Fluorinated hydroxypiperidines as selective β-glucosidase inhibitors.
A new series of fluoroallylamines derived from hydroxypiperidines was prepared and evaluated against various glycosidases. The short synthesis of target molecules involved the modified Julia reaction between aldehydes and functionalized fluoroaminosulfones. Biological studies revealed good and selective β-glucosidase inhibition in the micromolar range for two compounds, while the non-fluorinated analogue of the most active compound was selective towards α-glucosidase.
Laboratoire de Chimie Moléculaire et Thioorganique, UMR CNRS 6507, FR 3038, ENSICAEN Université de Caen Basse-Normandie, 6 Bd. du Maréchal Juin, 14050 Caen Cedex, France. thierry.lequeux@ensicaen.fr.
Clothilde
C
Le Guen
Teresa
T
Mena-Barragán
Carmen
C
Ortiz Mellet
David
D
Gueyrard
Emmanuel
E
Pfund
Thierry
T
Lequeux
D000499:Allylamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D055808:Drug Discovery; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D054879:Halogenation; D006801:Humans; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D065089:Glycoside Hydrolase Inhibitors; D000499:Allylamine; D000520:alpha-Glucosidases; D001617:beta-Glucosidase