Synthesis and SAR of 1,3-disubstituted cyclohexylmethyl urea and amide derivatives as non-peptidic motilin receptor antagonists

A series of 1,3-disubstituted cyclohexylmethyl urea and amide derivatives were synthesized as motilin receptor antagonists. Starting from known motilin antagonists, 1a and 1b, the cyclopentene scaffold was replaced and the four recognition elements optimized to arrive at a potent novel series.

Graphical abstractA novel and potent motilin antagonist series was derived based on an understanding of the key binding elements of a known motilin antagonist.Figure optionsDownload full-size imageDownload as PowerPoint slide