KETOPHENYLBUTAZONE

Originator

Chebutan,Bioindustria,Italy,1961

The Uses of KETOPHENYLBUTAZONE

Antirheumatic.

Definition

ChEBI: A pyrazolidine that is phenylbutazone in which the two methylene hydrogens at postion 3 on the butyl chain are replaced by an oxo group.

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.

brand name

Benjor;Chebutan;Chepirol;Chetazolidin;Chetosol;Copirene;Gammachetone;Hichillos;Kentan-s;Kenta-s;Kenzon r;Ketobutane-jade;Ketofen;Neo-panalgyl;Neufenil;Neuphenyl;Phloguron;Recheton;Reuchetal;Reumo;Tkb;Vintab;Vintop.

Therapeutic Function

Antirheumatic

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