Antineoplastic activity of 3'-(chloroethyl)nitrosourea analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine

J Med Chem. 1986 May;29(5):862-5. doi: 10.1021/jm00155a044.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkylation
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Deoxyuridine / analogs & derivatives*
  • Deoxyuridine / chemical synthesis
  • Deoxyuridine / toxicity
  • Dideoxynucleosides*
  • Female
  • Floxuridine / analogs & derivatives*
  • Floxuridine / chemical synthesis
  • Floxuridine / toxicity
  • Leukemia L1210 / drug therapy
  • Mice
  • Nitrosourea Compounds / chemical synthesis*
  • Nitrosourea Compounds / toxicity
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Dideoxynucleosides
  • Nitrosourea Compounds
  • Floxuridine
  • 3'-(3-(2-chloroethyl)-3-nitrosoureido)-2',3'-dideoxy-5-fluorouridine
  • 3' (3-(2-chloroethyl)-3-nitrosoureido)-2',3'-dideoxyuridine
  • Deoxyuridine