New azomycin acyclonucleoside. Synthesis and biodistribution of radiohalogenated analogues in tumor‐bearing mice

Abstract

AbstractThe design, synthesis and biological activities of several acyclonucleoside analogues related to misoni‐dazole are described. The hydroxy‐5, bromo‐6, iodo‐7, and fluoro‐8 derivatives of ethoxymethylazomycin and iodopropenyloxymethylazomycin (12) have been prepared. Alkylation of silylated azomycin with haloethoxy‐methylene chloride gave the corresponding acyclonucleosides. Similarly, propargyloxymethylene chloride gave propargyloxymethylazomycin (10), which after hydrostannylation and subsequent iododestannylation yielded iodopropenyloxymethylazomycin (12). The radiolabeled [125I] or [18F] compounds were prepared from the corresponding substrates. Biodistribution results of the radiolabeled analogues in mice showed that compound 7 had good tumor uptake (2.0% injected dose/g at 1 hour). The high radioactive levels in blood and stomach, however, were perhaps due to in vivo deiodination or metabolism. Compound [125I]‐12 showed the highest tumor uptake (4.8 and 3.6% injected dose/g at 1 and 4 hours respectively) of all of the compounds tested. Relatively low thyroid uptake of radioactivity in mice dosed with compound [125I]‐12 indicates significantly reduced in vivo deiodination in comparison to compound [125I]‐7.