Design and synthesis of N-alkyldeoxynojirimycin derivatives with improved metabolic stability as inhibitors of BVDV and Tacaribe virus

Bioorg Med Chem Lett. 2013 Jul 15;23(14):4258-62. doi: 10.1016/j.bmcl.2013.04.052. Epub 2013 May 9.

Abstract

Novel N-alkyldeoxynojirimycins (NADNJs) based on our previous lead 3 were designed, synthesized and tested in metabolic assays and in virus cultures. NADNJs containing terminal tertiary benzamide, sulfonamide, urea, and oxazolidinone moieties were discovered to have improved metabolic stability compared to 3, while maintaining submicromolar EC50 against BVDV and Tacaribe virus; and low cytotoxicity.

Publication types

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

MeSH terms

  • 1-Deoxynojirimycin / chemistry
  • 1-Deoxynojirimycin / metabolism
  • 1-Deoxynojirimycin / pharmacology
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Arenaviruses, New World / physiology*
  • Diarrhea Viruses, Bovine Viral / physiology*
  • Drug Design*
  • Glucosamine / analogs & derivatives*
  • Glucosamine / chemistry
  • Glucosamine / metabolism
  • Glucosamine / pharmacology
  • Humans
  • Mice
  • Microsomes, Liver / metabolism
  • Oxazolidinones / chemistry
  • Rats
  • Sulfonamides / chemistry
  • Urea / chemistry
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Oxazolidinones
  • Sulfonamides
  • deoxynojirimycine
  • 1-Deoxynojirimycin
  • Urea
  • Glucosamine