Discovery of imidazole carboxamides as potent and selective CCK1R agonists

The discovery and optimization of a novel class of 1,2-diaryl imidazole carboxamides as CCK1R agonists are reported. Compound 44 exhibited excellent lean mouse overnight food intake reduction. High-throughput screening revealed diaryl pyrazole 3 as a selective albeit modest cholecystokinin 1 recepto...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry 2008-08, Vol.18 (15), p.4393-4396
Hauptverfasser:	Zhu, Cheng, Hansen, Alexa R., Bateman, Thomas, Chen, Zhesheng, Holt, Tom G., Hubert, James A., Karanam, Bindhu V., Lee, Susan J., Pan, Jie, Qian, Su, Reddy, Vijay B.G., Reitman, Marc L., Strack, Alison M., Tong, Vincent, Weingarth, Drew T., Wolff, Michael S., MacNeil, Doug J., Weber, Ann E., Duffy, Joseph L., Edmondson, Scott D.
Format:	Artikel
Sprache:	eng
Schlagworte:	1,2-Diaryl imidazole Amides - chemical synthesis Amides - chemistry Amides - pharmacology Animals Anti-Obesity Agents - chemical synthesis Anti-Obesity Agents - chemistry Anti-Obesity Agents - pharmacology Biological and medical sciences CCK1R agonist Chemokines, CC Cholecystokinin Combinatorial Chemistry Techniques Eating - drug effects Food intake reduction Gallbladder Emptying - drug effects General and cellular metabolism. Vitamins Humans Imidazoles - chemical synthesis Imidazoles - chemistry Imidazoles - pharmacology Medical sciences Mice Molecular Structure Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Obesity Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Receptors, Cholecystokinin - agonists Structure-Activity Relationship
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	The discovery and optimization of a novel class of 1,2-diaryl imidazole carboxamides as CCK1R agonists are reported. Compound 44 exhibited excellent lean mouse overnight food intake reduction. High-throughput screening revealed diaryl pyrazole 3 as a selective albeit modest cholecystokinin 1 receptor (CCK1R) agonist. SAR studies led to the discovery and optimization of a novel class of 1,2-diaryl imidazole carboxamides. Compound 44, which was profiled extensively, showed good in vivo mouse gallbladder emptying (mGBE) and lean mouse overnight food intake (ONFI) reduction activities.
ISSN:	0960-894X 0968-0896 1464-3405 1464-3391
DOI:	10.1016/j.bmcl.2008.06.057