2-(2, 6-二氯苯胺基)苯乙酸(3-硝氧甲基)苯酯的合成及抗炎镇痛活性

目的：获得抗炎活性强、胃肠道副作用小的新型非甾体抗炎药。方法：以间羟基苯甲醛为原料，经还原、溴代和硝氧化，最后与双氯芬酸进行酯化反应，制备2-(2,6-二氯苯胺基）苯乙酸（3－硝氧甲基）苯酯（ZLR－9）；观察ZLR－9对二甲苯致炎小鼠和角叉菜胶致炎大鼠的抗炎活性，对热板法实验和扭体实验小鼠的镇痛活性及致大鼠胃肠道反应，研究体内外ZLR－9的NO释放。结果：ZLR－9结构经MS、IR、^1HNMR确证，它的抗炎镇痛活性强于DC－Na，胃肠道副作用显著小于DC－Na，并小于文献报道的硝酸酯类DO－DC，体内有明显的NO释放。结论：ZLR－9值得深入研究。

Synthesis and Anti-inflammatory Analgesic Activities of 2-(2,6-dichlorophenylamino)-benzeneacetic Acid(3-nitroxymethyl) Phenyl Ester

AIM:To obtain novel nonsteroidal anti inflammatory drug with higher potency and lower undesirable effects. METHOD:Synthesizing 2 (2, 6 dichlorophenylamino)benzeneacetic acid (3 nitroxy methyl) phenyl ester (ZLR 9) from m hydroxybenzaldehyde through reduction, bromination, nitroxation, and esterification with DC; evaluating anti inflammatory activity against xylene induced mice ear swelling and carrageenin induced rat paw edema, and analgesic activity using mice hot plate and mice writhing methods respectively; observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo. RESULT:ZLR 9 was obtained,and its structure was determined by MS, IR and 1HNMR. It showed stronger anti inflammatory analgesic activities and less GI side effects than DC Na, and released NO in vivo. CONCLUSION:ZLR 9 is worthy to be intensively studied further.