N-Alkyldeoxynojirimycin derivatives with novel terminal tertiary amide substitution for treatment of bovine viral diarrhea virus (BVDV), Dengue, and Tacaribe virus infections

Bioorg Med Chem Lett. 2013 Apr 1;23(7):2172-6. doi: 10.1016/j.bmcl.2013.01.108. Epub 2013 Feb 1.

Abstract

Novel N-alkyldeoxynojirimycins (NADNJs) with two hydrophobic groups attached to a nitrogen linker on the alkyl chain were designed. A novel NADNJ containing a terminal tertiary carboxamide moiety was discovered that was a potent inhibitor against BVDV. Further optimization resulted in a structurally more stable lead compound 24 with a submicromolar EC50 against BVDV, Dengue, and Tacaribe; and low cytotoxicity.

Publication types

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

MeSH terms

  • 1-Deoxynojirimycin / chemical synthesis
  • 1-Deoxynojirimycin / chemistry
  • 1-Deoxynojirimycin / pharmacology
  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cricetinae
  • Defective Viruses / drug effects*
  • Dengue / drug therapy*
  • Diarrhea Viruses, Bovine Viral / drug effects*
  • Dose-Response Relationship, Drug
  • Glucosamine / analogs & derivatives*
  • Glucosamine / chemical synthesis
  • Glucosamine / chemistry
  • Glucosamine / pharmacology
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amides
  • Antiviral Agents
  • deoxynojirimycine
  • 1-Deoxynojirimycin
  • Glucosamine