The identification of pyrimidine-diazabicyclo[3.3.0]octane derivatives as 5-HT2C receptor agonists.

Abstract

The 5-HT2C receptor has been implicated in the regulation of appetite. As such, small molecule agonists to this receptor may serve as novel therapies to combat obesity. We describe here the identification, synthesis, and SAR of a 5-HT2C agonist from a unique pyrimidine-diazabicyclo[3.3.0]octane series. This compound displayed good potency at the 5-HT2C receptor, modest selectivity relative to other 5-HT2 receptors, and was efficacious in an acute feeding study in rats.

• Authors: Bayard R Huck, Luis Llamas, Michael J Robarge, Thomas C Dent, Jianping Song, William F Hodnick, Chris Crumrine, Alain Stricker-Krongrad, John Harrington, Kurt R Brunden, Youssef L Bennani
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 11 Pg. 2891-4 (Jun 01 2006) ISSN: 0960-894X [Print] England
• PMID: 16546379 (Publication Type: Journal Article)

Chemical References

• Amines
• Aza Compounds
• Bridged Bicyclo Compounds
• Pyrimidines
• Receptor, Serotonin, 5-HT2C
• Serotonin 5-HT2 Receptor Agonists

Topics

• Amines (chemistry)
• Animals
• Aza Compounds (chemical synthesis, chemistry, pharmacology)
• Bridged Bicyclo Compounds (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Pyrimidines (chemical synthesis, chemistry, pharmacology)
• Rats
• Receptor, Serotonin, 5-HT2C (metabolism)
• Serotonin 5-HT2 Receptor Agonists
• Stereoisomerism
• Structure-Activity Relationship