57-53-4

Usage

Uses

Used in Pharmaceutical Industry:
Meprobamate is used as an anxiolytic for treating anxiety disorders. It helps in reducing anxiety and promoting relaxation without causing drowsiness or significant sedation.
Used in Medical Field:
Meprobamate is used as a sedative-hypnotic agent for inducing sleep and treating insomnia. It is also effective against absence seizures and may be prescribed for this purpose.
Used in Controlled Substances:
Meprobamate is a controlled substance due to its potential for abuse and dependence. It is regulated to ensure that it is used appropriately and safely in medical settings.

Originator

Equanil,Wyeth,US,1955

Manufacturing Process

A solution containing 52.8 parts of 2-methyl-2-n-propyl-1,3-propanediol and 128 parts of acetone is added with stirring to 112 parts of liquid phosgene at such a rate that the temperature of the reaction is maintained at -5° to 0°C. The reaction is stirred one hour at about 0°C then cooled to -15°C. A cooled 30% solution of 32 parts of sodium hydroxide is added with stirring to the reaction at such a rate that the temperature is maintained at -15° to -5°C. The mixture is stirred for an additional ? hour at about 0°C then cooled to - 20°C. 180 parts of cooled ammonium hydroxide solution (28.6% NH3) are added while cooling and with stirring at such a rate that the temperature rises slowly to 20°C and stirring is continued for an additional ? hour. The mixture is poured with agitation into 1,700 parts of ice water. The solid which separates is removed by filtration and dried. Recrystallization from water gives 55 parts (63% of theoretical yield) of 2-methyl-2-n-propyl-1,3-propanediol dicarbamate, MP 104° to 105°C.

Therapeutic Function

Tranquilizer

World Health Organization (WHO)

Meprobamate, a bis-carbamate ester, was introduced in 1955 for the treatment of anxiety and was subsequently used as a sedative-hypnotic drug. Psychological and physical dependence can occur and abuse has been reported. Meprobamate is controlled under Schedule IV of the 1971 Convention on Psychotropic Substances. (Reference: (UNCPS4) United Nations Convention on Psychotropic Substances (IV), , , 1971)

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Meprobamate is a carbamate ester. Carbamates are chemically similar to, but more reactive than amides. Like amides they form polymers such as polyurethane resins. Carbamates are incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. Flammable gaseous hydrogen is produced by the combination of active metals or nitrides with carbamates. Strongly oxidizing acids, peroxides, and hydroperoxides are incompatible with carbamates.

Hazard

Central nervous system depressant, use restricted by law.

Fire Hazard

Flash point data for Meprobamate are not available; however, Meprobamate is probably combustible.

Clinical Use

Meprobamate is also a centrally acting skeletal musclerelaxant. The agents in this group find use in several conditions,such as strains and sprains that may produce acutemuscle spasm. They have interneuronal blocking propertiesat the level of the spinal cord, which are said to bepartly responsible for skeletal muscle relaxation.Also,the general CNS depressant properties they possess maycontribute to, or be mainly responsible for, the skeletalmuscle relaxant activity.

Safety Profile

Human poison by unspecified routes. Moderately toxic to humans and experimentally by ingestion. Experimental poison by intravenous, intraperitoneal, and subcutaneous routes. An experimental teratogen. Human systemic effects by ingestion: coma, blood pressure decrease, regional or general arteriolar constriction, dyspnea, cyanosis, respiratory depression, nausea or vomiting, and allergic skin dermatitis. Experimental reproductive effects. Mutation data reported. Implicated in aplastic anemia. Used as a tranquilizer. When heated to decomposition it emits toxic fumes of NOx.

Purification Methods

Crystallise it from hot water, aqueous EtOH (m 104-105.5o) or xylene (m 104.1-105.3o). It can be an addictive drug. [Beilstein 3 IV 73.]

InChI:InChI=1/C9H18N2O4/c1-3-4-9(2,5-14-7(10)12)6-15-8(11)13/h3-6H2,1-2H3,(H2,10,12)(H2,11,13)

Upstream product

• 78-26-2 2-methyl-2-propyl-1,3-propanediol 
• 57-13-6 urea 
• 51-79-6 urethane 
• 143-33-9 sodium cyanide 
• 93047-97-3 2-Methyl-2-propyl-1,3-propandiol-bis-thioncarbamat 
• 1885-14-9 phenyl chloroformate 
• 75-44-5 phosgene 

Downstream Products

• 1672-86-2 N,N'-Diacetyl-2-methyl-2-propyl-1,3-dicarbamoyloxy-propan 
• 1672-82-8 N,N'-Bis-diphenylmethyl-meprobamat 
• 25652-14-6 N,N'-Dinitro-2-methyl-2-propyl-1,3-dicarbamoyl-oxy-propan 
• 25648-69-5 N,N'-Bis-(2,2,2-trichlor-hydroxy-aethyl)-2-methyl-2-propyl-1,3-dicarbamoyloxy-propan 
• 78-26-2 2-methyl-2-propyl-1,3-propanediol 

Relevant academic research and scientific papers

Iron-catalyzed reaction of urea with alcohols and amines: A safe alternative for the synthesis of primary carbamates

A general study of the iron-catalyzed reaction of urea with nucleophiles is here presented. The carbamoylation of alcohols allows for the synthesis of N-unsubstituted (primary) carbamates, including present drugs (Felbamate and Meprobamat, without the necessity to apply phosgene and related derivatives. Using amines as nucleophiles gave rise to the respective mono-and disubstituted ureas via selective transamidation reaction. These atom-economical transformations provide a direct and selective access to valuable compounds from cheap and readily available urea using a simple Lewis-acidic iron(Icatalyst.

Benzo-as-triazine derivatives

The invention relates to new benzo-as-triazine derivatives of the formulae (I) and (Ia) and pharmaceutically acceptable acid addition salts thereof, STR1 wherein R1 and R2 each represent hydrogen, a C1-20 alkylcarbonyl group, a phenylcarbonyl or phenyl-(C1-4 alkyl)-carbonyl group having optionally one or more halogen, hydroxy or C1-3 alkoxy substituents which may be the same or different, furthermore a pyridylcarbonyl, a pyrazinylcarbonyl, a furylcarbonyl, a chloroacetyl or a C1-4 alkoxycarbonyl group, or R1 and R2 may form, together with the adjacent nitrogen atoms, a pyrazole ring having optionally a C1-6 alkyl substituent in position 4, with the proviso that one of R1 and R2 is always different from hydrogen, R3 stands for hydrogen, mercapto group, a C1-4 alkylmercapto group, amino group, a C1-4 alkylamino group, a piperazino group having optionally an N-alkyl or 2-pyridyl substituent, a morpholino group or a piperidino group, and R4 stands for hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy group. The compounds of the formulae (I) and (Ia) are prepared by acylating the respective 2,4,5-unsubstituted 4,5-dihydro-benzo-as-triazine derivatives. The new compounds of the formulae (I) and (Ia) possess analgesic, antiphlogistic and narcosis-potentiating effects.

Pharmaceutical composition and process of treatment

A process for alleviating proliferative skin diseases such as psoriasis, atopic dermatitis, etc. comprising administering to humans, or domesticated animals, topically and/or systemically a composition comprising a pharmaceutical carrier and at least one active compound selected from the groups, substituted alkyl zanthines, tricyclic antidepressants, organic nitrates, antihypertensives, anti-asthma agents and central nervous system depressants and combinations of certain compounds from specifically named groups of compounds.