The medicinal chemistry of ibuprofen

In 1952 the research programme of Boots Pure Drug Company underwent a radical realignment under the new Research Director Dr. Gordon Hobday when attention was concentrated on ‘diseases of civilization’, in which was included rheumatic conditions. The 4-biphenylyl compound was selected for a clinical trial in 1960; mindful of the adverse gastric effects of aspirin, believed to be due to the carboxylic acid group, the team elected to use the ethyl ester instead of the acid. The compound was totally inactive when given to rheumatoid patients at 1.8 g/day. This setback represented the first major crisis point in the project as it cast doubts on the relevance of the utltraviolet erythema (UVE) test to the human disease condition. The abandonment of ibufenac was the second major crisis point in the project: phenylacetic acids had been eliminated by reason of side-effects in three clinically effective compounds, not detected in laboratory testing.