メシル酸ガベキサート

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.