Synthesis and biological activities of novel indole derivatives as potent and selective PPARgamma modulators

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1399-404. doi: 10.1016/j.bmcl.2009.12.107. Epub 2010 Jan 4.

Abstract

Starting from the structure of Telmisartan, a new series of potent and selective PPARgamma modulators was identified. The synthesis, in vitro and in vivo evaluation of the most potent compounds are reported and the X-ray structure of compound 7b bound to the PPARgamma ligand binding domain is described.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology
  • Benzoates / chemistry
  • Benzoates / pharmacology
  • Crystallography, X-Ray
  • Drug Design*
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • PPAR gamma / drug effects*
  • Rats
  • Structure-Activity Relationship
  • Telmisartan

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Benzoates
  • Indoles
  • PPAR gamma
  • Telmisartan