{[5-methoxy-2-(4-methoxyphenyl)-1H-indol-3-yl]methylene}malononitrile | 957059-50-6

• 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: {[5-methoxy-2-(4-methoxyphenyl)-1H-indol-3-yl]methylene}malononitrile
• 英文别名: 2-[[5-methoxy-2-(4-methoxyphenyl)-1H-indol-3-yl]methylidene]propanedinitrile
• CAS: 957059-50-6
• 化学式: C₂₀H₁₅N₃O₂
• 分子量: 329.358
• InChiKey: QFOWLDPQDYHOIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  81.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-甲氧基-2-(4-甲氧基苯基)吲哚 在 苯甲酰氯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 {[5-methoxy-2-(4-methoxyphenyl)-1H-indol-3-yl]methylene}malononitrile
  参考文献：
  名称：

  通过亚胺盐与活性亚甲基试剂的原位缩合非常规立体选择性一锅合成Knoevenagel型吲哚

  摘要：

  描述了一种简单的一锅法，用于立体选择性合成Knoevenagel型吲哚。该方法基于在三乙胺存在下吲哚亚胺盐（已充分表征其中的四种）与无环对称和不对称活性亚甲基试剂的原位反应。总的来说，总产量是中等至良好。讨论了影响立体选择性的一些相关反应参数和空间效应。

  DOI：

  10.1016/j.tet.2013.10.086

文献信息

• Domino Process in Silver-Catalyzed Reactions of <i>N</i>-Arylformimidates and Active Methylene Compounds Involving Cycloisomerization and 1,3-Alkenyl Shift
  作者：Chang Ho Oh、Swastik Karmakar、HyoSeung Park、YoungCheon Ahn、Jung Wook Kim

  DOI：10.1021/ja9106226

  日期：2010.2.17

  3-disubstituted indoles from alkyne iminoethers 1 that employs a domino process involving Ag-catalyzed condensation followed by a tandem Ag-induced cycloisomerization and 1,3-alkenyl shift to Ag-activated carbon. This methodology can be useful in regioselectively constructing 3-alkylated indoles, which are part of the structures of biologically active compounds and important alkaloids.

  我们开发了一种从炔亚氨基醚 1 合成 2,3-二取代吲哚的有效方法，该方法采用多米诺过程，包括银催化缩合，然后是串联银诱导的环异构化和 1,3-烯基转移到银活性炭. 这种方法可用于区域选择性地构建 3-烷基化吲哚，这是生物活性化合物和重要生物碱结构的一部分。
• Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents
  作者：Andrea Spallarossa、Chiara Caneva、Matteo Caviglia、Silvana Alfei、Stefania Butini、Giuseppe Campiani、Sandra Gemma、Margherita Brindisi、Daniela M. Zisterer、Sandra A. Bright、Clive D. Williams、Emmanuele Crespan、Giovanni Maga、Giuseppina Sanna、Ilenia Delogu、Gabriella Collu、Roberta Loddo

  DOI：10.1016/j.ejmech.2015.08.009

  日期：2015.9

  A new series of indole-based analogues were recently identified as potential anticancer agents. The Knoevenagel-type indoles herein presented were prepared via a one-pot condensation of iminium salts with active methylene reagents and were isolated as single geometric isomers. Biological evaluation in different cell-based assays revealed an antiproliferative activity for some analogues already in the nanomolar range against leukaemia, breast. and renal cancer cell lines. To explain these effects, the most promising analogues of the series were engaged in further cell-based studies. Compounds 5e, I, p and 6a, b highlighted a pro-apoptotic potential being able to induce apoptosis in HL60, K562 and MCF-7 cell lines in a dose and time-dependent manner. The ability of these compounds to arrest cell cycle at the G2/M phase inspired the immunofluorescence studies which allowed us to identify tubulin as a potential target for compounds 5l and 6b. (C) 2015 Elsevier Masson SAS. All rights reserved.
• [(2-Phenylindol-3-yl)methylene]propanedinitriles inhibit the growth of breast cancer cells by cell cycle arrest in G2/M phase and apoptosis
  作者：Michaela Pojarová、Doris Kaufmann、Robert Gastpar、Tsuyuki Nishino、Przemyslaw Reszka、Patrick J. Bednarski、Erwin von Angerer

  DOI：10.1016/j.bmc.2007.07.046

  日期：2007.12

  Cell cycle arrest of malignant cells is an important option for cancer treatment. In this study, we modified the structure of antimitotic 2-phenylindole-3-carbaldehydes by condensation with malononitrile. The resulting methylene propanedinitriles inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC50 values below 100 nM. Though they exhibited similar structure-activity relationships as the aldehydes, they did not inhibit tubulin polymerization but were capable of blocking the cell cycle in G(2)/M phase. The cell cycle arrest was accompanied by apoptosis as demonstrated by the activation of caspases 3 and 9. Since the new 2-phenylindole derivatives also inhibited the growth of transplanted MXT mouse mammary tumors, they are interesting candidates for further development. (C) 2007 Elsevier Ltd. All rights reserved.
• Unconventional stereoselective one-pot synthesis of Knoevenagel-type indoles via in situ condensation of iminium salts with active methylene reagents
  作者：Angelo Ranise、Francesco Lucchesini、Matteo Caviglia、Silvana Alfei、Andrea Spallarossa、Chiara Caneva

  DOI：10.1016/j.tet.2013.10.086

  日期：2013.12

  Knoevenagel-type indoles is described. The method is based on the in situ reaction of indole iminium salts (four of them are fully characterized) with acyclic symmetrical and unsymmetrical active methylene reagents in the presence of triethylamine. In general, the overall yields are moderate to good. Some of relevant reaction parameters and steric effects affecting stereoselectivity are discussed.

  描述了一种简单的一锅法，用于立体选择性合成Knoevenagel型吲哚。该方法基于在三乙胺存在下吲哚亚胺盐（已充分表征其中的四种）与无环对称和不对称活性亚甲基试剂的原位反应。总的来说，总产量是中等至良好。讨论了影响立体选择性的一些相关反应参数和空间效应。