(3-Amino-7-methoxy-1-methylindol-2-yl)-(3,4,5-trimethoxyphenyl)methanone | 1012370-38-5

• 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-Amino-7-methoxy-1-methylindol-2-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1012370-38-5
• 化学式: C₂₀H₂₂N₂O₅
• 分子量: 370.405
• InChiKey: OOAFPLDVRMZKOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3-Amino-7-methoxy-1-methylindol-2-yl)-(3,4,5-trimethoxyphenyl)methanone 在 吡啶 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 19.0h， 生成 2-iodo-N-(7-methoxy-1-methyl-2-(3,4,5-trimethoxybenzoyl)-1H-indol-3-yl)acetamide
  参考文献：
  名称：

  Novel iodoacetamido benzoheterocyclic derivatives with potent antileukemic activity are inhibitors of STAT5 phosphorylation

  摘要：

  Signal Transducer and Activator of Transcription 5 (STAT5) protein, a component of the STAT family of signaling proteins, is considered to be an attractive therapeutic target because of its involvement in the progression of acute myeloid leukemia. In an effort to discover potent molecules able to inhibit the phosphorylation-activation of STAT5, twenty-two compounds were synthesized and evaluated on the basis of our knowledge of the activity of 2-(3',4',5'-trimethoxybenzoyl)-3-iodoacetamido-6-methoxy benzo[b]furan derivative I as a potent STAT5 inhibitor. Most of these molecules, structurally related to compound 1, were characterized by the presence of a common 3',4',5'-trimethoxybenzoyl moiety at the 2-position of different benzoheterocycles such as benzo[b]furan, benzo[b]thiophene, indole and N-methylindole. Effects on biological activity of the iodoacetamido group and of different moieties (methyl and methoxy) at the C-3 to C-7 positions were examined. In the series of benzo[b]furan derivatives, moving the iodoacetylamino group from the C-4 to the C-5 or C-6 positions did not significantly affect antiproliferative activity. Compounds 4, 15, 20 and 23 blocked STAT5 signals and induced apoptosis of K562 BCR-ABL positive cells. For compound 23, the trimethoxybenzoyl moiety at the 2-position of the benzo[b]furan core was not essential for potent inhibition of STAT5 activation. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.022
• 作为产物：
  描述：

  2-[7-methoxy-2-(3,4,5-trimethoxybenzoyl)-1-methyl-indol-3-yl]-isoindole-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以91%的产率得到(3-Amino-7-methoxy-1-methylindol-2-yl)-(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1-Methyl-2-(3′,4′,5′-trimethoxybenzoyl)-3-aminoindoles as a New Class of Antimitotic Agents and Tubulin Inhibitors

  摘要：

  The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent anti proliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.

  DOI：

  10.1021/jm7011547

文献信息

• Synthesis and Biological Evaluation of 1-Methyl-2-(3′,4′,5′-trimethoxybenzoyl)-3-aminoindoles as a New Class of Antimitotic Agents and Tubulin Inhibitors
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Taradas Sarkar、Maria Dora Carrion、Carlota Lopez Cara、Olga Cruz-Lopez、Delia Preti、Mojgan Aghazadeh Tabrizi、Manlio Tolomeo、Stefania Grimaudo、Antonella Di Cristina、Nicola Zonta、Jan Balzarini、Andrea Brancale、Hsing-Pang Hsieh、Ernest Hamel

  DOI：10.1021/jm7011547

  日期：2008.3.13

  The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent anti proliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.
• Novel iodoacetamido benzoheterocyclic derivatives with potent antileukemic activity are inhibitors of STAT5 phosphorylation
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Filippo Prencipe、Carlota Lopez-Cara、Riccardo Rondanin、Daniele Simoni、Ernest Hamel、Stefania Grimaudo、Rosaria Maria Pipitone、Maria Meli、Manlio Tolomeo

  DOI：10.1016/j.ejmech.2015.11.022

  日期：2016.1

  Signal Transducer and Activator of Transcription 5 (STAT5) protein, a component of the STAT family of signaling proteins, is considered to be an attractive therapeutic target because of its involvement in the progression of acute myeloid leukemia. In an effort to discover potent molecules able to inhibit the phosphorylation-activation of STAT5, twenty-two compounds were synthesized and evaluated on the basis of our knowledge of the activity of 2-(3',4',5'-trimethoxybenzoyl)-3-iodoacetamido-6-methoxy benzo[b]furan derivative I as a potent STAT5 inhibitor. Most of these molecules, structurally related to compound 1, were characterized by the presence of a common 3',4',5'-trimethoxybenzoyl moiety at the 2-position of different benzoheterocycles such as benzo[b]furan, benzo[b]thiophene, indole and N-methylindole. Effects on biological activity of the iodoacetamido group and of different moieties (methyl and methoxy) at the C-3 to C-7 positions were examined. In the series of benzo[b]furan derivatives, moving the iodoacetylamino group from the C-4 to the C-5 or C-6 positions did not significantly affect antiproliferative activity. Compounds 4, 15, 20 and 23 blocked STAT5 signals and induced apoptosis of K562 BCR-ABL positive cells. For compound 23, the trimethoxybenzoyl moiety at the 2-position of the benzo[b]furan core was not essential for potent inhibition of STAT5 activation. (C) 2015 Elsevier Masson SAS. All rights reserved.