Mazapertine (RWJ-37796) is an antipsychotic agent that was developed by Johnson & Johnson but never marketed. It exerts its pharmacological effect through affinity for dopamine D<sub>2</sub>, serotonin 5-HT<sub>1A</sub>, and ñ<sub>1</sub>-adrenergic receptors.
Mazapertine is safe and well tolerated when administered orally.
Analogs of mazapertine with conformational restriction have been prepared and have greater affinity for the 5-HT<sub>1A</sub> receptor.
The laboratory synthesis of mazapertine has been reported. It begins with alkylation of 2-nitrophenol (1) with isopropyl bromide to give 2-isopropoxynitrobenzene (2). Catalytic hydrogenation of nitro group gives 2-isopropoxyaniline (3). Intermolecular ring formation of this aniline with bis(2-chloroethyl)amine yields 1-(2-isopropoxyphenyl)piperazine (4). Separately, amide formation of 3-(chloromethyl)benzoyl chloride (5) with piperidine gives 1-[3-(chloromethyl)benzoyl]piperidine (6). The last step is the convergent synthesis between the above two arms of the synthesis to afford the alkylation product mazapertine (7).