Synthesis and antiviral evaluation of 2-amino-6-carbamoylpurine dioxolane nucleoside derivatives and their phosphoramidates prodrugs

Bioorg Med Chem. 2014 Dec 1;22(23):6665-6671. doi: 10.1016/j.bmc.2014.10.003. Epub 2014 Oct 13.

Abstract

The synthesis of 9-(β-d-1,3-dioxolan-4-yl)2,6-diaminopurine nucleoside phosphoramidate prodrugs as well as various 2-amino-6-carbamoylpurine dioxolane derivatives and their phosphoramidates prodrugs is reported. Their ability to block HIV and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM and Vero cells was also assessed.

Keywords: Anti-HBV; Anti-HIV; Antiviral agent; DAPD; β-d-1,3-Dioxolan-4-yl nucleosides.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dioxolanes / chemical synthesis
  • Dioxolanes / chemistry
  • Dioxolanes / pharmacology*
  • Dose-Response Relationship, Drug
  • HIV-1 / drug effects*
  • Hepatitis B virus / drug effects*
  • Microbial Sensitivity Tests
  • Nucleosides / chemical synthesis
  • Nucleosides / chemistry
  • Nucleosides / pharmacology*
  • Phosphoric Acids / chemical synthesis
  • Phosphoric Acids / chemistry
  • Phosphoric Acids / pharmacology*
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Antiviral Agents
  • Dioxolanes
  • Nucleosides
  • Phosphoric Acids
  • Prodrugs
  • ethyl 2-((((4-(2-amino-6-hydroxy-9H-purin-9-yl)-1,3-dioxolan-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate
  • phosphoramidic acid
  • Adenosine