Structure-activity relationships of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the treatment of cough

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6340-3. doi: 10.1016/j.bmcl.2008.10.088. Epub 2008 Nov 1.

Abstract

A series of 3-axial-aminomethyl-N-benzhydryl-nortropane analogs have been synthesized and identified to bind to the nociceptin receptor with high affinity. Many of these analogs showed high binding selectivity over classic opioid receptors such as mu receptor. The synthesis and structure-activity relationships around the C-3 nortropane substitution are described. Selected compounds with potent oral antitussive activity in the guinea pig model are disclosed.

MeSH terms

  • Animals
  • CHO Cells
  • Chemistry, Pharmaceutical / methods
  • Cough / drug therapy*
  • Cough / pathology
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Guinea Pigs
  • Kinetics
  • Ligands
  • Models, Chemical
  • Nociceptin Receptor
  • Nortropanes / chemical synthesis*
  • Nortropanes / metabolism
  • Receptors, Opioid / chemistry*
  • Structure-Activity Relationship

Substances

  • Ligands
  • Nortropanes
  • Receptors, Opioid
  • Nociceptin Receptor