title: Synthesis of novel purine-based coxsackievirus inhibitors bearing polycylic substituents at the N-9 position.
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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Gilead Sciences & IOCB Research Centre, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Dejmek
authors.forename: Michal
authors.initials: M
authors.lastname: Sála
authors.forename: Pavla
authors.initials: P
authors.lastname: Plačková
authors.forename: Hubert
authors.initials: H
authors.lastname: Hřebabecký
authors.forename: Laura
authors.initials: L
authors.lastname: Mascarell Borredà
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Martin
authors.initials: M
authors.lastname: Dračínský
authors.forename: Eliška
authors.initials: E
authors.lastname: Procházková
authors.forename: Petr
authors.initials: P
authors.lastname: Jansa
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.forename: Helena
authors.initials: H
authors.lastname: Mertlíková-Kaiserová
authors.forename: Radim
authors.initials: R
authors.lastname: Nencka
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004770:Enterovirus / Q000187:drug effects* / Q000502:physiology; D015394:Molecular Structure; D009636:Norbornanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001952:Bridged-Ring Compounds; D009636:Norbornanes; D011687:Purines
keywords: Antiviral; Coxsackievirus B3; Enteroviruses; Phosphatidylinositol 4-kinase (PI4K); Purines