Kang Iou-Jiun, Wang Li-Wen, Lee Chung-Chi, Lee Yen-Chun, Chao Yu-Sheng, Hsu Tsu-An, Chern Jyh-Haur
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC.
Bioorg Med Chem Lett. 2009 Apr 1;19(7):1950-5. doi: 10.1016/j.bmcl.2009.02.048. Epub 2009 Feb 20.
A series of thiourea derivatives were synthesized and their antiviral activity was evaluated in a cell-based HCV subgenomic replicon assay. SAR studies revealed that the chain length and the position of the alkyl linker largely influenced the in vitro anti-HCV activity of this class of potent antiviral agents. Among this series of compounds synthesized, the thiourea derivative with a six-carbon alkyl linker at the meta-position of the central phenyl ring (10) was identified as the most potent anti-HCV inhibitor (EC(50) = 0.047 microM) with a selectivity index of 596.
合成了一系列硫脲衍生物，并在基于细胞的丙型肝炎病毒亚基因组复制子试验中评估了它们的抗病毒活性。构效关系研究表明，烷基连接链的长度和位置在很大程度上影响了这类强效抗病毒剂的体外抗丙型肝炎病毒活性。在合成的这一系列化合物中，中心苯环间位带有六碳烷基连接链的硫脲衍生物（10）被确定为最有效的抗丙型肝炎病毒抑制剂（半数有效浓度=0.047微摩尔），选择性指数为596。
