Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/101685
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: http://dx.doi.org/10.1039/c5ob00507h |
It is part of: | Organic & Biomolecular Chemistry, 2015, vol. 13, p. 6500-6510 |
URI: | http://hdl.handle.net/2445/101685 |
Related resource: | http://dx.doi.org/10.1039/c5ob00507h |
ISSN: | 1477-0520 |
Appears in Collections: | Articles publicats en revistes (Química Inorgànica i Orgànica) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
652729.pdf | 420.64 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.