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1. 发明申请

WO2004002409A2 CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： CYCLOOXGENASE-2选择性抑制剂，组合物和使用方法
公开(公告)号：WO2004002409A2
公开(公告)日：2004-01-08
申请号：PCT/US2003/019850
申请日：2003-06-25
申请人： NITROMED, INC. , BANDARAGE, Upul, K. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GARVEY, David, S. , KHANAPURE, Subhash, P. , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , SCHROEDER, Joseph, D. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
发明人： BANDARAGE, Upul, K. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GARVEY, David, S. , KHANAPURE, Subhash, P. , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , SCHROEDER, Joseph, D. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
IPC分类号： A61K
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：本发明描述了新颖的环加氧酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂和任选地至少一种化合物的新型组合物，或释放一氧化氮，刺激一氧化氮的内源性合成，提高内源性内皮细胞衍生的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选择性抑制剂（任选亚硝化和/或亚硝基化）和任选地至少一种一氧化氮供体和/或任选地至少一种治疗剂的新型试剂盒。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/或亚硝基化。本发明还提供治疗炎症，疼痛和发热的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性; 用于促进伤口愈合; 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特征。

2. 发明申请

WO2004004648A3 NITROSATED NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
公开(公告)号：WO2004004648A3
公开(公告)日：2004-01-15
申请号：PCT/US2003/021026
申请日：2003-07-03
申请人： NITROMED, INC. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GARVEY, David, S. , GASTON, Ricky, D. , KHANAPURE, Subhash, P. , LETTS, Gordon, L. , LIN, Chia-En , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , SCHROEDER, Joseph, D. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
发明人： EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GARVEY, David, S. , GASTON, Ricky, D. , KHANAPURE, Subhash, P. , LETTS, Gordon, L. , LIN, Chia-En , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , SCHROEDER, Joseph, D. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
IPC分类号： C07D333/22
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.

3. 发明申请

WO2006091716A2 NITRIC OXIDE ENHANCING DIURETIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸氧化物增强化学复合物，组合物和使用方法
公开(公告)号：WO2006091716A2
公开(公告)日：2006-08-31
申请号：PCT/US2006/006375
申请日：2006-02-24
申请人： NITROMED, INC. , GARVEY, David, S. , LETTS, Gordon, L. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D. , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
发明人： GARVEY, David, S. , LETTS, Gordon, L. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D. , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
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; (1) 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; （1）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。

4. 发明申请

WO2005030135A2 NITROSATED GLUTAMIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸盐谷氨酸化合物，组合物和使用方法
公开(公告)号：WO2005030135A2
公开(公告)日：2005-04-07
申请号：PCT/US2004/031372
申请日：2004-09-27
申请人： NITROMED, INC. , GARVEY, David, S. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D. , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
发明人： GARVEY, David, S. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D. , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
IPC分类号： A61K
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; (1) 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基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化谷氨酸化合物和任选地至少一种一氧化氮供体和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝基化谷氨酸化合物和任选地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。本发明还提供了用于（a）治疗心血管疾病的方法; （b）治疗肾血管性疾病; （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; （1）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酶γ-谷氨酰转肽酶的器官，细胞或组织。

5. 发明申请

WO2005023183A2 NITROSATED AD NITROSYLATED DIURETIC COMPOUDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸盐的硝酸盐溶液，组合物和使用方法
公开(公告)号：WO2005023183A2
公开(公告)日：2005-03-17
申请号：PCT/US2004/026911
申请日：2004-08-20
申请人： NITROMED, INC. , GARVEY, David, S. , LETTS, L., Gordon , WORCEL, Manuel , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A.
发明人： GARVEY, David, S. , LETTS, L., Gordon , WORCEL, Manuel , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A.
IPC分类号： A61K
CPC分类号： C07D403/10 , C07C205/40 , C07D233/68 , C07D235/18 , C07D257/04 , C07D307/52 , C07D401/12 , C07D401/14 , C07D405/06 , C07D405/12 , C07D405/14 , C07D409/04 , C07D409/06 , C07D409/14 , C07D413/10 , C07D471/04 , C07D487/04 , C07D495/04 , C07D498/04
摘要： The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor 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; and (1) treating nephropathy.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的利尿剂或其药学上可接受的盐，以及包含至少一种亚硝化和/或亚硝基化的利尿剂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。本发明还提供了包含至少一种本发明的利尿剂化合物，其任选被亚硝化和/或亚硝基化的新组合物和试剂盒，以及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（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; 和（1）治疗肾病。

6. 发明申请

WO2004010945A2 CYCLOOXYGENASE- 2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： CYCLOOXYGENASE-2选择性抑制剂，组合物和使用方法
公开(公告)号：WO2004010945A2
公开(公告)日：2004-02-05
申请号：PCT/US2003/023605
申请日：2003-07-29
申请人： NITROMED, INC. , GARVEY, David, S. , KHANAPURE, Subhash, P. , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , SCHROEDER, Joseph, D.
发明人： GARVEY, David, S. , KHANAPURE, Subhash, P. , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , SCHROEDER, Joseph, D.
IPC分类号： A61K
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 endotheliumderived 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：本发明描述了新颖的环加氧酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂和任选地至少一种化合物的新型组合物，或释放一氧化氮，刺激一氧化氮的内源性合成，提高内皮细胞和内皮细胞水平的内皮细胞衍生的舒张因子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选择性抑制剂（任选亚硝化和/或亚硝基化）和任选地至少一种一氧化氮供体和/或任选地至少一种治疗剂的新型试剂盒。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/或亚硝基化。本发明还提供治疗炎症，疼痛和发热的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性; 用于促进伤口愈合; 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特征。

7. 发明申请

WO2002060378A3 SUBSTITUTED ARYL COMPOUNDS AS CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
公开(公告)号：WO2002060378A3
公开(公告)日：2002-08-08
申请号：PCT/US2001/048823
申请日：2001-12-21
申请人： NITROMED, INC. , KHANAPURE, Subhash, P. , GARVEY, David, S. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D.
发明人： KHANAPURE, Subhash, P. , GARVEY, David, S. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D.
IPC分类号： A61K31/36
摘要： The invention describes substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and compositions comprising at elast 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, optionally, at least one therapeutic agent, such as, steroids, nonsterodal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B 4 (LTB 4 ) receptor antagonists, leukotriene A 4 (LTA 4 ) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H 2 antagonists, antineoplastic agents, antiplatelet agents,thrombin inhibitors, thromboxane inhibitors, 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 invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The 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 toxicity or other toxicities; 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.

8. 发明申请

WO2002060378A2 SUBSTITUTED ARYL COMPOUNDS AS NOVEL CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：取代的芳基化合物作为新一代CYCLOOXYGENASE-2选择性抑制剂，组合物和使用方法
公开(公告)号：WO2002060378A2
公开(公告)日：2002-08-08
申请号：PCT/US2001/048823
申请日：2001-12-21
申请人： NITROMED, INC. , KHANAPURE, Subhash, P. , GARVEY, David, S. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D.
发明人： KHANAPURE, Subhash, P. , GARVEY, David, S. , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , GASTON, Ricky, D.
IPC分类号： A61K
CPC分类号： C07D319/08 , A61K45/06 , C07D317/56 , C07D319/18 , C07D319/20 , C07D405/06
摘要： The invention describe novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at elast 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, optionally, at least one therapeutic agent, such as, steroids, nonsterodal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B 4 (LTB 4 ) receptor antagonists, leukotriene A 4 (LTA 4 ) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H 2 antagonists, antineoplastic agents, antiplatelet agents,thrombin inhibitors, thromboxane inhibitors, 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 invention also provides novel kits comprising at least one COX-2 selective inhibitor, 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 toxicity or other toxicities; 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：本发明描述了作为环氧合酶2（COX-2）选择性抑制剂的新型取代的芳基化合物和包含弹性一环氧合酶2（COX-2）选择性抑制剂的新组合物，以及任选的至少一种捐赠，转移或释放硝酸的化合物刺激内源性合成一氧化氮，提高内源性内皮水平的内源性松弛因子，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，非典型抗炎化合物（NSAID），5-脂氧合酶（5-LO）抑制剂，白三烯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）抑制剂，H2拮抗剂抗肿瘤剂，抗血小板药，凝血酶抑制剂，凝血恶烷抑制剂，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COX-2选择性抑制剂和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的新型试剂盒。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/或预防肾毒性或其他毒性; 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。

9. 发明申请

WO2004098538A2 NITROSATED AND NITROSYLATED COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝基和硝基化合物，组合物和使用方法
公开(公告)号：WO2004098538A2
公开(公告)日：2004-11-18
申请号：PCT/US2004/007943
申请日：2004-03-15
申请人： NITROMED, INC. , EARL, Richard, A. , GARVEY, David, S. , GASTON, Ricky, D. , LIN, Chia-En , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , STEVENSON, Cheri, A.
发明人： EARL, Richard, A. , GARVEY, David, S. , GASTON, Ricky, D. , LIN, Chia-En , RANATUNGE, Ramani, R. , RICHARDSON, Stewart, K. , STEVENSON, Cheri, A.
IPC分类号： A61K
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是雌二醇化合物，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。

10. 发明申请

WO2007019448A3 NITRIC OXIDE ENHANCING ANGIOTENSIN II ANTAGONIST COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
公开(公告)号：WO2007019448A3
公开(公告)日：2007-02-15
申请号：PCT/US2006/030733
申请日：2006-08-07
申请人： NITROMED, INC. , GARVEY, David, S. , CAI, Xiong , FANG, Xinqin , RANATUNGE, Ramani, R. , WEY, Shiow-Jyi , ZHAI, Hai-Xiao
发明人： GARVEY, David, S. , CAI, Xiong , FANG, Xinqin , RANATUNGE, Ramani, R. , WEY, Shiow-Jyi , ZHAI, Hai-Xiao
IPC分类号： A01N43/42 , A61K31/44
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; (1) 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.

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