Identification of fused bicyclic heterocycles as potent and selective 5-HT(2A) receptor antagonists for the treatment of insomnia.

Abstract

A series of fused bicyclic heterocycles was identified as potent and selective 5-HT(2A) receptor antagonists. Optimization of the series resulted in compounds that had improved PK properties, favorable CNS partitioning, good pharmacokinetic properties, and significant improvements on deep sleep (delta power) and sleep consolidation.

• Authors: Yifeng Xiong, Brett Ullman, Jin-Sun Karoline Choi, Martin Cherrier, Sonja Strah-Pleynet, Marc Decaire, Konrad Feichtinger, John M Frazer, Woo H Yoon, Kevin Whelan, Erin K Sanabria, Andrew J Grottick, Hussien Al-Shamma, Graeme Semple
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 5 Pg. 1870-3 (Mar 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22325948 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Receptor, Serotonin, 5-HT2A
• Serotonin 5-HT2 Receptor Antagonists

Topics

• Animals
• Bridged Bicyclo Compounds, Heterocyclic (chemistry, therapeutic use)
• Humans
• Rats
• Receptor, Serotonin, 5-HT2A (metabolism)
• Serotonin 5-HT2 Receptor Antagonists (chemistry, pharmacokinetics, therapeutic use)
• Sleep (drug effects)
• Sleep Initiation and Maintenance Disorders (drug therapy)
• Structure-Activity Relationship