Discovery of a novel series of melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity

A new class of MCHR1 antagonists was discovered via a high-throughput screen. Optimization of the lead structure resulted in the identification of indole 10e. This compound possesses good pharmacokinetic properties across preclinical species and is efficacious in reducing food consumption in an MCH cannulated rat model and a cynomolgus monkey food consumption model. (C) 2011 Elsevier Ltd. All rights reserved.