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

Yisheng Lai; Lin Ma; Wenxing Huang; Xing Yu; Yihua Zhang; Hui Ji; Jide Tian

doi:10.1016/j.bmcl.2010.10.056

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. Epub 2010 Oct 20.

Authors

Yisheng Lai¹, Lin Ma, Wenxing Huang, Xing Yu, Yihua Zhang, Hui Ji, Jide Tian

Affiliation

¹ Center of Drug Discovery, China Pharmaceutical University, Nanjing, PR China. lcpu333@yahoo.com.cn

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.

MeSH terms

Analgesics / chemical synthesis
Analgesics / chemistry
Analgesics / pharmacology
Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacology
Arachidonate 5-Lipoxygenase / chemistry*
Arachidonate 5-Lipoxygenase / metabolism
Benzylidene Compounds / chemical synthesis*
Benzylidene Compounds / chemistry
Benzylidene Compounds / pharmacology
Cyclooxygenase 1 / chemistry*
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / chemistry*
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / chemical synthesis*
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacology
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology
Lipoxygenase Inhibitors / chemical synthesis*
Lipoxygenase Inhibitors / chemistry
Lipoxygenase Inhibitors / pharmacology
Male
Mice
Rats
Structure-Activity Relationship

Substances

Analgesics
Anti-Inflammatory Agents
Benzylidene Compounds
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Indoles
Lipoxygenase Inhibitors
indolin-2-one
Arachidonate 5-Lipoxygenase
Cyclooxygenase 1
Cyclooxygenase 2