Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists.

Abstract The design, synthesis and structure–activity relationships of a novel class of N -phenylpyridone MCH1R antagonists are described. The core part of the N -phenylpyridone structure was newly designed and the side chain moieties that were attached to the core part were extensively explored. As a result of optimization of the N -phenylpyridone leads, we successfully developed the orally available, and brain-penetrable MCH1R selective antagonist 7c , exhibiting excellent anti-obese effect in diet-induced obese (DIO) mice.