Synthesis and evaluation of D-gluco-pyranocyclopropyl amines as potential glucosidase inhibitors

Martijn D P Risseeuw; Richard J B H N van den Berg; Wilma E Donker-Koopman; Gijs A van der Marel; Johannes M F G Aerts; Mark Overhand; Herman S Overkleeft

doi:10.1016/j.bmcl.2009.10.022

Synthesis and evaluation of D-gluco-pyranocyclopropyl amines as potential glucosidase inhibitors

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6600-3. doi: 10.1016/j.bmcl.2009.10.022. Epub 2009 Oct 8.

Authors

Martijn D P Risseeuw¹, Richard J B H N van den Berg, Wilma E Donker-Koopman, Gijs A van der Marel, Johannes M F G Aerts, Mark Overhand, Herman S Overkleeft

Affiliation

¹ Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA Leiden, The Netherlands.

PMID: 19853441
DOI: 10.1016/j.bmcl.2009.10.022

Abstract

In the recent past sugar-derived cyclopropylamines were proposed as structurally new glycosidase inhibitors. In this Letter we report our efforts in the synthesis of a set of alpha-glucose configured oxabicyclo[4.1.0] heptanes, based on this hypothesis, bearing an amine substituent on the propyl ring and reveal that their inhibitory potential towards a range of mammalian glucosidases is modest.

Publication types

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

MeSH terms

Amines / chemical synthesis*
Amines / chemistry
Amines / pharmacology*
Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
Bridged Bicyclo Compounds, Heterocyclic / chemistry
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Glucosidases / antagonists & inhibitors*
Molecular Conformation
Structure-Activity Relationship

Substances

Amines
Bridged Bicyclo Compounds, Heterocyclic
Enzyme Inhibitors
Glucosidases