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    Cyclooxygenase-2 selective inhibitors, compositions and methods of use
    11.
    发明授权
    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：US07244753B2

    公开(公告)日：2007-07-17

    申请号：US10628375

    申请日：2003-07-29

    申请人： David S. Garvey ,  Subhash P. Khanapure ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder

    发明人： David S. Garvey ,  Subhash P. Khanapure ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder

    IPC分类号： A61K31/427 ,  A61K31/422 ,  A61K31/4015 ,  C07D417/02 ,  C07D413/02

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

    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。

    Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use
    12.
    发明授权
    Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use 有权
    硝化非甾体抗炎化合物，组合物和使用方法

    公开(公告)号：US07163958B2

    公开(公告)日：2007-01-16

    申请号：US10612014

    申请日：2003-07-03

    申请人： Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    发明人： Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    IPC分类号： A61K31/21 ,  C07C203/04

    CPC分类号： C07D493/04 ,  C07C291/02 ,  C07C311/17 ,  C07C317/18 ,  C07C323/12 ,  C07C327/28 ,  C07D209/18 ,  C07D211/22 ,  C07D211/56

    摘要： The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, 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 NSAID, 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 NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

    摘要翻译： 本发明描述了新型亚硝化非甾体抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID的新组合物，以及任选地至少一种捐赠，转移或释放一氧化氮的化合物，刺激一氧化氮的内源性合成 升高内源性内源性松弛因子水平，或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NSAID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舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物 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NSAID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炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

    Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use
    13.
    发明授权
    Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use 有权
    硝化非甾体抗炎化合物，组合物和使用方法

    公开(公告)号：US08088762B2

    公开(公告)日：2012-01-03

    申请号：US12636316

    申请日：2009-12-11

    申请人： Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    发明人： Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    IPC分类号： A61K31/54 ,  A61K31/44 ,  A61K31/425 ,  C07D498/02 ,  C07D295/02 ,  C07D333/22

    CPC分类号： C07D493/04 ,  C07C291/02 ,  C07C311/17 ,  C07C317/18 ,  C07C323/12 ,  C07C327/28 ,  C07D209/18 ,  C07D211/22 ,  C07D211/56

    摘要： The invention describes novel nitrosated nonsteroidal anti-inflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, 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 NSAID, 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 NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

    摘要翻译： 本发明描述了新的亚硝化非甾体抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID的新组合物，和任选的至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性合成 一氧化氮，提高内源性内源水平的内源性松弛因子，或者是一氧化氮合成酶的底物和/或至少一种治疗剂。 本发明还提供了包含至少一种亚硝化NSAID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舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物 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NSAID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炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

    NITRIC OXIDE DONATING DIURETIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    16.
    发明申请
    NITRIC OXIDE DONATING DIURETIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE 失效
    硝酸氧化物滴定化合物，组合物和使用方法

    公开(公告)号：US20080255101A1

    公开(公告)日：2008-10-16

    申请号：US12136531

    申请日：2008-06-10

    申请人： David S. GARVEY ,  L. Gordon LETTS ,  Richard A. EARL ,  Maiko EZAWA ,  Xinqin FANG ,  Ricky D. GASTON ,  Subhash P. KHANAPURE ,  Chia-En LIN ,  Ramani R. RANATUNGE ,  Cheri A. STEVENSON ,  Shiow-Jyi WEY

    发明人： David S. GARVEY ,  L. Gordon LETTS ,  Richard A. EARL ,  Maiko EZAWA ,  Xinqin FANG ,  Ricky D. GASTON ,  Subhash P. KHANAPURE ,  Chia-En LIN ,  Ramani R. RANATUNGE ,  Cheri A. STEVENSON ,  Shiow-Jyi WEY

    IPC分类号： A61K31/549 ,  A61P9/00 ,  A61P13/00 ,  C07D285/24 ,  C07D417/04 ,  C07D513/10

    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。

    ORGANIC NITRIC OXIDE ENHANCING SALTS OF ANGIOTENSIN II ANTAGONISTS, COMPOSITIONS AND METHODS OF USE
    19.
    发明申请
    ORGANIC NITRIC OXIDE ENHANCING SALTS OF ANGIOTENSIN II ANTAGONISTS, COMPOSITIONS AND METHODS OF USE 审中-公开
    有机氮氧化物增强血管紧张素Ⅱ拮抗剂，组合物和使用方法

    公开(公告)号：US20090215838A1

    公开(公告)日：2009-08-27

    申请号：US11815518

    申请日：2006-03-09

    申请人： David S. Garvey ,  Xiong Cai ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    发明人： David S. Garvey ,  Xiong Cai ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    IPC分类号： A61K31/44 ,  A61K31/41 ,  C07D213/56 ,  C07D257/04

    CPC分类号： C07D257/04 ,  C07C291/02 ,  C07D213/82

    摘要： The invention describes compositions and kits comprising at least one organic nitric oxide enhancing salt of an angiotensin π antagonist, 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; (n) treating ophthalmic disorders; (o) treating metabolic syndrome; and (p) treating hyperlipidemia. The organic nitric oxide enhancing compounds that form salts with the angiotensin II antagonists are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.

    摘要翻译： 本发明描述了包含血管紧张素pi拮抗剂的至少一种有机一氧化氮增强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组合物和试剂盒。 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）治疗外周血管疾病; （m）治疗门静脉高压; （n）治疗眼科疾病; （o）治疗代谢综合征; 和（p）治疗高脂血症。 与血管紧张素II拮抗剂形成盐的有机一氧化氮增强化合物是有机硝酸盐，有机亚硝酸盐，亚硝基硫醇，硫堇啶，硫堇酸盐，非硝酸盐，杂环一氧化氮供体和/或氮氧化物。 杂环一氧化氮供体是呋喃糖，苏氨酸，氧杂三唑-5-酮和/或氧杂三唑-5-亚胺。

    Diuretic Compounds Comprising Heterocyclic Nitric Oxide Donor Groups, Compositions and Methods of Use
    20.
    发明申请
    Diuretic Compounds Comprising Heterocyclic Nitric Oxide Donor Groups, Compositions and Methods of Use 审中-公开
    包含杂环一氧化氮供体组的利尿剂，组合物和使用方法

    公开(公告)号：US20080275093A1

    公开(公告)日：2008-11-06

    申请号：US11793724

    申请日：2005-11-15

    申请人： David S. Garvey ,  Ramani R. Ranatunge

    发明人： David S. Garvey ,  Ramani R. Ranatunge

    IPC分类号： A61K31/4245 ,  C07D413/12 ,  A61P3/10

    CPC分类号： A61K31/541 ,  C07D271/08 ,  C07D413/12

    摘要： The invention describes novel diuretic compounds comprising at least one heterocyclic nitric oxide donor group, or pharmaceutically acceptable salts thereof, and novel composition comprising at least one diuretic compound comprising at least one heterocyclic nitric oxide donor group, and optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention comprising at least one heterocyclic nitric oxide donor group, 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 oxidatives 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; and (p) treating sexual dysfunctions. The heterocyclic nitric oxide donors are preferably furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.

    摘要翻译： 本发明描述了包含至少一种杂环一氧化氮供体基团的新型利尿剂化合物或其药学上可接受的盐，以及包含至少一种包含至少一种杂环一氧化氮供体基团的至少一种利尿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。 本发明还提供了包含至少一种本发明的利尿剂化合物的新型组合物和试剂盒，其包含至少一种杂环一氧化氮供体基团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）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; 和（p）治疗性功能障碍。 杂环一氧化氮供体优选呋喃香糖，苏氨酸亚胺，氧杂三唑-5-酮和/或氧杂三唑-5-亚胺。