Uniprofen

Originator

Opren,Dista Lilly,UK,1980

The Uses of Uniprofen

A non-steroidal anti-inflammatory ophthalmic agent.

Background

The use of benoxaprofen, formerly marketed as Oraflex tablets, was associated with fatal cholestatic jaundice among other serious adverse reactions. The holder of the approved application voluntarily withdrew Oraflex tablets from the market on August 5, 1982.

Definition

ChEBI: A monocarboxylic acid that is propionic acid substituted at position 2 by a 2-(4-chlorophenyl)-1,3-benzoxazol-5-yl group. It was used as a non-steroidal anti-inflammatory drug until 1982 when it was withdrawn from the market due to adverse side-effects inc uding liver necrosis, photosensitivity, and carcinogenicity in animals.

Manufacturing Process

The 6-benzoxazolyl analog of the 5-benzoxazolyl product is prepared as follows:
(a) Ethyl 2-(2-p-chlorophenyl-6-benzoxazolyl)propionate: A solution of ethyl 2-(3-hydroxy-4-aminophenyl)propionate (2.5 g) in pyridine (15 ml) was treated with p-chlorobenzoyl chloride (1.65 ml) at 5°C. After stirring for 2 hours at room temperature the solution was evaporated to dryness.
The residue was heated at 220°C until no more water was evolved, then was allowed to cool. This yielded ethyl 2-(2-p-Chlorophenyl-6- benzoxazolyl)propionate.
(b) 2-(2-p-Chlorophenyl-6-benzoxazolyl)propionic acid: A solution of ethyl 2- (2-chlorophenyl-6-benzoxazolyl)propionate (4 g) in aqueous sodium hydroxide (30 ml) was heated on a steam bath for one-half hour. On cooling the black solution was washed with chloroform. On acidification of the black solution with hydrochloric acid the mixture was extracted with chloroform. This solution on evaporation yielded 2-(2-p-chlorophenyl-6-benzoxazolyl)propionic acid, MP 196°C.

brand name

Oraflex (Lilly);90459 compound;Benoxapran;Bexopron;Compound 90459;Lilly 3794;Lilly 90459;Lrcl 3794;Oprenal.

Therapeutic Function

Antiinflammatory, Analgesic

World Health Organization (WHO)

Benoxaprofen, a nonsteroidal antiinflammatory agent, was introduced in 1980 for the treatment of rheumatic disorders. Following reports of serious adverse effects, some of which were fatal, it was withdrawn in several countries prior to worldwide withdrawal by the manufacturer in 1982.

Safety Profile

Poison by ingestion, subcutaneous, and intraperitoneal routes. Moderately toxic to humans by ingestion.Human systemic effects by ingestion: jaundice and gynecomastia (excessive development of the male mammary glands), changes in kidney tubules, decreased

Metabolism

Not Available