Synthesis and structure-activity relationships of pre-activated analogs of cyclophosphamide (NSC-26271)

The synthesis of approximately 80 cyclic or acyclic analogs of cyclophosphamide, isophosphamide, triphosphamide, and phosphoramide mustard is outlined briefly. All of the analogs contain at least one 2-chloroethyl or bis(2-chloroethyl)-amino group bound to phosphorus. Representatives of some of the various classes of analogs were evaluated against murine L1210 leukemia in vivo. Some of the cyclic oxidized derivatives and a phosphorodiamidic chloride yielded long-term survivors. 4-Peroxycyclophosphamide was also active against ic implanted L1210 leukemia and against two other murine tumors, Lewis lung carcinoma and C3H mammary tumor.