3-Phenylpiperidines. Central dopamine-autoreceptor stimulating activity

Abstract

Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine were synthesized and tested for central dopamine-autoreceptor stimulating activity [in rat brain]. 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 [norepinephrine] or serotonin-receptor stimulating activity.