6-Acylamino-2-amino-4-methylquinolines as potent melanin-concentrating hormone 1 receptor antagonists: Structure–activity exploration of eastern and western parts

SAR explorations of the eastern and western parts of recently disclosed 2-aminoquinoline MCH1R-antagonists are reported. Eastern part investigations confirmed a high degree of structural freedom, and a number of additional single digit nanomolar antagonists were identified. Investigations of the western part also confirmed the initial SAR analysis, requiring a para-substituted phenyl ring spaced from the 6-amide by two connecting atoms. The exploration led to the discovery of a novel sub-series with a 4-biphenylcarboxamide western part, also exhibiting single digit nanomolar affinity.

Graphical abstractFurther SAR investigations of the previously disclosed 2-aminoquinoline MCH1R antagonists resulted in identification of a novel biphenylcarboxamide antagonist.Figure optionsDownload full-size imageDownload as PowerPoint slide