[Synthesis and anti-inflammatory activity of alpha-substituted p-(methanesulfonyl)phenylpropenamides].
OBJECTIVE
To search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects.


METHODS
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.


RESULTS
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).


CONCLUSIONS
alpha-Substituted p-(methanesulfonyl)phenylpropenamides showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.
Ao
Gui-zhen
GZ
Center of Drug Discovery, 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* / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D010437:Peptic Ulcer / Q000139:chemically induced; D010666:Phenylpropionates / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D014992:Xylenes
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; D013450:Sulfones; D014992:Xylenes; D002351:Carrageenan