Identification of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the management of cough and anxiety.

Abstract

A series of nortropane analogs based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. The synthesis and structure-activity relationships around the C-3 nortropane substitution are described. From the SAR study and hPXR screening effort, compound 15 was identified to possess potent oral antitussive and anxiolytic-like activities in the guinea pig models.

• Authors: Shu-Wei Yang, Ginny Ho, Deen Tulshian, William J Greenlee, Zheng Tan, Hongtao Zhang, April Smith-Torhan, Ahmad Fawzi, John Anthes, Sherry Lu, Geoffrey Varty, Xiomara Fernandez, Robbie L McLeod, John Hey
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 9 Pg. 2482-6 (May 01 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19332374 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Antitussive Agents
• Ligands
• Nortropanes
• Receptors, Opioid
• Nociceptin Receptor

Topics

• Administration, Oral
• Animals
• Anti-Anxiety Agents (pharmacology)
• Antitussive Agents (pharmacology)
• Anxiety (drug therapy)
• Chemistry, Pharmaceutical (methods)
• Cough (drug therapy)
• Drug Design
• Guinea Pigs
• Kinetics
• Ligands
• Molecular Structure
• Nortropanes (chemical synthesis, pharmacology)
• Receptors, Opioid (chemistry, metabolism)
• Structure-Activity Relationship
• Nociceptin Receptor