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1. 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.

2. 发明申请

WO2003086282A3 NITRIC OXIDE DONORS, COMPOSITIONS AND METHODS OF USE 审中-公开
公开(公告)号：WO2003086282A3
公开(公告)日：2003-10-23
申请号：PCT/US2003/010562
申请日：2003-04-07
申请人： NITROMED, INC. , FANG, Xinqin , GARVEY, David, S. , GASTON, Ricky, D. , LIN, Chia-En , RANATUNGA, Ramani, R. , RICHARDSON, Stewart, K. , WANG, Tiansheng , WANG, Weiheng , WEY, Shiow-Jyi
发明人： FANG, Xinqin , GARVEY, David, S. , GASTON, Ricky, D. , LIN, Chia-En , RANATUNGA, Ramani, R. , RICHARDSON, Stewart, K. , WANG, Tiansheng , WANG, Weiheng , WEY, Shiow-Jyi
IPC分类号： C07D235/00
摘要： The invention describes novel nitric oxide donors and novel compositions comprising at least one nitric oxide donor. The invention also provides novel compositions comprising at least one nitric oxide donor, and, optionally, 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 the inhibition of 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, vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering the nitric oxide donor optionally in combination with at least one therapeutic agent. The invention also provides methods for treating inflammation, pain, fever, gastrointestinal disorders, respiratory disorders and sexual dysfunctions. The nitric oxide donors donate, transfer or release nitric oxide, and/or elevate endogenous levels of endothelium-derived relaxing factor, and/or stimulate endogenous synthesis of nitric oxide and/or are substrates for nitric oxide synthase and are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The therapeutic agent can optionally be substituted with at least one NO and/or NO 2 group (i.e., nitrosylated and/or nitrosated). The invention also provides novel compositions and kits comprising at least one nitric oxide donor and/or at least one therapeutic agent.

3. 发明申请

WO2006099416A1 2-METHYL INDOLE CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： 2-甲基吲哚环糊精选择性抑制剂，组合物和使用方法
公开(公告)号：WO2006099416A1
公开(公告)日：2006-09-21
申请号：PCT/US2006/009127
申请日：2006-03-13
申请人： NITROMED, INC. , WEY, Shiow-Jyi , GARVEY, David, S. , FANG, Xinqin , RICHARDSON, Stewart, K.
发明人： WEY, Shiow-Jyi , GARVEY, David, S. , FANG, Xinqin , RICHARDSON, Stewart, K.
IPC分类号： C07D209/18
CPC分类号： C07F9/5728 , C07D209/12 , C07D209/16
摘要： The invention describes compositions and kits comprising 2-methyl indole cyclooxygenase 2 (COX-2) selective inhibitors or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The 2-methyl indole cyclooxygenase 2 selective inhibitors can be optionally substituted with at least one nitric oxide enhancing group. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders and/or improving the gastrointestinal properties of COX-2 selective inhibitors; (c) facilitating wound healing; (d) treating renal and/or respiratory toxicities; (e) treating disorders resulting from elevated levels of cyclooxygenase-2; (f) improving the cardiovascular profile of COX-2 selective inhibitors; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; (j) treating diseases caused by endothelial dysfunctions; (k) treating inflammatory disease states and/or disorders; (1) treating ophthalmic disorders; and (m) treating peripheral vascular diseases. The nitric oxide enhancing groups 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2-甲基吲哚环加氧酶2（COX-2）选择性抑制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组合物和试剂盒。 2-甲基吲哚环氧合酶2选择性抑制剂可以任选地被至少一个一氧化氮增强基团取代。本发明还提供了（a）治疗炎症，疼痛和发烧的方法; （b）治疗胃肠道疾病和/或改善COX-2选择性抑制剂的胃肠性质; （c）促进伤口愈合; （d）治疗肾脏和/或呼吸毒性; （e）治疗由环氧合酶-2水平升高引起的疾病; （f）改善COX-2选择性抑制剂的心血管状态; （g）治疗由氧化应激引起的疾病; （h）治疗内皮功能障碍; （j）治疗由内皮功能障碍引起的疾病; （k）治疗炎性疾病状态和/或病症; （1）治疗眼科疾病; 和（m）治疗外周血管疾病。一氧化氮增强基团是有机硝酸盐，有机亚硝酸盐，亚硝基硫醇，硫堇，硫酸盐，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，恶三唑-5-酮和/或氧杂三唑-5-亚胺。

4. 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。

5. 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。

6. 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.

7. 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。

8. 发明申请

WO2006099058A2 ORGANIC NITRIC OXIDE ENHANCING SALTS OF ANGIOTENSIN II ANTAGONISTS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：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：WO2006099058A2
公开(公告)日：2006-09-21
申请号：PCT/US2006/008441
申请日：2006-03-09
申请人： NITROMED, INC. , GARVEY, David, S. , CAI, Xiong , LIN, Chia-En , RANATUNGE, Ramini, R. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
发明人： GARVEY, David, S. , CAI, Xiong , LIN, Chia-En , RANATUNGE, Ramini, R. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
IPC分类号： A61K31/4245
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; (1) 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p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; （1）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，恶三唑-5-酮和/或氧杂三唑-5-亚胺。

9. 发明公开

EP1861093A2 ORGANIC NITRIC OXIDE ENHANCING SALTS OF ANGIOTENSIN II ANTAGONISTS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：有机氮氧化物增强血管紧张素Ⅱ拮抗剂，组合物和盐的使用方法
公开(公告)号：EP1861093A2
公开(公告)日：2007-12-05
申请号：EP06737602.0
申请日：2006-03-09
申请人： Nitromed, Inc.
发明人： GARVEY, David, S. , CAI, Xiong , LIN, Chia-En , RANATUNGE, Ramini, R. , STEVENSON, Cheri, A. , WEY, Shiow-Jyi
IPC分类号： A61K31/41 , 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; (1) 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.

10. 发明公开

EP1534683A2 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：EP1534683A2
公开(公告)日：2005-06-01
申请号：EP03762000.2
申请日：2003-06-25
申请人： Nitromed, Inc.
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： C07D231/12 , 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捐赠，转移或释放一氧化氮的化合物的新组合物，刺激内源性合成的一氧化氮，提高内源性内皮细胞衍生的松弛因子的水平，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。

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