2-羟基-5-丁酰胺基苯甲酸的合成及药效学研究

Synthesis of 2-hydroxyl-5-butyramidobenzoic acid and its effect on acetic acid-induced colitis in rats

目的研究2-羟基-5-丁酰胺基苯甲酸合成方法及其抗溃疡性结肠炎的作用。方法以5-氨基水杨酸为原料,与丁酰氯反应,而后水解,合成2-羟基-5-丁酰胺基苯甲酸。采用大鼠乙酸性结肠炎模型研究2-羟基-5-丁酰胺基苯甲酸的抗溃疡性结肠炎的作用。结果经IR和1HNMR分析证明合成产物为2-羟基-5-丁酰胺基苯甲酸。结肠炎大鼠给予2-羟基-5-丁酰胺基苯甲酸,可减轻乙酸性结肠炎大鼠的结肠粘膜损伤指数和粪便隐血程度,降低MPO水平,并可改善结肠粘膜病理损伤。结论2-羟基-5-丁酰胺基苯甲酸合成工艺简单,条件温和;而且2-羟基-5-丁酰胺基苯甲酸具有抗溃疡性结肠炎的作用。

Objective To study the method for synthesis of2-hydroxyl-5- butyramidobenzoic acid and test its effect on acetic acid-induced colitis in rats. Methods 2-hydroxyl-5-butyramidobenzoic acid was synthesized from 5-aminosalicylic acid and butyric acid by amidation, esterification and hydrolization. The effect of 2-hydroxyl-5-butyramidobenzoic acid on acetic acid enema-induced colitis in rats was investigated. Results The structure of 2-hydroxyl-5-butyramidobenzoic acid was identified by IR and 1H-NMR. After treatment with acetic acid, the colon mucosal damage index （CMDI）, fecal occult blood （OB） test, and activity ofmyelperoxidase （MPO） increased significantly in the rats as compared to the control levels. 2-hydroxyl-5- butyramidobenzoic acid obviously reduced the CMDI and OB, and reduced the level of MPO in the rats with colitis. Conclusion The synthesis of 2-hydroxyl-5-butyramidobenzoic acid requires only mild conditions with simple procedures, and the synthesized 2-hydroxyl-5-butyramidobenzoic acid shows obvious therapeutic effects on mucosal damage of in rats with acetic acid-induced colitis.