Synthesis and evaluation of novel alkylpiperazines as potential dopamine antagonists

Article abstract of DOI:10.1021/jm00138a007

Several alkylpiperazines, monocyclic subfragments of known tricyclic neuroleptic agents, were evaluated as dopamine antagonists in the isolated rabbit ear artery preparation. Compounds prepared and evaluated are of the general structure Ar-X-(CH₂)(n)-Y, where X = C, O, and N, n = 1-3, and Y, for the most part, was 4-methylpiperazine. Those compounds where X = NH, n = 3, and X = (Z)-CH=CH, n = 2, with an electron-witdrawing group meta to the side chain, possess dopamine antagonist activity comparable to that of clozapine. It is concluded that the entire tricyclic structure of phenothiazine-like agents (or at least more than a monocyclic ring system) is necessary for optimal activity as a dopamine antagonist in the receptor preparation used in this study.