5-NITROFURAN-2-YLMETHYL GROUP AS A POTENTIAL BIOREDUCTIVELY ACTIVATEDPRO-DRUG SYSTEM

5-Substituted isoquinolin-1-ones have been synthesised by one-pot Curt ius rearrangement of the corresponding substituted 3-phenylpropenoyl a zides and cyclisation. Arylmethylation of the anions of the isoquinoli nones with benzyl halides [4-methoxybenzyl chloride, 2-(chloromethyl)f uran and 5-nitrol-2-(tosyloxymethyl)furan] takes place exclusively at nitrogen. Nitration of 2-(furan-2-ylmethyl)isoquinolin-1-one in strong ly acidic medium gives 2-(5-nitrofuran-2-ylmethyl)isoquinqlin-2-one, w hereas weaker acidic conditions lead to dinitration. Curtius rearrange ment of 3-carboranylbutanoyl azide and trapping with 5-nitrofuran-2-yl methanol gives 5-nitrofuran-2-ylmethyl N-(3-carboranylpropyl)carbamate . Biomimetic reduction of these nitrofuranylmethyl derivatives of anti cancer drugs triggers release of the parent drugs. Thus, these nitrofu rans have potential applications as pro-drug for selective release of therapeutic drugs in hypoxic solid tumours.