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公开(公告)号：US20130247233A1
公开(公告)日：2013-09-19
申请号：US13796312
申请日：2013-03-12
申请人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
发明人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
IPC分类号： C12Q1/68 , C07K14/705
CPC分类号： G01N33/74 , A61K38/00 , C07K14/705 , C07K14/723 , C12Q1/6883 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , G01N2333/726 , G01N2500/04 , G01N2500/10 , Y02A50/463 , Y02A50/469 , Y02A50/475 , Y02A50/48
摘要： The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.
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公开(公告)号：US08278327B2
公开(公告)日：2012-10-02
申请号：US12848766
申请日：2010-08-02
申请人： John E. Bergmann , Neil S. Cutshall , Rene Onrust , Hongkui Zeng , Jennifer Lynn Gage , Derek Johnston , Sándor Cseh , László Ürögdi , Ákos Papp
发明人： John E. Bergmann , Neil S. Cutshall , Rene Onrust , Hongkui Zeng , Jennifer Lynn Gage , Derek Johnston , Sándor Cseh , László Ürögdi , Ákos Papp
IPC分类号： A01N43/42 , A61K31/47 , C07D215/00
CPC分类号： A61K31/341 , A61K31/404 , A61K31/4184 , A61K31/4409 , A61K31/47 , A61K31/4965 , A61K31/5415 , C07D209/18 , C07D213/81 , C07D215/36 , C07D235/16 , C07D235/28 , C07D249/18 , C07D279/16 , C07D333/24 , C07D405/12
摘要： Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. The compounds have the general structure: wherein m, n, p, x, R, R1, R2, R3, R4, R5, A and B, are defined herein, including pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.
摘要翻译： 公开了抑制PDE10的化合物，其可用于治疗各种病症，包括（但不限于）精神病性，焦虑症，运动障碍和/或神经障碍，例如帕金森病，亨廷顿氏病，阿尔茨海默病，脑炎，恐惧症 癫痫，失语症，贝尔麻痹，脑性麻痹，睡眠障碍，疼痛，图雷特综合征，精神分裂症，妄想症，药物诱发的精神病，恐慌和强迫症。 该化合物具有以下通式：其中m，n，p，x，R，R 1，R 2，R 3，R 4，R 5，A和B在本文中定义，包括其药学上可接受的盐，立体异构体，溶剂合物或前药。 还公开了含有本发明化合物与药学上可接受的载体的组合物的组合物，以及涉及其在需要其的温血动物中用于抑制PDE10的方法。
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公开(公告)号：US20110091388A1
公开(公告)日：2011-04-21
申请号：US12974693
申请日：2010-12-21
申请人： John E. Bergmann , Neil S. Cutshall , Gregory A. Demopulos , Vincent A. Florio , George A. Gaitanaris , Patrick Gray , John Hohmann , Rene Onrust , Hongkui Zeng
发明人： John E. Bergmann , Neil S. Cutshall , Gregory A. Demopulos , Vincent A. Florio , George A. Gaitanaris , Patrick Gray , John Hohmann , Rene Onrust , Hongkui Zeng
IPC分类号： A61K49/00 , A61K31/197 , A61K31/519 , A61K31/517 , A61K31/433 , A61P25/14 , A61P25/16 , A61P25/00
CPC分类号： A61K31/195 , A61K31/433 , A61K31/519 , A61K31/527
摘要： A method of treating a movement abnormality associated with the pathology of a neurological movement disorder, such as Parkinson's disease or Restless Leg(s) Syndrome by administering a therapeutically effective amount of a PDE7 inhibitory agent. An aspect of the invention provides for the administration of a PDE& inhibitory agent in conjunction with a dopamine agonist or precursor, such as levodopa. In another aspect of the invention, the PDE7 inhibitory agent may be selective for PDE7 relative to other molecular targets (i) known to be involved with the pathology of Parkinson's disease or (ii) at which other drug(s) that are therapeutically effective to treat Parkinson's disease act.
摘要翻译： 通过施用治疗有效量的PDE7抑制剂来治疗与神经运动障碍的病理学相关的运动异常的方法，例如帕金森病或不宁腿综合症。 本发明的一个方面提供了与多巴胺激动剂或前体如左旋多巴结合施用PDE和抑制剂。 在本发明的另一方面，PDE7抑制剂可以相对于已知与帕金森病病理学有关的其它分子靶标（i）可能对PDE7具有选择性，或（ii）其他治疗有效的药物 治疗帕金森病。
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4.发明授权公开(公告)号：US08999654B2
公开(公告)日：2015-04-07
申请号：US12916227
申请日：2010-10-29
申请人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
发明人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
IPC分类号： G01N33/566 , C07K14/72 , C12Q1/68 , C07K14/705 , A61K38/00
CPC分类号： A01K67/0278 , A01K2217/00 , A01K2217/052 , A01K2227/105 , A01K2267/03 , A61K38/00 , A61K49/0008 , C07K14/723 , C12Q1/6883 , C12Q2600/106 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , G01N33/5023 , G01N2333/726 , G01N2800/04 , G01N2800/28 , G01N2800/50
摘要： The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.
摘要翻译： 本发明提供GPCR多肽和多核苷酸，重组材料和转基因小鼠，以及其生产方法。 多肽和多核苷酸可用于例如诊断和治疗疾病和病症的方法。 本发明还提供使用本发明的GPCR多肽和多核苷酸鉴定化合物（例如激动剂或拮抗剂）以及用GPCR多肽，多核苷酸或鉴定的化合物治疗与GPCR功能障碍相关的病症的方法。 本发明还提供用于检测与不适当GPCR活性或水平相关的疾病或病症的诊断测定。
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公开(公告)号：US08637528B2
公开(公告)日：2014-01-28
申请号：US12435347
申请日：2009-05-04
申请人： John E Bergmann , Neil S Cutshall , Gregory A Demopulos , Vincent A Florio , George Gaitanaris , Patrick Gray , John Hohmann , Rene Onrust , Hongkui Zeng
发明人： John E Bergmann , Neil S Cutshall , Gregory A Demopulos , Vincent A Florio , George Gaitanaris , Patrick Gray , John Hohmann , Rene Onrust , Hongkui Zeng
IPC分类号： A61K31/519 , A61K31/505 , A61K31/41
CPC分类号： A61K31/551 , A61K31/00 , A61K31/085 , A61K31/122 , A61K31/137 , A61K31/192 , A61K31/195 , A61K31/198 , A61K31/381 , A61K31/4025 , A61K31/4162 , A61K31/425 , A61K31/433 , A61K31/4439 , A61K31/4985 , A61K31/505 , A61K31/506 , A61K31/519 , A61K31/527 , A61K31/542 , A61K45/06 , C07D471/04 , A61K2300/00
摘要： A method of treating a movement abnormality associated with the pathology of a neurological movement disorder, such as Parkinson's disease or Restless Leg(s) Syndrome by administering a therapeutically effective amount of a PDE7 inhibitory agent. An aspect of the invention provides for the administration of a PDE& inhibitory agent in conjunction with a dopamine agonist or precursor, such as levodopa. In another aspect of the invention, the PDE7 inhibitory agent may be selective for PDE7 relative to other molecular targets (i) known to be involved with the pathology of Parkinson's disease or (ii) at which other drug(s) that are therapeutically effective to treat Parkinson's disease act.
摘要翻译： 通过施用治疗有效量的PDE7抑制剂来治疗与神经运动障碍的病理学相关的运动异常的方法，例如帕金森病或不宁腿综合症。 本发明的一个方面提供了与多巴胺激动剂或前体如左旋多巴结合施用PDE和抑制剂。 在本发明的另一方面，PDE7抑制剂可以相对于已知与帕金森病病理学有关的其它分子靶标（i）可能对PDE7具有选择性，或（ii）其他治疗有效的药物 治疗帕金森病。
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公开(公告)号：US20080260744A1
公开(公告)日：2008-10-23
申请号：US11940917
申请日：2007-11-15
申请人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. Mcllwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
发明人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. Mcllwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
IPC分类号： A61K39/395 , A61K31/70 , C12Q1/68 , C12Q1/02 , A01K67/027 , G01N33/00 , C12N5/06 , G01N33/569 , A61P25/00
CPC分类号： A01K67/0278 , A01K2217/00 , A01K2217/052 , A01K2227/105 , A01K2267/03 , A61K38/00 , A61K49/0008 , C07K14/723 , C12Q1/6883 , C12Q2600/106 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , G01N33/5023 , G01N2333/726 , G01N2800/04 , G01N2800/28 , G01N2800/50
摘要： The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.
摘要翻译： 本发明提供GPCR多肽和多核苷酸，重组材料和转基因小鼠，以及其生产方法。 多肽和多核苷酸可用于例如诊断和治疗疾病和病症的方法。 本发明还提供使用本发明的GPCR多肽和多核苷酸鉴定化合物（例如激动剂或拮抗剂）以及用GPCR多肽，多核苷酸或鉴定的化合物治疗与GPCR功能障碍相关的病症的方法。 本发明还提供用于检测与不适当GPCR活性或水平相关的疾病或病症的诊断测定。
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公开(公告)号：US20110214189A1
公开(公告)日：2011-09-01
申请号：US12916227
申请日：2010-10-29
申请人： GEORGE A. GAITANARIS , JOHN E. BERGMANN , ALEXANDER GRAGEROV , JOHN HOHMANN , FUSHENG LI , LINDA MADISEN , KELLIE L. MCILWAIN , MARIA N. PAVLOVA , DEMETRI VASSILATIS , HONGKUI ZENG
发明人： GEORGE A. GAITANARIS , JOHN E. BERGMANN , ALEXANDER GRAGEROV , JOHN HOHMANN , FUSHENG LI , LINDA MADISEN , KELLIE L. MCILWAIN , MARIA N. PAVLOVA , DEMETRI VASSILATIS , HONGKUI ZENG
IPC分类号： A61K49/00 , C12N5/10 , C12Q1/02 , A01K67/027
CPC分类号： A01K67/0278 , A01K2217/00 , A01K2217/052 , A01K2227/105 , A01K2267/03 , A61K38/00 , A61K49/0008 , C07K14/723 , C12Q1/6883 , C12Q2600/106 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , G01N33/5023 , G01N2333/726 , G01N2800/04 , G01N2800/28 , G01N2800/50
摘要： The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.
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公开(公告)号：US20110185439A1
公开(公告)日：2011-07-28
申请号：US12970094
申请日：2010-12-16
申请人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
发明人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demetri Vassilatis , Hongkui Zeng
IPC分类号： G01N33/48 , A01K67/027 , C12N15/87 , C12N5/10 , C07K14/47 , C07H21/04 , A61K31/7088 , A61P25/00 , A61P3/00 , C12Q1/68 , A61P9/00 , A61P17/00 , G01N33/53
CPC分类号： G01N33/74 , A61K38/00 , C07K14/705 , C07K14/723 , C12Q1/6883 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , G01N2333/726 , G01N2500/04 , G01N2500/10 , Y02A50/463 , Y02A50/469 , Y02A50/475 , Y02A50/48
摘要： The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.
摘要翻译： 本发明提供GPCR多肽和多核苷酸，重组材料和转基因小鼠，以及其生产方法。 多肽和多核苷酸可用于例如诊断和治疗疾病和病症的方法。 本发明还提供使用本发明的GPCR多肽和多核苷酸鉴定化合物（例如激动剂或拮抗剂）以及用GPCR多肽，多核苷酸或鉴定的化合物治疗与GPCR功能障碍相关的病症的方法。 本发明还提供用于检测与不适当GPCR活性或水平相关的疾病或病症的诊断测定。
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公开(公告)号：US20110021509A1
公开(公告)日：2011-01-27
申请号：US12848766
申请日：2010-08-02
申请人： John E. Bergmann , Neil S. Cutshall , Rene Onrust , Hongkui Zeng , Jennifer Lynn Gage , Derek Johnston , Sándor Cseh , László Ürögdi , Ákos Papp
发明人： John E. Bergmann , Neil S. Cutshall , Rene Onrust , Hongkui Zeng , Jennifer Lynn Gage , Derek Johnston , Sándor Cseh , László Ürögdi , Ákos Papp
IPC分类号： A61K31/5415
CPC分类号： A61K31/341 , A61K31/404 , A61K31/4184 , A61K31/4409 , A61K31/47 , A61K31/4965 , A61K31/5415 , C07D209/18 , C07D213/81 , C07D215/36 , C07D235/16 , C07D235/28 , C07D249/18 , C07D279/16 , C07D333/24 , C07D405/12
摘要： Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. The compounds have the general structure: wherein m, n, p, x, R, R1, R2, R3, R4, R5, A and B, are defined herein, including pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.
摘要翻译： 公开了抑制PDE10的化合物，其可用于治疗各种病症，包括（但不限于）精神病性，焦虑症，运动障碍和/或神经障碍，例如帕金森病，亨廷顿氏病，阿尔茨海默病，脑炎，恐惧症 癫痫，失语症，贝尔麻痹，脑性麻痹，睡眠障碍，疼痛，图雷特综合征，精神分裂症，妄想症，药物诱发的精神病，恐慌和强迫症。 该化合物具有以下通式：其中m，n，p，x，R，R 1，R 2，R 3，R 4，R 5，A和B在本文中定义，包括其药学上可接受的盐，立体异构体，溶剂合物或前药。 还公开了含有本发明化合物与药学上可接受的载体的组合物的组合物，以及涉及其在需要其的温血动物中用于抑制PDE10的方法。
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公开(公告)号：US20090178153A1
公开(公告)日：2009-07-09
申请号：US12243731
申请日：2008-10-01
申请人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demitri Vassilatis , Hongkui Zeng
发明人： George A. Gaitanaris , John E. Bergmann , Alexander Gragerov , John Hohmann , Fusheng Li , Linda Madisen , Kellie L. McIlwain , Maria N. Pavlova , Demitri Vassilatis , Hongkui Zeng
IPC分类号： A01K67/027 , C12Q1/68 , A61K31/7088 , G01N33/53 , C12N15/00 , C12N5/10 , A61K49/00
CPC分类号： G01N33/74 , A61K38/00 , C07K14/705 , C07K14/723 , C12Q1/6883 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , G01N2333/726 , G01N2500/04 , G01N2500/10 , Y02A50/463 , Y02A50/469 , Y02A50/475 , Y02A50/48
摘要： The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.
摘要翻译： 本发明提供GPCR多肽和多核苷酸，重组材料和转基因小鼠，以及其生产方法。 多肽和多核苷酸可用于例如诊断和治疗疾病和病症的方法。 本发明还提供使用本发明的GPCR多肽和多核苷酸鉴定化合物（例如激动剂或拮抗剂）以及用GPCR多肽，多核苷酸或鉴定的化合物治疗与GPCR功能障碍相关的病症的方法。 本发明还提供用于检测与不适当GPCR活性或水平相关的疾病或病症的诊断测定。
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