Synthesis, in vitro metabolic studies, and antitumour activity of methyl analogues of ifosfamide

Synthesis of 2-chloro-1,1-dimethylethyl and 2-chloro-2,2-dimethylethyl anal ogues of ifosfamide was performed via aziridine intermediate. In vitro meta bolic activation showed that both compounds are metabolised at a rate simil ar to the parent drug. However, their anticancer activity against L1210 leu kaemia in mice was lower as compared with ifosfamide. The reduction of anti tumour efficiency of examined analogues is probably caused by a lower abili ty to cross-link DNA by their final, active metabolites.