Referenced in: none

Automatically associated channels: Kv11.1

Title: Optimization of piperidin-4-yl-urea-containing melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Reducing hERG-associated liabilities.

Authors: Susanne Berglund, Bryan J Egner, Henrik Gradén, Joakim Gradén, David G A Morgan, Tord Inghardt, Fabrizio Giordanetto

Journal, date & volume: Bioorg. Med. Chem. Lett., 2009 Aug 1 , 19, 4274-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19500982

Abstract
The discovery and optimization of piperidin-4-yl-urea derivatives as MCH-R1 antagonists is herein described. Previous work around the piperidin-4-yl-amides led to the discovery of potent MCH-R1 antagonists. However, high affinity towards the hERG potassium channel proved to be an issue. Different strategies to increase hERG selectivity were implemented and resulted in the identification of piperidin-4-yl-urea compounds as potent MCH-R1 antagonists with minimized hERG inhibition.