[Synthesis and anti-inflammatory activity of p-(methanesulfonyl) styrene-linked cyclic ketone derivatives].
OBJECTIVE
To search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects.


METHODS
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.


RESULTS
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).


CONCLUSIONS
p-(Methanesulfonyl) styrene-linked cyclic ketone derivatives showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.
Ao
Gui-zhen
GZ
Center of Drug Research, China Pharmaceutical University, Nanjing 210009, China.
Zhang
Yi-hua
YH
Ji
Hui
H
Deng
Gang
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D051379:Mice; D010437:Peptic Ulcer / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis* / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007659:Ketones; D013343:Styrenes; D002351:Carrageenan