3-amino-6-methyl-2-(3,4,5-trimethoxybenzoyl) benzothiophene | 864378-35-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-amino-6-methyl-2-(3,4,5-trimethoxybenzoyl) benzothiophene
• 英文别名: 2-(3,4,5-Trimethoxybenzoyl)-3-amino-6-methylbenzo[b]thiophene；(3-amino-6-methyl-1-benzothiophen-2-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 864378-35-8
• 化学式: C₁₉H₁₉NO₄S
• 分子量: 357.43
• InChiKey: DUHXHINAOXQPMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-amino-6-methyl-2-(3,4,5-trimethoxybenzoyl) benzothiophene 在 亚硝酸特丁酯 、 copper(ll) bromide 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以67%的产率得到(3-bromo-6-methylbenzo[b]thiophen-2-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  2-(3',4',5'-三甲氧基苯甲酰基)-3-芳基/芳基氨基苯并[b]噻吩衍生物作为一类新型抗增殖剂的合成和生物学评价

  摘要：

  微管在有丝分裂和间期的生物学重要性使它们成为开发抗癌剂的有趣目标。苯并[ b ]噻吩等小分子作为微管蛋白聚合的抑制剂很有吸引力。因此，一类新的化合物结合了 2-(3',4',5'-三甲氧基苯甲酰基)-3-芳基/芳氨基苯并[ b ]噻吩分子骨架的结构基序，具有给电子（Me, OMe 、SMe 或 OEt) 或 B 环上的吸电子（F 和 Cl）取代基，合成并评估其抗增殖活性、抑制微管蛋白聚合和细胞周期效应。该系列中最有前途的化合物是2-(3',4',5'-三甲氧基苯甲酰基)-3-(4'-乙氧基苯基)-苯并[ b ]噻吩(4e )，在亚微摩尔浓度下显着抑制癌细胞生长，尤其是对 HeLa 和 Jurkat 细胞的抑制，并与微管蛋白相互作用。通过流式细胞术分析确定，4e以时间和浓度依赖性方式引起 G2/M 期阻滞和细胞凋亡。G2/M 的阻断与细胞周期蛋白 B1 的表达增加和 cdc25c 的磷酸化相关。此外，4e扰乱线粒体膜电位并引起

  DOI：

  10.1016/j.ejmech.2010.09.038
• 作为产物：
  描述：

  4-甲基-2-硝基苯腈 在 氢氧化钾 、 三氯化铝 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 、 苯 为溶剂， 反应 68.0h， 生成 3-amino-6-methyl-2-(3,4,5-trimethoxybenzoyl) benzothiophene
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2- and 3-Aminobenzo[b]thiophene Derivatives as Antimitotic Agents and Inhibitors of Tubulin Polymerization

  摘要：

  Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.

  DOI：

  10.1021/jm070050f

文献信息

• Synthesis and Evaluation of Haloacetyl, α-Bromoacryloyl and Nitrooxyacetyl Benzo[b]furan and Benzo[b]thiophene Derivatives as Potent Antiproliferative Agents Against Leukemia L1210 and K562 Cells
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Alberto Casolari、Ernest Hamel、Enrica Fabbri、Roberto Gambari

  DOI：10.2174/157018010791526296

  日期：2010.8.1

  at the 6-position of the benzo[b]furan skeleton, were identified as potent antiproliferative agents against the human chronic myelogenous K562 and murine L1210 leukemia cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 6- to the 5- or 7-position yielded inactive compounds. The effects of a selected series of compounds on cell cycle progression correlated well

  鉴定新型和选择性抗癌剂仍然是药理学研究中一个重要且具有挑战性的目标。为了寻找具有强抗增殖活性和简单分子结构的新化合物，我们合成了三个不同系列的化合物，其中不同的取代基连接到 2-(3', 4', 5'-三甲氧基苯甲酰基) 的 3-氨基位置-苯并[b]呋喃或苯并[b]噻吩环系。这些取代基对应于乙酰基/卤代乙酰基、α-溴丙烯酰基和硝基氧乙酰基部分，具有不同的亲电特性。选择苯并杂环母体结构是因为它们具有生物活性。在苯并[b]呋喃骨架的6-位带有甲氧基的化合物，被鉴定为针对人慢性骨髓性 K562 和鼠 L1210 白血病细胞系的有效抗增殖剂。位置异构体的比较表明，将甲氧基从 6- 位移动到 5- 或 7- 位会产生无活性的化合物。选定的一系列化合物对细胞周期进程的影响与其强大的抗增殖活性和微管蛋白聚合的抑制作用密切相关。在此处描述的一系列化合物中观察到的构效关系分析可能代表了设计更活跃分子的平台。
• Synthesis and preliminary biological evaluation of new anti-tubulin agents containing different benzoheterocycles
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、M. Katherine Jung、Maria Antonietta Iaconinoto、Maria Dora Carrion、Vincent Remusat、Delia Preti、Mojgan Aghazadeh Tabrizi、Fruttarolo Francesca、Erik De Clercq、Jan Balzarini、Ernest Hamel

  DOI：10.1016/j.bmcl.2005.06.022

  日期：2005.9

  A new series of compounds, in which the 2-amino-4-methoxyphenyl ring of phenstatin analogue 5 was replaced with 2- or 3-amino-benzoheterocycles, was synthesized and evaluated for antiproliferative activity and inhibition of colchicine binding. The lack of activity of 3 ',4 '-dimethoxy- and 4 '-methoxy-benzoyl derivatives (8 and 9, respectively) indicates that the 3 ',4 ',5 '-trimethoxybenzoyl moiety is critical for the activity. Two compounds, 7 and 11, displayed potent antiproliferative activity, with IC50 values ranging from 25 to 100 nM against a variety of cancer cell lines. Derivative 11 was more active than CA-4 as an inhibitor of tubulin polymerization. The results demonstrated that the antiproliferative activity was correlated with inhibition of tubulin polymerization. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Evaluation of 2- and 3-Aminobenzo[<i>b</i>]thiophene Derivatives as Antimitotic Agents and Inhibitors of Tubulin Polymerization
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Delia Preti、Francesca Fruttarolo、Maria Giovanna Pavani、Mojgan Aghazadeh Tabrizi、Manlio Tolomeo、Stefania Grimaudo、Antonella Di Cristina、Jan Balzarini、John A. Hadfield、Andrea Brancale、Ernest Hamel

  DOI：10.1021/jm070050f

  日期：2007.5.1

  Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
• Synthesis and biological evaluation of 2-(3′,4′,5′-trimethoxybenzoyl)-3-aryl/arylaminobenzo[b]thiophene derivatives as a novel class of antiproliferative agents
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Carlota Lopez Cara、Ernest Hamel、Giuseppe Basso、Roberta Bortolozzi、Giampietro Viola

  DOI：10.1016/j.ejmech.2010.09.038

  日期：2010.12

  the B-ring, was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. The most promising compound in this series was 2-(3′,4′,5′-trimethoxybenzoyl)-3-(4′-ethoxyphenyl)-benzo[b]thiophene (4e), which significantly inhibited cancer cell growth at submicromolar concentrations, especially against HeLa and Jurkat cells, and interacted with tubulin

  微管在有丝分裂和间期的生物学重要性使它们成为开发抗癌剂的有趣目标。苯并[ b ]噻吩等小分子作为微管蛋白聚合的抑制剂很有吸引力。因此，一类新的化合物结合了 2-(3',4',5'-三甲氧基苯甲酰基)-3-芳基/芳氨基苯并[ b ]噻吩分子骨架的结构基序，具有给电子（Me, OMe 、SMe 或 OEt) 或 B 环上的吸电子（F 和 Cl）取代基，合成并评估其抗增殖活性、抑制微管蛋白聚合和细胞周期效应。该系列中最有前途的化合物是2-(3',4',5'-三甲氧基苯甲酰基)-3-(4'-乙氧基苯基)-苯并[ b ]噻吩(4e )，在亚微摩尔浓度下显着抑制癌细胞生长，尤其是对 HeLa 和 Jurkat 细胞的抑制，并与微管蛋白相互作用。通过流式细胞术分析确定，4e以时间和浓度依赖性方式引起 G2/M 期阻滞和细胞凋亡。G2/M 的阻断与细胞周期蛋白 B1 的表达增加和 cdc25c 的磷酸化相关。此外，4e扰乱线粒体膜电位并引起