Synthesis and anti-inflammatory activity of p-(methanesulfonyl) styrene-linked cyclic ketone derivatives / 药学学报

<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 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.</p><p><b>RESULTS</b>Nine target compounds (ZA(1-9)) were obtained, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compared with controls diclofenac (DC) and rofecoxib (RC) , ZA(3, 5-9) showed no significant difference in anti-inflammatory activity against xylene-induced ear swelling in mice. ZA(3, 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. ZA(3, 5-9) showed less GI side effects than DC (P < 0.05, P < 0.01) and no significant difference compared with RC (P > 0.05).</p><p><b>CONCLUSION</b>p-(Methanesulfonyl) styrene-linked cyclic ketone derivatives showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.</p>

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

<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>