Antineoplastic Activity of 3'-(Chloroethyl)nitrosourea Analogues of 2'-Deoxyuridine and 2'-Deoxy-5-fluorouridine

Article abstract of DOI:10.1021/jm00155a044

The (chloroethyl)nitrosourea analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine, 3'-<3-(2-chloroethyl)-3-nitrosoureido>-2',3'-dideoxyuridine (3'-CdUNU, 7) and 3'-<3-(2-chloroethyl)-3-nitrosoureido>-2',3'-dideoxy-5-fluorouridine (3'-CFdUNU, 8), have been synthesized by treatment of the corresponding 3'-amino nucleosides with chloroethyl isocyanate, followed by nitrosation of the resulting ureas.Nucleoside nitrosoureas 7 and 8 exhibited marked anticancer activity against L1210 leukemia in tumor-bearing mice.At an optimum dosage level of 40 mg/kg, 7 and 8 produced 90percent and 60percent "cures" (>60-day survivors), respectively.The structure-activity relationships are discussed.