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

AimTo search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects. MethodsA 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. ResultsNine 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 (P0.05) in the treatment of carrageenan-induced rat paw edema. ZA_3,5-9 showed less GI side effects than DC (P0.05, P<0.01) and no significant difference compared with RC (P>0.05). ConclusionP- (Methanesulfonyl) styrene-linked cyclic ketone derivatives showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.