Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors.
Org Biomol Chem
; 13(23): 6500-10, 2015 Jun 21.
Article
em En
| MEDLINE
| ID: mdl-25975710
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 ß-hexosaminidases, including the human enzyme, being the first examples of neutral sp(2)-iminosugar-type inhibitors reported for these enzymes. Moreover, the amphiphilic character of the new ureido-DNJNAc is expected to confer better drug-like properties.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Beta-N-Acetil-Hexosaminidases
/
1-Desoxinojirimicina
/
Inibidores Enzimáticos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article