Synthesis and SAR of 4-aryl-1-(indazol-5-yl)pyridin-2(1H)ones as MCH-1 antagonists for the treatment of obesity

Mark Hadden; Dustin M Deering; Alan J Henderson; Matthew D Surman; Michele Luche; Yuri Khmelnitsky; Steven Vickers; Jean Viggers; Sharon Cheetham; Peter R Guzzo

doi:10.1016/j.bmcl.2010.09.037

Synthesis and SAR of 4-aryl-1-(indazol-5-yl)pyridin-2(1H)ones as MCH-1 antagonists for the treatment of obesity

Bioorg Med Chem Lett. 2010 Dec 1;20(23):7020-3. doi: 10.1016/j.bmcl.2010.09.037. Epub 2010 Sep 21.

Authors

Mark Hadden¹, Dustin M Deering, Alan J Henderson, Matthew D Surman, Michele Luche, Yuri Khmelnitsky, Steven Vickers, Jean Viggers, Sharon Cheetham, Peter R Guzzo

Affiliation

¹ AMRI, 26 Corporate Circle, Albany, NY 12212-5098, USA. mark.hadden@amriglobal.com

PMID: 20951036
DOI: 10.1016/j.bmcl.2010.09.037

Abstract

A new series of 4-aryl-1-(indazol-5-yl)pyridin-2(1H)ones possessing MCH-1 receptor antagonism is presented. Suzuki coupling of boronic acids with key triflate 6 allowed rapid generation of a range of analogs. The SAR of the MCH-1 receptor was explored with a variety of aryl and heterocyclic moieties. Selected compounds were studied in a five-day diet induced obese mouse model to evaluate their potential use as weight loss agents.

MeSH terms

Animals
Anti-Obesity Agents / chemistry*
Anti-Obesity Agents / pharmacology
Mice
Obesity / drug therapy*
Pyridines / chemistry*
Pyridines / pharmacology
Receptors, Pituitary Hormone / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Anti-Obesity Agents
Pyridines
Receptors, Pituitary Hormone
melanin-concentrating hormone receptor