N,N'-bis(6-aminohexyl)-N,N'-dimethyl-1,8-octanediamine | 115962-75-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N,N'-bis(6-aminohexyl)-N,N'-dimethyl-1,8-octanediamine
• 英文别名: N,N'-bis(6-aminohexyl)-N,N'-dimethyloctane-1,8-diamine
• CAS: 115962-75-9
• 化学式: C₂₂H₅₀N₄
• 分子量: 370.666
• InChiKey: DMWBCGUKIPQQNO-UHFFFAOYSA-N

物化性质

• 沸点：
  480.4±40.0 °C(predicted)
• 密度：
  0.896±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  58.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N'-bis(6-aminohexyl)-N,N'-dimethyl-1,8-octanediamine 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 氢气 、 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~50.0 ℃ 、506.62 kPa 条件下， 反应 93.0h， 生成 11-[2-[6-[8-[6-[benzyl-[2-oxo-2-(6-oxo-5H-pyrido[2,3-b][1,4]benzodiazepin-11-yl)ethyl]amino]hexyl-methylamino]octyl-methylamino]hexylamino]acetyl]-5H-pyrido[2,3-b][1,4]benzodiazepin-6-one
  参考文献：
  名称：

  带有11-乙酰基5,11-二氢-6H-吡啶并[2,3-b] [1,4]-苯并二氮杂-6-一个部分作为抗毒蕈碱的一些与甲基辛巴胺有关的四胺的合成和生物活性：第二代高度选择性的M2毒蕈碱受体拮抗剂。

  摘要：

  DOI：

  10.1021/jm00075a032

文献信息

• Universal Template Approach to Drug Design:  Polyamines as Selective Muscarinic Receptor Antagonists
  作者：Maria L. Bolognesi、Anna Minarini、Roberta Budriesi、Silvia Cacciaguerra、Alberto Chiarini、Santi Spampinato、Vincenzo Tumiatti、Carlo Melchiorre

  DOI：10.1021/jm981038d

  日期：1998.10.1

  The concept that polyamines may represent a universal template in the receptor recognition process is embodied in the design of new selective muscarinic ligands. Tetraamines 4-7 and 16-20 and diamine diamides 8-15 were synthesized, and their pharmacological profiles at muscarinic receptor subtypes were assessed by functional experiments in isolated guinea pig left atrium (M2) and ileum (M3) and by

  在新的选择性毒蕈碱配体的设计中体现了多胺可能在受体识别过程中代表通用模板的概念。合成了四胺4-7和16-20以及二胺二酰胺8-15，并通过在分离的豚鼠左心房（M2）和回肠（M3）中进行的功能实验以及在大鼠中的结合试验评估了毒蕈碱受体亚型的药理学特征皮层（M1），心脏（M2），上颌下腺（M3）和NG 108-15细胞（M4）。已经证实，四胺模板的末端氮上的适当取代基可以调节对毒蕈碱受体的亲和力和选择性。与其他亚型相比，新型四胺C-三苯胺（17）能够明显地区分M1和M2受体，此外，它的亲脂性是铅化合物三苯丙胺的100倍。其中四胺主链被转化为二胺二酰胺的化合物14（三甲酰胺），对毒蕈碱型亚型保持高亲和力，在质量上显示出与三甲胺类似的结合亲和力分布（M2> M1> M4> M3）。这两种配体由于相对于曲普他明和甲基辛特拉明改善了亲脂性，因此可以用作研究中枢神经系统胆碱能功能的工具。此外，尽管最高亲
• Design, Synthesis, and Biological Activity of Methoctramine-Related Tetraamines Bearing a 11-Acetyl-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one Moiety: Structural Requirements for Optimum Occupancy of Muscarinic Receptor Subtypes As Revealed by Symmetrical and Unsymmetrical Polyamines
  作者：Anna Minarini、Maria L. Bolognesi、Roberta Budriesi、Marco Canossa、Alberto Chiarini、Santi Spampinato、Carlo Melchiorre

  DOI：10.1021/jm00046a021

  日期：1994.9

  Tetraamines 5-13 and diamines 14-17 as well as monoamine 18 were synthesized, and their biological profiles at muscarinic receptor subtypes were assessed by functional experiments in isolated guinea pig left atrium (M2) and ileum (M3) and by binding assays in rat cortex (M1), heart (M2), and submaxillary gland (M3) homogenates and NG 108-15 cells (M4). An appropriate number and type of substituents

  合成了四胺5-13和二胺14-17以及单胺18，并通过在分离的豚鼠左心房（M2）和回肠（M3）中进行的功能实验以及在大鼠中的结合试验评估了毒蕈碱受体亚型的生物学特性皮质（M1），心脏（M2）和上颌下腺（M3）匀浆和NG 108-15细胞（M4）。在四胺主链的末端氮上适当数量和类型的取代基提供了化合物，例如三苯丙胺（8）和地皮胺（6），它们具有不同的亲和力和选择性。雷帕曲明是一种不对称的四胺，是迄今为止可获得的最有效，最具选择性的M2毒蕈碱受体拮抗剂（pA2 = 9.75 +/- 0.02； pKi = 9.54 +/- 0.08）。然而，它无法区分M1和M4毒蕈碱受体亚型（选择性比：M2 / M3，1600-2200; M2 / M1，81; M2 / M4，41; M1 / M3，28; M4 / M3，55; M4 / M1 ，2）。Dipitramine是在同一末端氮上带有两个取代基
• Structure−Activity Relationships of Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists. 3. Effect of Inserting the Tetraamine Backbone into a Macrocyclic Structure
  作者：Maria L. Bolognesi、M. Gabriele Bixel、Gabriella Marucci、Manuela Bartolini、Michael Krauss、Piero Angeli、Alessandra Antonello、Michela Rosini、Vincenzo Tumiatti、Ferdinand Hucho、Carlo Melchiorre

  DOI：10.1021/jm020835f

  日期：2002.7.1

  prototypes, were potent noncompetitive antagonists at both frog and Torpedo nAChRs, suggesting that polyamines do not need to be linear or in extended conformation to optimally interact with the nicotinic channel; rather, they may bind in a U-shaped conformation. Relative to muscarinic activity, macrocyclic compounds 10, 13, 14, and 20, in contrast with the profile displayed by 2, were almost devoid of

  本文扩展了对聚亚甲基四胺结构-活性关系的另一个方面的研究，即，将四胺主链插入大环结构的作用。为此，通过将原型甲基辛特拉明2的两个末端氮原子连接至芳基部分来设计化合物8-12。或者，首先将2修饰以获得化合物6和7，然后通过将两个末端伯胺官能团连接到聚苯基间隔基上将其环化，得到13-20。所有化合物均在肌肉型nAChRs上进行了测试，并且大多数化合物也在AChE上测试。此外，所选的化合物也在外围M（2）和M（3）mAChRs上进行了测试。所有这些环状衍生物都像原型一样，在青蛙和鱼雷nAChRs上都是有效的非竞争性拮抗剂，提示多胺不需要为线性或延伸构象即可与烟碱通道最佳相互作用；相反，它们可能以U形构象结合。相对于毒蕈碱活性，大环化合物10、13、14和20与2显示的特征相反，几乎没有亲和力。推导出芳基间隔基不利于多胺与mAChR的相互作用。最后，在这项研究中研究的所有二胺二酰胺在抑制AChE活
• Structure-activity relationships among methoctramine-related polymethylenetetramines. Chain length and substituent effects on M-2 muscarinic receptor blocking activity
  作者：Carlo Melchiorre、Wilma Quaglia、Maria T. Picchio、Dario Giardina、Livio Brasili、Piero Angeli

  DOI：10.1021/jm00121a017

  日期：1989.1

  Several polymethylene tetraamines related to methoctramine (1) were prepared and evaluated for their blocking activity on M-2 muscarinic receptors in guinea pig atria and ileum. It turned out that antimuscarinic potency depends on the following parameters: (a) nature of the substituent on both inner and outer nitrogens and (b) carbon chain length separating the inner nitrogens as well as the inner and outer nitrogens. Optimum activity at cardiac M-2 muscarinic receptors was associated with the chain lengths present in 1, that is, eight methylenes between the inner nitrogens and six methylenes between the inner and outer nitrogens. With regard to the substituents, replacement of the benzylic moiety of 1 by a 2-furyl or a 5-methyl-2-furyl nucleus resulted in enhanced potency toward cardiac M-2 muscarinic receptors. In fact, furtramine (18) and mefurtramine (19) proved to be more potent and more selective than 1. Moreover, N-methylation of the four nitrogens of 1 gave different effects: methylation of the outer nitrogens, giving 22, caused a significant decrease in activity whereas methylation of the inner nitrogens, yielding 23, resulted in an increase in activity in both atria and ileum.
• Minarini Anna, Bolognesi Maria L., Budriesi Roberta, Canossa Marco, Chiar+, J. Med. Chem, 37 (1994) N 20, S 3363-3372
  作者：Minarini Anna, Bolognesi Maria L., Budriesi Roberta, Canossa Marco, Chiar+

  DOI：——

  日期：——