[2-(ω-Phenylalkyl)phenoxy]alkylamines II : Synthesis and Selective Serotonin-2-Receptor Binding

Abstract

A series of [2-(ω-phenylalkyl)phenoxy]alkylamines was synthesized and thir receptor binding affinity was examined in vitro. These compounds showed an affinity for serotonin-2 (5-HT₂) and dopamine-2 (D₂) receptors. [2-(2-phenylethyl)phenoxy]alkylamine derivatives with a pyrrolidine or piperidine moiety in the structure showed higher affinity for 5-HT₂ receptors but lower affinity for D₂ receptors. Among these compounds, (S)-2-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]1-methylpyrrolidine, (S)-27, exhibited the most potent and selective affinity for 5-HT₂ receptors. Furthermore, (S)-27 was effective in inhibiting 5-HT-induced vasoconstriction in vitro and platelet aggregation both in vitro and ex vivo.