Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity.

Abstract

A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor antagonists has been discovered. Compound 17 was identified as a centrally penetrant molecule with high receptor occupancy which demonstrates robust oral activity in rodent models of obesity. In addition compound 17 possesses clean CYP and hERG profiles and shows no behavioral changes in the Irwin test.

• Authors: Manuel de Lera Ruiz, Junying Zheng, Michael Y Berlin, Kevin D McCormick, Robert G Aslanian, Robert West, Joyce Hwa, Jean Lachowicz, Margaret van Heek
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 21 Pg. 6004-9 (Nov 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 24035485 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Histamine H3 Antagonists
• Receptors, Histamine H3

Topics

• Animals
• Histamine H3 Antagonists (chemistry, metabolism, pharmacokinetics, therapeutic use)
• Humans
• Microsomes, Liver (metabolism)
• Obesity (drug therapy)
• Rats
• Receptors, Histamine H3 (metabolism)