An efficient, short synthesis and potent anti-hepatitis B viral activity of a novel ring-expanded purine nucleoside analogue containing a 5:7-fused, planar, aromatic, imidazo[4,5-e][1,3]diazepine ring system

Nucleosides Nucleotides. 1999 Mar;18(3):331-5. doi: 10.1080/15257779908043079.

Abstract

An efficient, short synthesis of a ring-expanded nucleoside analogue containing a novel 5:7-fused, planar, and potentially aromatic imidazo[4,5-e][1,3]diazepine heterocyclic ring system is reported. The target compound, 6-amino-8-hydroxy-4H-1-beta-D- ribofuranosylimidazo[4,5-e][1,3]diazepin-4-one (2) was synthesized in a single step in > or = 90% yield by condensation of guanidine with either methyl 1-beta-D-ribofuranosylimidazole-4,5- dicarboxylate(1a) or its 2',3',5'-tri-O-benzoyl derivative (1b). Compound 2 showed potent anti-hepatitis B virus (anti-HBV) activity with an EC50 value of 0.17 microM in the transfected hepatoma cell line 2.2.15, and a low cellular toxicity with a CC50 value of 2.4 mM (TI > 14,000).

Publication types

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

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Azepines / pharmacology
  • Carcinoma, Hepatocellular
  • Cell Survival / drug effects
  • Hepatitis B virus / drug effects*
  • Humans
  • Liver Neoplasms
  • Purine Nucleosides / chemical synthesis*
  • Purine Nucleosides / chemistry
  • Purine Nucleosides / pharmacology
  • Transfection
  • Tumor Cells, Cultured

Substances

  • 6-amino-8-hydroxy-4H-1-ribofuranosylimidazo(4,5-e)(1,3)diazepin-4-one
  • Antiviral Agents
  • Azepines
  • Purine Nucleosides