Norbornane-based Nucleoside and Nucleotide Analogues Locked in North Conformation

Milan Dejmek, Michal Šála, Hubert Hřebabecký, Martin Dračínský, Eliška Procházková, Dominika Chalupská, Martin Klíma, Pavla Plačková, Miroslav Hájek, Graciela Andrei, Lieve Naesens, Pieter Leyssen, Johan Neyts, etc.

Bioorg Med Chem. 2015 Jan 1;23(1):184-91.

PMID: 25435471

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP172015791	Abacavir Related Compound C		172015-79-1	Price