Aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists—Increasing selectivity over hERG

A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 μM.

A direct correlation between hERG binding and QTc prolongation was established for this series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists.Figure optionsDownload as PowerPoint slide