公开(公告)号：US20100292224A1

公开(公告)日：2010-11-18

申请号：US12747995

申请日：2008-12-05

申请人： Daryl Simon Walter

发明人： Daryl Simon Walter

IPC分类号： A61K31/54 ,  C07D275/03 ,  A61K31/425 ,  C07D279/02 ,  A61P29/00 ,  A61P25/28 ,  A61P25/00 ,  A61P25/14

CPC分类号： C07D275/03 ,  C07D279/02

摘要： The present invention provides a compound of formula (1) or a pharmaceutically acceptable salt thereof: wherein R1 represents optionally substituted C1-4 alkyl; X represents —(CR10R11)n— in which n represents 1 or 2; R2, R3 and R4 independently represent H, F or Me; and R5; R6; R7; R8 and R9 independently represent hydrogen, halogen, or cyano; or optionally substituted C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl or C3-6 cycloalkyl, such that at least one of R5 and R9 represents a group other than hydrogen. 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 prevention of inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis or osteoarthritis.

摘要翻译： 本发明提供式（1）化合物或其药学上可接受的盐：其中R 1表示任选取代的C 1-4烷基; X表示 - （CR10R11）n-，其中n表示1或2; R2，R3和R4独立地表示H，F或Me; 和R5; R6; R7; R8和R9独立地表示氢，卤素或氰基; 或任选取代的C 1-6烷基，C 2-6烯基，C 2-6炔基或C 3-6环烷基，使得R 5和R 9中的至少一个表示除氢以外的基团。 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炎性疼痛，神经性疼痛，内脏痛，类风湿性关节炎或骨关节炎中的用途。

公开(公告)号：US20100144727A1

公开(公告)日：2010-06-10

申请号：US12593357

申请日：2008-03-20

申请人： Paul John Beswick ,  Daryl Simon Walter

发明人： Paul John Beswick ,  Daryl Simon Walter

IPC分类号： A61K31/421 ,  C07D263/20 ,  C07D265/32 ,  A61K31/5375 ,  A61P25/00 ,  A61P29/00

CPC分类号： C07D263/24 ,  C07D265/32

摘要： The present invention relates to a compound of formula (I): The compounds modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of such compounds, or pharmaceutical compositions thereof, in the treatment or prevention of disorders mediated by the P2X7 receptor, for example pain, inflammation or a neurodegenerative disease, in particular pain such as inflammatory pain, neuropathic pain or visceral pain.

摘要翻译： 本发明涉及式（I）化合物：该化合物调节P2X7受体功能并且能够拮抗ATP在P2X7受体上的作用。 本发明还提供了这些化合物或其药物组合物在治疗或预防P2X7受体介导的病症中的用途，例如疼痛，炎症或神经变性疾病，特别是疼痛，例如炎性疼痛，神经性疼痛或内脏 疼痛。

公开(公告)号：US07935832B2

公开(公告)日：2011-05-03

申请号：US12532868

申请日：2008-03-20

申请人： Robert James Gleave ,  David George Hubert Livermore ,  Daryl Simon Walter

发明人： Robert James Gleave ,  David George Hubert Livermore ,  Daryl Simon Walter

IPC分类号： C07D209/44 ,  C07D207/24 ,  C07D213/02 ,  C07D401/06 ,  A61K31/44 ,  A61K31/40

CPC分类号： C07D207/38 ,  C07D209/46

摘要： The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein: R2 represents hydrogen, halogen, C1-6 alkyl, C6-10 arylmethyl-, C2-6 alkenyl, C2-6 alkynyl or C3-6 cycloalkylmethyl-; and any of said C1-6 alkyl, C6-10 arylmethyl-, C2-6 alkenyl, C2-6 alkynyl or C3-6 cycloalkylmethyl- is optionally substituted with 1, 2 or 3 halogen atoms; and R3 represents hydrogen, fluorine or methyl; or R2 and R3 together with the carbon atoms to which they are attached form a benzene ring optionally substituted with 1, 2 or 3 substituents, which may be the same or different, selected from the group consisting of C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl. The compounds or salts modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of such compounds or salts, or pharmaceutical compositions thereof, in the treatment of disorders mediated by the P2X7 receptor, for example pain, inflammation or neurodegeneration.

摘要翻译： 本发明涉及式（I）化合物或其药学上可接受的盐：其中：R 2表示氢，卤素，C 1-6烷基，C 6-10芳甲基 - ，C 2-6烯基，C 2-6炔基或C 3 -C 6炔基， 6环烷基甲基 - ; 任何所述C 1-6烷基，C 6-10芳基甲基 - ，C 2-6烯基，C 2-6炔基或C 3-6环烷基甲基 - 任选被1,2或3个卤素原子取代; 并且R 3表示氢，氟或甲基; 或R 2和R 3与它们所连接的碳原子一起形成任选被1,2或3个取代基取代的苯环，所述取代基可以相同或不同，选自C 1-6烷基，C 2-6 烯基和C 2-6炔基。 化合物或盐调节P2X7受体功能，并能够拮抗ATP在P2X7受体上的作用。 本发明还提供了这些化合物或其盐或其药物组合物在治疗P2X7受体介导的病症中的用途，例如疼痛，炎症或神经变性。

公开(公告)号：US20090197928A1

公开(公告)日：2009-08-06

申请号：US12303262

申请日：2007-06-05

申请人： Paul John Beswick ,  Daryl Simon Walter

发明人： Paul John Beswick ,  Daryl Simon Walter

IPC分类号： A61K31/42 ,  C07D261/06 ,  A61P25/28

CPC分类号： C07D261/08

摘要： The present invention relates to novel isoxazole derivatives of formula (I) which bind to the P2X7 receptor and are capable of interfering with the effects of ATP at the P2X7 receptor: and the use of such compounds or pharmaceutical compositions thereof in the treatment of disorders mediated by the P2X7 receptor, for example pain, inflammation and neurodegeneration.

摘要翻译： 本发明涉及结合P2X7受体并能够干扰ATP在P2X7受体上的作用的式（I）的异恶唑衍生物，以及这些化合物或其药物组合物在治疗疾病介导中的应用 通过P2X7受体，例如疼痛，炎症和神经变性。

公开(公告)号：US06518293B2

公开(公告)日：2003-02-11

申请号：US09993848

申请日：2001-11-06

申请人： Brian William Dymock ,  Philip Stephen Jones ,  John Herbert Merrett ,  Kevin Edward Burdon Parkes ,  Martin John Parratt ,  Daryl Simon Walter

发明人： Brian William Dymock ,  Philip Stephen Jones ,  John Herbert Merrett ,  Kevin Edward Burdon Parkes ,  Martin John Parratt ,  Daryl Simon Walter

IPC分类号： C07D40106

CPC分类号： C07D401/12 ,  C07D233/78 ,  C07D233/86

摘要： The invention is concerned with novel imidazolone derivatives, a process for their manufacture, pharmaceutical compositions and the use of such compounds in medicine. In particular, the compounds are inhibitors of the human immunodeficiency virus reverse transcriptase enzyme which is involved in viral replication. Consequently the compounds of this invention may be advantageously used as therapeutic agents against HIV infection.

公开(公告)号：US06265446B1

公开(公告)日：2001-07-24

申请号：US09444861

申请日：1999-11-22

申请人： Michael John Broadhurst ,  William Henry Johnson ,  Daryl Simon Walter

发明人： Michael John Broadhurst ,  William Henry Johnson ,  Daryl Simon Walter

IPC分类号： A61K3118

CPC分类号： C07D295/088 ,  C07C311/49 ,  C07D213/34 ,  Y10S514/824 ,  Y10S514/863

摘要： Hydrazine derivatives of the formula wherein R1 represents lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl, R2 represents heterocyclyl or NR5R6, R3 represents hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, hydroxy-lower alkyl, amino-lower alkyl, lower alkoxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, lower cycloalkyl-lower alkyl, aryl-lower alkyl, heterocyclyl-lower alkyl, heterocyclylcarbonyl-lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl, heteroaryl or aryl-lower alkyl, R4 represents lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl or a grouping of the formula -Z-aryl, -Z-heterocyclyl or —(CH2)n—, CH═CR7R8, R5 and R6 each independently represent hydrogen or lower alkyl, R7 and R8 each independently represent hydrogen or lower alkyl or R7 and R8 together represent lower alkylene in which one CH2 group is optionally replaced by a hetero atom, X and Z each represent a spacer group, and n stands for 0, 1 or 2, and their pharmaceutically acceptable salts thereof, inhibit the release of tumor necrosis factor alpha (TNF-&agr;) from cells. They can be used as medicaments, especially in the treatment of inflammatory and autoimmune diseases, osteoarthritis, respiratory diseases, tumors, cachexia, cardiovascular diseases, fever, haemorrhage and sepsis.

摘要翻译： 式中R 1的肼衍生物代表低级烷基，低级链烯基，低级环烷基，低级环烷基 - 低级烷基，芳基或芳基 - 低级烷基，R2代表杂环基或NR5R6，R3代表氢，低级烷基，卤代低级烷基，氰基低级 烷基，羟基 - 低级烷基，氨基 - 低级烷基，低级烷氧基 - 低级烷基，低级烷氧基羰基 - 低级烷基，低级环烷基 - 低级烷基，芳基 - 低级烷基，杂环基 - 低级烷基，杂环基羰基 - 低级烷基，低级烯基， ，低级环烷基，芳基，杂芳基或芳基 - 低级烷基，R4代表低级烷基，低级烯基，低级环烷基，低级环烷基 - 低级烷基或式-Z-芳基，-Z-杂环基或 - （CH2）n - ，CH = CR 7 R 8，R 5和R 6各自独立地表示氢或低级烷基，R 7和R 8各自独立地表示氢或低级烷基，或者R 7和R 8一起表示低级亚烷基，其中一个CH 2基团任选地被杂原子X， Z各自表示间隔物 并且n代表0,1或2及其药学上可接受的盐，从细胞中抑制肿瘤坏死因子α（TNF-α）的释放。 它们可以用作药物，特别是用于治疗炎性和自身免疫性疾病，骨关节炎，呼吸系统疾病，肿瘤，恶病质，心血管疾病，发烧，出血和败血症。