Structure-activity relationship studies in the hemicholinium ('HC-3') series.

A series of congeners of hemicholinium ('HC-3') has been synthesized, in which the central biphenyl portion of the molecule has been modified, in order to gain insight into possible structural requirements of the biphenyl moiety needed for inhibition of choline uptake into nerve terminals. All molecular modifications resulted in compounds with qualitatively and quantitatively similar pharmacological properties to hemicholinium. It is concluded that the biphenyl portion of the hemicholinium molecule serves as a spacer for maintaining the separation of either the quaternary nitrogens, or the oxazonium rings, at an optimal distance for appropriate interaction with receptor site(s).