title: NMR-based conformational analysis of 2',6-disubstituted uridines and antiviral evaluation of new phosphoramidate prodrugs.
abstract: Six novel phosphoramidate prodrugs of uridine analogues, with structural modifications introduced at the 6- and 2',6-positions, have been prepared and evaluated for selective antiviral activity against hepatitis C virus, as well as other positive-stranded RNA viruses. An analysis of the conformational properties of the parent nucleosides was carried out using two-dimensional NMR spectroscopy based experiments, highlighting a 3'-endo (North) sugar puckering preference and syn orientation.
authors.affiliation: Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Fábio
authors.initials: F
authors.lastname: da Paixão Soares
authors.affiliation: Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Groaz
authors.affiliation: Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Eveline
authors.initials: E
authors.lastname: Lescrinier
authors.affiliation: Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium. Electronic address: Piet.Herdewijn@rega.kuleuven.be.
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
mesh_terms: D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008968:Molecular Conformation; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D014529:Uridine / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D009705:Nucleosides; D011355:Prodrugs; D014529:Uridine
keywords: Conformation; HCV; Nucleosides; Phosphoramidates; Prodrugs