A novel imidazole nucleoside containing a diaminodihydro-S-triazine as a substituent: inhibitory activity against the West Nile virus NTPase/helicase

Nucleosides Nucleotides Nucleic Acids. 2005;24(10-12):1775-88. doi: 10.1080/15257770500267063.

Abstract

The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2'-deoxy-beta-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2'-deoxy-beta-D-erythropentofuranosyl)-5-(2, 4-diamino-3, 6-dihydro-1,3, 5-triazin-6-yl)imidazole-4-carboxamide (7). The structure as well as the pathway of formation of 7 was corroborated by isolation of the intermediate, followed by its conversion to the product. Nucleoside 7 showed promising in vitro anti-helicase activity against the West Nile virus NTPase/helicase with an IC50 of 3-10 microg/mL.

Publication types

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

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Dose-Response Relationship, Drug
  • Guanosine / analogs & derivatives
  • Guanosine / chemistry
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry*
  • Nucleoside-Triphosphatase / antagonists & inhibitors
  • Nucleoside-Triphosphatase / chemistry
  • RNA Helicases / antagonists & inhibitors*
  • RNA Helicases / chemistry
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry
  • West Nile virus / enzymology*

Substances

  • Antiviral Agents
  • Imidazoles
  • Viral Proteins
  • Guanosine
  • imidazole
  • Nucleoside-Triphosphatase
  • RNA Helicases