Discovery of novel phenethylpyridone derivatives as potent melanin-concentrating hormone 1 receptor antagonists

Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand moiety led to the identification of a number of potent derivatives.

Graphical abstractA series of phenethylpyridones was identified as a potent melanin-concentrating hormone 1 receptor antagonist. The synthesis and structure–activity relationships (SAR) are described.Figure optionsDownload full-size imageDownload as PowerPoint slide