Synthesis of 4-hydroperoxy derivatives of ifosfamide and trofosfamide by direct ozonation and preliminary antitumor evaluation in vivo.
A one-step synthesis of 4-hydroperoxyifosfamide and 4-hydroperoxytrofosfamide is described. The method involves direct ozonation of ifosfamide and trofosfamide and offers improved yields in comparison with Fenton oxidation and greater convenience in comparison with ozonation of the appropriate 3-butenyl phosphorodiamidate. Evaluation of the 4-hydroperoxy derivatives of cyclophosphamide, ifosfamide, and trofosfamide against leukemia L1210 in vivo suggests a superior effect for the ifosfamide derivatie.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D010126:Ozone
D000970:Antineoplastic Agents; D010126:Ozone; D003520:Cyclophosphamide; D007069:Ifosfamide