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

  • Bioorg Med Chem Lett. 2010 Dec 15;20(24):7349-53. doi: 10.1016/j.bmcl.2010.10.056.
Yisheng Lai  1 ,  Lin Ma ,  Wenxing Huang ,  Xing Yu ,  Yihua Zhang ,  Hui Ji ,  Jide Tian
Affiliations
  • 1. Center of Drug Discovery, China Pharmaceutical University, Nanjing, PR China. [email protected]
PMID: 21055929 DOI: 10.1016/j.bmcl.2010.10.056
Abstract

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 IC(50) in the range of 0.10-9.87 μM. Particularly, 10f exhibited well balanced inhibitory action on these Enzymes (IC(50)=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.

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