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1. 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。

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

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。

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

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。

6. 发明申请

WO2004098538A3 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：WO2004098538A3
公开(公告)日：2005-03-31
申请号：PCT/US2004007943
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： A61K20060101 , A61K31/56 , A61K31/58 , C07J1/00 , C07J17/00 , C07J43/00
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。

7. 发明申请

WO2004010945A3 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：WO2004010945A3
公开(公告)日：2004-04-22
申请号：PCT/US0323605
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： A61K31/167 , A61K31/192 , A61K31/196 , A61K31/198 , A61K31/223 , A61K31/4015 , A61K31/405 , A61K31/415 , A61K31/422 , A61K31/427 , A61K31/4402 , A61K31/444 , A61K31/616 , A61K45/00 , A61P1/00 , A61P1/04 , A61P3/00 , A61P7/02 , A61P9/00 , A61P9/10 , A61P11/00 , A61P11/02 , A61P11/06 , A61P13/02 , A61P13/12 , A61P15/00 , A61P17/00 , A61P19/02 , A61P25/04 , A61P25/28 , A61P27/02 , A61P29/00 , A61P31/04 , A61P35/00 , A61P35/02 , A61P37/08 , A61P43/00 , C07D207/325 , C07D213/38 , C07D213/50 , C07D213/55 , C07D231/12 , C07D231/14 , C07D413/02 , C07D417/02 , A61K31/40 , A61K31/4155 , C07D231/06 , C07D237/14 , C07D401/04 , C07D403/04 , C07D405/04 , C07D413/04
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，提高内源性释放因子的内源水平，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。

8. 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。

9. 发明申请

WO2004002420A2 OXIME AND/OR HYDRAZONE CONTAINING NITROSATED AND/OR NITROSYLATED CYCLOOXIGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：含有硝化和/或硝化的环己糖合酶-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：WO2004002420A2
公开(公告)日：2004-01-08
申请号：PCT/US0320421
申请日：2003-06-30
申请人： NITROMED INC , GARVEY DAVID S , RANATUNGE RAMANI R , RICHARDSON STEWART K
发明人： GARVEY DAVID S , RANATUNGE RAMANI R , RICHARDSON STEWART K
IPC分类号： A61K31/415 , A61K45/00 , A61P1/00 , A61P1/04 , A61P7/00 , A61P7/02 , A61P9/00 , A61P9/10 , A61P11/00 , A61P11/02 , A61P11/06 , A61P13/00 , A61P13/02 , A61P13/12 , A61P15/00 , A61P17/00 , A61P19/02 , A61P25/00 , A61P25/02 , A61P25/28 , A61P27/02 , A61P29/00 , A61P31/00 , A61P35/00 , A61P37/08 , A61P43/00 , C07D231/12 , A61K
CPC分类号： C07D231/12
摘要： The invention describes novel cyclooxygenase 2(COX-2) selective inhibitors having at least one oxime group or hydrazone group and novel compositions comprising at least one cyclooxigenase 2(COX-2) selective inhibitor having at least one oxime group or hydrazone group, 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 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 cyclooxigenase 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 cyclooxigenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.
摘要翻译：本发明描述了具有至少一个肟基团或腙基团的新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种具有至少一个肟基团或腙基团的环氧合酶2（COX-2）选择性抑制剂的新型组合物，，至少一种捐赠，转移或释放一氧化氮的化合物，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。本发明还提供包含至少一种COX-2选择性抑制剂的新型试剂盒，所述抑制剂具有至少一个任选亚硝化和/或亚硝基化的肟基团或腙基团，和任选地至少一个一氧化氮供体，和/或任选地至少一种治疗剂。具有至少一个肟基团或腙基团的本发明的新型环氧合酶2选择性抑制剂可以任选被亚硝化和/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。

10. 发明申请

WO2006055542A3 DIURETIC COMPOUNDS COMPRISING HETEROCYCLIC NITRIC OXIDE DONOR GROUPS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：含有杂环氧化物离子基团的化合物，组合物和使用方法
公开(公告)号：WO2006055542A3
公开(公告)日：2006-09-08
申请号：PCT/US2005041321
申请日：2005-11-15
申请人： NITROMED INC , GARVEY DAVID S , RANATUNGE RAMANI R
发明人： GARVEY DAVID S , RANATUNGE RAMANI R
IPC分类号： C07D285/16 , A61K31/41 , A61K31/5375 , A61K31/54 , C07D269/00 , C07D295/00
CPC分类号： A61K31/541 , C07D271/08 , C07D413/12
摘要： The invention describes novel diuretic compounds comprising at least one heterocyclic nitric oxide donor group, or pharmaceutically acceptable salts thereof, and novel composition comprising at least one diuretic compound comprising at least one heterocyclic nitric oxide donor group, and optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention comprising at least one heterocyclic nitric oxide donor group, 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 oxidatives 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; and (p) treating sexual dysfunctions. The heterocyclic nitric oxide donors are preferably furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.
摘要翻译：本发明描述了包含至少一种杂环一氧化氮供体基团的新型利尿剂化合物或其药学上可接受的盐，以及包含至少一种包含至少一种杂环一氧化氮供体基团的至少一种利尿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。本发明还提供了包含至少一种本发明的利尿剂化合物的新型组合物和试剂盒，其包含至少一种杂环一氧化氮供体基团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）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; 和（p）治疗性功能障碍。杂环一氧化氮供体优选呋喃香糖，苏氨酸亚胺，氧杂三唑-5-酮和/或氧杂三唑-5-亚胺。

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