公开(公告)号：EP1943361A2

公开(公告)日：2008-07-16

申请号：EP06825494.5

申请日：2006-10-04

申请人： Nitromed, Inc. ,  University of Pittsburgh of the Commonwealth System of Higher Education

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.

公开(公告)号：EP1945030A2

公开(公告)日：2008-07-23

申请号：EP06816322.9

申请日：2006-10-04

申请人： Nitromed, Inc. ,  University of Pittsburgh of the Commonwealth System of Higher Education

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

IPC分类号： A01N43/58

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.

公开(公告)号：EP1246621A1

公开(公告)日：2002-10-09

申请号：EP00989422.1

申请日：2000-12-22

申请人： Nitromed, Inc.

发明人： BANDARAGE, Ramani, R. ,  BANDARAGE, Upul, K. ,  FANG, Xinqin ,  GARVEY, David, S. ,  LETTS, L., Gordon ,  SCHROEDER, Joseph, D. ,  TAM, Sang, William

IPC分类号： A61K31/40 ,  A61K31/415 ,  A61K31/421 ,  A61K31/50 ,  C07D207/325 ,  C07D231/06 ,  C07D237/14 ,  C07D263/04 ,  C07D263/06

CPC分类号： C07D207/333 ,  C07C317/46 ,  C07C381/00 ,  C07D209/12 ,  C07D209/18 ,  C07D231/12 ,  C07D231/14 ,  C07D233/64 ,  C07D237/14 ,  C07D261/08 ,  C07D263/20 ,  C07D307/58 ,  C07D311/12 ,  C07D413/12 ,  C07D471/04

摘要： The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound taht 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, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2 antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.

公开(公告)号：EP1154771A1

公开(公告)日：2001-11-21

申请号：EP00910039.7

申请日：2000-02-25

申请人： Nitromed, Inc.

发明人： GARVEY, David, S. ,  LETTS, L., Gordon ,  TAM, Sang, William ,  WANG, Tiansheng ,  RICHARDSON, Stewart, K.

IPC分类号： A61K31/437 ,  A61K31/4184 ,  A61K31/4439 ,  C07D471/04 ,  C07D401/12 ,  C07D235/28

CPC分类号： C07D401/12 ,  A61K31/00 ,  A61K31/4184 ,  A61K31/433 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4706 ,  A61K31/506 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention describes novel nitrosated and/or nitrosylated proton pump inhibitor compounds, and novel compositions comprising at lease one proton pump inhibitor compound that is optionally substituted with at least one NO and/or NO2 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 nonsteroidal antiinflammatory drug, selective COX-2 inhibitor antacid, bismuth-containing reagent, acid-degradable antibacterial compound, and mixtures thereof. The present invention also provides methods for treating and/or preventing gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylori properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating Helicobacter pylori and viral infections. The compounds and/or compositions of the present invention can also be provided in the form of a pharmaceutical kit.