メシル酸ガベキサート 化学特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
用途
膵酵素阻害剤です。トロンビン、 トリプシン、カリクレインなどのタンパク分 解酵素を阻害作用を示します。
効能
抗凝固薬, 血漿カリクレイン阻害薬
商品名
エフオーワイ (丸石製薬); エフオーワイ (丸石製薬)
化学的特性
Gabexate mesylate is supplied as a crystalline solid. A stock solution may be made by dissolving the gabexate (mesylate) in the solvent of choice. Gabexate (mesylate) is soluble in organic solvents such as DMSO and dimethyl formamide, which should be purged with an inert gas. The solubility of gabexate (mesylate) in these solvents is approximately 25 mg/ml.
Gabexate is a competitive inhibitor of serine proteases that inhibits human thrombin, urokinase, plasmin, and Factor Xa (Kis = 0.97, 1.3, 1.6, and 8.5 μM, respectively). It also inhibits bovine thrombin, Factor Xa, and trypsin, and porcine plasma kallikrein (Kis = 1.4, 2.1, 2.6, and 0.2 μM, respectively). In vitro, gabexate inhibits clotting activity of thrombin (IC50 = 10 μM).In vivo, it inhibits fibrin formation in rats when administered at a continuous infusion of 120 μmol/kg per hour. Gabexate inhibits LPS-stimulated TNF-α production from monocytes by inhibiting binding of NF-κB and activator protein 1 (AP-1) to target sites and inducing degradation of IκBα.
製造方法
Guanidinocaproic acid p-tosyl salt and thionyl chloride were mixed together toreact at the room temperature. An endothermic reaction occurred and thecaproic acid gradually dissolved. Then the reaction mixture was left standingfor 1 to 2 h and was extracted with ether. The lower oily layer and the etherlayer were separated from each other and the lower layer was repeatedlywashed with ether. Then the oily substance (caproic acid chloride) was addedwith benzoic acid ethyl ester in tetrahydrofuran, and the mixture was stirred.After the mixture became a uniform solution, of pyridine were graduallyadded. An exothermic reaction occurred and an oily substance came to beseparated in the lower layer. After the completion of the reaction, the oilysubstance was washed with water and then recrystallized from hot water onceor twice. Thus 4-(6-guanidino-hexanoyloxy)-benzoic acid ethyl ester salt wasobtained as white crystals.
To obtained the base 4-(6-guanidino-hexanoyloxy)-benzoic acid ethyl esterthe 4-(6-guanidino-hexanoyloxy)-benzoic acid ethyl ester salt must be treatedby, for example, sodium hydroxide.
In practice it is usually used as gabexate Mesylate.
作用機序
Gabexate mesilate (FOY-007) is a protease inhibitor with a broad spectrum inhibiting not only trypsin and kallikrein, but also plasmin, thrombin,factor Xa, elastase, complement 1 (C1), esterase and phospholipase A2. Prophylactic application of FOY-007 or Camostat mesilate (FOY-305) showed some beneficial effect in CDEinduced pancreatitis, cerulein-induced panceratitis and sodium taurocholate-induced panceratitis. The therapeutic effect of FOY-007 in acute panceratitis has been ascribed to its inhibition of pancreatic enzyme activity, like trypsin, thus preventing autodigestion.
臨床応用
Gabexate mesylate inhibits proteases and suppresses endothelial cell injury and may be used to treat DIC ascribed to various kinds of diseases.
Therapeutic Function: Enzyme inhibitor
メシル酸ガベキサート 上流と下流の製品情報
原材料
準備製品