doi:10.1016/j.ejmech.2019.03.019engGálvez, José A.Clavería-Gimeno, RafaelGalano-Frutos, Juan J.Sancho, JavierVelázquez-Campoy, AdrianAbian, OlgaDíaz-de-Villegas, María D.Stereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-positionART-2019-111123GSK3082 e a hepatitis C virus RNA polymerase inhibitor e and a series of analogues with structural diversity at the 5-position were prepared from a 2,2,4,5 -tetrasubstituted pyrrolidine obtained with a well-defined stereochemistry from the 1,3-dipolar cycloaddition of the chiral imino ester derived from leucine tert-butyl ester and (R)-2,3-O-isopropylideneglyceraldehyde with methyl acrylate. The chiral 2,2-dimethyl-1,3-dioxolane moiety provided by the glyceraldehyde served as a synthetic equivalent for different substituents and functional groups and these transformations usually required mild reaction conditions and simple work-up procedures. The inhibitory activity of the resulting GSK3082 analogues was studied in vitro in a cell-based assay of the subgenomic HCV RNA replication system. Some of the analogues showed good inhibitory activity with IC50 values in the nanomolar concentration range.2019http://zaguan.unizar.es/record/8822710.1016/j.ejmech.2019.03.019http://zaguan.unizar.es/record/88227oai:zaguan.unizar.es:88227info:eu-repo/grantAgreement/ES/DGA/E45-17Rinfo:eu-repo/grantAgreement/ES/FIS/PI15-00663info:eu-repo/grantAgreement/ES/ISCIII/CPII13-0017info:eu-repo/grantAgreement/ES/MEC/FPU13-3870info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-PEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 171 (2019), 401-419by-nc-ndhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccess