3-[(E)-2-(pyridin-2-yl)vinyl]-1H-indole | 53645-36-6

• 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: 3-[(E)-2-(pyridin-2-yl)vinyl]-1H-indole
• 英文别名: 3-[(E)-2-pyridin-2-yl-ethenyl]-1H-indole；3-<2-(2-Pyridyl)vinyl>indol；(E)-3-(2-(pyridin-2-yl)vinyl)-1H-indole；3-(2-pyridin-2-yl-vinyl)-indole；3-((E)-2-Pyridin-2-yl-vinyl)-1H-indole；3-[(E)-2-pyridin-2-ylethenyl]-1H-indole
• CAS: 53645-36-6
• 化学式: C₁₅H₁₂N₂
• 分子量: 220.274
• InChiKey: OZPYZRJHDWCCQM-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-bromopropyl (4α)-13-hydroxykaur-16-en-18-oate 、 3-[(E)-2-(pyridin-2-yl)vinyl]-1H-indole 以 N,N-二甲基甲酰胺 为溶剂， 以30 %的产率得到3-{2-[(E)-2-(1H-indol-3-yl)-ethenyl]-pyridinium-1-yl}-propyl(4α)-13-hydroxykaur-16-en-18-oate bromide
  参考文献：
  名称：

  源自甜菊醇或异甜菊醇的 F16 杂交体积累在肿瘤细胞的线粒体中并克服耐药性

  摘要：

  甜菊醇和异甜菊醇由市售甜味剂甜菊糖苷制备，并转化为亲脂性 F16 杂交体。它们的细胞毒性在 SRB 测定中测定，并显示取决于芳香族取代基的取代模式以及间隔区长度。因此，化合物 25 的 IC50 （A2780） 为 180 nM，从而超过了同类罗丹明杂交体的活性。几种化合物也能够克服 A2780/A2780cis 模型中的耐药性。额外的染色实验显示，F16 杂交体与成熟的有丝分裂聚糖具有相似的亚细胞积累模式，因此证明了优先的线粒体积累，但也证明了其他细胞区域的一些其他积累。

  DOI：

  10.3390/molecules29020381
• 作为产物：
  描述：

  碳酸甲丙酯 、 3-吲哚甲醛 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 neat (no solvent) 为溶剂， 反应 2.0h， 以72%的产率得到3-[(E)-2-(pyridin-2-yl)vinyl]-1H-indole
  参考文献：
  名称：

  Microwave synthesis of 2-[(E)-2-(1H-indol-3-yl)vinyl]hetarenes

  摘要：

  A new highly efficient method for the condensation of (indol-3-yl)carbaldehydes with 2-methylazoles and 2-methylazines under activation with microwave irradiation is developed. The method provides high yields of structural scaffolds of bishetarylethylene fluorescent sensors that found widespread application in medicinal, bioorganic, and pharmaceutical chemistry.

  DOI：

  10.1007/s10593-015-1788-0

文献信息

• Tryptophan 2,3-Dioxygenase (TDO) Inhibitors. 3-(2-(Pyridyl)ethenyl)indoles as Potential Anticancer Immunomodulators
  作者：Eduard Dolušić、Pierre Larrieu、Laurence Moineaux、Vincent Stroobant、Luc Pilotte、Didier Colau、Lionel Pochet、Benoît Van den Eynde、Bernard Masereel、Johan Wouters、Raphaël Frédérick

  DOI：10.1021/jm2006782

  日期：2011.8.11

  Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure- activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His(55) and Thr(254) residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (K-i = 5.5 mu M), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.
• Novel tryptophan dioxygenase inhibitors and combined tryptophan dioxygenase/5-HT reuptake inhibitors
  作者：D.J. Madge、R. Hazelwood、R. Iyer、H.T. Jones、M. Salter

  DOI：10.1016/0960-894x(96)00124-2

  日期：1996.4

  Tryptophan dioxygenase (TDO) is a liver enzyme that is responsible for the majority of the metabolism of tryptophan. A series of novel 3-(2-pyridylethenyl)indoles are shown to be potent inhibitors of TDO with selected members of the series also having 5-hydroxy tryptamine (5-HT) reuptake inhibitory activity. These compounds are shown to provide significant increases in the levels of tryptophan and 5-HT in the cerebrospinal fluid and are thus of interest for antidepressant therapy. Copyright (C) 1996 Elsevier Science Ltd
• Kynurenine Pathway Biomarkers Predictive of Anti-Immune Checkpoint Inhibitor Response
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20160299146A1

  公开（公告）日：2016-10-13

  The present invention is based on the identification of novel biomarkers predictive of responsiveness to anti-immune checkpoint inhibitor therapies.
• Microwave synthesis of 2-[(E)-2-(1H-indol-3-yl)vinyl]hetarenes
  作者：Alexander V. Aksenov、Oleg N. Nadein、Nicolai A. Aksenov、Anton A. Skomorokhov、Inna V. Aksenova、Michael A. Rubin

  DOI：10.1007/s10593-015-1788-0

  日期：2015.10

  A new highly efficient method for the condensation of (indol-3-yl)carbaldehydes with 2-methylazoles and 2-methylazines under activation with microwave irradiation is developed. The method provides high yields of structural scaffolds of bishetarylethylene fluorescent sensors that found widespread application in medicinal, bioorganic, and pharmaceutical chemistry.
• F16 Hybrids Derived from Steviol or Isosteviol Are Accumulated in the Mitochondria of Tumor Cells and Overcome Drug Resistance
  作者：Niels V. Heise、Julia Heisig、Kristof Meier、René Csuk、Thomas Mueller

  DOI：10.3390/molecules29020381

  日期：——

  Steviol and isosteviol were prepared from the commercially available sweetener stevioside and converted into lipophilic F16 hybrids. Their cytotoxicity was determined in SRB assays and showed to depend on both the substitution pattern of the aromatic substituent as well as on the spacer length. Therefore, compound 25 held an IC50 (A2780) of 180 nM, thus surpassing the activity of comparable rhodamine

  甜菊醇和异甜菊醇由市售甜味剂甜菊糖苷制备，并转化为亲脂性 F16 杂交体。它们的细胞毒性在 SRB 测定中测定，并显示取决于芳香族取代基的取代模式以及间隔区长度。因此，化合物 25 的 IC50 （A2780） 为 180 nM，从而超过了同类罗丹明杂交体的活性。几种化合物也能够克服 A2780/A2780cis 模型中的耐药性。额外的染色实验显示，F16 杂交体与成熟的有丝分裂聚糖具有相似的亚细胞积累模式，因此证明了优先的线粒体积累，但也证明了其他细胞区域的一些其他积累。