Design and Synthesis of Highly Potent and Selective Pharmacological Chaperones for the Treatment of Gaucher's disease

Abstract

Remove to improve. Removal of the hydroxymethyl groups in 1 to give 2 significantly enhances inhibitory potency towards glucosylceramide β-glucosidase (GCase) and abolishes inhibition towards α-glucosidases. Xylitol 2 doubles the residual activity of GCase in fibroblasts from Gaucher patients at subinhibitory concentration (10 nM). This compound is therefore a promising candidate for the development of small-molecule drugs for the treatment of Gaucher's disease without the side effects associated with α-glucosidase inhibition.