Bioreductively-activated prodrugs for targeting hypoxic tissues: Elimination of aspirin from 2-nitroimidazole derivatives

2-Nitroimidazoles were synthesised substituted with aspirin or salicylic ac id, as leaving groups linked through the (imidazol-5-yl)methyl position. Ac tivation of aqueous solutions by CO2- (a model one-electron reductant) resu lted in release of aspirin or salicylate, probably via the 2-hydroxyaminoim idazole. The analogous 2-nitroimidazole with bromide as leaving group elimi nated bromide in < 1 ms via the radical-anion. (C) 1999 Elsevier Science Lt d. All rights reserved.