Discovery of benzoylisoindolines as a novel class of potent, selective and orally active GlyT1 inhibitors

Benzoylisoindolines were discovered as a novel structural class of GlyT1 inhibitors. SAR studies and subsequent lead optimization efforts focused primarily on addressing hERG liability and on improving in vivo efficacy resulted in the identification of potent GlyT1 inhibitors displaying excellent selectivity and in vivo PD and PK profiles.

Graphical abstractBenzoylisoindolines were discovered as a novel structural class of GlyT1 inhibitors. The SAR studies followed by the lead optimization effort focused primarily on addressing hERG liability and on improving oral activity resulted in the identification of potent GlyT1 inhibitors displaying excellent selectivity and in vivo profiles.Figure optionsDownload full-size imageDownload as PowerPoint slide