3-Amino-2-ethoxycarbonyl-6-furyl-4-trifluoromethyl-thieno[2,3-b]pyridine | 607696-90-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 3-Amino-2-ethoxycarbonyl-6-furyl-4-trifluoromethyl-thieno[2,3-b]pyridine
• 英文别名: Ethyl 3-amino-6-(furan-2-yl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxylate
• CAS: 607696-90-2
• 化学式: C₁₅H₁₁F₃N₂O₃S
• 分子量: 356.325
• InChiKey: WASMHHKYMMDXMJ-UHFFFAOYSA-N

物化性质

• 沸点：
  489.1±45.0 °C(Predicted)
• 密度：
  1.457±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-Amino-2-ethoxycarbonyl-6-furyl-4-trifluoromethyl-thieno[2,3-b]pyridine 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 3-Amino-6-(furan-2-yl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxylic acid
  参考文献：
  名称：

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

  摘要：

  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 mu M, SI > 30.3, 12b, EC50 = 3.5 mu M, SI > 28.6, 10l, EC50 = 3.9 mu M, SI > 25.6, 12o, EC50 = 4.5 mu M, 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. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.075
• 作为产物：
  描述：

  4,4,4-三氟-1-(2-呋喃基)-1,3-丁二酮 在 三乙烯二胺 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-Amino-2-ethoxycarbonyl-6-furyl-4-trifluoromethyl-thieno[2,3-b]pyridine
  参考文献：
  名称：

  Discovery and Structure-Resistance Relationship Study of New Thieno[2,3-b] Pyridine HCV NS4B Inhibitors

  摘要：

  丙型肝炎病毒（HCV）的非结构蛋白 4B（NS4B）已成为治疗慢性丙型肝炎的一个有希望的靶点。噻吩并[2,3-b]吡啶 HCV 抑制剂 2 具有 NS4B 抑制剂的特性。随后，我们将 2 与最近发表的咪唑并[2,1-b]噻唑 NS4B 抑制剂 3 进行杂交，发现了几种对 HCV 基因型 1b 复制子具有亚微摩尔 EC50 的更强效化合物。更重要的是，新合成的 HCV 抑制剂的耐药谱研究表明，双环支架将介导 H3R 和 Q26R 突变的耐药性，而哌嗪酮基团将介导 H94R、F98C 和 V105M 突变的耐药性，C3- 氨基基团将破坏哌嗪酮基团与 NS4B 之间的相互作用。这一结构-耐药性关系细节有助于我们在未来开发出具有更高耐药屏障的新型 NS4B 抑制剂。

  DOI：

  10.1691/ph.2019.8960

文献信息

• Discovery and structure–activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors
  作者：Ning-Yu Wang、Wei-Qiong Zuo、Ying Xu、Chao Gao、Xiu-Xiu Zeng、Li-Dan Zhang、Xin-Yu You、Cui-Ting Peng、Yang Shen、Sheng-Yong Yang、Yu-Quan Wei、Luo-Ting Yu

  DOI：10.1016/j.bmcl.2014.01.075

  日期：2014.3

  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 mu M, SI > 30.3, 12b, EC50 = 3.5 mu M, SI > 28.6, 10l, EC50 = 3.9 mu M, SI > 25.6, 12o, EC50 = 4.5 mu M, 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. (C) 2014 Elsevier Ltd. All rights reserved.
• Discovery and Structure-Resistance Relationship Study of New Thieno[2,3-b] Pyridine HCV NS4B Inhibitors
  作者：Xiao, Kun-Jie、Zuo, Wei-Qiong、Xu, Ying、Tao, Xin、Yu, Luo-Ting、Wang, Ning-Yu

  DOI：10.1691/ph.2019.8960

  日期：——

  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.

  丙型肝炎病毒（HCV）的非结构蛋白 4B（NS4B）已成为治疗慢性丙型肝炎的一个有希望的靶点。噻吩并[2,3-b]吡啶 HCV 抑制剂 2 具有 NS4B 抑制剂的特性。随后，我们将 2 与最近发表的咪唑并[2,1-b]噻唑 NS4B 抑制剂 3 进行杂交，发现了几种对 HCV 基因型 1b 复制子具有亚微摩尔 EC50 的更强效化合物。更重要的是，新合成的 HCV 抑制剂的耐药谱研究表明，双环支架将介导 H3R 和 Q26R 突变的耐药性，而哌嗪酮基团将介导 H94R、F98C 和 V105M 突变的耐药性，C3- 氨基基团将破坏哌嗪酮基团与 NS4B 之间的相互作用。这一结构-耐药性关系细节有助于我们在未来开发出具有更高耐药屏障的新型 NS4B 抑制剂。