Identification of the first potent, selective and bioavailable PPARα antagonist

  • Bioorg Med Chem Lett. 2014 May 15;24(10):2267-72. doi: 10.1016/j.bmcl.2014.03.090.
Yalda Bravo  1 ,  Christopher S Baccei  2 ,  Alex Broadhead  2 ,  Richard Bundey  2 ,  Austin Chen  2 ,  Ryan Clark  2 ,  Lucia Correa  2 ,  Jason D Jacintho  2 ,  Daniel S Lorrain  2 ,  Davorka Messmer  2 ,  Karin Stebbins  2 ,  Peppi Prasit  2 ,  Nicholas Stock  2
Affiliations
  • 1. Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA. Electronic address: [email protected].
  • 2. Inception Sciences, 5871 Oberlin Drive Suite 100, San Diego, CA 92121, USA.
PMID: 24745969 DOI: 10.1016/j.bmcl.2014.03.090
Abstract

The discovery and SAR of a novel series of potent and selective PPARα antagonists are herein described. Exploration of replacements for the labile acyl sulfonamide linker led to a biaryl sulfonamide series of which compound 33 proved to be suitable for further profiling in vivo. Compound 33 demonstrated excellent potency, selectivity against Other nuclear hormone receptors, and good pharmacokinetics in mouse.

Keywords
Antagonist; Cancer; Fatty acid oxidation; Nuclear hormone receptor; PPAR alpha.
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