Nine of 16 Stereoisomeric Polyhydroxylated Proline Amides Are Potent β-N-Acetylhexosaminidase Inhibitors
| Autor: | Sarah F. Jenkinson, Isao Adachi, Benjamin James Ayers, Atsushi Kato, Mark R. Wormald, Chu-Yi Yu, Nigel Ngo, Zilei Liu, Robert J. Nash, George W. J. Fleet, R. Fernando Martínez, Shinpei Nakagawa, Andreas F. G. Glawar, Terry D. Butters |
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| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
β n acetylhexosaminidase Proline Stereochemistry Carboxylic acid Organic Chemistry Azetidine Stereoisomerism Amides beta-N-Acetylhexosaminidases Kinetics chemistry.chemical_compound chemistry Amide Acetamides Hydroxymethyl Enantiomer Glucuronolactone Azetidinecarboxylic Acid |
| Zdroj: | The Journal of Organic Chemistry. 79:3398-3409 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo500157p |
| Popis: | 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 β-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. β-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. |
| Databáze: | OpenAIRE |
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