N-[2-(5-chloro-1H-indol-3-yl)ethyl]formamide | 1408315-36-5

• 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
• 英文名称: N-[2-(5-chloro-1H-indol-3-yl)ethyl]formamide
• CAS: 1408315-36-5
• 化学式: C₁₁H₁₁ClN₂O
• 分子量: 222.674
• InChiKey: BPGFZCQUCKYGEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-[2-(5-chloro-1H-indol-3-yl)ethyl]formamide 在 sodium hydride 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.5h， 生成 7-Chloro-3-(4-chlorobenzoyl)-21-methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4(9),5,7,15,17,19-heptaen-14-one
  参考文献：
  名称：

  New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations

  摘要：

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.

  DOI：

  10.1021/jm300605m
• 作为产物：
  描述：

  5-chloro-3-(2-nitrovinyl)indole 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 N-[2-(5-chloro-1H-indol-3-yl)ethyl]formamide
  参考文献：
  名称：

  3-(2-异氰乙基)吲哚与1-磺酰基-1,2,3-三唑级联反应无催化剂合成多环螺吲哚啉

  摘要：

  实现了3-(2-异氰乙基)吲哚和1-磺酰基-1,2,3-三唑的无催化剂级联反应。这种脱芳螺环化提供了一种有效的方案，可以在热反应条件下一步合成一系列带有螺-α-咔啉的多环二氢吲哚，并以中等至高产率一步合成。

  DOI：

  10.1021/acs.joc.3c00800

文献信息

• Visible-Light-Induced Trifluoromethylation of Isonitrile-Substituted Indole Derivatives: Access to 1-(Trifluoromethyl)-4,9-dihydro-3<i>H</i>-pyrido[3,4-b]indole and<i>β</i>-Carboline Derivatives
  作者：Jiaxin Liu、Longhai Li、Liuzhu Yu、Lisha Tang、Qin Chen、Min Shi

  DOI：10.1002/adsc.201800568

  日期：2018.8.6

  visible‐light‐induced trifluoromethylation of isonitrile‐substituted indole derivatives has been developed from the reaction of isonitrile‐substituted indoles with Togni II reagent, affording 1‐(trifluoromethyl)‐4,9‐dihydro‐3H‐pyrido[3,4‐b]indoles in moderate to good yields. The further transformations to β‐carboline derivatives and a harmacine derivative have been performed, demonstrating the potential synthetic

  的可见光诱导的异腈基取代的吲哚衍生物的三氟甲基化已经从与TOGNI II试剂异腈取代的吲哚的反应研制，得到1-（三氟甲基）-4,9-二氢-3- ħ -吡啶并[3,4 ‐b]吲哚产量中等至良好。已经进行了向β-咔啉衍生物和harmacine衍生物的进一步转化，证明了该方法的潜在合成效用。一项初步的生物学研究表明，含有CF 3的harmine类似物可显着刺激胰高血糖素样肽1（GLP-1）的分泌，表明糖尿病的治疗有所改善。
• Asymmetric Dearomatization of Indoles through a Michael/Friedel-Crafts-Type Cascade To Construct Polycyclic Spiroindolines
  作者：Xiaohu Zhao、Xiaohua Liu、Hongjiang Mei、Jing Guo、Lili Lin、Xiaoming Feng

  DOI：10.1002/anie.201410814

  日期：2015.3.23

  through a cascade reaction between 2‐isocyanoethylindole and alkylidene malonates catalyzed by a chiral N,N′‐dioxide/MgII catalyst. Fused polycyclic indolines containing three stereocenters were afforded in good yields with excellent diastereo‐ and enantioselectivities through a Michael/Friedel–Crafts/Mannich cascade. When 2‐substituted 2‐isocyanoethylindoles were used, spiroindoline derivatives were obtained

  通过手性N，N'-二氧化物/ Mg II催化剂催化2-异氰基乙基吲哚和亚烷基丙二酸酯之间的级联反应，实现了吲哚的高效不对称脱芳香化。通过Michael / Friedel-Crafts / Mannich级联反应，可以很好地获得具有三个立体中心的熔融多环二氢吲哚，并具有出色的非对映异构和对映选择性。当使用2-取代的2-异氰基乙基吲哚时，螺二氢吲哚衍生物是通过Michael / Friedel-Crafts反应获得的。
• Hydrogen‐Bonding‐Promoted Cascade Rearrangement Involving the Enlargement of Two Rings: Efficient Access to Polycyclic Quinoline Derivatives
  作者：Wen‐Bin Cao、Shijun Li、Meng‐Meng Xu、Haiyan Li、Xiao‐Ping Xu、Yu Lan、Shun‐Jun Ji

  DOI：10.1002/anie.202008110

  日期：2020.11.23

  An efficient cascade reaction of tryptamine‐derived isocyanides with C,N‐cyclic azomethine imines is described. The polycyclic pyrrolo[2,3‐c]quinoline derivatives, which benefited from rearrangement process driven by hydrogen bonding, could be directly assembled in moderate to good yields (40–87 %) under metal‐free and mild conditions. This transformation involved four new heterocyclic rings formations

  描述了一种由色胺衍生的异氰酸酯与C，N-环偶氮甲亚胺的有效级联反应。多环吡咯并[2,3-c]喹啉衍生物得益于氢键驱动的重排过程，可以在无金属和温和条件下以中等到良好的产率（40-87％）直接组装。这种转化涉及四个新的杂环形成，并且独特地是吲哚的开环以及C，N-环偶氮甲亚胺亚胺的环扩展。实验研究和DFT研究都为深入了解反应途径提供了指导，并发现氢键可降低过渡态的自由能垒。这项工作是基于色胺的异氰酸酯级联反应的罕见例子，
• Synthesis of polycyclic spiroindolines by highly diastereoselective interrupted Ugi cascade reactions of 3-(2-isocyanoethyl)indoles
  作者：Jordy M. Saya、Barry Oppelaar、Răzvan C. Cioc、Gydo van der Heijden、Christophe M. L. Vande Velde、Romano V. A. Orru、Eelco Ruijter

  DOI：10.1039/c6cc07459f

  日期：——

  We report a highly diastereoselective interrupted Ugi reaction to construct a broad range of structurally congested and stereochemically complex spiroindolines from tryptamine-derived isocyanides. The reaction is facilitated by using fluorinated...

  我们报告了高度非对映选择性中断的Ugi反应，以从色胺中衍生的异氰酸酯构建广泛的结构拥挤和立体化学复杂的螺二氢吲哚。通过使用氟化的...可以促进反应。
• Bioactivity-Guided Synthesis Accelerates the Discovery of Evodiamine Derivatives as Potent Insecticide Candidates
  作者：Jingbo Liu、Yabing Shi、Zhicheng Tian、Fengyun Li、Zesheng Hao、Wen Wen、Li Zhang、Yuanhong Wang、Yuxin Li、Zhijin Fan

  DOI：10.1021/acs.jafc.1c08297

  日期：2022.4.27

  design and structural optimization have been one of the most effective ways to innovate pesticides for integrated insect management. To continue our previous studies on the discovery of insecticidal lead, a series of evodiamine derivatives were designed, synthesized, and evaluated for their insecticidal activities. The bioassay results demonstrated that compounds Ian and Iao exhibited 90 and 80% insecticidal

  害虫通过降低作物产量和损害其质量来威胁全球粮食安全。基于天然产物的分子设计和结构优化一直是创新农药以实现昆虫综合治理的最有效方法之一。为了继续我们先前对发现杀虫铅的研究，我们设计、合成了一系列吴茱萸碱衍生物，并对其杀虫活性进行了评估。生物测定结果表明，化合物Ian和Iao在 2.5 mg/L 时对Mythimna separata的杀虫活性分别为 90% 和 80%，优于吴茱萸碱（10%，10 mg/L）、苦参碱（45%，600 mg/L）。 L) 和鱼藤酮 (30% at 200 mg/L)。化合物Ian-Iap对小菜蛾的杀虫活性为 1.0 mg/L，远高于吴茱萸碱、苦参碱和鱼藤酮。化合物Ian在5.0 mg/L时对棉铃虫的杀虫活性为60% ，而吴茱萸碱、苦参碱和鱼藤酮的杀虫活性很差。通过钙成像实验对杀虫作用机制的研究表明，昆虫兰尼碱受体（RyRs）可能是Ian的潜在靶点。此外，分子对接