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