An approach to the design and synthesis of mercaptoimidazole derivatives containing oxidized sulfur based on electron affinity sensitization.

New mercaptoimidazole derivatives containing oxidized sulfur were designed and synthesized for screening with hypoxic radioresistant cells in place of nitroimidazoles, which are well-known radiosensitizing agents. The electron affinities of various mercaptoimidazole derivatives such as the sulfoxide (4) and sulfone (5) were estimated on the basis of the lowest unoccupied molecular orbital (LUMO) by using the CDNO/2 method. Compounds (4) and (5) thus designed were synthesized from the sulfide (3) by metaperiodate oxidation in 72% and 89% yields, respectively. No appreciable activity was observed with these compounds upon in vitro screening, probably due to their low water-solubility. Nevertheless, this approach may be useful for the development of improved radiosensitizers provided that mercaptoimidazole derivatives with adequate water-solubility can be obtained.