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

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.

• Authors: Shu-Wei Yang, Ginny Ho, Deen Tulshian, William J Greenlee, Xiomara Fernandez, Robbie L McLeod, Stephen Eckel, John Anthes
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 24 Pg. 6340-3 (Dec 15 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18990569 (Publication Type: Journal Article)

Chemical References

• Ligands
• Nortropanes
• Receptors, Opioid
• Nociceptin Receptor

Topics

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