Synthesis and evaluation of 5,5-diphenylimidazolones as potent human neuropeptide Y5 receptor antagonists

Kevin W Gillman; Mendi A Higgins; Graham S Poindexter; Marc Browning; Wendy J Clarke; Sharon Flowers; James E Grace Jr; John B Hogan; Rachel T McGovern; Lawrence G Iben; Gail K Mattson; Astrid Ortiz; Stefanie Rassnick; John W Russell; Ildiko Antal-Zimanyi

doi:10.1016/j.bmc.2006.04.042

Synthesis and evaluation of 5,5-diphenylimidazolones as potent human neuropeptide Y5 receptor antagonists

Bioorg Med Chem. 2006 Aug 15;14(16):5517-26. doi: 10.1016/j.bmc.2006.04.042. Epub 2006 May 11.

Authors

Kevin W Gillman¹, Mendi A Higgins, Graham S Poindexter, Marc Browning, Wendy J Clarke, Sharon Flowers, James E Grace Jr, John B Hogan, Rachel T McGovern, Lawrence G Iben, Gail K Mattson, Astrid Ortiz, Stefanie Rassnick, John W Russell, Ildiko Antal-Zimanyi

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, Richard L. Gelb Center for Pharmaceutical Research and Development, Wallingford, CT 06492, USA. gillmank@bms.com

PMID: 16697206
DOI: 10.1016/j.bmc.2006.04.042

Abstract

A series of novel 5,5-diphenylimidazolones was synthesized and evaluated for activity against the human neuropeptide Y5 receptor. The 3-pyridyl analog 46 demonstrated an IC(50) of 8.3 nM with a favorable pharmacokinetic profile in rats, but was ineffective in reducing food intake.

Publication types

Evaluation Study

MeSH terms

Animals
Anti-Obesity Agents / chemical synthesis
Anti-Obesity Agents / pharmacology*
Eating / drug effects*
Humans
Imidazoles / chemical synthesis
Imidazoles / pharmacology*
Inhibitory Concentration 50
Radioligand Assay
Rats
Rats, Sprague-Dawley
Receptors, Neuropeptide Y / antagonists & inhibitors*
Receptors, Neuropeptide Y / metabolism
Structure-Activity Relationship
Time Factors

Substances

Anti-Obesity Agents
Imidazoles
Receptors, Neuropeptide Y
neuropeptide Y5 receptor