Synthetic analogs of antitumor drugs under development in Japan

Synthetic studies on new antitumor drugs in Japan are mainly oriented toward analogs of known active structures. In the nitrosourea area ACNU, a pyrimidine analog of CCNU, is currently under clinical investigation and has myelosuppression as a side effect Nitrosoureas with a sugar moiety are of great interest and two compounds called GANU and MCNU are now ready for phase I study in Japan. Among new alkylating agents are included a series of bis-methanesulfonate of aminoglycols, an analog of cyclophosphamide called 4-hydroperoxy-cyclophosphamide, and aziridine derivatives which include the now commercially available carbazilquinone. In the antimetabolite field cyclocytidine is an analog of arabinosyl cytosine which has been extensively studied. A newer analog called N4-behenoyl-cytosine arabinoside is now being studied experimentally. In the fluorinated pyrimidine area Ftorafur has been extensively studied and a new compound FD-1 is of interest.