Novel selective PPARdelta agonists: optimization of activity by modification of alkynylallylic moiety

Bioorg Med Chem Lett. 2007 Aug 1;17(15):4144-9. doi: 10.1016/j.bmcl.2007.05.051. Epub 2007 May 21.

Abstract

Y-shaped molecules bearing alkynylallylic moieties were found to be potent and selective PPARdelta activators. The alkynylallylic moiety was synthesized from alkyn-1-ols by hydroalumination followed by a cross-coupling reaction. Series of active compounds 6 were obtained by stepwise changing the structure of the known PPARpan agonist 5 into Y-shaped compounds. The most active and selective compound, 6f, had a PPARdelta potency of 0.13 microM, which is 50-fold more potent than compound 5.

MeSH terms

  • Models, Molecular
  • Molecular Structure
  • PPAR delta / agonists*

Substances

  • PPAR delta