Download PDF (external access)

Archiv der Pharmazie

Publication date: 2014-07
Volume: 347 Pages: 478 - 85
ISSN: 0365-6233, 1521-4184 PMID: 24652670
Publisher: VCH Verlagsgesellschaft mbH

Author:

Dejmek, Milan
Sála, Michal ; Plačková, Pavla ; Hřebabecký, Hubert ; Mascarell Borredà, Laura ; Neyts, Johan ; Dračínský, Martin ; Procházková, Eliška ; Jansa, Petr ; Leyssen, Pieter ; Mertlíková-Kaiserová, Helena ; Nencka, Radim

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Chemistry, Medicinal, Chemistry, Multidisciplinary, Pharmacology & Pharmacy, Chemistry, Antiviral, Coxsackievirus B3, Enteroviruses, Phosphatidylinositol 4-kinase (PI4K), Purines, 9-NORBORNYLPURINES, DISEASE, Animals, Antiviral Agents, Bridged-Ring Compounds, Cell Survival, Cells, Cultured, Cytopathogenic Effect, Viral, Enterovirus, Molecular Structure, Norbornanes, Virus Replication, 0304 Medicinal and Biomolecular Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry

Abstract:

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 KIIIβ inhibitory activity, it is clear that the inhibition of this host factor cannot explain the observed antiviral potency.