Chemical Properties
Light Beige Solid
Originator
Tanderil,Geigy,UK,1960
Uses
Anti-inflammatory;Cyclooxygenase inhibito
Indications
Oxyphenbutazone (Oxalid, Tandearil) is the principal
uricosuric metabolite of phenylbutazone. It has the
same indications and toxicities as phenylbutazone.
Definition
ChEBI: A metabolite of phenylbutazone obtained by hydroxylation at position 4 of one of the phenyl rings. Commonly used (as its hydrate) to treat pain, swelling and stiffness associated with arthritis and gout, it was withdrawn from the market 1984 following asso
iation with blood dyscrasis and Stevens-Johnson syndrome.
Manufacturing Process
43.2 parts of n-butyl malonic acid ethyl ester are added to a solution of 4.6 parts of sodium in 92 parts by volume of absolute alcohol. 39 parts of pbenzyloxy hydrazobenzene (MP 88° to 90°C) are added. About two-thirds of the alcohol is distilled off and 92 parts by volume of absolute xylene are added. Without removing the sloping condenser, the mixture is stirred for 12 hours at a bath temperature of 140° to 145°C. It is then cooled to 0° to 5°C, 100 parts of ice are added, the xylene is removed, the aqueous solution is extracted twice with chloroform and made acid to Congo red at 0° to 5°C with 6 N hydrochloric acid.
The precipitate is taken up in chloroform, the solution obtained is washed twice with water, then with saturated salt solution, dried over Na2SO4and evaporated under vacuum (bath temperature 20°C). The residue is recrystallized from alcohol and produces 1-(p-benzyloxyphenyl)-2-phenyl-4-nbutyl-3,5-dioxo-pyrazolidine (C) as tiny white needles which melt at 132° to 133°C.
16.6 parts of (C) are suspended in 166 parts by volume of ethyl acetate and, in the presence of 16.6 parts of Raney nickel, hydrogen is allowed to act at room temperature and atmospheric pressure.
After 6 hours the calculated amount of hydrogen has been taken up. The residue obtained after filtering and evaporating is taken up in benzene and extracted twice with diluted sodium carbonate solution. The alkali extract is then made acid to Congo red with 6 N hydrochloric acid and the precipitate is taken up in ethyl acetate. The solution obtained is washed twice with salt solution, dried with sodium sulfate and evaporated. The residue is recrystallized from ether/petroleum ether. 1-(p-hydroxyphenyl)-2-phenyl-4-n
Trade butyl-3,5-dioxo-pyrazolidine melts at 124° to 125°C.
brand name
Tandearil (Novartis);Algi-tandril;Anarreumol-b;Artzone;Buteril;Campozim;Defolgin;Difmedol;Dolo-phlogase;Dolo-tandril;Fibutrox;Gp 40705;Iltazon;Iltoxon;Inflamil;Mindaril;Miyadril;Oflamin;Otone;Oxybutazone;Oxybutol;Oxyperol;Oxyphenbutone;Phlogistol;Phlogont;Phloguran;Pilabutina;Realin;Rheumapax;Segudol;Suganril;Tanal;Tandacot;Teneral;Vefren.
Therapeutic Function
Antiinflammatory
World Health Organization (WHO)
Oxyphenbutazone, a pyrazolone derivative with anti-inflammatory,
analgesic and antipyretic activity, was introduced in 1955 for the treatment of
rheumatic disorders. It is one of the active metabolites of phenylbutazone and has
a similar spectrum of activity including an association with serious and sometimes
fatal adverse reactions, notably cases of aplastic anaemia and agranulocytosis.
Many national drug regulatory authorities consider that more recently introduced drugs offer a safer alternative for most, if not all, patients requiring
antiinflammatory agents. Although oxyphenbutazone has been widely withdrawn it
remains available in some countries.
General Description
Oxyphenbutazone is a derivative compound of phenylbutazone. Oxyphenbutazone is one of the metabolites
formed in the liver following administration of
phenylbutazone. Given orally it causes fewer
gastrointestinal adverse effects than phenylbutazone and is used at 300 – 400 mg/d for the same
indications as the parent drug.
Biochem/physiol Actions
Oxyphenbutazone is a non-steroid anti inflammatory; anti Mycobacterium tuberculosis agent. Oxyphenbutazone is known to cause inflammatory effects on tissues. Oxyphenbutazone, as a drug, decreases cellular exudates, without involving the pituitary-adrenal axis or the immunity response. Though the drug delivers a number of side effects, it is considered to be less toxic than phenylbutazone, due to decreased rate of intestinal absorption.
Clinical Use
Oxyphenbutazone is a nonsteroidal
anti-inflammatory drug, which was
used by oral, rectal, or topical administration
(400 - 600 mg/d) for the acute treatment of ankylosing
spondylitis, chronic polyarthritis, and
gout. Because of a high incidence of severe side
effects including disturbances of the hematopoietic
system like agranulocytosis and aplastic
anemia the compound is no longer used.
Oxyphenbutazone is a metabolite of phenylbutazone.
