Spirocyclopropyl pyrrolidines as a new series of alpha-L-fucosidase inhibitors

Christophe Laroche; Jean-Bernard Behr; Jan Szymoniak; Philippe Bertus; Catherine Schütz; Pierre Vogel; Richard Plantier-Royon

doi:10.1016/j.bmc.2006.02.005

Spirocyclopropyl pyrrolidines as a new series of alpha-L-fucosidase inhibitors

Bioorg Med Chem. 2006 Jun 15;14(12):4047-54. doi: 10.1016/j.bmc.2006.02.005. Epub 2006 Feb 20.

Authors

Christophe Laroche¹, Jean-Bernard Behr, Jan Szymoniak, Philippe Bertus, Catherine Schütz, Pierre Vogel, Richard Plantier-Royon

Affiliation

¹ Laboratoire Réactions Sélectives et Applications, Université de Reims Champagne-Ardenne, UMR URCA/CNRS 6519, UFR Sciences, BP 1039, F-51687 Reims Cedex 2, France.

PMID: 16488612
DOI: 10.1016/j.bmc.2006.02.005

Abstract

Polyhydroxy 4-azaspiro[2.4]heptane derivatives (spirocyclopropyl iminosugars) were prepared in four to six steps from readily available protected aldoses. The key step of the reaction sequence involves a titanium-mediated aminocyclopropanation of glycononitriles with subsequent cyclization. Five new polyhydroxypyrrolidines so-obtained have been evaluated for their ability to inhibit 16 glycosidases. One of them exhibits selective inhibition of alpha-L-fucosidase from bovine kidney (Ki=1.6 microM, competitive).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cattle
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Kidney / enzymology
Molecular Conformation
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry
Pyrrolidines / pharmacology*
Spiro Compounds / chemistry*
Stereoisomerism
Structure-Activity Relationship
alpha-L-Fucosidase / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Pyrrolidines
Spiro Compounds
alpha-L-Fucosidase