公开(公告)号：WO2005107384A3

公开(公告)日：2006-12-07

申请号：PCT/US2005010935

申请日：2005-03-31

申请人： NITROMED INC ,  WORCEL MANUEL

发明人： WORCEL MANUEL

IPC分类号： A01N33/26

CPC分类号： A61K31/198 ,  A61K31/21 ,  A61K31/34 ,  A61K31/502 ,  A61K45/06 ,  A61K2300/00

摘要： The invention describes methods for treating blood disorders or for treating the symptoms and/or complications associated with blood disorders by administering a therapeutically effective amount of at least one nitric oxide donor compound and optionally at least one antioxidant, or a pharmaceutically acceptable salt thereof, and/or at least one therapeutic agent. The antioxidant is preferably a hydralazine compound or a pharmaceutically acceptable salt thereof. The nitric oxide donor compound is preferably N-hydroxy-L-arginine and/or isosorbide dinitrate and/or isosorbide mononitrate. The blood disorder is preferably sickle cell anemia. The complication resulting from a blood disorder is preferably pulmonary hypertension.

摘要翻译： 本发明描述了通过施用治疗有效量的至少一种一氧化氮供体化合物和任选的至少一种抗氧化剂或其药学上可接受的盐来治疗血液病症或用于治疗与血液病症有关的症状和/或并发症的方法，以及 /或至少一种治疗剂。 抗氧化剂优选为肼azine嗪化合物或其药学上可接受的盐。 一氧化氮供体化合物优选为N-羟基-L-精氨酸和/或硝酸异山梨酯和/或一硝酸异山梨酯。 血液病最好是镰状细胞性贫血。 由血液病引起的并发症优选为肺动脉高压。

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。

公开(公告)号：WO2007041676A2

公开(公告)日：2007-04-12

申请号：PCT/US2006038956

申请日：2006-10-04

申请人： NITROMED INC ,  UNIV PITTSBURGH ,  WORCEL MANUEL ,  SABOLINSKI MICHAEL L ,  TAM SANG WILLIAM ,  MCNAMARA DENNIS M

发明人： WORCEL MANUEL ,  SABOLINSKI MICHAEL L ,  TAM SANG WILLIAM ,  MCNAMARA DENNIS M

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/118 ,  C12Q2600/156 ,  C12Q2600/172

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; (Ic) 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; or (r) treating cardiovascular diseases; in a patient in need thereof, wherein the patient has a -344 (T/T) polymorphism or a -344 (C/C) polymorphism in an aldosterone synthase CYPl1B2 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.

摘要翻译： 本发明提供了（a）降低与心力衰竭相关的死亡率的方法; （b）改善耗氧量; （c）治疗心力衰竭; （d）治疗高血压; （e）改善心力衰竭患者的生活质量; （f）抑制左心室重构; （g）减少与心力衰竭相关的住院; （h）提高运动耐力; （j）增加左室射血分数; （Ic）降低B型利尿钠蛋白水平; （1）治疗血管性疾病; （m）治疗终末期肾病; （n）减轻心脏肥大; （o）治疗由氧化应激引起的疾病; （p）治疗内皮功能障碍; （q）治疗由内皮功能障碍引起的疾病; 或（r）治疗心血管疾病; 在有需要的患者中，其中所述患者在醛固酮合酶CYP1B2基因中具有-344（T / T）多态性或-344（C / C）多态性，其包括给予所述患者（i）至少一种抗氧化剂化合物 或其药学上可接受的盐; （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，抗氧化剂是肼屈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/或单硝酸异山梨酯。

公开(公告)号：WO2006020244A3

公开(公告)日：2006-10-26

申请号：PCT/US2005025455

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： A61K38/00 ,  A61K31/135 ,  A61K31/34 ,  A61K31/35 ,  A61K31/40 ,  A61K31/495

CPC分类号： A61K31/15 ,  A61K31/34 ,  A61K31/502 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention is directed, in general, to methods for prolonging time to hospitalization for heart failure in a patient in need thereof which includes the administration to such patients of effective amounts of hydralazine hydrochloride and isosorbide dinitrate.

摘要翻译： 本发明总体上涉及延长有需要的患者心脏衰竭住院时间的方法，包括给予这些患者有效量的盐酸肼屈嗪和硝酸异山梨酯。

公开(公告)号：WO2006110601A2

公开(公告)日：2006-10-19

申请号：PCT/US2006013185

申请日：2006-04-07

申请人： NITROMED INC ,  UNIV PITTSBURGH ,  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 ,  C12Q1/68

CPC分类号： A61K31/34 ,  A61K31/502 ,  A61K45/06 ,  A61K2300/00

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.

摘要翻译： 本发明提供了（a）降低与心力衰竭相关的死亡率的方法; （b）提高耗氧量; （c）治疗心力衰竭; （d）治疗高血压; （e）改善心力衰竭患者的生活质量; （f）抑制左心室重构; （g）减少与心力衰竭有关的住院; （h）提高运动耐力; （j）增加左心室射血分数; （k）B型利尿钠蛋白水平降低; （1）治疗血管性疾病; （m）治疗终末期肾病; （n）减轻心脏肥大; （o）治疗由氧化应激引起的疾病; （p）治疗内皮功能障碍; （q）治疗由内皮功能障碍引起的疾病; （r）治疗心血管疾病; 在患有需要的患者中，其中所述患者在所述内皮一氧化氮合酶（NOS3）基因中具有至少一种多态性，其包括给予所述患者（i）至少一种抗氧化剂化合物或其药学上可接受的盐; （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，抗氧化剂是肼屈嗪化合物或其药学上可接受的盐，并且一氧化氮增强化合物是硝酸异山梨酯和/或一硝酸异山梨酯。

公开(公告)号：WO8807986A3

公开(公告)日：1988-12-01

申请号：PCT/FR8800188

申请日：1988-04-15

申请人： IRE CELLTARG SA ,  QUIVY JACQUES ,  ZEICHER MARC ,  WORCEL MANUEL

发明人： QUIVY JACQUES ,  ZEICHER MARC ,  WORCEL MANUEL

IPC分类号： C07H19/06 ,  A61K47/00 ,  A61K47/02 ,  A61K47/28 ,  A61K49/04 ,  A61K51/00 ,  A61K51/04 ,  C07B31/00 ,  C07B59/00 ,  C07C67/00 ,  C07D405/04 ,  C07J7/00 ,  A61K43/00 ,  A61K49/02

CPC分类号： A61K51/0493 ,  A61K2121/00

摘要： Compound useful particularly for the treatment by targetted radiotherapy or imaging of cancer, characterized in that the compound is comprised of a molecule susceptible of fixing itself or passing close to the DNA of the target cells, said molecule being radiolabelled with iodine 123. The invention also relates to new ligands specific of steroid hormone receivers useful for the targetted therapy or imaging particularly of cancer and presenting a structural base skeleton having the formula (I). According to the invention these ligands comprise particularly a) a hydroxyl or ketone function in position C3; b) a beta chloromethyl function on position C11; c) an alpha methyl or vinyl function on position C17 and d) a substituted radioactive iodine on an alkyl or alkenyl group attached to the skeleton, particularly methyl or vinyl.

公开(公告)号：WO2007041680A2

公开(公告)日：2007-04-12

申请号：PCT/US2006038964

申请日：2006-10-04

申请人： NITROMED INC ,  UNIV PITTSBURGH ,  WORCEL MANUEL ,  SABOLINSKI MICHAEL L ,  TAM SANG WILLIAM ,  MCNAMARA DENNIS M

发明人： WORCEL MANUEL ,  SABOLINSKI MICHAEL L ,  TAM SANG WILLIAM ,  MCNAMARA DENNIS M

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  A61K31/34 ,  A61K31/502 ,  A61K45/06 ,  C12Q2600/106 ,  C12Q2600/156 ,  A61K2300/00

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; or (r) treating cardiovascular diseases; in a patient in need thereof, wherein the patient has a Arg389Arg polymorphism and/or a Gly389Gly polymorphism in the beta 1 adrenergic receptor gene, compiising 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： 本发明提供了用于（a）降低与心力衰竭相关的死亡率的方法; （b）改善耗氧量; （c）治疗心力衰竭; （d）治疗高血压; （e）提高心力衰竭患者的生活质量; （f）抑制左心室重构; （g）减少与心力衰竭有关的住院治疗; （h）提高运动耐力; （j）增加左心室射血分数; （k）B型利钠肽蛋白水平降低; （1）治疗肾血管性疾病; （m）治疗终末期肾脏疾病; （n）减少心脏肿大; （o）治疗由氧化应激引起的疾病; （p）治疗内皮功能障碍; （q）治疗由内皮功能障碍引起的疾病; 或（r）治疗心血管疾病; 其中所述患者在所述β1肾上腺素能受体基因中具有Arg389Arg多态性和/或Gly389Gly多态性，包括向所述患者施用（i）至少一种抗氧化剂化合物或其药学上可接受的盐; （ii）至少一种一氧化氮增强化合物; 和（iii）任选地用于治疗心血管疾病的最佳当前疗法。 在一个实施方案中，所述抗氧化剂是肼屈嗪化合物或其药学上可接受的盐，并且所述一氧化氮增强化合物是二硝酸异山梨酯和/或单硝酸异山梨酯。

公开(公告)号：WO2007041676A3

公开(公告)日：2007-04-12

申请号：PCT/US2006/038956

申请日：2006-10-04

申请人： NITROMED, INC. ,  UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION ,  WORCEL, Manuel ,  SABOLINSKI, Michael, L. ,  TAM, Sang, William ,  McNAMARA, Dennis, M.

发明人： WORCEL, Manuel ,  SABOLINSKI, Michael, L. ,  TAM, Sang, William ,  McNAMARA, Dennis, M.

IPC分类号： C12Q1/68

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; (Ic) 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; or (r) treating cardiovascular diseases; in a patient in need thereof, wherein the patient has a -344 (T/T) polymorphism or a -344 (C/C) polymorphism in an aldosterone synthase CYPl1B2 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.

公开(公告)号：WO2005018561A3

公开(公告)日：2005-03-03

申请号：PCT/US2004/026909

申请日：2004-08-20

申请人： NITROMED, INC. ,  GARVEY, David, S. ,  LETTS, Gordon, L. ,  WORCEL, Manuel ,  GASTON, Ricky, D.

发明人： GARVEY, David, S. ,  LETTS, Gordon, L. ,  WORCEL, Manuel ,  GASTON, Ricky, D.

IPC分类号： A61K31/405

摘要： 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.

公开(公告)号：WO0049993A2

公开(公告)日：2000-08-31

申请号：PCT/US0004507

申请日：2000-02-23

申请人： NITROMED INC ,  GARVEY DAVID S ,  WORCEL MANUEL

发明人： GARVEY DAVID S ,  WORCEL MANUEL

IPC分类号： A61K31/58 ,  A61K45/06 ,  A61K47/48 ,  A61L27/54 ,  A61L29/16 ,  A61L31/16 ,  A61K

CPC分类号： A61K31/573 ,  A61K31/58 ,  A61K45/06 ,  A61K47/554 ,  A61K47/56 ,  A61L27/54 ,  A61L29/16 ,  A61L31/16 ,  A61L2300/114 ,  A61L2300/416

摘要： The present invention relates to nitrosated and/or nitrosylated steroids and to methods for the treatment of cardiovascular diseases and disorders, particularly the prophylactic and/or therapeutic treatment of restenosis, by administering nitrosated and/or nitrosylated steroids that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The methods for the treatment of cardiovascular diseases and disorders may further comprise administering at least one compound that donates, transfers, or releases nitric oxide and/or elevate endogenous nitric oxide or endothelium-derived relaxing factor in vivo and/or is a substrate for nitric oxide synthase.

摘要翻译： 本发明涉及亚硝化和/或亚硝基化的类固醇，以及通过施用能够释放一氧化氮的亚硝化和/或亚硝基化的类固醇来治疗心血管疾病和病症，特别是预防和/或治疗再狭窄的方法， 在生理条件下将一氧化氮间接递送或转移到目标部位。 用于治疗心血管疾病和病症的方法还可以包括在体内施用至少一种捐赠，转移或释放一氧化氮和/或提升内源性一氧化氮或内皮衍生的松弛因子的化合物和/或作为硝酸的底物 氧化物合酶。