Synthesis of a novel human PPARδ selective agonist and its stimulatory effect on oligodendrocyte differentiation

Bioorg Med Chem Lett. 2011 Jan 1;21(1):240-4. doi: 10.1016/j.bmcl.2010.11.030. Epub 2010 Nov 11.

Abstract

We successfully synthesized a novel peroxisome proliferator-activated receptor (PPAR)δ selective agonist, namely, compound 20, with a characteristic benzisoxazole ring. Compound 20 exhibited potent human PPARδ transactivation activity and high δ selectivity. Further, it stimulated differentiation of primary oligodendrocyte precursor cells in vitro, indicating that it may be an effective drug in the treatment of demyelinating disorders such as multiple sclerosis.

MeSH terms

  • Animals
  • Brain / pathology
  • Cell Differentiation
  • Humans
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / chemistry
  • Isoxazoles / therapeutic use
  • Multiple Sclerosis / drug therapy
  • Oligodendroglia / cytology*
  • Oxazoles / chemical synthesis*
  • Oxazoles / chemistry
  • Oxazoles / therapeutic use
  • PPAR delta / agonists*
  • PPAR delta / metabolism
  • Rats
  • Transcriptional Activation

Substances

  • Isoxazoles
  • Oxazoles
  • PPAR delta