Discovery of isoindoline and tetrahydroisoquinoline derivatives as potent, selective PPARδ agonists

  • Bioorg Med Chem Lett. 2011 Jan 1;21(1):492-6. doi: 10.1016/j.bmcl.2010.10.117.
Christopher A Luckhurst  1 ,  Linda A Stein ,  Mark Furber ,  Nicola Webb ,  Marianne J Ratcliffe ,  Gary Allenby ,  Sara Botterell ,  Wendy Tomlinson ,  Barrie Martin ,  Andrew Walding
Affiliations
  • 1. Medicinal Chemistry, AstraZeneca R&D Charnwood, Loughborough, Leicestershire LE11 5RH, UK. [email protected]
PMID: 21094606 DOI: 10.1016/j.bmcl.2010.10.117
Abstract

Small molecule isoindoline and tetrahydroisoquinoline derivatives have been identified as selective agonists of human Peroxisome Proliferator-activated Receptor δ (PPARδ. Compound 18 demonstrated efficacy in a biomarker for increased fatty acid oxidation, with upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4) in human primary myotubes.