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    Nitrosated and nitrosylated alpha-adrenergic receptor antagonist compounds
    1.
    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 and nitrosylated prostaglandins, compositions and methods of use
    3.
    发明申请
    Nitrosated and nitrosylated prostaglandins, compositions and methods of use 失效
    亚硝化和亚硝酰化前列腺素，组合物和使用方法

    公开(公告)号：US20070112067A1

    公开(公告)日：2007-05-17

    申请号：US11641050

    申请日：2006-12-19

    申请人： David Garvey ,  Ricky Gaston ,  L. Letts ,  Inigo de Tejada ,  Sang Tam ,  Manuel Worcel

    发明人： David Garvey ,  Ricky Gaston ,  L. Letts ,  Inigo de Tejada ,  Sang Tam ,  Manuel Worcel

    IPC分类号： A61K31/21 ,  C07C203/02

    CPC分类号： A61K31/5575

    摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, and, optionally, 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 vasoactive agent. The invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The 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 cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.

    摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松 因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E 1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导 堕胎

    Nitrosated glutamic acid compounds, compositions and methods of use
    4.
    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。

    Nitric oxide enhancing diuretic compounds, compositions and methods of use
    5.
    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
    10.
    发明申请
    Cyclooxygenase-2 selective inhibitors, compositions and methods of use 审中-公开
    环氧合酶-2选择性抑制剂，组合物和使用方法

    公开(公告)号：US20070238735A1

    公开(公告)日：2007-10-11

    申请号：US11802161

    申请日：2007-05-21

    申请人： David Garvey ,  Subhash Khanapure ,  Ramani Ranatunge ,  Stewart Richardson ,  Joseph Schroeder

    发明人： David Garvey ,  Subhash Khanapure ,  Ramani Ranatunge ,  Stewart Richardson ,  Joseph Schroeder

    IPC分类号： A61K31/495 ,  A61K31/415 ,  C07D213/00 ,  C07D241/10

    CPC分类号： C07D213/55 ,  C07D213/50 ,  C07D231/12 ,  C07D231/14

    摘要： The invention provides novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions and kits 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 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： 本发明提供新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环加氧酶2（COX-2）选择性抑制剂的新型组合物和试剂盒，以及任选地，至少一种捐赠，转移或释放一氧化氮的化合物， 内源性合成一氧化氮，提高内源性内源性松弛因子水平，或是一氧化氮合成酶的底物和/或至少一种治疗剂。 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。