Mazapertine


Mazapertine is an antipsychotic agent that was developed by Johnson & Johnson but never marketed. It exerts its pharmacological effect through affinity for dopamine D2, serotonin 5-HT1A, and Alpha-1 [adrenergic receptor|α1-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-HT1A receptor.

Synthesis

The laboratory synthesis of mazapertine has been reported. It begins with alkylation of 2-nitrophenol with isopropyl bromide to give 2-isopropoxynitrobenzene. Catalytic hydrogenation of nitro group gives 2-isopropoxyaniline. Intermolecular ring formation of this aniline with bisamine yields 1-piperazine. Separately, amide formation of 3-benzoyl chloride with piperidine gives 1-piperidine . The last step is the convergent synthesis between the above two arms of the synthesis to afford the alkylation product mazapertine.