Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands

Bioorg Med Chem. 2012 Dec 15;20(24):7149-54. doi: 10.1016/j.bmc.2012.09.063. Epub 2012 Oct 12.

Abstract

We report the synthesis of a small series of 6"-triazol-1-yl-substituted α-GalCer analogues by late-stage conversion of the 6"-OH to an azide group, copper-catalyzed azide-alkyne cycloaddition and final deprotection. When evaluated for their capacity to induce IL-2 secretion in vitro, all compounds proved equally potent or superior to α-GalCer. The S.A.R suggests that the improved antigenic activity is mainly triggered by the triazole functionalization in se. While the introduction of selected substitutuents at C-4 of this heterocyclic ring is tolerated, this generally fails to further improve antigenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Galactosylceramides / chemical synthesis*
  • Galactosylceramides / chemistry
  • Galactosylceramides / pharmacology*
  • Ligands
  • Mice
  • Natural Killer T-Cells / drug effects*
  • Natural Killer T-Cells / immunology
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Galactosylceramides
  • Ligands
  • Triazoles
  • alpha-galactosylceramide