Chemical Properties
Pink Solid
Originator
Mogadan,Roche,W. Germany,1965
Uses
Anticonvulsant; hypnotic.
Controlled substance (depressant)
Definition
ChEBI: A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one which is substituted at positions 5 and 7 by phenyl and nitro groups, respectively. It is used as a hypnotic for the short-term management of insomnia and for the trea
ment of epileptic spasms in infants (West's syndrome).
Manufacturing Process
A mixture of 16.8 g of 2 -aminobenzophenone, 11.9 g of glycine ethyl ester
hydrochloride and 200 cc of pyridine was heated to reflux. After one hour, 20
cc of pyridine was distilled off. The solution was refluxed for 15 hours, then
11.9 g of glycine ethyl ester hydrochloride was added and the refluxing was
continued for an additional 4 hours. The reaction mixture was continued for
an additional 4 hours. The reaction mixture was concentrated in vacuo, then
diluted with ether and water. The reaction product, 5-phenyl-3H-1,4-
benzodiazepin-2(1H)-one, crystallized out, was filtered off, and then
recrystallized from acetone in the form of colorless rhombic prisms, MP 182°C
to 183°C.
48 g (0.2 mol) of 5-phenyl-3H-1 ,4-benzodiazepin-2(1 H)-one was dissolved
in 250 cc of concentrated sulfuric acid by stirring at 15°C for ? hour. The
solution was then cooled to 0°C and a mixture of 9.1 cc of fuming nitric acid
(90%, sp. gr. = 1.50) and 11.8 cc of concentrated sulfuric acid was added
dropwise with stirring, keeping the temperature of the reaction mixture
between -5°C and 0°C. After completion of the addition of the nitric acidsulfuric acid mixture, stirring was continued for 1 hour and the reaction
mixture was stored in the refrigerator overnight.
The mixture was then added dropwise to 2 kg of crushed ice with stirring and
cooling, keeping the temperature at 0°C. After 1 hour of stirring in the cold,
640 cc of concentrated ammonium hydroxide was added dropwise at 0°C to
pH 8. Stirring was continued for ? hour and the crude product was filtered off, washed with a small amount of ice water and sucked dry overnight. The
crude product was suspended in a mixture of 100 cc of methylene chloride
and 1,700 cc of alcohol. 50 g of decolorizing charcoal was added and the
mixture was refluxed with stirring for 2 hours. After standing overnight at
room temperature 15 g of diatomaceous earth filter aid was added and the
refluxing was resumed for 1? hours. The mixture was filtered while hot. The
clear, light yellow filtrate was concentrated in vacuo on the steam bath with
stirring to about 600 cc. The concentrate was stirred and cooled in ice for
about 2 hours; the precipitated crystalline product was filtered off, washed
with some petroleum ether and sucked dry. The product, 7-nitro-5-phenyl-3H-
1,4-benzodiazepin-2(1H)-one, was recrystallized from a mixture of 1,000 cc of
alcohol and 50 cc of methylene chloride to obtain white prisms melting at
224°C to 225°C.
Brand name
Mogadon (HoffmannLaRoche).
Therapeutic Function
1,3-Dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one
Clinical Use
Benzodiazepine:
Hypnotic
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: metabolism possibly increased by
rifampicin.
Antipsychotics: increased sedative effects; risk of
serious adverse effects in combination with clozapine.
Antivirals: concentration possibly increased by
ritonavir.
Disulfiram: metabolism of nitrazepam inhibited,
increased sedative effects.
Sodium oxybate: enhanced effects of sodium oxybate
- avoid
Metabolism
Metabolised in the liver, mainly by nitroreduction
followed by acetylation; none of the metabolites possess
significant activity.
Excreted in the urine mainly as metabolites.
