对甲磺酰基苯乙烯环酮类衍生物的合成及抗炎活性

目的寻找新型高效低毒的非甾体抗炎药。方法合成对甲磺酰基苯乙烯环酮类衍生物，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，并考察连续经口给药对大鼠胃肠道（GI）的影响。结果合成了9个新化合物（ZA_1-9），结构经IR，¹HNMR，MS和元素分析确证。小鼠试验表明ZA_3,5-9的抗炎活性与双氯芬酸钠(DC)和罗非昔布(RC)相当(P>0.05)，大鼠试验显示ZA_3,7,8的抗炎活性与DC和RC相当(P>0.05)， ZA₆的抗炎作用显著强于DC和RC(P<0.05)，ZA_3,5-9对GI损伤显著小于DC (P<0.05，P<0.01)，与RC相当(P>0.05)。结论对甲磺酰基苯乙烯环酮类衍生物的抗炎作用较强，GI不良反应小，值得进一步研究。

Synthesis and anti-inflammatory activity of P-(methanesulfonyl) styrene-linked cyclic ketone derivatives

Aim To search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects. Methods A series of p-( methanesulfonyl) styrene-linked cyclic, ketone derivatives were synthesized. Their anti-inflammatory activities against xylene-induced mice ear swelling and carrageenan-induced rat paw edema were evaluated, and their GI side effects in the rats were examined. Results Nine target compounds (ZA1-9) were obtained, and their structures were determined by IR, 1 HNMR, MS and elemental analysis. Compared with controls diclofenac ( DC ) and rofecoxib (RC) , ZA3,5-9 showed no significant difference in anti-inflammatory activity against xylene-induced ear swelling in mice. ZA3,7,8 showed potency comparable to DC and RC (P >0. 05) and ZA6 was more potent than DC and RC (P <0. 05) in the treatment of carrageenan-induced rat paw edema. ZA3,5-9 showed less GI side effects than DC ( P < 0. 05 , P < 0. 01 ) and no significant difference compared with RC ( P >.05). Conclusion p- (Methanesulfonyl) styrene-linked cyclic ketone derivatives showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.