Synthesis and biological evaluation of 3-[4-(amino/methylsulfonyl)phenyl]methylene-indolin-2-one derivatives as novel COX-1/2 and 5-LOX inhibitors

Fourteen new 3-[4-(amino/methylsulfonyl)phenyl]methylene-indolin-2-one derivatives were synthesized. Six compounds displayed potent inhibitory activities against COX-1/2 and 5-LOX with IC50 in the range of 0.10–9.87 μM. Particularly, 10f exhibited well balanced inhibitory action on these enzymes (IC50 = 0.10–0.56 μM). More importantly, 10f and several other compounds had comparable or stronger anti-inflammatory and analgesic activities, but better gastric tolerability in vivo, as compared with darbufelone mesilate and tenidap sodium. Therefore, our findings may aid in the design of new and safe anti-inflammatory reagents for the intervention of painful inflammatory diseases, such as rheumatoid arthritis at clinic.

A series of novel 3-[4-(amino/methylsulfonyl)phenyl]methylene-indolin-2-ones were synthesized. Some of them displayed potent inhibitory activities against COX-1/2 and 5-LOX in vitro, and strong anti-inflammatory and analgesic activities, and well gastric tolerability in vivo.Figure optionsDownload as PowerPoint slide