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    Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use
    1.
    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.

    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。

    Nitrosated and nitrosylated compounds, compositions and methods use
    5.
    发明申请
    Nitrosated and nitrosylated compounds, compositions and methods use 审中-公开
    亚硝化和亚硝化化合物，组合物和方法用途

    公开(公告)号：US20060009431A1

    公开(公告)日：2006-01-12

    申请号：US11221901

    申请日：2005-09-09

    申请人： Richard Earl ,  David Garvey ,  Ricky Gaston ,  Chia-En Lin ,  Ramani Ranatunge ,  Stewart Richardson ,  Cheri Stevenson

    发明人： Richard Earl ,  David Garvey ,  Ricky Gaston ,  Chia-En Lin ,  Ramani Ranatunge ,  Stewart Richardson ,  Cheri Stevenson

    IPC分类号： A61K31/56 ,  A61K31/21

    CPC分类号： C07J17/00 ,  C07J1/00 ,  C07J31/006 ,  C07J41/0044 ,  C07J43/00 ,  C07J43/003

    摘要： The invention describes novel nitrosated and/or nitrosylated compounds of the invention, and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated compound of the invention, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one compound of the invention, that is optionally nitrosated and/or nitrosylated, and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating cardiovascular diseases, for inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering at least one compound of the invention that is optionally nitrosated and/or nitrosylated, in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The compounds of the invention are preferably estradiol compounds, troglitazone compounds, tranilast compounds, retinoic acid compounds, resveratol compounds, myophenolic acid compounds, acid compounds, anthracenone compounds and trapidil compounds.

    摘要翻译： 本发明描述了本发明的新型亚硝化和/或亚硝基化化合物及其药学上可接受的盐，以及包含至少一种本发明的亚硝基化和/或亚硝化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。 本发明还提供了包含至少一种本发明的化合物，其任选被亚硝化和/或亚硝基化的新化合物，以及至少一种一氧化氮供体化合物和/或至少一种治疗剂。 本发明的化合物和组合物也可以结合到基质上。 本发明还提供了治疗心血管疾病的方法，用于抑制由血液暴露于医疗器械引起的血小板聚集和血小板粘附，用于治疗由异常细胞增殖引起的病理状况; 移植排斥，自身免疫，炎症，增殖，过度增生或血管疾病; 用于减少瘢痕组织或抑制伤口收缩，特别是预防和/或治疗再狭窄的方法，通过给予至少一种任选地亚硝化和/或亚硝基化的本发明化合物与能够释放硝酸的一氧化氮供体组合 在生理条件下氧化或间接地将一氧化氮递送或转移到靶位点。 本发明的化合物优选为雌二醇化合物，曲格列酮化合物，曲尼司特化合物，视黄酸化合物，白藜芦醇化合物，肌醇酸化合物，酸化合物，蒽酮化合物和捕获剂化合物。

    Nitrosated glutamic acid compounds, compositions and methods of use
    6.
    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 alpha-adrenergic receptor antagonist compounds
    8.
    发明申请
    Nitrosated and nitrosylated alpha-adrenergic receptor antagonist compounds 审中-公开
    亚硝化和亚硝酰化α-肾上腺素能受体拮抗剂化合物

    公开(公告)号：US20050187222A1

    公开(公告)日：2005-08-25

    申请号：US11109761

    申请日：2005-04-20

    申请人： David Garvey ,  Inigo De Tejada ,  Ricky Gaston ,  Subhash Khanapure ,  Tatiana Shelekhin ,  Tiansheng Wang

    发明人： David Garvey ,  Inigo De Tejada ,  Ricky Gaston ,  Subhash Khanapure ,  Tatiana Shelekhin ,  Tiansheng Wang

    IPC分类号： A61K45/06 ,  C07C381/00 ,  C07D211/62 ,  C07D233/24 ,  C07D239/95 ,  C07D401/04 ,  C07D405/12 ,  C07D459/00 ,  C07D43/02 ,  A61K31/517

    CPC分类号： C07D459/00 ,  A61K45/06 ,  C07C381/00 ,  C07D211/62 ,  C07D233/24 ,  C07D239/95 ,  C07D401/04 ,  C07D405/12

    摘要： The present invention describes novel nitrosated and/or nitrosylated α-adrenergic receptor antagonists, and novel compositions containing at least one nitrosated and/or nitrosylated α-adrenergic receptor antagonist, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or are a substrate for nitric oxide synthase, and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one α-adrenergic receptor antagonist, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, neurodegenerative disorders, vasospastic diseases, cognitive disorders, urge incontinence, or overactive bladder, and for reversing the state of anesthesia.

    摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的α-肾上腺素能受体拮抗剂，以及含有至少一种亚硝化和/或亚硝基化的α-肾上腺素能受体拮抗剂的新组合物，以及任选的一种或多种捐赠，转移或释放一氧化氮的化合物 提高内源性舒张因子的内源水平，刺激一氧化氮的内源性合成，或是一氧化氮合酶的底物和/或一种或多种血管活性剂。 本发明还提供含有至少一种α-肾上腺素能受体拮抗剂和一种或多种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮水平的内源性松弛因子，刺激一氧化氮的内源性合成，或是一种 一氧化氮合酶的底物和/或一种或多种血管活性剂。 本发明还提供了用于治疗或预防男性和女性性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防良性前列腺增生，高血压，充血性心力衰竭，变体（印刷金属）心绞痛，青光眼，神经变性 疾病，血管痉挛性疾病，认知障碍，急迫性尿失禁或膀胱过度活动，以及扭转麻醉状态。

    NITROSATED PROTON PUMP INHIBITORS, COMPOSITIONS AND METHODS OF USE
    10.
    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。