Norbornane-based nucleoside and nucleotide analogues locked in North conformation. Issue 1 (1st January 2015)

• Record Type: Journal Article
• Authors: Dejmek, Milan; Šála, Michal; Hřebabecký, Hubert; Dračínský, Martin; Procházková, Eliška; Chalupská, Dominika; Klíma, Martin; Plačková, Pavla; Hájek, Miroslav; Andrei, Graciela; Naesens, Lieve; Leyssen, Pieter; Neyts, Johan; Balzarini, Jan; Boura, Evzen; Nencka, Radim
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 1(2015)
• Page Start: 184
• Page End: 191
• Publication Date: 2015-01-01
• Subjects: Carbocyclic nucleosides -- Purines -- Norbornane -- Antiviral -- PI4KIIα; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2014.11.011
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: We report on the synthesis of novel conformationally locked nucleoside and nucleotide derivatives, which are structurally closely related to clinically used antivirals such as didanosine and abacavir. As a suitable conformationally rigid substitute of the sugar/pseudosugar ring allowing a permanent stabilization of the nucleoside in North conformation we employed bicyclo[2.2.1]heptane (norbornane) substituted in the bridgehead position with a hydroxymethyl group and in the C-3 position with a nucleobase. Prepared nucleoside derivatives were also converted into appropriate phosphoramidate prodrugs (ProTides) in order to increase delivery of the compounds in the cells. All target compounds were evaluated in a broad antiviral and cytostatic assay panel.