ethyl 7-carbamoyl-4,6-dimethoxy-3-methyl-1-benzofuran-2-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: ethyl 7-carbamoyl-4,6-dimethoxy-3-methyl-1-benzofuran-2-carboxylate
• 英文别名: ethyl 7-carbamoyl-4,6-dimethoxy-3-methylbenzofuran-2-carboxylate；Ethyl 7-carbamoyl-4,6-dimethoxy-3-methyl-1-benzofuran-2-carboxylate
• 化学式: C₁₅H₁₇NO₆
• 分子量: 307.303
• InChiKey: XHXPBGAQFOFRHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 7-carbamoyl-4,6-dimethoxy-3-methyl-1-benzofuran-2-carboxylate 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Design and synthesis of novel 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide derivatives as potent Mnks inhibitors by fragment-based drug design

  摘要：

  A novel series of 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide derivatives featured with various C-2 substituents were designed and synthesized as Mnks inhibitors through fragment-based drug design. Among them, 5b, 51, 5o and 8k showed the best Mnk2 inhibitory activity with IC 50 values of 1.45, 1.16, 3.55 and 0.27 mu M, respectively. And these compounds inhibited the activity of Mnkl at the same time. Furthermore, compounds 50 and 8k exhibited anti-proliferative effects to human leukemia cancer THP-1 and MOLM-13 cell lines and colon cancer HCT-116 cell line. Moreover, Western blot assay suggested that 8k could decrease the levels of p-eIF4E in a dose-dependent manner in HCT-116 cells. Docking studies demonstrated strong interactions between 8k and Mnk2. Therefore, this unique benzofuran scaffold demonstrated great potential to be further explored as potent Mnks inhibitors with improved potency. (C) 2018 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2018.05.004
• 作为产物：
  描述：

  2-羟基-4,6-二甲氧基苯乙酮 在 硫酸 、 溴 、 potassium carbonate 、 溶剂黄146 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.67h， 生成 ethyl 7-carbamoyl-4,6-dimethoxy-3-methyl-1-benzofuran-2-carboxylate
  参考文献：
  名称：

  Synthesis and antiproliferative activity of benzofuran-based analogs of cercosporamide against non-small cell lung cancer cell lines

  摘要：

  A novel series of 3-methyl-1-benzofuran derivatives were synthesized and screened in vitro for their antiproliferative activity against two human NSCLC cell lines (NSCLC-N6 mutant p53 and A549 wild type p53). Most promising compounds presented a structural analogy with the west part of cercosporamide, a natural product of biological interest. In particular, compounds 10, 12 and 31 showed cytotoxic activities at micromolar concentrations (IC50 < 9.3 mu M) and compounds 13, 18 and 32 displayed moderate ICso values (25-40 mu M). (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.013

文献信息

• Synthesis and antiproliferative activity of benzofuran-based analogs of cercosporamide against non-small cell lung cancer cell lines
  作者：Marc-Antoine Bazin、Lizeth Bodero、Christophe Tomasoni、Bénédicte Rousseau、Christos Roussakis、Pascal Marchand

  DOI：10.1016/j.ejmech.2013.09.013

  日期：2013.11

  A novel series of 3-methyl-1-benzofuran derivatives were synthesized and screened in vitro for their antiproliferative activity against two human NSCLC cell lines (NSCLC-N6 mutant p53 and A549 wild type p53). Most promising compounds presented a structural analogy with the west part of cercosporamide, a natural product of biological interest. In particular, compounds 10, 12 and 31 showed cytotoxic activities at micromolar concentrations (IC50 < 9.3 mu M) and compounds 13, 18 and 32 displayed moderate ICso values (25-40 mu M). (C) 2013 Elsevier Masson SAS. All rights reserved.
• Design and synthesis of novel 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide derivatives as potent Mnks inhibitors by fragment-based drug design
  作者：Shuxiang Wang、Bo Li、Bo Liu、Min Huang、Deyi Li、Lihong Guan、Jie Zang、Dan Liu、Linxiang Zhao

  DOI：10.1016/j.bmc.2018.05.004

  日期：2018.9

  A novel series of 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide derivatives featured with various C-2 substituents were designed and synthesized as Mnks inhibitors through fragment-based drug design. Among them, 5b, 51, 5o and 8k showed the best Mnk2 inhibitory activity with IC 50 values of 1.45, 1.16, 3.55 and 0.27 mu M, respectively. And these compounds inhibited the activity of Mnkl at the same time. Furthermore, compounds 50 and 8k exhibited anti-proliferative effects to human leukemia cancer THP-1 and MOLM-13 cell lines and colon cancer HCT-116 cell line. Moreover, Western blot assay suggested that 8k could decrease the levels of p-eIF4E in a dose-dependent manner in HCT-116 cells. Docking studies demonstrated strong interactions between 8k and Mnk2. Therefore, this unique benzofuran scaffold demonstrated great potential to be further explored as potent Mnks inhibitors with improved potency. (C) 2018 Published by Elsevier Ltd.