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

• Published in: Bioorganic & medicinal chemistry letters Vol. 6; no. 14; pp. 1641 - 1646
• Main Authors: Meanwell, Nicholas A., Sit, Sing-Yuen, Gao, Jinnian, Boissard, Christopher G., Lum-Ragan, Janet, Dworetzky, Steven I., Gribkoff, Valentin K.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 1996
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/0960-894X(96)00296-X

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-NO 2 analogue 4i. A series of benzimidazol-2-ones 4 structurally homologous to the maxi-K channel opener NS-004 were synthesized and evaluated by electrophysiological techniques as openers of the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes. The most efficacious activators of this channel were the 5-Cl and the 5-NO 2 analogues.