Synthesis of N-(halogenated) benzyl analogs of superpotent serotonin ligands

Abstract

In the last four years a group of extremely potent designer drugs, the N-benzylated phenylethylamines known as the NBOMe series, has surfaced on the street and in the news media. Although data documenting their high affinity and preference for 5-HT2 serotonin receptors abound (5-HT2A receptor activation is generally associated with the action of the "classical" hallucinogens), relatively little is known about the molecular basis of their potency and selectivity. In the setting of a project aiming to evaluate the possible involvement of halogen bonds in the binding of monoaminergic ligands to their receptors, we have begun to synthesize halogenated derivatives of known N-benzylated compounds for their pharmacological study. Here we report the synthesis of new phenylethylamine and tryptamine derivatives incorporating bromine atoms in their N-benzyl moiety.