Metitepine (; developmental code names Ro 8-6837 (

maleate Maleic acid or ''cis''-butenedioic acid is an organic compound that is a dicarboxylic acid, a molecule with two carboxyl groups. Its chemical formula is HO2CCH=CHCO2H. Maleic acid is the ''cis'' isomer of butenedioic acid, whereas fumaric acid ...

), VUFB-6276 (

mesylate In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the gr ...

)), also known as methiothepin, is a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

described as a " psychotropic agent" of the tricyclic or

tetracyclic Tetracyclics are cyclic compound, cyclic chemical compounds that contain four fused ring (chemistry), rings of atoms, for example, Tröger's base. Some tricyclic compounds having three fused and one tethered ring (connected to main nucleus by ...

group which was never marketed. It acts as a non-selective

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, and

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like b ...

s, including of the serotonin 5-HT₁, 5-HT₂, 5-HT₅, 5-HT₆, and 5-HT₇ receptors. The drug has

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 ...

properties.

Pharmacology

Pharmacodynamics

Chemistry

Analogues

Metitepine is closely structurally related to certain other tetracyclic compounds including

amoxapine Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylation, demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximat ...

, batelapine, clorotepine, clotiapine,

clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

, flumezapine, fluperlapine, loxapine, metiapine,

olanzapine Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomitin ...

, oxyprothepin, perathiepin, perlapine, quetiapine, tampramine, and tenilapine.

Synthesis

The reduction of 2-(4-methylsulfanylphenyl)sulfanylbenzoic acid
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(1) gives -(4-methylsulfanylphenyl)sulfanylphenylethanol
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(2). Halogenating with thionyl chloride gives 1-(chloromethyl)-2-(4-methylsulfanylphenyl)sulfanylbenzene
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(3). FGI with cyanide gives 2- -(4-methylsulfanylphenyl)sulfanylphenylcetonitrile
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(4). Alkali hydrolysis of the nitrile to 2- -(4-methylsulfanylphenyl)sulfanylphenylcetic acid
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(5). PPA cyclization to 3-methylsulfanyl-6H-benzo 1]benzothiepin-5-one
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(6). The reduction with sodium borohydride gives 3-methylsulfanyl-5,6-dihydrobenzo 1]benzothiepin-5-ol
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(7). Halogenating with a second round of thionyl chloride gives 5-chloro-3-methylsulfanyl-5,6-dihydrobenzo 1]benzothiepine
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Alkylation with 1-methylpiperazine 09-01-3completed the synthesis of Metitepine (9).

References

External links

* {{Tricyclics 5-HT1A antagonists 5-HT1E antagonists 5-HT1F antagonists 5-HT2A antagonists 5-HT6 antagonists 5-HT7 antagonists Abandoned drugs Alpha-1 blockers Antipsychotics Dibenzothiepines Dopamine antagonists 4-Methylpiperazin-1-yl compounds Serotonin receptor antagonists Thioethers