Referenced in: none

Automatically associated channels: Kv11.1

Title: 5-(pyridinon-1-yl)indazoles and 5-(furopyridinon-5-yl)indazoles as MCH-1 antagonists.

Authors: Matthew D Surman, Emily E Freeman, James F Grabowski, Mark Hadden, Alan J Henderson, Guowei Jiang, Xiaowu May Jiang, Michele Luche, Yuri Khmelnitsky, Steven Vickers, Jean Viggers, Sharon Cheetham, Peter R Guzzo

Journal, date & volume: Bioorg. Med. Chem. Lett., 2010 Dec 1 , 20, 7015-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20961756

Abstract
A new series of 5-(pyridinon-1-yl)indazoles with MCH-1 antagonist activity were synthesized. Potential cardiovascular risk for these compounds was assessed based upon their interaction with the hERG potassium channel in a mini-patch clamp assay. Selected compounds were studied in a 5-day diet-induced obese mouse model to evaluate their potential use as weight loss agents. Structural modification of the 5-(pyridinon-1-yl)indazoles to give 5-(furopyridinon-5-yl)indazoles provided compounds with enhanced pharmacokinetic properties and improved efficacy.