Pirprofen

Originator

Rengasil, Ciba Geigy ,France ,1981

Uses

Pirprofen is a non-steroidal anti-inflammatory drug.

Uses

Anti-inflammatory.

Definition

ChEBI: Pirprofen is a pyrroline.

Manufacturing Process

To the mixture of 85.5 g ethyl α-(3-chloro-4-aminophenyl)-propionate hydrochloride, 142 g sodium carbonate and 600 ml dimethyl formamide, 107g 1,4-dibromo-2-butene are added dropwise while stirring and the whole is refluxed for 5 hours and allowed to stand overnight at room temperature. The mixture is filtered, the filtrate evaporated in vacuo, the residue is triturated with hexane, the mixture filtered, the residue washed with petroleum ether and the filtrate evaporated. The residue is combined with 280 ml 25% aqueous sodium hydroxide and the mixture refluxed for 8 hours. After cooling, it is diluted with water, washed with diethyl ether, the pH adjusted to 5 to 5.2 with hydrochloric acid and extracted with diethyl ether. The extract is dried, filtered, evaporated and the residue crystallized from benzene-hexane, to yield the α-(3-chloro-4-pyrrolinophenyl)-propionic acid melting at 94°C to 96°C.

Therapeutic Function

Antiinflammatory

World Health Organization (WHO)

Pirprofen, a nonsteroidal anti-inflammatory agent, was introduced in 1982 primarily for the treatment of rheumatic diseases, as well as for use in posttraumatic and post-operative inflammatory conditions, acute gout and dysmenorrhoea. Reports of serious adverse effects, in particular cases of liver toxicity, some of which were fatal, led the manufacturer, in 1985 and in 1989, to amend the approved product information of the drug, limiting duration of treatment and lowering the recommended doses. In the light of these successive restrictions, which have considerably reduced the field of application of pirprofen and in view of available alternatives, the manufacturer has decided to discontinue the drug worldwide.

Trade name

Rengasil (Ciba, Greece), Seflenyl (Geigy, Argentina).

Clinical Use

Pirprofen has been used to treat rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. An optimal dosing regimen of 200 mg three times a day has been developed for maximal activity with minimal adverse effects. Pirprofen also is effective in relieving pain from malignant disease and oral surgery.

Synthesis

Synthesis: treatment of the sodium salt of diethyl methylmalonate with 2,4- dichloronitrobenzene yields diethyl (3-chloro- 4-nitrophenyl)methylmalonate. Saponification, decarboxylation, and subsequent reesterification followed by catalytic reduction gives ethyl 4-amino-3-chloro-α-methylbenzeneacetate hydrochloride. Treatment of the latter with 1,4- dichloro-2-butene in the presence of sodium carbonate followed by saponification affords pirprofen.

Raw materials

Preparation Products