A new type of pharmacological chaperone for GM1-gangliosidosis related human lysosomal β-galactosidase: N-Substituted 5-amino-1-hydroxymethyl-cyclopentanetriols. Issue 15 (1st August 2017)

• Record Type: Journal Article
• Authors: Schalli, Michael; Weber, Patrick; Tysoe, Christina; Pabst, Bettina M.; Thonhofer, Martin; Paschke, Eduard; Stütz, Arnold E.; Tschernutter, Marion; Windischhofer, Werner; Withers, Stephen G.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 15(2017)
• Page Start: 3431
• Page End: 3435
• Publication Date: 2017-08-01
• Subjects: Aminocyclopentane -- Carbafuranose -- Galactosidase inhibitor -- Pharmacological chaperone -- GM1-Gangliosidosis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.05.086
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: A short and high yielding route enables access to N -substituted amino(hydroxymethyl)pentanetriols. Final products are potent inhibitors of a panel of β-galactosidases. New compounds are efficient pharmacological chaperones for GM1 -gangliosidosis-related human lysosomal β-galactosidase. Abstract: N -Functionalized amino(hydroxymethyl)cyclopentanetriols are potent inhibitors of β-d -galactosidases and, for the first time, could be shown to act as pharmacological chaperones for GM1 -gangliosidosis-associated lysosomal acid β-galactosidase thus representing a new structural type of pharmacological chaperones for this lysosomal storage disease.