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

A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were sy nthesised, substituted with a 2-acetoxybenzoate leaving group linked throug h the (indol-2-yl)methyl or (indol-3-yl)methyl (or propenyl) positions. Red uctive elimination of the leaving group occurred from the (indol-3-yl)methy l derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drug delivery, which was demonstrated with an aspirin prodrug. (C) 1998 Elsevier Science Ltd. All rights reserved.