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1. 发明申请

WO2004012659A3 NITROSATED PROTON PUMP INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：氮化质子泵抑制剂，组合物和使用方法
公开(公告)号：WO2004012659A3
公开(公告)日：2004-10-07
申请号：PCT/US0323963
申请日：2003-08-01
申请人： NITROMED INC , FANG XINQIN , GARVEY DAVID S , LETTS GORDON L
发明人： FANG XINQIN , GARVEY DAVID S , LETTS GORDON L
IPC分类号： A61K31/44 , A61K31/4439 , A61K45/00 , A61P1/00 , A61P1/04 , A61P1/10 , A61P1/14 , A61P3/04 , A61P17/02 , A61P27/16 , A61P29/00 , A61P31/04 , A61P31/12 , A61P31/14 , A61P31/22 , A61P35/02 , A61P43/00 , C07D233/54 , C07D401/12 , A61K31/415 , C07D235/04 , C07D401/00 , C07D471/02
CPC分类号： C07D401/12
摘要： The invention describes novel nitrosated proton pump inhibitor compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated proton pump inhibitor compound, 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 proton pump inhibitor compound, 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 proton pump inhibitor compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylori properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating bacterial infections and/or viral infections.
摘要翻译：本发明描述了新的亚硝化质子泵抑制剂化合物及其药学上可接受的盐，并且包含至少一种亚硝化质子泵抑制剂化合物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硝酸盐氧化物，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。本发明还提供了新组合物，其包含至少一种亚硝基化质子泵抑制剂化合物和至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的内皮衍生的松弛因子，刺激一氧化氮的内源合成或是底物用于一氧化氮合酶和/或至少一种治疗剂。本发明还提供了新型试剂盒，其包含至少一种亚硝化质子泵抑制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。本发明还提供了治疗胃肠疾病的方法; 促进溃疡愈合; 减少溃疡的复发; 改善质子泵抑制剂的胃保护特性，抗幽门螺杆菌特性或抗酸特性; 减少或减少与使用非甾体抗炎化合物相关的胃肠毒性; 治疗细菌感染和/或病毒感染。

2. 发明申请

WO2006091716A3 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：WO2006091716A3
公开(公告)日：2007-07-12
申请号：PCT/US2006006375
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。

3. 发明申请

WO2004004648A2 NITROSATED NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸化的非甾体抗炎药化合物，组合物和使用方法
公开(公告)号：WO2004004648A2
公开(公告)日：2004-01-15
申请号：PCT/US0321026
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： C07D295/08 , A61K31/21 , A61K31/405 , A61K31/445 , A61K45/00 , A61P1/00 , A61P1/04 , A61P1/10 , A61P1/14 , A61P3/04 , A61P17/02 , A61P25/28 , A61P27/02 , A61P29/00 , A61P35/00 , A61P35/02 , A61P43/00 , C07C203/04 , C07C205/40 , C07C205/56 , C07C219/10 , C07C229/42 , C07C235/08 , C07C235/12 , C07C235/34 , C07C235/42 , C07C237/08 , C07C243/28 , C07C271/16 , C07C271/64 , C07C291/02 , C07C311/17 , C07C317/18 , C07C317/32 , C07C317/46 , C07C323/12 , C07C327/28 , C07D209/18 , C07D209/28 , C07D211/22 , C07D211/56 , C07D493/04 , C07F9/40 , A61K
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：本发明描述了新的亚硝化非甾族抗炎药（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。本发明还提供了新组合物，其包含至少一种亚硝基化的NSAID和至少一种提供，转移或释放一氧化氮，提高内源性内皮水平的内皮衍生的松弛因子，刺激内源性合成一氧化氮或者是一氧化氮的底物合酶和/或至少一种治疗剂。本发明还提供了新颖的试剂盒，其包含至少一种亚硝化的NSAID和任选的至少一种一氧化氮供体和/或至少一种治疗剂。本发明还提供治疗炎症，疼痛和发热的方法; 用于治疗胃肠疾病; 用于促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠，肾和/或呼吸毒性; 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。

4. 发明申请

WO2004002409A3 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：WO2004002409A3
公开(公告)日：2004-08-19
申请号：PCT/US0319850
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： A61K31/415 , C07D231/12 , C07D261/08 , C07D401/04
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）选择性抑制剂的新型组合物，以及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，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。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。

5. 发明申请

WO03086282A2 NITRIC OXIDE DONORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸氧化物，组合物和使用方法
公开(公告)号：WO03086282A2
公开(公告)日：2003-10-23
申请号：PCT/US0310562
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： C07D295/10 , A61K31/095 , A61K31/10 , A61K31/13 , A61K31/16 , A61K31/166 , A61K31/17 , A61K31/19 , A61K31/215 , A61K31/216 , A61K31/275 , A61K31/357 , A61K31/4035 , A61K31/4166 , A61K31/4375 , A61K31/445 , A61K31/472 , A61K31/495 , A61K31/4965 , A61K31/505 , A61K31/662 , A61K45/00 , A61P1/04 , A61P3/10 , A61P5/14 , A61P7/00 , A61P7/02 , A61P9/00 , A61P9/10 , A61P9/12 , A61P11/00 , A61P13/12 , A61P17/00 , A61P19/02 , A61P21/04 , A61P25/00 , A61P29/00 , A61P35/00 , A61P35/02 , A61P37/06 , A61P37/08 , C07C313/36 , C07C323/03 , C07C323/08 , C07D209/48 , C07D211/22 , C07D211/54 , C07D211/86 , C07D213/74 , C07D217/02 , C07D217/04 , C07D233/02 , C07D233/96 , C07D239/42 , C07D239/46 , C07D241/08 , C07D241/24 , C07D241/28 , C07D295/155 , C07D317/22 , C07D453/02 , C07F9/38 , C07F9/40 , A61K
CPC分类号： C07D213/74 , C07C313/36 , C07C2602/08 , C07C2602/42 , C07C2603/74 , C07D211/54 , C07D217/02 , C07D233/96 , C07D239/47 , C07D241/08 , C07D241/24 , C07D295/155 , C07D317/22 , C07D453/02 , C07F9/383 , C07F9/4018
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 NO2 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.
摘要翻译：本发明描述了新一代氧化氮供体和包含至少一种一氧化氮供体的新型组合物。本发明还提供包含至少一种一氧化氮供体和任选的至少一种治疗剂的新型组合物。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，过度增殖，血管疾病; 用于减少瘢痕组织或抑制伤口收缩，特别是通过给予任选与至少一种治疗剂组合的一氧化氮供体的再狭窄的预防和/或治疗性治疗。本发明还提供了治疗炎症，疼痛，发热，胃肠道疾病，呼吸障碍和性功能障碍的方法。一氧化氮供体捐赠，转移或释放一氧化氮，和/或提升内源性内源性松弛因子水平，和/或刺激一氧化氮的内源性合成和/或是一氧化氮合成酶的底物，并能够释放一氧化氮或在生理条件下将一氧化氮间接递送或转移到靶位点。治疗剂可任选地被至少一种NO和/或NO 2基团取代（即亚硝基化和/或亚硝基化）。本发明还提供了包含至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物和试剂盒。

6. 发明申请

WO2005023183A3 NITROSATED AD NITROSYLATED DIURETIC COMPOUDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸酯化的硝酸酯化的药物组合物，组合物和使用方法
公开(公告)号：WO2005023183A3
公开(公告)日：2005-10-13
申请号：PCT/US2004026911
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： A61K20060101 , A61K31/4523 , A61K31/517 , A61K31/5415 , A61K31/549 , C07D211/00 , C07D285/22 , C07D295/00 , C07D307/00 , C07D417/12 , C07D417/14
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/或亚硝化化利尿化合物或其药学上可接受的盐，以及包含至少一种亚硝化和/或亚硝化化利尿化合物以及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本发明的任选亚硝化和/或亚硝基化的利尿化合物和任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂的新组合物和试剂盒。本发明还提供了用于（a）处理由过量的水和/或电解质保留引起的状况的方法; （b）治疗心血管疾病; （c）治疗肾血管性疾病; （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。

7. 发明申请

WO2007019448A2 NITRIC OXIDE ENHANCING ANGIOTENSIN II ANTAGONIST COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸氧化物增强ANGONTENSIN II拮抗剂化合物，组合物和使用方法
公开(公告)号：WO2007019448A2
公开(公告)日：2007-02-15
申请号：PCT/US2006030733
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： A61K31/4245 , A61K31/42 , A61K31/433
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; (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.
摘要翻译：本发明描述了包含至少一种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地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; （1）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。

8. 发明申请

WO2005030135A3 NITROSATED GLUTAMIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸谷氨酸化合物，组合物和使用方法
公开(公告)号：WO2005030135A3
公开(公告)日：2005-06-16
申请号：PCT/US2004031372
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： A61K20060101 , C07C229/24 , C07C237/12 , C07C271/22 , C07D295/185 , C07K5/06
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酸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酸化谷氨酸化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物。本发明还提供了包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型试剂盒。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γ-谷氨酰转肽酶的器官，细胞或组织。

9. 发明专利

DE60122939T2 未知
公开(公告)号：DE60122939T2
公开(公告)日：2007-01-11
申请号：DE60122939
申请日：2001-12-21
申请人： NITROMED INC
发明人： KHANAPURE P , GARVEY S , EARL A , EZAWA MAIKO , FANG XINQIN , GASTON D
IPC分类号： A61K31/36 , A61K31/10 , A61K31/357 , A61K31/443 , A61K31/4525 , A61K45/00 , A61K45/06 , A61P1/04 , A61P1/14 , A61P7/02 , A61P7/04 , A61P9/10 , A61P11/00 , A61P11/06 , A61P11/08 , A61P13/02 , A61P13/12 , A61P15/04 , A61P15/08 , A61P17/00 , A61P17/02 , A61P19/02 , A61P21/02 , A61P25/28 , A61P27/02 , A61P27/16 , A61P29/00 , A61P31/04 , A61P35/00 , A61P35/02 , A61P37/08 , A61P39/02 , A61P43/00 , C07C317/14 , C07C317/22 , C07C317/24 , C07D317/56 , C07D319/08 , C07D319/18 , C07D319/20 , C07D323/02 , C07D405/06 , C07D413/06
摘要： The invention describes novel substituted aryl compounds that are 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, optionally, at least one therapeutic agent, such as, steroids, nonsterodal anti-inflammatory 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, H2 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.

10. 发明专利

AT338544T 未知
公开(公告)号：AT338544T
公开(公告)日：2006-09-15
申请号：AT01998052
申请日：2001-12-21
申请人： NITROMED INC
发明人： KHANAPURE SUBHASH P , GARVEY DAVID S , EARL RICHARD A , EZAWA MAIKO , FANG XINQIN , GASTON RICKY D
IPC分类号： A61K31/10 , A61K31/357 , A61K31/36 , A61K31/443 , A61K31/4525 , A61K45/00 , A61K45/06 , A61P1/04 , A61P1/14 , A61P7/02 , A61P7/04 , A61P9/10 , A61P11/00 , A61P11/06 , A61P11/08 , A61P13/02 , A61P13/12 , A61P15/04 , A61P15/08 , A61P17/00 , A61P17/02 , A61P19/02 , A61P21/02 , A61P25/28 , A61P27/02 , A61P27/16 , A61P29/00 , A61P31/04 , A61P35/00 , A61P35/02 , A61P37/08 , A61P39/02 , A61P43/00 , C07C317/14 , C07C317/22 , C07C317/24 , C07D317/56 , C07D319/08 , C07D319/18 , C07D319/20 , C07D405/06 , C07D413/06 , C07D323/02
摘要： The invention describes novel substituted aryl compounds that are 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, optionally, at least one therapeutic agent, such as, steroids, nonsterodal anti-inflammatory 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, H2 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.

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