1-(2,5-二甲氧基-4-氰基苯基)-2-氨基乙烷盐酸盐 | 88441-08-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(2,5-二甲氧基-4-氰基苯基)-2-氨基乙烷盐酸盐
• 英文名称: 4-(2-aminoethyl)-2,5-dimethoxybenzonitrile hydrochloride
• 英文别名: 2,5-Dimethoxy-4-cyanophenethylamine hydrochloride；4-(2-aminoethyl)-2,5-dimethoxybenzonitrile;hydrochloride
• CAS: 88441-08-1
• 化学式: C₁₁H₁₄N₂O₂*ClH
• 分子量: 242.705
• InChiKey: UTIJAZMOSJQGGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  68.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯并[b]呋喃-7-甲醛 、 1-(2,5-二甲氧基-4-氰基苯基)-2-氨基乙烷盐酸盐 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成
  参考文献：
  名称：

  选择性5-HT2A受体激动剂25CN-NBOH：[3H] 25CN-NBOH的结构活性关系，体内药理以及体外和离体结合特征。

  摘要：

  在最近的临床试验中，经典迷幻药所表现出的显着效果已引起人们对5-HT2A受体（5-HT2AR）活化作为多种精神/认知障碍治疗策略的浓厚兴趣。在这项研究中，我们继续开发25CN-NBOH（迄今为止报道的对5-HT2AR选择性最强的激动剂之一），作为探索5-HT2AR表达和功能的药理学工具。25CN-NBOH中2'和3'位置作为其5-HT2AR活性的结构热点的重要性通过结合和功能测定法在5-HT2AR和5-HT2CR上的六个新类似物的合成和药理学表征进行了研究。虽然25CN-NBOH的5-HT2AR活性保留在3'-甲基，2'，3'-苯并二氢吡喃，2'，3'-二氢呋喃和2'，3'-呋喃类似物中，但3' 与25CN-NBOH相比，-甲氧基和3'-乙基类似物显示出更低的结合亲和力和激动剂效力。有趣的是，2'，3'取代模式也是激动剂功效的关键决定因素，因为在功能测定中，所有六个类似物在5-HT2AR处

  DOI：

  10.1016/j.bcp.2020.113979
• 作为产物：
  描述：

  2,5-二甲氧基苯甲醛 在 苯酐 、 ammonium acetate 、 溴 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 生成 1-(2,5-二甲氧基-4-氰基苯基)-2-氨基乙烷盐酸盐
  参考文献：
  名称：

  Discovery of β-Arrestin-Biased 25CN-NBOH-Derived 5-HT_2A Receptor Agonists

  摘要：

  DOI：

  10.1021/acs.jmedchem.2c00702

文献信息

• Convergent 18F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands
  作者：Ida Nymann Petersen、Jonas Villadsen、Hanne Demant Hansen、Anders A. Jensen、Szabolcs Lehel、Nic Gillings、Matthias M. Herth、Gitte M. Knudsen、Jesper L. Kristensen

  DOI：10.1016/j.bmc.2016.08.056

  日期：2016.11

  Positron emission tomography (PET) investigations of the 5-HT2A receptor (5-HT2AR) system can be used as a research tool in diseases such as depression, Alzheimer's disease and schizophrenia. We have previously developed a C-11-labeled agonist PET ligand ([C-11]Cimbi-36), and the aim of this study was to identify a F-18-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different F-18-labeled ligands structurally related to Cimbi-36 from a common F-18-labeled intermediate. After intravenous injection, all ligands entered the pig brain. However, since within-scan intervention with ketanserin, a known orthosteric 5-HT2A receptor antagonist, did not result in significant blocking, the radioligands seem unsuitable for neuroimaging of the 5-HT2AR in vivo. (C) 2016 Elsevier Ltd. All rights reserved.
• Synthesis and Structure–Activity Relationships of <i>N</i>-Benzyl Phenethylamines as 5-HT_2A/2C Agonists
  作者：Martin Hansen、Karina Phonekeo、James S. Paine、Sebastian Leth-Petersen、Mikael Begtrup、Hans Bräuner-Osborne、Jesper L. Kristensen

  DOI：10.1021/cn400216u

  日期：2014.3.19

  N-Benzyl substitution of 5-HT2A receptor agonists of the phenethylamine structural class of psychedelics (such as 4-bromo-2,5-dimethoxyphenethylamine, often referred to as 2C-B) confer a significant increase in binding affinity as well as functional activity of the receptor. We have prepared a series of 48 compounds with structural variations in both the phenethylamine and N-benzyl part of the molecule to determine the effects on receptor binding affinity and functional activity at 5-HT2A and 5-HT2c receptors. The compounds generally had high affinity for the 5-HT2A receptor with 8b having the highest affinity at 0.29 nM but with several other compounds also exhibiting subnanomolar binding affinities. The functional activity of the compounds was distributed over a wider range with lb being the most potent at 0.074 nM. Most of the compounds exhibited low to moderate selectivity (1- to 40-fold) for the 5-HT2A receptor in the binding assays, although one compound 6b showed an impressive 100-fold selectivity for the 5-HT2A receptor. In the functional assay, selectivity was generally higher with lb being more than 400-fold selective for the 5-HT2A receptor.
• The selective 5-HT2A receptor agonist 25CN-NBOH: Structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH
  作者：Anders A. Jensen、Adam L. Halberstadt、Emil Märcher-Rørsted、Anna U. Odland、Muhammad Chatha、Nikolaj Speth、Gudrun Liebscher、Martin Hansen、Hans Bräuner-Osborne、Mikael Palner、Jesper T. Andreasen、Jesper L. Kristensen

  DOI：10.1016/j.bcp.2020.113979

  日期：2020.7

  hotspots for its 5-HT2AR activity was investigated by synthesis and pharmacological characterization of six novel analogs at 5-HT2AR and 5-HT2CR in binding and functional assays. While the 5-HT2AR activity of 25CN-NBOH was retained in 3'-methyl, 2',3'-chroman, 2',3'-dihydrofuran and 2',3'-furan analogs, the 3'-methoxy and 3'-ethyl analogs displayed substantially lower binding affinities and agonist potencies

  在最近的临床试验中，经典迷幻药所表现出的显着效果已引起人们对5-HT2A受体（5-HT2AR）活化作为多种精神/认知障碍治疗策略的浓厚兴趣。在这项研究中，我们继续开发25CN-NBOH（迄今为止报道的对5-HT2AR选择性最强的激动剂之一），作为探索5-HT2AR表达和功能的药理学工具。25CN-NBOH中2'和3'位置作为其5-HT2AR活性的结构热点的重要性通过结合和功能测定法在5-HT2AR和5-HT2CR上的六个新类似物的合成和药理学表征进行了研究。虽然25CN-NBOH的5-HT2AR活性保留在3'-甲基，2'，3'-苯并二氢吡喃，2'，3'-二氢呋喃和2'，3'-呋喃类似物中，但3' 与25CN-NBOH相比，-甲氧基和3'-乙基类似物显示出更低的结合亲和力和激动剂效力。有趣的是，2'，3'取代模式也是激动剂功效的关键决定因素，因为在功能测定中，所有六个类似物在5-HT2AR处
• Discovery of β-Arrestin-Biased 25CN-NBOH-Derived 5-HT_2A Receptor Agonists
  作者：Christian B. M. Poulie、Eline Pottie、Icaro A. Simon、Kasper Harpsøe、Laura D’Andrea、Igor V. Komarov、David E. Gloriam、Anders A. Jensen、Christophe P. Stove、Jesper L. Kristensen

  DOI：10.1021/acs.jmedchem.2c00702

  日期：2022.9.22