公开(公告)号：US08735384B2

公开(公告)日：2014-05-27

申请号：US13522823

申请日：2011-01-14

申请人： Nick A. Paras ,  James Brown ,  Yuan Cheng ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Ana Elena Minatti ,  Thomas Nixey ,  Timothy Powers ,  Christopher M. Tegley ,  Qiufen Xue ,  Bryant Yang ,  Wenge Zhong

发明人： Nick A. Paras ,  James Brown ,  Yuan Cheng ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Ana Elena Minatti ,  Thomas Nixey ,  Timothy Powers ,  Christopher M. Tegley ,  Qiufen Xue ,  Bryant Yang ,  Wenge Zhong

IPC分类号： A61K31/535 ,  A01N57/00 ,  A61K31/675

CPC分类号： C07D401/10 ,  C07D215/38 ,  C07D403/10 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D413/10 ,  C07D471/04 ,  C07D471/08 ,  C07D498/08

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I); wherein ring A, B1, B2, B3, L, R1, R2, ring Z, m and n of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula (I), intermediates and processes useful for the preparation of compounds of Formula (I).

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式（I）; 其中式I中的环A，B1，B2，B3，L，R1，R2，环Z，m和n定义在本文中。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这些疾病包括例如阿尔茨海默氏病（AD），认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式（I）的其它实施方案，可用于制备式（I）化合物的中间体和方法。

公开(公告)号：US20120329830A1

公开(公告)日：2012-12-27

申请号：US13511359

申请日：2010-11-19

申请人： Yuan Cheng ,  Timothy Powers ,  Kate Ashton ,  James Brown ,  Scott Harried ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Thomas Nixey ,  Nick A. Paras ,  Steve F. Poon ,  David J. St. Jean, JR. ,  Qiufen Xue ,  Wenge Zhong

发明人： Yuan Cheng ,  Timothy Powers ,  Kate Ashton ,  James Brown ,  Scott Harried ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Thomas Nixey ,  Nick A. Paras ,  Steve F. Poon ,  David J. St. Jean, JR. ,  Qiufen Xue ,  Wenge Zhong

IPC分类号： C07D215/38 ,  C07D405/10 ,  A61K31/4709 ,  C07D401/10 ,  A61K31/47 ,  C07D417/10

CPC分类号： C07D215/38 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D417/04

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein ring A, B1, B2, B3, L, R1, R4, R5 and m of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中式I的环A，B 1，B 2，B 3，L，R 1，R 4，R 5和m如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这些疾病包括例如阿尔茨海默氏病（AD），认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

公开(公告)号：US09296698B2

公开(公告)日：2016-03-29

申请号：US13511359

申请日：2010-11-19

申请人： Yuan Cheng ,  Timothy Powers ,  Kate Ashton ,  James Brown ,  Scott Harried ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Thomas Nixey ,  Nick A. Paras ,  Steve F. Poon ,  David J. St. Jean, Jr. ,  Qiufen Xue ,  Wenge Zhong

发明人： Yuan Cheng ,  Timothy Powers ,  Kate Ashton ,  James Brown ,  Scott Harried ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Thomas Nixey ,  Nick A. Paras ,  Steve F. Poon ,  David J. St. Jean, Jr. ,  Qiufen Xue ,  Wenge Zhong

IPC分类号： C07D215/38 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D417/04

CPC分类号： C07D215/38 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D417/04

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein ring A, B1, B2, B3, L, R1, R4, R5 and m of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中式I的环A，B 1，B 2，B 3，L，R 1，R 4，R 5和m如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这些疾病包括例如阿尔茨海默氏病（AD），认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

公开(公告)号：US20130040931A1

公开(公告)日：2013-02-14

申请号：US13522823

申请日：2011-01-14

申请人： Nick A. Paras ,  James Brown ,  Yuan Cheng ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Ana Elena Minatti ,  Thomas Nixey ,  Timothy Powers ,  Christopher M. Tegley ,  Qiufen Xue ,  Bryant Yang ,  Wenge Zhong

发明人： Nick A. Paras ,  James Brown ,  Yuan Cheng ,  Stephen A. Hitchcock ,  Ted Judd ,  Patricia Lopez ,  Ana Elena Minatti ,  Thomas Nixey ,  Timothy Powers ,  Christopher M. Tegley ,  Qiufen Xue ,  Bryant Yang ,  Wenge Zhong

IPC分类号： A61K31/5377 ,  C07D413/04 ,  C07D471/04 ,  A61P25/16 ,  A61K31/4709 ,  C07D417/14 ,  A61P25/28 ,  A61P25/00 ,  C07D413/14 ,  C07D405/14

CPC分类号： C07D401/10 ,  C07D215/38 ,  C07D403/10 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D413/10 ,  C07D471/04 ,  C07D471/08 ,  C07D498/08

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I); wherein ring A, B1, B2, B3, L, R1, R2, ring Z, m and n of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula (I), intermediates and processes useful for the preparation of compounds of Formula (I).

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式（I）; 其中式I中的环A，B1，B2，B3，L，R1，R2，环Z，m和n定义在本文中。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这些疾病包括例如阿尔茨海默氏病（AD），认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式（I）的其它实施方案，可用于制备式（I）化合物的中间体和方法。

公开(公告)号：US08633315B2

公开(公告)日：2014-01-21

申请号：US13427802

申请日：2012-03-22

申请人： Wenge Zhong ,  Stephen Hitchcock ,  Patel F. Vinod ,  Michael Croghan ,  Bryant Yang

发明人： Wenge Zhong ,  Stephen Hitchcock ,  Patel F. Vinod ,  Michael Croghan ,  Bryant Yang

IPC分类号： C07D491/107 ,  C07D311/96 ,  C07D471/10

CPC分类号： C07D491/107 ,  C07D221/06 ,  C07D311/96 ,  C07D471/10 ,  C07D491/10 ,  C07D493/10 ,  C07D495/10

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein R1a, R1b, R1c, B, W, R3, R4 and R5 are defined herein. In another embodiment, the invention provides compounds of general Formula II wherein A1, A2, A3, A4, R1a, R1b, R1c, R2, R4, R5, W, X and Z are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions. The invention also comprises further embodiments of Formula II, intermediates and processes useful for the preparation of compounds of Formulas I and II.

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中R 1a，R 1b，R 1c，B，W，R 3，R 4和R 5在本文中定义。 在另一个实施方案中，本发明提供通式II的化合物，其中A1，A2，A3，A4，R1a，R1b，R1c，R2，R4，R5，W，X和Z如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这些疾病包括例如阿尔茨海默病（AD），认知缺陷和损伤，精神分裂症和其他类似的中枢神经系统疾病。 本发明还包括式II的其它实施方案，可用于制备式I和II化合物的中间体和方法。

公开(公告)号：US08497264B2

公开(公告)日：2013-07-30

申请号：US13047693

申请日：2011-03-14

申请人： Jian J. Chen ,  Wenge Zhong ,  Bryant Yang ,  Ryan White ,  Matthew Weiss ,  Timothy Powers ,  Yuan Cheng

发明人： Jian J. Chen ,  Wenge Zhong ,  Bryant Yang ,  Ryan White ,  Matthew Weiss ,  Timothy Powers ,  Yuan Cheng

IPC分类号： C07D513/10 ,  C07D498/20 ,  A61K31/547 ,  A61K31/5386

CPC分类号： C07D513/10 ,  C07D498/10 ,  C07D498/20 ,  C07D513/20

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

公开(公告)号：US20110306587A1

公开(公告)日：2011-12-15

申请号：US13105860

申请日：2011-05-11

申请人： Jennifer R. ALLEN ,  Jian J. Chen ,  Michael J. Frohn ,  Essa Hu ,  Qingyian Liu ,  Alexander J. Pickrell ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Wenge Zhong

发明人： Jennifer R. ALLEN ,  Jian J. Chen ,  Michael J. Frohn ,  Essa Hu ,  Qingyian Liu ,  Alexander J. Pickrell ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Wenge Zhong

IPC分类号： A61K31/4439 ,  A61K31/497 ,  C07D417/14 ,  A61K31/4545 ,  C07D413/14 ,  C07D409/14 ,  C07D491/107 ,  C07D487/10 ,  C07D405/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/00 ,  A61P25/28 ,  A61P25/30 ,  A61P25/24 ,  A61P3/04 ,  A61P25/14 ,  C07D401/14

CPC分类号： C07D401/14 ,  C07C53/18 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/056 ,  C07D491/08 ,  C07D491/107 ,  C07D513/04

摘要： Unsaturated nitrogen heterocyclic compounds of formula (I): as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

摘要翻译： 式（I）的不饱和氮杂环化合物：如说明书中所定义，含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症，亨廷顿舞蹈病，非胰岛素依赖性糖尿病，精神分裂症，双相障碍，强迫症等。

公开(公告)号：US08957073B2

公开(公告)日：2015-02-17

申请号：US13105860

申请日：2011-05-11

申请人： Jennifer R. Allen ,  Jian J. Chen ,  Michael J. Frohn ,  Essa Hu ,  Qingyian Liu ,  Alexander J. Pickrell ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Wenge Zhong

发明人： Jennifer R. Allen ,  Jian J. Chen ,  Michael J. Frohn ,  Essa Hu ,  Qingyian Liu ,  Alexander J. Pickrell ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Wenge Zhong

IPC分类号： C07D403/14 ,  A61K31/517 ,  C07D239/42 ,  C07D237/26 ,  A61K31/497 ,  C07D401/14 ,  C07D241/38 ,  C07D413/14 ,  A61K31/5355 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D491/08 ,  C07D487/08 ,  C07D487/10 ,  C07D491/107 ,  A61P3/04 ,  A61P7/12 ,  A61P25/18

CPC分类号： C07D401/14 ,  C07C53/18 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/056 ,  C07D491/08 ,  C07D491/107 ,  C07D513/04

摘要： Unsaturated nitrogen heterocyclic compounds of formula (I): as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

摘要翻译： 式（I）的不饱和氮杂环化合物：如说明书中所定义，含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症，亨廷顿舞蹈病，非胰岛素依赖性糖尿病，精神分裂症，双相障碍，强迫症等。

公开(公告)号：US08778941B2

公开(公告)日：2014-07-15

申请号：US13529880

申请日：2012-06-21

申请人： James Brown ,  Jian J. Chen ,  Vijay Keshav Gore ,  Scott Harried ,  Daniel B. Horne ,  Matthew R. Kaller ,  Qingyian Liu ,  Holger Monenschein ,  Thomas T. Nguyen ,  Nobuko Nishimura ,  Wenge Zhong

发明人： James Brown ,  Jian J. Chen ,  Vijay Keshav Gore ,  Scott Harried ,  Daniel B. Horne ,  Matthew R. Kaller ,  Qingyian Liu ,  Holger Monenschein ,  Thomas T. Nguyen ,  Nobuko Nishimura ,  Wenge Zhong

IPC分类号： C07D401/14 ,  C07D213/75 ,  C07D213/40 ,  C07D405/12 ,  C07D413/12

CPC分类号： C07D213/53 ,  C07C275/30 ,  C07D213/40 ,  C07D213/75 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12

摘要： Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

公开(公告)号：US20070032518A1

公开(公告)日：2007-02-08

申请号：US10936538

申请日：2004-09-09

申请人： Mark Norman ,  Hui-Ling Wang ,  Robert Rzasa ,  Wenge Zhong ,  Thomas Nguyen ,  Matthew Kaller ,  Hu Liu

发明人： Mark Norman ,  Hui-Ling Wang ,  Robert Rzasa ,  Wenge Zhong ,  Thomas Nguyen ,  Matthew Kaller ,  Hu Liu

IPC分类号： C07D471/02 ,  C07D491/02 ,  C07D498/02

CPC分类号： C07D417/14 ,  C07D471/04 ,  C07D491/04 ,  C07D513/04

摘要： Selected compounds are effective for treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stroke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

摘要翻译： 选择的化合物对于治疗疾病如细胞增殖或细胞凋亡介导的疾病是有效的。 本发明包括新型化合物，类似物，前药及其药学上可接受的衍生物，用于预防和治疗疾病和其它疾病或涉及中风，癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。