8-(4-nitrobenzylamino)-8,11-oxapentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 8-(4-nitrobenzylamino)-8,11-oxapentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane
• 英文别名: N-[(4-nitrophenyl)methyl]-5-oxahexacyclo[5.4.1.02,6.03,10.04,8.09,12]dodecan-4-amine
• 化学式: C₁₈H₁₈N₂O₃
• 分子量: 310.353
• InChiKey: WBMNXQSYOIMHCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(4-nitrobenzylamino)-8,11-oxapentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane 在 盐酸 、 tin 作用下， 以 乙醇 、 水 为溶剂， 反应 1.17h， 以44.11%的产率得到N-[(4-aminophenyl)methyl]-5-oxahexacyclo[5.4.1.0^2,6.0^3,10.0^4,8.0^9,12]dodecan-4-amine
  参考文献：
  名称：

  Physicochemical prediction of a brain–blood distribution profile in polycyclic amines

  摘要：

  Recent investigation into the pharmacological character of the pentacyclo[5.4.0.0(2,6).0(3.10).0(5.9)]undecyl and related polycyclic amines has revealed interesting facts regarding their possible use as neuroprotective agents. At this stage however, a clear shortcoming in the quest for further development of this novel class of compounds is the lack of concrete data on their ability to cross the blood-brain barrier (131313). Working towards the aim of predicting BBB permeability, a series of related N-substituted 8-amino-8,1 1-oxapentacyclo[5.4.0.0(2.6).0(3,10).0(5,9)]undecanes were synthesised. Compounds were characterised by both experimental and calculative methods, followed by biological assessment and statistical manipulation of the results obtained. In doing so, a simple biological model was established for the comparative evaluation of brain-blood distribution properties within the class. A highly sensitive ESI-MS.MS analytical procedure was developed for the detection of these compounds in biological tissues, indicating significant drug concentrations in the brain after intraperitoneal administration to C57B1/6 mice. Stepwise multiple linear regression analysis of all data yielded two meaningful models (R-2 = 0.9996 and R-2 = 0.7749) depicting lipophilicity (log P-oct), solvent accessible molecular volume (SV), molar refractivity (MR) and system energy as the prime determinants of the brain-blood profile for these amines. The inherently high lipophilicity potential within the series is attributed to strong hydrophobic influences dominating hydrogen bonding effects. A possible conformational and energy dependent preference at the site of permeation is also suggested. The proposed estimations allo, v for the expedient and reliable prediction of brain partitioning behaviour for related polycyclic amines, facilitating the early rejection of unsuitable candidates and enabling research to focus on neuroprotective activity. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00365-1
• 作为产物：
  描述：

  NGP 1-01 在 palladium 10% on activated carbon 、 氢气 、 四丁基硫酸氢铵 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 50.0~70.0 ℃ 、206.0 kPa 条件下， 反应 34.0h， 生成 8-(4-nitrobenzylamino)-8,11-oxapentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane
  参考文献：
  名称：

  Synthesis and Biological Evaluations of NO-Donating Oxa- and Aza-Pentacycloundecane Derivatives as Potential Neuroprotective Candidates

  摘要：

  为了利用多环笼状化合物的神经保护特性，并探究硝基苯基团的NO供体能力，合成了一系列化合物，其中不同的硝基苯基团被附加在氧和氮桥接的笼状衍生物上。对这些化合物进行了生物学评估，包括细胞毒性、神经保护能力、抑制N-甲基-D-天冬氨酸（NMDA）介导的Ca²⁺流入、抑制电压介导的Ca²⁺流入以及S-亚硝基化能力。所有化合物都显示出低毒性。除了少数例外，大多数化合物表现出良好的神经保护作用，并对NMDA介导和电压门控钙流入显示出抑制活性，抑制范围从高（>70%）到低（20-39%）。在S-亚硝基化试验中，带有硝基作为NO供体基团的化合物显示出与阳性对照相比从低到良好的亚硝基化效力。从对这些化合物的生物学评估中，无法获得一个简单的相关性来解释所有生物学研究领域的结果。这可以归因于在不同试验中评估的独立过程，这再次强调了神经保护是多因素生化机制和相互作用的结果。然而，这些结果表明了五环十一烷胺神经保护剂在不同生物学研究领域的重要方面。

  DOI：

  10.3390/molecules23020308

文献信息

• Structure-Activity Relationships of Polycyclic Aromatic Amines with Calcium Channel Blocking Activity
  作者：Sarel F. Malan、J. Jurgens Van der Walt、Cornelius J. Van der Schyf

  DOI：10.1002/(sici)1521-4184(200001)333:1<10::aid-ardp10>3.0.co;2-5

  日期：2000.1

  11‐oxapentacyclo[5.4.0.02,6.03,10.05,9]undecane (1) inhibits the calcium current in L‐type calcium channels. A series of nitrobenzylamines (2, 3, 4), methoxybenzylamines (5, 6, 7), methylpyridines (8, 9, 10), and a phenylhydrazine derivative (11) of 8,11‐oxapentacyclo[5.4.0.02,6.03,10.05,9]undecane was synthesized. By substituting the 8,11‐oxapentacyclo‐[5.4.0.02,6.03,10.05,9]undecane skeleton with

  8-Benzylamino-8,11-oxapentacyclo [5.4.0.02.6.03.10.05.9] 十一烷 (1) 抑制 L 型钙通道中的钙电流。一系列硝基苄胺 (2, 3, 4)，甲氧基苄胺 (5, 6, 7)，甲基吡啶 (8, 9, 10) 和 8,11-氧杂五环的苯肼衍生物 (11) [5.4.0.02,6.03, 10.05,9]十一烷合成。通过用 3-羟基六环-[6.5.0.0.3,7.04,12.05,10.09,13] 十三烷取代 8,11-氧杂五环-[5.4.0.02.6.03.10.05.9] 十一烷骨架 (12), 8,13 -Dioxapenta-cyclo [6.5.0.02,6.05,10.03,11] tridecane-9-one (13) 和五环-[5.4.0.02,6.03,10.05,9]十一烷 (14)，多环骨架的作用可以也进行调查。在五