Discovery, oral pharmacokinetics and in vivo efficacy of a highly selective 5-HT4 receptor agonist: Clinical compound TD-2749

Further application of our multivalent approach to drug discovery directed to 5-HT4 receptor agonists is described. Optimization of the linker and secondary binding amine in the indazole-tropane primary binding group series, for binding affinity and functional potency at the 5-HT4 receptor, selectivity over the 5-HT3 receptor, oral pharmacokinetics, and in vivo efficacy in models of GI motility, resulted in the identification of clinical compound TD-2749.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide