3-heterocyclyl quinolone inhibitors of the HCV NS5B polymerase.


The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles. An X-ray crystal structure of a key analog bound to NS5B facilitated the optimization of this series of compounds to afford increased activity against the target enzyme and in the cell-based replicon assay system.

DOI: 10.1016/j.bmcl.2011.11.013

Cite this paper

@article{Kumar20123heterocyclylQI, title={3-heterocyclyl quinolone inhibitors of the HCV NS5B polymerase.}, author={D. Vijay Kumar and Roopa Rai and Ken A. Brameld and Jennifer R Riggs and John R. Somoza and Ravi Rajagopalan and James W. Janc and Yu M Xia and Tony L Ton and Huiyong Hu and Isabelle E Lehoux and Joseph D. Ho and Wendy B. Young and Barry Hart and Michael J. Green}, journal={Bioorganic & medicinal chemistry letters}, year={2012}, volume={22 1}, pages={300-4} }