3-[(6-{[8-({6-[(2-methoxybenzyl)amino]hexyl}amino)octyl]amino}hexyl)amino]propanenitrile | 253877-99-5

• 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: 3-[(6-{[8-({6-[(2-methoxybenzyl)amino]hexyl}amino)octyl]amino}hexyl)amino]propanenitrile
• 英文别名: 3-[6-[8-[6-[(2-Methoxyphenyl)methylamino]hexylamino]octylamino]hexylamino]propanenitrile
• CAS: 253877-99-5
• 化学式: C₃₁H₅₇N₅O
• 分子量: 515.826
• InChiKey: UQRVPPIJWPMJOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  37
• 可旋转键数：
  28
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  81.1
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[(6-{[8-({6-[(2-methoxybenzyl)amino]hexyl}amino)octyl]amino}hexyl)amino]propanenitrile 在 镍 氢气 作用下， 以 乙醇 、 氯仿 为溶剂， 20.0 ℃ 、103.42 kPa 条件下， 反应 6.0h， 生成 [8-({6-[(3-aminopropyl)-tert-butoxycarbonylamino]hexyl}-tert-butoxycarbonylamino)octyl]-{6-[tert-butoxycarbonyl-(2-methoxybenzyl)amino]hexyl}carbamic acid tert-butyl ester
  参考文献：
  名称：

  甲基辛巴胺相关多胺作为肌肉烟碱样受体非竞争性拮抗剂的构效关系。2.分隔胺官能团的聚亚甲基链长和末端氮原子上的取代基的作用。

  摘要：

  聚亚甲基四胺甲辛胺（1）是一种典型的抗毒蕈碱配体，对肌肉nAChR具有显着的亲和力。因此，根据通用模板方法，对1进行结构修饰以提高对肌肉型nAChR的亲和力和选择性。合成的多胺衍生物分别在蛙直肌和鱼雷nAChRs和豚鼠左心房（M（2））和回肠纵肌（M（3））mAChRs上进行测试。所有化合物，如原型1，都是烟碱样受体的非竞争性拮抗剂，同时是M（2）和M（3）mAChRs的竞争性拮抗剂。多胺4-7的生物学特性表明，增加胺官能团的数量和分隔这些氮原子的链长导致nAChRs的效力显着提高。此外，通过合成化合物9和10，进一步研究了胺官能团的数量和类型在与nAChRs相互作用中的作用，显示了四胺8和11，在氮原子之间带有相当刚性的间隔基，而不是非常柔软的聚亚甲基链，在nAChRs处的分布类似于1，而在mAChRs处观察到效力显着降低。带有2-甲氧基苯乙基的四胺12的效力比1低，而带有二苯乙基部分的

  DOI：

  10.1021/jm011067f
• 作为产物：
  描述：

  N,N'-bis(6-aminohexyl)-1,8-octanediamine 在 sodium tetrahydroborate 、 3 A molecular sieve 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 8.5h， 生成 3-[(6-{[8-({6-[(2-methoxybenzyl)amino]hexyl}amino)octyl]amino}hexyl)amino]propanenitrile
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Symmetrically and Unsymmetrically Substituted Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists

  摘要：

  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.

  DOI：

  10.1021/jm991110n