Hepatitis C virus inhibitors having the general formula
are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
Discovery of a Potent Acyclic, Tripeptidic, Acyl Sulfonamide Inhibitor of Hepatitis C Virus NS3 Protease as a Back-up to Asunaprevir with the Potential for Once-Daily Dosing
作者:Li-Qiang Sun、Eric Mull、Barbara Zheng、Stanley D’Andrea、Qian Zhao、Alan Xiangdong Wang、Ny Sin、Brian L. Venables、Sing-Yuen Sit、Yan Chen、Jie Chen、Anthony Cocuzza、Donna M. Bilder、Arvind Mathur、Richard Rampulla、Bang-Chi Chen、Theerthagiri Palani、Sivakumar Ganesan、Pirama Nayagam Arunachalam、Paul Falk、Steven Levine、Chaoqun Chen、Jacques Friborg、Fei Yu、Dennis Hernandez、Amy K. Sheaffer、Jay O. Knipe、Yong-Hae Han、Richard Schartman、Maria Donoso、Kathy Mosure、Michael W. Sinz、Tatyana Zvyaga、Ramkumar Rajamani、Kevin Kish、Jeffrey Tredup、Herbert E. Klei、Qi Gao、Alicia Ng、Luciano Mueller、Dennis M. Grasela、Stephen Adams、James Loy、Paul C. Levesque、Huabin Sun、Hong Shi、Lucy Sun、William Warner、Danshi Li、Jialong Zhu、Ying-Kai Wang、Hua Fang、Mark I. Cockett、Nicholas A. Meanwell、Fiona McPhee、Paul M. Scola
DOI:10.1021/acs.jmedchem.6b00821
日期:2016.9.8
The discovery of a back-up to the hepatitisCvirus NS3 proteaseinhibitor asunaprevir (2) is described. The objective of this work was the identification of a drug with antiviral properties and toxicology parameters similar to 2, but with a preclinical pharmacokinetic (PK) profile that was predictive of once-daily dosing. Critical to this discovery process was the employment of an ex vivo cardiovascular