Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease

  • Bioorg Med Chem Lett. 2010 Dec 15;20(24):7317-22. doi: 10.1016/j.bmcl.2010.10.071.
Charles Z Ding  1 ,  Yong-Kang Zhang ,  Xianfeng Li ,  Yang Liu ,  Suoming Zhang ,  Yasheen Zhou ,  Jacob J Plattner ,  Stephen J Baker ,  Liang Liu ,  Maosheng Duan ,  Richard L Jarvest ,  Jingjing Ji ,  Wieslaw M Kazmierski ,  Matthew D Tallant ,  Lois L Wright ,  Gary K Smith ,  Renae M Crosby ,  Amy A Wang ,  Zhi-Jie Ni ,  Wuxin Zou ,  Jon Wright
Affiliations
PMID: 21067923 DOI: 10.1016/j.bmcl.2010.10.071
Abstract

We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV Protease Inhibitors. These inhibitors are potent against HCV NS3 Protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2∗ groups. P2∗ 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein.