Santhosh F Neelamkavil, Sony Agrawal, Thomas Bara, Chad Bennett, Sathesh Bhat, Dipshikha Biswas, Linda Brockunier, Nicole Buist, Duane Burnette, Mark Cartwright, Samuel Chackalamannil, Robert Chase, Mariappan Chelliah, Austin Chen, Martin Clasby, Vincent J Colandrea, Ian W Davies, Keith Eagen, Zhuyan Guo, Yongxin Han, John Howe, Charles Jayne, Hubert Josien, Stacia Kargman, Karen Marcantonio, Shouwu Miao, Randy Miller, Andrew Nolting, Patrick Pinto, Murali Rajagopalan, Rebecca T Ruck, Unmesh Shah, Aileen Soriano, Donald Sperbeck, Francisco Velazquez, Jin Wu, Yan Xia, Srikanth Venkatraman
We have been focused on identifying a structurally different next generation inhibitor to MK-5172 (our Ns3/4a protease inhibitor currently under regulatory review), which would achieve superior pangenotypic activity with acceptable safety and pharmacokinetic profile. These efforts have led to the discovery of a novel class of HCV NS3/4a protease inhibitors containing a unique spirocyclic-proline structural motif. The design strategy involved a molecular-modeling based approach, and the optimization efforts on the series to obtain pan-genotypic coverage with good exposures on oral dosing...
January 14, 2016: ACS Medicinal Chemistry Letters