000088227 001__ 88227 000088227 005__ 20200716101518.0 000088227 0247_ $$2doi$$a10.1016/j.ejmech.2019.03.019 000088227 0248_ $$2sideral$$a111123 000088227 037__ $$aART-2019-111123 000088227 041__ $$aeng 000088227 100__ $$0(orcid)0000-0002-4972-7476$$aGálvez, José A.$$uUniversidad de Zaragoza 000088227 245__ $$aStereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-position 000088227 260__ $$c2019 000088227 5060_ $$aAccess copy available to the general public$$fUnrestricted 000088227 5203_ $$aGSK3082 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. 000088227 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00663$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-0017$$9info:eu-repo/grantAgreement/ES/MEC/FPU13-3870$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P 000088227 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000088227 590__ $$a5.572$$b2019 000088227 591__ $$aCHEMISTRY, MEDICINAL$$b5 / 61 = 0.082$$c2019$$dQ1$$eT1 000088227 592__ $$a1.144$$b2019 000088227 593__ $$aDrug Discovery$$c2019$$dQ1 000088227 593__ $$aPharmacology$$c2019$$dQ1 000088227 593__ $$aOrganic Chemistry$$c2019$$dQ1 000088227 593__ $$aMedicine (miscellaneous)$$c2019$$dQ1 000088227 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000088227 700__ $$aClavería-Gimeno, Rafael 000088227 700__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos, Juan J.$$uUniversidad de Zaragoza 000088227 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza 000088227 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrian$$uUniversidad de Zaragoza 000088227 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza 000088227 700__ $$0(orcid)0000-0001-9033-8459$$aDíaz-de-Villegas, María D. 000088227 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica 000088227 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000088227 773__ $$g171 (2019), 401-419$$pEur. j. med. chem.$$tEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY$$x0223-5234 000088227 8564_ $$s576501$$uhttps://zaguan.unizar.es/record/88227/files/texto_completo.pdf$$yPostprint 000088227 8564_ $$s329346$$uhttps://zaguan.unizar.es/record/88227/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000088227 909CO $$ooai:zaguan.unizar.es:88227$$particulos$$pdriver 000088227 951__ $$a2020-07-16-09:24:55 000088227 980__ $$aARTICLE