Norbornane-based nucleoside and nucleotide analogues locked in North conformation

0443135 - ÚOCHB 2016 RIV GB eng J - Článek v odborném periodiku
Dejmek, Milan - Šála, Michal - Hřebabecký, Hubert - Dračínský, Martin - Procházková, Eliška - Chalupská, Dominika - Klíma, Martin - Plačková, Pavla - Hájek, Miroslav - Andrei, G. - Naesens, L. - Leyssen, P. - Neyts, J. - Balzarini, J. - Bouřa, Evžen - Nencka, Radim
Norbornane-based nucleoside and nucleotide analogues locked in North conformation.
Bioorganic & Medicinal Chemistry. Roč. 23, č. 1 (2015), s. 184-191. ISSN 0968-0896. E-ISSN 1464-3391
Grant CEP: GA ČR GPP207/12/P625; GA MŠMT LO1302
Institucionální podpora: RVO:61388963
Klíčová slova: carbocyclic nucleosides * purines * norbornane * antiviral * PI4KIIalpha
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 2.923, rok: 2015

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.
Trvalý link: http://hdl.handle.net/11104/0245898