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：US07462619B2

公开(公告)日：2008-12-09

申请号：US11097047

申请日：2005-04-01

申请人： Nicholas D. Cosford ,  Jeffrey R. Roppe ,  Lida R. Tehrani ,  Nicholas D. Smith ,  Brian Stearns ,  Dehua Huang ,  Bowei Wang ,  Thomas J. Seiders

发明人： Nicholas D. Cosford ,  Jeffrey R. Roppe ,  Lida R. Tehrani ,  Nicholas D. Smith ,  Brian Stearns ,  Dehua Huang ,  Bowei Wang ,  Thomas J. Seiders

IPC分类号： C07D401/12 ,  C07D239/30 ,  A61K31/444

CPC分类号： C07D213/16 ,  C07D213/30 ,  C07D239/26 ,  C07D241/12 ,  C07D249/08 ,  C07D263/32 ,  C07D271/06 ,  C07D277/22 ,  C07D277/24 ,  C07D277/40 ,  C07D285/01 ,  C07D333/08 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14

摘要： In accordance with the present invention, there is provided a novel class of heterocyclic compounds. Compounds of the invention contain a substituted or unsubstituted six membered heterocyclic ring that includes at least two nitrogen atoms. The ring additionally includes four carbon atoms. The heterocyclic ring has at least one substituent located at a ring position adjacent to a ring nitrogen atom. This mandatory substituent of the ring includes a moiety (B), linked to the heterocyclic ring via a carbon-carbon triple bond. The mandatory substituent is positioned adjacent to the ring nitrogen atom. Invention compounds are capable of a wide variety of uses. For example heterocyclic compounds can act to modulate physiological processes by functioning as agonists and antagonists of receptors in the nervous system. Invention compounds may also act as insecticides, and as fungicides. Pharmaceutical compositions containing invention compounds also have wide utility.

摘要翻译： 根据本发明，提供了一类新的杂环化合物。 本发明化合物含有至少两个氮原子的取代或未取代的六元杂环。 该环另外包括四个碳原子。 该杂环具有至少一个位于与环氮原子相邻的环位置的取代基。 该环的强制取代基包括通过碳 - 碳三键与杂环连接的部分（B）。 强制性取代基位于环氮原子附近。 本发明化合物能够具有多种用途。 例如，杂环化合物可以通过在神经系统中作为受体的激动剂和拮抗剂起作用来调节生理过程。 本发明的化合物也可以作为杀虫剂和杀真菌剂。 含有本发明化合物的药物组合物也具有广泛的用途。

公开(公告)号：US07365074B2

公开(公告)日：2008-04-29

申请号：US10874835

申请日：2004-06-23

申请人： Nicholas D. Cosford ,  Jeffrey R. Roppe ,  Lida R. Tehrani ,  Nicholas D. Smith ,  Brian Stearns ,  Dehua Huang ,  Bowei Wang

发明人： Nicholas D. Cosford ,  Jeffrey R. Roppe ,  Lida R. Tehrani ,  Nicholas D. Smith ,  Brian Stearns ,  Dehua Huang ,  Bowei Wang

IPC分类号： C07D401/06 ,  A61K31/444

CPC分类号： C07D239/26 ,  C07D213/16 ,  C07D213/30 ,  C07D241/12 ,  C07D249/08 ,  C07D263/32 ,  C07D271/06 ,  C07D277/22 ,  C07D277/24 ,  C07D277/40 ,  C07D285/01 ,  C07D333/08 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14

摘要： In accordance with the present invention, there is provided a novel class of heterocyclic compounds. Compounds of the invention contain a substituted, unsaturated five, six or seven membered heterocyclic ring that includes at least one nitrogen atom and at least one carbon atom. The ring additionally includes three, four or five atoms independently selected from carbon, nitrogen, sulfur and oxygen atoms. The heterocyclic ring has at least one substituent located at a ring position adjacent to a ring nitrogen atom. This mandatory substituent of the ring includes a moiety (B), linked to the heterocyclic ring via a carbon-carbon double bond, a carbon-carbon triple bond or an azo group. The mandatory substituent is positioned adjacent to the ring nitrogen atom. Invention compounds are capable of a wide variety of uses. For example heterocyclic compounds can act to modulate physiological processes by functioning as agonists and antagonists of receptors in the nervous system. Invention compounds may also act as insecticides, and as fungicides. Pharmaceutical compositions containing invention compounds also have wide utility.

摘要翻译： 根据本发明，提供了一类新的杂环化合物。 本发明的化合物含有包含至少一个氮原子和至少一个碳原子的取代的，不饱和的五，六或七元杂环。 该环另外包括独立地选自碳，氮，硫和氧原子的三个，四个或五个原子。 该杂环具有至少一个位于与环氮原子相邻的环位置的取代基。 该环的强制取代基包括通过碳 - 碳双键，碳 - 碳三键或偶氮基与杂环连接的部分（B）。 强制性取代基位于环氮原子附近。 本发明化合物能够具有多种用途。 例如，杂环化合物可以通过作为神经系统中受体的激动剂和拮抗剂起作用来调节生理过程。 本发明的化合物也可以作为杀虫剂和杀真菌剂。 含有本发明化合物的药物组合物也具有广泛的用途。

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：US07393959B2

公开(公告)日：2008-07-01

申请号：US10551574

申请日：2004-03-31

申请人： Nicholas D. P. Cosford ,  Dehua Huang ,  Jeffrey R. Roppe ,  Nicholas D. Smith ,  Lida R. Tehrani

发明人： Nicholas D. P. Cosford ,  Dehua Huang ,  Jeffrey R. Roppe ,  Nicholas D. Smith ,  Lida R. Tehrani

IPC分类号： C07D401/14 ,  A61K31/4418 ,  A61K31/4439

CPC分类号： A61K31/4439 ,  A61K31/444 ,  A61K31/485 ,  A61K31/551 ,  A61K33/00 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D417/04 ,  C07D417/14 ,  A61K2300/00

摘要： Pyrrole compounds of Formula (I): and pharmaceutically acceptable salts thereof (where A, B, R11, R12, R13, W, X, Y and Z are as defined herein), which are 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： 式（I）的吡咯化合物及其药学上可接受的盐（其中A，B，R 11，R 12，R 13，W ，X，Y和Z如本文所定义），其直接取代或通过桥连，其中i）杂芳基部分，其含有与杂芳基的连接点相邻的N，和ii）另一个杂芳基或芳基环， 至少一个被另一个环进一步取代的环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的mGluR5调节剂 ，帕金森病，认知功能障碍，癫痫，昼夜节律紊乱，药物成瘾，药物滥用，戒毒，肥胖等疾病