Replacement of the 3'-CH group by nitrogen in the carbocyclic analogue of thymidine.
We have prepared (4R)-4-thyminyl-D-prolinol, an analogue of 3'-deoxythymidine in which the sugar has been replaced by D-prolinol. This strongly basic secondary amine has been converted to the corresponding hydroxylamine, an analogue of either thymidine or 2'-deoxyxylofuranosylthymine. We have also synthesized a number of simple derivatives of the amine for testing in vitro activity against herpes simplex 1 (HSV-1), human immunodeficiency virus 1 (HIV-1), and a panel of human tumor cell lines. Among these compounds, the hydroxylamine 12 proved active against the human tumor cell lines of breast, colon, and lung origin, with IC50 values of 0.08, 14.02, and 6.91 microM, respectively.
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Salk Institute for Biological Studies, San Diego, California 92138.
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D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004354:Drug Screening Assays, Antitumor; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018139:Simplexvirus / Q000187:drug effects; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D013936:Thymidine