(E)-4-(2-(1H-indol-3-yl)vinyl)-pyridine | 53645-38-8

• 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
• 英文名称: (E)-4-(2-(1H-indol-3-yl)vinyl)-pyridine
• 英文别名: (E)-3-(2-(pyridine-4yl)vinyl)-1H-indole；3-(2-(4-Pyridinyl)ethenyl)-1h-indole；3-[(E)-2-pyridin-4-ylethenyl]-1H-indole
• CAS: 53645-38-8
• 化学式: C₁₅H₁₂N₂
• 分子量: 220.274
• InChiKey: GWFLOYNQTNXGOJ-AATRIKPKSA-N

物化性质

• 沸点：
  435.9±14.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 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：

  (E)-4-(2-(1H-indol-3-yl)vinyl)-pyridine 、 3β,28-diacetoxy-30-bromolup-20(29)-ene 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以79%的产率得到
  参考文献：
  名称：

  五环三萜酸与线粒体靶向阳离子F16共轭：细胞毒性活性的合成和评估

  摘要：

  合成了F16缀合的五环三萜类化合物，桦木素和桦木酸，熊醛，齐墩果酸和甘草次酸衍生物的第一个代表。三萜核在С-3，С-28或С-30位置与一个或两个靶向线粒体的离域亲脂性阳离子F16连接通过丁烷或三甘醇间隔基。使用人类癌细胞系U937（白血病单核细胞淋巴瘤），K562（慢性髓细胞性白血病）和Jurkat（T淋巴细胞白血病）以及人类非恶性成纤维细胞系来评估产品的细胞毒活性。与亲本桦木酸相比，大多数获得的缀合物显示出显着的抗肿瘤作用增强（约100-200倍），并且相对于健康的成纤维细胞，其对肿瘤细胞系的细胞毒性作用明显更高。在一系列测试化合物中，具有桦木素和桦木酸6、8和11的F16缀合物具有最高的选择性，显示出可接受的选择性指数值（≥10）。

  DOI：

  10.1007/s00044-021-02702-z
• 作为产物：
  描述：

  3-吲哚甲醛 、 4-吡啶乙酸盐酸盐 在 三乙胺 、 哌啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 192.17h， 以49%的产率得到(E)-4-(2-(1H-indol-3-yl)vinyl)-pyridine
  参考文献：
  名称：

  两亲性花青-铂结合为荧光纳米药物。

  摘要：

  通过纳米沉淀法制备了两种基于小分子花青-铂结合物的荧光纳米药物，并通过透射电子显微镜（TEM）和动态光散射（DLS）对其进行了表征。与溶液中的缀合物相比，缀合物在其纳米颗粒制剂中表现出增强的荧光。共聚焦激光扫描显微镜（CLSM）显示，纳米药物可被癌细胞内吞，并显示出高度的细胞增殖抑制作用。直接从小分子制备的荧光铂纳米药物可能是开发同时具有细胞成像和癌症治疗功能的新药物的替代策略。

  DOI：

  10.1002/asia.201501163

文献信息

• Conjugated 5-fluorouracil with mitochondria-targeting lipophilic cation: design, synthesis and biological evaluation
  作者：Jia Wang、Xiao-Yang Fan、Li-Yun Yang、Huan He、Rong Huang、Feng-Lei Jiang、Yi Liu

  DOI：10.1039/c6md00268d

  日期：——

  5-Fluorouracil (5-FU) was linked with F16 by vulnerable bonds to selectively target cancer mitochondria which resulted in conjugated compounds, including F16–5-FU, F16–OOC-FU, F16–NHOC-FU and F16–SS-FU. F16–OOC-FU decreased the antiproliferative activity of 5-FU on the nontumor cell line, and the cytotoxicity of F16–SS-FU significantly increased when administered with dithiothreitol (DTT).

  5-氟尿嘧啶（5-FU）通过易碎键与F16相连，以选择性地靶向癌症线粒体，从而产生共轭化合物，包括F16–5-FU，F16–OOC-FU，F16–NHOC-FU和F16–SS-FU 。F16–OOC-FU降低了5-FU对非肿瘤细胞系的抗增殖活性，与二硫苏糖醇（DTT）一起使用时，F16–SS-FU的细胞毒性显着增加。
• Dual Inhibition of Pyruvate Dehydrogenase Complex and Respiratory Chain Complex Induces Apoptosis by a Mitochondria‐Targeted Fluorescent Organic Arsenical in vitro and in vivo
  作者：Yu‐Jiao Liu、Xiao‐Yang Fan、Dong‐Dong Zhang、Yin‐Zheng Xia、Yan‐Jun Hu、Feng‐Lei Jiang、Fu‐Ling Zhou、Yi Liu

  DOI：10.1002/cmdc.201900686

  日期：2020.3.18

  targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria-targeted organic arsenical PDT-PAO-F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti-cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT-PAO-F16 mainly accumulated into

  基于靶向线粒体的潜在治疗价值和荧光团的追踪能力，制备了靶向荧光线粒体的有机砷PDT-PAO-F16，它不仅可视化细胞分布，而且在体内外均具有抗癌活性。通过靶向线粒体中的丙酮酸脱氢酶复合物（PDHC）和呼吸链复合物。详细地，PDT-PAO-F16主要在数小时内积累到线粒体中，并且抑制PDHC的活性，从而抑制了ATP合成和生热障碍。此外，抑制呼吸链复合体I和IV加速了线粒体功能障碍，导致caspase家族依赖性细胞凋亡。在体内，在APL小鼠模型中，PDT-PAO-F16治疗组的急性早幼粒细胞白血病得到极大缓解。
• 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。
• 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