Optimized synthesis and pharmacological evaluation of HCN channel inhibitor EC18

Marius Patberg; Tengiz Oniani; Paul Disse; Stefan Peischard; Laura Vinnenberg; Mehrnoush Zobeiri; Maria N. Romanelli; Lisa Epping; Heinz Wiendl; Sven G. Meuth; Petra Hundehege; Guiscard Seebohm; Thomas Budde; Anna Junker

Zusammenfassung

HCN4 channels are considered to be a promising target for cardiac pathologies, epilepsy, and multiple sclerosis. However, there are no subtype-selective HCN channel blockers available, and only a few compounds are reported to display subtype preferences, one of which is EC18 (cis-1). Herein, we report the optimized synthetic route for the preparation of EC18 and its evaluation in three different pharmacological models, allowing us to assess its activity on cardiac function, thalamocortical neurons, and immune cells.