PRODRUGS - PART 3 - 2-FORMYLPHENYL EATERS OF INDOMETHACIN, KETOPROFENAND IBUPROFEN AND 6-SUBSTITUTED 2-FORMYL AND 2-ACYLPHENYL ESTERS OF ASPIRIN

The synthesis and study of a novel series of potential prodrugs of ind omethacin, ketoprofen, ibuprofen and aspirin are reported. 2-Formylphe nyl eaters of the NSAIDs, together with two 6-substituted 2-formyl and two 2-acylphenyl aspirins and 4-formylphenylindomethacin, have been p repared. A study of their alkaline and neutral hydrolysis shows that t hese compounds, with the exception of 2-acetylphenyl aspirin, act as t rue prodrugs of the NSAIDs, giving the NSAID and acylphenol. The rates of hydrolysis and activation parameters indicate that the 2-acylpheny l eaters employ an intramolecular catalytic route. The 2-formylphenyl testers were more potent as anti-inflammatory agents than the parent c ompounds in the carragheenan-induced paw oedema test. (C) 1998 Elsevie r Science S.A. All rights reserved.