Synthesis and biological activity of several amino analogues of thymidine.
3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had potent antiviral activity relative to the 3'-amino analogue 8, the latter is a potent inhibitor of the replication of both murine sarcoma 180 cells (ED50 = 5 micrometer) and of murine L1210 cells (ED50 = 1 micrometer) in vitro. Most unexpectedly, however, was the finding of complete lack of either antiviral or antineoplastic activity by the 3',5'-diamino analogue 7 which appears to have acquired the undesirable qualities of both the 3'-amino and 5'-amino analogues of thymidine.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D007939:Leukemia L1210 / Q000473:pathology; D012510:Sarcoma 180 / Q000473:pathology; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D013936:Thymidine