Synthesis and anti-inflammatory activity of alpha-substituted p-(methanesulfonyl)phenylpropenamides / 药学学报

ABSTRACT

<p><b>AIM</b>To search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects.</p><p><b>METHODS</b>A series of alpha-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.</p><p><b>RESULTS</b>Twenty-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).</p><p><b>CONCLUSION</b>alpha-Substituted p-(methanesulfonyl)phenylpropenamides showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.</p>