Prodrugs - Part 3. 2-formylphenyl eaters of indomethacin, ketoprofen and ibuprofen and 6-substituted 2-formyl and 2-acylphenyl esters of aspirin

The synthesis and study of a novel series of potential prodrugs of indomethacin, ketoprofen, ibuprofen and aspirin are reported. 2-Formylphenyl esters of the NSAIDs, together with two 6-substituted 2-formyl and two 2-acylphenyl aspirins and 4-formylphenylindomethacin, have been prepared. A study of their alkaline and neutral hydrolysis shows that these compounds, with the exception of 2-acetylphenyl aspirin, act as true prodrugs of the NSAIDs, giving the NSAID and acylphenol. The rates of hydrolysis and activation parameters indicate that the 2-acylphenyl esters employ an intramolecular catalytic route. The 2-formylphenyl testers were more potent as anti-inflammatory agents than the parent compounds in the carragheenan-induced paw oedema test. (C) 1998 Elsevier Science S.A. All rights reserved.