625377-79-9Relevant academic research and scientific papers
A new series of HCV inhibitors based on a 2-(thieno[2,3B]pyridin-2-yl)-1,3,4-oxadiazole scaffold
Zuo, Wei-Qiong,Wang, Ning-Yu,Zhu, Yong-Xia,Liu, Li,Xiao, Kun-Jie,Zhang, Li-Dan,Gao, Chao,Liu, Zhi-Hao,You, Xin-Yu,Shi, Yao-Jie,Peng, Cui-Ting,Ran, Kai,Tang, Hong,Yu, Luo-Ting
, p. 40277 - 40286 (2016)
A new series of HCV inhibitors based on a 2-(thieno[2,3-b]pyridin-2-yl)-1,3,4-oxadiazole scaffold was developed. Detailed SAR investigations revealed the HCV inhibitory activity was sensitive to the size of C5, the C6-fused ring, and the size and flexibility of C5′ cycloalkane, which led to the identification of several compounds with potent inhibitory activity against HCV genotype 1b replicon. The most potent compound 10d showed ～100-fold improvement in potency compared with compound 1, with an EC50 of 0.039 μM, but without obvious cytotoxicity in vitro.
Discovery and structure-resistance relationship study of new thieno[2,3-b] pyridine HCV NS4B inhibitors
Xiao, Kun-Jie,Zuo, Wei-Qiong,Xu, Ying,Tao, Xin,Yu, Luo-Ting,Wang, Ning-Yu
, p. 321 - 325 (2019/08/22)
The non-structural protein 4B (NS4B) of hepatitis C virus (HCV) has emerged as a promising target for chronic hepatitis C treatment. The thieno[2,3-b]pyridine HCV inhibitor 2 has demonstrated properties as a NS4B inhibitor. Subsequent hybridization of 2 with our recently published imidazo[2,1-b]thiazole NS4B inhibitor 3 resulted in the discovery of several more potent compounds with sub-micromolar EC50 against HCV genotype 1b replicon. More importantly, the resistant profile study of the new synthesized HCV inhibitors illustrated that the bicyclic scaffold would mediate the resistance of H3R and Q26R mutations, while the piperazinone motif would mediate the resistance of H94R, F98C and V105M mutations, and the C3- amino group would disrupt the interaction between piperazinone motif and NS4B. This structure-resistance relationship detail could help us to develop new NS4B inhibitors with higher resistant barrier in the future.
Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors
Wang, Ning-Yu,Zuo, Wei-Qiong,Xu, Ying,Gao, Chao,Zeng, Xiu-Xiu,Zhang, Li-Dan,You, Xin-Yu,Peng, Cui-Ting,Shen, Yang,Yang, Sheng-Yong,Wei, Yu-Quan,Yu, Luo-Ting
, p. 1581 - 1588 (2014/03/21)
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 = 3.3 μM, SI >30.3, 12b, EC50 = 3.5 μM, SI >28.6, 10l, EC50 = 3.9 μM, SI >25.6, 12o, EC 50 = 4.5 μM, 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.
