3-methoxy-4-(2-(piperidin-1-yl)ethoxy)aniline

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-methoxy-4-(2-(piperidin-1-yl)ethoxy)aniline
• 英文别名: 3-methoxy-4-(2-piperidin-1-yl-ethoxy)-phenylamine；3-Methoxy-4-(2-piperidin-1-ylethoxy)aniline
• 化学式: C₁₄H₂₂N₂O₂
• 分子量: 250.341
• InChiKey: FLXRDTKLWGZCTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 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：
  47.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-methoxy-4-(2-(piperidin-1-yl)ethoxy)aniline 在 三乙胺 作用下， 以 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：

  1-(2-氯乙基)哌啶盐酸盐 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 24.0h， 生成 3-methoxy-4-(2-(piperidin-1-yl)ethoxy)aniline
  参考文献：
  名称：

  SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): Discovery of antagonist SB-568849

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.06.056

文献信息

• SUBSTITUTED THIATRIAZAACENAPHTHYLENE-6-CARBONITRILE KINASE INHIBITORS
  申请人：Connolly J. Peter

  公开号：US20070225309A1

  公开（公告）日：2007-09-27

  The present invention is directed to substituted thiatriazaacenaphthylene-6-carbonitrile compounds of formula (I): and forms thereof, their synthesis and use for treating, preventing or ameliorating a chronic or acute protein kinase mediated disease, disorder or condition.

  本发明涉及公式(I)的取代噻三氮杂蒽-6-碳腈化合物及其形式，它们的合成和用于治疗、预防或改善慢性或急性蛋白激酶介导的疾病、紊乱或状况的用途。
• Thia-tetraazaacenaphthylene kinase inhibitors
  申请人：Battista A. Kathleen

  公开号：US20070265264A1

  公开（公告）日：2007-11-15

  The present invention is directed to novel thia-tetraazaacenaphthylene compounds of Formula (I): and pharmaceutically acceptable forms thereof and their synthesis and use as inhibitors of ATP-protein kinase interactions.

  本发明涉及公式(I)的新型硫代四氮杂蒽化合物及其药学上可接受的形式，以及它们的合成和用作ATP-蛋白激酶相互作用抑制剂的用途。
• 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.
• 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.
• US7427625B2
  申请人：——

  公开号：US7427625B2

  公开（公告）日：2008-09-23