51. The 'mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as α-l-fucosidase inhibitors.
- Author
-
Stocker BL, Jongkees SA, Win-Mason AL, Dangerfield EM, Withers SG, and Timmer MS
- Subjects
- Molecular Structure, Structure-Activity Relationship, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Pyrrolidines chemistry, Pyrrolidines pharmacology, alpha-L-Fucosidase antagonists & inhibitors
- Abstract
The ability of a series of pyrrolidines to inhibit several glycosidases was investigated. Using Fleet's 'mirror-image postulate', it was proposed that enantiomeric derivatives of 1,4-dideoxy-1,4-imino-d-lyxitol (a known α-d-galactosidase inhibitor) would show inhibitory activity against α-l-fucosidases. Some modest α-l-fucosidase inhibitory activity was observed for selected compounds (particularly an aminomethyl pyrrolidine) and it was proposed that better activity could be obtained by modifying the C-2 side chain of the pyrrolidine core. The d-galacto carbamate scaffold also exhibited somewhat selective, albeit modest, α-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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