2-(7-氯-1H-吲哚-3-基)乙胺 | 3804-16-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 2-(7-氯-1H-吲哚-3-基)乙胺
• 英文名称: 7-chlorotryptamine
• 英文别名: 1H-Indole-3-ethanamine, 7-chloro-；2-(7-chloro-1H-indol-3-yl)ethanamine
• CAS: 3804-16-8
• 化学式: C₁₀H₁₁ClN₂
• 分子量: 194.664
• InChiKey: QKRNGBURTLCWBQ-UHFFFAOYSA-N

物化性质

• 熔点：
  96 °C
• 沸点：
  375.7±27.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  41.8
• 氢给体数：
  2
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(7-氯-1H-吲哚-3-基)乙胺 在 bis{rhodium[3,3'-(1,3-phenylene)bis(2,2-dimethylpropanoic acid)]} 、 2,4-二硝基苯基羟胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 5.0h， 生成 methyl 3a-amino-7-chloro-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indole-1(2H)-carboxylate
  参考文献：
  名称：

  裸氨基pyrroloindoline的合成经色胺的直接aminocyclization †

  摘要：

  已经描述了通过色胺和色氨酸的氨基环化首次直接进入未保护的氨基-吡咯并吲哚啉。在催化的Rh 2（esp）2存在下，通过使用O-（2,4-二硝基苯基）羟胺（DPH）作为氮源，可以提供多种结构多样的氨基-吡咯啉二氢吲哚。

  DOI：

  10.1039/c5ob00546a
• 作为产物：
  描述：

  7-氯吲哚 在 lithium aluminium tetrahydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 2-(7-氯-1H-吲哚-3-基)乙胺
  参考文献：
  名称：

  N-水杨酰色胺衍生物通过 STAT3 途径限制小胶质细胞激活作为有效的神经炎症抑制剂

  摘要：

  神经炎症是加剧神经退行性疾病（NDD）中神经元死亡和突触功能异常的重要因素。由于发病机制复杂，且存在血脑屏障（BBB），目前临床尚无有效药物。先前的结果表明， N-水杨酰色胺衍生物具有抑制神经炎症过程的潜力。在本研究中，设计并合成了30种新的N-水杨酰色胺衍生物，以研究色胺吲哚环的构效关系（SAR），以增强其抗神经炎症作用。其中，化合物18在体外和体内均通过抑制小胶质细胞的激活而发挥最佳的抗神经炎症作用，而小胶质细胞是神经炎症的罪魁祸首。其抗神经炎症作用的潜在机制可能与抑制信号转导子和转录激活子3（STAT3）的转录、表达和磷酸化有关，随后调节下游环氧合酶-2（COX-2）的表达和活性。凭借其优异的血脑屏障通透性和药代动力学特性，化合物18对脂多糖（LPS）诱导的小鼠海马区表现出比以前的N-水杨酰色胺衍生物L7显着的神经保护作用。总之，化合物18为开发靶向小胶质细胞激活的高效抗神经炎症治疗药物提供了新途径。

  DOI：

  10.1021/acschemneuro.4c00060

文献信息

• Facile in Vitro Biocatalytic Production of Diverse Tryptamines
  作者：Allwin D. McDonald、Lydia J. Perkins、Andrew R. Buller

  DOI：10.1002/cbic.201900069

  日期：2019.8

  the product line: Tryptamines are important synthons in bioactive natural products, but general synthetic routes to tryptamine analogues are limited. We present a highly active and promiscuous biosynthetic cascade using an engineered tryptophan synthase (TrpB) and native tryptophan decarboxylase (TDC) capable of producing a diverse set of tryptamines from readily accessible indoles.

  产品线多样化：色胺是生物活性天然产物中的重要合成子，但色胺类似物的一般合成路线有限。我们提出了一种高度活跃且混杂的生物合成级联，使用工程色氨酸合酶（TrpB）和天然色氨酸脱羧酶（TDC），能够从容易获得的吲哚中产生多种色胺。
• A Versatile Linkage Strategy for Solid-Phase Synthesis of <i>N</i>,<i>N</i>-Dimethyltryptamines and β-Carbolines
  作者：Tom Y. H. Wu、Peter G. Schultz

  DOI：10.1021/ol026729p

  日期：2002.11.1

  Various tryptamines are captured by a vinylsulfonylmethyl polystyrene resin, generating a safety-catch linkage. Beta-carbolines can be formed from 4 by a Pictet-Spengler reaction with the introduction of R(1). Tryptamine 4 can also be derivatized by acylation or copper-mediated coupling to introduce R(2). If X = Br, Suzuki coupling can be used to introduce R(3). After derivatization, the indole derivatives

  乙烯基磺酰基甲基聚苯乙烯树脂可捕获各种色胺，从而产生安全连接。β-咔啉可通过引入R（1）的Pictet-Spengler反应由4形成。色胺4也可以通过酰化或铜介导的偶联引入R（2）衍生化。如果X = Br，则可以使用Suzuki耦合来引入R（3）。衍生化后，吲哚衍生物被甲基碘活化并在温和的碱性条件下释放。[反应：看文字]
• Metal‐Free Dearomatization: Direct Access to Spiroindol(en)ines in Batch and Continuous‐Flow
  作者：Prabhat Ranjan、Gerardo M. Ojeda、Upendra K. Sharma、Erik V. Van der Eycken

  DOI：10.1002/chem.201805945

  日期：2019.2.18

  A metal‐free, phosphine‐catalyzed intramolecular “umpolung Michael addition” on alkynes to form spiroindol(en)ines is reported. This nucleophilic catalysis enables the formation of a wide scope of five‐ and six‐membered spiroindol(en)ines in moderate to excellent yields in batch as well as under continuous‐flow conditions. Triphenylphosphine‐catalyzed nucleophilic activation of alkynes allows the exclusive

  据报道，炔烃上无金属，磷化氢催化的分子内“ umpolung Michael加成反应”可形成螺环吲哚（en）ines。这种亲核催化作用能够以中等至极好的分批产率以及在连续流动条件下形成五元和六元螺环吲哚（en）胺类化合物。三苯基膦催化的炔烃亲核活化作用可在温和的反应条件下独家形成外泌产物。
• Integrating carbon–halogen bond formation into medicinal plant metabolism
  作者：Weerawat Runguphan、Xudong Qu、Sarah E. O’Connor

  DOI：10.1038/nature09524

  日期：2010.11

  Medicinal plants produce a variety of structurally complex, pharmaceutically important products, but generate relatively few halogenated compounds. Runguphan et al. remedy that omission by introducing the biosynthetic machinery responsible for chlorination in soil bacteria into the genome of the periwinkle, Catharanthus roseus. The prokaryotic halogenases function within the plant cells to generate chlorinated tryptophan, which is then utilized by the monoterpene indole alkaloid metabolic pathways to yield chlorinated alkaloids. Halogen atoms have been observed in several different classes of natural product, but very few halogenated natural products have been isolated from terrestrial plants. These authors show that biosynthetic machinery responsible for chlorination events in bacteria could be introduced into the medicinal plant Catharanthus roseus. Prokaryotic halogenases function within the plant cells to generate chlorinated tryptophan, which is then used by the monoterpene indole alkaloid metabolic pathways to yield chlorinated alkaloids. Halogenation, which was once considered a rare occurrence in nature, has now been observed in many natural product biosynthetic pathways1. However, only a small fraction of halogenated compounds have been isolated from terrestrial plants2. Given the impact that halogenation can have on the biological activity of natural products1, we reasoned that the introduction of halides into medicinal plant metabolism would provide the opportunity to rationally bioengineer a broad variety of novel plant products with altered, and perhaps improved, pharmacological properties. Here we report that chlorination biosynthetic machinery from soil bacteria can be successfully introduced into the medicinal plant Catharanthus roseus (Madagascar periwinkle). These prokaryotic halogenases function within the context of the plant cell to generate chlorinated tryptophan, which is then shuttled into monoterpene indole alkaloid metabolism to yield chlorinated alkaloids. A new functional group—a halide—is thereby introduced into the complex metabolism of C. roseus, and is incorporated in a predictable and regioselective manner onto the plant alkaloid products. Medicinal plants, despite their genetic and developmental complexity, therefore seem to be a viable platform for synthetic biology efforts.

  药用植物产生多种结构复杂且在药理上重要的产品，但生成的卤素化合物相对较少。Runguphan等人为了解决这一缺陷，将负责土壤细菌氯化的生物合成机械引入了长春花（Catharanthus roseus）的基因组。原核卤素化酶在植物细胞内发挥作用，生成氯化色氨酸，然后通过单萜吲哚生物碱代谢通路产生成氯生物碱。已经在几种不同类别的天然产物中观察到卤素原子，但从陆生植物中分离出的卤素化天然产品非常少。这些作者展示了可以将细菌中负责氯化事件的生物合成机械引入药用植物长春花。原核卤素化酶在植物细胞内发挥作用，生成氯化色氨酸，然后被用于单萜吲哚生物碱的代谢通路，从而获得氯化生物碱。曾经被认为在自然界中很少见的卤化现象，现在已在许多天然产物的生物合成途径中被观察到。然而，从陆生植物中分离的卤素化合物仅占一小部分。考虑到卤化可能对天然产物的生物活性产生的影响，我们认为，将卤素引入药用植物的代谢中，将提供理性生物工程广泛新型植物产品的机会，这些产品可能具有改变甚至改善的药理特性。在这里，我们报告了土壤细菌中的氯化生物合成机械可以成功地引入药用植物长春花（马达加斯加长春花）。这些原核卤素化酶在植物细胞的背景下发挥作用，生成氯化色氨酸，然后转入单萜吲哚生物碱的代谢中，生成氯化生物碱。由此，在C. roseus复杂的代谢中引入了一种新的功能基团——卤素，并以可预测和区域选择性的方式将其结合到植物生物碱产品中。因此，尽管药用植物具有遗传和发育上的复杂性，但似乎仍然是合成生物学努力的可行平台。
• N-Skatyltryptamines—Dual 5-HT6R/D2R Ligands with Antipsychotic and Procognitive Potential
  作者：Agata Hogendorf、Adam S. Hogendorf、Rafał Kurczab、Grzegorz Satała、Bernadeta Szewczyk、Paulina Cieślik、Gniewomir Latacz、Jadwiga Handzlik、Tomasz Lenda、Katarzyna Kaczorowska、Jakub Staroń、Ryszard Bugno、Beata Duszyńska、Andrzej J. Bojarski

  DOI：10.3390/molecules26154605

  日期：——

  A series of N-skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT1A, 5-HT2A, 5-HT6, and D2 receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Chosen hits were screened to determine their metabolism, permeability, hepatotoxicity, and CYP inhibition. Several D2 receptor antagonists with additional 5-HT6R antagonist and agonist properties were identified. The former combination resembled known antipsychotic agents, while the latter was particularly interesting due to the fact that it has not been studied before. Selective 5-HT6R antagonists have been shown previously to produce procognitive and promnesic effects in several rodent models. Administration of 5-HT6R agonists was more ambiguous—in naive animals, it did not alter memory or produce slight amnesic effects, while in rodent models of memory impairment, they ameliorated the condition just like antagonists. Using the identified hit compounds 15 and 18, we tried to sort out the difference between ligands exhibiting the D2R antagonist function combined with 5-HT6R agonism, and mixed D2/5-HT6R antagonists in murine models of psychosis.

  合成了一系列N-斯卡提尔色胺类化合物，并确定了它们对5-羟色胺和多巴胺受体的亲和力。这些化合物对5-HT1A、5-HT2A、5-HT6和D2受体表现出活性。通过同源建模鉴定并研究了导致亲和力/活性变化的取代模式。选择的化合物被筛选以确定它们的代谢、渗透性、肝毒性和CYP抑制作用。鉴定了几种具有额外5-HT6R拮抗剂和激动剂特性的D2受体拮抗剂。前者的组合类似于已知的抗精神病药物，而后者尤为有趣，因为以前尚未进行研究。先前已经显示，选择性的5-HT6R拮抗剂在几种啮齿动物模型中产生了促认知和促记忆效应。5-HT6R激动剂的给药效果更加模棱两可——在原始动物中，它不会改变记忆或产生轻微的遗忘效应，而在记忆障碍的啮齿动物模型中，它们像拮抗剂一样改善了状况。使用鉴定出的化合物15和18，我们尝试区分表现出D2R拮抗功能与5-HT6R激动作用相结合的配体，以及在小鼠精神病模型中混合D2/5-HT6R拮抗剂。