公开(公告)号：US08772504B2

公开(公告)日：2014-07-08

申请号：US13144557

申请日：2010-02-15

申请人： Henricus Jacobus Maria Gijsen ,  François Paul Bischoff ,  Wei Zhuang ,  Sven Franciscus Anna Van Brandt ,  Michel Surkyn ,  Mirko Zaja ,  Didier Jean-Claude Berthelot ,  Michel Anna Jozef De Cleyn ,  Gregor James MacDonald ,  Daniel Oehlrich

发明人： Henricus Jacobus Maria Gijsen ,  François Paul Bischoff ,  Wei Zhuang ,  Sven Franciscus Anna Van Brandt ,  Michel Surkyn ,  Mirko Zaja ,  Didier Jean-Claude Berthelot ,  Michel Anna Jozef De Cleyn ,  Gregor James MacDonald ,  Daniel Oehlrich

IPC分类号： C07D235/00 ,  C07D403/02

CPC分类号： C07D413/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04

摘要： The present invention is concerned with novel substituted benzoxazole, benzimidazole, oxazolopyridine and imidazopyridine derivatives of Formula (I) wherein R1, R2, R3, R4, X, A1, A2, A3, A4, Y1, Y2, Y3 and Z 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 compounds 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）的新的取代苯并恶唑，苯并咪唑，恶唑并吡啶和咪唑并吡啶衍生物，其中R1，R2，R3，R4，X，A1，A2，A3，A4，Y1，Y2，Y3和Z具有含义 在权利要求中限定。 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：US08946426B2

公开(公告)日：2015-02-03

申请号：US13144554

申请日：2010-02-02

申请人： Henricus Jacobus Maria Gijsen ,  Adriana Ingrid Velter ,  Gregor James MacDonald ,  François Paul Bischoff ,  Tongfei Wu ,  Sven Franciscus Anna Van Brandt ,  Michel Surkyn ,  Mirko Zaja ,  Serge Maria Aloysius Pieters ,  Didier Jean-Claude Berthelot ,  Michel Anna Jozef De Cleyn ,  Daniel Oehlrich

发明人： Henricus Jacobus Maria Gijsen ,  Adriana Ingrid Velter ,  Gregor James MacDonald ,  François Paul Bischoff ,  Tongfei Wu ,  Sven Franciscus Anna Van Brandt ,  Michel Surkyn ,  Mirko Zaja ,  Serge Maria Aloysius Pieters ,  Didier Jean-Claude Berthelot ,  Michel Anna Jozef De Cleyn ,  Daniel Oehlrich

IPC分类号： A61K31/437 ,  C07D471/04 ,  C07D487/04 ,  C07D403/10 ,  C07D413/10

CPC分类号： C07D487/04 ,  C07D401/12 ,  C07D403/10 ,  C07D403/12 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04

摘要： The present invention is concerned with substituted bicyclic heterocyclic compounds of Formula (I) wherein Het1, Het2, A1, A2, A3 and A4 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 compounds as an active ingredient as well as the use of said compounds as a medicament.

摘要翻译： 本发明涉及其中Het1，Het2，A1，A2，A3和A4具有权利要求中限定的含义的式（I）的取代双环杂环化合物。 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：US20110281881A1

公开(公告)日：2011-11-17

申请号：US13144554

申请日：2010-02-02

申请人： Henricus, Jacobus, Maria Gijsen ,  Adriana Ingrid Velter ,  Gregor James MacDonald ,  Francois Paul Bischoff ,  Tongfei Wu ,  Sven, Franciscus, Anna Van Brandt ,  Michel Surkyn ,  Mirko Zaja ,  Serge, Maria, Aloysius Pieters ,  Didier Jean-Claude Berthelot ,  Michel, Anna, Josef De Cleyn ,  Daniel Oehlrich

发明人： Henricus, Jacobus, Maria Gijsen ,  Adriana Ingrid Velter ,  Gregor James MacDonald ,  Francois Paul Bischoff ,  Tongfei Wu ,  Sven, Franciscus, Anna Van Brandt ,  Michel Surkyn ,  Mirko Zaja ,  Serge, Maria, Aloysius Pieters ,  Didier Jean-Claude Berthelot ,  Michel, Anna, Josef De Cleyn ,  Daniel Oehlrich

IPC分类号： A61K31/437 ,  C07D403/12 ,  C07D413/14 ,  C07D403/14 ,  C07D487/04 ,  C07D413/12 ,  C07D417/12 ,  C07D401/14 ,  A61K31/4184 ,  A61K31/4439 ,  A61K31/506 ,  A61K31/5025 ,  A61K31/4985 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/4192 ,  A61K31/4196 ,  A61K31/444 ,  A61K31/501 ,  A61P25/28 ,  A61P25/00 ,  A61P25/16 ,  C07D471/04

CPC分类号： C07D487/04 ,  C07D401/12 ,  C07D403/10 ,  C07D403/12 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04

摘要： The present invention is concerned with substituted bicyclic heterocyclic compounds of Formula (I) wherein Het1, Het2, A1, A2, A3 and A4 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 compounds as an active ingredient as well as the use of said compounds as a medicament.

摘要翻译： 本发明涉及其中Het1，Het2，A1，A2，A3和A4具有权利要求中限定的含义的式（I）的取代双环杂环化合物。 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：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：US08937060B2

公开(公告)日：2015-01-20

申请号：US13319541

申请日：2010-05-11

申请人： Jose Maria Cid-Nunez ,  Daniel Oehlrich ,  Andres Avelino Trabanco-Suarez ,  Gary John Tresadern ,  Juan Antonio Vega Ramiro ,  Gregor James MacDonald

发明人： Jose Maria Cid-Nunez ,  Daniel Oehlrich ,  Andres Avelino Trabanco-Suarez ,  Gary John Tresadern ,  Juan Antonio Vega Ramiro ,  Gregor James MacDonald

IPC分类号： C07D487/04 ,  C07D241/04 ,  C07D265/30 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/496

CPC分类号： A61K31/496 ,  A61K9/0019 ,  A61K9/0095 ,  A61K9/06 ,  A61K9/10 ,  A61K9/2059 ,  A61K31/437 ,  A61K31/438 ,  A61K31/4545 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D471/04 ,  C07D519/00 ,  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。

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：US20130338185A1

公开(公告)日：2013-12-19

申请号：US13883906

申请日：2011-11-08

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

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

IPC分类号： C07D471/04 ,  A61K45/06 ,  A61K31/437

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：US20120184525A1

公开(公告)日：2012-07-19

申请号：US13319541

申请日：2010-05-11

申请人： Jose Maria Cid-Nunez ,  Daniel Oehlrich ,  Andres Avelino Trabanco-Suarez ,  Gary John Tresadern ,  Juan Antonio Vega Ramiro ,  Gregor James MacDonald

发明人： Jose Maria Cid-Nunez ,  Daniel Oehlrich ,  Andres Avelino Trabanco-Suarez ,  Gary John Tresadern ,  Juan Antonio Vega Ramiro ,  Gregor James MacDonald

IPC分类号： A61K31/5377 ,  A61K31/496 ,  A61K31/438 ,  A61K31/437 ,  C07D471/10 ,  C07D491/20 ,  C07D471/04 ,  A61P25/00 ,  A61P25/22 ,  A61P25/18 ,  A61P25/30 ,  A61P25/06 ,  A61P25/08 ,  A61P25/28 ,  A61P25/24 ,  A61K31/506

CPC分类号： A61K31/496 ,  A61K9/0019 ,  A61K9/0095 ,  A61K9/06 ,  A61K9/10 ,  A61K9/2059 ,  A61K31/437 ,  A61K31/438 ,  A61K31/4545 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D471/04 ,  C07D519/00 ,  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。