酮洛芬丹皮酚酯及其类似物的合成及抗炎活性研究

目的 合成5种酮洛芬酯类化合物，并研究其抗炎活性和胃肠道不良反应。方法 以丹皮酚及结构类似物和酮洛芬为原料，通过碳二亚胺法合成5种化合物；采用二甲苯致小鼠耳廓肿胀模型和角叉菜胶致大鼠足趾肿胀试验对化合物抗炎活性做了初步的药理学筛选；同时考察化合物对胃肠道不良反应的影响。结果 化合物的结构经¹H-NMR及MS得到确证；5个目标化合物均能显著地减轻小鼠的耳肿胀和大鼠的足趾肿胀程度，与其相应的阳性和阴性对照组相比，都具有良好的抗炎效果；同时，5个目标化合物对胃肠损伤面积明显小于阳性组和阴性组，能够明显地减轻胃肠道的不良反应。结论 合成了5种酮洛芬酯类化合物；抗炎活性均明显强于酮洛芬；且对胃肠道的不良反应明显地减轻。

Synthesis and anti-inflammatory activity of ketoprofen esters of Paeonol and its analogues

OBJECTIVE To synthesize five esters of ketoprofen and study their anti-inflammatory activities and gastrointestinal side effects. METHODS Five compounds were synthesized by paeonol and its structural analogues with ketoprofen by DCC method; anti-inflammatory activities of the compounds were evaluated with xylene-induced mice ear swelling model and carrageenan-induced rat paw swelling test; the research about the mice gastrointestinal side effects also was explored. RESULTS Five compounds were synthesized and their structures were confirmed by ¹H-NMR and MS. Compared with the corresponding positive and negative control group, the five target compounds could significantly reduce the mice ear swelling and rat paw swelling, all compounds showed anti-inflammatory activities. Five target compounds on gastrointestinal lesion area were significantly less than positive and negative groups and significantly reduced gastrointestinal side effects. CONCLUSION Five esters of ketoprofen are synthesized. Compared with the ketoprofen, they show significant anti-inflammatory activity and obviously reduce gastrointestinal side effects.