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1.发明申请公开(公告)号：US20070238735A1
公开(公告)日：2007-10-11
申请号：US11802161
申请日：2007-05-21
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。
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2.发明申请公开(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。
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3.发明申请公开(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。
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4.发明申请Oxime and/or hydrazone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use 审中-公开含有亚硝基化和/或亚硝基化的环氧合酶-2选择性抑制剂的肟和/或腙，组合物和使用方法公开(公告)号：US20070155734A1
公开(公告)日：2007-07-05
申请号：US11705773
申请日：2007-02-14
IPC分类号： A61K31/541 , A61K31/5377 , A61K31/496 , A61K31/655 , A61K31/55 , A61K31/454 , A61K31/4196 , A61K31/4192 , A61K31/4164 , A61K31/415
CPC分类号： C07D231/12
摘要： The invention provides novel cyclooxygenase 2 (COX-2) selective inhibitors having at least one oxime group or hydrazone group and novel compositions and kits comprising at least one COX-2 selective inhibitor having at least one oxime group or hydrazone group, 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 having at least one oxime group or hydrazone group 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： 本发明提供具有至少一个肟基或腙基团的新型环加氧酶2（COX-2）选择性抑制剂，以及包含至少一种具有至少一个肟基或腙基团的COX-2选择性抑制剂的新组合物和试剂盒，任选地亚硝化和/ 或亚硝酰化，和任选地至少一种一氧化氮供体，和/或任选的至少一种治疗剂。 具有至少一个肟基或腙基团的本发明的新型环加氧酶2选择性抑制剂可任选被亚硝化和/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。
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5.发明申请公开(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
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。
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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。
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