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    • 6. 发明申请
    • NITROSATED AND NITROSYLATED COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    • 硝基和硝基化合物,组合物和使用方法
    • WO2004098538A2
    • 2004-11-18
    • PCT/US2004/007943
    • 2004-03-15
    • NITROMED, INC.EARL, Richard, A.GARVEY, David, S.GASTON, Ricky, D.LIN, Chia-EnRANATUNGE, Ramani, R.RICHARDSON, Stewart, K.STEVENSON, Cheri, A.
    • EARL, Richard, A.GARVEY, David, S.GASTON, Ricky, D.LIN, Chia-EnRANATUNGE, Ramani, R.RICHARDSON, Stewart, K.STEVENSON, Cheri, A.
    • A61K
    • C07J17/00C07J1/00C07J31/006C07J41/0044C07J43/00C07J43/003
    • 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.
    • 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。
    • 8. 发明申请
    • CYCLOOXYGENASE- 2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE
    • CYCLOOXYGENASE-2选择性抑制剂,组合物和使用方法
    • WO2004010945A2
    • 2004-02-05
    • PCT/US2003/023605
    • 2003-07-29
    • NITROMED, INC.GARVEY, David, S.KHANAPURE, Subhash, P.RANATUNGE, Ramani, R.RICHARDSON, Stewart, K.SCHROEDER, Joseph, D.
    • GARVEY, David, S.KHANAPURE, Subhash, P.RANATUNGE, Ramani, R.RICHARDSON, Stewart, K.SCHROEDER, Joseph, D.
    • A61K
    • C07D213/55C07D213/50C07D231/12C07D231/14
    • 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.
    • 本发明描述了新颖的环加氧酶2(COX-2)选择性抑制剂和包含至少一种环氧合酶2(COX-2)选择性抑制剂和任选地至少一种化合物的新型组合物, 或释放一氧化氮,刺激一氧化氮的内源性合成,提高内皮细胞和内皮细胞水平的内皮细胞衍生的舒张因子或是一氧化氮合酶的底物,和/或至少一种治疗剂。 本发明还提供了包含至少一种选择性抑制剂(任选亚硝化和/或亚硝基化)和任选地至少一种一氧化氮供体和/或任选地至少一种治疗剂的新型试剂盒。 本发明的新型环加氧酶2选择性抑制剂可以任选地亚硝化和/或亚硝基化。 本发明还提供治疗炎症,疼痛和发热的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性; 用于促进伤口愈合; 用于治疗和/或预防肾和/或呼吸毒性; 用于治疗和/或预防由环氧合酶-2水平升高引起的其他疾病; 并用于改善COX-2选择性抑制剂的心血管特征。
    • 9. 发明申请
    • DIURETIC COMPOUNDS COMPRISING HETEROCYCLIC NITRIC OXIDE DONOR GROUPS, COMPOSITIONS AND METHODS OF USE
    • 包含杂环氧化氮供体组的化合物,组合物和使用方法
    • WO2006055542A2
    • 2006-05-26
    • PCT/US2005/041321
    • 2005-11-15
    • NITROMED, INC.GARVEY, David, S.RANATUNGE, Ramani, R.
    • GARVEY, David, S.RANATUNGE, Ramani, R.
    • A61K31/541
    • A61K31/541C07D271/08C07D413/12
    • 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.
    • 本发明描述了包含至少一个杂环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个杂环氧化氮供体基团的利尿化合物的新组合物, 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。 本发明还提供了包含至少一种本发明的利尿化合物的新型组合物和药盒,其包含至少一种杂环氧化氮供体基团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; (1)治疗肾病; (m)治疗外周血管疾病; (n)治疗门静脉高压症; (o)治疗中枢神经系统疾病; 和(p)治疗性功能障碍。 杂环氧化氮供体优选为氧化呋喃,sydnonimines,恶三唑-5-酮和/或恶三唑-5-亚胺。
    • 10. 发明申请
    • FUROXAN COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    • 呋喃类化合物,组合物和使用方法
    • WO2007059311A2
    • 2007-05-24
    • PCT/US2006/044680
    • 2006-11-16
    • NITROMED, INC.GARVEY, David, S.RANATUNGE, Ramani, R.
    • GARVEY, David, S.RANATUNGE, Ramani, R.
    • A61K31/445
    • C07D271/08
    • The invention provides novel furoxan compounds, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The inventio also provides methods for (a) treating cardiovascular diseases; (b) inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device; (c) treating pathological conditions resulting from abnormal cell proliferation; (d) treating transplantation rejections, (e) treating autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; (f) reducing scar tissue or for inhibiting wound contraction; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; and (j) treating diseases caused by endothelial dysfunctions.
    • 本发明提供了新型呋喃咯烷化合物或其药学上可接受的盐以及包含至少一种化合物和任选的至少一种促氧化氮化合物和/或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。 本发明还提供了用于(a)治疗心血管疾病的方法; (b)抑制由血液暴露于医疗装置引起的血小板聚集和血小板粘附; (c)治疗由异常细胞增殖引起的病理状况; (d)治疗移植排斥,(e)治疗自身免疫,炎症,增殖,过度增殖或血管疾病; (f)减少疤痕组织或抑制伤口收缩; (g)治疗由氧化应激引起的疾病; (h)治疗内皮功能障碍; 和(j)治疗由内皮功能障碍引起的疾病。