Referenced in: none

Automatically associated channels: Kv11.1

Title: Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition.

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, 4268-73

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19500979

Abstract
Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration.