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-HT 2 serotonin receptors abound (5-HT 2A 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. Keywords: designer drugs, N -benzylphenylethylamine, N -benzyltryptamine, synthesis INTRODUCTION The last three years have seen the appearance on the informal market of a novel, extremely potent group of designer drugs commonly known as the NBOMe series. These compounds were first described in conference proceedings and in a Ph.D. thesis and shown to be at least partial agonists at the 5-HT