6-(2-methoxybenzylamino)hexanoic acid [4-(2-{4-[6-(2-methoxybenzylamino)hexanoylamino]phenyl}ethyl)phenyl]amide | 797805-26-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 6-(2-methoxybenzylamino)hexanoic acid [4-(2-{4-[6-(2-methoxybenzylamino)hexanoylamino]phenyl}ethyl)phenyl]amide
• 英文别名: Mao-IN-3；6-[(2-methoxyphenyl)methylamino]-N-[4-[2-[4-[6-[(2-methoxyphenyl)methylamino]hexanoylamino]phenyl]ethyl]phenyl]hexanamide
• CAS: 797805-26-6
• 化学式: C₄₂H₅₄N₄O₄
• 分子量: 678.915
• InChiKey: LCXUWGQUUVIMKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  50
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(2-methoxybenzylamino)hexanoic acid [4-(2-{4-[6-(2-methoxybenzylamino)hexanoylamino]phenyl}ethyl)phenyl]amide 在 borane N-ethyl-N-isopropylaniline complex 作用下， 以 四氢呋喃 、 二乙二醇二甲醚 为溶剂， 反应 5.0h， 以40%的产率得到N-[(2-methoxyphenyl)methyl]-N'-[4-[2-[4-[6-[(2-methoxyphenyl)methylamino]hexylamino]phenyl]ethyl]phenyl]hexane-1,6-diamine
  参考文献：
  名称：

  Structure–activity relationships of methoctramine-related polyamines as muscarinic antagonist: Effect of replacing the inner polymethylene chain with cyclic moieties

  摘要：

  The aim of the present paper was to investigate the role of the octamethylene spacer of methoctramine (1) on the biological profile. Thus, this spacer was incorporated into a dianiline or dipiperidine moiety to determine whether flexibility and the basicity of the inner nitrogen atoms are important determinants of potency with respect to muscarinic receptors. The most potent compound was 4, which displayed, in the functional assays, a comparable potency at muscarinic M-2 receptors with respect to 1, and, in the binding assays, a loss of potency and selectivity toward muscarinic M-1 and M-3 receptor subtypes. Both compounds were endowed with antinociceptive activity. Furthermore, in microdialysis tests in rat parietal cortex, they enhanced acetylcholine release, most likely by antagonizing presynaptic muscarinic receptor subtypes. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.022
• 作为产物：
  描述：

  N-苄氧羰基--6-氨基己酸 在 sodium tetrahydroborate 、 氢溴酸 、 氯甲酸乙酯 、 溶剂黄146 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 甲苯 为溶剂， 反应 88.5h， 生成 6-(2-methoxybenzylamino)hexanoic acid [4-(2-{4-[6-(2-methoxybenzylamino)hexanoylamino]phenyl}ethyl)phenyl]amide
  参考文献：
  名称：

  基于多胺骨架的乙酰胆碱酯酶非共价抑制剂的构效关系。3.用环状部分取代内部多亚甲基链的效果。

  摘要：

  在本文中，我们通过研究其八亚甲基间隔基通过取代二哌啶和二苯胺部分来分离两个酰胺功能的作用，扩展了AChE抑制剂己二胺（2）的乙基类似物3的SAR研究。化合物4和8是这两个系列化合物中最有趣的。化合物4是最有效的AChE抑制剂，pIC50值为8.48 +/- 0.02，同时还显示出显着的毒蕈碱M2拮抗活性（pKb值为6.18 +/- 0.20）。合适的检测方法的可用性使我们能够验证2、3、4和8是否抑制AChE诱导的Abeta聚集。尽管所有四种衍生物都导致混合的AChE抑制类型（活性位点和PAS），但只有4和8带有内部受约束的间隔子，与多奈哌齐相比，它们能够更大程度地抑制AChE诱导的Abeta聚集。显然，基于线性多胺骨架的AChE抑制剂结合两个AChE位点的能力可能不足以抑制AChE诱导的Abeta聚集。双哌啶衍生物4成为一种有价值的药理学工具，并有望成为新的配体用于研究和有望治疗阿尔茨海默氏病的先导化合物。

  DOI：

  10.1021/jm0494366

文献信息

• Structure−Activity Relationships of Acetylcholinesterase Noncovalent Inhibitors Based on a Polyamine Backbone. 3. Effect of Replacing the Inner Polymethylene Chain with Cyclic Moieties
  作者：Vincenzo Tumiatti、Vincenza Andrisano、Rita Banzi、Manuela Bartolini、Anna Minarini、Michela Rosini、Carlo Melchiorre

  DOI：10.1021/jm0494366

  日期：2004.12.1

  whether 2, 3, 4, and 8 inhibit AChE-induced Abeta aggregation. Although all four derivatives caused a mixed type of AChE inhibition (active site and PAS), only 4 and 8, which bear an inner constrained spacer, were able to inhibit AChE-induced Abeta aggregation to a greater extent than donepezil. Clearly, the ability of an AChE inhibitor, based on a linear polyamine backbone, to bind both AChE sites

  在本文中，我们通过研究其八亚甲基间隔基通过取代二哌啶和二苯胺部分来分离两个酰胺功能的作用，扩展了AChE抑制剂己二胺（2）的乙基类似物3的SAR研究。化合物4和8是这两个系列化合物中最有趣的。化合物4是最有效的AChE抑制剂，pIC50值为8.48 +/- 0.02，同时还显示出显着的毒蕈碱M2拮抗活性（pKb值为6.18 +/- 0.20）。合适的检测方法的可用性使我们能够验证2、3、4和8是否抑制AChE诱导的Abeta聚集。尽管所有四种衍生物都导致混合的AChE抑制类型（活性位点和PAS），但只有4和8带有内部受约束的间隔子，与多奈哌齐相比，它们能够更大程度地抑制AChE诱导的Abeta聚集。显然，基于线性多胺骨架的AChE抑制剂结合两个AChE位点的能力可能不足以抑制AChE诱导的Abeta聚集。双哌啶衍生物4成为一种有价值的药理学工具，并有望成为新的配体用于研究和有望治疗阿尔茨海默氏病的先导化合物。
• Structure–activity relationships of methoctramine-related polyamines as muscarinic antagonist: Effect of replacing the inner polymethylene chain with cyclic moieties
  作者：Vincenzo Tumiatti、Anna Minarini、Andrea Milelli、Michela Rosini、Michela Buccioni、Gabriella Marucci、Carla Ghelardini、Cristina Bellucci、Carlo Melchiorre

  DOI：10.1016/j.bmc.2007.01.022

  日期：2007.3

  The aim of the present paper was to investigate the role of the octamethylene spacer of methoctramine (1) on the biological profile. Thus, this spacer was incorporated into a dianiline or dipiperidine moiety to determine whether flexibility and the basicity of the inner nitrogen atoms are important determinants of potency with respect to muscarinic receptors. The most potent compound was 4, which displayed, in the functional assays, a comparable potency at muscarinic M-2 receptors with respect to 1, and, in the binding assays, a loss of potency and selectivity toward muscarinic M-1 and M-3 receptor subtypes. Both compounds were endowed with antinociceptive activity. Furthermore, in microdialysis tests in rat parietal cortex, they enhanced acetylcholine release, most likely by antagonizing presynaptic muscarinic receptor subtypes. (c) 2007 Elsevier Ltd. All rights reserved.