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1. 发明授权

US08710092B2 Substituted indolo 4,3 FG quinolines useful for treating migraine 有权
标题翻译：取代吲哚4,3吡啶喹啉可用于治疗偏头痛
公开(公告)号：US08710092B2
公开(公告)日：2014-04-29
申请号：US12978314
申请日：2010-12-23
申请人： Jian Zhang , Robert O. Cook , Thomas A. Armer , Sergey Alexandrovich Kosarev , Dejian Xie
发明人： Jian Zhang , Robert O. Cook , Thomas A. Armer , Sergey Alexandrovich Kosarev , Dejian Xie
IPC分类号： A61K31/40
CPC分类号： C07D519/02 , C07D457/04
摘要： Provided herein are substituted indolo[4,3-fg]quinolines of Formula (I) and (II) where R1-R6 and R13 are as defined in the specification and pharmaceutical compositions thereof which are useful in treating, preventing, or ameliorating a variety of medical disorders such as, for example, migraine. In other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and or 5-HT1B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein.
摘要翻译：本文提供了式（I）和（II）的取代的吲哚并[4,3-f]喹啉，其中R 1 -R 6和R 13如说明书及其药物组合物中所定义，其可用于治疗，预防或改善品种的医学病症，例如偏头痛。在其它实施方案中，本文提供了使用本文公开的化合物和组合物来激发受体例如5-HT1D和/或5-HT1B受体的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物拮抗或抑制受体例如5-HT 2B受体的活性的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物调节5-羟色胺转运的方法。

2. 发明申请

US20120329806A1 NOVEL FLUOROERGOLINE ANALOGS 有权
标题翻译：新型荧光素类似物
公开(公告)号：US20120329806A1
公开(公告)日：2012-12-27
申请号：US13531371
申请日：2012-06-22
申请人： Robert O. Cook , Jian Zhang , Thomas A. Armer
发明人： Robert O. Cook , Jian Zhang , Thomas A. Armer
IPC分类号： C07D519/02 , A61P25/06 , A61K31/4985
CPC分类号： C07D519/02 , A61K9/0075 , A61K9/0078 , A61K31/495 , A61K31/4985 , C07D457/04 , C07D498/04 , C07D498/14 , C07D519/00
摘要： Provided herein are novel fluoroergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2B receptors using the compounds and compositions disclosed herein.
摘要翻译：本文提供新的氟麦角灵衍生物及其组合物。在其它实施方案中，本文提供了使用本文公开的化合物和组合物治疗，预防或改善各种医学病症例如偏头痛的方法。在其它实施方案中，本文提供的是使用本文公开的化合物和组合物来激发受体例如5-HT1D和/或5-HT1B受体而不激发5-HT 2B受体的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物来拮抗或抑制受体例如肾上腺素α2A和/或α2B受体的活性的方法。

3. 发明授权

US08119639B2 Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile 有权
标题翻译： DHE的治疗性给药方法，能够快速缓解偏头痛，同时尽量减少副作用
公开(公告)号：US08119639B2
公开(公告)日：2012-02-21
申请号：US12839190
申请日：2010-07-19
申请人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
发明人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
IPC分类号： A61K31/48
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
摘要翻译：公开了含有二氢麦角胺（DHE）的药物组合物和其中向患者施用DHE以治疗偏头痛而没有副作用或副作用的方法。公开了用DHE快速治疗偏头痛的方法，其包括：抑制峰值血浆浓度（C max）并稍微延迟峰值，以避免激活多巴胺能和肾上腺素能受体，同时实现足够的活性结合5-羟色胺受体以缓解偏头痛在允许快速解决偏头痛症状的时间范围内的症状。公开了适用于该方法的吸入器。公开了实施发明方法的试剂盒。

4. 发明授权

US07994197B2 Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile 有权
标题翻译： DHE的治疗性给药方法，能够快速缓解偏头痛，同时尽量减少副作用
公开(公告)号：US07994197B2
公开(公告)日：2011-08-09
申请号：US12548292
申请日：2009-08-26
申请人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
发明人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
IPC分类号： A61K31/445
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
摘要翻译：公开了含有二氢麦角胺（DHE）的药物组合物和其中向患者施用DHE以治疗偏头痛而没有副作用或副作用的方法。公开了用DHE快速治疗偏头痛的方法，其包括：抑制峰值血浆浓度（C max）并稍微延迟峰值，以避免激活多巴胺能和肾上腺素能受体，同时实现足够的活性结合5-羟色胺受体以缓解偏头痛在允许快速解决偏头痛症状的时间范围内的症状。公开了适用于该方法的吸入器。公开了实施发明方法的试剂盒。

5. 发明申请

US20110152280A1 NOVEL ERGOLINE ANALOGS 有权
标题翻译：新的胆固醇类似物
公开(公告)号：US20110152280A1
公开(公告)日：2011-06-23
申请号：US12978314
申请日：2010-12-23
申请人： ROBERT O. COOK , Thomas A. Armer , Sergey Alexandrovich Kosarev , Dejian Xie
发明人： ROBERT O. COOK , Thomas A. Armer , Sergey Alexandrovich Kosarev , Dejian Xie
IPC分类号： A61K31/4985 , C07D519/02 , A61P25/06 , A61P25/16 , A61P25/24 , A61P25/00 , A61P1/08 , A61P3/00
CPC分类号： C07D519/02 , C07D457/04
摘要： Provided herein are novel ergoline derivatives and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and or 5-HT1B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein.
摘要翻译：本文提供了新的麦角灵衍生物及其药物组合物。在其它实施方案中，本文提供的是使用本文公开的化合物和组合物治疗，预防或改善各种医学病症例如偏头痛的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物来激发受体例如5-HT1D和/或5-HT1B受体的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物拮抗或抑制受体例如5-HT 2B受体的活性的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物调节5-羟色胺转运的方法。

6. 发明申请

US20100081664A1 METHOD OF THERAPEUTIC ADMINISTRATION OF DHE TO ENABLE RAPID RELIEF OF MIGRAINE WHILE MINIMIZING SIDE EFFECT PROFILE 审中-公开
公开(公告)号：US20100081664A1
公开(公告)日：2010-04-01
申请号：US12548304
申请日：2009-08-26
申请人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
发明人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
IPC分类号： A61K31/4985 , A61P25/06 , A61M15/00
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

7. 发明申请

US20100081663A1 METHOD OF THERAPEUTIC ADMINISTRATION OF DHE TO ENABLE RAPID RELIEF OF MIGRAINE WHILE MINIMIZING SIDE EFFECT PROFILE 有权
标题翻译： DHE治疗方法可以使最小化侧面影响特征的影像快速缓解
公开(公告)号：US20100081663A1
公开(公告)日：2010-04-01
申请号：US12548292
申请日：2009-08-26
申请人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
发明人： Robert O. Cook , Stephen B. Shrewsbury , Nabih N. Ramadan , Thomas A. Armer
IPC分类号： A61K31/4985 , A61P25/06 , A61M15/00
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
摘要翻译：公开了含有二氢麦角胺（DHE）的药物组合物和其中向患者施用DHE以治疗偏头痛而没有副作用或副作用的方法。公开了用DHE快速治疗偏头痛的方法，其包括：抑制峰值血浆浓度（C max）并稍微延迟峰值，以避免激活多巴胺能和肾上腺素能受体，同时实现足够的活性结合5-羟色胺受体以缓解偏头痛在允许快速解决偏头痛症状的时间范围内的症状。公开了适用于该方法的吸入器。公开了实施发明方法的试剂盒。

8. 发明授权

US08604035B2 Fluoroergoline analogs 有权
公开(公告)号：US08604035B2
公开(公告)日：2013-12-10
申请号：US13531371
申请日：2012-06-22
申请人： Robert O. Cook , Jian Zhang , Thomas A. Armer
发明人： Robert O. Cook , Jian Zhang , Thomas A. Armer
IPC分类号： A01N43/58 , A01N43/60 , A61K31/50 , A61K31/495
CPC分类号： C07D519/02 , A61K9/0075 , A61K9/0078 , A61K31/495 , A61K31/4985 , C07D457/04 , C07D498/04 , C07D498/14 , C07D519/00
摘要： Provided herein are novel fluoroergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2B receptors using the compounds and compositions disclosed herein.

9. 发明授权

US08592445B2 Iso-ergoline derivatives 失效
标题翻译：异麦角灵衍生物
公开(公告)号：US08592445B2
公开(公告)日：2013-11-26
申请号：US13531416
申请日：2012-06-22
申请人： Jian Zhang , Robert O. Cook
发明人： Jian Zhang , Robert O. Cook
IPC分类号： A01N43/42 , A61K31/44
CPC分类号： C07D457/12 , C07D519/00 , C07D519/02
摘要： Provided herein are novel iso-ergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1Breceptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2Breceptors using the compounds and compositions disclosed herein.
摘要翻译：本文提供新颖的异麦角灵衍生物及其组合物。在其它实施方案中，本文提供了使用本文公开的化合物和组合物治疗，预防或改善各种医学病症例如偏头痛的方法。在其它实施方案中，本文提供的是使用本文公开的化合物和组合物来激发受体例如5-HT1D和/或5-HT1B受体而不激发5-HT 2B受体的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物拮抗或抑制受体例如肾上腺素α2A和/或α2B受体的活性的方法。

10. 发明申请

US20130158064A1 NOVEL ISO-ERGOLINE DERIVATIVES 失效
标题翻译：新型的ISO-ERGOLINE衍生物
公开(公告)号：US20130158064A1
公开(公告)日：2013-06-20
申请号：US13531416
申请日：2012-06-22
申请人： Jian Zhang , Robert O. Cook
发明人： Jian Zhang , Robert O. Cook
IPC分类号： C07D457/12 , A61P25/06 , A61P25/16 , A61K31/48
CPC分类号： C07D457/12 , C07D519/00 , C07D519/02
摘要： Provided herein are novel iso-ergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1Breceptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2Breceptors using the compounds and compositions disclosed herein.
摘要翻译：本文提供新颖的异麦角灵衍生物及其组合物。在其它实施方案中，本文提供了使用本文公开的化合物和组合物治疗，预防或改善各种医学病症例如偏头痛的方法。在其它实施方案中，本文提供的是使用本文公开的化合物和组合物来激发受体例如5-HT1D和/或5-HT1B受体而不激发5-HT 2B受体的方法。在其它实施方案中，本文提供了使用本文公开的化合物和组合物拮抗或抑制受体例如肾上腺素α2A和/或α2B受体的活性的方法。

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