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1. 发明申请

US20090306159A1 Inhibition of Intermediate-Conductance Calcium Activated Potassium Channels in the Treatment and/or Prevention of Atherosclerosis 审中-公开
标题翻译：中等电导钙激活钾通道在治疗和/或预防动脉粥样硬化中的抑制作用
公开(公告)号：US20090306159A1
公开(公告)日：2009-12-10
申请号：US12066381
申请日：2006-09-12
申请人： Heike Wulff , George K. Chandy , Hiroto Miura
发明人： Heike Wulff , George K. Chandy , Hiroto Miura
IPC分类号： A61K31/415 , A61K31/41 , A61P9/10
CPC分类号： A61K31/415 , A61K31/41
摘要： Methods for treating or preventing atherosclerosis in human or non-human animal subjects by inhibiting or blocking intermediate-conductance calcium activated potassium channels associated with vascular smooth muscle and/or other cells which play a role in the pathogenesis of atherosclerosis (e.g., KCa3.1, KCNN4, IKCa1, IK1, SK4 channels).
摘要翻译：通过抑制或阻断与在动脉粥样硬化发病机制中起作用的血管平滑肌和/或其它细胞相关的中间电导钙激活钾通道来治疗或预防人或非人动物受试者的动脉粥样硬化的方法（例如KCa3.1 ，KCNN4，IKCa1，IK1，SK4通道）。

2. 发明授权

US07772408B1 Substituted 5-alkoxypsoralens as inhibitors of potassium channel activity in lymphocytes and other cells 有权
标题翻译：取代的5-烷氧基补骨脂素作为淋巴细胞和其他细胞中钾通道活性的抑制剂
公开(公告)号：US07772408B1
公开(公告)日：2010-08-10
申请号：US10651618
申请日：2003-08-29
申请人： Julia Vennekamp , Heike Wulff , K. George Chandy , Stephan Grissmer , Wolfram Hansel
发明人： Julia Vennekamp , Heike Wulff , K. George Chandy , Stephan Grissmer , Wolfram Hansel
IPC分类号： C07D317/08 , C07D305/00 , C07D493/00
CPC分类号： C07D493/04
摘要： Compositions of matter comprising 5-phenylalkoxypsoralen compounds and their method of synthesis and use. The compounds are useable to treat diseases or disorders in human or veterinary patients, including autoimmune diseases such as multiple sclerosis. The compounds inhibit potassium channels, including the Kv1.3 channel and at least some of the therapeutic effects of such compounds may be due at least in part to potassium channel inhibition.
摘要翻译：包含5-苯基烷氧基补骨脂素化合物的物质组合物及其合成和使用方法。这些化合物可用于治疗人或兽医患者中的疾病或病症，包括自身免疫性疾病如多发性硬化症。该化合物抑制钾通道，包括Kv1.3通道，并且这些化合物的至少一些治疗作用可能至少部分是由钾通道抑制引起的。

3. 发明申请

US20080221194A1 Novel Potassium channel Blockers and Uses Thereof 有权
标题翻译：新型钾通道阻滞剂及其用途
公开(公告)号：US20080221194A1
公开(公告)日：2008-09-11
申请号：US11886210
申请日：2006-03-15
申请人： Andrew J. Harvey , Jonathan B. Baell , Heike Wulff
发明人： Andrew J. Harvey , Jonathan B. Baell , Heike Wulff
IPC分类号： A61K38/00 , A61K31/38 , C07D209/42
CPC分类号： C07D493/04 , C07D307/86 , C07D401/12 , C07D403/12 , C07D405/12 , C07D407/12
摘要： The invention relates to compounds of Formula (1) for use in modulating potassium channel activity in cells.
摘要翻译：本发明涉及用于调节细胞中钾通道活性的式（1）化合物。

4. 发明授权

US06803375B1 Non-peptide inhibition of T-lymphocyte activation and therapies related thereto 失效
标题翻译：非肽抑制T淋巴细胞活化和与之相关的疗法
公开(公告)号：US06803375B1
公开(公告)日：2004-10-12
申请号：US09479391
申请日：2000-01-06
申请人： K. George Chandy , Heike Wulff
发明人： K. George Chandy , Heike Wulff
IPC分类号： A01K43495
CPC分类号： A61K31/415 , A61K31/065 , A61K31/16 , A61K31/277 , A61K31/40 , A61K31/41 , A61K31/425
摘要： Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K+ channel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca++ activated K+ channel (IKCa1) prevents the pre-Ca++ stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.
摘要翻译：用于免疫抑制治疗自身免疫疾病，移植物排斥和/或移植物/宿主疾病的化合物，制剂和方法。向哺乳动物患者施用治疗有效量的某些取代的三芳基甲烷化合物，例如1 - [（2-氯苯基）二苯基甲基] -1H-吡唑，以选择性抑制淋巴细胞，单核细胞中钙激活的K +通道（IKCa1），巨噬细胞，血小板或内皮细胞，而不伴随着P450依赖性酶系统的抑制，导致通过这些细胞中存储的钙通道降低抗原，细胞因子或丝裂原诱导的钙进入，抑制这些细胞的细胞因子产生，并抑制这些细胞的活化。 Ca ++活化的K +通道（IKCa1）的这种抑制可预防细胞活化前的Ca ++阶段，从而引起免疫抑制和抗炎反应。

5. 发明申请

US20130281504A1 Reduction of Microglia-Mediated Neurotoxicity by KCa3.1 Inhibition 审中-公开
标题翻译：通过KCa3.1抑制减少小胶质细胞介导的神经毒性
公开(公告)号：US20130281504A1
公开(公告)日：2013-10-24
申请号：US13807245
申请日：2011-06-28
申请人： Heike Wulff , Lee-Way Jin , Izumi Maezawa
发明人： Heike Wulff , Lee-Way Jin , Izumi Maezawa
IPC分类号： A61K31/415
CPC分类号： A61K31/415
摘要： Methods for deterring microglia-mediated neurotoxicity in a human or non-human animal subjects comprising the step of inhibiting or blocking the intermediate-conductance calcium-activated potassium channel KCa3.1 in microglia, such as in subjects how suffer from neurodegenerative diseases (e.g., Alzeheimer's Disease) or ischemic/anoxic/hypoxic conditions. The inhibition or blocking of the KCa1.3 channels may be accomplished by administering a KCa3.1 inhibiting substance, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34).
摘要翻译：包括抑制或阻断小胶质细胞中的中间电导钙激活钾通道KCa3.1的步骤的方法，所述方法包括在受试者中如何患有神经变性疾病（例如，阿尔海默氏病）或缺血/缺氧/缺氧条件。 KCa1.3通道的抑制或阻断可以通过施用KCa3.1抑制物质如1 - [（2-氯苯基）二苯基甲基] -1H-吡唑（TRAM-34）来实现。

6. 发明授权

US08067460B2 5-phenoxyalkoxypsoralens and methods for selective inhibition of the voltage gated Kv1.3 potassium channel 有权
标题翻译： 5-phenoxyalkoxypsoralens和选择性抑制电压门控Kv1.3钾通道的方法
公开(公告)号：US08067460B2
公开(公告)日：2011-11-29
申请号：US12498334
申请日：2009-07-06
申请人： Heike Wulff , Ananthakrishnan Sankaranarayanan , Wolfram Haensel , Alexander Schmitz , Kristina Schmidt-Lassen
发明人： Heike Wulff , Ananthakrishnan Sankaranarayanan , Wolfram Haensel , Alexander Schmitz , Kristina Schmidt-Lassen
IPC分类号： A61K31/37 , C07D493/04
CPC分类号： C07D493/04
摘要： Compositions of matter comprising 5-phenoxyalkoxypsoralen compounds and their method of synthesis and use. The compounds are useable to treat diseases or disorders in human or animal subjects, including autoimmune diseases. The compounds inhibit potassium channels, including the Kv1.3 channel and at least some of the therapeutic effects of such compounds may be due at least in part to potassium channel inhibition. In some embodiments, the compounds are more selective for certain potassium channels (e.g., Kv1.3 channels) than other potassium channels (e.g., Kv1.5 channels).
摘要翻译：包含5-苯氧基亚油氧补骨脂素化合物的物质组合物及其合成和使用方法。该化合物可用于治疗人或动物受试者中的疾病或病症，包括自身免疫性疾病。该化合物抑制钾通道，包括Kv1.3通道，并且这些化合物的至少一些治疗作用可能至少部分是由钾通道抑制引起的。在一些实施方案中，化合物对于某些钾通道（例如Kv1.3通道）比其它钾通道（例如，Kv1.5通道）更具选择性。

7. 发明申请

US20070293554A1 Non-peptide inhibition of T-lymphocyte activation and therapies related thereto 审中-公开
标题翻译：非肽抑制T淋巴细胞活化和与之相关的疗法
公开(公告)号：US20070293554A1
公开(公告)日：2007-12-20
申请号：US11805763
申请日：2007-05-25
申请人： K. Chandy , Heike Wulff , Michael Cahalan , Stephan Grismer , Heiko Rauer , Mark Miller
发明人： K. Chandy , Heike Wulff , Michael Cahalan , Stephan Grismer , Heiko Rauer , Mark Miller
IPC分类号： A61K31/40 , A61K31/065 , A61K31/41 , A61K31/415 , A61P37/02
CPC分类号： A61K31/415 , A61K31/065 , A61K31/16 , A61K31/277 , A61K31/40 , A61K31/41 , A61K31/425
摘要： Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K+ channel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca++ activated K+ channel (IKCa1) prevents the pre-Ca++ stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.
摘要翻译：用于免疫抑制治疗自身免疫疾病，移植物排斥和/或移植物/宿主疾病的化合物，制剂和方法。向哺乳动物患者施用治疗有效量的某些取代的三芳基甲烷化合物，例如1 - [（2-氯苯基）二苯基甲基] -1H-吡唑，以选择性抑制钙激活的K + ）在淋巴细胞，单核细胞，巨噬细胞，血小板或内皮细胞中，而不伴随P450依赖性酶系统的抑制，导致通过这些细胞中存储的钙通道降低抗原，细胞因子或丝裂原诱导的钙进入，抑制细胞因子这些细胞产生，抑制这些细胞的活化。这种抑制Ca ++活化的K + SUP通道（IKCa1）可以预防细胞活化前期的Ca ++阶段，从而引起免疫抑制和抗炎反应。

8. 发明申请

US20140171455A1 Reduction of Microglia-Mediated Neurotoxicity by Kv1.3 Inhibition 审中-公开
标题翻译：通过Kv1.3抑制降低小胶质细胞介导的神经毒性
公开(公告)号：US20140171455A1
公开(公告)日：2014-06-19
申请号：US14124226
申请日：2012-06-08
申请人： Heike Wulff , Lee-Way Jin , Izumi Meezawa
发明人： Heike Wulff , Lee-Way Jin , Izumi Meezawa
IPC分类号： A61K31/37 , A61K31/4709 , A61K31/517 , A61K31/353 , A61K31/47 , A61K31/472
CPC分类号： A61K31/353 , A61K31/085 , A61K31/37 , A61K31/47 , A61K31/4709 , A61K31/472 , A61K31/517
摘要： Methods for deterring microglia-mediated neurotoxicity in a human or non-human animal subjects comprising the step of inhibiting or blocking the intermediate-conductance calcium-activated potassium channel Kv1.3 in microglia, such as in subjects how suffer from neurodegenerative diseases (e.g., Alzheimer's Disease) or ischemic/anoxic/hypoxic conditions. The inhibition or blocking of the KCa1.3 channels may be accomplished by administering a substance that inhibits Kv1.3 in microglia. Examples of Kv1.3 inhibiting substances include certain 5-phenoxyalkoxypsoralens, such as (4-Phenoxybutoxy)psoralen (PAP-1) as well as certain 4-phenoxybutoxy-substituted heterocyclic compounds.
摘要翻译：包括抑制或阻断小胶质细胞中的中间电导钙激活钾通道Kv1.3的步骤的人或非人动物受试者中的小胶质细胞介导的神经毒性的方法，例如受试者患有神经变性疾病（例如，阿尔茨海默病）或缺血/缺氧/缺氧条件。 KCa1.3通道的抑制或阻断可以通过在小胶质细胞中施用抑制Kv1.3的物质来实现。 Kv1.3抑制物质的实例包括某些4-苯氧基丁氧基取代的杂环化合物，例如（4-苯氧基丁氧基）补骨脂素（PAP-1）以及某些4-苯氧基丁氧基取代的杂环化合物。

9. 发明申请

US20090048270A1 Compounds, Methods And Devices for Inhibiting Neoproliferative Changes in Blood Vessel Walls 有权
标题翻译：用于抑制血管壁新生血管变化的化合物，方法和装置
公开(公告)号：US20090048270A1
公开(公告)日：2009-02-19
申请号：US10533060
申请日：2003-10-30
申请人： Ralf Koehler , Heike Wulff , Joachim Hoyer , K. George Chandy
发明人： Ralf Koehler , Heike Wulff , Joachim Hoyer , K. George Chandy
IPC分类号： A61K31/505 , A61K31/136 , A61K31/165 , A61K31/426 , A61K31/4184 , A61P9/00 , A61K31/415 , A61K31/41 , A61K31/4035 , A61K31/44
CPC分类号： A61K31/415
摘要： Methods, compositions and devices for inhibiting neoproliferative changes in blood vessel walls or other anatomical structures. One or more compounds of Formula I or I-A set forth herein are administered systemically and/or locally to human or veterinary patients to deter or prevent unwanted proliferative changes in blood vessels or other anatomical structures. The invention may be used to deter or prevent stenosis or restenosis of arteries following angioplasty and/or stent placement. In one embodiment, there is provided an implantable stent or stent graft from which one or more compounds of the present invention will elute or otherwise be delivered into an affected blood vessel wall.
摘要翻译：用于抑制血管壁或其他解剖结构中新生血管变化的方法，组合物和装置。本文所述的一种或多种式I或I-A化合物全身和/或局部施用于人或兽医患者以阻止或预防血管或其他解剖结构中不期望的增殖性变化。本发明可用于阻止或预防血管成形术和/或支架放置后的动脉狭窄或再狭窄。在一个实施方案中，提供了可植入支架或支架移植物，其中一种或多种本发明化合物将从其中洗脱或以其它方式递送到受影响的血管壁。

10. 发明授权

US07235577B1 Non-peptide inhibition of T-lymphocyte activation and therapies related thereto 有权
公开(公告)号：US07235577B1
公开(公告)日：2007-06-26
申请号：US10402532
申请日：2003-03-28
申请人： K. George Chandy , Heike Wulff
发明人： K. George Chandy , Heike Wulff
IPC分类号： A61K31/415
CPC分类号： A61K31/415 , A61K31/065 , A61K31/16 , A61K31/277 , A61K31/40 , A61K31/41 , A61K31/425
摘要： Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K+ channel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca++ activated K+ channel (IKCa1) prevents the pre-Ca++ stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.

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