Synthesis and qsar of dequalinium analogues AS K+ channel blockers. investigations on the role of the 4-amino group

Dequalinium (1) is a potent and selective non-peptidic blocker of the SKCa channel. The contribution of the 4-amino group to activity was investigated by replacing it by other groups R4. The size or lipophilicity of R4 was found to be unimportant and a good correlation was obtained between σR for R4 and the blocking potency of the analogues, suggesting that the role of the NH2 group is electronic.