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Synthesis, Antiviral Evaluation, and Computational Studies of Cyclobutane and Cyclobutene L ‐Nucleoside Analogues
Author(s) -
MirallesLlumà Rosa,
Figueras Antoni,
Busqué Félix,
AlvarezLarena Angel,
Balzarini Jan,
Figueredo Marta,
Font Josep,
Alibés Ramon,
Maréchal JeanDidier
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301097
Subject(s) - chemistry , cyclobutane , docking (animal) , thymine , stereochemistry , nucleoside , cyclobutene , nucleobase , nucleoside analogue , guanine , prodrug , combinatorial chemistry , biochemistry , dna , nucleotide , organic chemistry , medicine , ring (chemistry) , nursing , gene
This paper describes the stereoselective synthesis of a series of functionalized cyclobutane and cyclobutene L ‐nucleoside analogues featuring a methylene spacer between the carbocycle and the nucleobase. These L ‐nucleoside analogues were subjected to comprehensive screening for antiviral activity. To obtain knowledge at the molecular structural level relevant for designing future analogues, the mechanism of action of these L ‐nucleoside analogues as anti‐herpes simplex virus agents was investigated by computational approaches. In particular, protein–ligand docking calculations were used to rationalize the ability of the prodrug candidates to be activated. Docking experiments were performed on the three kinases involved in the activation process of thymine and guanine derivatives.