公开(公告)号：US08242143B2

公开(公告)日：2012-08-14

申请号：US13016304

申请日：2011-01-28

申请人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

发明人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

IPC分类号： A61P25/00 ,  A61K31/44 ,  C07D417/00

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地说，通过亚乙炔基连接到吡啶环的3位或嘧啶环的5位上的1,3-噻唑-2-基环成员的选择，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：US20090203903A1

公开(公告)日：2009-08-13

申请号：US11664902

申请日：2005-10-06

申请人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

发明人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

IPC分类号： C07D417/14 ,  C07D417/06

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地说，通过亚乙炔基连接到吡啶环的3位或嘧啶环的5位上的1,3-噻唑-2-基环成员的选择，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：US20110230526A1

公开(公告)日：2011-09-22

申请号：US13016304

申请日：2011-01-28

申请人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

发明人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

IPC分类号： A61K31/4439 ,  A61P25/00 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于它们在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地说，通过亚乙炔基连接到吡啶环的3位或嘧啶环的5位上的1,3-噻唑-2-基环成员的选择，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：US20120289696A1

公开(公告)日：2012-11-15

申请号：US13558537

申请日：2012-07-26

申请人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

发明人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

IPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地说，通过亚乙炔基连接到吡啶环的3位或嘧啶环的5位上的1,3-噻唑-2-基环成员的选择，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：US07879882B2

公开(公告)日：2011-02-01

申请号：US11664902

申请日：2005-10-06

申请人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

发明人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

IPC分类号： A61P25/00 ,  A61K31/44 ,  C07D417/14

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于它们在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地说，通过亚乙炔基连接到吡啶环的3位或嘧啶环的5位上的1,3-噻唑-2-基环成员的选择，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：US08609852B2

公开(公告)日：2013-12-17

申请号：US13558537

申请日：2012-07-26

申请人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

发明人： Nicholas D. Cosford ,  Thomas J. Seiders ,  Joseph E. Payne ,  Jeffrey R. Roppe ,  Dehua Huang ,  Nicholas D. Smith ,  Steve F. Poon ,  Chris King ,  Brian W. Eastman ,  Bowei Wang ,  Jeannie M. Arruda ,  Jean-Michel Vernier ,  Xiumin Zhao

IPC分类号： A61P25/00 ,  A61K31/55 ,  A61K31/54 ,  A61K31/505 ,  A61K31/44 ,  A61K31/47 ,  A61K31/445 ,  C07D401/00 ,  C07D403/00 ,  C07D417/00 ,  C07D239/02 ,  C07D211/00

CPC分类号： C07D417/06 ,  C07D417/14 ,  C07D471/04

摘要： The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

摘要翻译： 由于在效力和/或药代动力学和/或选择性和/或体内受体占有性方面具有有利的性质，鉴定了具有药物性质特征的独特系列化合物。 具体地说，通过亚乙炔基连接到吡啶环的3位或嘧啶环的5位上的1,3-噻唑-2-基环成员的选择，其中环被选定的取代基取代，得到 具有优异药物性质的化合物。 本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。

公开(公告)号：US07592337B2

公开(公告)日：2009-09-22

申请号：US10506479

申请日：2003-03-07

申请人： Chixu Chen ,  Nicholas D. P. Cosford ,  Brian W. Eastman ,  Dehua Huang ,  Steve F. Poon ,  Thomas S. Reger ,  Jeffrey R. Roppe ,  Nicholas D. Smith

发明人： Chixu Chen ,  Nicholas D. P. Cosford ,  Brian W. Eastman ,  Dehua Huang ,  Steve F. Poon ,  Thomas S. Reger ,  Jeffrey R. Roppe ,  Nicholas D. Smith

IPC分类号： A61K31/535 ,  A61K31/4965 ,  A61K31/44 ,  A61K31/47 ,  A61K31/425 ,  A61K31/41 ,  A61K31/415 ,  A61K31/385 ,  A61K31/38 ,  A61K31/335 ,  A61K31/34 ,  C07D413/00 ,  C07D239/00 ,  C07D241/00 ,  C07D221/02 ,  C07D421/00 ,  C07D277/04

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04

摘要： Tetrazole compounds substituted directly, or by a bridge, with i) a heteroaryl moiety containing N adjacent to the point of connection of the heteroaryl and ii) another heteroaryl or aryl ring, with at least one of the rings being further substituted with another ring, are mGluR5 modulators useful in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, panic, and bipolar disorder, as well as in the treatment of pain, Parkinson's disease, cognitive dysfunction, epilepsy, circadian rhythm disorders, drug addiction, drug abuse, drug withdrawal, obesity and other diseases.

摘要翻译： 直接或桥接的四唑化合物与i）杂芳基部分，该杂芳基部分含有邻近杂芳基的连接点的N，和ii）另一个杂芳基或芳基环，其中至少一个环进一步被另一个环取代， 是用于治疗精神病和情绪障碍（例如精神分裂症，焦虑，抑郁，恐慌和双相情感障碍）以及治疗疼痛，帕金森病，认知功能障碍，癫痫，昼夜节律紊乱的mGluR5调节剂 药物成瘾，药物滥用，戒毒，肥胖等疾病。

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。