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    • 4. 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
    • WO2004098538A3
    • 2005-03-31
    • PCT/US2004007943
    • 2004-03-15
    • NITROMED INCEARL RICHARD AGARVEY DAVID SGASTON RICKY DLIN CHIA-ENRANATUNGE RAMANI RRICHARDSON STEWART KSTEVENSON CHERI A
    • EARL RICHARD AGARVEY DAVID SGASTON RICKY DLIN CHIA-ENRANATUNGE RAMANI RRICHARDSON STEWART KSTEVENSON CHERI A
    • A61K20060101A61K31/56A61K31/58C07J1/00C07J17/00C07J43/00
    • 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。
    • 6. 发明申请
    • NITROSATED AND NITROSYLATED CARDIOVASCULAR COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    • 硝酸和硝基化血管化合物,组合物和使用方法
    • WO2005018561A2
    • 2005-03-03
    • PCT/US2004026909
    • 2004-08-20
    • NITROMED INCGARVEY DAVID SLETTS GORDON LWORCEL MANUELGASTON RICKY D
    • GARVEY DAVID SLETTS GORDON LWORCEL MANUELGASTON RICKY D
    • A61K20060101A61K31/405A61K31/44A61K31/535C07D209/04C07D221/02C07D415/00A61K
    • C07D493/04C07D407/04C07K5/06026
    • The invention describes novel nitrosated and/or nitrosylated cardiovascular compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated cardiovascular 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 cardiovascular 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 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; and (k) treating nephropathy. The nitrosated and/or nitrosylated cardiovascular compounds are preferably nitrosated and/or nitrosylated P-adrenergic antagonists, nitrosated and/or nitrosylated angiotensin­converting enzyme (ACE) inhibitors, nitrosated and/or nitrosylated anti-hyperlipidemic compounds, and nitrosated and/or nitrosylated antithrombotic and vasodilator compounds.
    • 本发明描述了新的亚硝化和/或亚硝基化的心血管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/或亚硝基化的心血管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组合物 。 本发明还提供了包含至少一种本发明的心血管化合物,其任选被亚硝化和/或亚硝基化的新组合物和试剂盒,以及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(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; 和(k)治疗肾病。 亚硝化和/或亚硝基化的心血管化合物优选为亚硝化和/或亚硝化的P-肾上腺素能拮抗剂,亚硝化和/或亚硝化的血管紧张素转换酶(ACE)抑制剂,亚硝化和/或亚硝化的抗高脂血症化合物,以及亚硝化和/或亚硝化的抗血栓形成和/ 血管扩张剂化合物。