N,N'-(1,3-phenylene)bis(3,4,5-trimethoxybenzamide) | 547710-56-5

• 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: N,N'-(1,3-phenylene)bis(3,4,5-trimethoxybenzamide)
• 英文别名: N,N'-benzene-1,3-diylbis(3,4,5-trimethoxybenzamide)；3,4,5-trimethoxy-N-[3-[(3,4,5-trimethoxybenzoyl)amino]phenyl]benzamide
• CAS: 547710-56-5
• 化学式: C₂₆H₂₈N₂O₈
• 分子量: 496.517
• InChiKey: BKRWTXFJEFCZMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N'-(1,3-phenylene)bis(3,4,5-trimethoxybenzamide) 在 劳森试剂 作用下， 以 四氢呋喃 为溶剂， 以34.7%的产率得到N,N'-(1,3-phenylene)bis(3,4,5-trimethoxybenzothioamide)
  参考文献：
  名称：

  A journey from benzanilides to dithiobenzanilides: Synthesis of selective spasmolytic compounds

  摘要：

  A series of dithiobenzanilide derivatives was synthesized and each compound was evaluated for its ability to reduce KCl-induced contractions of smooth muscle preparations of the guinea pig. Starting from a recent publication describing benzanilide derivatives as antispasmodic agents, structure-activity guided synthesis was performed to obtain compounds with improved spasmolytic activity. First, compounds with two amide bonds were designed and second, both amide oxygens were replaced by two sp(2) sulfur atoms resulting in dithiobenzanilide derivatives. The most potent antispasmodic dithiobenzanilide 19 showed improved activity with an IC50 value of 0.4 mu M. Moreover, the study also demonstrated that these active compounds were able to antagonize the effect of spasmogens like acetylcholine and phenylephrine and that the activity is not mediated by activation of ATP-dependent potassium channels (K-ATP-channels) or inhibition of endothelial nitric oxide synthase (eNOS). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.043
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酰氯 、 间苯二胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以72.81 %的产率得到N,N'-(1,3-phenylene)bis(3,4,5-trimethoxybenzamide)
  参考文献：
  名称：

  新型苯甲酰胺作为多靶点化合物：合成、AChE 和 BACE1 抑制活性及分子对接研究

  摘要：

  设计了十一种新的和以前未描述的苯甲酰胺的合成。这些化合物被明确预测为乙酰胆碱酯酶 (AChE) 和 β-分泌酶 (BACE1) 的潜在抑制剂。N,N'-(1,4-亚苯基)双(3-甲氧基苯甲酰胺)对AChE最有活性，AChE的抑制浓度IC50 = 0.056 µM，而多奈哌齐的IC50为0.046 µM。该化合物也是对抗 BACE1 酶最活跃的。与槲皮素相比，IC50 值为 9.01 µM，IC50 = 4.89 µM。定量结果表明该衍生物是最有前途的。进行分子建模以阐明该化合物的潜在作用机制。动态模拟表明，新配体对AChE的稳定作用有限，但都明显降低了酶的灵活性。因此，可以得出结论，可能的抑制机制增加了酶的硬度并降低了酶的灵活性，这显然阻碍了其正常功能。对氢键模式的分析表明，当最活跃的衍生物与酶相互作用时，存在不同的机制（与其他配体不同）。

  DOI：

  10.3390/ijms241914901

文献信息

• A journey from benzanilides to dithiobenzanilides: Synthesis of selective spasmolytic compounds
  作者：Gerda Brunhofer、Walter H. Granig、Christian R. Studenik、Thomas Erker

  DOI：10.1016/j.bmc.2010.11.043

  日期：2011.1

  A series of dithiobenzanilide derivatives was synthesized and each compound was evaluated for its ability to reduce KCl-induced contractions of smooth muscle preparations of the guinea pig. Starting from a recent publication describing benzanilide derivatives as antispasmodic agents, structure-activity guided synthesis was performed to obtain compounds with improved spasmolytic activity. First, compounds with two amide bonds were designed and second, both amide oxygens were replaced by two sp(2) sulfur atoms resulting in dithiobenzanilide derivatives. The most potent antispasmodic dithiobenzanilide 19 showed improved activity with an IC50 value of 0.4 mu M. Moreover, the study also demonstrated that these active compounds were able to antagonize the effect of spasmogens like acetylcholine and phenylephrine and that the activity is not mediated by activation of ATP-dependent potassium channels (K-ATP-channels) or inhibition of endothelial nitric oxide synthase (eNOS). (C) 2010 Elsevier Ltd. All rights reserved.