Synthesis and hypoxia-selective cytotoxicity of a 2-nitroimidazole mustard

A four-step synthesis of 5-[ N,N-bis(2-chloroethyl)amino]-1-methyl-2-nitroimidazole from 1-methyl-2-nitroimidazole is described. This compound showed similar hypoxia-selective cytotoxicity to the dinitrobenzamide mustard SN 23862 in UV4 cells (ca. 40-fold), and superior selectivity (>7-fold) in repaircompetent AA8 cells. The 2-nitroimidazole mustard ( 6) (was prepared in four steps from 1-methyl-2-nitroimidazole ( 7). It showed significant hypoxia-selective cytotoxicity in both repair-deficient UV4 cells (ca. 40-fold) and repair-competent AA8 cells (>7-fold).