MCH-R1 antagonists as potential anti-obesity drugs. Design strategies and structure-activity relationship

Obesity is a chronic disease that is characterized by an accumulation of excess adipose tissue. Actually, there are few safe and effective drugs for pharmacological treatment of obesity. Therefore, it becomes necessary the development of new drugs. In the last decade, the most promising target for obesity was melanin-concentrating hormone. Thereat, diverse pharmaceutical companies developed peptides and small molecules as MCH-R1 antagonists, but, these compounds had problems as affinity for hERG channel and poor pharmacokinetic profile. In this manuscript, we made a brief review of the most relevant strategy design and structure-activity relationships in the development of carboxamide, ureas, quinoline, and quinazoline derivatives as MCH-R1 antagonists.