2-nitro-N-(2-phenylethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine

• 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: 2-nitro-N-(2-phenylethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine
• 英文别名: 3-nitro-N-(2-phenylethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine
• 化学式: C₁₉H₂₂N₂O₂
• 分子量: 310.396
• InChiKey: DYOFAMKWNXOMBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  57.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5,6,8,9-四氢-苯并环庚烯-7-酮 在 硫酸 、 硝酸 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-nitro-N-(2-phenylethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine
  参考文献：
  名称：

  Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position

  摘要：

  Benzo[7]annulen-7-amines 7 without further polar substituents have been reported as conformationally restricted Ro 25-6981 analogs and show unexpectedly high GluN2B affinity. Herein the corresponding 2-NO2 derivatives 8 were synthesized and pharmacologically evaluated. NO2 derivatives 8 show 5- to 10-fold higher GluN2B affinity than the unsubstituted ligands 7. Docking studies of ligands 7c and 8c reveal an important contribution of the 2-NO2-substituent in determining the binding pose and modulating the GluN2B affinity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.076

文献信息

• Design, Synthesis, Pharmacological Evaluation and Docking Studies of GluN2B-Selective NMDA Receptor Antagonists with a Benzo[7]annulen-7-amine Scaffold
  作者：Sandeep Gawaskar、Louisa Temme、Julian A. Schreiber、Dirk Schepmann、Alessandro Bonifazi、Dina Robaa、Wolfgang Sippl、Nathalie Strutz-Seebohm、Guiscard Seebohm、Bernhard Wünsch

  DOI：10.1002/cmdc.201700311

  日期：2017.8.8

  Antagonists that selectively target GluN2B-subunit-containing N-methyl-d-aspartate (NMDA) receptors are of major interest for the treatment of various neurological disorders. In this study, relationships between variously substituted benzo[7]annulen-7-amines and their GluN2B affinity were investigated. 2-Nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one (8) represents the central building block for the

  选择性靶向含GluN2B亚基的N-甲基-d-天冬氨酸（NMDA）受体的拮抗剂是治疗各种神经系统疾病的主要兴趣。在这项研究中，研究了各种取代的苯并[7]年环七胺与它们的GluN2B亲和力之间的关系。2-硝基-5,6,8,9-四氢苯并[7]环戊烯-7-（8）表示在2位上引入各种取代基和各种7-氨基部分的中心结构单元。具有2-NO 2（7 c），2-Cl（15 c）或2-的N-（3-苯基丙基）-6,7,8,9-四氢-5H-苯并[7]年戊烯-7-胺OBn组（22 c）显示出很高的GluN2B亲和力（Ki = 1.6-3.6 nm）。对接研究表明，在GluN1b和GluN2B亚基的界面上，苯并[7]环戊烯7-胺和艾芬地尔具有相同的结合姿势。22 c的较大的2-OBn部分占据了以前无法识别的子口袋，这解释了其较高的GluN2B亲和力（Ki = 3.6 nm）。在两电极电压钳实验和细胞保护试验中，高亲和
• Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position
  作者：Sandeep Gawaskar、Dirk Schepmann、Alessandro Bonifazi、Dina Robaa、Wolfgang Sippl、Bernhard Wünsch

  DOI：10.1016/j.bmcl.2015.10.076

  日期：2015.12

  Benzo[7]annulen-7-amines 7 without further polar substituents have been reported as conformationally restricted Ro 25-6981 analogs and show unexpectedly high GluN2B affinity. Herein the corresponding 2-NO2 derivatives 8 were synthesized and pharmacologically evaluated. NO2 derivatives 8 show 5- to 10-fold higher GluN2B affinity than the unsubstituted ligands 7. Docking studies of ligands 7c and 8c reveal an important contribution of the 2-NO2-substituent in determining the binding pose and modulating the GluN2B affinity. (C) 2015 Elsevier Ltd. All rights reserved.