CAS: 111223-26-8; 1-[6-Amino-2-[hydroxy(4-Phenylbutyl)Phosphoryl]Oxyhexanoyl]Pyrrolidine-2-Carboxylic Acid

📜1-<(S)-2-Hydroxy-1-Oxo-6-<<(Phenylmethoxy)Carbonyl>Amino>Hexyl>-L-Proline Phenylmethyl Ester置于palladium Dihydroxide 4-二甲氨基吡啶,Sodium Periodate,氢气,N,N'-二环己基碳二亚胺体系中,用 四氢呋喃,1,4-二氧六环,甲醇,水 用作溶剂,化学反应 21.0H,反应生成西罗普利
参考文献:血管紧张素转换酶(ace)的(磷脂酰氧基)酰基氨基酸抑制剂.1.发现(S)-1-[6-氨基-2-[[羟基(4-苯基丁基)亚膦酰基]氧基]-1-氧己基]-L-脯氨酸是一种新型的ace口服活性抑制剂.
标题:血管紧张素转换酶(ace)的(磷脂酰氧基)酰基氨基酸抑制剂.1.发现(S)-1-[6-氨基-2-[[羟基(4-苯基丁基)亚膦酰基]氧基]-1-氧己基]-L-脯氨酸是一种新型的ace口服活性抑制剂.
摘要:描述了一系列血管紧张素转化酶(ace)的口服活性,次膦酰氧基酰基脯氨酸抑制剂的合成.报告了每种化合物的体外和体内ace抑制活性.讨论了该系列化合物与羧烷基二肽ace抑制剂以及其他类型的含羟基亚膦酰基的ace抑制剂(例如,相应的氮和碳等排烃)的结构活性关系.在基于赖氨酰脯氨酸末端二肽序列的一系列等排的含磷抑制剂中,只有膦酸酯(氧等排体)显示出高水平的口服活性.膦酸酯系列中的最佳效力和口服活性与(苯基丁基)-和正己基膦酸酯侧链一起发生.P1'中的氨基丁基侧链 残留物是完整表达口腔活性的绝对要求.这些化合物中最有效的化合物8B(sq 29,852)的静脉和口服活性在血压正常的大鼠中均优于卡托普利.
Doi:10.1021/jm00396A033

专利信息

专利号:US-8431712-B2
优先权日:2004-02-09
标 题 :Methods for the synthesis of pyridoxamine
发明人：KHALIFAH RAJA G; KEILITZ ROLAND; KOELLNER CHRISTOPH; DEGENHARDT THORSTEN; BRAND STEPHEN ROBERT
权利人:KHALIFAH RAJA G; KEILITZ ROLAND; KOELLNER CHRISTOPH; DEGENHARDT THORSTEN; BRAND STEPHEN ROBERT; NEPHROGENEX INC
摘要:The invention provides non-oxidative methods for the large scale manufacture of pyridoxamine (I) (4-aminomethyl-3-hydroxy-5-hydroxymethyl-2-methylpyridine): n nand salts thereof.n nThe invention also provides intermediate compounds for the synthesis of pyridoxamine, as well as compositions and methods for the treatment and/or prevention of conditions associated with the formation of post-Amadori advanced glycation end-products.

专利号:US-2003050305-A1
优先权日:2000-05-22
标题:Thromboxane inhibitors, compositions and methods of use
发明人：TEJADA INIGO SAENZ DE
摘要:The present invention describes methods for treating or preventing sexual dysfunctions in males and females, and for enhancing sexual responses in males and females by administering a therapeutically effective amount of at least one thromboxane inhibitor, and, optionally, 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 vasoactive agent. The male or female may preferably be diabetic. The present invention also provides novel compositions comprising at least one thromboxane inhibitor, 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, optionally, at least one therapeutic agent, such as, vasoactive agents, nonsteroidal antiinflanmmatory compounds (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, anticoagulants, angiotensin converting enzymes (ACE) inhibitors, angiotensin II receptor antagonists, renin inhibitors, and mixtures thereof. The present invention also provides methods for treating or preventing ischemic heart disorders, myocardial infarction, angina pectoris, stroke, migraine, cerebral hemorrhage, cardiac fatalities, transient ischaemic attacks, complications following organ transplants, coronary artery bypasses, angioplasty, endarterectomy, atherosclerosis, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, circulatory shock of various organs, nephritis, graft rejection, cancerous metastases, pregnancy-induced hypertension, preeclampsia, eclampsia, thrombotic and thromboembolic disorders, intrauterine growth, gastrointestinal disorders, renal diseases and disorders, disorders resulting from elevated uric acid levels and dysmenorrhea, and for inhibiting platelet aggregation or platelet adhesion or relaxing smooth muscles.

专利号:US-2008287407-A1
优先权日:2003-12-10
标题 :Nitric Oxide Releasing Pyruvate Compounds, Compositions and Methods of Use
发明人：GARVEY DAVID S; FANG XINQIN; KHANAPURE SUBHASH P; RANATUNGA RAMANI R; WEY SHIOW-JYI
权利人:NITROMED INC
摘要:The invention describes novel nitrosated and/or nitrosylated pyruvate compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated pyruvate compound, 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 pyruvate compound 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 pyruvate compound, that is optionally nitrosated 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 diseases resulting from oxidative stress, diabetes, reperfusion injury following ischemia, preservation of tissues, organs, organ parts and/or limbs.

专利号:US-7708989-B2
优先权日:1999-10-29
标题 :Methods of treating vascular diseases characterized by nitric oxide insufficiency
发明人：LOSCALZO JOSEPH; VITA JOSEPH A; LOBERG MICHAEL D; WORCEL MANUEL
权利人:NITROMED INC
摘要:The invention provides methods of treating and/or preventing vascular diseases characterized by nitric oxide insufficiency by administering a therapeutically effective amount of at least one nitrosated angiotensin-converting enzyme inhibitor, nitrosated beta-adrenergic blocker, nitrosated cholesterol reducer, nitrosated calcium channel blocker, nitrosated endothelin antagonist, nitrosated angiotensin II receptor antagonist, nitrosated renin inhibitor, and optionally at least one compound used to treat cardiovascular diseases and/or at least one antioxidant, or a pharmaceutically acceptable salt thereof, and/or 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. The antioxidant may preferably be a hydralazine compound or a pharmaceutically acceptable salt thereof. The 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 may preferably be isosorbide dinitrate and/or isosorbide mononitrate. The vascular diseases characterized by nitric oxide insufficiency include a cardiovascular disease and a disease resulting from oxidative stress.

专利号:US-6869973-B2
优先权日:2000-06-22
标题:Nitrosated and nitrosylated taxanes, compositions and methods of use
发明人：GARVEY DAVID S; LETTS L GORDON; LIN CHIA-EN; RICHARDSON STEWART K; WANG TIANSHENG
权利人:NITROMED INC
摘要:The present invention describes novel nitrosated and/or nitrosylated taxanes, and novel compositions comprising at least one nitrosated and/or nitrosylated taxane, and, optionally, 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 present invention also provides novel compositions comprising at least one taxane 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 compounds and compositions of the present invention can also be bound to a matrix. The present invention also provides methods for treating or preventing cardiovascular diseases and disorders, autoimmune diseases, pathological conditions resulting from abnormal cell proliferation, polycystic kidney disease, inflammatory disease, preserving organs and/or tissues or to inhibit wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis, by administering nitrosated and/or nitrosylated taxane or parent taxanes 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.

专利号:US-2003203915-A1
优先权日:2002-04-05
标题 :Nitric oxide donors, compositions and methods of use related applications
发明人：FANG XINQIN; GARVEY DAVID S; GASTON RICKY D; LIN CHIA-EN; RANATUNGA RAMANI R; RICHARDSON STEWART K; WANG TIANSHENG; WANG WEIHENG; WEY SHIOW-JYI
权利人:FANG XINQIN; GARVEY DAVID S; GASTON RICKY D; LIN CHIA-EN; RANATUNGA RAMANI R; RICHARDSON STEWART K; WANG TIANSHENG; WANG WEIHENG; WEY SHIOW-JYI
摘要:The invention describes novel nitric oxide donors and novel compositions comprising at least one nitric oxide donor. The invention also provides novel compositions comprising at least one nitric oxide donor, and, optionally, 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 the inhibition of 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, vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering the nitric oxide donor optionally in combination with at least one therapeutic agent. The invention also provides methods for treating inflammation, pain, fever, gastrointestinal disorders, respiratory disorders and sexual dysfunctions. The nitric oxide donors donate, transfer or release nitric oxide, and/or elevate endogenous levels of endothelium-derived relaxing factor, and/or stimulate endogenous synthesis of nitric oxide and/or are substrates for nitric oxide synthase and are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The therapeutic agent can optionally be substituted with at least one NO and/or NO 2 group (i.e., nitrosylated and/or nitrosated). The invention also provides novel compositions and kits comprising at least one nitric oxide donor and/or at least one therapeutic agent.