1-(2-(2-methoxy-4-nitrophenoxy)ethyl)piperidine | 136616-35-8

• 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: 1-(2-(2-methoxy-4-nitrophenoxy)ethyl)piperidine
• 英文别名: 1-[2-(2-Methoxy-4-nitrophenoxy)ethyl]piperidine
• CAS: 136616-35-8
• 化学式: C₁₄H₂₀N₂O₄
• 分子量: 280.324
• InChiKey: VDGRRCKEPRCFMX-UHFFFAOYSA-N

物化性质

• 沸点：
  428.4±35.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  67.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-(2-methoxy-4-nitrophenoxy)ethyl)piperidine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 1-(3-methoxy-4-(2-(piperidin-1-yl)ethoxy)phenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
  参考文献：
  名称：

  基于合理设计发现有效的人谷氨酰胺基环化酶抑制剂作为抗阿尔茨海默氏病的药物

  摘要：

  谷氨酰胺基环化酶（QC）通过产生β淀粉样肽（pGlu-Aβ）的N末端焦谷氨酸与毒性淀粉样蛋白斑块的形成有关，因此可能参与了阿尔茨海默氏病（AD）的发病机理。我们基于优选底物Aβ3E-42的拟议结合模式设计了谷氨酰环化酶（QC）抑制剂库。一项体外结构-活性关系研究确定了几种出色的QC抑制剂，与已知的QC抑制剂相比，其效能提高了5至40倍。在AD的小鼠模型中测试时，化合物212显着降低了焦状Aβ和总Aβ的大脑浓度，并恢复了认知功能。这种强大的Aβ降低作用是通过将一个额外的结合区并入我们先前建立的药效团模型中而实现的，从而导致在QC结合位点与Glu327的羧酸酯基团发生强相互作用。我们的研究为设计新型QC抑制剂作为AD的潜在治疗方法提供了有用的见识。

  DOI：

  10.1021/acs.jmedchem.7b00098
• 作为产物：
  描述：

  4-硝基愈创木酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1-(2-(2-methoxy-4-nitrophenoxy)ethyl)piperidine
  参考文献：
  名称：

  基于合理设计发现有效的人谷氨酰胺基环化酶抑制剂作为抗阿尔茨海默氏病的药物

  摘要：

  谷氨酰胺基环化酶（QC）通过产生β淀粉样肽（pGlu-Aβ）的N末端焦谷氨酸与毒性淀粉样蛋白斑块的形成有关，因此可能参与了阿尔茨海默氏病（AD）的发病机理。我们基于优选底物Aβ3E-42的拟议结合模式设计了谷氨酰环化酶（QC）抑制剂库。一项体外结构-活性关系研究确定了几种出色的QC抑制剂，与已知的QC抑制剂相比，其效能提高了5至40倍。在AD的小鼠模型中测试时，化合物212显着降低了焦状Aβ和总Aβ的大脑浓度，并恢复了认知功能。这种强大的Aβ降低作用是通过将一个额外的结合区并入我们先前建立的药效团模型中而实现的，从而导致在QC结合位点与Glu327的羧酸酯基团发生强相互作用。我们的研究为设计新型QC抑制剂作为AD的潜在治疗方法提供了有用的见识。

  DOI：

  10.1021/acs.jmedchem.7b00098

文献信息

• Effect of Topologically Controlled Coulombic Interactions on the Dynamic Behavior of Photoexcited Nitrophenyl Alkyl Ethers in the Presence of Tertiary Amines with Limited Motion Freedom
  作者：Roberto Gonzalez-Blanco、José L. Bourdelande、Jordi Marquet

  DOI：10.1021/jo961821i

  日期：1997.10.1

  Time-resolved electronic absorption spectroscopy has been successfully applied to clarify the mechanism of the ''abnormal'' photochemical cleavage of 4-nitrophenyl piperidinoalkyl ethers induced by controlled Coulombic disturbance of the ''normal'' electronic distribution of the radical anion intermediate. Thus, photolysis of 1-piperidino-2-(2-methoxy-4-nitrophenoxy (a system with an amine with limited freedom of motion) in acetonitrile leads to C-O bond photocleavage in a relatively slow process (k approximate to 4 x 10(5) s(-1)) from intermediate species that show radical-ion pair behavior. Systems with higher freedom of motion of the amine moiety, such as 1-piperidino-5-(2-methoxy-4-nitrophenoxy)pentane or 4-nitroveratrole + triethylamine, show the intermediate radical-ion pairs mainly evolving to reduction products, probably a result of intermediates with geometries not allowed for the system with limited freedom of motion of the amine.
• SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): Discovery of antagonist SB-568849
  作者：David R. Witty、John H. Bateson、Guillaume J. Hervieu、Phillip Jeffrey、Christopher N. Johnson、Alison I. Muir、Peter J. O’Hanlon、Geoffrey Stemp、Alex J. Stevens、Kevin M. Thewlis、Shelagh Wilson、Kim Y. Winborn

  DOI：10.1016/j.bmcl.2006.06.056

  日期：2006.9

  We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were utilised to allow rapid exploration of the structure-activity relationship around this template, leading to compound SB-568849 which possessed good receptor affinity and selectivity. This compound proved to be an antagonist with stability in vivo, an acceptable brain-blood ratio and oral bioavailability. (c) 2006 Elsevier Ltd. All rights reserved.
• Topologically Controlled Coulombic Interactions, a New Tool in the Developing of Novel Reactivity. Photochemical and Electrochemical Cleavage of Phenyl Alkyl Ethers
  作者：Jorge Marquet、Eduard Cayon、Xavier Martin、Francisco Casado、Iluminada Gallardo、Miquel Moreno、Jose M. Lluch

  DOI：10.1021/jo00117a037

  日期：1995.6

  The hypothesis that a specific placement of a positive charge would dramatically alter the behavior of a charged intermediate has been tested. Phenyl ethers substituted by electron-attracting groups do not undergo reductive fragmentation. However, related alpha-piperidino-omega-(4-substituted-phenoxy)-alkanes give alkyl ether photocleavage when the linker between the redox centers is short, or the usual substitution-reduction photochemistry when it is long. Mechanistic experiments suggest that the photofragmentation process operates through space intramolecular electron transfer to the triplet aromatic chromophore and that a coplanar relative orientation of the alkyl ether bond and the phenyl ring is compulsory for the photofragmentation to be observed. Configuration interaction AM1 calculations justify the described facts, indicating that the fragmentation process is only operative when a Coulombic stabilization of a sigma* intramolecular electron transfer excited state is produced. Electrochemical studies carried out with the corresponding quaternary salts (intermolecular generation of the phenyl ether radical anion) confirm the conclusions derived from the photochemical experiments.
• Discovery of novel anti-breast cancer agents derived from deguelin as inhibitors of heat shock protein 90 (HSP90)
  作者：Cong-Truong Nguyen、Jihyae Ann、Raghaba Sahu、Woong Sub Byun、Sangkook Lee、Gibeom Nam、Hyun-Ju Park、Soeun Park、Yoon-Jae Kim、Ji Young Kim、Jae Hong Seo、Jeewoo Lee

  DOI：10.1016/j.bmcl.2020.127374

  日期：2020.9

  A series of O-substituted analogues of the B,C-ring truncated scaffold of deguelin were designed as C-terminal inhibitors of heat shock protein 90 (HSP90) and investigated as novel antiproliferative agents against HER2-positive breast cancer. Among the synthesized compounds, compound 80 exhibited significant inhibition in both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells, whereas compound 80 did not show any cytotoxicity in normal cells. Compound 80 markedly downregulated the expression of the major client proteins of HSP90 in both cell types, indicating that the cytotoxicity of 80 in breast cancer cells is attributed to the destabilization and inactivation of HSP90 client proteins and that HSP90 inhibition represents a promising strategy to overcome trastuzumab resistance. A molecular docking study of 80 with the homology model of a HSP90 homodimer showed that 80 fit nicely in the C-terminal domain with a higher electrostatic complementary score than that of ATP.