Synthetic deoxynojirimycin derivatives bearing a thiolated, fluorinated or unsaturated N-alkyl chain: identification of potent α-glucosidase and trehalase inhibitors as well as F508del-CFTR correctors.
In: ISSN: 1477-0520, 2015
Online
academicJournal
Zugriff:
International audience ; The synthesis of eleven 1-deoxynojirimycin (DNJ) derivatives presenting either a monofluoro, difluoro, thiolated or unsaturated N-alkyl chain of various length is described. Exploiting the unsaturated moiety on the nitrogen, fluorine has been introduced through a HF/SbF5 superacid catalysed hydrofluorination and thiol–ene click chemistry allowed introduction of sulfur. The synthetic derivatives have been tested for their ability to inhibit glycosidases and correct F508del-CFTR. Two of the unsaturated iminosugars exhibited potency similar to Miglustat as F508del-CFTR correctors. The thioalkyl iminosugars as well as the corresponding alkyl iminosugars demonstrated low micromolar α-glucosidases and trehalases inhibition. Introduction of fluorine abolished F508del-CFTR correction and trehalase inhibition.
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Synthetic deoxynojirimycin derivatives bearing a thiolated, fluorinated or unsaturated N-alkyl chain: identification of potent α-glucosidase and trehalase inhibitors as well as F508del-CFTR correctors.
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Autor/in / Beteiligte Person: | Cendret, V. ; Legigan, T. ; Martin-Mingot, A. ; Thibaudeau, S. ; Adachi, I. ; Forcella, M. ; Parenti, P. ; Bertrand, J. ; Becq, F. ; Norez, C. ; Désiré, J. ; Kato, A. ; Blériot, Y. ; Institut de chimie des milieux et matériaux de Poitiers UMR 7285 (IC2MP Poitiers ) ; Université de Poitiers = University of Poitiers (UP)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) ; Department of Hospital Pharmacy Toyama ; University of Toyama ; Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB) ; Signalisation et Transports Ioniques Membranaires (STIM Poitiers ) ; Université de Poitiers = University of Poitiers (UP)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) |
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Zeitschrift: | ISSN: 1477-0520, 2015 |
Veröffentlichung: | HAL CCSD ; Royal Society of Chemistry, 2015 |
Medientyp: | academicJournal |
DOI: | 10.1039/c5ob01526j |
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