利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

11 条记录 (耗时 0.032 秒)

    Selective maxi-K potassium channel openers functional under conditions of high intracellular calcium concentration, methods and uses thereof
    3.
    发明申请
    Selective maxi-K potassium channel openers functional under conditions of high intracellular calcium concentration, methods and uses thereof 审中-公开
    选择性的maxi-K钾通道开放剂在高细胞内钙浓度的条件下起作用，其方法和用途

    公开(公告)号：US20050043293A1

    公开(公告)日：2005-02-24

    申请号：US10952523

    申请日：2004-09-28

    申请人： Valentin Gribkoff ,  Debra Post-Munson ,  Sarita Yeola ,  Christopher Boissard ,  Piyasena Hewawasam ,  John Starrett

    发明人： Valentin Gribkoff ,  Debra Post-Munson ,  Sarita Yeola ,  Christopher Boissard ,  Piyasena Hewawasam ,  John Starrett

    IPC分类号： G01N33/50 ,  A61K31/40 ,  A61K31/404 ,  A61K45/00 ,  A61P9/10 ,  A61P25/00 ,  A61P25/06 ,  A61P25/08 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D209/34 ,  G01N27/416 ,  G01N33/15 ,  A61K31/554 ,  A61K31/455 ,  A61K31/549

    CPC分类号： A61K31/40

    摘要： The present invention describes calcium sensitive and selective maxi-K potassium channel opener/activator compounds that function to open maxi-K channels under conditions of high intracellular calcium concentrations, and which do not significantly affect the opening of maxi-K channel proteins under conditions of low or physiologically normal intracellular calcium concentrations. Methods of assaying for and using such compounds are also provided. According to the invention, whole cell voltage patch-clamp studies newly demonstrated that the ability of opener compounds, e.g., fluoro-oxindoles and chloro-oxindoles, to open maxi-K channels was sensitive to the intracellular Ca2+ concentration ([Ca2+])i, i.e., more channels opened at more negative potentials. Particular fluoro-oxindole and chloro-oxindole compounds produced significant increases in whole-cell maxi-K potassium channel-mediated outward currents only in cells having higher [Ca2+]i, compared with effects in lower [Ca2+]i. Such compounds provide Ca2+-sensitive and selective openers of maxi-K channels which show maximum effectiveness under conditions of increased [Ca2+]i and, as such, provide treatments for diseases and disorders in which cells undergo, or are subject to, traumatic stress due to high internal calcium levels, such as stroke.

    摘要翻译： 本发明描述了钙敏感和选择性的max-K钾通道开放剂/活化剂化合物，其在高细胞内钙浓度的条件下起作用以开启max-K通道，并且不显着影响maxi-K通道蛋白在条件 低或生理正常的细胞内钙浓度。 还提供了测定和使用这些化合物的方法。 根据本发明，全细胞电压膜片钳研究新近证明，开放剂化合物（例如氟 - 羟基吲哚和氯 - 羟基吲哚）开放大通道的能力对细胞内Ca 2+浓度敏感（[ Ca 2 +]]）i，即更多的通道在更多的负电位下打开。 特别是氟代羟基吲哚和氯代羟吲哚化合物仅在具有较高[Ca 2+] i的细胞中产生的全细胞最大K钾通道介导的外向电流显着增加，与较低[Ca 2+] ]一世。 这样的化合物提供了在增加[Ca 2+] i的条件下显示出最大有效性的max-K通道的Ca 2+敏感性和选择性开放剂，因此提供细胞经历的疾病和病症的治疗， 或由于内部钙含量高，例如中风而遭受创伤性压力。

    Compositions and Methods of Using (R)- Pramipexole
    10.
    发明申请
    Compositions and Methods of Using (R)- Pramipexole 审中-公开
    使用（R） - 普拉克索的组合物和方法

    公开(公告)号：US20110190356A1

    公开(公告)日：2011-08-04

    申请号：US13059713

    申请日：2009-08-19

    申请人： Michael E. Bozik ,  Valentin Gribkoff

    发明人： Michael E. Bozik ,  Valentin Gribkoff

    IPC分类号： A61K31/428 ,  A61P25/00 ,  A61P25/28 ,  A61P25/08 ,  A61P25/16

    CPC分类号： A61K31/428 ,  A61K9/0053 ,  A61K9/1623 ,  A61K9/1635 ,  A61K9/1652 ,  A61K9/2018 ,  A61K9/2027 ,  A61K9/2054 ,  A61K31/197 ,  A61K31/425 ,  A61K45/06 ,  A61K2300/00

    摘要： Pharmaceutical compositions of (R)-pramipexole and one or more secondary therapeutic agents such as, for example dopamine agonists, dopaminergic agonists, COMT inhibitors, MOA inhibitors, excitatory amino acid antagonists, growth factors, neurotrophic factors, antioxidants, anti-inflammatory agents, immunomodulators, anti-glutamatergics, ion channel blockers, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, heat shock protein inducers/protein disaggregators and downregulators, monoamine oxidase type B (MOAB) inhibitors, multi-target agents, kinase inhibitors, Bcl inducers, histone deacetylase (HDAC) mediators, glial modulators, mitochondrial energy promoting agents, myostatin inhibitors, caspase inhibitors and combinations thereof or those related to mitochondrial dysfunction or increased oxidative stress are disclosed.

    摘要翻译： （R） - 普拉克索和一种或多种二级治疗药物的药物组合物，例如多巴胺激动剂，多巴胺能激动剂，COMT抑制剂，MOA抑制剂，兴奋性氨基酸拮抗剂，生长因子，神经营养因子，抗氧化剂，抗炎剂， 免疫调节剂，抗谷氨酸药，离子通道阻断剂，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂，热休克蛋白诱导物/蛋白质解聚物和下调剂，单胺氧化酶B（MOAB）抑制剂 ，多靶标试剂，激酶抑制剂，Bcl诱导剂，组蛋白脱乙酰酶（HDAC）介质，胶质调节剂，线粒体能量促进剂，肌生成抑制素抑制剂，半胱天冬酶抑制剂及其组合或与线粒体功能障碍或增加的氧化应激相关的那些。