公开(公告)号：US20060194791A1

公开(公告)日：2006-08-31

申请号：US10545411

申请日：2004-02-16

申请人： Graeme Bilbe ,  John Cryan ,  Conrad Gentsch ,  Kevin McAllister ,  Markus Schmutz ,  Annick Vassout

发明人： Graeme Bilbe ,  John Cryan ,  Conrad Gentsch ,  Kevin McAllister ,  Markus Schmutz ,  Annick Vassout

IPC分类号： A61K31/55

CPC分类号： A61K31/55

摘要： The present invention relates to the use of a racemate of the compound of formula (1) consisting of at least 85% S-enantiomer and not more than 15% R-enantiomer or of pharmaceutically acceptable salts of said racemate or of the S-enantiomer of formula I or of pharmaceutically acceptable salts of said enantiomer for the treatment of anxiety or other psychiatric disorders with underlying anxiety symptomatologies or for the treatment of affective and attention disorders; pharmaceutical compositions for that purpose and packages comprising said pharmaceutical compositions together with instructions for the use of said compositions for the treatment of anxiety or other psychiatric disorders with underlying anxiety symptomatologies or of affective and attention disorders.

公开(公告)号：US20100063029A1

公开(公告)日：2010-03-11

申请号：US12616192

申请日：2009-11-11

申请人： Graeme Bilbe ,  John F. Cryan ,  Conrad Gentsch ,  Kevin Hall Mcallister ,  Markus Schmutz ,  Annick Vassout

发明人： Graeme Bilbe ,  John F. Cryan ,  Conrad Gentsch ,  Kevin Hall Mcallister ,  Markus Schmutz ,  Annick Vassout

IPC分类号： A61K31/55 ,  A61P25/00

CPC分类号： A61K31/55

摘要： The present invention relates to the use of a racemate of the compound of formula (I) consisting of at least 85% S-enantiomer and not more than 15% R-enantiomer or of pharmaceutically acceptable salts of said racemate or of the S-enantiomer of formula I or of pharmaceutically acceptable salts of said anantiomer for the treatment of anxiety or other psychiatric disorders with underlying anxiety symptomatologies or for the treatment of affective and attention disorders; pharmaceutical compositions for that purpose and packages comprising said pharmaceutical compositions together with instructions for the use of said compositions for the treatment of anxiety or other psychiatric disorders with underlying anxiety symptomatologies or of affective and attention disorders.

摘要翻译： 本发明涉及由至少85％S-对映体和不超过15％R-对映异构体或所述外消旋物或S-对映异构体的药学上可接受的盐组成的式（I）化合物的外消旋体的用途 式I的药学上可接受的盐或所述对映异构体的药学上可接受的盐，用于治疗焦虑症或具有潜在焦虑症状学的其他精神疾病或用于治疗情感和注意力障碍; 用于该目的的药物组合物和包含所述药物组合物的包装以及使用所述组合物治疗焦虑症或其他具有潜在焦虑症状或精神障碍的精神疾病的说明书。

公开(公告)号：US07638510B2

公开(公告)日：2009-12-29

申请号：US10545411

申请日：2004-02-16

申请人： Graeme Bilbe ,  John F. Cryan ,  Conrad Gentsch ,  Kevin Hall McAllister ,  Markus Schmutz ,  Annick Vassout

发明人： Graeme Bilbe ,  John F. Cryan ,  Conrad Gentsch ,  Kevin Hall McAllister ,  Markus Schmutz ,  Annick Vassout

IPC分类号： A01N43/46 ,  A01N43/00 ,  A61K31/55 ,  A61K31/5517

CPC分类号： A61K31/55

摘要： The present invention relates to the use of a racemate of the compound of formula (1) consisting of at least 85% S-enantiomer and not more than 15% R-enantiomer or of pharmaceutically acceptable salts of said racemate or of the S-enantiomer of formula I or of pharmaceutically acceptable salts of said enantiomer for the treatment of anxiety or other psychiatric disorders with underlying anxiety symptomatologies or for the treatment of affective and attention disorders; pharmaceutical compositions for that purpose and packages comprising said pharmaceutical compositions together with instructions for the use of said compositions for the treatment of anxiety or other psychiatric disorders with underlying anxiety symptomatologies or of affective and attention disorders.

摘要翻译： 本发明涉及由至少85％S-对映异构体和不超过15％R-对映异构体或所述外消旋物或S-对映异构体的药学上可接受的盐组成的式（1）化合物的外消旋物的用途 所述对映异构体的药学上可接受的盐用于治疗焦虑症或具有潜在焦虑症状症状的其他精神障碍或治疗情感和注意力障碍; 用于该目的的药物组合物和包含所述药物组合物的包装以及使用所述组合物治疗焦虑症或其他具有潜在焦虑症状或精神障碍的精神疾病的说明书。

公开(公告)号：US20080306081A1

公开(公告)日：2008-12-11

申请号：US11718668

申请日：2005-11-03

申请人： Hans O. Kalkman ,  Joachim Nozulak ,  Annick Vassout ,  Konstanze Hurth ,  Dominik Feuerbach ,  Conrad Gentsch ,  Graeme Bilbe

发明人： Hans O. Kalkman ,  Joachim Nozulak ,  Annick Vassout ,  Konstanze Hurth ,  Dominik Feuerbach ,  Conrad Gentsch ,  Graeme Bilbe

IPC分类号： A61K31/501 ,  A61P25/18 ,  A61P25/24

CPC分类号： A61K31/46 ,  A61K45/06 ,  A61K2300/00

摘要： Combinations which comprise at least one nicotinic acetylcholine alpha 7 receptor agonist and at least one compound selected from the group consisting of (a) conventional antipsychotics (b) atypical antipsychotics (c) cognition, attention and/or memory enhancers (d) and to use of these combinations in the treatment of psychiatric disorders.

摘要翻译： 包含至少一种烟碱乙酰胆碱α7受体激动剂和选自（a）常规抗精神病药（b）非典型抗精神病药（c）认知，注意力和/或记忆增强剂（d）的至少一种化合物的组合，并使用 的这些组合在治疗精神疾病。

公开(公告)号：US20100093672A1

公开(公告)日：2010-04-15

申请号：US12598771

申请日：2008-05-01

申请人： Yves-Alain Barde ,  Graeme Bilbe ,  Ruben Deogracias ,  Rainer R. Kuhn ,  Tomoya Matsumoto ,  Anis K. Mir ,  Anna S. Schubart

发明人： Yves-Alain Barde ,  Graeme Bilbe ,  Ruben Deogracias ,  Rainer R. Kuhn ,  Tomoya Matsumoto ,  Anis K. Mir ,  Anna S. Schubart

IPC分类号： A61K31/66 ,  A61K31/135 ,  A61K31/40 ,  A61P3/10 ,  A61P25/22 ,  A61P25/28 ,  A61P3/04

CPC分类号： A61K31/397 ,  A61K31/137 ,  A61K31/138 ,  A61K31/145 ,  A61K45/06

摘要： Use of an S1P receptor modulator in the treatment or prevention of a disease or condition dependent on brain-derived neurotrophic factor (BDNF) expression.

摘要翻译： 使用S1P受体调节剂治疗或预防依赖于脑源性神经营养因子（BDNF）表达的疾病或病症。

公开(公告)号：US20070129389A1

公开(公告)日：2007-06-07

申请号：US10576175

申请日：2004-10-26

申请人： Graeme Bilbe

发明人： Graeme Bilbe

IPC分类号： A61K31/506

CPC分类号： A61K31/506

摘要： The invention relates to the use of an inhibitor of formula I or a N-Oxide or a pharmaceutically acceptable salt thereof having an activity on protein kinases VEGFR-2, Tie-2, c-Src, c-Met, FGFR-1, Flt-1, HER-2, c-Abl, c-Raf, PDGFR-beta, c-Kit, or on a combination of the above enzymes, for the treatment and/or prevention of neurological and vascular disorders related to beta-amyloid generation and/or aggregation such as neurodegenerative diseases like Alzheimer's disease, Down's Syndrome, memory and cognitive impairment, dementia, amyloid neuropathies, brain inflammation, nerve and brain trauma, vascular amyloidosis, or cerebral hemorrhage with amyloidosis

摘要翻译： 本发明涉及对蛋白激酶VEGFR-2，Tie-2，c-Src，c-Met，FGFR-1，Flt具有活性的式I抑制剂或N-氧化物或其药学上可接受的盐的用途 -1，HER-2，c-Abl，c-Raf，PDGFR-β，c-Kit或上述酶的组合，用于治疗和/或预防与β-淀粉样蛋白产生相关的神经和血管疾病 和/或诸如阿尔茨海默病，唐氏综合征，记忆和认知障碍，痴呆，淀粉样蛋白神经病，脑炎症，神经和脑创伤，血管性淀粉样变性或淀粉样变性脑出血等神经退行性疾病

公开(公告)号：US07687512B2

公开(公告)日：2010-03-30

申请号：US10576175

申请日：2004-10-26

申请人： Graeme Bilbe

发明人： Graeme Bilbe

IPC分类号： A61K31/506 ,  A61P25/00

CPC分类号： A61K31/506

摘要： The invention relates to the use of an inhibitor of formula I or a N-Oxide or a pharmaceutically acceptable salt thereof having an activity on protein kinases VEGFR-2, Tie-2, c-Src, c-Met, FGFR-1, Flt-1, HER-2, c-Abl, c-Raf, PDGFR-beta, c-Kit, or on a combination of the above enzymes, for the treatment and/or prevention of neurological and vascular disorders related to beta-amyloid generation and/or aggregation such as neurodegenerative diseases like Alzheimer's disease, Down's Syndrome, memory and cognitive impairment, dementia, amyloid neuropathies, brain inflammation, nerve and brain trauma, vascular amyloidosis, or cerebral hemorrhage with amyloidosis

摘要翻译： 本发明涉及对蛋白激酶VEGFR-2，Tie-2，c-Src，c-Met，FGFR-1，Flt具有活性的式I抑制剂或N-氧化物或其药学上可接受的盐的用途 -1，HER-2，c-Abl，c-Raf，PDGFR-β，c-Kit或上述酶的组合，用于治疗和/或预防与β-淀粉样蛋白产生相关的神经和血管疾病 和/或诸如阿尔茨海默病，唐氏综合征，记忆和认知障碍，痴呆，淀粉样蛋白神经病，脑炎症，神经和脑创伤，血管性淀粉样变性或淀粉样变性脑出血等神经退行性疾病

公开(公告)号：US20070142401A1

公开(公告)日：2007-06-21

申请号：US10576176

申请日：2004-10-26

申请人： Yves Auberson ,  Graeme Bilbe ,  Rainer Kuhn ,  Peter Von Matt ,  Heinrich Rueger ,  Matthias Staufenbiel ,  Jurgen Wagner ,  Kaspar Zimmermann

发明人： Yves Auberson ,  Graeme Bilbe ,  Rainer Kuhn ,  Peter Von Matt ,  Heinrich Rueger ,  Matthias Staufenbiel ,  Jurgen Wagner ,  Kaspar Zimmermann

IPC分类号： A61K31/519 ,  A61K31/506 ,  A61K31/4709 ,  A61K31/404

CPC分类号： A61K31/00 ,  A61K31/496 ,  A61K31/517

摘要： The invention relates to the use of an inhibitor of formula (I), or a pharmaceutically acceptable salt thereof having an activity on protein kinases PKC alpha, PKC beta, PKC gamma, PKC epsilon, PKC theta, CDK-1, KDR, PKA, Flt-1, Flt-2, Flt-3 or Flt-4, or on a combination of the above enzymes, for the treatment and/or prevention of neurological and vascular disorders related to beta-amyloid generation and/or aggregation such as neurodegenerative diseases like Down's Syndrome, memory and cognitive impairment, dementia, amyloid neuropathies, brain inflammation, nerve and brain trauma, vascular amyloidosis, or cerebral hemorrhage with amyloidosis.

摘要翻译： 本发明涉及对蛋白激酶PKCα，PKCβ，PKCγ，PKCε，PKCθ，CDK-1，KDR，PKA等具有活性的式（I）抑制剂或其药学上可接受的盐的用途， Flt-1，Flt-2，Flt-3或Flt-4，或上述酶的组合，用于治疗和/或预防与β-淀粉样蛋白产生和/或聚集相关的神经和血管障碍，例如神经变性 疾病如唐氏综合征，记忆和认知障碍，痴呆，淀粉样蛋白神经病，脑炎症，神经和脑外伤，血管淀粉样变性或淀粉样变性脑出血。

公开(公告)号：US20110212980A1

公开(公告)日：2011-09-01

申请号：US13125331

申请日：2009-10-21

申请人： Graeme Bilbe ,  Baltazar Gomez-Mancilla ,  Daniel Hoyer ,  Donald Johns ,  Hans O. Kalkman ,  Kevin Hall Mcallister

发明人： Graeme Bilbe ,  Baltazar Gomez-Mancilla ,  Daniel Hoyer ,  Donald Johns ,  Hans O. Kalkman ,  Kevin Hall Mcallister

IPC分类号： A61K31/517 ,  A61P25/06

CPC分类号： A61K31/4045 ,  A61K31/404 ,  A61K31/4196 ,  A61K31/422 ,  A61K31/4439 ,  A61K31/517 ,  A61K2300/00

摘要： The present invention relates to novel combinations suitable for the treatment of migraine of various genesis or aetiology, which comprise, as active ingredients, at least one 5-HT1 B/1 D receptor agonist and at least one selective, competitive AMPA receptor antagonist being a 1 H-quinazoline-2,4-dione of formula (I) as defined in the claims; to their preparation; to their use as medicaments and to medicaments comprising them.

摘要翻译： 本发明涉及适用于治疗各种发病或病因偏头痛的新型组合物，其包含作为活性成分的至少一种5-HT 1B / 1D受体激动剂和至少一种选择性竞争性AMPA受体拮抗剂，其为 如权利要求中定义的式（I）的1H-喹唑啉-2,4-二酮; 准备; 用作药物和包含它们的药物。

公开(公告)号：US20100035251A1

公开(公告)日：2010-02-11

申请号：US12305053

申请日：2007-06-18

申请人： Yunsheng He ,  Baltazar Gomez-Mancilla ,  Joanne Meyer ,  Giorgio Rovelli ,  Graeme Bilbe

发明人： Yunsheng He ,  Baltazar Gomez-Mancilla ,  Joanne Meyer ,  Giorgio Rovelli ,  Graeme Bilbe

IPC分类号： C12Q1/68 ,  C07D209/04

CPC分类号： C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Q2600/172

摘要： The genetic polymorphism LRRK2 (leucine-rich repeat kinase 2)-T1602S is significantly associated with conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD), with the patients with TT genotype being at greater risk to progress to Alzheimer's disease. The LRRK2-T2352 also showed a trend for conversion to Alzheimer's disease, with the patients with CC genotype tending to progress to Alzheimer's disease. Similar to the APOE-E4 allele, in the presence of a BuChE-K variant, LRRK2-T1602S and LRRK2-T2352 showed a greater association with the rate of conversion from mild cognitive impairment to Alzheimer's disease. In another study with placebo-treated Alzheimer's disease patients, LRRK2-T1602S and LRRK2-T2352 showed a same trend of association. The Alzheimer's disease patients with TT genotype of LRRK2-T1602S or CC genotype of LRRK2-T2352 tended to decline faster on cognitive performance over 6 months, especially in the presence of a BuChE-K variant. The association between the two common LRRK2 polymorphisms and Alzheimer's disease progression shows that LRRK2 may play a role in Alzheimer's disease pathogenesis, especially disease progression, and that polymorphisms of LRRK2 can be used as biomrkers of this progression.

摘要翻译： 遗传多态性LRRK2（富含亮氨酸的重复激酶2）-T1602S与轻度认知障碍（MCI）与阿尔茨海默病（AD）的转化显着相关，TT基因型患者进入阿尔茨海默氏病的风险更大。 LRRK2-T2352也显示出转变为阿尔茨海默病的趋势，CC基因型患者往往进展为阿尔茨海默氏病。 与APOE-E4等位基因相似，在BuChE-K变体存在下，LRRK2-T1602S和LRRK2-T2352显示与从轻度认知障碍转变为阿尔茨海默氏病的速率更大的关联。 在安慰剂治疗的阿尔茨海默病患者的另一项研究中，LRRK2-T1602S和LRRK2-T2352显示出相同的关联趋势。 具有LRRK2-T1602S的TT基因型或LRRK2-T2352的CC基因型的阿尔茨海默氏病患者在6个月以上的认知功能上往往更快下降，特别是在存在BuChE-K变体的情况下。 两种常见的LRRK2多态性与阿尔茨海默病进展的关系表明，LRRK2可能在阿尔茨海默氏病发病机制中发挥重要作用，特别是疾病进展，LRRK2的多态性可作为这一进展的生物学家。