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1. 发明申请

US20100284913A1 Methods and compositions for studying, imaging, and treating pain 有权
标题翻译：用于研究，成像和治疗疼痛的方法和组合物
公开(公告)号：US20100284913A1
公开(公告)日：2010-11-11
申请号：US12800053
申请日：2010-05-07
申请人： Justin Du Bois , John Mulcahy , Brian Andresen , David C. Yeomans , Sandip Biswal
发明人： Justin Du Bois , John Mulcahy , Brian Andresen , David C. Yeomans , Sandip Biswal
IPC分类号： A61K51/04 , C07D487/14 , C07K16/00 , C07K14/00 , C07H21/04 , A61K31/519 , A61K47/48 , A61K38/02 , A61P1/00 , A61P13/00 , A61P25/00 , A61P25/08 , A61P29/00 , A61K49/16 , A61K49/14 , A61K49/12 , A61K49/10 , A61K38/43 , A61P17/00 , A61K31/58 , C12N9/96
CPC分类号： C07D487/16 , A61K8/4953 , A61K49/0002 , A61K49/0004 , A61K49/0032 , A61K49/0052 , A61K51/0459 , A61Q19/02 , A61Q19/08 , C07D487/14
摘要： Saxitoxin analogue compounds, compositions, pharmaceutical compositions, methods of synthesis of saxitoxin analogues, methods of imaging, methods of treatment, including methods of treating pain, are provided. Saxitoxin (STX), gonyautoxin (GTX), and zetekitoxin, and variant STX compounds bind to sodium channels and are effective to reduce or block flow of sodium ions through such channels. Such channel block affects nerve and muscle action, and may be effective to reduce or block pain sensations, relax muscles, reduce muscle spasm, and reduce wrinkles. STX analogue binding to sodium channels may also be useful to locate, image, or mark sodium channels, and so be useful in studying sodium channels and sodium channel disorders, and in the diagnosis and treatment of patients suffering from sodium channel disorders. In embodiments, the variant STX compounds include conjugates having increased serum half-life as compared to STX when administered to a subject.In embodiments, the present disclosure provides a method for alleviating pain in a subject in need of treatment, the method comprising administering to the subject an effective amount of a saxitoxin analogue compound, or a pharmaceutically acceptable salt, isomer, tautomer or prodrug thereof, whereby pain in said subject is alleviated.
摘要翻译：提供了类似萨克西汀类似物，组合物，药物组合物，合成硫氧还蛋白类似物的方法，成像方法，治疗方法，包括治疗疼痛的方法。沙眼毒素（STX），戈毒毒素（GTX）和泽西酮毒素，和变体STX化合物结合钠通道，并有效减少或阻断钠离子通过这些通道的流动。这种通道阻滞影响神经和肌肉的作用，并且可以有效地减少或阻止疼痛感觉，放松肌肉，减少肌肉痉挛和减少皱纹。与钠通道的STX类似物结合也可用于定位，成像或标记钠通道，因此可用于研究钠通道和钠通道障碍，以及用于诊断和治疗患有钠通道障碍的患者。在实施方案中，变体STX化合物包括与施用于受试者时相比于STX相比具有增加的血清半衰期的结合物。在实施方案中，本公开提供了一种减轻需要治疗的受试者的疼痛的方法，所述方法包括向受试者施用有效量的沙克西毒素类似物化合物或其药学上可接受的盐，异构体，互变异构体或前药，由此所述受试者的疼痛缓解。

2. 发明授权

US09174999B2 Methods and compositions for studying, imaging, and treating pain 有权
标题翻译：用于研究，成像和治疗疼痛的方法和组合物
公开(公告)号：US09174999B2
公开(公告)日：2015-11-03
申请号：US12800053
申请日：2010-05-07
申请人： Justin Du Bois , John Mulcahy , Brian Andresen , David C. Yeomans , Sandip Biswal
发明人： Justin Du Bois , John Mulcahy , Brian Andresen , David C. Yeomans , Sandip Biswal
IPC分类号： C07D487/14
CPC分类号： C07D487/16 , A61K8/4953 , A61K49/0002 , A61K49/0004 , A61K49/0032 , A61K49/0052 , A61K51/0459 , A61Q19/02 , A61Q19/08 , C07D487/14
摘要： Saxitoxin analog compounds, compositions, pharmaceutical compositions, methods of synthesis of saxitoxin analogs, methods of imaging, methods of treatment, including methods of treating pain, are provided. Saxitoxin (STX), gonyautoxin (GTX), and zetekitoxin, and variant STX compounds bind to sodium channels and are effective to reduce or block flow of sodium ions through such channels. Such channel block affects nerve and muscle action, and may be effective to reduce or block pain sensations, relax muscles, reduce muscle spasm, and reduce wrinkles. STX analog binding to sodium channels may also be useful to locate, image, or mark sodium channels, and so be useful in studying sodium channels and sodium channel disorders, and in the diagnosis and treatment of patients suffering from sodium channel disorders. In embodiments, the variant STX compounds include conjugates having increased serum half-life as compared to STX when administered to a subject.In embodiments, the present disclosure provides a method for alleviating pain in a subject in need of treatment, the method comprising administering to the subject an effective amount of a saxitoxin analog compound, or a pharmaceutically acceptable salt, isomer, tautomer or prodrug thereof, whereby pain in said subject is alleviated.
摘要翻译：提供萨克西汀类似物，组合物，药物组合物，合成沙星毒素类似物的方法，成像方法，治疗方法，包括治疗疼痛的方法。沙眼毒素（STX），戈毒毒素（GTX）和泽西酮毒素，和变体STX化合物结合钠通道，并有效减少或阻断钠离子通过这些通道的流动。这种通道阻滞影响神经和肌肉的作用，并且可以有效地减少或阻止疼痛感觉，放松肌肉，减少肌肉痉挛和减少皱纹。与钠通道的STX类似物结合也可用于定位，成像或标记钠通道，因此可用于研究钠通道和钠通道障碍，以及用于诊断和治疗患有钠通道障碍的患者。在实施方案中，变体STX化合物包括与施用于受试者时相比于STX相比具有增加的血清半衰期的结合物。在实施方案中，本公开提供了一种减轻需要治疗的受试者的疼痛的方法，所述方法包括向受试者施用有效量的沙克西毒素类似物化合物或其药学上可接受的盐，异构体，互变异构体或前药，由此所述受试者的疼痛缓解。

3. 发明授权

US09085536B2 Aconitine compounds, compositions, uses, and preparation thereof 有权
标题翻译：乌头碱化合物，组合物，用途及其制备
公开(公告)号：US09085536B2
公开(公告)日：2015-07-21
申请号：US13421809
申请日：2012-03-15
申请人： Justin Du Bois , Brian M. Andresen , Frederic Menard , Andrew W. Patterson
发明人： Justin Du Bois , Brian M. Andresen , Frederic Menard , Andrew W. Patterson
IPC分类号： A61K31/439 , C07D221/22
CPC分类号： C07D221/22 , A61K31/439 , A61K31/695
摘要： Compound derivatives of aconitine are provided, in particular derivatives that modulate the activity of sodium channels. Also provided are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier. The subject compounds are useful in treatments, including treatments to modulate neuronal activity or to bring about muscular relaxation. The compounds also find use in the treatment of subjects suffering from a voltage-gated sodium channel-enhanced ailment or from pain. Further methods are provided for the preparation of the aconitine derivatives.
摘要翻译：提供乌头碱的复合衍生物，特别是调节钠通道活性的衍生物。还提供了包含本发明化合物和药学上可接受的载体的药物组合物。主题化合物可用于治疗，包括调节神经元活动或引起肌肉松弛的治疗。该化合物还可用于治疗患有电压门控钠通道增强性疾病或疼痛的受试者。提供了用于制备乌头碱衍生物的其它方法。

4. 发明申请

US20140171410A1 Batrachotoxin Analogues, Compositions, Uses, and Preparation Thereof 有权
标题翻译： Batrachotoxin类似物，组合物，用途及其制备方法
公开(公告)号：US20140171410A1
公开(公告)日：2014-06-19
申请号：US14106115
申请日：2013-12-13
申请人： Justin Du Bois , Abigail Sloan Devlin , Matthew M. Logan , Frederic Menard , Tatsuya Toma
发明人： Justin Du Bois , Abigail Sloan Devlin , Matthew M. Logan , Frederic Menard , Tatsuya Toma
IPC分类号： C07D498/08
CPC分类号： C07D498/08
摘要： Compounds relating to batrachotoxin are provided, in particular analogues that modulate the activity of sodium channels. Also provided are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier, including vehicles that modulate transdermal permeation of the compound. The subject compounds are useful in treatments, including treatments to reduce neuronal activity or to bring about muscular relaxation. The compounds also find use in the treatment of subjects suffering from a voltage-gated sodium channel-enhanced ailment or from pain. Further methods are provided for the preparation of the batrachotoxin-related compounds.
摘要翻译：提供了与紫草素相关的化合物，特别是调节钠通道活性的类似物。还提供了包含本发明化合物和药学上可接受的载体的药物组合物，包括调节化合物透皮渗透的载体。主题化合物可用于治疗，包括减少神经元活动或引起肌肉松弛的治疗。该化合物还可用于治疗患有电压门控钠通道增强性疾病或疼痛的受试者。提供了用于制备蝙蝠素相关化合物的其它方法。

5. 发明申请

US20120238526A1 ACONITINE COMPOUNDS, COMPOSITIONS, USES, AND PREPARATION THEREOF 有权
标题翻译：丙烯酸酯化合物，组合物，用途及其制备方法
公开(公告)号：US20120238526A1
公开(公告)日：2012-09-20
申请号：US13421809
申请日：2012-03-15
申请人： Justin Du Bois , Brian M. Andresen , Frederic Menard
发明人： Justin Du Bois , Brian M. Andresen , Frederic Menard
IPC分类号： A61K31/439 , C07D405/12 , C07F7/18 , A61K31/695 , A61P25/00 , A61P21/02 , A61P29/00 , A61P1/00 , A61P19/02 , A61P25/06 , A61P35/00 , A61P9/06 , A61P25/08 , A61P21/00 , A61P13/10 , A61P17/00 , C07D221/22
CPC分类号： C07D221/22 , A61K31/439 , A61K31/695
摘要： Compound derivatives of aconitine are provided, in particular derivatives that modulate the activity of sodium channels. Also provided are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier. The subject compounds are useful in treatments, including treatments to modulate neuronal activity or to bring about muscular relaxation. The compounds also find use in the treatment of subjects suffering from a voltage-gated sodium channel-enhanced ailment or from pain. Further methods are provided for the preparation of the aconitine derivatives.
摘要翻译：提供乌头碱的复合衍生物，特别是调节钠通道活性的衍生物。还提供了包含本发明化合物和药学上可接受的载体的药物组合物。主题化合物可用于治疗，包括调节神经元活动或引起肌肉松弛的治疗。该化合物还可用于治疗患有电压门控钠通道增强性疾病或疼痛的受试者。提供了用于制备乌头碱衍生物的其它方法。

6. 发明授权

US09090627B2 Batrachotoxin analogues, compositions, uses, and preparation thereof 有权
标题翻译： Batrachotoxin类似物，组合物，用途及其制备方法
公开(公告)号：US09090627B2
公开(公告)日：2015-07-28
申请号：US14106115
申请日：2013-12-13
申请人： Justin Du Bois , Abigail Sloan Devlin , Matthew M. Logan , Frederic Menard , Tatsuya Toma
发明人： Justin Du Bois , Abigail Sloan Devlin , Matthew M. Logan , Frederic Menard , Tatsuya Toma
IPC分类号： C07D267/12 , C07D413/02 , C07D498/08
CPC分类号： C07D498/08
摘要： Compounds relating to batrachotoxin are provided, in particular analogs that modulate the activity of sodium channels. Also provided are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier, including vehicles that modulate transdermal permeation of the compound. The subject compounds are useful in treatments, including treatments to reduce neuronal activity or to bring about muscular relaxation. The compounds also find use in the treatment of subjects suffering from a voltage-gated sodium channel-enhanced ailment or from pain. Further methods are provided for the preparation of the batrachotoxin-related compounds.
摘要翻译：提供了与紫草素相关的化合物，特别是调节钠通道活性的类似物。还提供了包含本发明化合物和药学上可接受的载体的药物组合物，包括调节化合物透皮渗透的载体。主题化合物可用于治疗，包括减少神经元活动或引起肌肉松弛的治疗。该化合物还可用于治疗患有电压门控钠通道增强性疾病或疼痛的受试者。提供了用于制备蝙蝠素相关化合物的其它方法。

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