NMR-based conformational analysis of 2 ',6-disubstituted uridines and antiviral evaluation of new phosphoramidate prodrugs

作者:Soares Fabio da Paixao; Groaz Elisabetta; Lescrinier Eveline; Neyts Johan; Leyssen Pieter; Herdewijn Piet*
来源:Bioorganic & Medicinal Chemistry, 2015, 23(17): 5809-5815.
DOI:10.1016/j.bmc.2015.07.003

摘要

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.