Synthesis and biological activity of several amino analogues of thymidine

J Med Chem. 1978 Jan;21(1):109-12.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antiviral Agents / chemical synthesis
  • Cell Division / drug effects
  • Cells, Cultured
  • Leukemia L1210 / pathology
  • Sarcoma 180 / pathology
  • Thymidine / analogs & derivatives*
  • Thymidine / chemical synthesis
  • Thymidine / pharmacology
  • Virus Replication / drug effects

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Thymidine