In the Search for New Anticancer Drugs, VI+ Structural Modifications of Cyclophosphamide

Moderate to high activity was found with 5 (T/C X 100 = 243 at a dose of 300 mg/kg), 7 (T/C x 100 = 173 at a dose of 10 mg/kg), 9 (T/C X 100 = 248 at a dose of 100 mg/kg) and 11 (T/C X 100 = 155 at a dose of 55 mg/kg). None of these compounds was found to be more active than 1 (T/C X 100 = 339 at a dose of 65 mg/kg). Although the essential position C4 for the enzymatic activation is completely blocked in 5, the compound possesses a high degree of activity. This result justifies a reevaluation of the proposed mechanism of drug action of 1 and its analogs.