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1. 发明申请

US20050261301A1 Therapeutic ion channel blocking agents and methods of use thereof 失效
标题翻译：治疗离子通道阻断剂及其使用方法
公开(公告)号：US20050261301A1
公开(公告)日：2005-11-24
申请号：US10507925
申请日：2003-03-20
申请人： Jonathan Baell , Heike Wulff , Andrew Harvey , Raymond Norton , George Chandy
发明人： Jonathan Baell , Heike Wulff , Andrew Harvey , Raymond Norton , George Chandy
IPC分类号： A61K31/343 , A61P29/00 , A61P37/00 , A61P37/06 , C07D307/86 , C07D405/14 , C07D409/14 , C07D417/14 , A61K31/506 , A61K31/381 , A61K31/427 , A61K31/4433 , A61K31/497 , A61K31/501 , C07D45/14
CPC分类号： C07D417/14 , C07D307/86 , C07D405/14 , C07D409/14
摘要： Various divalent ligands based on khellinone derivatives are described. These derivatives can be useful in the modulation of potassium channel activity in cells, including among others Kv1.3 channels found in T-cells. The compounds may also be useful in the treatment or prevention of autoimmune and inflammatory diseases, including multiple sclerosis.
摘要翻译：描述了基于凯芬酮衍生物的各种二价配体。这些衍生物可用于细胞中钾通道活性的调节，包括在T细胞中发现的Kv1.3通道。所述化合物还可用于治疗或预防自身免疫性和炎性疾病，包括多发性硬化。

2. 发明申请

US20050176813A1 Novel chalcone derivatives and uses thereof 审中-公开
标题翻译：新型查耳酮衍生物及其用途
公开(公告)号：US20050176813A1
公开(公告)日：2005-08-11
申请号：US10507782
申请日：2003-03-14
申请人： Jonathan Baell , Heike Wulff , George Chandy , Raymond Norton
发明人： Jonathan Baell , Heike Wulff , George Chandy , Raymond Norton
IPC分类号： C07D333/54 , A61K31/12 , A61K31/343 , A61K31/36 , A61K31/381 , A61K31/4025 , A61K31/403 , A61K31/404 , A61K31/41 , A61K31/423 , A61K31/428 , A61K31/443 , A61K31/47 , A61K31/4709 , A61K31/472 , A61P1/02 , A61P1/04 , A61P1/16 , A61P1/18 , A61P3/06 , A61P3/10 , A61P5/14 , A61P7/00 , A61P7/02 , A61P7/06 , A61P9/00 , A61P9/06 , A61P9/10 , A61P11/00 , A61P11/02 , A61P11/06 , A61P13/00 , A61P13/10 , A61P13/12 , A61P17/00 , A61P17/02 , A61P17/06 , A61P17/14 , A61P17/16 , A61P19/00 , A61P19/02 , A61P19/10 , A61P21/00 , A61P21/04 , A61P25/00 , A61P25/04 , A61P25/06 , A61P25/08 , A61P25/28 , A61P27/02 , A61P27/12 , A61P27/14 , A61P29/00 , A61P31/00 , A61P31/04 , A61P31/14 , A61P31/18 , A61P31/20 , A61P31/22 , A61P35/00 , A61P35/02 , A61P35/04 , A61P37/00 , A61P37/02 , A61P37/06 , A61P37/08 , A61P39/00 , A61P41/00 , A61P43/00 , C07C49/755 , C07C49/84 , C07D215/26 , C07D217/02 , C07D263/54 , C07D277/62 , C07D307/86 , C07D307/91 , C07D405/06 , C07D405/10 , C07D407/06 , C07D409/06
CPC分类号： A61K31/47 , A61K31/343 , A61K31/381 , A61K31/403 , A61K31/404 , A61K31/41 , A61K31/423 , A61K31/428
摘要： Various chalcone derivatives of the general formula (I) are described and the variables, A, B, m and R1 to R10 are as defined in the specification. These derivatives can be useful in the modulation of potassium channel activity in cells and may be useful in the treatment or prevention of autoimmune and inflammatory diseases.
摘要翻译：描述通式（I）的各种查耳酮衍生物，并且变量A，B，m和R 1至R 10如说明书中所定义。这些衍生物可用于调节细胞中钾通道活性，并且可用于治疗或预防自身免疫性和炎性疾病。

3. 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。

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

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。

6. 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.

7. 发明授权

US06541494B1 Non-peptide inhibition of T-lymphocyte activation and therapies related thereto 有权
公开(公告)号：US06541494B1
公开(公告)日：2003-04-01
申请号：US09479391
申请日：2000-01-06
申请人： K. George Chandy , Heike Wulff , Michael D. Cahalan , Stephan Grismer , Heiko J. Rauer , Mark J. Miller
发明人： K. George Chandy , Heike Wulff , Michael D. Cahalan , Stephan Grismer , Heiko J. Rauer , Mark J. Miller
IPC分类号： A61K31425
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.

8. 发明授权

US08026263B2 Methods for inhibiting neoproliferative changes in blood vessel walls 有权
标题翻译：抑制血管壁新生血管变化的方法
公开(公告)号：US08026263B2
公开(公告)日：2011-09-27
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： A61K31/425
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。

9. 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）。

10. 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。

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