2-[({4-[({4-[({6-[(E)-2-(4-methoxyphenyl)ethenyl]-3-pyridinyl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]ethyl acetate | 1108614-49-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-[({4-[({4-[({6-[(E)-2-(4-methoxyphenyl)ethenyl]-3-pyridinyl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]ethyl acetate
• 英文别名: 2-[[4-[[4-[[6-[(E)-2-(4-methoxyphenyl)ethenyl]pyridine-3-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]ethyl acetate
• CAS: 1108614-49-8
• 化学式: C₃₁H₃₂N₆O₆
• 分子量: 584.632
• InChiKey: SXEXLYWRJVBVEP-WEVVVXLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[({4-[({4-[({6-[(E)-2-(4-methoxyphenyl)ethenyl]-3-pyridinyl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]ethyl acetate 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以23%的产率得到N-[5-[[5-(2-hydroxyethylcarbamoyl)-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-6-[(E)-2-(4-methoxyphenyl)ethenyl]pyridine-3-carboxamide
  参考文献：
  名称：

  A divergent synthesis of minor groove binders with tail group variation

  摘要：

  描述了一种新的聚酰胺小沟结合剂的合成方法，该方法通过挥发性的二级胺亲核试剂对2-硫代-1,3,2-二氮杂膦啉氧取代基进行亲核取代，从而引入了多样性。这种方法在经济上研究这一重要化合物类的结构-活性关系方面具有潜在价值，通过文库合成进行探讨。作为这种方法的一个例子，合成了两种新的小沟结合剂，分别具有吡咯烷基或哌啶基尾部，它们与带有吗啉基尾部的高活性抗菌小沟结合剂密切相关。针对金黄色葡萄球菌和分枝杆菌群体的抗菌活性表明，这类化合物的pKa并不是决定抗菌活性的主导因素。

  DOI：

  10.1039/b814452d
• 作为产物：
  描述：

  6-[(E)-2-(4-甲氧基苯基)乙烯基]烟酸 在 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-[({4-[({4-[({6-[(E)-2-(4-methoxyphenyl)ethenyl]-3-pyridinyl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}-carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]ethyl acetate
  参考文献：
  名称：

  Design, synthesis and antibacterial activity of minor groove binders: The role of non-cationic tail groups

  摘要：

  The design and synthesis of a new class of minor groove binder (MGBs) in which, the cationic tail group has been replaced by a neutral, polar variant including cyanoguanidine, nitroalkene, and trifluoroacetamide groups. Antibacterial activity (against Gram positive bacteria) was found for both the nitroalkene and trifluoroacetamide groups. For the case of the nitroalkene tail group, strong binding of a minor groove binder containing this tail group was demonstrated by both DNA footprinting and melting temperature measurements, showing a correlation between DNA binding and antibacterial activity. The compounds have also been evaluated for binding to the hERG ion channel to determine whether non-cationic but polar substituents might have an advantage compared with conventional cationic tail groups in avoiding hERG binding. In this series of compounds, it was found that whilst non-cationic compounds generally had lower affinity to the hERG ion channel, all of the compounds studied bound weakly to the hERG ion channel, probably associated with the hydrophobic head groups. (c) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.013

文献信息

• A divergent synthesis of minor groove binders with tail group variation
  作者：David Breen、Alan R. Kennedy、Colin J. Suckling

  DOI：10.1039/b814452d

  日期：——

  A new synthesis of polyamide minor groove binders in which diversity is introduced by the nucleophilic substitution of a 2-sulfido-1,3,2-diazaphospholidinyloxy substituent by volatile secondary amine nucleophiles is described. Such a method has potential value for economically investigating structure–activity relationships in this important class of compounds through library synthesis. As an example using this method are prepared two new minor groove binders with pyrrolidinyl or piperidinyl tail groups that are close relatives of highly active antibacterial minor groove binders with morpholinyl tail groups. The antibacterial activity found against Staphylococcus aureus and Mycobacterium spp. indicates that the pKa of this set of compounds is not the dominant factor in determining the antibacterial activity.

  描述了一种新的聚酰胺小沟结合剂的合成方法，该方法通过挥发性的二级胺亲核试剂对2-硫代-1,3,2-二氮杂膦啉氧取代基进行亲核取代，从而引入了多样性。这种方法在经济上研究这一重要化合物类的结构-活性关系方面具有潜在价值，通过文库合成进行探讨。作为这种方法的一个例子，合成了两种新的小沟结合剂，分别具有吡咯烷基或哌啶基尾部，它们与带有吗啉基尾部的高活性抗菌小沟结合剂密切相关。针对金黄色葡萄球菌和分枝杆菌群体的抗菌活性表明，这类化合物的pKa并不是决定抗菌活性的主导因素。
• Design, synthesis and antibacterial activity of minor groove binders: The role of non-cationic tail groups
  作者：Abedawn I. Khalaf、Claire Bourdin、David Breen、Gavin Donoghue、Fraser J. Scott、Colin J. Suckling、Donna MacMillan、Carol Clements、Keith Fox、Doreen A.T. Sekibo

  DOI：10.1016/j.ejmech.2012.08.013

  日期：2012.10

  The design and synthesis of a new class of minor groove binder (MGBs) in which, the cationic tail group has been replaced by a neutral, polar variant including cyanoguanidine, nitroalkene, and trifluoroacetamide groups. Antibacterial activity (against Gram positive bacteria) was found for both the nitroalkene and trifluoroacetamide groups. For the case of the nitroalkene tail group, strong binding of a minor groove binder containing this tail group was demonstrated by both DNA footprinting and melting temperature measurements, showing a correlation between DNA binding and antibacterial activity. The compounds have also been evaluated for binding to the hERG ion channel to determine whether non-cationic but polar substituents might have an advantage compared with conventional cationic tail groups in avoiding hERG binding. In this series of compounds, it was found that whilst non-cationic compounds generally had lower affinity to the hERG ion channel, all of the compounds studied bound weakly to the hERG ion channel, probably associated with the hydrophobic head groups. (c) 2012 Elsevier Masson SAS. All rights reserved.