Diaminocyclopentane-derived O -GlcNAcase inhibitors for combating tau hyperphosphorylation in Alzheimer's disease

We developed potent and selective aminocyclopentane-derived inhibitors of human O-N -acetyl-β- d -glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over human HexB. It was non-toxic and increased protein O...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2022-08, Vol.58 (63), p.8838-8841
Main Authors: Weber, Patrick, Mészáros, Zuzana, Jagečić, Denis, Hribljan, Valentina, Mitrečić, Dinko, Bojarová, Pavla, Slámová, Kristýna, Vrba, Jiří, Kulik, Natalia, Křen, Vladimír, Stütz, Arnold E.
Format: Article
Language:English
Subjects:
Alzheimer's disease
Inhibitors
Selectivity
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Summary:We developed potent and selective aminocyclopentane-derived inhibitors of human O-N -acetyl-β- d -glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over human HexB. It was non-toxic and increased protein O -GlcNAcylation in the culture of murine neural cells, showing new alternatives in the treatment of tauopathies.
ISSN:1359-7345
1364-548X
DOI:10.1039/d2cc02712g