NGP 1-01 | 33226-54-9

• 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: NGP 1-01
• 英文别名: N-benzyl-5-oxahexacyclo[5.4.1.02,6.03,10.04,8.09,12]dodecan-4-amine
• CAS: 33226-54-9
• 化学式: C₁₈H₁₉NO
• 分子量: 265.355
• InChiKey: AVESFRBKERIICX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 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：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  NGP 1-01 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 5.0~20.0 ℃ 、101.33 kPa 条件下， 反应 14.0h， 生成
  参考文献：
  名称：

  S-Nitrosylation and Attenuation of Excessive Calcium Flux by Pentacycloundecane Derivatives

  摘要：

  一系列新型多环胺类化合物被合成，并测试其对钙通道和N-甲基-D-天冬氨酸受体的调节活性。这些合成化合物根据其氮氧化物供体部分分为两组：不饱和硝基化合物（1、2和3）和硝酸酯或硝酸盐（4、5和6）。硝酸盐通过羟基功能团与亚硫酰氯硝酸盐反应获得。所有合成的化合物均显示出显著的（p < 0.01）S-亚硝基化能力。采用氯化钾介导的荧光钙通量测定法评估多环胺的钙通道活性。所有化合物均表现出比先导结构NGP1-01更好的钙通道拮抗作用，化合物1在10 μM和1 μM浓度下显示出与市面上可获得的尼莫地平相当的钙通道阻断效果。化合物3和4在10 μM浓度下抑制钙通量至这些水平。使用荧光钙通量测定法在100 µM浓度下评估NMDA/甘氨酸介导的N-甲基-D-天冬氨酸受体（NMDAR）钙内流抑制作用。所有化合物均显示NMDAR拮抗作用，其中化合物1（25.4%）、2（20.24%）、3（33.14%）和6（24.55%）显示出最显著的NMDAR抑制活性（p < 0.01）。没有观察到化合物S-亚硝基化能力与其钙通道活性或NMDAR通道拮抗之间的明确相关性，这表明其他因素可能在五环十一烷胺通道调节机制中起更决定性的作用。这可能包括已描述的对五环十一烷胺通道活性有贡献的几何和立体体积考虑。所有合成的化合物均显示出有前景的钙通道和NMDAR通道抑制活性，并有望作为针对神经退行性疾病的潜在先导化合物用于药物开发。

  DOI：

  10.2174/1573406411208030361
• 作为产物：
  描述：

  8-benzyliminopentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane-11-one 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 24.0h， 生成 NGP 1-01
  参考文献：
  名称：

  多环芳胺与钙通道阻滞活性的构效关系

  摘要：

  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

  DOI：

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

文献信息

• Synthesis and Biological Evaluations of NO-Donating Oxa- and Aza-Pentacycloundecane Derivatives as Potential Neuroprotective Candidates
  作者：Rajan Sharma、Jacques Joubert、Sarel Malan

  DOI：10.3390/molecules23020308

  日期：——

  In order to utilize the neuroprotective properties of polycyclic cage compounds, and explore the NO-donating ability of nitrophenyl groups, an array of compounds was synthesized where the different nitrophenyl groups were appended on oxa and aza-bridged cage derivatives. Biological evaluations of the compounds were done for cytotoxicity, neuroprotective abilities, the inhibition of N-methyl-d-aspartate (NMDA)-mediated Ca2+ influx, the inhibition of voltage-mediated Ca2+ influx, and S-nitrosylation abilities. All of the compounds showed low toxicity. With a few exceptions, most of the compounds displayed good neuroprotection and showed inhibitory activity for NMDA-mediated and voltage-gated calcium influx, ranging from high (>70%) to low (20–39%) inhibition. In the S-nitrosylation assay, the compounds with the nitro moiety as the NO-donating group exhibited low to good nitrosylation potency compared to the positive controls. From the biological evaluation of the tested compounds, it was not possible to obtain a simple correlation that could explain the results across all of the biological study domains. This can be ascribed to the independent processes evaluated in the different assays, which reiterate that neuroprotection is a result of multifactorial biochemical mechanisms and interactions. However, these results signify the important aspects of the pentacylcoundecylamine neuroprotectants across different biological study realms.

  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。
• 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
• Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents
  作者：Frank T. Zindo、Sarel F. Malan、Sylvester I. Omoruyi、Adaze B. Enogieru、Okobi E. Ekpo、Jacques Joubert

  DOI：10.1016/j.ejmech.2018.11.051

  日期：2019.2

  The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The mirr cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 mu M. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 M, when assayed on SHSYSY human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 mu M; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 mu M. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 mu M). Generally, the compounds were about 3-52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Physicochemical prediction of a brain–blood distribution profile in polycyclic amines
  作者：Jaco Zah、Gisella Terre'Blanche、Elardus Erasmus、Sarel F. Malan

  DOI：10.1016/s0968-0896(03)00365-1

  日期：2003.8

  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.
• Du Preez; Loetter; Guillory, Pharmazie, 1996, vol. 51, # 4, p. 223 - 227
  作者：Du Preez、Loetter、Guillory

  DOI：——

  日期：——