Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists

  • Bioorg Med Chem Lett. 2012 Jun 15;22(12):3890-4. doi: 10.1016/j.bmcl.2012.04.122.
Rong Jiang  1 ,  Xinyi Song ,  Purva Bali ,  Anthony Smith ,  Claudia Ruiz Bayona ,  Li Lin ,  Michael D Cameron ,  Patricia H McDonald ,  Paul J Kenny ,  Theodore M Kamenecka
Affiliations
  • 1. Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #2A1, Jupiter, FL 33458, USA.
PMID: 22617492 DOI: 10.1016/j.bmcl.2012.04.122
Abstract

A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.