Synthesis and anti-inflammatory activity of α-substituted P-(methanesulfonyl)phenylpropenamides

AimTo search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects. MethodsA series of α-substituted P-(methanesulfonyl)phenyl-propenamides 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 rats were examined. ResultsTwenty-five target compounds (II1-25) were obtained, and their structures were determined by IR, ¹H NMR, MS and elemental analysis. Thirteen compounds (II1,3,5,8-13,15,18,19,23) exhibited marked anti-inflammatory activity comparable to diclofenac sodium (DC) and rofecoxib (RC) in xylene-induced mice ear swelling model, and twelve compounds (II1,3,5,7,8,10-12,17,18,20,23) showed remarkable anti-inflammatory activity comparable to DC and RC in carrageenan-induced rat paw edema. Compounds II3,8,10,11,18,20 showed GI side effects less than DC (P<0.01), and no significant difference compared with RC and CMC-Na (P>0.05). Conclusionα-Substituted P-(methanesulfonyl)phenylpropenamides showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.