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    NITROSATED PROTON PUMP INHIBITORS, COMPOSITIONS AND METHODS OF USE
    1.
    发明申请
    NITROSATED PROTON PUMP INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
    硝基脲泵抑制剂，组合物和使用方法

    公开(公告)号：US20070179150A1

    公开(公告)日：2007-08-02

    申请号：US11689568

    申请日：2007-03-22

    申请人： Xinqin Fang ,  David Garvey ,  L. Letts

    发明人： Xinqin Fang ,  David Garvey ,  L. Letts

    IPC分类号： A61K31/496 ,  A61K31/4745 ,  A61K31/4709 ,  C07D471/02 ,  C07D401/02 ,  C07D403/02

    CPC分类号： C07D401/12

    摘要： The invention describes novel nitrosated proton pump inhibitor compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated proton pump inhibitor compound, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylori properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating bacterial infections and/or viral infections.

    摘要翻译： 本发明描述了新的亚硝化质子泵抑制剂化合物及其药学上可接受的盐，以及包含至少一种亚硝化质子泵抑制剂化合物和任选的至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性硝酸合成的新型组合物 氧化物，提高内源性内源性水平的内源性松弛因子，或者是一氧化氮合酶的底物和/或至少一种治疗剂。 本发明还提供了包含至少一种亚硝化质子泵抑制剂化合物和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮衍生的松弛因子水平，刺激一氧化氮的内源性合成或是底物 用于一氧化氮合酶和/或至少一种治疗剂。 本发明还提供了包含至少一种亚硝化质子泵抑制剂化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。 本发明还提供了治疗胃肠道疾病的方法; 促进溃疡愈合; 减少溃疡复发; 改善胃保护性质，抗幽门螺旋杆菌性质或质子泵抑制剂的抗酸性; 降低或减少与使用非甾体抗炎化合物相关的胃肠道毒性; 治疗细菌感染和/或病毒感染。

    Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
    3.
    发明申请
    Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use 失效
    亚硝基化和亚硝基化环加氧酶-2抑制剂，组合物和使用方法

    公开(公告)号：US20070060571A1

    公开(公告)日：2007-03-15

    申请号：US11599519

    申请日：2006-11-15

    申请人： Ramani Bandarage ,  Upul Bandarage ,  Xinqin Fang ,  David Garvey ,  L. Letts ,  Joseph Schroeder ,  Sang Tam

    发明人： Ramani Bandarage ,  Upul Bandarage ,  Xinqin Fang ,  David Garvey ,  L. Letts ,  Joseph Schroeder ,  Sang Tam

    IPC分类号： A61K31/55 ,  A61K31/541 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/454 ,  C07D417/02 ,  C07D413/02 ,  C07D403/02

    CPC分类号： C07D207/333 ,  C07C317/46 ,  C07C381/00 ,  C07D209/12 ,  C07D209/18 ,  C07D231/12 ,  C07D231/14 ,  C07D233/64 ,  C07D237/14 ,  C07D261/08 ,  C07D263/20 ,  C07D307/58 ,  C07D311/12 ,  C07D413/12 ,  C07D471/04

    摘要： The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.

    摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的环氧合酶2（COX-2）抑制剂和包含至少一种亚硝化和/或亚硝基化的环氧合酶2（COX-2）抑制剂的新组合物，和任选的至少一种可以提供， 转移或释放一氧化氮，刺激一氧化氮的内源性合成，提高内皮衍生的松弛因子的内源水平，或者是一氧化氮合酶的底物和/或任选的至少一种治疗剂。 本发明还提供了包含至少一种母体COX-2抑制剂和至少一种一氧化氮供体以及任选的至少一种治疗剂的新型组合物。 本发明还提供用于治疗炎症，疼痛和发烧的试剂盒和方法; 用于治疗和/或改善COX-2抑制剂的胃肠性质; 促进伤口愈合; 用于治疗和/或预防肾毒性; 并且用于治疗和/或预防由环氧合酶-2水平升高引起的其它疾病。

    Nitric oxide enhancing diuretic compounds, compositions and methods of use
    4.
    发明申请
    Nitric oxide enhancing diuretic compounds, compositions and methods of use 失效
    一氧化氮增强利尿剂，组合物和使用方法

    公开(公告)号：US20060189603A1

    公开(公告)日：2006-08-24

    申请号：US11360599

    申请日：2006-02-24

    申请人： David Garvey ,  L. Letts ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunge ,  Cheri Stevenson ,  Shiow-Jyi Wey

    发明人： David Garvey ,  L. Letts ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunge ,  Cheri Stevenson ,  Shiow-Jyi Wey

    IPC分类号： A61K31/549 ,  C07D417/02

    CPC分类号： C07D285/30 ,  C07D285/28 ,  C07D285/32 ,  C07D417/04 ,  C07D417/06 ,  C07D513/10

    摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

    摘要翻译： 本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。 本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （l）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合征; （q）治疗性功能障碍; 和（r）高脂血症。 一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。

    Cyclooxygenase-2 selective inhibitors, compositions and methods of use
    5.
    发明申请
    Cyclooxygenase-2 selective inhibitors, compositions and methods of use 失效
    环氧合酶-2选择性抑制剂，组合物和使用方法

    公开(公告)号：US20060194861A1

    公开(公告)日：2006-08-31

    申请号：US11418187

    申请日：2006-05-05

    申请人： Ipul Bandarage ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David Garvey ,  Subhash Khanapure ,  Ramani Ranatunge ,  Stewart Richardson ,  Joseph Schroeder ,  Cheri Stevenson ,  Shiow-Jyi Wey

    发明人： Ipul Bandarage ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David Garvey ,  Subhash Khanapure ,  Ramani Ranatunge ,  Stewart Richardson ,  Joseph Schroeder ,  Cheri Stevenson ,  Shiow-Jyi Wey

    IPC分类号： C07D231/06 ,  A61K31/415

    CPC分类号： C07D231/12 ,  C07D261/08 ,  C07D401/04

    摘要： The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

    摘要翻译： 本发明描述了新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及任选地至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性合成 的一氧化氮，提高内源性内源性释放因子水平，或者是一氧化氮合酶的底物和/或至少一种治疗剂。 本发明还提供了包含至少一种COX-2选择性抑制剂，任选地亚硝基化和/或亚硝基化的新的试剂盒，以及任选的至少一种一氧化氮供体，和/或任选的至少一种治疗剂。 本发明的新型环加氧酶2选择性抑制剂可以任选地亚硝化和/或亚硝化。 本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠性质; 促进伤口愈合; 用于治疗和/或预防肾和/或呼吸毒性; 用于治疗和/或预防由环氧合酶-2水平升高引起的其他疾病; 并用于改善COX-2选择性抑制剂的心血管外形。

    Nitric oxide enhancing angiotensin II antagonist compounds, compositions and methods of use
    6.
    发明申请
    Nitric oxide enhancing angiotensin II antagonist compounds, compositions and methods of use 审中-公开
    一氧化氮增强型血管紧张素II拮抗剂化合物，组合物和使用方法

    公开(公告)号：US20070032533A1

    公开(公告)日：2007-02-08

    申请号：US11499770

    申请日：2006-08-07

    申请人： David Garvey ,  Xiong Cai ,  Xinqin Fang ,  Ramani Ranatunge ,  Shiow-Jyi Wey ,  Hai-Xiao Zhai

    发明人： David Garvey ,  Xiong Cai ,  Xinqin Fang ,  Ramani Ranatunge ,  Shiow-Jyi Wey ,  Hai-Xiao Zhai

    IPC分类号： A61K31/433 ,  A61K31/4245 ,  A61K31/42

    CPC分类号： C07D257/04 ,  C07D401/12 ,  C07D403/10 ,  C07D403/12 ,  C07D471/04

    摘要： The invention describes compositions and kits comprising at least one nitric oxide enhancing angiotensin II antagonist compound, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitric oxide enhancing angiotensin II antagonist compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating peripheral vascular diseases; (m) treating portal hypertension (o) treating central nervous system disorders; (p) treating metabolic syndrome; and (q) treating hyperlipidemia. The nitric oxide enhancing angiotensin II antagonist compounds comprise at least one nitric oxide enhancing group linked to the angiotensin II antagonist compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

    摘要翻译： 本发明描述了包含至少一种一氧化氮增强型血管紧张素II拮抗剂化合物或其药学上可接受的盐的组合物和试剂盒，以及包含至少一种一氧化氮增强型血管紧张素II拮抗剂化合物和任选的至少一种一氧化氮增强化合物 和/或至少一种治疗剂。 本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （l）治疗外周血管疾病; （m）治疗门静脉高压（​​o）治疗中枢神经系统疾病; （p）治疗代谢综合征; 和（q）治疗高脂血症。 一氧化氮增强型血管紧张素II拮抗剂化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与血管紧张素II拮抗剂化合物连接的至少一个一氧化氮增强基团。

    Nitrosated glutamic acid compounds, compositions and methods of use
    7.
    发明申请
    Nitrosated glutamic acid compounds, compositions and methods of use 审中-公开
    亚硝酸谷氨酸化合物，组合物和使用方法

    公开(公告)号：US20070037821A1

    公开(公告)日：2007-02-15

    申请号：US10573030

    申请日：2004-09-27

    申请人： David Garvey ,  Richard Earl ,  Malko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunga ,  Cheri Stevenson ,  Shiow-Jyi Wey

    发明人： David Garvey ,  Richard Earl ,  Malko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunga ,  Cheri Stevenson ,  Shiow-Jyi Wey

    IPC分类号： A61K31/495 ,  C07D241/04 ,  A61K31/21 ,  C07C203/02

    CPC分类号： C07C271/22 ,  C07C229/24 ,  C07C237/12 ,  C07D295/185

    摘要： The invention describes novel nitrosated glutamic acid compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated glutamic acid compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated glutamic acid compound, and, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (m) the targeted delivery of compounds and nitric oxide to organs, cells or tissues containing the enzyme gamma-glutamyl transpeptidase.

    摘要翻译： 本发明描述了新的亚硝酸化谷氨酸化合物及其药学上可接受的盐，以及包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物。 本发明还提供了包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型试剂盒。 本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （l）治疗由γ-谷氨酰转肽酶水平升高引起的疾病和（m）将化合物和一氧化氮靶向递送至含有γ-谷氨酰转肽酶的器官，细胞或组织。

    Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use
    10.
    发明申请
    Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use 失效

    公开(公告)号：US20070004788A1

    公开(公告)日：2007-01-04

    申请号：US11518231

    申请日：2006-09-11

    申请人： David Garvey ,  L. Letts ,  Chia-En Lin ,  Tiansheng Wang

    发明人： David Garvey ,  L. Letts ,  Chia-En Lin ,  Tiansheng Wang

    IPC分类号： A61K31/426

    CPC分类号： C07D233/54 ,  C07D233/64 ,  C07D277/48 ,  C07D295/092 ,  C07D295/096

    摘要： The invention describes novel nitrosated and/or nitrosylated H2 receptor antagonist compounds, and novel compositions comprising at least one H2 receptor antagonist compound that is optionally substituted with at least one NO and/or NO2 group, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase and/or at least one nonsteroidal antiinflammatory drug, antacid, bismuth-containing reagent or anti-viral agent. The invention also describes methods for treating and/or preventing gastrointestinal disorders; improving gastroprotective properties of H2 receptor antagonists; decreasing the recurrence of ulcers; facilitating ulcer healing; preventing and/or treating inflammations and microbial infections, ophthalmic diseases and disorders, multiple sclerosis, and viral infections; and decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds.