(Z)-2-(3,4-dimethoxyphenyl)-3-(1H-indol-3-yl)acrylonitrile | 108479-44-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z)-2-(3,4-dimethoxyphenyl)-3-(1H-indol-3-yl)acrylonitrile
• 英文别名: 2-(3,4-dimethoxy-phenyl)-3-indol-3-yl-acrylonitrile；2-(3,4-Dimethoxy-phenyl)-3-indol-3-yl-acrylonitril；(Z)-2-(3,4-dimethoxyphenyl)-3-(1H-indol-3-yl)prop-2-enenitrile
• CAS: 108479-44-3
• 化学式: C₁₉H₁₆N₂O₂
• 分子量: 304.348
• InChiKey: HKGQRKMBBSEUMP-NTEUORMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  58
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-吲哚甲醛 、 3,4-二甲氧基苯乙腈 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 (Z)-2-(3,4-dimethoxyphenyl)-3-(1H-indol-3-yl)acrylonitrile
  参考文献：
  名称：

  Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents

  摘要：

  A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI(50) values of <10 nM against 74% and 70%, respectively, of the human cancer cell lines in the 60-cell panel. Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of alpha- and beta-tubulin that is occupied by colchicine, and were stabilized by van der Waals' interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.050

文献信息

• Notes - Substituted Acrylonitriles from Heterocyclic Aldehydes and 3,4-Dimethoxyphenylacetonitrile
  作者：Lavagnino、Shepard

  DOI：10.1021/jo01355a614

  日期：1957.4
• [EN] METHODS OF PROTECTING AGAINST NEURODEGENERATION<br/>[FR] PROCÉDÉS DE PROTECTION CONTRE LA NEURODÉGÉNÉRESCENCE
  申请人：BIOVENTURES LLC

  公开号：WO2018144910A1

  公开（公告）日：2018-08-09

  The disclosure provides a method of preventing or reducing protein aggregates using combretastatin-A4 (CA4) or an analog thereof. The disclosure also provides methods of reducing the risk, delaying the onset, delaying or slowing the progression, or reversing the signs or symptoms of a neurodegenerative (or other age-progressive) disease using a combretastatin-A4 (CA4) or an analog thereof. The combretastatin-A4 (CA4) or an analog thereof may bind glial fibrillary acidic protein (GFAP). The combretastatin-A4 (CA4) or an analog thereof is described by compounds of Formula (I).
• Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents
  作者：Narsimha Reddy Penthala、Hongliang Zong、Amit Ketkar、Nikhil Reddy Madadi、Venumadav Janganati、Robert L. Eoff、Monica L. Guzman、Peter A. Crooks

  DOI：10.1016/j.ejmech.2014.12.050

  日期：2015.3

  A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI(50) values of <10 nM against 74% and 70%, respectively, of the human cancer cell lines in the 60-cell panel. Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of alpha- and beta-tubulin that is occupied by colchicine, and were stabilized by van der Waals' interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.