2. Academic Validation
  3. Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors

Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors

  • Bioorg Med Chem Lett. 2014 Mar 15;24(6):1581-8. doi: 10.1016/j.bmcl.2014.01.075.
Ning-Yu Wang 1,  Wei-Qiong Zuo 1,  Ying Xu 1,  Chao Gao 1,  Xiu-Xiu Zeng 2,  Li-Dan Zhang 3,  Xin-Yu You 3,  Cui-Ting Peng 3,  Yang Shen 4,  Sheng-Yong Yang 1,  Yu-Quan Wei 1,  Luo-Ting Yu 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
  • 2 Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
  • 3 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China; Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
  • 4 WuXi PharmaTech Co., Ltd., No. 1 Building, 288 FuTe ZhongLu, WaiGaoQiao Free Trade Zone, Shanghai 200131, China.
  • 5 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
PMID: 24529869 DOI: 10.1016/j.bmcl.2014.01.075
Abstract

Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus Infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50=3.3μM, SI >30.3, 12b, EC50=3.5μM, SI >28.6, 10l, EC50=3.9μM, SI >25.6, 12o, EC50=4.5μM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.

Keywords

Hepatitis C virus (HCV); Structure activity relationship (SAR); Thieno[2,3-b]pyridine.

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