TUMOR-TARGETED BORANES .4. SYNTHESIS OF NITROIMIDAZOLE-CARBORANES WITH POLYETHER-ISOXAZOLE LINKS

Carboranes targeted to specific tumor tissues are important for boron neutron capture therapy (BNCT) of cancer. Previous attempts to use iso xazolylphenyl-linked nitroimidazole-carboranes for targeting to hypoxi c tumors were hampered by the low polarity and very low aqueous solubi lity of the compounds. Syntheses of polyether-linked nitroimidazole-is oxazole-carborane 17, 25, and 26 via 1,3-dipolar cycloaddition of appr opriate nitroimidazole-alkynes with nitrile oxides derived from alipha tic aldehyde oximes linked by a varying number of water-solubilizing e ther units to carborane have been developed. The stabilities of the ni trile oxides were much less than that of the corresponding 4-(carboran ylmethoxy)phenyl nitrile oxide and depended on their structure. The yi elds of isoxazoles varied accordingly and cycloaddition failed when ei ght ether units were included in the chain. Compounds 17, 25, and 26, with four, five, and six ether units, respectively, had increasingly c onvenient physical properties to permit biological evaluation.