Highly functionalized diaminocyclopentanes: A new route to potent and selective inhibitors of human O-GlcNAcase

Abstract

A new class of compounds inhibiting de-O-glycosylation of proteins has been identified. Highly substituted diaminocyclopentanes are impressively selective reversible non-transition state O-β-N-acetyl-d-glucosaminidase (O-GlcNAcase) inhibitors. The ease of preparative access and remarkable biological activities provide highly viable leads for the development of anti-tau-phosphorylation agents with a view to eventually ameliorating Alzheimer's disease.

Keywords: Alzheimer’s disease; Diaminocyclopentane; Glycosidase inhibition; O-GlcNAcase.