公开(公告)号：US20100022536A1

公开(公告)日：2010-01-28

申请号：US12488182

申请日：2009-06-19

申请人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A61K31/5377 ,  A61K31/405 ,  A61K31/497 ,  A61P29/00 ,  A61P11/06 ,  A61P19/02 ,  A61P25/16 ,  A61P25/00 ,  A61P7/02

CPC分类号： C07D209/14 ,  C07D209/18

摘要： This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A2 enzymes (cPLA2), more particularly including inhibitors of cytosolic phospholipase A2 alpha enzymes (cPLA2α). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

公开(公告)号：US07557135B2

公开(公告)日：2009-07-07

申请号：US11442199

申请日：2006-05-26

申请人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A61K31/404 ,  C07D209/14

CPC分类号： C07D209/14 ,  C07D209/18

摘要： This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A2 enzymes (cPLA2), more particularly including inhibitors of cytosolic phospholipase A2 alpha enzymes (cPLA2α). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

摘要翻译： 本发明提供了各种磷脂酶，特别是细胞溶质磷脂酶A2酶（cPLA2）的活性的化学抑制剂，更具体地包括胞浆磷脂酶A2α酶（cPLA2α）的抑制剂。 在一些实施方案中，抑制剂具有式I：其中组成变量如本文所定义。

公开(公告)号：US20100029645A1

公开(公告)日：2010-02-04

申请号：US12488020

申请日：2009-06-19

申请人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A61K31/5377 ,  C07D209/04 ,  C07D403/02 ,  C07D413/02 ,  A61K31/405 ,  A61K31/497 ,  A61P29/00 ,  A61P19/02 ,  A61P25/00 ,  A61P7/02

CPC分类号： C07D209/14 ,  C07D209/18

摘要： This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A2 enzymes (cPLA2), more particularly including inhibitors of cytosolic phospholipase A2 alpha enzymes (cPLA2α). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

摘要翻译： 本发明提供了各种磷脂酶，特别是细胞溶质磷脂酶A2酶（cPLA2）的活性的化学抑制剂，更具体地包括胞浆磷脂酶A2α酶（cPLA2α）的抑制剂。 在一些实施方案中，抑制剂具有式I：其中组成变量如本文所定义。

公开(公告)号：US08283373B2

公开(公告)日：2012-10-09

申请号：US12488182

申请日：2009-06-19

申请人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John C. McKew ,  Katherine L. Lee ,  Lihren Chen ,  Richard Vargas ,  James D. Clark ,  Cara Williams ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A61K31/404

CPC分类号： C07D209/14 ,  C07D209/18

摘要： This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A2 enzymes (cPLA2), more particularly including inhibitors of cytosolic phospholipase A2 alpha enzymes (cPLA2α). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

摘要翻译： 本发明提供各种磷脂酶，特别是细胞溶质磷脂酶A2酶（cPLA2）的活性的化学抑制剂，更具体地包括胞浆磷脂酶A2α酶（cPLA2α）的抑制剂。 在一些实施方案中，抑制剂具有式I：其中组成变量如本文所定义。

公开(公告)号：US20100035957A1

公开(公告)日：2010-02-11

申请号：US12539074

申请日：2009-08-11

申请人： John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A61K31/405 ,  A61P9/10 ,  A61P25/28

CPC分类号： A61K31/505 ,  C07D209/14 ,  C07D209/16 ,  C07D209/20 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D487/08 ,  C07D491/10

摘要： This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor.

摘要翻译： 本发明提供了使用通式的取代的吲哚化合物及其药学上可接受的盐形式的方法。 本发明提供了使用化合物作为各种磷脂酶，特别是磷脂酶A2酶的活性的抑制剂的方法，以及用于医学治疗，预防和抑制疾病和病症，包括哮喘，中风，动脉粥样硬化，多发性硬化，帕金森病， 关节炎疾病，风湿病，中风引起的中枢神经系统损伤，由缺血引起的中枢神经系统损伤，由创伤引起的中枢神经系统损伤，由前列腺素引起或增强的炎症，由白细胞三烯引起或增强的炎症，血小板引起或增强的炎症 活化因子，由前列腺素引起或增强的疼痛，由白三烯引起或加剧的疼痛，以及血小板激活因子引起或增强的疼痛。

公开(公告)号：US07605156B2

公开(公告)日：2009-10-20

申请号：US11140390

申请日：2005-05-27

申请人： John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A61K31/54

CPC分类号： A61K31/505 ,  C07D209/14 ,  C07D209/16 ,  C07D209/20 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D487/08 ,  C07D491/10

摘要： This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor.

摘要翻译： 本发明提供了使用通式的取代的吲哚化合物及其药学上可接受的盐形式的方法。 本发明提供了使用化合物作为各种磷脂酶，特别是磷脂酶A2酶的活性的抑制剂的方法，以及用于医学治疗，预防和抑制疾病和病症，包括哮喘，中风，动脉粥样硬化，多发性硬化，帕金森病， 关节炎疾病，风湿病，中风引起的中枢神经系统损伤，由缺血引起的中枢神经系统损伤，由创伤引起的中枢神经系统损伤，由前列腺素引起或增强的炎症，由白细胞三烯引起或增强的炎症，血小板引起或增强的炎症 活化因子，由前列腺素引起或增强的疼痛，由白三烯引起或加剧的疼痛，以及血小板激活因子引起或增强的疼痛。

公开(公告)号：US07906548B2

公开(公告)日：2011-03-15

申请号：US12539074

申请日：2009-08-11

申请人： John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A01N43/38

CPC分类号： A61K31/505 ,  C07D209/14 ,  C07D209/16 ,  C07D209/20 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D487/08 ,  C07D491/10

摘要： This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor.

摘要翻译： 本发明提供了使用通式的取代的吲哚化合物及其药学上可接受的盐形式的方法。 本发明提供了使用化合物作为各种磷脂酶，特别是磷脂酶A2酶的活性的抑制剂的方法，以及用于医学治疗，预防和抑制疾病和病症，包括哮喘，中风，动脉粥样硬化，多发性硬化，帕金森病， 关节炎疾病，风湿病，中风引起的中枢神经系统损伤，由缺血引起的中枢神经系统损伤，由创伤引起的中枢神经系统损伤，由前列腺素引起或增强的炎症，由白细胞三烯引起或增强的炎症，血小板引起或增强的炎症 活化因子，由前列腺素引起或增强的疼痛，由白三烯引起或加剧的疼痛，以及血小板激活因子引起或增强的疼痛。

公开(公告)号：US20070004719A1

公开(公告)日：2007-01-04

申请号：US11442199

申请日：2006-05-26

申请人： John McKew ,  Katherine Lee ,  Lihren Chen ,  Richard Vargas ,  James Clark ,  Cara Williams ,  Valerie Clerin ,  Suzan Marusic ,  Kevin Pong

发明人： John McKew ,  Katherine Lee ,  Lihren Chen ,  Richard Vargas ,  James Clark ,  Cara Williams ,  Valerie Clerin ,  Suzan Marusic ,  Kevin Pong

IPC分类号： A61K31/5377 ,  A61K31/496 ,  A61K31/405 ,  C07D413/02 ,  C07D403/02 ,  C07D209/18

CPC分类号： C07D209/14 ,  C07D209/18

摘要： This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A2 enzymes (cPLA2), more particularly including inhibitors of cytosolic phospholipase A2 alpha enzymes (cPLA2α). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

摘要翻译： 本发明提供了各种磷脂酶，特别是胞质磷脂酶A 2 N 2酶（cPLA 2 N）的活性的化学抑制剂，更具体地包括胞质磷脂酶A 2的抑制剂 α酶（cPLA2α）。 在一些实施方案中，抑制剂具有式I：其中组成变量如本文所定义。

公开(公告)号：US20060014759A1

公开(公告)日：2006-01-19

申请号：US11140390

申请日：2005-05-27

申请人： John McKew ,  Steven Tam ,  Katherine Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark Behnke ,  Baihua Hu ,  James Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

发明人： John McKew ,  Steven Tam ,  Katherine Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark Behnke ,  Baihua Hu ,  James Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC分类号： A61K31/505 ,  C07D239/02

CPC分类号： A61K31/505 ,  C07D209/14 ,  C07D209/16 ,  C07D209/20 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D487/08 ,  C07D491/10

摘要： This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor.

摘要翻译： 本发明提供了使用通式的取代的吲哚化合物及其药学上可接受的盐形式的方法。 本发明提供了使用化合物作为各种磷脂酶，特别是磷脂酶2酶的活性抑制剂的方法，以及用于治疗，预防和抑制疾病和病症的方法，包括哮喘，中风， 动脉粥样硬化，多发性硬化，帕金森病，关节炎疾病，风湿病，由中风引起的中枢神经系统损伤，由缺血引起的中枢神经系统损伤，由创伤引起的中枢神经系统损伤，由前列腺素引起或增强的炎症，由...引起或增强的炎症 白细胞三烯，血小板活化因子引起或增强的炎症，前列腺素引起或加剧的疼痛，白细胞三烯引起或增强的疼痛，以及血小板激活因子引起或增强的疼痛。

公开(公告)号：US20060155164A1

公开(公告)日：2006-07-13

申请号：US11273888

申请日：2005-11-14

申请人： Valerie Clerin ,  Rebecca Gusic ,  Keith Gooch

发明人： Valerie Clerin ,  Rebecca Gusic ,  Keith Gooch

IPC分类号： A61F2/04

CPC分类号： A61L27/3695 ,  A61F2/062 ,  A61L27/3625 ,  A61L27/3691 ,  C12N5/0691 ,  Y10S623/916

摘要： The present invention provides an ex vivo vascular remodeling methods and system by which an excised, small diameter blood vessel can be harvested and expanded to provide viable vascular grafts, as demonstrated at the physical and molecular levels, and as optimized in vivo. The tissue-engineered vessels generated by the present invention closely resemble native vessels in terms of structure, histologically, including endothelial coverage and intricate structural components such as the internal elastic lamina, viability (as measured with the MTT assay and TUNEL analysis), and function (vasoactivity, mechanical and biomechanical properties). Thus, the resulting vascular grafts behave in a manner similar to native arteries in terms of mechanical integrity, and provide clinically relevant patency rates when implanted in vivo. Moreover, the ex vivo methods and system permit the precise control of the mechanical environment involving the excised vessel, while at the same time permitting carefully monitoring of the resulting growth/remodeling, thereby opening new avenues of research regarding the mechanical stimuli responsible for specific aspects of remodeling in vivo.