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ID: ALA1681653

Journal: Bioorg Med Chem Lett

Title: Synthesis of N-alkylated noeurostegines and evaluation of their potential as treatment for Gaucher's disease.

Authors: Rasmussen TS, Allman S, Twigg G, Butters TD, Jensen HH.

Abstract: The potent and selective inhibitor of β-glucosidases, noeurostegine, was evaluated as an inhibitor of glucocerebrosidase (GCase) to give an IC(50) value of 0.4 μM, being 250- and 150-fold better than N-butyl and N-nonyl noeurostegine, respectively. The parent noeurostegine and its N-butyl and N-nonyl alkylated congeners were also tested as pharmacological chaperones against a N370S GCase mutant. Of these, only noeurostegine, was found to increase enzyme activity, which in potency was comparable to that previously reported for isofagomine.

CiteXplore: 21292481

DOI: 10.1016/j.bmcl.2010.12.106