📜乙酸酐,2-羟丙基三甲基氯化铵 反应生成 氯化乙酰甲胆碱 参考文献:Preparation And Properties Of Alpha-And Beta-Methylcholine And Gamma-Homocholine1 标题:Preparation And Properties Of Alpha-And Beta-Methylcholine And Gamma-Homocholine1 摘要: DOI:10.1021/ja01340A036
专利号:US-9662347-B2 优先权日:2010-05-11 标题 :Method for inhibiting the induction of cell death by inhibiting the synthesis or secretion of age-albumin in cells of the mononuclear phagocyte system 发明人:LEE BONG HEE; BYUN KYUNG HEE 权利人:LEE BONG HEE; BYUN KYUNG HEE; GACHON UNIV OF INDUSTRY-ACADEMIC COOP FOUND 摘要:The present invention relates to a method for inhibiting the induction of cell death by inhibiting the synthesis or secretion of AGE-albumin in cells of the mononuclear phagocyte system, to an AGE-albumin synthesis inhibitor, and to a pharmaceutical composition comprising the AGE-albumin synthesis inhibitor for preventing or treating degenerative disease and autoimmune disease. The AGE-albumin of the present invention is synthesized and secreted in human microglia or human macrophages in an Alzheimer's model, stroke model, Parkinson's disease model and rheumatoid arthritis model. The AGE-albumin synthesis and secretion are caused by oxidative stress. The expression of RAGE increases in first-order human neurons or cartilage cells to which AGE-albumin is administered, whereupon a MAPK signaling pathway is activated and the expression of Bax increases to induce an increase in calcium in mitochondria, thus finally inducing cell death. Therefore, the AGE-albumin synthesis inhibitor of the present invention can be valuably used in the diagnosis or treatment of degenerative diseases or autoimmune diseases such as Alzheimer's disease, strokes, Parkinson's disease, amyotrophic lateral sclerosis, rheumatoid arthritis, diabetic retinopathy, AIDS, aging, pulmonary fibrosis, spinal cord injuries, etc.
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-12006337-B2 优先权日:2018-05-30 标题:Mitogen-activated protein kinase inhibitors, methods of making, and methods of use thereof 发明人:HOLTZMAN MICHAEL J; ROMERO ARTHUR G; GEROVAC BENJAMIN J; HAN ZHENFU; KEELER SHAMUS P; WU KANGYUN; ZHANG YONG 权利人:WASHINGTON UNIVERSITY ST LOUIS 摘要:Compounds that inhibit mitogen-activated protein kinases (MAPKs) are disclosed. Some inhibitor compounds specifically target a single MAPK such as MAPK13, while others target multiple MAPKs such as MAPK13 and MAPK12. The compounds can be used therapeutically for a variety of diseases, including cancer and respiratory diseases. Methods of synthesis of the compounds are also disclosed.
专利号:US-2008300418-A1 优先权日:2004-11-08 标 题:Synthesis of Cardiolipin Analogues and Uses Thereof 发明人:AHMAD MOGHIS U; UKKALAM MURALI K; ALI SHOUKATH M; AHMAD IMRAN 权利人:AHMAD MOGHIS U; UKKALAM MURALI K; ALI SHOUKATH M; AHMAD IMRAN 摘要:The invention provides novel synthetic methodologies for preparing cardiolipin, migrated caridiolipin (1,2-positional isomer of cardiolipin) and their analogues having varying fatty acids and/or alkyl chains with varying length and degrees of saturation/unsaturation. The method comprises (a) reacting an optically pure 1,2-O-dialkyl-sn-glycerol or 1,2-O-dialkyl-sn-glycerol with one or more phosphoramidite reagent(s), wherein a phosphite triester is produced; (b) coupling the product of (a) with glycerol, wherein a protected cardiolipin is produced; and (c) deprotecting the protected cardiolipin, such that cardiolipin is prepared. The cardiolipins and analogues thereof, prepared by the present methods, can be incorporated into liposomes, which can also include active agents such as hydrophobic or hydrophilic drugs, antisense nucleotides or diagnostic agents. Such liposomes can be used to treat diseases or can be used in diagnostic and/or analytical assays.
专利号:US-7994346-B2 优先权日:2001-11-06 标题 :Intermediates for the preparation of lipoxin A4 analogs 发明人:GROSSBACH DANJA; GUILFORD WILLIAM; SANDER MICHAEL 权利人:BAYER SCHERING PHARMA AG 摘要:This invention is directed to compounds useful as intermediates in the synthesis of lipoxin A 4 analogs of the following formulas (I) and (II): n nwherein R 1 , R 2 , R 3 , R 4 and R 5 are described herein. These analogs are useful in treating inflammatory and autoimmune disorders in humans. These analogs are also useful in treating pulmonary or respiratory tract inflammation in humans.
1: Sagara H, Tanaka A, Ohta S, Jinno E, Uchida N, Sambe T, Hida N, Suehiro Y, Doi S, Kameda M, Yoshida Y, Fukuoka J, Kinoshita Y. The Safety and efficacy of airway-hyperresponsiveness test for asthma using by SK-1211 (Methacholine Chloride). Arerugi. 2016;65(1):32-40. doi: 10.15036/arerugi.65.32. Japanese. Japanese. Japanese.
合成参考文献
参考文献:10.2746/042516409x479586 摘要:LAUMEN E, DOHERR MG, GERBER V. Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families. Equine Veterinary Journal. 2010 Feb 09;42(2):142–8. doi: 10.2746/042516409x479586. 参考文献:10.1186/2047-783x-14-s4-170 摘要:Nensa F, Marek W, Marek E, Smith H, Kohlhäufl M. Assessment of airway hyperreactivity: comparison of forced spirometry and body plethysmography for methacholine challenge tests. European Journal of Medical Research. 2009 Dec 07;14(Suppl 4):170. doi: 10.1186/2047-783x-14-s4-170. 参考文献:10.1186/1465-9921-12-96 摘要:Mendonça NT, Kenyon J, LaPrad AS, Syeda SN, O'Connor GT, Lutchen KR. Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness. Respiratory Research. 2011 Dec 01;12(1):96. doi: 10.1186/1465-9921-12-96. 参考文献:10.1073/pnas.1106582108 摘要:Cozzi E, Ackerman KG, Lundequist A, Drazen JM, Boyce JA, Beier DR. The naïve airway hyperresponsiveness of the A/J mouse is Kit -mediated. Proc. Natl. Acad. Sci. U.S.A. 2011 Jul 18;108(31):12787–92. doi: 10.1073/pnas.1106582108.