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：US07569592B2

公开(公告)日：2009-08-04

申请号：US10497122

申请日：2002-12-13

申请人： Nicholas D. P. Cosford ,  Chixu Chen ,  Brian W. Eastman ,  Dehua Huang ,  Benito Munoz ,  Petpiboon Prasit ,  Nicholas D. Smith

发明人： Nicholas D. P. Cosford ,  Chixu Chen ,  Brian W. Eastman ,  Dehua Huang ,  Benito Munoz ,  Petpiboon Prasit ,  Nicholas D. Smith

IPC分类号： A61K31/4439 ,  A61K31/4155 ,  C07D401/04

CPC分类号： C07D231/38 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04

摘要： Pyrazole compounds substituted directly, or by a bridge, with a heteroaryl moiety containing N adjacent to the point of connection of the heteroaryl, are mGluR5 modulators useful in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, bipolar disorder and panic, as well as in the treatment of pain, circadian rhythm disorders, and other diseases.

摘要翻译： 直接或通过桥连与杂芳基相连接的杂芳基部分的吡唑化合物是可用于治疗精神病和情绪障碍（例如精神分裂症，焦虑症，抑郁症）的mGluR5调节剂， 双相情感障碍和恐慌，以及治疗疼痛，昼夜节律紊乱和其他疾病。

公开(公告)号：US20080280899A1

公开(公告)日：2008-11-13

申请号：US11547113

申请日：2005-04-05

申请人： Mark T. Bilodeau ,  Chixu Chen ,  Nicholas D.P. Cosford ,  Brian W. Eastman ,  John C. Hartnett ,  Essa H. Hu ,  Peter J. Manley ,  Lou Anne Neilson ,  Lida R. Tehrani ,  Zhicai Wu

发明人： Mark T. Bilodeau ,  Chixu Chen ,  Nicholas D.P. Cosford ,  Brian W. Eastman ,  John C. Hartnett ,  Essa H. Hu ,  Peter J. Manley ,  Lou Anne Neilson ,  Lida R. Tehrani ,  Zhicai Wu

IPC分类号： A61K31/519 ,  C07D471/04 ,  A61K31/4375 ,  A61P35/00 ,  A61K31/5377 ,  C07D413/12

CPC分类号： C07D471/04 ,  C07D519/00

摘要： The present invention is directed to compounds which contain substituted napthyridines which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

摘要翻译： 本发明涉及含有抑制Akt（丝氨酸/苏氨酸蛋白激酶）活性的取代萘啶的化合物。 本发明还涉及含有本发明化合物的治疗组合物和治疗癌症的方法，包括施用本发明化合物。

公开(公告)号：US20090062327A1

公开(公告)日：2009-03-05

申请号：US11918386

申请日：2006-04-10

申请人： Chixu Chen ,  Brian W. Eastman ,  Essa H. Hu

发明人： Chixu Chen ,  Brian W. Eastman ,  Essa H. Hu

IPC分类号： C07D471/04 ,  A61K31/4375 ,  A61P35/00

CPC分类号： C07D471/04 ,  C07D519/00

摘要： The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.

摘要翻译： 本发明提供抑制Akt活性的化合物。 特别地，所公开的化合物选择性地抑制一种或两种Akt同种型。 本发明还提供了包含这种抑制化合物的组合物和通过将该化合物给予需要治疗癌症的患者来抑制Akt活性的方法。