4-苯磺酰氧基-苯并口恶唑酮衍生物的合成及其抗炎镇痛作用  

Synthesis,anti-inflammatory and analgesic activities of 4-benzenesulfonyl-2( 3H)-benzoxazolone derivatives

作　　者：马文华[1] 唐莉[1] 梁泰刚[1] 班树荣[1] 李青山[1] 

机构地区：[1]山西医科大学药学院,山西太原030001

出　　处：《中国药物化学杂志》2013年第5期358-362,共5页Chinese Journal of Medicinal Chemistry

基　　金：山西省科技攻关项目(20110321076-01)

摘　　要：目的合成天然产物4-取代苯并口恶唑酮衍生物并对其抗炎镇痛活性进行初步评价。方法以2-氨基间苯二酚为原料,与三光气缩合制得4-羟基-苯并口恶唑酮;以2-取代苯酚为起始物,经取代、重排、氧化反应得到取代苯磺酰氯,取代磺酰氯与4-羟基-苯并口恶唑酮反应制得4-苯磺酰氧基-苯并口恶唑酮酯类化合物。采用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定目标化合物的抗炎及镇痛活性。结果与结论共合成了11个目标化合物,其中10个化合物未见文献报道,目标化合物的结构经ESI-MS、1H-NMR、13C-NMR谱确证;活性实验结果显示,化合物5g具有一定的抗炎活性,化合物5a、5d、5j具有较好的镇痛活性。Benzoxazolones are special materials which are not only the defense compounds towards pests, fungi, bacteria ,but also important chemicals widely used in medicine. Our previous studies have shown that 4-substituted benzoxazolone derivatives presented high anti-inflammatory and analgesic activity. Therefore, ten new 4-substituted benzoxazolone derivatives were synthesized, characterized and evaluated as anti-inflammatory and analgesic agents using xylene-induced mice ear edema model and acetic acid induced mice writhing model. The key intermediate 4-hydroxy-benzoxazolone （4） was prepared by the condensation of 2-aminoresorcinol with triphosgene under N2 atmosphere, and then reacted with sulfonyl chloride at 0 ℃ to gain the 4-benzenesulfonyl-2 （3H）-benzoxazolone derivatives. Target compound structures were confm-ned by ESI-MS, i H-NMR and 13 C-NMR. The active assay demonstrated that compound 5g exhibited definite anti-inflammatory activity at 150 mg. kg-1, the compounds Sa,Sd ,Sj exhibited high analgesic activity at 150 mg. kg -1 , compounds 5b ,5e ,5f,5i ,Sk showed moderate analgesic activity.

关 键 词：4-取代苯并口恶唑酮 化学合成 抗炎 镇痛 

分 类 号：R914[医药卫生—药物化学]