Mazapertine (RWJ-37796) is an
antipsychotic
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
agent that was developed by
Johnson & Johnson
Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...
but never marketed. It exerts its pharmacological effect through affinity for
dopamine D2,
serotonin 5-HT1A, and
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
![Mazapertine synthesis](https://upload.wikimedia.org/wikipedia/commons/a/a1/Mazapertine_synthesis.svg)
Alkylation of
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 formula HOC6H4NO2. Three isomeric nitrophenols exist: ...
8-75-5(1) with
isopropyl bromide gives 2-isopropoxynitrobenzene
8753-50-3(2). Catalytic hydrogenation of nitro group gives 2-isopropoxyaniline
9026-74-2(3). Intermolecular ring formation of this aniline with nornitrogen mustard
34-22-5yields 1-(2-isopropoxyphenyl)piperazine
4013-91-1(4).
Amide formation of 3-(chloromethyl)benzoyl chloride
3024-77-1(5) with piperidine gives 1-
-(chloromethyl)benzoyliperidine
48583-64-6(6).
Ex 1: The last step is the convergent synthesis between the above two arms of the synthesis to afford the alkylation product mazapertine (7).
References
Antipsychotics
1-Piperidinyl compounds
Piperazines
Phenol ethers
Isopropyl compounds
Carboxamides
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