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Title: Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors
Author: Fuente Cebrián, Àlex de la
Mena-Barragán, Teresa
Farrar-Tobar, Ronald A.
Verdaguer i Espaulella, Xavier
García-Fernández, J. M.
Ortiz Mellet, Carmen
Riera i Escalé, Antoni
Keywords: Inhibidors enzimàtics
Disseny de medicaments
Enzyme inhibitors
Drug design
Issue Date: 2015
Publisher: Royal Society of Chemistry
Abstract: 2-Acetamido-1,2-dideoxyiminosugars are selective and potent inhibitors of hexosaminidases and therefore show high therapeutic potential for the treatment of various diseases, including several lysosomal storage disorders. A stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc), the iminosugar analog of N-acetylglucosamine, with a high overall yield is here described. This novel procedure further allowed accessing ureido-DNJNAc conjugates through derivatization of the endocyclic amine on a key pivotal intermediate. Remarkably, some of the ureido-DNJNAc representatives behaved as potent and selective inhibitors of β-hexosaminidases, including the human enzyme, being the first examples of neutral sp2-iminosugar-type inhibitors reported for these enzymes. Moreover, the amphiphilic character of the new ureido-DNJNAc is expected to confer better drug-like properties.
Note: Versió postprint del document publicat a:
It is part of: Organic & Biomolecular Chemistry, 2015, vol. 13, p. 6500-6510
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ISSN: 1477-0520
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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