Norbornane-based nucleoside and nucleotide analogues locked in North conformation.


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.

DOI: 10.1016/j.bmc.2014.11.011

Cite this paper

@article{Dejmek2015NorbornanebasedNA, title={Norbornane-based nucleoside and nucleotide analogues locked in North conformation.}, author={Milan Dejmek and Michal {\vS}{\'a}la and Hubert Hřebabeck{\'y} and Martin Dra{\vc}{\'i}nsk{\'y} and Eli{\vs}ka Proch{\'a}zkov{\'a} and Dominika Chalupsk{\'a} and Martin Kl{\'i}ma and Pavla Pla{\vc}kov{\'a} and Miroslav H{\'a}jek and Graciella Andrei and Lieve M J Naesens and Pieter Leyssen and Johan Neyts and Jan Balzarini and Evzen Boura and Radim Nencka}, journal={Bioorganic & medicinal chemistry}, year={2015}, volume={23 1}, pages={184-91} }