwab ,  Doris Hafenbradl

发明人： Jan Eike Eikhoff ,  Mark Richard Ashton ,  Stephen Martin Courtney ,  Christopher John Yarnold ,  Maurizio Varrone ,  Pui Leng Loke ,  Thomas Herget ,  Wilfried Schwab ,  Doris Hafenbradl

IPC分类号： A61K31/4985 ,  C07D487/04 ,  C07D241/10 ,  A61K31/4965 ,  A61P31/00 ,  A61P37/00 ,  A61P25/16 ,  A61P25/28

CPC分类号： C07D401/04 ,  C07D241/20 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14

摘要： The present invention relates to pyrazine derivatives according to the general formula (I) and pharmaceutically acceptable salts thereof and their use as pharmaceutical compounds as well as the use of these compounds for the preparation of a pharmaceutical composition for the prophylaxis and/or treatment of infectious diseases, including opportunistic diseases, prion diseases, immunological diseases, autoimmune diseases, bipolar and clinical disorders, cardiovascular diseases, cell proliferative diseases, diabetes, inflammation, transplant rejections, erectile dysfunction, neurodegenerative diseases, stroke and especially for the treatment of herpesviral induced infections, including opportunistic infections as well as infections and diseases caused by human cytomegalovirus (HCMV).

摘要翻译： 本发明涉及根据通式（I）的吡嗪衍生物及其药学上可接受的盐及其作为药物化合物的用途，以及这些化合物在制备用于预防和/或治疗感染性疾病的药物组合物中的用途 疾病，包括机会性疾病，朊病毒疾病，免疫疾病，自身免疫性疾病，双相和临床病症，心血管疾病，细胞增殖性疾病，糖尿病，炎症，移植排斥，勃起功能障碍，神经变性疾病，中风，特别是治疗疱疹病毒诱导的感染 ，包括机会性感染以及由巨细胞病毒（HCMV）引起的感染和疾病。