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    Bridged bicyclic RHO kinase inhibitor compounds, compositions and use
    3.
    发明授权
    Bridged bicyclic RHO kinase inhibitor compounds, compositions and use 有权
    桥联的双环RHO激酶抑制剂化合物，组合物和用途

    公开(公告)号：US08835457B2

    公开(公告)日：2014-09-16

    申请号：US13918020

    申请日：2013-06-14

    申请人： John W. Lampe ,  Paul S. Watson ,  David J. Slade

    发明人： John W. Lampe ,  Paul S. Watson ,  David J. Slade

    IPC分类号： C07D451/04 ,  C07D401/12

    CPC分类号： C07D451/04 ,  A61K31/46 ,  A61K31/4725 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D453/06 ,  C07D471/08 ,  C07D487/08

    摘要： The present invention is directed to synthetic bridged bicyclic compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. The method comprises administering to a subject a therapeutically effective amount of a Rho kinase inhibitory compound of Formula I, wherein said amount is effective to influence the actomyosin interactions, for example, by leading to cellular relaxation and alterations in cell-substratum adhesions. In one embodiment, the method treats increased intraocular pressure, such as primary open-angle glaucoma. In another embodiment, the method treats diseases or conditions of the lung associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema.

    摘要翻译： 本发明涉及作为rho相关蛋白激酶抑制剂的合成桥联双环化合物。 本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。 本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。 该方法包括向受试者施用治疗有效量的式I的Rho激酶抑制性化合物，其中所述量有效地影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞 - 基底粘连的改变。 在一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。 在另一个实施方案中，该方法治疗与过度细胞增殖，重塑，炎症，血管收缩，支气管收缩，气道高反应性和水肿相关的肺的疾病或病症。

    BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITIONS AND USE
    6.
    发明申请
    BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITIONS AND USE 有权
    BRIDGED BICYCLIC RHO激酶抑制剂化合物，组合物和用途

    公开(公告)号：US20130281485A1

    公开(公告)日：2013-10-24

    申请号：US13918020

    申请日：2013-06-14

    申请人： John W. Lampe ,  Paul S. Watson ,  David J. Slade

    发明人： John W. Lampe ,  Paul S. Watson ,  David J. Slade

    IPC分类号： C07D451/04 ,  C07D401/12

    CPC分类号： C07D451/04 ,  A61K31/46 ,  A61K31/4725 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D453/06 ,  C07D471/08 ,  C07D487/08

    摘要： The present invention is directed to synthetic bridged bicyclic compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. The method comprises administering to a subject a therapeutically effective amount of a Rho kinase inhibitory compound of Formula I, wherein said amount is effective to influence the actomyosin interactions, for example, by leading to cellular relaxation and alterations in cell-substratum adhesions. In one embodiment, the method treats increased intraocular pressure, such as primary open-angle glaucoma. In another embodiment, the method treats diseases or conditions of the lung associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema.

    摘要翻译： 本发明涉及作为rho相关蛋白激酶抑制剂的合成桥联双环化合物。 本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。 本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。 该方法包括向受试者施用治疗有效量的式I的Rho激酶抑制性化合物，其中所述量有效地影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞 - 基底粘连的改变。 在一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。 在另一个实施方案中，该方法治疗与过度细胞增殖，重塑，炎症，血管收缩，支气管收缩，气道高反应性和水肿相关的肺的疾病或病症。

    Cytoskeletal active compounds, composition and use
    7.
    发明授权
    Cytoskeletal active compounds, composition and use 失效
    细胞骨架活性化合物，组成和用途

    公开(公告)号：US08039465B2

    公开(公告)日：2011-10-18

    申请号：US12695348

    申请日：2010-01-28

    申请人： John W. Lampe ,  Robert Plourde, Jr. ,  Jin She ,  Jason L. Vittitow ,  Paul S. Watson ,  Michael T. Crimmins ,  David J. Slade

    发明人： John W. Lampe ,  Robert Plourde, Jr. ,  Jin She ,  Jason L. Vittitow ,  Paul S. Watson ,  Michael T. Crimmins ,  David J. Slade

    IPC分类号： A61K31/54

    CPC分类号： C07D491/08 ,  C07D277/06 ,  C07D277/14 ,  C07D277/16 ,  C07D277/34 ,  C07D277/56 ,  C07D417/04 ,  C07D493/08 ,  C07D497/18

    摘要： The present invention is directed to synthetic cytoskeletal active compounds that are related to natural Latrunculin A or Latrunculin B. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with actin polymerization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or II, wherein said amount is effective to influence the cytoskeleton, for example by inhibiting actin polymerization.

    摘要翻译： 本发明涉及与天然的秋水仙素A或梭菌素B相关的合成细胞骨架活性化合物。本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。 本发明另外涉及预防或治疗与肌动蛋白聚合相关的疾病或病症的方法。 在本发明的一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。 该方法包括向受试者施用治疗有效量的式I或II的细胞骨架活性化合物，其中所述量有效影响细胞骨架，例如通过抑制肌动蛋白聚合。

    BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE
    8.
    发明申请
    BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE 有权
    BRIDGED BICYCLIC RHO激酶抑制剂化合物，组合物和用途

    公开(公告)号：US20110144150A1

    公开(公告)日：2011-06-16

    申请号：US12965615

    申请日：2010-12-10

    申请人： John W. Lampe ,  Paul S. Watson ,  David J. Slade

    发明人： John W. Lampe ,  Paul S. Watson ,  David J. Slade

    IPC分类号： A61K31/46 ,  C07D401/12 ,  A61K31/4725 ,  A61P27/02 ,  A61P27/06 ,  A61P9/10 ,  A61P11/06 ,  A61P11/00

    CPC分类号： C07D451/04 ,  A61K31/46 ,  A61K31/4725 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D453/06 ,  C07D471/08 ,  C07D487/08

    摘要： The present invention is directed to synthetic bridged bicyclic compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. The method comprises administering to a subject a therapeutically effective amount of a Rho kinase inhibitory compound of Formula I, wherein said amount is effective to influence the actomyosin interactions, for example, by leading to cellular relaxation and alterations in cell-substratum adhesions. In one embodiment, the method treats increased intraocular pressure, such as primary open-angle glaucoma. In another embodiment, the method treats diseases or conditions of the lung associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema.

    摘要翻译： 本发明涉及作为rho相关蛋白激酶抑制剂的合成桥联双环化合物。 本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。 本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。 该方法包括向受试者施用治疗有效量的式I的Rho激酶抑制性化合物，其中所述量有效地影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞 - 基底粘连的改变。 在一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。 在另一个实施方案中，该方法治疗与过度细胞增殖，重塑，炎症，血管收缩，支气管收缩，气道高反应性和水肿相关的肺的疾病或病症。