N1,N4-di{3-[(2-methoxybenzyl)amino]propyl}-1,4-butanediamine

• 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: N1,N4-di{3-[(2-methoxybenzyl)amino]propyl}-1,4-butanediamine
• 英文别名: N,N'-bis[3-[(2-methoxyphenyl)methylamino]propyl]butane-1,4-diamine
• 化学式: C₂₆H₄₂N₄O₂
• 分子量: 442.645
• InChiKey: SPIYLWWOSSDUFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  66.6
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 sodium cyanoborohydride 作用下， 反应 24.0h， 生成 N1,N4-di{3-[(2-methoxybenzyl)amino]propyl}-1,4-butanediamine
  参考文献：
  名称：

  活细胞模板动态组合化学。

  摘要：

  动态共价化学在一个步骤中结合了用于生物分子识别的配体的筛选和合成。为此，将化学实体用作相互转换物种的动态组合库中的模板，以便由于与目标的有效相互作用而扩增了较强的结合剂。在这里，我们将整个A549活细胞用作亚胺动态混合物中的模板，其扩增反应了与相应细胞外基质的高效选择性相互作用。扩增的多胺在细胞内NMR实验中显示出与A549细胞外基质的强相互作用，而NMR，SPR和模型系统中分子动力学模拟的结合提供了有关分子识别事件的见解。值得注意的是

  DOI：

  10.1002/anie.202004745

文献信息

• Design, Synthesis, and Biological Evaluation of Symmetrically and Unsymmetrically Substituted Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists
  作者：Michela Rosini、Roberta Budriesi、M. Gabriele Bixel、Maria L. Bolognesi、Alberto Chiarini、Ferdinand Hucho、Povl Krogsgaard-Larsen、Ian R. Mellor、Anna Minarini、Vincenzo Tumiatti、Peter N. R. Usherwood、Carlo Melchiorre

  DOI：10.1021/jm991110n

  日期：1999.12.1

  The universal template approach to drug design foresees that a polyamine can be modified in such a way to recognize any neurotransmitter receptor. Thus, hybrids of polymethylene tetraamines and philanthotoxins, exemplified by methoctramine (1) and PhTX-343 (2), respectively, were synthesized to produce novel inhibitors of muscular nicotinic acetylcholine receptors. Polyamines 3-25 were synthesized and their biological profiles were evaluated at frog rectus abdominis muscle nicotinic receptors and guinea pig left atria (M-2) and ileum longitudinal muscle (M-3) muscarinic acetylcholine receptors. All of the compounds, like prototypes 1 and 2, were noncompetitive antagonists of nicotinic receptors while being, like 1, competitive antagonists at,muscarinic M-2 and M-3 receptor subtypes. interestingly, polyamines bearing a low number of methylenes between the nitrogen atoms, as in 3, 6, and 7, displayed a biological profile similar to that of 2: a noncompetitive antagonism at nicotinic receptors in the 7-25 mu M range while not showing any antagonism for muscarinic receptors up to 10 mu M. increasing the number of methylenes separating these nitrogen atoms in methoctramine related tetraamines resulted in a significant improvement; in potency at nicotinic receptors. The most potent tetraamine was 19, bearing a 12 methylene spacer between the nitrogen atoms, which was 12-fold and 250-fold more potent than prototypes 1 and 2, respectively. Tetraamines 9-11, bearing a rather rigid spacer between the nitrogen atoms instead of the very flexible polymethylene chain, displayed a profile similar to that of 1 at nicotinic receptors, whereas a significant decrease in potency was observed at muscarinic M-2 receptors. This finding may have relevance in understanding the mode of interaction with these receptors. Similarly, the constrained analogue 12 of methoctramine showed a decrease in potency at nicotinic and muscarinic M-2 receptors, revealing that the tricyclic system, which incorporates the 2-methoxybenzylamine moiety of 1, does not represent a good pharmacophore for activity at these sites. A most intriguing finding was the observation that the photolabile tetraamine 22 was more potent than methoctramine at nicotinic receptors and, what is more important, it inhibited a closed stale of the receptor.
• Live‐Cell‐Templated Dynamic Combinatorial Chemistry
  作者：Daniel Carbajo、Yolanda Pérez、Jordi Bujons、Ignacio Alfonso

  DOI：10.1002/anie.202004745

  日期：2020.9.21

  Dynamic covalent chemistry combines in a single step the screening and synthesis of ligands for biomolecular recognition. In order to do that, a chemical entity is used as template within a dynamic combinatorial library of interconverting species, so that the stronger binders are amplified due to the efficient interaction with the target. Here we employed whole A549 living cells as template in a dynamic

  动态共价化学在一个步骤中结合了用于生物分子识别的配体的筛选和合成。为此，将化学实体用作相互转换物种的动态组合库中的模板，以便由于与目标的有效相互作用而扩增了较强的结合剂。在这里，我们将整个A549活细胞用作亚胺动态混合物中的模板，其扩增反应了与相应细胞外基质的高效选择性相互作用。扩增的多胺在细胞内NMR实验中显示出与A549细胞外基质的强相互作用，而NMR，SPR和模型系统中分子动力学模拟的结合提供了有关分子识别事件的见解。值得注意的是