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Clomethiazole

Clomethiazole structure

CAS No:
533-45-9
Formula:
C6H8ClNS
Chemical Name:
Clomethiazole
Synonyms:
Thiazole,5-(2-chloroethyl)-4-methyl-;5-(2-Chloroethyl)-4-methylthiazole;Chlorethiazol;Chlormethiazole;Clomethiazole;Distraneurin;4-Methyl-5-(β-chloroethyl)thiazole;Chlormethiazol;Chlorethiazole;Clomethiazolum;Emineurina;Somnevrin;5-(β-Chloroethyl)-4-methylthiazole
Categories:
Organic Chemistry > Alcohols, Phenols, Phenol Alcohols

Description

Chlormethiazole is an potent and orally active GABAA agonist[1]. Chlormethiazole inhibits cytochrome P450 isoforms: CYP2A6 and CYP2E1 in human liver microsomes. Chlormethiazole is an anticonvulsant agent and has the potential for treating convulsive status epilepticus[2].

5-(2-chloroethyl)-4-methylthiazole is a member of thiazoles.|Clomethiazole is a well-established γ-aminobutyric acid (GABAA)-mimetic drug. It is a sedative and hypnotic that is widely used in treating and preventing symptoms of acute alcohol withdrawal. It is a drug which is structurally related to thiamine (vitamin B1) but acts like a sedative, hypnotic, muscle relaxant and anticonvulsant. It is also used for the management of agitation, restlessness, short-term insomnia and Parkinson's disease in the elderly.|A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors.

Clomethiazole Basic Attributes

Molecular Weight：

161.647

Exact Mass：

161.65

EC Number：

208-565-7

UNII：

0C5DBZ19HV

DSSTox ID：

DTXSID6022842

ATC Code：

N - Nervous system

HScode：

2934100090

Characteristics

PSA：

41.1

XLogP3：

2.1

Density：

1.233 g/cm³ @ Temp: 25 °C

Melting Point：

127-128 °C

Boiling Point：

92 °C

Flash Point：

102.4ºC

Storage Conditions：

Desiccate at RT

Safety Information

Precautionary statement(s)：

P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

Hazard Statements：

H302

GHS Classification：

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 6 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Drug Information

Drug Indication：

Investigated for use/treatment in strokes.

MeSH：

Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)|Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here. (See all compounds classified as GABA Modulators.)|Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. (See all compounds classified as Hypnotics and Sedatives.)|Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. (See all compounds classified as Neuroprotective Agents.)

Metabolism/Metabolites：

Clomethiazole has known human metabolites that include NLA-715.

Mechanism of Action：

clomethiazole interacts with the GABAA receptor complex. It inhibits the binding of [35S]butyl-bicyclophosphorothionate (TBPS), an effect indicative of GABAA receptor-channel activation, by increasing the rate of [35S]TBPS dissociation and decreasing the binding affinity. Gamma-aminobutyric acid (GABA), acting at GABAA receptors, is the main fast inhibitory neurotransmitter in mammalian central nervous system

MeSH Entry Terms：

Chlormethiazole

Clomethiazole Use and Manufacturing

Methods of Manufacturing

Reference 4-Methyl-5-thiazoleethanol (39.0 g, 272 mmol) was dissolved in CHCl3 (270 mL) and SOCl2 (40 mL, 0.55 mol, 2 equiv) was added dropwise with cooling on a water bath. The mixture was refluxed for 4 h, cooled to rt and evaporated. The residue was suspended in CH2Cl2 and aqueous K2CO3 (38 g, 0.28 mol, 1 equiv in 200 ml H2O). After stirring for 10 min the organic layer was separated and the aqueous layer was extracted with CH2Cl2 (2 x 100 mL). The combined organic layers were dried over Na2SO4 and evaporated. The residue was purified by distillation at reduced pressure. bp: 77–78 C (1–2 torr.); Yield: 84percent (36.97 g).

Uses

Hypnotic.

Computed Properties

Molecular Weight:161.65
XLogP3:2.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:161.0065981
Monoisotopic Mass:161.0065981
Topological Polar Surface Area:41.1
Heavy Atom Count:9
Complexity:89.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes