公开(公告)号：US07432285B2

公开(公告)日：2008-10-07

申请号：US11599519

申请日：2006-11-15

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

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

IPC分类号： C07D207/325 ,  A61K31/415

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. 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，提高内皮衍生的松弛因子的内源水平，或者是一氧化氮合酶的底物和/或任选的至少一种治疗剂。 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。

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。