Originator
Chebutan,Bioindustria,Italy,1961
Manufacturing Process
(a) 3,3-ethylene dioxyburyl malonic acid diethyl ester: Diethylmalonate is
reacted with methyl vinyl ketone and the resulting oxobutyl diethylmalonate is
reacted with ethylene glycol.
(b) 1,2-diphenyl-4-(3',3'-ethylene dioxybutyl)3,5-dioxopyrazolidine: 274 parts
of (3,3-ethylene dioxybutyl)-malonic acid diethyl ester are dissolved in 100
parts by volume of abs. benzene and 57 parts of sodium ethylate and 184
parts of hydrazobenzene are added. Heat is generated. The reaction mass is
boiled for 15 hours under reflux. After cooling, it is poured into water,
separated and the aqueous part is washed twice with benzene. The benzene
solutions are washed three times with 2N sodium carbonate solution and the
unified aqueous solutions are acidified with 2N hydrochloric acid. The 1,2-
phenyl-4-(3',3'-ethylene dioxybutyl)-3,5-dioxopyrazolidine which precipitates
can be recrystallized from alcohol. Melting point 165°C to 167°C.
(c) 1,2-diphenyl-4-(3'-oxobutyl)-3,5-dioxopyrazolidine: 36.6 parts of 1,2-
diphenyl-4-(3',3'-ethylene dioxybutyl)-3,5-dioxopyrazolidine in 750 parts byvolume of acetone are boiled under reflux for 18 hours with 0.35 part of ptoluene sulfonic acid. The solution is then filtered, 1,500 parts of water are
added and the whole is allowed to stand for 24 hours at 5°C. The 1,2-
diphenyl-4-(3'-oxobutyl)-3,5-dioxopyrazolidine which precipitates is filtered off
under suction and washed with 50% acetone. Melting point from alcohol/water
mixture: 115.5°C to 116.5°C. Sometimes a crystal form is obtained which
melts at 127.5°C to 128.5°C.
World Health Organization (WHO)
Kebuzone, a pyrazolone derivative with anti-inflammatory,
analgesic and antipyretic activity, was introduced in 1973 for the treatment of
rheumatic disorders. As it is structurally related to phenylbutazone it is subjected
to rigorously restricted indications by some national regulatory authorities. See
WHO comment for phenylbutazone.
Clinical Use
Kebuzone is a nonsteroidal
anti-inflammatory drug used for the
treatment of acute and chronic pain and inflammation
states like musculoskeletal, joint, and
soft-tissue disorders. Kebuzone is administered
orally, rectally, or intramuscular (up to 1500
mg/d i
