- Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4 capping groups.
Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4 capping groups.
Bioorganic & medicinal chemistry letters (2012-11-13)
Xianfeng Li, Yang Liu, Yong-Kang Zhang, Jacob J Plattner, Stephen J Baker, Wei Bu, Liang Liu, Yasheen Zhou, Charles Z Ding, Suoming Zhang, Wieslaw M Kazmierski, Robert Hamatake, Maosheng Duan, Lois L Wright, Gary K Smith, Richard L Jarvest, Jing-Jing Ji, Joel P Cooper, Matthew D Tallant, Renae M Crosby, Katrina Creech, Amy Wang
PMID23142614
ZUSAMMENFASSUNG
We have synthesized and evaluated a series of novel HCV NS3 protease inhibitors with various P4 capping groups, which include urea, carbamate, methoxy-carboxamide, cyclic carbamate and amide, pyruvic amide, oxamate, oxalamide and cyanoguanidine. Most of these compounds are remarkably potent, exhibiting single-digit to sub-nanomolar activity in the enzyme assay and cell-based replicon assay. Selected compounds were also evaluated in the protease-inhibitor-resistant mutant transient replicon assay, and they were found to show quite different potency profiles against a panel of HCV protease-inhibitor-resistant mutants.