Bromomisonidazole: Synthesis and Characterization of a New Radiosensitizer

4-Bromomisonidazole has been synthesized by direct bromination of misonidazole and has been characterized chemically and in animals. The compound is highly stable in vitro and in vivo and, relative to misonidazole, has an increased partition coefficient of 2.9 in octanol-water. In EMT-6/UW tumor-bearing mice, misonidazole and 4-bromomisonidazole (1 mmole/kg) sensitize tumors equally well to137Cs γ rays; sensitizer enhancement ratios of$1.9\ [D_{0}\ (-\text{sensitizer})/D_{0}\ (+\text{sensitizer})]$were obtained for both drugs. Toxicity studies (${\rm LD}_{50/2\ \text{days}}$) showed that 4-bromomisonidazole is more toxic (${\rm LD}_{50}