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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-methanesulfonylmethylene) -5-methyl-2-indolone-1-carboxamides. METHODS: Tenidap was used as the lead compound with dual inhibition of COX / 5-LOX and cytokine inhibitory activity to synthesize 3- (hydroxy-p-methanesulfonylmethylene) -5-methyl- 2-indolone-1-carboxamides. The anti-inflammatory activity of xylene-induced mouse ear swelling model and carrageenan-induced rat paw swelling model were evaluated and the effects of continuous oral administration on the gastrointestinal tract of rats were investigated. Results: 14 target compounds (Ⅰ-14) were synthesized and their structures were confirmed by IR1, 1H NMR and MS and elemental analysis. Mouse ear swelling model showed Ⅰ 5,8,9 has obvious anti-inflammatory activity; carrageenan-induced rat paw swelling model shows Ⅰ 8,9 has a strong anti-inflammatory activity; Ⅰ 5,8,9 gastrointestinal tract Adverse reactions were not significantly different from those of CMC-Na (P> 0.05), among which I5,8 was significantly less than diclofenac sodium (P <0.05) and tenuipat sodium (P <0.05, P <0.01). CONCLUSION: 3- (Hydroxy-p-mesyloxybenzylidene) -5-methyl-2-indolinone-1-carboxamide compounds have some anti-inflammatory activity with mild gastrointestinal adverse reactions.