3-Phenylpiperidines. Central Dopamine-Autoreceptor Stimulating Activity

Article abstract of DOI:10.1021/jm00144a021

Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity.The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity.Introduction of an additional hydroxyl group into the 4-position of the aromatic ring gives a compound with dopaminergic activity but lacking selectivity for autoreceptors. 3-(3-Hydroxyphenyl)-N-n-propylpyrrolidine, 3-(3-hydroxy)-N-n-propylperhydroazepine, and 3-(3-hydroxyphenyl)quinuclidine were all inactive.The most potent compounds were the N-isopropyl-, N-n-butyl-, N-n-pentyl-, and N-phenethyl-substituted 3-(3-hydroxyphenyl)piperidine derivatives.None of the compounds investigated seemed to have central noradrenaline- or serotonin-receptor stimulating activity.