N,N'-dimethylmethoctramine | 115962-57-7

• 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'-dimethylmethoctramine
• 英文别名: N,N'-bis[6-[(2-methoxybenzyl)amino]hexyl]-N,N'-dimethyl-1,8-octanediamine；N,N'-bis[6-[(2-methoxyphenyl)methylamino]hexyl]-N,N'-dimethyloctane-1,8-diamine
• CAS: 115962-57-7
• 化学式: C₃₈H₆₆N₄O₂
• 分子量: 610.968
• InChiKey: HXDUHTQOUIWFQN-UHFFFAOYSA-N

物化性质

• 沸点：
  683.7±55.0 °C(predicted)
• 密度：
  0.975±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  44
• 可旋转键数：
  29
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  49
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,11-二氢-11-氯乙酰基-6H-吡啶并[2.3-b][1,4]苯并二氮卓-6-酮 、 N,N'-dimethylmethoctramine 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以44%的产率得到1,24-bis<<(5,11-dihydro-6-oxo-6H-pyrido<2,3-b><1,4>benzodiazepin-11-yl)carbonyl>methyl>-1,24-bis(2-methoxybenzyl)-8,17-dimethyl-1,8,17,24-tetraazatetracosane
  参考文献：
  名称：

  具有11-乙酰基5,11-二氢-6H-吡啶基[2,3-b] [1,4]苯并二氮杂-6-一个部分的甲基辛巴胺相关四胺的设计，合成和生物学活性：最佳结构要求对称和不对称多胺揭示了毒蕈碱受体亚型的存在。

  摘要：

  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

  DOI：

  10.1021/jm00046a021
• 作为产物：
  描述：

  N,N'-bis(6-aminohexyl)-N,N'-dimethyl-1,8-octanediamine 在 sodium tetrahydroborate 作用下， 以 乙醇 、 苯 为溶剂， 反应 11.0h， 生成 N,N'-dimethylmethoctramine
  参考文献：
  名称：

  Structure-activity relationships among methoctramine-related polymethylenetetramines. Chain length and substituent effects on M-2 muscarinic receptor blocking activity

  摘要：

  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.

  DOI：

  10.1021/jm00121a017

文献信息

• 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 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.