N-Benzylated benzimidazol-2-one derivatives: activators of large-conductance Ca2+-dependent K+ channels

A series of benzimidazol-2-ones structurally homologous to the known maxi-K opener NS-004 (2) were synthesized and evaluated by electrophysiological techniques as openers of the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes. The structure-activity relationships reveal tolerance in the topological relationship between the heterocycle and the phenol hydroxy and indicate the importance of an electron withdrawing substituent on the heterocycle for expression of maxi-K opening properties. The most efficacious activators of this channel were the 5-Cl derivative 4f and the 5-NO2 analogue 4i.