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

  • Bioorg Med Chem Lett. 2010 Dec 1;20(23):7015-9. doi: 10.1016/j.bmcl.2010.09.039.
Matthew D Surman  1 ,  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
Affiliations
PMID: 20961756 DOI: 10.1016/j.bmcl.2010.09.039
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.