| Summary: | The scope of a series of <i>N</i>-alkylated iminosugar based inhibitors in the <span style="font-variant: small-caps;">d</span>-<i>gluco</i> as well as <span style="font-variant: small-caps;">d</span>-<i>xylo</i> configuration towards their interaction with human lysosomal β-glucocerebrosidase has been evaluated. A versatile synthetic toolbox has been developed for the synthesis of <i>N</i>-alkylated iminosugar scaffolds conjugated to a variety of terminal groups via a benzoic acid ester linker. The terminal groups such as nitrile, azide, alkyne, nonafluoro-<i>tert</i>-butyl and amino substituents enable follow-up chemistry as well as visualisation experiments. All compounds showed promising inhibitory properties as well as selectivities for β-glucosidases, some exhibiting activities in the low nanomolar range for β-glucocerebrosidase.
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