公开(公告)号：WO2007075541A3

公开(公告)日：2008-11-27

申请号：PCT/US2006048193

申请日：2006-12-19

申请人： NITROMED INC ,  GARVEY DAVID S

发明人： GARVEY DAVID S

IPC分类号： A01N65/00 ,  A61K36/00

CPC分类号： A61K31/4245

摘要： The invention provides novel compositions and kits comprising at least one nitric oxide enhancing glutamic acid compound, or a pharmaceutically acceptable salt 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; (j) treating osteoporosis; (k) treating nephropathy; (1) treating peripheral vascular diseases; (m) treating portal hypertension; (n) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (o) targeting the delivery of compounds and nitric oxide to organs, cells or tissues that contain the enzyme gamma-glutamyl transpeptidase. The nitric oxide enhancing glutamic acid compounds comprise at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group.

摘要翻译： 本发明提供了包含至少一种一氧化氮增强型谷氨酸化合物或其药学上可接受的盐，以及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）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; （n）治疗由γ-谷氨酰转肽酶水平升高引起的疾病，和（o）靶向化合物和一氧化氮向含有γ-谷氨酰转肽酶的器官，细胞或组织的递送。 一氧化氮增强型谷氨酸化合物包含至少一种杂环一氧化氮供体基团和/或至少一种氮氧自由基。

公开(公告)号：WO2007123818A2

公开(公告)日：2007-11-01

申请号：PCT/US2007/008427

申请日：2007-04-04

申请人： NITROMED, INC. ,  GARVEY, David, S.

发明人： GARVEY, David, S.

IPC分类号： A61K31/4245

CPC分类号： C07C405/00 ,  C07C2601/08 ,  C07C2601/10 ,  C07D207/40 ,  C07D211/28 ,  C07D211/54 ,  C07D211/94 ,  C07D213/82 ,  C07D413/04 ,  C07D413/12 ,  C07D453/02

摘要： The invention provides compositions and kits comprising at least one organic nitric oxide enhancing salt of a prostaglandin, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods, for'(a) treating ophthalmic disorders; (b) treating cerebrovascular disorders; (c) treating cardiovascular disorders; (d) treating benign prostatic hyperplasia (BPH); (e) treating peptic ulcers; (e) treating sexual dysfunctions and (f) inducing abortions. The organic nitric oxide enhancing compounds that form salts with the prostaglandins 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： 本发明提供了包含前列腺素的至少一种有机一氧化氮增强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）治疗眼科疾病的方法， （b）治疗脑血管障碍; （c）治疗心血管疾病; （d）治疗良性前列腺增生（BPH）; （e）治疗消化性溃疡; （e）治疗性功能障碍和（f）诱导堕胎。 与前列腺素形成盐的有机一氧化氮增强化合物是有机硝酸盐，有机亚硝酸盐，亚硝基硫醇，硫堇啶，硫堇酸盐，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。

公开(公告)号：WO2007086884A3

公开(公告)日：2007-08-02

申请号：PCT/US2006/005416

申请日：2006-02-16

申请人： NITROMED, INC. ,  ELLIS, James, L. ,  GARVEY, David, S. ,  LIN, Chia-En

发明人： ELLIS, James, L. ,  GARVEY, David, S. ,  LIN, Chia-En

IPC分类号： A01N43/04 ,  C07D277/00 ,  A61K31/44 ,  A61K31/70 ,  C07H15/00 ,  C07H17/00 ,  C07H5/04 ,  C07H5/06

摘要： The invention describes novel organic nitric oxide donor salts of a antimicrobial . compounds, and novel compositions and kits comprising at least one organic nitric oxide donor salt of an 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. In one embodiment the antimicrobial compounds of the invention are aztreonam, ciprofloxacin, doripenam, duramycin and tobramycin. The organic nitric oxide donors that form salts are preferably organic nitrates, organic nitrites, nitrosothiols, thionitrites and heterocyclic nitric oxide donors. The heterocyclic nitric oxide donors are preferably furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines. The methods of the invention are preferably for the treatment of bacterial infections associated with pulmonary diseases such as cystic fibrosis and for treating Bacillus anthracis infections.

公开(公告)号：WO2007075541A2

公开(公告)日：2007-07-05

申请号：PCT/US2006/048193

申请日：2006-12-19

申请人： NITROMED, INC. ,  GARVEY, David, S.

发明人： GARVEY, David, S.

IPC分类号： A61K31/4245

CPC分类号： A61K31/4245

摘要： The invention provides novel compositions and kits comprising at least one nitric oxide enhancing glutamic acid compound, or a pharmaceutically acceptable salt 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; (j) treating osteoporosis; (k) treating nephropathy; (1) treating peripheral vascular diseases; (m) treating portal hypertension; (n) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (o) targeting the delivery of compounds and nitric oxide to organs, cells or tissues that contain the enzyme gamma-glutamyl transpeptidase. The nitric oxide enhancing glutamic acid compounds comprise at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group.

摘要翻译： 本发明提供了包含至少一种一氧化氮增强型谷氨酸化合物或其药学上可接受的盐，以及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）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; （n）治疗由γ-谷氨酰转肽酶水平升高引起的疾病，和（o）靶向化合物和一氧化氮向含有γ-谷氨酰转肽酶的器官，细胞或组织的递送。 一氧化氮增强型谷氨酸化合物包含至少一种杂环一氧化氮供体基团和/或至少一种氮氧自由基。

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。

公开(公告)号：WO2006091716A2

公开(公告)日：2006-08-31

申请号：PCT/US2006/006375

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。

公开(公告)号：WO2004010945A2

公开(公告)日：2004-02-05

申请号：PCT/US2003/023605

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： A61K

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。

公开(公告)号：WO2004004648A3

公开(公告)日：2004-01-15

申请号：PCT/US2003/021026

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： C07D333/22

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.

公开(公告)号：WO2004002420A3

公开(公告)日：2004-01-08

申请号：PCT/US2003/020421

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： C07C251/32

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.

公开(公告)号：WO2003103602A3

公开(公告)日：2003-12-18

申请号：PCT/US2003/018052

申请日：2003-06-10

申请人： NITROMED, INC. ,  LETTS, L., Gordon ,  GARVEY, David, S.

发明人： LETTS, L., Gordon ,  GARVEY, David, S.

IPC分类号： A61K31/34

摘要： The invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated 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, optionally, at least one therapeutic agent. The invention also provides novel compositions comprising at least one COX-2 selective inhibitor, that is optionally sitrosated and/or nitrosylated, 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 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. 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 are preferably 2(2-((2-chloro-6-fluorophenyl) amino)5-methylphenyl)acetic acid and nitrosated derivatives thereof.