New azomycin acyclonucleosides. Synthesis and biodistribution of radiohalogenated analogues in tumor-bearing mice [1]

Article abstract of DOI:10.1002/jhet.5570300528

The design, synthesis and biological activities of several acyclonucleoside analogues related to misonidazole 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.