Glutethimide

Structural formula
	Simplified structural formula without stereochemistry
General
Non-proprietary name	Glutethimide
other names	3-ethyl-3-phenyl-2,6-piperidinedione; ( RS ) -3-Ethyl-3-phenylpiperidine-2,6-dione ( IUPAC ); (±) -3-Ethyl-3-phenylpiperidine-2,6-dione; rac -3-ethyl-3-phenylpiperidine-2,6-dione;
Molecular formula	C 13 H 15 NO 2
External identifiers / databases
EC number	201-012-0
ECHA InfoCard	100,000,921
PubChem	3487
DrugBank	DB01437
Wikidata	Q414236
Drug information
ATC code	N05 CE01
Drug class	Sedative, hypnotic
properties
Molar mass	217.26 g mol −1
Physical state	firmly
Melting point	84 ° C
pK s value	9.2
solubility	practically insoluble in water (999 mg · L −1 at 30 ° C); Easily soluble in ethyl acetate , acetone and diethyl ether ; soluble in methanol
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	600 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Glutethimide is a drug that has been used as a sedative and hypnotic . It was patented by Ciba in 1954 and was on the market in Germany under the trade name Doriden ^® .

From a chemical point of view it belongs to the group of piperidinediones - like methylprylon , pyrithyldione and thalidomide . These, in turn, are structural modifications of the barbiturates .

Mechanism of action

The duration of action of glutethimide corresponds to that of medium-active barbiturates. Its elimination half-life is 5–22 h. It has no advantages over barbiturates.

unwanted effects

An intoxication with glutethimide expressed similar to intoxication with barbiturates. Long-term use can lead to dependence .

synthesis

Glutethimide can be synthesized from benzyl cyanide . This is deprotonated with sodium amide and alkylated with ethyl bromide . The 2-phenylbutanoic acid nitrile obtained in this way is then subjected to a Michael addition to acrylonitrile , the 2-ethyl-2-phenyl-1,5-pentanedioic acid dinitrile obtained is then cyclocondensed in glacial acetic acid under the action of sulfuric acid to give glutethimide. The intermediate 2-phenylbutanoic acid nitrile can also be reacted with methyl acrylate . The resulting methyl 4-cyano-4-ethyl-4-phenylpentanoate can then be cyclized to the target compound in an analogous manner using glacial acetic acid and sulfuric acid. Racemic starting materials and intermediate compounds are used throughout the synthesis sequence. Glutethimide is thus obtained as a racemate in the synthesis variants.

Legal status

Glutethimide is listed in Annex II of the German Narcotics Act and is therefore one of the narcotics that are marketable but not prescribable.

literature

HPT Ammon (Ed.): Hunnius Pharmaceutical Dictionary. 9th edition. Walter de Gruyter, Berlin / New York 2004, ISBN 3-11-017487-1 , p. 662.
Entry on glutethimide. In: Römpp Online . Georg Thieme Verlag, accessed on January 2, 2015.
HJ Roth, H. Fenner: Medicines . Thieme, Stuttgart / New York 1988, ISBN 3-13-673501-3 , pp. 270-271.

Individual evidence

↑ ^a ^b ^c ^d Entry on glutethimide in the ChemIDplus database of the United States National Library of Medicine (NLM) .
^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X .
↑ ^a ^b data sheet glutethimide from Sigma-Aldrich , accessed on April 3, 2011 ( PDF ).
^ F. Hampl, J. Paleček: Farmakochemie. VŠCHT, Praha 2002, ISBN 80-7080-495-5 , p. 116. (Czech).
^ A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications. 4th edition. Thieme-Verlag, Stuttgart 2001, ISBN 1-58890-031-2 .

[ChemIDplus-1] Entry on glutethimide in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[MERCK_Index-2] The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X .

[Sigma-3] ta sheet glutethimide from Sigma-Aldrich , accessed on April 3, 2011 ( PDF ).

[4] F. Hampl, J. Paleček: Farmakochemie. VŠCHT, Praha 2002, ISBN 80-7080-495-5 , p. 116. (Czech).

[Kleemann-5] A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications. 4th edition. Thieme-Verlag, Stuttgart 2001, ISBN 1-58890-031-2 .