ethyl 3-amino-4-(trifluoromethyl)-6-(thiophen-2-yl)thieno[2,3-b]pyridine-2-carboxylate | 340816-56-0

• 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: ethyl 3-amino-4-(trifluoromethyl)-6-(thiophen-2-yl)thieno[2,3-b]pyridine-2-carboxylate
• 英文别名: ethyl 3-amino-6-(thiophen-2-yl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxylate；ethyl 3-cyano-6-(2-thienyl)-4-trifluoromethylthieno[2,3-b]pyridine-2-carboxylate；ethyl 3-amino-6-thiophen-2-yl-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxylate
• CAS: 340816-56-0
• 化学式: C₁₅H₁₁F₃N₂O₂S₂
• 分子量: 372.392
• InChiKey: JRWHOUVTUVBFIT-UHFFFAOYSA-N

物化性质

• 熔点：
  187-188 °C(Solv: ethanol (64-17-5))
• 沸点：
  511.2±50.0 °C(Predicted)
• 密度：
  1.482±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 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：
  122
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 3-amino-4-(trifluoromethyl)-6-(thiophen-2-yl)thieno[2,3-b]pyridine-2-carboxylate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以65%的产率得到3-amino-6-(2-thienyl)-4-trifluoromethylthieno[2,3-b]pyridine-2-carbohydrazide
  参考文献：
  名称：

  4-三氟甲基-3-氰基吡啶-2(1H)-硫酮/一衍生物的合成与反应

  摘要：

  4,4,4-Trifluoro-1-(thiophen-2-yl)butane-1,3-dione 通过与氰硫代乙酰胺和氰基乙酰胺在 25 °C 无溶剂条件下研磨反应得到吡啶-2(1H) 硫酮/one 衍生物以优异的产量。这些化合物通过与不同的卤化试剂研磨进一步反应，得到 2-S/O-烷基吡啶衍生物。后一种化合物用于合成噻吩并[2,3-b]吡啶、吡唑并吡啶、吡啶并噻吩并嘧啶和吡啶并噻吩并恶嗪酮衍生物。

  DOI：

  10.1080/17415993.2011.628994
• 作为产物：
  描述：

  2-噻吩甲酰三氟丙酮 在 sodium ethanolate 、 potassium hydroxide 作用下， 反应 3.0h， 生成 ethyl 3-amino-4-(trifluoromethyl)-6-(thiophen-2-yl)thieno[2,3-b]pyridine-2-carboxylate
  参考文献：
  名称：

  4-三氟甲基-3-氰基吡啶-2(1H)-硫酮/一衍生物的合成与反应

  摘要：

  4,4,4-Trifluoro-1-(thiophen-2-yl)butane-1,3-dione 通过与氰硫代乙酰胺和氰基乙酰胺在 25 °C 无溶剂条件下研磨反应得到吡啶-2(1H) 硫酮/one 衍生物以优异的产量。这些化合物通过与不同的卤化试剂研磨进一步反应，得到 2-S/O-烷基吡啶衍生物。后一种化合物用于合成噻吩并[2,3-b]吡啶、吡唑并吡啶、吡啶并噻吩并嘧啶和吡啶并噻吩并恶嗪酮衍生物。

  DOI：

  10.1080/17415993.2011.628994

文献信息

• Synthesis and reactions of 4-trifluoromethyl-3-cyano pyridine-2(<i>1H</i>)-thione/one derivatives
  作者：Nora M. Rateb

  DOI：10.1080/17415993.2011.628994

  日期：2011.12.1

  cyanothioacetamide and cyanoacetamide under solvent-free conditions at 25 °C to give pyridine-2(1H)thione/one derivatives in excellent yields. These compounds were further reacted by grinding with different halogenated reagents to give 2-S/O-alkyl pyridine derivatives. The latter compounds were utilized for the synthesis of thieno[2,3-b]pyridine, pyrazolopyridine, pyridothienopyrimidine and pyridothienooxazinone

  4,4,4-Trifluoro-1-(thiophen-2-yl)butane-1,3-dione 通过与氰硫代乙酰胺和氰基乙酰胺在 25 °C 无溶剂条件下研磨反应得到吡啶-2(1H) 硫酮/one 衍生物以优异的产量。这些化合物通过与不同的卤化试剂研磨进一步反应，得到 2-S/O-烷基吡啶衍生物。后一种化合物用于合成噻吩并[2,3-b]吡啶、吡唑并吡啶、吡啶并噻吩并嘧啶和吡啶并噻吩并恶嗪酮衍生物。
• 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。
• Synthesis of Novel Trifluoromethyl Group Containing Pyrido Furo/Thieno Pyrimidinone Derivatives and Their Anticancer Activity
  作者：Hanumandlu Racha、Balakishan Vadla、Kavitha Peddolla、Sailu Betala

  DOI：10.1002/jhet.3566

  日期：2019.6

  Compound 4 on reaction with trifluoroacetic acid and obtained novel trifluoromethyl group containing pyridofuro/thieno pyrimidinone derivatives 5a–p. All the synthesized compounds 5a–p were tested for anticancer activity on four cancer cell lines such as HeLa cervical cancer (CCL‐2), COLO 205 colon cancer (CCL‐222), HepG2 liver cancer (HB‐8065), MCF7 breast cancer (HTB‐22), and one normal cell line

  从2-氧代/硫代氧-6-苯基/噻吩-2-基-4-（三氟甲基）-1,2-二氢吡啶-3-碳腈开始制备了一系列新颖的含三氟甲基/吡啶酮/噻吩并嘧啶酮衍生物5a-p 1化合物与溴乙酸乙酯和其他不同的脂肪族伯胺在回流条件下反应，得到酰胺标记的呋喃/噻吩并吡啶衍生物4。化合物4与三氟乙酸反应，获得了新颖的含三氟甲基的吡啶并/噻吩并嘧啶酮衍生物5a-p。所有合成的化合物5a–p测试了四种癌细胞系的抗癌活性，例如HeLa宫颈癌（CCL-2），COLO 205结肠癌（CCL-222），HepG2肝癌（HB-8065），MCF7乳腺癌（HTB-22）和1个正常细胞系（HEK 293）；发现化合物5m，5n和5p在微摩尔浓度下具有更好的抗癌活性，并且对正常细胞系无毒。
• Synthesis of Novel Alkyl Amide Functionalized Trifluoromethyl Substituted Furo/thieno Pyridine Derivatives: Their Anticancer Activity and CoMFA and CoMSIA Studies
  作者：Srinu Bhoomandla、Shravan Kumar Gunda、Srawanthi Kotoori、Phani Raja Kanuparthy

  DOI：10.1002/jhet.3578

  日期：2019.7

  6a–h were screened for anticancer activity against four cancer cell lines such as HeLa—cervical cancer (CCL‐2), COLO205—colon cancer (CCL‐222), HepG2—liver cancer (HB‐8065), and MCF7—breast cancer (HTB‐22). Compounds 4g and 4h are found to have promising anticancer activity at micromolar concentration. CoMFA and CoMSIA methods were applied to derive 3D‐QSAR models for alkyl amide tagged furo/thieno

  从2-氧代/硫代氧-6-苯基/噻吩-2-基-4-（三氟甲基）开始制备了一系列新颖的烷基酰胺官能化的三氟甲基取代的呋喃/硫代吡啶衍生物4a-h，5a-d和6a-h）1,2-二氢吡啶-3-腈1与溴乙酸乙酯反应，然后在不同的条件下与不同的脂肪族伯胺，环状仲胺或l-氨基酸反应。所有合成的化合物4a–h，5a–d和6a–h筛选了针对四种癌细胞系的抗癌活性，例如HeLa-宫颈癌（CCL-2），COLO205-结肠癌（CCL-222），HepG2-肝癌（HB-8065）和MCF7-乳腺癌（HTB- 22）。发现化合物4g和4h在微摩尔浓度下具有有希望的抗癌活性。应用CoMFA和CoMSIA方法获得了3D-QSAR模型，用于烷基酰胺标记的呋喃/噻吩并吡啶衍生物作为潜在的抗癌抑制剂。3D-QSAR模型为将来更合理地设计更具活性和选择性的HeLa，COLO205，HepG2和MCF-7细胞系抑制剂提供了坚实的基础。
• 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.