Etifoxine Chemical Properties

Melting point:

90-92℃

Boiling point:

421.2±55.0 °C(Predicted)

Density 

1.1716 (rough estimate)

vapor pressure 

0-1Pa at 20-25℃

refractive index 

1.5800 (estimate)

storage temp. 

Store at -20°C

solubility 

DMSO:60.0(Max Conc. mg/mL);199.47(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);99.74(Max Conc. mM)
DMF:PBS (pH 7.2) (1:8):0.1(Max Conc. mg/mL);0.33(Max Conc. mM)
Ethanol:20.0(Max Conc. mg/mL);66.49(Max Conc. mM)

form 

Solid:particulate/powder

pka

4.89±0.40(Predicted)

color 

Light yellow to yellow

LogP

4.09-4.52 at 21-25℃ and pH7

Safety Information

Toxicity

LD50 orally in mice: 12 g/kg (Hoffmann)

Etifoxine Usage And Synthesis

Description

Etifoxine is a positive allosteric modulator of α1β2γ2 and α1β3γ2 subunit-containing GABAA receptors.1 It selectively increases GABA-induced currents in X. laevis oocytes expressing α1β2γ2 or α1β3γ2 over α1β1γ2 subunit-containing receptors at 20 µM. Etifoxine inhibits binding of the GABAA receptor agonist muscimol in rat corticol membranes with a Kd value of 23 nM in a radioligand binding assay.2 It increases NGF-induced neurite outgrowth in PC12 cells when used at a concentration of 20 µM.3 Etifoxine (12.5 mg/kg, i.p.) increases the percentage of time spent in the open arms of the elevated plus maze in high-anxiety BALB/cByJ, but not C57BL/6, mice, indicating anxiolytic-like activity.4 It increases the seizure threshold in a mouse model of seizures induced by picrotoxin (Item No. 20771) with a minimum effective dose (MED) of 75 mg/kg.2 Etifoxine (50 mg/kg, i.p.) also increases the paw withdrawal threshold on the ipsilateral side in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant.5WARNING This product is not for human or veterinary use.

Originator

Circupon,Troponwerke,W. Germany

Definition

ChEBI: Etifoxine is a benzoxazine.

Manufacturing Process

30 parts of 1-(3'-hydroxyphenyl)-2-(N-benzylaminomethyl)-ethan-1-one are mixed with 100 parts of pyridine and 30 parts of pivalic anhydride and dissolved while warming. After heating for 1 hour under reflux, the acylation is complete. After concentrating the reaction solution, the product is precipitated from acetone/ether. Yield: 96.4% of 1-(3'-pivaloyloxyphenyl)-2- (N-benzylaminomethyl)-ethan-1-one.
3 parts of palladium/charcoal (10% strength) are prehydrogenated in water, thereafter 10 parts of 1-(3'-pivaloyloxyphenyl)-2-(N-benzylaminoethyl)-ethan- 1-one, dissolved in a 10-fold amount of water, are added dropwise at room temperature and hydrogenation is carried out until 1 mol of hydrogen has been taken up. After filtering off the catalyst, a further 3 parts of palladium/charcoal are added and hydrogenation is carried out until a further mol of hydrogen has been taken up. The catalyst is separated off and after removal of the solvent the hydrogenation product is reprecipitated from acetone/petroleum ether and from methanol/ether until it is pure according to thin layer chromatography. Yield: 38.8% of 1-(3'-pivaloyloxyphenyl)-2- ethylaminoethanol-1 hydroxide, melting point 208°C to 209°C.

Therapeutic Function

Tranquilizer

Etifoxine(21715-46-8)Related Product Information

• 2-amino-5-chloro-diphenyl methanol
• O-ISOPROPYLISOUREA HYDROCHLORIDE
• N,N-didemethylchlordimeform
• O-Ethylisourea hydrochloride
• demethylchlordimeform
• O-Methylisourea hydrochloride
• Etifoxine
• ISOPROPYL FORMIMIDATE HYDROCHLORIDE
• 4H-BENZO[D][1,3]OXAZIN-2-AMINE