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91 条记录 (耗时 0.064 秒)

    Selective maxi-K potassium channel openers functional under conditions of high intracellular calcium concentration, methods and uses thereof
    52.
    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。

    Imidazo[4,5-b]quinolinyl oxy alkyl sulfonyl piperidine derivatives
    55.
    发明授权
    Imidazo[4,5-b]quinolinyl oxy alkyl sulfonyl piperidine derivatives 失效
    咪唑并[4,5-b]喹啉基氧基烷基磺酰基哌啶衍生物

    公开(公告)号：US5158958A

    公开(公告)日：1992-10-27

    申请号：US863278

    申请日：1992-04-03

    申请人： Piyasena Hewawasam ,  Nicholas A. Meanwell

    发明人： Piyasena Hewawasam ,  Nicholas A. Meanwell

    IPC分类号： C07D471/04

    CPC分类号： C07D471/04

    摘要： A novel series of 1,3-dihydro-2H-imidazo [4,5-b]quinolin-2-ones having enhanced water solubility bioavailability and metabolic stability is disclosed in the Formula I ##STR1## wherein R.sup.1 is H, or C.sub.1 -C.sub.4 lower alkyl;R.sup.2 is H, or (CH.sub.2).sub.m R.sup.3 ;R.sup.3 is tetrahydro-2H-pyranyl, C.sub.1 -C.sub.8 alkyl, C.sub.4 -C.sub.8 cycloalkyl, or substituted or unsubstituted phenyl in which the substituents are halogen, alkoxy, or trifluoromethyl;m is an integer of 1-3; and n is an integer of 1-5; or pharmaceutically acceptable salt thereof.the compounds are useful as inhibitors of ADP-induced blood platelet aggregation in human platelet-rich plasma.

    摘要翻译： 具有增强的水溶性生物利用度和代谢稳定性的新一系列1,3-二氢-2H-咪唑并[4,5-b]喹啉-2-酮公开在式I的化合物中，其中R 1是H或C1- C4低级烷基; R2是H或（CH2）mR3; R3是四氢-2H-吡喃基，C1-C8烷基，C4-C8环烷基或取代或未取代的苯基，其中取代基是卤素，烷氧基或三氟甲基; m为1-3的整数; n为1-5的整数; 或其药学上可接受的盐。 该化合物可用作人富血小板血浆中ADP诱导的血小板聚集抑制剂。