摘要
目的:研究3-(羟基-p-甲磺酰苯甲撑基)-5-甲基-2-吲哚酮-1-羧酰胺类化合物的合成及其抗炎活性。方法:以具有COX/5-LOX双重抑制作用并兼有细胞因子抑制活性的替尼达普为先导物,合成3-(羟基-p-甲磺酰苯甲撑基)-5-甲基-2-吲哚酮-1-羧酰胺类化合物。应用二甲苯致小鼠耳肿胀模型和角叉菜胶致大鼠足跖肿胀模型评价其抗炎活性,并考察连续口服给药对大鼠胃肠道的影响。结果:合成了14个目标物(Ⅰ1-14),其结构经IR1、H NMR和MS和元素分析确证。小鼠耳肿胀模型显示Ⅰ5,8,9具有明显的抗炎活性;角叉菜胶致大鼠足跖肿胀模型显示Ⅰ8,9具有较强的抗炎活性;Ⅰ5,8,9的胃肠道不良反应,与CMC-Na无明显差别(P>0.05),其中Ⅰ5,8显著小于双氯芬酸钠(P<0.05)和替尼达普钠(P<0.05,P<0.01)。结论:3-(羟基-p-甲磺酰苯甲撑基)-5-甲基-2-吲哚酮-1-羧酰胺类化合物具有一定的抗炎活性,胃肠道不良反应较轻。
AIM： To study the synthesis and anti-inflammatory activity of 3-（hydroxy-p-methanesulfonyl- phenylmethylene）-5-methyl-2-oxindole-1-carboxamides. METHODS： A series of 3-（hydroxy-p-methanesulfonyl- phenylmethylene）-5-methyl-2-oxindole-1-carboxamides were designed and synthesized by using tenidap as lead compound, a COX/5-LOX and cytokine inhibitor. Their anti-inflammatory activity against xylene-induced mice ear swelling and carrageenan-induced rat paw edema were evaluated, and their gastrointestinal tract （GI） side effects in the rats were examined. RESULTS： Fourteen novel compounds （Ⅰ1-14） were obtained, whose structures were determined by IR, ^1H NMR, MS and elemental analysis. Ⅰ5,8,9 exhibited marked anti-inflammatory activity in xylene-induced mice ear swelling model. Ⅰ8,9 showed significant anti-inflammatory activity in carrageenan-induced rat paw edema model. Ⅰ5,8 had less GI side effects than diclofenac and tenidap sodium. CONCLUSION： 3-（Hydroxy-p-methanesulfonyl- phenylmethylene）-5-methyl-2-oxindole-1-carboxamides possess some anti-inflammatory activity and few GI side effects.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2005年第6期511-516,共6页
Journal of China Pharmaceutical University
作者简介
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