公开(公告)号：US20100130572A1

公开(公告)日：2010-05-27

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： A61K31/427 ,  C07D417/04 ,  C07D493/08 ,  A61K31/426 ,  A61P27/00

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。

公开(公告)号：US20130012543A1

公开(公告)日：2013-01-10

申请号：US13614641

申请日：2012-09-13

申请人： John W. LAMPE ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

发明人： John W. LAMPE ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

IPC分类号： C07D401/14 ,  A61P27/02 ,  C07D409/14 ,  A61K31/454 ,  C07D405/14

CPC分类号： C07D401/12 ,  A61F9/00781 ,  A61K9/0048 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14

摘要： The present invention is directed to synthetic cytoskeletal active 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. 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 Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

摘要翻译： 本发明涉及作为rho相关蛋白激酶抑制剂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细胞骨架重组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或式II的细胞骨架活性化合物，其中所述量可有效影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞粘附的变化。

公开(公告)号：US20130005756A1

公开(公告)日：2013-01-03

申请号：US13612511

申请日：2012-09-12

申请人： Tomas NAVRATIL ,  Ward M. PETERSON ,  John W. LAMPE ,  Emilee H. FULCHER ,  Scott D. SORENSEN

发明人： Tomas NAVRATIL ,  Ward M. PETERSON ,  John W. LAMPE ,  Emilee H. FULCHER ,  Scott D. SORENSEN

IPC分类号： A61K31/4725 ,  A61P11/06 ,  A61P11/00 ,  A61K31/506 ,  A61K31/475

CPC分类号： A61K31/4545 ,  A61K31/4025 ,  A61K31/416 ,  A61K31/437 ,  A61K31/454 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/55 ,  C07D401/12

摘要： This invention is directed to methods of preventing or treating diseases or conditions of the lungs associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema. Particularly, this invention is directed to methods of treating pulmonary diseases such as asthma; chronic obstructive pulmonary disease; respiratory tract illness caused by respiratory syncytial virus; pulmonary arterial hypertension; acute respiratory distress syndrome and ventilator induced lung injury; cystic fibrosis; bronchiectasis; alpha-1-antitrypsin deficiency; rhinitis; rhinosinusitis; primary ciliary dyskinesia; pneumonia; bronchiolitis caused by agents other than respiratory syncytial virus; and interstitial lung disease including lymphangioleiomyomatosis; idiopathic pulmonary fibrosis; obliterative bronchiolitis or bronchiolitis obliterans organizing pneumonia due to lung transplantation or HSCT; nonspecific interstitial pneumonia; cryptogenic organizing pneumonia; acute interstitial pneumonia; respiratory bronchiolitis-associated interstitial lung disease; or pulmonary sarcoidosis. The method comprises administering to a subject an effective amount of a rho kinase inhibitor compound to treat the disease.