Substituted pyrimidines as cannabinoid CB1 receptor ligands.

Abstract

Cannabinoid CB1 receptors have been the avenue of extensive studies since the first clinical results of rimonabant (SR141716) for the treatment of obesity and obesity-related metabolic disorders were reported in 2001. To further evaluate the properties of CB receptors, we have designed and efficiently prepared a series of substituted pyrimidines based on chemical structure of Merck's taranabant, a cannabinoid CB1 receptor inverse agonist. Noticeably, N4-((2S,3S)-3-(3-bromophenyl)-4-(4-chlorophenyl)butan-2-yl)-N6-butylpyrimidine-4,6-diamine (13b) demonstrated good binding affinity and decent selectivity for CB1 receptor (IC(50)=16.3nM, CB2/CB1=181.6).

• Authors: Min Ju Kim, Jong Yup Kim, Hee Jeong Seo, Junwon Lee, Sung-Han Lee, Mi-Soon Kim, Jahyo Kang, Jeongmin Kim, Jinhwa Lee
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 16 Pg. 4692-7 (Aug 15 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19596576 (Publication Type: Journal Article)

Chemical References

• Anti-Obesity Agents
• Ligands
• Pyrimidines
• Receptor, Cannabinoid, CB1

Topics

• Animals
• Anti-Obesity Agents (chemical synthesis, chemistry, pharmacology)
• Ligands
• Pyrimidines (chemical synthesis, chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors, metabolism)