Synthesis and pharmacological evaluation of novel benzoylazole-based PPAR α/γ activators

Bioorg Med Chem Lett. 2011 Apr 1;21(7):1978-82. doi: 10.1016/j.bmcl.2011.02.032. Epub 2011 Feb 13.

Abstract

In our search for new PPARα/γ agonists, we designed and synthesized a series of benzoylazole-based carboxylic acids. Compound 9 showed potent PPARγ partial agonistic activity with modest PPARα agonistic activity. The sodium salt of 9 (9Na) demonstrated potent efficacy in lowering both blood glucose and lipids in an animal model without causing significant body weight gain, a well-known side effect associated with PPARγ full agonists.

MeSH terms

  • Animals
  • Azoles / chemical synthesis*
  • Azoles / chemistry
  • Azoles / pharmacology*
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacology
  • Mice
  • Models, Animal
  • Models, Molecular
  • PPAR alpha / agonists*
  • PPAR gamma / agonists*

Substances

  • Azoles
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • PPAR alpha
  • PPAR gamma