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.
Keywords: Antiviral; Coxsackievirus B3; Enteroviruses; Phosphatidylinositol 4-kinase (PI4K); Purines.
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