芳基烷酸类NSAIDs四乙酰基葡萄糖衍生物的制备及抗炎活性

Synthesis and anti-inflammatory activities of aryl alkyl acid NSAIDs tetra-acetylated glucoside derivatives

目的:制备3种NSAIDs(双氯芬酚钠,萘普生和吲哚美辛)的葡萄糖酯,考察其生物活性。方法:用均相反应法制备葡萄糖酯,用1H NMR、13C NMR、IR和MS确认结构,用小鼠耳肿胀法评价其抗炎活性。结果:用羧酸盐均相反应法和羧酸-有机碱均相反应法合成了3个乙酰基葡萄糖酯,收率为53%～67%;所合成的3个目标化合物其抗炎活性均高于原药,刺激性低于原药。结论:均相反应法制备糖酯简便易行,优于相转移催化法;糖酯化修饰可提高芳基烷酸类NSAIDs的生物活性,降低刺激性。

Aim： To prepare NSAIDs （ diclofenac sodium, naproxen and indometacin） glu cosides and evaluate their anti-inflammatory bioactivities. Methods： The NSAIDs glycosides were synthesized with homogeneous reactions, and the structures of the products were identified by ^1H NMR,^13C NMR, IR and MS. Their anti-inflammatory activities were evaluated by the models of mice ear edema induced by xylene. Results： Three NSAIDs tetra-acetylated glucosides were for the first time synthesized through carboxylation or carboxylic acid-organic base homogeneous reaction, and the yields of the products were about 53% to 67%. And the products were found to be superior to their primary drug in anti-inflammatory activity. Conclusion： Synthesis of NSAIDs glycosides by homogeneous reaction was operated easily and better than the method of phase-transfer catalysis-based methods. The glucosidation of aryl alkyl acid NSMDs could increase the bioactivities of their corresponding primary drug.