Synthesis of new beta-1-C-alkylated imino-L-iditols: A comparative study of their activity as beta-glucocerebrosidase inhibitors

Bioorg Med Chem. 2010 Apr 1;18(7):2645-50. doi: 10.1016/j.bmc.2010.02.027. Epub 2010 Feb 20.

Abstract

A short synthesis of new beta-1-C-alkyl-1,5-dideoxy-1,5-imino-l-iditols by means of the diastereoselective addition of Grignard reagents onto a glucopyranosylamine is described. These compounds were evaluated as beta-glucocerebrosidase inhibitors and their activity was compared with that of related iminosugar derivatives in the d-gluco and d-xylo series. The results allowed us to conclude on the influence of the hydroxymethyl moiety and of the piperidine-ring conformation on the inhibitory activity.

Publication types

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

MeSH terms

  • Alkylation
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Glucosylceramidase / antagonists & inhibitors*
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Models, Molecular
  • Molecular Conformation
  • Recombinant Proteins / chemistry
  • Spectrometry, Fluorescence
  • Stereoisomerism
  • Sugar Alcohols / chemical synthesis*
  • Sugar Alcohols / pharmacology*

Substances

  • Enzyme Inhibitors
  • Indicators and Reagents
  • Recombinant Proteins
  • Sugar Alcohols
  • iditol
  • Glucosylceramidase