Synthesis and biological activity of 2'-deoxy-4'-thio-pyrazolo[3,4-d]pyrimidine nucleosides

Nucleosides Nucleotides Nucleic Acids. 2005;24(5-7):911-4. doi: 10.1081/ncn-200059266.

Abstract

The coupling of 4-aminopyrazolo [3, 4-d]pyrimidine with the appropriate thio sugar gave a 3:1 ratio of alpha,beta blocked 4-amino-1-(2-deoxy-4-thio-D-erythropentofuranosyl)-1H pyrazolo[3,4-d]pyrimidine nucleosides. The mixture was deblocked, both the anomers were separated, and the beta-anomer was readily deaminated by adenosine deaminase. The nucleosides have been characterized, and their anomeric configurations have been determined by proton NMR. All three nucleosides were evaluated against a panel of human tumor cell lines for cytotoxicity in vitro. The details of a convenient and high yielding synthesis of these nucleosides are described.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / chemistry*
  • Cell Line, Tumor
  • Drug Design
  • Drug Screening Assays, Antitumor / methods
  • Humans
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy / methods
  • Models, Chemical
  • Molecular Biology / methods*
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry*
  • Protons
  • Purine Nucleosides / chemical synthesis*
  • Purine Nucleosides / chemistry
  • Pyrimidine Nucleosides / chemistry
  • Pyrimidines / chemistry*

Substances

  • Nucleosides
  • Protons
  • Purine Nucleosides
  • Pyrimidine Nucleosides
  • Pyrimidines
  • Adenosine
  • pyrimidine