Chlormezanone

Originator

Trancopal,Winthrop-Breon,US,1958

Uses

Skeletal muscle relaxant

Uses

The use of chlormezanone is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

Uses

Chlormezanone improves the emotional state of the patient, relieving moderate anxiety and stress. However, it has a number of side effects, and because it does not have any advantage over other anxiolytics, it is rarely used in practice.

Definition

ChEBI: A 1,3-thiazine that is 1,3-thiazinan-4-one S,S-dioxide in which a hydrogen at position 2 is substituted by a 4-chlorophenyl group and the hydrogen attached to the nitrogen is substituted by methyl. A non-benzodiazepine muscle relaxant, it was used in the management of anxiety and in the treatment of muscle spasms until being discontinued worldwide by its manufacturer in 1996, due to rare but serious cutaneous reactions.

Manufacturing Process

A solution of 4-chlorobenzaldehyde is reacted with beta-mercaptopropionic acid and with methylamine. The mixture is refluxed in benzene and water is removed from an overhead separator. The reaction mixture was cooled, washed with dilute ammonium hydroxide and water, and the benzene was removed by distillation in vacuo. The oily residue was taken up in ether from which it crystallized. The precipitate was recrystallized twice from ether to yield 2-(4-chlorophenyl)-3-methyl-4-metathiazanone.
A solution of 11.2 g of potassium permanganate in 100 ml of warm water was added dropwise to a well stirred solution of 10 g of 2-(4-chlorophenyl)-3- methyl-4-metathiazanone in 50 ml of glacial acetic acid. The temperature was kept below 30°C with external cooling. An aqueous sodium bisulfite solution was then added to remove the manganese dioxide. The thick whitish oil which separated was taken up in chloroform and the extract was washed with water. Removal of the chloroform by distillation in vacuo yielded an oily residue which solidified. The solid was recrystallized from isopropyl alcohol to give 5 gof the product, 2-(4-chlorophenyl)-3-methyl-4-metathiazanone-1,1-dioxide, MP 116.2° to 118.6°C (corr.).

brand name

Trancopal (Sanofi Aventis).

Therapeutic Function

Tranquilizer

World Health Organization (WHO)

Chlormezanone is a sedative with antianxiety properties and a central skeletal muscle relaxant effect. It had already been falling into obsolescence for several years.

Biological Activity

Anxiolytic and skeletal muscle relaxant that acts at the benzodiazepine site of GABA A receptors.

Synthesis

Chlormezanone, 2-(p-chlorophenyl)-tetrahydro-3-methyl-4H-1,3- tiazin-4-on-1,1-dioxide (5.2.8), is synthesized by joint condensation of mercaptopropionic acid, methylamine, and 4-chlorobenzaldehyde, evidently through the intermediate stage of formation of 4-chlorobenzylidenemethylamine, giving the aminothioacetal 2- (p-chlorophenyl)-tetrahydro-3-methyl-4H-1,3-tiazin-4-one (5.2.7). Oxidation of the sulfur atom using potassium permanganate gives chlormezanone (5.2.8) [62,63].

storage

Room temperature