2-heteroaryl benzimidazole derivatives as melanin concentrating hormone receptor 1 (MCH-R1) antagonists

Abstract

A novel series of 2-heteroaryl substituted benzimidazole derivatives, containing the piperidinylphenyl acetamide group at the 1-position, were synthesized and evaluated as MCH-R1 antagonists. Extensive SAR investigation probing the effects of C-2 heteroaryl group led to the identification of 2-[2-(pyridin-3-yl)ethyl] analog 3o, which exhibits highly potent MCH-R1 binding activity with an IC50 value of 1 nM. This substance 3o also has low hERG binding activity, good metabolic stability, and favorable pharmacokinetic properties.