Fuente Cebrián, Àlex de laMena-Barragán, TeresaFarrar-Tobar, Ronald A.Verdaguer i Espaulella, XavierGarcía-Fernández, J. M.Ortiz Mellet, CarmenRiera i Escalé, Antoni2016-09-092016-12-3120151477-0520https://hdl.handle.net/2445/1016852-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.11 p.application/pdfeng(c) Fuente Cebrián, Àlex de la et al., 2015Inhibidors enzimàticsDisseny de medicamentsEnzyme inhibitorsDrug designinfo:eu-repo/semantics/article6527292016-09-09info:eu-repo/semantics/openAccess25975710