Liang Liu

Publications (5)15.4 Total impact

• Article: Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4 capping groups.

  Xianfeng Li, Yang Liu, Yong-Kang Zhang, Jacob J Plattner, Stephen J Baker, Wei Bu, Liang Liu, Yasheen Zhou, Charles Z Ding, Suoming Zhang, [......], 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
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  ABSTRACT: 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.
  Bioorganic & medicinal chemistry letters 10/2012; · 2.65 Impact Factor
• Article: Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor-resistant mutants.

  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, [......], Xianfeng Li, Suoming Zhang, Yong-Kang Zhang, Yang Liu, Charles Z Ding, Yasheen Zhou, Jacob J Plattner, Stephen J Baker, Wei Bu, Liang Liu
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  ABSTRACT: The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.
  Journal of Medicinal Chemistry 04/2012; 55(7):3021-6. · 4.80 Impact Factor
• Source

  Available from: Maosheng Duan

  Article: Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties.

  Xianfeng Li, Suoming Zhang, Yong-Kang Zhang, Yang Liu, Charles Z Ding, Yasheen Zhou, Jacob J Plattner, Stephen J Baker, Wei Bu, Liang Liu, [......], Gary K Smith, Richard L Jarvest, Jing-Jing Ji, Joel P Cooper, Matthew D Tallant, Renae M Crosby, Katrina Creech, Zhi-Jie Ni, Wuxin Zou, Jon Wright
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  ABSTRACT: We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series.
  Bioorganic & medicinal chemistry letters 02/2011; 21(7):2048-54. · 2.65 Impact Factor
• Source

  Available from: Maosheng Duan

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

  Charles Z Ding, Yong-Kang Zhang, Xianfeng Li, Yang Liu, Suoming Zhang, Yasheen Zhou, Jacob J Plattner, Stephen J Baker, Liang Liu, Maosheng Duan, [......], 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
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  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.
  Bioorganic & medicinal chemistry letters 10/2010; 20(24):7317-22. · 2.65 Impact Factor
• Source

  Available from: Maosheng Duan

  Article: Synthesis of new acylsulfamoyl benzoxaboroles as potent inhibitors of HCV NS3 protease.

  Xianfeng Li, Yong-Kang Zhang, Yang Liu, Suoming Zhang, Charles Z Ding, Yasheen Zhou, Jacob J Plattner, Stephen J Baker, Liang Liu, Wei Bu, [......], Richard L Jarvest, Maosheng Duan, Jing-Jing Ji, Joel P Cooper, Matthew D Tallant, Renae M Crosby, Katrina Creech, Zhi-Jie Ni, Wuxin Zou, Jon Wright
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  ABSTRACT: HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1' region was synthesized and evaluated. The resulting P1-P3 and P2-P4 macrocyclic inhibitors exhibited sub-nanomolar potency in the enzymatic assay and low nanomolar activity in the cell-based replicon assay. The in vivo PK evaluations of selected compounds are also described.
  Bioorganic & medicinal chemistry letters 10/2010; 20(24):7493-7. · 2.65 Impact Factor