公开(公告)号：US07626056B2

公开(公告)日：2009-12-01

申请号：US11446735

申请日：2006-06-05

申请人： Wesley Peter Blackaby ,  Jose Luis Castro Pineiro ,  Richard Thomas Lewis ,  Elizabeth Mary Naylor ,  Leslie Joseph Street

发明人： Wesley Peter Blackaby ,  Jose Luis Castro Pineiro ,  Richard Thomas Lewis ,  Elizabeth Mary Naylor ,  Leslie Joseph Street

IPC分类号： C07C233/65 ,  A61K31/16

CPC分类号： C07D213/82 ,  C07C233/70 ,  C07C233/76 ,  C07C317/30 ,  C07C2601/02 ,  C07C2601/14 ,  C07D231/12 ,  C07D231/18 ,  C07D239/28 ,  C07D249/04 ,  C07D285/125 ,  C07D295/108 ,  C07D295/135 ,  C07D307/68 ,  C07D333/38 ,  C07D471/04 ,  C07D495/04

摘要： The present invention provides compounds of formula I: wherein R1 is an alkyl, phenyl, heterocyclyl, cycloalkyl, alkoxy, ester, amino or amide group; R2 is a phenyl, heterocyclyl, alkyl, cycloalkyl or cycloalkylalkyl group; R3 is an alkyl, cycloalkyl, cycloalkylalkyl, amino or heterocyclyl group; R4 and R5 are hydrogen or alkyl or form a cycloalkyl ring; A is O or N; and m is zero or one; as inhibitors of GlyT1 and thus as useful for treating or preventing diseases such as schizophrenia; with the provision of pharmaceutical compositions, first and second medical uses and methods of treatment.

摘要翻译： 本发明提供式I化合物：其中R 1是烷基，苯基，杂环基，环烷基，烷氧基，酯，氨基或酰胺基; R2是苯基，杂环基，烷基，环烷基或环烷基烷基; R3是烷基，环烷基，环烷基烷基，氨基或杂环基; R4和R5是氢或烷基或形成环烷基环; A是O或N; m为零或一; 作为GlyT1的抑制剂，因此可用于治疗或预防精神分裂症等疾病; 提供药物组合物，第一和第二医疗用途和治疗方法。

公开(公告)号：US07030128B2

公开(公告)日：2006-04-18

申请号：US10472680

申请日：2002-03-19

申请人： Wesley Peter Blackaby ,  Jose Luis Castro Pineiro ,  Mark Stuart Chambers ,  Simon Charles Goodacre ,  David James Hallett ,  Philip Jones ,  Richard Thomas Lewis ,  Angus Murray MacLeod ,  Robert James Maxey ,  Kevin William Moore ,  Leslie Joseph Street

发明人： Wesley Peter Blackaby ,  Jose Luis Castro Pineiro ,  Mark Stuart Chambers ,  Simon Charles Goodacre ,  David James Hallett ,  Philip Jones ,  Richard Thomas Lewis ,  Angus Murray MacLeod ,  Robert James Maxey ,  Kevin William Moore ,  Leslie Joseph Street

IPC分类号： A61K31/519 ,  C07D487/04 ,  A61P25/22

CPC分类号： C07D487/04 ,  A61K31/519

摘要： A class of imidazo[1,2-α]pyrimidine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, are selective ligands for GABAA receptors, in particular having good affinity for the α2 and/or α3 and/or α5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

摘要翻译： 一类由任选取代的五元或六元杂芳环在3-位上被取代的咪唑并[1,2-α]嘧啶衍生物，是GABA A A受体的选择性配体， 特别是对α2和/或α3和/或α5亚基具有良好的亲和力，因此有益于治疗和/或预防中枢神经系统的不利条件，包括焦虑，抽搐和认知障碍。

公开(公告)号：US06914063B2

公开(公告)日：2005-07-05

申请号：US10333964

申请日：2001-07-18

申请人： Simon Charles Goodacre ,  David James Hallett ,  Leslie Joseph Street

发明人： Simon Charles Goodacre ,  David James Hallett ,  Leslie Joseph Street

IPC分类号： A61K31/4985 ,  A61P25/08 ,  A61P25/22 ,  A61P25/28 ,  C07B61/00 ,  C07D487/04 ,  A61P25/06

CPC分类号： C07D487/04

摘要： A class of imidazo[1,2-α]pyrazine analogues substituted in the 3-position by a substituted phenyl ring, being selective ligands for GABAA receptors which interact more favourably with the α2 and/or α3 subunit than with the α1 subunit, are accordingly of benefit in the treatment and/or prevention of a variety of disorders of the central nervous system, including anxiety and convulsions, with a reduced propensity to cause sedation.

摘要翻译： 通过取代的苯环在3-位上被取代的一类咪唑并[1,2-α]吡嗪类似物，是与α2和/或α3相互作用更好的GABA A A受体的选择性配体 亚单位与α1亚基相比，因此在治疗和/或预防中枢神经系统的各种障碍（包括焦虑和惊厥）中具有降低的引起镇静倾向的益处。

公开(公告)号：US06828322B2

公开(公告)日：2004-12-07

申请号：US10463075

申请日：2003-06-17

申请人： William Robert Carling ,  Jose Luis Castro Pineiro ,  Ian James Collins ,  Alexander Richard Guiblin ,  Timothy Harrison ,  Andrew Madin ,  Kevin William Moore ,  Michael Geoffrey Russell ,  Gayle Scott ,  Leslie Joseph Street

发明人： William Robert Carling ,  Jose Luis Castro Pineiro ,  Ian James Collins ,  Alexander Richard Guiblin ,  Timothy Harrison ,  Andrew Madin ,  Kevin William Moore ,  Michael Geoffrey Russell ,  Gayle Scott ,  Leslie Joseph Street

IPC分类号： A61K315025

CPC分类号： C07D487/04

摘要： A class of substituted 1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing a fluoro-substituted phenyl ring at the 3-position and a heteroaryl-methoxy moiety at the 6-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.

摘要翻译： 在3-位上具有氟取代的苯环和6-位上的杂芳基 - 甲氧基部分的一类取代的1,2,4-三唑并[4,3-b]哒嗪衍生物是GABAA的选择性配体 受体，特别是对其α2和/或α3亚基具有高亲和力，因此有益于治疗和/或预防中枢神经系统疾病，包括焦虑和抽搐。

公开(公告)号：US06448249B1

公开(公告)日：2002-09-10

申请号：US09600988

申请日：2000-07-24

申请人： William Robert Carling ,  Tamara Ladduwahetty ,  Angus Murray MacLeod ,  Kevin John Merchant ,  Kevin William Moore ,  Francine Sternfeld ,  Leslie Joseph Street

发明人： William Robert Carling ,  Tamara Ladduwahetty ,  Angus Murray MacLeod ,  Kevin John Merchant ,  Kevin William Moore ,  Francine Sternfeld ,  Leslie Joseph Street

IPC分类号： A61K315025

CPC分类号： C07D487/04

摘要： A substituted triazolopyridazine derivative, its use in cognition enhancement therapy, compositions containing it and processes for its manufacture.

摘要翻译： 取代的三唑并哒嗪衍生物，其在认知增强疗法中的应用，含有其的组合物及其制备方法。

公开(公告)号：US5981529A

公开(公告)日：1999-11-09

申请号：US043440

申请日：1998-03-18

申请人： Raymond Baker ,  Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Angus Murray MacLeod ,  Austin John Reeve ,  Francine Sternfeld ,  Leslie Joseph Street

发明人： Raymond Baker ,  Mark Stuart Chambers ,  Sarah Christine Hobbs ,  Angus Murray MacLeod ,  Austin John Reeve ,  Francine Sternfeld ,  Leslie Joseph Street

IPC分类号： C07D403/04 ,  A61K31/00 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/4196 ,  A61P25/06 ,  A61P43/00 ,  C07D403/06 ,  C07D521/00 ,  A61K31/495 ,  C07D403/14 ,  C07D413/14

CPC分类号： C07D249/08 ,  C07D231/12 ,  C07D233/56

摘要： A class of 1-[3-(1H-indol-3-yl)propyl]-4-(2-phenylethyl)piperazine derivatives, substituted at the 5-position of the indole nucleus by a five-membered heteroaromatic moiety, on one or other of the ethylene carbon atoms of the phenethyl moiety by halogen, trifluoromethyl, alkyl, hydroxyalkyl or alkoxyalkyl, and optionally on the phenyl ring of the phenethyl moiety by halogen, trifluoromethyl, alkoxy or an oxazolidinone group and optionally by one or two further substituents, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D .alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D .alpha. receptor subtype relative to the 5-HT.sub.1D .beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.

摘要翻译： PCT No.PCT / GB96 / 02309 Sec。 371日期1998年3月18日 102（e）1998年3月18日PCT PCT 1996年9月19日PCT公布。 公开号WO97 / 11695 日期1997年4月3日一类1- [3-（1H-吲哚-3-基）丙基] -4-（2-苯基乙基）哌嗪衍生物，其在吲哚核的5-位被五元 三氟甲基，烷基，羟基烷基或烷氧基烷基，以及任选地在苯乙基部分的苯环上被卤素，三氟甲基，烷氧基或恶唑烷酮基团任选地在苯乙基部分的一个或另外的乙烯碳原子上， 一个或两个另外的取代基是5-HT1样受体的选择性激动剂，是人类5-HT1Dα受体亚型的有效激动剂，同时对5-HT1Dα受体亚型具有至少10倍的选择性亲和力 5-HT1D beta亚型; 因此，它们可用于治疗和/或预防临床状况，特别是偏头痛和相关疾病，其中指出5-HT1D受体的亚型选择性激动剂，同时引起较少的副作用，特别是不利的心血管事件，比 与非亚型选择性5-HT1D受体激动剂相关的那些。

公开(公告)号：US07851638B2

公开(公告)日：2010-12-14

申请号：US12571904

申请日：2009-10-01

申请人： Wesley Peter Blackaby ,  Jose Luis Castro Pineiro ,  Richard Thomas Lewis ,  Elizabeth Mary Naylor ,  Leslie Joseph Street

发明人： Wesley Peter Blackaby ,  Jose Luis Castro Pineiro ,  Richard Thomas Lewis ,  Elizabeth Mary Naylor ,  Leslie Joseph Street

IPC分类号： C07D249/02 ,  A61K31/4192

CPC分类号： C07D213/82 ,  C07C233/70 ,  C07C233/76 ,  C07C317/30 ,  C07C2601/02 ,  C07C2601/14 ,  C07D231/12 ,  C07D231/18 ,  C07D239/28 ,  C07D249/04 ,  C07D285/125 ,  C07D295/108 ,  C07D295/135 ,  C07D307/68 ,  C07D333/38 ,  C07D471/04 ,  C07D495/04

摘要： The present invention provides compounds of formula I: wherein R1 is an alkyl, phenyl, heterocyclyl, cycloalkyl, alkoxy, ester, amino or amide group; R2 is a phenyl, heterocyclyl, alkyl, cycloalkyl or cycloalkylalkyl group; R3 is an alkyl, cycloalkyl, cycloalkylalkyl, amino or heterocyclyl group; R4 and R5 are hydrogen or alkyl or form a cycloalkyl ring; A is O or N; and m is zero or one; as inhibitors of GlyT1 and thus as useful for treating or preventing diseases such as schizophrenia; with the provision of pharmaceutical compositions, first and second medical uses and methods of treatment.

摘要翻译： 本发明提供式I化合物：其中R 1是烷基，苯基，杂环基，环烷基，烷氧基，酯，氨基或酰胺基; R2是苯基，杂环基，烷基，环烷基或环烷基烷基; R3是烷基，环烷基，环烷基烷基，氨基或杂环基; R4和R5是氢或烷基或形成环烷基环; A是O或N; m为零或一; 作为GlyT1的抑制剂，因此可用于治疗或预防精神分裂症等疾病; 提供药物组合物，第一和第二医疗用途和治疗方法。

公开(公告)号：US07176203B2

公开(公告)日：2007-02-13

申请号：US10512608

申请日：2003-05-01

申请人： Mark Stuart Chambers ,  Simon Charles Goodacre ,  David James Hallett ,  Robert James Maxey ,  Michael Geoffrey Neil Russell ,  Leslie Joseph Street

发明人： Mark Stuart Chambers ,  Simon Charles Goodacre ,  David James Hallett ,  Robert James Maxey ,  Michael Geoffrey Neil Russell ,  Leslie Joseph Street

IPC分类号： C07D487/04 ,  C07D403/04 ,  A61K31/53 ,  A61P25/22

CPC分类号： C07D487/04

摘要： A class of imidazo[1,2b][1,2,4]triazine derivatives, substituted at the 7-position by an optionally substituted five-membered or six-membered heteroaromatic ring, being selective ligands for GABAA receptors, in particular having good affinity for the α2 and/or α3 and/or α5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

摘要翻译： 一类由任选取代的五元或六元杂芳环在7-位取代的咪唑并[1,2b] [1,2,4]三嗪衍生物，是GABA A， 特别是具有对α2和/或α3和/或α5亚基具有良好亲和力的受体，因此在治疗和/或预防中枢神经系统的不良状况（包括焦虑，惊厥和认知障碍）方面是有益的 。

公开(公告)号：US06969716B2

公开(公告)日：2005-11-29

申请号：US10769070

申请日：2004-01-30

申请人： Wesley Peter Blackaby ,  Simon Charles Goodacre ,  David James Hallett ,  Andrew Jennings ,  Richard Thomas Lewis ,  Leslie Joseph Street ,  Kevin Wilson

发明人： Wesley Peter Blackaby ,  Simon Charles Goodacre ,  David James Hallett ,  Andrew Jennings ,  Richard Thomas Lewis ,  Leslie Joseph Street ,  Kevin Wilson

IPC分类号： A61K31/53 ,  C07D253/065 ,  A61P25/22

CPC分类号： A61K31/53

摘要： The present invention provides a compound of formula I, or an N-oxide thereof or a pharmaceutically acceptable salt thereof: wherein X1 represents hydrogen, halogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy;X2 represents hydrogen or halogen;Z represents hydrogen, halogen, cyano, cyanomethyl, trifluoromethyl, nitro, hydroxy, hydroxy(C1-6)alkyl, C1-6 alkoxy, C1-6 alkoxy(C1-6)alkyl, trifluoromethoxy, trifluoromethylthio, trifluoromethanesulfinyl, formyl, C2-6 alkoxycarbonyl, oxopyrrolidinyl, or an optionally substituted aryl, heteroaryl or heteroaryl(C1-6)alkoxy group; andR1 represents aryl or heteroaryl, either of which groups may be optionally substituted;pharmaceutical compositions comprising it, its use in therapy and methods of treatment of anxiety and/or depression using it.

摘要翻译： 本发明提供式I化合物或其N-氧化物或其药学上可接受的盐：其中X 1表示氢，卤素，C 1-6烷基 ，三氟甲基或C 1-6烷氧基; X 2表示氢或卤素; Z表示氢，卤素，氰基，氰基甲基，三氟甲基，硝基，羟基，羟基（C 1-6 - ）烷基，C 1-6烷氧基，C 1 C 1-6烷氧基（C 1-6）烷基，三氟甲氧基，三氟甲硫基，三氟甲磺酰基，甲酰基，C 2-6烷氧基羰基，氧代吡咯烷基或任选取代的芳基 ，杂芳基或杂芳基（C 1-6 - ）烷氧基; 且R 1表示芳基或杂芳基，其中任一个可以任选被取代; 包含它的药物组合物，其在治疗中的用途以及使用其治疗焦虑和/或抑郁症的方法。

公开(公告)号：US06936608B2

公开(公告)日：2005-08-30

申请号：US10416318

申请日：2001-11-08

申请人： Michela Bettati ,  Peter Blurton ,  William Robert Carling ,  Mark Stuart Chambers ,  David James Hallett ,  Andrew Jennings ,  Richard Thomas Lewis ,  Michael Geoffrey Neil Russell ,  Leslie Joseph Street ,  Helen Jane Szekeres ,  Monique Bodil Van Neil

发明人： Michela Bettati ,  Peter Blurton ,  William Robert Carling ,  Mark Stuart Chambers ,  David James Hallett ,  Andrew Jennings ,  Richard Thomas Lewis ,  Michael Geoffrey Neil Russell ,  Leslie Joseph Street ,  Helen Jane Szekeres ,  Monique Bodil Van Neil

IPC分类号： A61K31/53 ,  A61P25/00 ,  A61P25/22 ,  C07D487/04 ,  A61P25/08 ,  A61P25/28

CPC分类号： C07D487/04

摘要： A class of 7-phenylimidazo[1,2-b][1,2,4]triazine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, being selective ligands for GABAA receptors, in particular having good affinity for the α2 and/or α3 and/or α5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

摘要翻译： 一类7-苯基咪唑并[1,2-b] [1,2,4]三嗪衍生物，其在苯环的间位被任选取代的被氧原子连接或桥连的芳基或杂芳基取代 或-NH-连接，作为GABA A受体的选择性配体，特别是对α2和/或α3和/或α5亚基具有良好的亲和力，因此在治疗和/ 或预防中枢神经系统的不良状况，包括焦虑，抽搐和认知障碍。