公开(公告)号：US08841323B2

公开(公告)日：2014-09-23

申请号：US12282663

申请日：2007-03-15

申请人： Jose Maria Cid-Nunez ,  Jose Ignacio Andres-Gil ,  Andres Avelino Trabanco-Suarez ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Gregor James MacDonald ,  Shirley Elizabeth Pullan ,  Robert Johannes Lutjens ,  Guillaume Albert Jacques Duvey ,  Vanthea Nhem ,  Terry Patrick Finn ,  Gagik Melikyan ,  Vincent Mutel

发明人： Hassan Julien Imogai ,  Jose Maria Cid-Nunez ,  Jose Ignacio Andres-Gil ,  Andres Avelino Trabanco-Suarez ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Gregor James MacDonald ,  Shirley Elizabeth Pullan ,  Robert Johannes Lutjens ,  Guillaume Albert Jacques Duvey ,  Vanthea Nhem ,  Terry Patrick Finn ,  Gagik Melikyan

IPC分类号： A61K31/4439 ,  C07D213/85

CPC分类号： C07D213/85 ,  C07D213/84 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D487/08 ,  C07D491/04 ,  C07D491/10 ,  C07D495/04

摘要： The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-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. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

摘要翻译： 本发明涉及新型化合物，特别是根据式（I）的新型吡啶酮衍生物，其中所有基团在申请和权利要求书中定义。 根据本发明的化合物是代谢型受体亚型2（“mGluR2”）的正性变构调节剂，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障碍以及参与代谢型受体的mGluR2亚型的疾病 。 特别地，这些疾病是选自焦虑，精神分裂症，偏头痛，抑郁症和癫痫组的中枢神经系统疾病。 本发明还涉及制备这些化合物和组合物的药物组合物和方法，以及这些化合物用于预防和治疗其中涉及mGluR2的疾病的用途。

公开(公告)号：US20100166655A1

公开(公告)日：2010-07-01

申请号：US12282663

申请日：2007-03-15

申请人： Hassan Julien Imogai ,  Vincent Mutel ,  Jose Maria Cid-Nunez ,  Jose Ignacio Andres-Gil ,  Andres Avelino Trabanco-Suarez ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Gregor James MaCdonald ,  Shirley Elizabeth Pullan ,  Robert Johannes Lutjens ,  Guillaume Albert Jacques Duvey ,  Vanthea Nhem ,  Terry Palrick Finn ,  Gagik Melikyan

发明人： Hassan Julien Imogai ,  Vincent Mutel ,  Jose Maria Cid-Nunez ,  Jose Ignacio Andres-Gil ,  Andres Avelino Trabanco-Suarez ,  Julen Oyarzabal Santamarina ,  Frank Matthias Dautzenberg ,  Gregor James MaCdonald ,  Shirley Elizabeth Pullan ,  Robert Johannes Lutjens ,  Guillaume Albert Jacques Duvey ,  Vanthea Nhem ,  Terry Palrick Finn ,  Gagik Melikyan

IPC分类号： A61K49/00 ,  C07D213/84 ,  A61K31/44 ,  C07D401/04 ,  A61K31/496 ,  C07D413/12 ,  A61K31/5377 ,  A61K31/4439 ,  A61K31/4545 ,  C07D403/14 ,  A61K31/497 ,  A61K31/444 ,  A61P25/00 ,  A61P25/22 ,  A61P25/18 ,  A61P25/06 ,  A61P25/28

CPC分类号： C07D213/85 ,  C07D213/84 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D487/08 ,  C07D491/04 ,  C07D491/10 ,  C07D495/04

摘要： The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-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. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

摘要翻译： 本发明涉及新型化合物，特别是根据式（I）的新型吡啶酮衍生物，其中所有基团在申请和权利要求书中定义。 根据本发明的化合物是代谢型受体亚型2（“mGluR2”）的正性变构调节剂，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障碍以及参与代谢型受体的mGluR2亚型的疾病 。 特别地，这些疾病是选自焦虑，精神分裂症，偏头痛，抑郁症和癫痫组的中枢神经系统疾病。 本发明还涉及制备这些化合物和组合物的药物组合物和方法，以及这些化合物用于预防和治疗其中涉及mGluR2的疾病的用途。

公开(公告)号：US06534488B1

公开(公告)日：2003-03-18

申请号：US10031760

申请日：2002-05-08

申请人： Alexander Mark Gibson ,  Marivi Mendizabal ,  Richard Pither ,  Shirley Elizabeth Pullan ,  Vaughan Griffiths ,  Philip Duncanson

发明人： Alexander Mark Gibson ,  Marivi Mendizabal ,  Richard Pither ,  Shirley Elizabeth Pullan ,  Vaughan Griffiths ,  Philip Duncanson

IPC分类号： C07F938

CPC分类号： C07B59/004 ,  C07F9/386 ,  C07F9/3873 ,  C07F9/409

摘要： The present invention relates to 32P or 33P-labelled bisphosphonates as radiotherapeutic radiopharmaceuticals. The 32P- or 33P-labelled bisphosphonates, which are chemically identical to the unlabelled agent, are expected to target the lesion site in an identical manner, but also deliver a significant radiocytotoxic effect to the surrounding cells. This should result, given the favorable energetics of the &bgr; particle emission from the 33P nuclide, in a loss of proliferative capacity of cells associated with the tumor lesion. The relative stability and in vivo localisation of bisphosphonates makes them good candidates as 32P/33P delivery vehicles.

摘要翻译： 本发明涉及作为放射治疗放射性药物的32P或33P标记的双膦酸盐。 与未标记试剂化学相同的32P或33P标记的双膦酸盐预期以相同的方式靶向病变部位，但也对周围细胞产生显着的放射性细胞毒性作用。 考虑到来自33P核素的β粒子发射的有利能量，与肿瘤病变相关的细胞的增殖能力丧失将导致这一点。 双膦酸盐的相对稳定性和体内定位使其成为32P / 33P递送载体的良好候选物。