Pharmacology of Nitrosourea Anticancer Agents

In 1959, 1-methyl-1-nitroso-3-nitroguanidine (MNNG) was reported to have a measurable and reproducible antitumor activity against the murine ascitic leukemia, L1210 (1). This observation resulted in extensive study of the N-nitroso compounds of antitumor activity. It was demonstrated that the nitroso group was required for activity and that substitution of a chloroethyl on the terminal methyl group enhanced antitumor activity. This led to the development of l-(2-chloroethyl)-nitrosourea (2).