Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Chemistry, Nucleosides, Prodrugs, HCV, Conformation, Phosphoramidates, SUGAR RING, INHIBITORS, RIBONUCLEOSIDES, DECARBOXYLASE, NUCLEOTIDES, REPLICATION, NUCLEOSIDES, DERIVATIVES, POTENT, Humans, Magnetic Resonance Spectroscopy, Molecular Conformation, Molecular Structure, Uridine, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

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.