Antineoplastic activity of 3'-(chloroethyl)nitrosourea analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine.
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 90% and 60% "cures" (greater than 60-day survivors), respectively. The structure-activity relationships are discussed.
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D015224:Dideoxynucleosides; D005260:Female; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D009607:Nitrosourea Compounds; D005467:Floxuridine; C048809:3'-(3-(2-chloroethyl)-3-nitrosoureido)-2',3'-dideoxy-5-fluorouridine; C048808:3' (3-(2-chloroethyl)-3-nitrosoureido)-2',3'-dideoxyuridine; D003857:Deoxyuridine