Synthesis and biologic activity of 2'-fluoro-2-halo derivatives of 9-beta-D-arabinofuranosyladenine.

Academic Article

Abstract

  • The synthesis of 2-halo-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenines (4b and 4d) by coupling the 2,6-dihalopurine with 3-acetyl-5-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (2) followed by replacement of the 6-halogen with concomitant removal of the acyl blocking groups is described. 2-Fluoroadenine derivative 4g had to be prepared by the diazotization-fluorination of 2-aminoadenine nucleoside 4e. All three nucleosides provided good increases in life span of mice inoculated with P388 leukemia. The best results were obtained when the compounds were administered q3h x 8 on days 1, 5, and 9 after implantation of the leukemia cells. The 2',3'-dideoxynucleoside 5b, prepared by deacetylation of 4f and deoxygenation of the resultant 4h followed by removal of the benzoyl group of 5a, was slightly active against HIV in cell culture.
  • Published In

    Keywords

  • Animals, Antimetabolites, Antineoplastic, Escherichia coli, HIV, Humans, Leukemia P388, Mice, Purine-Nucleoside Phosphorylase, Structure-Activity Relationship, Tumor Cells, Cultured, Vidarabine
  • Author List

  • Montgomery JA; Shortnacy-Fowler AT; Clayton SD; Riordan JM; Secrist JA
  • Start Page

  • 397
  • End Page

  • 401
  • Volume

  • 35
  • Issue

  • 2