Synthesis and cyclization reactions of 4-[bis(2-hydroxyethyl)amino]-9-(3-dimethylaminopropylamino)-1-nitroacridines: approaches to the synthesis of ‘Nitracrine Mustard’

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Abstract
Compounds which can be selectively activated to cytotoxic species in hypoxic mammalian cells have potential for the treatment of solid tumours, which uniquely contain cells in such an environment. One approach to such drugs is exemplified by the title compound (2), ‘Nitracrine Mustard,’ where selective reduction of the nitro group in hypoxic cells (known to occur in the case of Nitracrine itself) would activate the mustard moiety. Synthetic routes to the penultimate dihydroxy derivative (22) are reported. Attempts to prepare the mustard derivative for this and a series of analogous compounds were frustrated by rapid intramolecular cyclization reactions to give the dihydroxprazinoacridines (25).