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    Bridged bicyclic RHO kinase inhibitor compounds, compositions and use
    11.
    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
    12.
    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。

    BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE
    13.
    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。

    Bridged bicyclic RHO kinase inhibitor compounds, composition and use
    14.
    发明授权
    Bridged bicyclic RHO kinase inhibitor compounds, composition and use 有权
    桥联双环RHO激酶抑制剂化合物，组成和用途

    公开(公告)号：US08476295B2

    公开(公告)日：2013-07-02

    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： A01N43/42 ,  A61K31/44 ,  C07D401/00 ,  C07D405/00 ,  C07D409/00 ,  C07D411/00

    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。

    Process for the preparation of Rho-kinase inhibitor compounds
    15.
    发明授权
    Process for the preparation of Rho-kinase inhibitor compounds 失效
    制备Rho激酶抑制剂化合物的方法

    公开(公告)号：US08158796B2

    公开(公告)日：2012-04-17

    申请号：US12470377

    申请日：2009-05-21

    申请人： Jin She ,  Jonathan Bryan deCamp ,  Paul S. Watson ,  David J. Slade

    发明人： Jin She ,  Jonathan Bryan deCamp ,  Paul S. Watson ,  David J. Slade

    IPC分类号： C07D217/22

    CPC分类号： C07D401/12 ,  C07C67/08 ,  C07C69/78

    摘要： The present invention is directed to practical high-yielding synthetic processes to prepare compounds of general Formula III, IV, V, VII, VIII, IX, X, XII, XIV, and XV. Such compounds are useful as final products or can be used as intermediates and be further modified to prepare other desired products such as rho-kinase inhibitors. The present invention is also directed to certain novel compounds and/or novel solid forms of certain compounds.

    摘要翻译： 本发明涉及制备通式III，IV，V，VII，VIII，IX，X，XII，XIV和XV的化合物的实际高产合成方法。 这些化合物可用作最终产物，或可用作中间体，并进一步修饰以制备其它所需产物如rho激酶抑制剂。 本发明还涉及某些新化合物和/或某些化合物的新型固体形式。

    PROCESS FOR THE PREPARATION OF RHO-KINASE INHIBITOR COMPOUNDS
    16.
    发明申请
    PROCESS FOR THE PREPARATION OF RHO-KINASE INHIBITOR COMPOUNDS 失效
    制备RHO-激酶抑制剂化合物的方法

    公开(公告)号：US20100022775A1

    公开(公告)日：2010-01-28

    申请号：US12470377

    申请日：2009-05-21

    申请人： Jin She ,  Jonathan Bryan deCamp ,  Paul S. Watson ,  David J. Slade

    发明人： Jin She ,  Jonathan Bryan deCamp ,  Paul S. Watson ,  David J. Slade

    IPC分类号： C07D217/22 ,  C07C65/30

    CPC分类号： C07D401/12 ,  C07C67/08 ,  C07C69/78

    摘要： The present invention is directed to practical high-yielding synthetic processes to prepare compounds of general Formula III, IV, V, VII, VIII, IX, X, XII, XIV, and XV. Such compounds are useful as final products or can be used as intermediates and be further modified to prepare other desired products such as rho-kinase inhibitors. The present invention is also directed to certain novel compounds and/or novel solid forms of certain compounds.

    摘要翻译： 本发明涉及制备通式III，IV，V，VII，VIII，IX，X，XII，XIV和XV的化合物的实际高产合成方法。 这些化合物可用作最终产物，或可用作中间体，并进一步修饰以制备其它所需产物如rho激酶抑制剂。 本发明还涉及某些新化合物和/或某些化合物的新型固体形式。