N-(3,4-dimethoxybenzylidene)-2-(1H-indol-3-yl)ethanamine

• 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: N-(3,4-dimethoxybenzylidene)-2-(1H-indol-3-yl)ethanamine
• 英文别名: 1-(3,4-dimethoxyphenyl)-N-[2-(1H-indol-3-yl)ethyl]methanimine
• 化学式: C₁₉H₂₀N₂O₂
• 分子量: 308.38
• InChiKey: WJAGMNYRVZDDLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  46.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

   N-(3,4-dimethoxybenzylidene)-2-(1H-indol-3-yl)ethanamine 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 N-allyl-N-(3,4-dimethoxy)benzyltryptamine
  参考文献：
  名称：

  通过N-烯丙基丙胺的异构化合成四氢β-咔啉：以Pictet-Spengler为主题的金属催化变体。

  摘要：

  提出了一种有效且广泛适用的四氢-β-咔啉的经典Pictet-Spengler合成方法。该方法依赖于烯丙基胺的金属催化异构化以形成反应性亚胺中间体，该中间体可以被束缚的吲哚亲核试剂捕获。

  DOI：

  10.1039/c2cc17704h
• 作为产物：
  描述：

  色胺 、 3,4-二甲氧基苯甲醛 以 甲醇 为溶剂， 反应 24.0h， 以73%的产率得到 N-(3,4-dimethoxybenzylidene)-2-(1H-indol-3-yl)ethanamine
  参考文献：
  名称：

  通过N-烯丙基丙胺的异构化合成四氢β-咔啉：以Pictet-Spengler为主题的金属催化变体。

  摘要：

  提出了一种有效且广泛适用的四氢-β-咔啉的经典Pictet-Spengler合成方法。该方法依赖于烯丙基胺的金属催化异构化以形成反应性亚胺中间体，该中间体可以被束缚的吲哚亲核试剂捕获。

  DOI：

  10.1039/c2cc17704h

文献信息

• Scalable methodologies for the synthesis of novel unsymmetrically-substituted secondary amines
  作者：Gheorghe Roman

  DOI：10.2298/jsc110408173r

  日期：——

  Fast, easy, and scalable methodologies for the synthesis of unsym- metrically substituted secondary amines containing naphthalene, indole, pyri- dine and imidazole moieties through reductive amination were explored. The investigated operating procedures were successful on a 50- to 30-mmol scale, and present a high potential for up-scaling.

  探索了快速，简便，可扩展的方法，用于通过还原胺化合成包含萘，吲哚，吡啶和咪唑部分的不对称取代的仲胺。所研究的操作程序在50至30 mmol的规模上是成功的，并且具有扩大规模的巨大潜力。
• 5-HT2 receptor binding, functional activity and selectivity in N-benzyltryptamines
  作者：Miguel Toro-Sazo、José Brea、María I. Loza、Marta Cimadevila、Bruce K. Cassels

  DOI：10.1371/journal.pone.0209804

  日期：——

  activity assays vs. the human 5-HT2 receptor subtypes. In the binding (radioligand displacement) studies some of these compounds exhibited only modest selectivity for either 5-HT2A or 5-HT2C receptors suggesting that a few of them, with affinities in the 10-100 nanomolar range for 5-HT2A receptors, might presumably be psychedelic. Unexpectedly, their functional (calcium mobilization) assays reflected

  在过去的十五年里，属于“NBOMe”系列的“超强”N-苄基化苯乙胺出现并进入了药物领域，并伴随着大量的研究文章。尽管已知 5-甲氧基色胺的 N-苄基取代可增加其对与致幻活性相关的 5-HT2 受体的亲和力和效力，但对 N-苄基化色胺的研究远少于其苯乙胺类似物。为了进一步了解 N-苄基色胺的活性，我们合成了一系列色胺衍生物，并合成了一些在苄基部分上具有许多不同取代模式的 5-甲氧基色胺类似物，并对它们进行了体外亲和力和功能测试。与人类 5-HT2 受体亚型的活性测定。在结合（放射性配体置换）研究中，其中一些化合物对 5-HT2A 或 5-HT2C 受体仅表现出适度的选择性，这表明其中一些对 5-HT2A 受体的亲和力在 10-100 纳摩尔范围内，可能可能是迷幻的。出乎意料的是，他们的功能（钙动员）测定反映了截然不同的趋势。所有这些化合物均被证明是 5-HT2C 受体完全激动剂，但大多数对 5-HT2A
• Synthesis Of 2-Acyltetrahydro-β-Carbolines By An Intramolecular α-Amidoalkylation Reaction
  作者：Atanas P. Venkov、Atanaska K. Boyadjieva

  DOI：10.1080/00397919908085791

  日期：1999.2

  2-Acyltetrahydro-beta-carbolines 7 have been obtained by cyclization of adducts 5 from imines 3 of tryptamine 1 and aldehydes 2 with acyl chlorides 4 as a result of an intramolecular alpha-amidoalkylation reaction in the presence of bases as N,N-dimethylaniline or Et3N.
• Synthesis of tetrahydro-β-carbolines via isomerization of N-allyltryptamines: a metal-catalyzed variation on the Pictet–Spengler theme
  作者：Erhad Ascic、Casper L. Hansen、Sebastian T. Le Quement、Thomas E. Nielsen

  DOI：10.1039/c2cc17704h

  日期：——

  An efficient and broadly applicable alternative to the classical Pictet-Spengler synthesis of tetrahydro-beta-carbolines is presented. The method relies on metal-catalyzed isomerization of allylic amines to form reactive iminium intermediates which can be trapped by a tethered indole nucleophile.

  提出了一种有效且广泛适用的四氢-β-咔啉的经典Pictet-Spengler合成方法。该方法依赖于烯丙基胺的金属催化异构化以形成反应性亚胺中间体，该中间体可以被束缚的吲哚亲核试剂捕获。
• Schiff bases of tryptamine as potent inhibitors of nucleoside triphosphate diphosphohydrolases (NTPDases): Structure-activity relationship
  作者：Kanwal、Khalid Mohammed Khan、Uzma Salar、Saira Afzal、Abdul Wadood、Muhammad Taha、Shahnaz Perveen、Huma Khan、Joanna Lecka、Jean Sévigny、Jamshed Iqbal

  DOI：10.1016/j.bioorg.2018.10.046

  日期：2019.2

  Overexpression of NTPDases leads to a number of pathological situations such as thrombosis, and cancer. Thus, effective inhibitors are required to combat these pathological situations. Different classes of NTPDase inhibitors are reported so far including nucleotides and their derivatives, sulfonated dyes such as reactive blue 2, suramin and its derivatives, and polyoxomatalates (POMs). Suramin is a well-known and potent NTPDase inhibitor, nonetheless, a range of side effects are also associated with it. Reactive blue 2 also had non-specific side effects that become apparent at high concentrations. In addition, most of the NTPDase inhibitors are high molecular weight compounds, always required tedious chemical steps to synthesize. Hence, there is still need to explore novel, low molecular weight, easy to synthesize, and potent NTPDase inhibitors.Keeping in mind the known NTPDase inhibitors with imine functionality and nitrogen heterocycles, Schiff bases of tryptamine, 1-26, were synthesized and characterized by spectroscopic techniques such as EI-MS, HREI-MS, H-1-, and C-13 NMR. All the synthetic compounds were evaluated for the inhibitory avidity against activities of three major isoforms of NTPDases: NTPDase-1, NTPDase-3, and NTPDase-8. Cumulatively, eighteen compounds were found to show potent inhibition (Ki = 0.0200-0.350 mu M) of NTPDase-1, twelve (Ki = 0.071-1.060 mu M) of NTPDase-3, and fifteen compounds inhibited (Ki = 0.0700-4.03 mu M) NTPDase-8 activity. As a comparison, the Kis of the standard inhibitor suramin were 1.260 +/- 0.007, 6.39 +/- 0.89 and 1.180 +/- 0.002 mu M, respectively. Kinetic studies were performed on lead compounds (6, 5, and 21) with human (h-) NTPDase-1, -3, and -8, and Lineweaver-Burk plot analysis showed that they were all competitive inhibitors. In silico study was conducted on compound 6 that showed the highest level of inhibition of NTPDase-1 to understand the binding mode in the active site of the enzyme.