3-deaza- and 7-deaza-5'-noraristeromycin and their antiviral properties

J Med Chem. 1995 Mar 17;38(6):1035-8. doi: 10.1021/jm00006a023.

Abstract

An enantiospecific synthesis of 3-deaza-5'-noraristeromycin as its dihydrochloride ((-)-6) has been accomplished in six steps beginning with the reaction of (+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate with 4-chloro-1H-imidazo[4,5-c]pyridine. The preparation of 7-deaza-5'-noraristeromycin ((-)-7) was described previously. Compounds (-)-6 and (-)-7 were evaluated for antiviral activity against a large number of viruses. Compound (-)-6 produced an antiviral activity pattern similar to 5'-noraristeromycin but was less potent. Compound (-)-6 inhibited CEM cell proliferation at a 50% inhibitory concentration of 27 micrograms/mL but proved not inhibitory to HEL cell proliferation and not toxic to E6SM, HeLa, Vero, and MDCK cells at concentrations up to 200 micrograms/mL. While (-)-6 showed inhibition of S-adenosyl-L-homocysteine (AdoHcy) hydrolase, it was less inhibitory than 5'-noraristeromycin. Compound (-)-7 displayed no antiviral properties or inhibitory effects toward AdoHcy hydrolase.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / pharmacology
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Cattle
  • Cell Division / drug effects
  • Cells, Cultured
  • Chlorocebus aethiops
  • HIV-1 / drug effects
  • HIV-2 / drug effects
  • HeLa Cells
  • Humans
  • Leukemia L1210 / drug therapy
  • Male
  • Methylation
  • Mice
  • Microbial Sensitivity Tests
  • T-Lymphocytes / drug effects
  • Vero Cells

Substances

  • 3-deaza-5'-noraristeromycin
  • 7-deaza-5'-noraristeromycin
  • Antiviral Agents
  • Adenosine