Prodrugs. Part 3. 2-Formylphenyl esters 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-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.
Abordo
E A
EA
Department of Biological and Chemical Sciences, University of Essex, Colchester, UK.
Bowden
K
K
Huntington
A P
AP
Powell
S L
SL
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D007660:Ketoprofen; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin