title: Prodrugs. Part 3. 2-Formylphenyl esters of indomethacin, ketoprofen and ibuprofen and 6-substituted 2-formyl and 2-acylphenyl esters of aspirin.
abstract: 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-formylphenyl indomethacin, 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 esters were more potent as anti-inflammatory agents than the parent compounds in the carragheenan-induced paw oedema test.
authors.affiliation: Department of Biological and Chemical Sciences, University of Essex, Colchester, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Abordo
authors.forename: K
authors.initials: K
authors.lastname: Bowden
authors.forename: A P
authors.initials: AP
authors.lastname: Huntington
authors.forename: S L
authors.initials: SL
authors.lastname: Powell
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D001241:Aspirin / Q000138:chemical synthesis*; D007052:Ibuprofen / Q000138:chemical synthesis*; D007213:Indomethacin / Q000138:chemical synthesis*; D007660:Ketoprofen / Q000138:chemical synthesis*; D008297:Male; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D007660:Ketoprofen; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin