Synthesis of new beta-1-C-alkylated imino-L-iditols: A comparative study of their activity as beta-glucocerebrosidase inhibitors.
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.
Schönemann
Wojciech
W
Institut de Chimie Organique et Analytique, UMR 6005, Université d'Orléans & CNRS, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France.
Gallienne
Estelle
E
Compain
Philippe
P
Ikeda
Kyoko
K
Asano
Naoki
N
Martin
Olivier R
OR
D000478:Alkylation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors*; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D013402:Sugar Alcohols / Q000138:chemical synthesis* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011994:Recombinant Proteins; D013402:Sugar Alcohols; C082913:iditol; D005962:Glucosylceramidase