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1. 发明申请

WO2007120555A2 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF THE GENETIC VARIATION OF G-PROTEIN BETA 3 SUBUNIT POLYMORPHISM 审中-公开
标题翻译：遗传遗传危害评估：G蛋白β亚基多态性遗传变异的影响
公开(公告)号：WO2007120555A2
公开(公告)日：2007-10-25
申请号：PCT/US2007/008426
申请日：2007-04-04
申请人： NITROMED, INC, , UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION , WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
发明人： WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
IPC分类号： A61K31/21
CPC分类号： A61K31/21 , A61K31/34 , A61K31/502 , A61K45/06 , A61K2300/00
摘要： The invention provides methods for treating various indications and diseases in a patient in need thereof, wherein the patient has a C825T polymorphism in the G protein beta3 subunit (GNB3), comprising administering to the patient (i) at least one antioxidant compound or a pharmaceutically acceptable salt thereof; (ii) at least one nitric oxide enhancing compound; and (iii) optionally the best current therapy for the treatment of cardiovascular diseases. In one embodiment the antioxidant is a hydralazine compound or a pharmaceutically acceptable salt thereof and the nitric oxide enhancing compound is isosorbide dinitrate and/or isosorbide mononitrate.
摘要翻译：本发明提供了在有需要的患者中治疗各种适应症和疾病的方法，其中所述患者在G蛋白β3亚基（GNB3）中具有C825T多态性，其包括给予所述患者（i）至少一种抗氧化剂化合物或药学上其可接受的盐; （ii）至少一种一氧化氮增强化合物; 和（iii）任选的治疗心血管疾病的最佳治疗方法。在一个实施方案中，抗氧化剂是肼azine嗪化合物或其药学上可接受的盐，一氧化氮增强化合物是硝酸异山梨酯和/或硝酸异山梨酯。

2. 发明申请

WO2007016677A2 NITRIC OXIDE ENHANCING ANTIMICROBIAL COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸氧化物增强抗微生物化合物，组合物和使用方法
公开(公告)号：WO2007016677A2
公开(公告)日：2007-02-08
申请号：PCT/US2006/030287
申请日：2006-08-02
申请人： NITROMED, INC. , ELLIS, James, L. , GARVEY, David, S.
发明人： ELLIS, James, L. , GARVEY, David, S.
IPC分类号： A61K31/5377
CPC分类号： C07D417/12 , C07D215/56 , C07D401/04 , C07D417/14 , C07D471/04 , C07D477/26
摘要： The invention describes compositions and kits comprising at least one nitric oxide enhancing group antimicrobial compound, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitric oxide enhancing antimicrobial 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 bacterial infections; (b) treating viral infections; (c) treating fungal infections; and (d) treating lesions. The antimicrobial compounds of the invention are preferably tobramycin, aztreonam, ciprofloxacin and doripenam. The nitric oxide enhancing antimicrobial compounds are substituted with at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group. The nitric oxide enhancing groups are nitroxides and/or heterocyclic nitric oxide donors. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines. In one embodiment the methods of the invention are for the treatment of bacterial infections associated with pulmonary diseases such as cystic fibrosis and for treating Bacillus anthracis infections.
摘要翻译：本发明描述了包含至少一种一氧化氮增强组抗微生物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抗微生物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（a）治疗细菌感染的方法; （b）治疗病毒感染; （c）治疗真菌感染; 和（d）治疗病变。本发明的抗微生物化合物优选为妥布霉素，氨曲南，环丙沙星和多瑞培南。一氧化氮增强抗微生物化合物被至少一个杂环一氧化氮供体基团和/或至少一个氮氧化物基团取代。一氧化氮增强基团是氮氧化物和/或杂环一氧化氮供体。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。在一个实施方案中，本发明的方法用于治疗与肺部疾病如囊性纤维化相关的细菌感染和用于治疗炭疽芽孢杆菌感染。

3. 发明申请

WO2007016095A2 CYCLOOXYGENASE-2 SELECTIVE INHIBITOR COMPOUNDS COMPRISING NITRIC OXIDE ENHANCING GROUPS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：包含氮氧化物增强组合物的CYCLOOXYGENASE-2选择性抑制剂化合物，组合物和使用方法
公开(公告)号：WO2007016095A2
公开(公告)日：2007-02-08
申请号：PCT/US2006/028856
申请日：2006-07-26
申请人： NITROMED, INC. , GARVEY, David, S.
发明人： GARVEY, David, S.
IPC分类号： A61K31/415
CPC分类号： C07C229/42
摘要： The invention describes compositions and kits comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor comprising at least one nitric oxide enhancing group, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor comprising at least one nitric oxide enhancing 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 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 cyclooxygenase 2 selective inhibitors of the invention are 2(2-((2-chloro-6-fluorophenyl) amino)5-methylphenyl)acetic acid derivatives comprising at least one nitric oxide enhancing group. The nitric oxide enhancing groups are nitroxides and/or heterocyclic nitric oxide donors.
摘要翻译：本发明描述了包含至少一种包含至少一种一氧化氮增强基团的环氧合酶2（COX-2）选择性抑制剂或其药学上可接受的盐的组合物和试剂盒，以及包含至少一种环氧合酶2（COX-2）选择性抑制剂包括至少一种一氧化氮增强基团，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）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。本发明的环氧合酶2选择性抑制剂是包含至少一种一氧化氮增强基团的2（2 - （（2-氯-6-氟苯基）氨基）5-甲基苯基）乙酸衍生物。一氧化氮增强基团是氮氧化物和/或杂环一氧化氮供体。

4. 发明申请

WO2006110601A3 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF THE GENETIC VARIATION OF NOS3 审中-公开
公开(公告)号：WO2006110601A3
公开(公告)日：2006-10-19
申请号：PCT/US2006/013185
申请日：2006-04-07
申请人： NITROMED, INC. , UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION , WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
发明人： WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
IPC分类号： A01N33/24 , A61K31/13
摘要： The invention provides methods for (a) reducing mortality associated with heart failure; (b) improving oxygen consumption; (c) treating heart failure; (d) treating hypertension; (e) improving the quality of life in a heart failure patient; (f) inhibiting left ventricular remodeling; (g) reducing hospitalizations related to heart failure; (h) improving exercise tolerance; (j) increasing left ventricular ejection fraction; (k) decreasing levels of B-type natriuretic protein; (1) treating renovascular diseases; (m) treating end-stage renal diseases; (n) reducing cardiomegaly; (o) treating diseases resulting from oxidative stress; (p) treating endothelial dysfunctions; (q) treating diseases caused by endothelial dysfunctions; (r) treating cardiovascular diseases; in a patient in need thereof, wherein the patient has at least one polymorphism in the endothelial nitric oxide synthase (NOS3) gene, comprising administering to the patient (i) at least one antioxidant compound or a pharmaceutically acceptable salt thereof; (ii) at least one nitric oxide enhancing compound; and (iii) optionally the best current therapy for the treatment of cardiovascular diseases. In one embodiment the antioxidant is a hydralazine compound or a pharmaceutically acceptable salt thereof and the nitric oxide enhancing compound is isosorbide dinitrate and/or isosorbide mononitrate.

5. 发明申请

WO2006041855A3 COMPOSITIONS AND METHODS USING APOCYNIN COMPOUNDS AND NITRIC OXIDE DONORS 审中-公开
标题翻译：使用APOCYNIN化合物和氮氧化物的组合物和方法
公开(公告)号：WO2006041855A3
公开(公告)日：2006-10-12
申请号：PCT/US2005035715
申请日：2005-10-03
申请人： NITROMED INC , GARVEY DAVID S
发明人： GARVEY DAVID S
IPC分类号： A61K31/21 , A61K31/04 , A61K31/12 , A61K31/13
CPC分类号： A61K31/12 , A61K31/198 , A61K2300/00
摘要： The invention describes novel compositions comprising at least one apocynin compound or a pharmaceutically acceptable salt thereof, and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The invention also provides novel kits comprising at least one apocynin compound or a pharmaceutically acceptable salt thereof, and at least one nitric oxide donor compound, and, optionally, 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 gastrointestinal disorders; (h) treating inflammatory disorders; (j) treating respiratory disorders; and (k) treating peripheral vascular diseases. The apocynin compound may be apocynin. The nitric oxide donor compound may be isosorbide dinitrate and/or isosorbide mononitrate.
摘要翻译：本发明描述了包含至少一种助播肽化合物或其药学上可接受的盐和至少一种一氧化氮供体以及任选的至少一种治疗剂的新型组合物。本发明还提供了包含至少一种助播肽化合物或其药学上可接受的盐以及至少一种一氧化氮供体化合物和任选的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）治疗胃肠疾病; （h）治疗炎症性疾病; （j）治疗呼吸系统疾病; 和（k）治疗外周血管疾病。 apocynin化合物可以是apocynin。一氧化氮供体化合物可以是硝酸异山梨酯和/或单硝酸异山梨酯。

6. 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。

7. 发明申请

WO2006093864A1 CARDIOVASCULAR COMPOUNDS COMPRISING NITRIC OXIDE ENHANCING GROUPS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：包含氧化亚铁增强组合物的心血管化合物，组合物和使用方法
公开(公告)号：WO2006093864A1
公开(公告)日：2006-09-08
申请号：PCT/US2006/006843
申请日：2006-02-28
申请人： NITROMED, INC. , GARVEY, David, S.
发明人： GARVEY, David, S.
IPC分类号： C07D257/04 , A61K31/41
CPC分类号： C07D409/06 , C07D233/84 , C07D235/20 , C07D257/04 , C07D403/10 , C07D405/06 , C07D405/12 , C07D409/14 , C07D471/04 , C07D487/04
摘要： The invention describes compositions and kits comprising at least one cardiovascular compound comprising at least one nitric oxide enhancing group, 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 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; Q) 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 cardiovascular compounds are angiotensin II antagonists, aldosterone antagonists, endothelin antagonists, hydralazine compounds, neutral endopeptidase inhibitors and renin inhibitors. The nitric oxide enhancing groups are nitroxides and/or heterocyclic nitric oxide donors.
摘要翻译：本发明描述了包含至少一种包含至少一种一氧化氮增强基团的心血管化合物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。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; Q）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。心血管化合物是血管紧张素II拮抗剂，醛固酮拮抗剂，内皮素拮抗剂，肼屈嗪化合物，中性内肽酶抑制剂和肾素抑制剂。一氧化氮增强基团是氮氧化物和/或杂环一氧化氮供体。

8. 发明申请

WO2006020244A2 COMPOSITIONS AND METHODS RELATED TO HEART FAILURE 审中-公开
标题翻译：与心脏失效相关的组合物和方法
公开(公告)号：WO2006020244A2
公开(公告)日：2006-02-23
申请号：PCT/US2005/025455
申请日：2005-07-18
申请人： NITROMED, INC. , WORCEL, Manuel , SABOLINSKI, Michael, L.
发明人： WORCEL, Manuel , SABOLINSKI, Michael, L.
IPC分类号： A61K31/34 , A61K31/15
CPC分类号： A61K31/15 , A61K31/34 , A61K31/502 , A61K45/06 , A61K2300/00
摘要： The invention provides methods for (a) prolonging time to hospitalization for heart failure; (b) prolonging time to first hospitalization for heart failure; (c) reducing the total number of days a patient with heart failure spends in the hospital for heart failure for a single hospital stay (i.e., reducing the duration of a single hospital stay for a patient with heart failure); (d) reducing the total number of days a patient spends in the hospital for heart failure for multiple hospital stays (i.e., two or more hospital stays); (e) reducing the number of hospital admissions for heart failure; (f) reducing mortality and reducing hospitalizations for heart failure (e.g., the total number of days in the hospital and/or the number of hospital visits); (g) increasing the left ventricular ejection fraction in a heart failure patient; (h) treating a sexual dysfunction (e.g., erectile dysfunction and female sexual dysfunction) (j) treating a headache in a heart failure patient by administering a non-steroidal antiinflammary compound (i.e., NSAIDs); (k) treating a heart failure patient who has a history of hypertension (but who is not currently diagnosed with hypertension); (1) improving the quality of life in a heart failure patient based on the Minnesota Living with heart failure questionnaire; (m) decreasing the levels of B-type natriuretic peptide; (n) treating hypertension in a heart failure patient; (o) lowering blood pressure in a heart failure patient; (p) treating labile hypertension; (q) treating idiopathic hypertension; (r) increasing patient compliance with medication dosing in a heart failure patient; (s) treating hypertension in a patient with a dilated heart; (t) treating ischemic disease and/or coronary artery disease; and (u) reducing cardiomegaly in a patient in need thereof comprising administering to the patient a therapeutically effective amount of (i) a hydralazine compound or pharmaceutically acceptable salt thereof, (ii) isosorbide dinitrate and/or isosorbide mononitrate, and (iii) optionally at least one compound selected from the group consisting of angiotensin converting enzyme inhibitors, ß-adrenergic antagonists, angiotensin II antagonists, aldosterone antagonists, cardiac glucosides (digitalis), and diuretic compounds.
摘要翻译：本发明提供了（a）延长心力衰竭住院时间的方法; （b）延长首次住院心脏衰竭的时间; （c）减少患有心力衰竭的患者在医院心脏衰竭的总天数，用于单次住院（即减少患有心力衰竭的患者的单次住院时间）; （d）减少病人在医院内为多次住院（即两个或两个以上住院期间）心衰的总天数; （e）减少住院心脏病的人数; （f）减少死亡率和减少心力衰竭的住院时间（例如医院总天数和/或住院次数）; （g）增加心力衰竭患者的左心室射血分数; （h）治疗性功能障碍（例如勃起功能障碍和女性性功能障碍）（j）通过施用非甾体抗炎症化合物（即NSAIDs）治疗心力衰竭患者的头痛; （k）治疗具有高血压病史（但目前尚未被诊断患有高血压症）的心力衰竭患者; （1）提高基于明尼苏达州心力衰竭问卷调查问卷的心力衰竭患者的生活质量; （m）降低B型利尿钠肽的含量; （n）治疗心力衰竭患者的高血压; （o）降低心力衰竭患者的血压; （p）治疗不稳定性高血压; （q）治疗特发性高血压; （r）增加患者对心力衰竭患者药物剂量的依从性; 在患有心脏扩张的患者中治疗高血压; （t）治疗缺血性疾病和/或冠状动脉疾病; 和（u）减少患有需要的患者的心脏肿大，其包括向患者施用治疗有效量的（i）肼屈嗪化合物或其药学上可接受的盐，（ii）硝酸异山梨酯和/或硝酸异山梨酯，和（iii）任选地选自血管紧张素转换酶抑制剂，β-肾上腺素能拮抗剂，血管紧张素II拮抗剂，醛固酮拮抗剂，心脏葡萄糖苷（洋地黄）和利尿剂的至少一种化合物。

9. 发明申请

WO2005060603A3 NITRIC OXIDE RELEASING PYRUVATE COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：氮氧化物释放吡咯化合物，组合物和使用方法
公开(公告)号：WO2005060603A3
公开(公告)日：2005-12-01
申请号：PCT/US2004041069
申请日：2004-12-10
申请人： NITROMED INC , GARVEY DAVID S , XINQIN FANG , SUBHASH P KHANAPURE , RAMANI R RANATUNGA , SHIOW-JYI WEY
发明人： GARVEY DAVID S , XINQIN FANG , SUBHASH P KHANAPURE , RAMANI R RANATUNGA , SHIOW-JYI WEY
IPC分类号： C07C203/04 , C07C219/22 , C07C233/05 , C07C235/74 , C07D211/38 , C07D211/46
CPC分类号： C07C203/04 , C07C219/22 , C07C235/74 , C07D211/46 , C07D271/08 , C07D273/00 , C07D333/32
摘要： The invention describes novel pyruvate compounds comprising at least one nitric oxide releasing group and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one pyruvate compound comprising at least one nitric oxide releasing group, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one pyruvate compound and at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one pyruvate compound, that is optionally substituted with at least one nitric oxide releasing group, and, optionally, at least one nitric oxide donor 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) reperfusing injury following ischemia; and/or (m) preserving tissues, organs, organ parts and/or limbs. The nitric oxide releasing group is preferably a nitro group (i.e. N0.2.), a nitroso group (i.e. NO) and/or a heterocyclic nitric oxide donor group. The heterocyclic nitric oxide donor group is preferably a furoxan, a sydnonimine, an oxatriazole-5-one and/or an oxatriazole-5-imine.
摘要翻译：本发明描述了包含至少一种一氧化氮释放基团及其药学上可接受的盐的新的丙酮酸盐化合物，以及包含至少一种包含至少一种一氧化氮释放基团的丙酮酸盐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丙酮酸化合物和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组合物。本发明还提供了包含至少一种丙酮酸盐化合物的新试剂盒，所述丙酮酸盐化合物任选被至少一种一氧化氮释放基团取代，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（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）缺血后再灌注损伤; 和/或（m）保存组织，器官，器官部分和/或肢体。一氧化氮释放基团优选为硝基（即N0.2。），亚硝基（即NO）和/或杂环一氧化氮供体基团。杂环一氧化氮供体基团优选为呋喃糖，苏氨酸，恶唑-5-酮和/或氧杂三唑-5-亚胺。

10. 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。

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