Large conductance calcium activated potassium ion channels are important in maintaining smooth muscle tone and a compound that increases this current could have potential therapeutic applications. The antifungal drug ketoconazole has been shown to increase current at these channels but only at high concentrations. Therefore partial structures of ketoconazole were synthesised and tested in order to identify the phannacophore The results from this series led to the synthesis of 2-(dichlorophenyl)-2-methyl-4- (phenoxymethyl)-1, 3-dioxolane which was a strong blocker of the channel and 2- (dichlorophenyl)-2-methyl-4-(4-aminophenoxymethyl)-l, 3-dioxolane which was a strong opener. Variation of the substituents at the 4-position of the phenoxy moiety was investigated and found to be crucial in determining the type of activity. Variation around the dichlorophenyl ring was performed but with no improvement for activity. Molecular modelling was used in the search for a replacement of the dioxolane ring. It was found that 1-(4-aminophenoxy)-2-hydroxy-3- (2,4-dichlorophenylmethyloxy)- propane folded in a similar fashion to the dioxolane, When synthesised and tested it was found to have and activity similar to ketoconazole. These results will be discussed together with a review of potassium channel biology and pharmacology.