Prodrugs for targeting hypoxic tissues: Regiospecific elimination of aspirin from reduced indolequinones

Article abstract of DOI:10.1016/S0960-894X(98)00695-7

A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were synthesised, substituted with a 2-acetoxybenzoate leaving group linked through the (indol-2-yl)methyl or (indol-3yl)methyl (or propenyl) positions. Reductive elimination of the leaving group occurred from the (indol- 3yl)methyl derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drag delivery, which was demonstrated with an aspirin prodrug.