Synthesis of phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides: novel inhibitors of reverse transcriptase

J Med Chem. 2005 Mar 10;48(5):1389-94. doi: 10.1021/jm049399i.

Abstract

Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / toxicity
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / pharmacology
  • Aza Compounds / toxicity
  • Humans
  • In Vitro Techniques
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / enzymology
  • Nitrogen Oxides / chemistry
  • Nucleosides / chemical synthesis*
  • Nucleosides / pharmacology
  • Nucleosides / toxicity
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / pharmacology
  • Organophosphonates / toxicity
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / toxicity
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Aza Compounds
  • Nitrogen Oxides
  • Nucleosides
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • nitrones