Structure-activity relationships for tumour radiosensitization by analogues of nicotinamide and benzamide

The authors synthesized 29 analogues of nicotinamide and benzamide and characterized them for their tumour radiosensitization and acute toxicity in mice. The data show that a wide range of additions to the nicotinamide and the benzamide ring produce tumour radiosensitization similar to that produced by equimolar doses of misonidazole, but that substitutions of the amide tend to reduce radiosensitization. Other structure-activity relationships are evident. Although some compounds produce similar tumour radiosensitization to nicotinamide at equimolar doses, and are comparably low in acute toxicity, none appears sufficiently superior to supplant nicotinamide itself as a candidate for clinical trials. (author)