2-[[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]imino]-5-(2,4-dichlorobenzylidene)-1,3-thiazolidin-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]imino]-5-(2,4-dichlorobenzylidene)-1,3-thiazolidin-4-one
• 英文别名: (2E,5Z)-5-[(2,4-dichlorophenyl)methylene]-2-[[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]imino]thiazolidin-4-one；(2E,5Z)-5-[(2,4-dichlorophenyl)methylidene]-2-[[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]imino]-1,3-thiazolidin-4-one
• 化学式: C₁₈H₉Cl₂FN₄OS₂
• 分子量: 451.332
• InChiKey: TVVFJSXFCORTCL-AUWJEWJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-5-(4-氟苯基)-1,3,4-噻重氮 在 sodium methylate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 2-[[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]imino]-5-(2,4-dichlorobenzylidene)-1,3-thiazolidin-4-one
  参考文献：
  名称：

  2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase

  摘要：

  Hepatitis C virus (HCV) NS5B polymerase is an important and attractive target for the development of anti-HCV drugs. Here we report on the design, synthesis and evaluation of twenty-four novel allosteric inhibitors bearing the 4-thiazolidinone scaffold as inhibitors of HCV NS5B polymerase. Eleven compounds tested were found to inhibit HCV NS5B with IC50 values ranging between 19.8 and 64.9 RM. Compound 24 was the most active of this series with an IC50 of 5.6 mu M. A number of these derivatives further exhibited strong inhibition against HCV lb and 2a genotypes in cell based antiviral assays. Molecular docking analysis predicted that the thiazolidinone derivatives bind to the NS5B thumb pocketII (TP-II). Our results suggest that further optimization of the thiazolidinone scaffold may be possible to yield new derivatives with improved enzyme- and cell-based activity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.043

文献信息

• 2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase
  作者：İlkay Küçükgüzel、Gökhan Satılmış、K.R. Gurukumar、Amartya Basu、Esra Tatar、Daniel B. Nichols、Tanaji T. Talele、Neerja Kaushik-Basu

  DOI：10.1016/j.ejmech.2013.08.043

  日期：2013.11

  Hepatitis C virus (HCV) NS5B polymerase is an important and attractive target for the development of anti-HCV drugs. Here we report on the design, synthesis and evaluation of twenty-four novel allosteric inhibitors bearing the 4-thiazolidinone scaffold as inhibitors of HCV NS5B polymerase. Eleven compounds tested were found to inhibit HCV NS5B with IC50 values ranging between 19.8 and 64.9 RM. Compound 24 was the most active of this series with an IC50 of 5.6 mu M. A number of these derivatives further exhibited strong inhibition against HCV lb and 2a genotypes in cell based antiviral assays. Molecular docking analysis predicted that the thiazolidinone derivatives bind to the NS5B thumb pocketII (TP-II). Our results suggest that further optimization of the thiazolidinone scaffold may be possible to yield new derivatives with improved enzyme- and cell-based activity. (C) 2013 Elsevier Masson SAS. All rights reserved.