Mazapertine (RWJ-37796) is an

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

agent that was developed by

Johnson & Johnson Johnson & Johnson (J&J) is an American multinational pharmaceutical, biotechnology, and medical technologies corporation headquartered in New Brunswick, New Jersey, and publicly traded on the New York Stock Exchange. Its common stock is a c ...

but never marketed. It exerts its pharmacological effect through affinity for dopamine D₂, serotonin 5-HT_1A, and α₁-adrenergic receptors. Mazapertine is safe and well tolerated when administered orally. Analogs of mazapertine with

conformational restriction In chemistry, rotamers are chemical species that differ from one another primarily due to rotations about one or more single bonds. Various arrangements of atoms in a molecule that differ by rotation about single bonds can also be referred to as ...

have been prepared and have greater affinity for the 5-HT_1A receptor.

Synthesis

The laboratory synthesis of mazapertine has been reported.Allen B. Reitz, (1996 to Ortho McNeil Pharmaceutical Inc) It begins with

alkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

2-nitrophenol Nitrophenols are compounds of the formula HOC6H5−x(NO2)x. The conjugate bases are called nitrophenolates. Nitrophenols are more acidic than phenol itself. Mono-nitrophenols with the chemical formula, formula HOC6H4NO2. Three isomeric ni ...

(1) with isopropyl bromide to give 2-isopropoxynitrobenzene (2).

Catalytic hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...

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- -(chloromethyl)benzoyliperidine (6). The last step is the convergent synthesis between the above two arms of the synthesis to afford the alkylation product mazapertine (7). : Mazapertine synthesis

References

Antipsychotics 1-Piperidinyl compounds Piperazines Phenol ethers Isopropyl compounds Carboxamides Abandoned drugs {{Antipsychotics