Design, synthesis and insulin-sensitizing activity of indomethacin and diclofenac derivatives

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3324-7. doi: 10.1016/j.bmcl.2009.04.050. Epub 2009 Apr 18.

Abstract

A series of aromatic acetic acid compounds were designed and synthesized on the basis of Non-steroidal anti-inflammatory drugs indomethacin and diclofenac. Compounds 5a, 7a, 5h, 7h and 17 could strongly promote insulin-regulated differentiation of 3T3-L1 cells in vitro. They acted as full or partial PPARgamma agonist, or improved insulin resistance through non-PPARgamma pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cell Differentiation / drug effects
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Diclofenac / chemistry
  • Diclofenac / pharmacology*
  • Drug Design
  • Indomethacin / chemistry
  • Indomethacin / pharmacology*
  • Insulin / pharmacology
  • Insulin Resistance*
  • Mice
  • PPAR gamma / agonists
  • PPAR gamma / metabolism
  • Rats

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Insulin
  • PPAR gamma
  • Diclofenac
  • Indomethacin