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    Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
    1.
    发明授权
    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：US07166618B2

    公开(公告)日：2007-01-23

    申请号：US10463671

    申请日：2003-06-18

    申请人： Ramani R. Bandarage ,  David S. Garvey ,  L. Gordon Letts ,  Joseph D. Schroeder ,  Sang William Tam

    发明人： Ramani R. Bandarage ,  David S. Garvey ,  L. Gordon Letts ,  Joseph D. Schroeder ,  Sang William Tam

    IPC分类号： C07D263/04 ,  A61K31/42 ,  C07D207/325

    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, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. 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，提高内源性内皮水平的内皮衍生的松弛因子，或是一氧化氮合酶的底物，和/或任选的至少一种治疗剂，例如类固醇，非甾体抗炎化合物 （NSAID），5-脂氧合酶（5-LO）抑制剂，白细胞三烯B 4（LTB 4 N）受体拮抗剂，白细胞三烯A 4（LTA 5-HT激动剂，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）抑制剂，H 2 N 2拮抗剂，抗肿瘤剂，抗血小板剂， 减充血剂，利尿剂，镇静剂或非镇静抗组胺，诱导型一氧化氮合酶 避孕药，阿片样物质，镇痛药，幽门螺杆菌抑制剂，质子泵抑制剂，异前列烷烷抑制剂及其混合物。 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。

    Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
    2.
    发明授权
    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：US06649629B2

    公开(公告)日：2003-11-18

    申请号：US09741816

    申请日：2000-12-22

    申请人： Upul K. Bandarage ,  Xinqin Fang ,  David S. Garvey ,  L. Gordon Letts ,  Joseph D. Schroeder ,  Sang William Tam

    发明人： Upul K. Bandarage ,  Xinqin Fang ,  David S. Garvey ,  L. Gordon Letts ,  Joseph D. Schroeder ,  Sang William Tam

    IPC分类号： C07D207325

    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, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2 antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. 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，提高内源性内皮水平的内皮衍生的松弛因子，或是一氧化氮合酶的底物，和/或任选的至少一种治疗剂，例如类固醇，非甾体抗炎化合物 （NSAID），5-脂氧合酶（5-LO）抑制剂，白细胞三烯B4（LTB4）受体拮抗剂，白细胞三烯A4（LTA4）水解酶抑制剂，5-HT激动剂，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA） ，H2拮抗剂，抗肿瘤药，抗血小板药，减充血剂，利尿剂，镇静剂或非镇静抗组胺药，诱导型一氧化氮合酶抑制剂，阿片样物质，镇痛药，幽门螺旋杆菌 异种子，质子泵抑制剂，异雄甾烷抑制剂及其混合物。 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。

    NITROSATED AND NITROSYLATED PROSTAGLANDINS, COMPOSITIONS AND METHODS OF USE
    5.
    发明申请
    NITROSATED AND NITROSYLATED PROSTAGLANDINS, COMPOSITIONS AND METHODS OF USE 失效
    硝基和硝基化前体，组合物和使用方法

    公开(公告)号：US20090088366A1

    公开(公告)日：2009-04-02

    申请号：US12237117

    申请日：2008-09-24

    申请人： David S. Garvey ,  Ricky D. Gaston ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

    发明人： David S. Garvey ,  Ricky D. Gaston ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

    IPC分类号： A61K38/02 ,  A61K31/215 ,  A61K31/4164 ,  A61K31/4375 ,  A61P15/00 ,  A61K31/496 ,  A61K31/7076

    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E1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 and nitrosylated prostaglandins, compositions and methods of use
    6.
    发明授权
    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：US07449595B2

    公开(公告)日：2008-11-11

    申请号：US11641050

    申请日：2006-12-19

    申请人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

    发明人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

    IPC分类号： C07C405/00 ,  A61K31/557

    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 and nitrosylated proton pump inhibitors, compositions and methods of use
    7.
    发明授权
    Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use 失效
    亚硝化和亚硝化质子泵抑制剂，组合物和使用方法

    公开(公告)号：US07332505B2

    公开(公告)日：2008-02-19

    申请号：US10866303

    申请日：2004-06-14

    申请人： David S. Garvey ,  L. Gordon Letts ,  Stewart K. Richardson ,  Sang William Tam ,  Tiansheng Wang

    发明人： David S. Garvey ,  L. Gordon Letts ,  Stewart K. Richardson ,  Sang William Tam ,  Tiansheng Wang

    IPC分类号： C07D471/04 ,  C07D401/12 ,  A61K31/437 ,  A61K31/4184

    CPC分类号： C07D401/12 ,  A61K31/00 ,  A61K31/4184 ,  A61K31/433 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4706 ,  A61K31/506 ,  A61K45/06 ,  A61K2300/00

    摘要： The present invention describes novel nitrosated and/or nitrosylated proton pump inhibitor compounds, and novel compositions comprising at least one proton pump inhibitor 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, induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one nonsteroidal antiinflammatory drug, selective COX-2 inhibitor, antacid, bismuth-containing reagent, acid-degradable antibacterial compound, and mixtures thereof. The present invention also provides methods for treating and/or preventing gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylon properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating Helicobacter pylori and viral infections. The compounds and/or compositions of the present invention can also be provided in the form of a pharmaceutical kit.

    摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的质子泵抑制剂化合物，以及包含至少一种任选被至少一个NO和/或NO 2 2个基团取代的质子泵抑制剂化合物的新型组合物，以及 任选地，至少一种捐赠，转移或释放一氧化氮的化合物诱导内源性一氧化氮或内皮衍生的松弛因子的产生，刺激一氧化氮的内源性合成或者是一氧化氮合酶的底物和/或在 至少一种非甾体抗炎药，选择性COX-2抑制剂，抗酸剂，含铋试剂，酸降解抗菌化合物及其混合物。 本发明还提供了治疗和/或预防胃肠道疾病的方法; 促进溃疡愈合; 减少溃疡复发; 改善胃保护性质，抗幽门螺杆菌特性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; 治疗幽门螺杆菌和病毒感染。 本发明的化合物和/或组合物也可以以药物试剂盒的形式提供。

    Nitrostated and nitrosylated prostaglandins, compositions and methods of use
    8.
    发明授权
    Nitrostated and nitrosylated prostaglandins, compositions and methods of use 失效
    硝基化和亚硝酰化前列腺素，组合物和使用方法

    公开(公告)号：US07176238B1

    公开(公告)日：2007-02-13

    申请号：US09516194

    申请日：2000-03-01

    申请人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

    发明人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

    IPC分类号： A61K31/557 ,  C07C405/00

    CPC分类号： A61K31/5575

    摘要： The present 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 present 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 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 cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions. The compounds and/or compositions of the present invention can also be provided in the form of a pharmaceutical kit.

    摘要翻译： 本发明描述了新的亚硝基化和/或亚硝基化的前列腺素，以及包含至少一种亚硝基化和/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，提高内源性的内皮水平 舒张因子，刺激一氧化氮的内源性合成或者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。 本发明还提供了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。 本发明的化合物和/或组合物也可以以药物试剂盒的形式提供。