Synthesis of N-alkylated noeurostegines and evaluation of their potential as treatment for Gaucher’s disease

Rasmussen, Tina S.; Allman, Sarah; Twigg, Gabriele; Butters, Terry D. and Jensen, Henrik H. (2011). Synthesis of N-alkylated noeurostegines and evaluation of their potential as treatment for Gaucher’s disease. Bioorganic & Medicinal Chemistry Letters, 21(5) pp. 1519–1522.

DOI: https://doi.org/10.1016/j.bmcl.2010.12.106

Abstract

The potent and selective inhibitor of β-glucosidases, noeurostegine, was evaluated as an inhibitor of glucocerebrosidase (GCase) to give an IC₅₀ 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.

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