88227 20200716101518.0 doi 10.1016/j.ejmech.2019.03.019 sideral 111123 ART-2019-111123 eng (orcid)0000-0002-4972-7476 Gálvez, José A. Universidad de Zaragoza Stereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-position 2019 Access copy available to the general public Unrestricted GSK3082 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. info:eu-repo/grantAgreement/ES/DGA/E45-17R info:eu-repo/grantAgreement/ES/FIS/PI15-00663 info:eu-repo/grantAgreement/ES/ISCIII/CPII13-0017 info:eu-repo/grantAgreement/ES/MEC/FPU13-3870 info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 5.572 2019 CHEMISTRY, MEDICINAL 5 / 61 = 0.082 2019 Q1 T1 1.144 2019 Drug Discovery 2019 Q1 Pharmacology 2019 Q1 Organic Chemistry 2019 Q1 Medicine (miscellaneous) 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Clavería-Gimeno, Rafael (orcid)0000-0002-1896-7805 Galano-Frutos, Juan J. Universidad de Zaragoza (orcid)0000-0002-2879-9200 Sancho, Javier Universidad de Zaragoza (orcid)0000-0001-5702-4538 Velázquez-Campoy, Adrian Universidad de Zaragoza (orcid)0000-0001-5664-1729 Abian, Olga Universidad de Zaragoza (orcid)0000-0001-9033-8459 Díaz-de-Villegas, María D. 2013 765 Universidad de Zaragoza Dpto. Química Orgánica Área Química Orgánica 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 171 (2019), 401-419 Eur. j. med. chem. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 0223-5234 576501 http://zaguan.unizar.es/record/88227/files/texto_completo.pdf Postprint 329346 http://zaguan.unizar.es/record/88227/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:88227 articulos driver 2020-07-16-09:24:55 ARTICLE