公开(公告)号：US08546440B2

公开(公告)日：2013-10-01

申请号：US13133027

申请日：2009-12-16

申请人： Henricus Jacobus Maria Gijsen ,  Gregor James MacDonald ,  François Paul Bischoff ,  Gary John Tresadern ,  Andrés Avelino Trabanco-Suárez ,  Sven Franciscus Anna Van Brandt ,  Didier Jean-Claude Berthelot

发明人： Henricus Jacobus Maria Gijsen ,  Gregor James MacDonald ,  François Paul Bischoff ,  Gary John Tresadern ,  Andrés Avelino Trabanco-Suárez ,  Sven Franciscus Anna Van Brandt ,  Didier Jean-Claude Berthelot

IPC分类号： A61K31/5377 ,  A61K31/506 ,  A61K31/4439 ,  A61K31/4196 ,  A61K31/4188 ,  C07D487/04

CPC分类号： C07D471/04

摘要： The present invention is concerned with novel substituted bicyclic imidazole derivatives of Formula (I) wherein R0, R1, R3, R4, X, A1, A2, A3, A4, Y1, Y2 and Y3 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said novel compound as an active ingredient as well as the use of said compounds as a medicament.

摘要翻译： 本发明涉及式（I）的新型取代双环咪唑衍生物，其中R 0，R 1，R 3，R 4，X，A 1，A 2，A 3，A 4，Y 1，Y 2和Y 3具有权利要求中定义的含义。 根据本发明的化合物可用作γ-分泌酶调节剂。 本发明还涉及制备这种新化合物的方法，包含所述新化合物作为活性成分的药物组合物以及所述化合物作为药物的用途。

公开(公告)号：US20110237580A1

公开(公告)日：2011-09-29

申请号：US13133027

申请日：2009-12-16

申请人： Henricus Jacobus Maria Gijsen ,  Gregor James MacDonald ,  François Paul Bischoff ,  Gary John Tresadern ,  Andrés Avelino Trabanco-Suárez ,  Sven Franciscus Anna Van Brandt ,  Didier Jean-Claude Berthelot

发明人： Henricus Jacobus Maria Gijsen ,  Gregor James MacDonald ,  François Paul Bischoff ,  Gary John Tresadern ,  Andrés Avelino Trabanco-Suárez ,  Sven Franciscus Anna Van Brandt ,  Didier Jean-Claude Berthelot

IPC分类号： A61K31/5377 ,  C07D471/04 ,  C07D487/04 ,  C07D413/14 ,  A61K31/437 ,  A61K31/5025 ,  A61K31/4985 ,  A61P25/28

CPC分类号： C07D471/04

摘要： The present invention is concerned with novel substituted bicyclic imidazole derivatives of Formula (I) wherein R0, R1, R3, R4, X, A1, A2, A3, A4, Y1, Y2 and Y3 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said novel compound as an active ingredient as well as the use of said compounds as a medicament.

摘要翻译： 本发明涉及式（I）的新型取代双环咪唑衍生物，其中R 0，R 1，R 3，R 4，X，A 1，A 2，A 3，A 4，Y 1，Y 2和Y 3具有权利要求中定义的含义。 根据本发明的化合物可用作γ-分泌酶调节剂。 本发明还涉及制备这种新化合物的方法，包含所述新化合物作为活性成分的药物组合物以及所述化合物作为药物的用途。

公开(公告)号：US20130109683A1

公开(公告)日：2013-05-02

申请号：US13703199

申请日：2011-06-08

申请人： Andrés Avelino Trabanco-Suárez ,  Frederik Jan Rita Rombouts ,  Gary John Tresadern ,  Michiel Luc Maria Van Gool ,  Gregor James MacDonald ,  Carolina Martinez Lamenca ,  Henricus Jacobus Maria Gijsen

发明人： Andrés Avelino Trabanco-Suárez ,  Frederik Jan Rita Rombouts ,  Gary John Tresadern ,  Michiel Luc Maria Van Gool ,  Gregor James MacDonald ,  Carolina Martinez Lamenca ,  Henricus Jacobus Maria Gijsen

IPC分类号： C07D413/10 ,  C07D265/30

CPC分类号： C07D265/30 ,  C07D413/04 ,  C07D413/10

摘要： The present invention relates to novel 5,6-dihydro-2H-[1,4]oxazin-3-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta-amyloid.

摘要翻译： 本发明涉及作为β-分泌酶抑制剂的新的5,6-二氢-2H- [1,4]恶嗪-3-基胺衍生物，也称为β位点淀粉样蛋白切割酶，BACE，BACE1，Asp2或memapsin2 。 本发明还涉及包含这些化合物的药物组合物，制备这些化合物和组合物的方法，以及这些化合物和组合物用于预防和治疗其中涉及β-分泌酶的疾病如阿尔茨海默病的用途（例如， AD），轻度认知障碍，衰老，痴呆，路易体痴呆，唐氏综合征，与中风相关的痴呆，与帕金森病相关的痴呆和与β-淀粉样蛋白相关的痴呆。

公开(公告)号：US09840507B2

公开(公告)日：2017-12-12

申请号：US13995523

申请日：2011-12-21

申请人： Andrés Avelino Trabanco-Suárez ,  Francisca Delgado-Jiménez ,  Juan Antonio Vega Ramiro ,  Gary John Tresadern ,  Henricus Jacobus Maria Gijsen ,  Daniel Oehlrich

发明人： Andrés Avelino Trabanco-Suárez ,  Francisca Delgado-Jiménez ,  Juan Antonio Vega Ramiro ,  Gary John Tresadern ,  Henricus Jacobus Maria Gijsen ,  Daniel Oehlrich

IPC分类号： A61K31/4985 ,  C07D487/04

CPC分类号： C07D487/04

摘要： The present invention relates to novel 5,6-dihydro-imidazo[1,2-a]pyrazin-8-ylamine inhibitors of beta-secretase, having the structure shown in Formula (I) wherein R1, R2, R3, R4, X1, X2, X3, X4, L and Ar are defined in the specification. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, cerebrovascular amyloid angiopathy, multi-infarct dementia, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.

公开(公告)号：US09174953B2

公开(公告)日：2015-11-03

申请号：US13516968

申请日：2010-12-16

申请人： Gregor James MacDonald ,  Gary John Tresadern ,  Andrés Avelino Trabanco-Suárez ,  Joaquin Pastor-Fernández

发明人： Gregor James MacDonald ,  Gary John Tresadern ,  Andrés Avelino Trabanco-Suárez ,  Joaquin Pastor-Fernández

IPC分类号： C07D513/04 ,  A61K31/4365 ,  C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12

CPC分类号： C07D277/60 ,  A61K31/4365 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D513/04

摘要： The present invention relates to novel bicyclic thiazoles which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”) and which are useful for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which mGluR5 is involved.

摘要翻译： 本发明涉及新的双环噻唑，其是代谢型谷氨酸受体亚型5（“mGluR5”）的正变构调节剂，其可用于治疗或预防与谷氨酸功能障碍相关的病症和其中受体的mGluR5亚型为 涉及。 本发明还涉及包含这些化合物的药物组合物，制备这些化合物和组合物的方法，以及这些化合物和组合物用于预防和治疗其中涉及mGluR5的病症的用途。

公开(公告)号：US09271967B2

公开(公告)日：2016-03-01

申请号：US13883906

申请日：2011-11-08

申请人： José Maria Cid-Núñez ,  Andrés Avelino Trabanco-Suárez ,  Juan Antonio Vega Ramiro ,  Daniel Oehlrich ,  Gary John Tresadern ,  Gregor James Macdonald

发明人： José Maria Cid-Núñez ,  Andrés Avelino Trabanco-Suárez ,  Juan Antonio Vega Ramiro ,  Daniel Oehlrich ,  Gary John Tresadern ,  Gregor James Macdonald

IPC分类号： A61K31/44 ,  C07D491/02 ,  A61K31/437 ,  A61K45/06 ,  C07D471/04 ,  A61K9/00 ,  A61K9/06 ,  A61K9/20

CPC分类号： A61K31/437 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0095 ,  A61K9/06 ,  A61K9/2059 ,  A61K45/06 ,  C07D471/04 ,  A61K2300/00

摘要： The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (“mGluR2”), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

公开(公告)号：US09040707B2

公开(公告)日：2015-05-26

申请号：US13516985

申请日：2010-12-16

申请人： Gregor James MacDonald ,  Andrés Avelino Trabanco-Suárez ,  Susana Conde-Ceide ,  Gary John Tresadern ,  José Manuel Bartolomé-Nebreda ,  Joaquin Pastor-Fernández

发明人： Gregor James MacDonald ,  Andrés Avelino Trabanco-Suárez ,  Susana Conde-Ceide ,  Gary John Tresadern ,  José Manuel Bartolomé-Nebreda ,  Joaquin Pastor-Fernández

IPC分类号： A61K31/4365 ,  C07D513/04

CPC分类号： C07D513/04 ,  A61K31/4365

摘要： The present invention relates to novel bicyclic thiazoles which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”) and which are useful for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which mGluR5 is involved.

公开(公告)号：US09012448B2

公开(公告)日：2015-04-21

申请号：US13884149

申请日：2011-11-08

申请人： José Maria Cid-Núñez ,  Andrés Avelino Trabanco-Suárez ,  Juan Antonio Vega Ramiro ,  Daniel Oehlrich ,  Gary John Tresadern ,  Gregor James MacDonald

发明人： José Maria Cid-Núñez ,  Andrés Avelino Trabanco-Suárez ,  Juan Antonio Vega Ramiro ,  Daniel Oehlrich ,  Gary John Tresadern ,  Gregor James MacDonald

IPC分类号： A61K31/5377 ,  A61K45/06 ,  C07D471/04 ,  A61K9/00 ,  A61K9/06 ,  A61K9/10 ,  A61K9/20 ,  A61K31/542

CPC分类号： A61K31/5377 ,  A61K9/0019 ,  A61K9/06 ,  A61K9/10 ,  A61K9/2009 ,  A61K31/542 ,  A61K45/06 ,  C07D471/04

摘要： The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (“mGluR2”), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

摘要翻译： 本发明涉及式（I）的新的三唑并[4,3-a]吡啶衍生物，其中所有基团如权利要求中所定义。 根据本发明的化合物是代谢型谷氨酸受体亚型2（“mGluR2”）的正变构调节剂，其可用于治疗或预防与谷氨酸功能障碍相关的神经和精神病学障碍以及代谢代谢受体的mGluR2亚型 参与。 本发明还涉及包含这种化合物的药物组合物，制备这些化合物和组合物的方法，以及这些化合物用于预防或治疗其中涉及mGluR2的神经和精神疾病和疾病的用途。

公开(公告)号：US20120258955A1

公开(公告)日：2012-10-11

申请号：US13516985

申请日：2010-12-16

申请人： Gregor James MacDonald ,  Andrés Avelino Trabanco-Suárez ,  Susana Conde-Ceide ,  Gary John Tresadern ,  José Manuel Bartolomé-Nebreda ,  Joaquin Pastor-Fernández

发明人： Gregor James MacDonald ,  Andrés Avelino Trabanco-Suárez ,  Susana Conde-Ceide ,  Gary John Tresadern ,  José Manuel Bartolomé-Nebreda ,  Joaquin Pastor-Fernández

IPC分类号： A61K31/437 ,  A61K31/55 ,  A61P25/00 ,  A61P25/18 ,  A61K31/444 ,  A61P25/22 ,  A61P25/30 ,  A61P25/28 ,  A61P25/16 ,  A61P3/04 ,  C07D513/04 ,  A61P25/24

CPC分类号： C07D513/04 ,  A61K31/4365

摘要： The present invention relates to novel bicyclic thiazoles which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”) and which are useful for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which mGluR5 is involved.

公开(公告)号：US08993591B2

公开(公告)日：2015-03-31

申请号：US13883818

申请日：2011-11-08

申请人： José Maria Cid-Núñez ,  Andrés Avelino Trabanco-Suárez ,  Juan Antonio Vega Ramiro ,  Daniel Oehlrich ,  Gary John Tresadern ,  Gregor James Macdonald

发明人： José Maria Cid-Núñez ,  Andrés Avelino Trabanco-Suárez ,  Juan Antonio Vega Ramiro ,  Daniel Oehlrich ,  Gary John Tresadern ,  Gregor James Macdonald

IPC分类号： A61K31/44 ,  C07D515/02 ,  A61K31/498 ,  A61K31/542 ,  A61K45/06 ,  C07D471/02 ,  C07D471/04 ,  A61K9/20 ,  A61K31/437 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/5377 ,  A61K9/00 ,  A61K47/06 ,  A61K47/10 ,  A61K47/26 ,  A61K9/06 ,  A61K47/38

CPC分类号： A61K31/498 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0095 ,  A61K9/06 ,  A61K9/2009 ,  A61K9/2018 ,  A61K9/2059 ,  A61K31/437 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/542 ,  A61K45/06 ,  A61K47/06 ,  A61K47/10 ,  A61K47/26 ,  A61K47/38 ,  C07D471/02 ,  C07D471/04 ,  A61K2300/00

摘要： The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (“mGluR2”), which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.

摘要翻译： 本发明涉及式（I）的新的三唑并[4,3-a]吡啶衍生物，其中所有基团如权利要求中所定义。 根据本发明的化合物是代谢型谷氨酸受体亚型2（“mGluR2”）的正变构调节剂，其可用于治疗或预防与谷氨酸功能障碍相关的神经和精神病学障碍以及代谢代谢受体的mGluR2亚型 参与。 本发明还涉及包含这种化合物的药物组合物，制备这些化合物和组合物的方法，以及这些化合物用于预防或治疗其中涉及mGluR2的神经和精神疾病和疾病的用途。