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
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alkylation
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / therapeutic use
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Deoxyuridine / analogs & derivatives*
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Deoxyuridine / chemical synthesis
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Deoxyuridine / toxicity
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Dideoxynucleosides*
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Female
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Floxuridine / analogs & derivatives*
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Floxuridine / chemical synthesis
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Floxuridine / toxicity
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Leukemia L1210 / drug therapy
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Mice
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Nitrosourea Compounds / chemical synthesis*
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Nitrosourea Compounds / toxicity
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Dideoxynucleosides
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Nitrosourea Compounds
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Floxuridine
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3'-(3-(2-chloroethyl)-3-nitrosoureido)-2',3'-dideoxy-5-fluorouridine
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3' (3-(2-chloroethyl)-3-nitrosoureido)-2',3'-dideoxyuridine
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Deoxyuridine