Synthesis of Novel Purine-Based Coxsackievirus Inhibitors Bearing Polycylic Substituents at the N-9 Position

0430390 - ÚOCHB 2015 RIV DE eng J - Journal Article
Dejmek, Milan - Šála, Michal - Plačková, Pavla - Hřebabecký, Hubert - Borreda, L. M. - Neyts, J. - Dračínský, Martin - Procházková, Eliška - Jansa, Petr - Leyssen, P. - Mertlíková-Kaiserová, Helena - Nencka, Radim
Synthesis of Novel Purine-Based Coxsackievirus Inhibitors Bearing Polycylic Substituents at the N-9 Position.
Archiv der Pharmazie. Roč. 347, č. 7 (2014), s. 478-485. ISSN 0365-6233. E-ISSN 1521-4184
R&D Projects: GA ČR GAP303/11/1297
Institutional support: RVO:61388963
Keywords : antiviral * coxsackievirus B3 * enteroviruses * phosphatidylinositol 4-kinase (PI4K) * purines
Subject RIV: CC - Organic Chemistry
Impact factor: 1.531, year: 2014

The synthesis of a novel library of purine derivatives bearing various bicyclic and polycylic substituents at the N-9 position is described. The series includes norbornanes, bicyclo[2.2.2] octanes, and bicyclo[3.2.1] octanes attached at the bridgehead position as well as bicyclo[3.1.1] heptanes, tetrahydro-1-naphthalenes, and adamantanes bonded either directly or via a linear chain to the 6-chloropurine nucleobase. A number of prepared derivatives exerted significant activity against the enterovirus. Despite attempts to correlate the activity against picornaviruses with their phosphatidylinositol 4-kinase KIII beta inhibitory activity, it is clear that the inhibition of this host factor cannot explain the observed antiviral potency.
Permanent Link: http://hdl.handle.net/11104/0235359