Nine of 16 stereoisomeric polyhydroxylated proline amides are potent ß-N-acetylhexosaminidase inhibitors.
J Org Chem
; 79(8): 3398-409, 2014 Apr 18.
Article
em En
| MEDLINE
| ID: mdl-24641544
ABSTRACT
All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of ß-N-acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. ß-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Azetidinocarboxílico
/
Beta-N-Acetil-Hexosaminidases
/
Prolina
/
Amidas
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Acetamidas
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido