公开(公告)号：US08501946B2

公开(公告)日：2013-08-06

申请号：US13266592

申请日：2010-04-28

申请人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Daryl Simon Walter

发明人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Daryl Simon Walter

IPC分类号： C07D495/00

CPC分类号： C07D487/04

摘要： The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐：其中A为氢，C 1-4烷基，C 3-6环烷基，C 1-3烷氧基，C 1-3烷氧基C 1-4烷基，C 1-2 - 氟烷基，卤素，NR 6 R 7， 任选取代的杂芳基（Het）或任选取代的苯基，并且R 1，R 2，R 3，R 4，R 5，R 6和R 7如说明书中所定义。 认为化合物或盐可以调节P2X7受体功能，并能够拮抗ATP在P2X7受体上的作用。 本发明还提供了化合物或盐在治疗或预防例如炎性疼痛，神经性疼痛，内脏痛，类风湿性关节炎，骨关节炎或神经变性疾病中的用途。

公开(公告)号：US20120157436A1

公开(公告)日：2012-06-21

申请号：US13266592

申请日：2010-04-28

申请人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Daryl Simon Walter

发明人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Daryl Simon Walter

IPC分类号： A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61P25/14 ,  A61P29/00 ,  A61P25/28 ,  A61P25/08 ,  A61P25/16 ,  C07D487/04 ,  A61K31/501

CPC分类号： C07D487/04

摘要： The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2-fluoroalkyl, halogen, NR6R7, optionally substituted heteroaryl, or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐：其中A为氢，C 1-4烷基，C 3-6环烷基，C 1-3烷氧基，C 1-3烷氧基C 1-4烷基，C 1-2 - 氟烷基，卤素， NR 6 R 7，任选取代的杂芳基或任选取代的苯基，并且R 1，R 2，R 3，R 4，R 5，R 6和R 7如说明书中所定义。 认为化合物或盐可以调节P2X7受体功能，并能够拮抗ATP在P2X7受体上的作用。 本发明还提供了化合物或盐在治疗或预防例如炎性疼痛，神经性疼痛，内脏痛，类风湿性关节炎，骨关节炎或神经变性疾病中的用途。

公开(公告)号：US08513248B2

公开(公告)日：2013-08-20

申请号：US13266557

申请日：2010-04-28

申请人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Ian David Wall ,  Daryl Simon Walter

发明人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Ian David Wall ,  Daryl Simon Walter

IPC分类号： A61K31/495

CPC分类号： C07D487/04

摘要： The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis or osteoarthritis or neurodegenerative disorders.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐：其中A为氢，C 1-4烷基，C 3-6环烷基，C 1-3烷氧基，C 1-3烷氧基C 1-4烷基，C 1-2 - 氟烷基，卤素，NR 6 R 7， 任选取代的杂芳基（Het）或任选取代的苯基，并且R 1，R 2，R 3，R 4，R 5，R 6和R 7如说明书中所定义。 认为化合物或盐可以调节P2X7受体功能，并能够拮抗ATP在P2X7受体上的作用。 本发明还提供了化合物或盐在治疗或预防例如炎性疼痛，神经性疼痛，内脏痛，类风湿性关节炎或骨关节炎或神经变性疾病中的用途。

公开(公告)号：US20120172366A1

公开(公告)日：2012-07-05

申请号：US13266557

申请日：2010-04-28

申请人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Ian David Wall ,  Daryl Simon Walter

发明人： David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Mairi Sime ,  Jon Graham Anthony Steadman ,  Rachel Elizabeth Anne Thewlis ,  Giancarlo Trani ,  Ian David Wall ,  Daryl Simon Walter

IPC分类号： A61K31/4985 ,  A61P29/00 ,  A61P25/16 ,  A61P25/08 ,  A61P25/14 ,  C07D487/04 ,  A61P25/28

CPC分类号： C07D487/04

摘要： The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6R7, optionally substituted heteroaryl, or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description.The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis or osteoarthritis or neurodegenerative disorders.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐：其中A为氢，C 1-4烷基，C 3-6环烷基，C 1-3烷氧基，C 1-3烷氧基C 1-4烷基，C 1-2 - 氟烷基，卤素，NR 6 R 7， 任选取代的杂芳基或任选取代的苯基，并且R 1，R 2，R 3，R 4，R 5，R 6和R 7如说明书中所定义。 认为化合物或盐可以调节P2X7受体功能，并能够拮抗ATP在P2X7受体上的作用。 本发明还提供了化合物或盐在治疗或预防例如炎性疼痛，神经性疼痛，内脏痛，类风湿性关节炎或骨关节炎或神经变性疾病中的用途。

公开(公告)号：US20100311749A1

公开(公告)日：2010-12-09

申请号：US12739462

申请日：2008-10-24

申请人： Laura Jane Chambers ,  Katharine Laura Collis ,  David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Jon Graham Anthony Steadman ,  Daryl Simon Walter

发明人： Laura Jane Chambers ,  Katharine Laura Collis ,  David Kenneth Dean ,  Jorge Munoz-Muriedas ,  Jon Graham Anthony Steadman ,  Daryl Simon Walter

IPC分类号： A61K31/5377 ,  C07D241/08 ,  A61K31/495 ,  C07D413/10 ,  C07D401/06 ,  A61K31/496 ,  C07D405/06 ,  C07D403/10 ,  A61P29/00 ,  A61P25/28 ,  A61P19/02

CPC分类号： C07D241/08 ,  C07D401/06 ,  C07D401/10 ,  C07D403/10 ,  C07D407/06

摘要： The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein: A is C1-6alkyl, C3-6cycloalkyl, —CH2—R6, —CHMe-R7, —CMe2-R7, or optionally substituted aryl; wherein, when A is optionally substituted aryl, said aryl group is optionally substituted with 1 to 3 substituents, which may be the same or different, selected from the group consisting of halogen, C1-6alkyl, —CF3, C1-4alkoxy, C1fluoroalkoxy, cyano, NR8R9, and pyridyl wherein the pyridyl is optionally substituted by one methyl; R1 is chlorine, fluorine, —CF3, cyano or C1-6alkyl; R2, R3 and R5 independently are hydrogen, fluorine, chlorine, —CF3, cyano or C1-6alkyl, such that at least one of R2, R3 and R5 is other than hydrogen; R4 is hydrogen. These compounds and salts are thought to be P2X7 receptor antagonists. The invention also provides for the treatment of pain, inflammation, rheumatoid arthritis, osteoarthritis, or a neurodegenerative disease.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐：其中：A为C 1-6烷基，C 3-6环烷基，-CH 2 -R 6，-CHMe-R 7，-CMe 2 -R 7或任选取代的芳基; 其中当A是任选取代的芳基时，所述芳基任选地被1至3个选自卤素，C 1-6烷基，-CF 3，C 1-4烷氧基，C 1-6烷氧基， 氰基，NR8R9和吡啶基，其中吡啶基任选被一个甲基取代; R1是氯，氟，-CF3，氰基或C1-6烷基; R2，R3和R5独立地是氢，氟，氯，-CF3，氰基或C1-6烷基，使得R2，R3和R5中的至少一个不是氢; R4是氢。 这些化合物和盐被认为是P2X7受体拮抗剂。 本发明还提供治疗疼痛，炎症，类风湿性关节炎，骨关节炎或神经变性疾病。