4-(4-甲氧羰基-苯基氨基)-3,5-二硝基苯甲酸 | 299965-41-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(4-甲氧羰基-苯基氨基)-3,5-二硝基苯甲酸
• 英文名称: 4-(4-(hexyloxycarbonyl)phenylamino)-3,5-dinitrobenzoic acid
• 英文别名: 4-(4-Hexoxycarbonylanilino)-3,5-dinitrobenzoic acid
• CAS: 299965-41-6
• 化学式: C₂₀H₂₁N₃O₈
• 分子量: 431.402
• InChiKey: IEYJQEQLVBVCAQ-UHFFFAOYSA-N

物化性质

• 沸点：
  563.4±50.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  167
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  己基4-氨基苯甲酸酯 、 4-氯-3,5-二硝基苯甲酸 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以40%的产率得到4-(4-甲氧羰基-苯基氨基)-3,5-二硝基苯甲酸
  参考文献：
  名称：

  Computational techniques are valuable tools for the discovery of protein–protein interaction inhibitors: The 14-3-3σ case

  摘要：

  Targeting the binding site of 14-3-3 proteins lets the release of partner proteins involved in cell cycle progression, apoptosis, cytoskeletal rearrangement and transcriptional regulation and may therefore be regarded as an alternative strategy to integrate conventional therapeutic approaches against cancer. In the present work, we report the identification of two new small molecule inhibitors of 14-3-3 sigma/c-Abl protein-protein interaction (BV01 and BV101) discovered by means of computational methods. The most interesting compound (BV01) showed a lethal dose (LD50) in the low micromolar range against Ba/F3 murine cell lines expressing the Imatinib (IM)-sensitive wild type Bcr-Abl construct and the IM-resistant Bcr-Abl mutation T315I. BV01 interaction with 14-3-3 sigma was demonstrated by NMR studies and elucidated by docking. It blocked the binding domain of 14-3-3 sigma, hence promoting the release of the partner protein c-Abl (the one not involved in Bcr rearrangement), and its translocation to both the nuclear compartment and mitochondrial membranes to induce a pro-apoptotic response. Our results advance BV01 as a confirmed hit compound capable of eliciting apoptotic death of Bcr-Abl-expressing cells by interfering with 14-3-3 sigma/c-Abl protein-protein interaction. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.011

文献信息

• NON PEPTIDIC 14-3-3 INHIBITORS AND THE USE THEREOF
  申请人：BOTTA Maurizio

  公开号：US20130203831A1

  公开（公告）日：2013-08-08

  The present invention refers to compounds with inhibitory activity against 14-3-3 proteins and their use in the treatment of tumors, in particular chronic myeloid leukemia. The invention also provides methods for the identification of 14-3-3 protein inhibitors.
• US8895600B2
  申请人：——

  公开号：US8895600B2

  公开（公告）日：2014-11-25
• Computational techniques are valuable tools for the discovery of protein–protein interaction inhibitors: The 14-3-3σ case
  作者：Valentina Corradi、Manuela Mancini、Maria Alessandra Santucci、Teresa Carlomagno、Domenico Sanfelice、Mattia Mori、Giulia Vignaroli、Federico Falchi、Fabrizio Manetti、Marco Radi、Maurizio Botta

  DOI：10.1016/j.bmcl.2011.09.011

  日期：2011.11

  Targeting the binding site of 14-3-3 proteins lets the release of partner proteins involved in cell cycle progression, apoptosis, cytoskeletal rearrangement and transcriptional regulation and may therefore be regarded as an alternative strategy to integrate conventional therapeutic approaches against cancer. In the present work, we report the identification of two new small molecule inhibitors of 14-3-3 sigma/c-Abl protein-protein interaction (BV01 and BV101) discovered by means of computational methods. The most interesting compound (BV01) showed a lethal dose (LD50) in the low micromolar range against Ba/F3 murine cell lines expressing the Imatinib (IM)-sensitive wild type Bcr-Abl construct and the IM-resistant Bcr-Abl mutation T315I. BV01 interaction with 14-3-3 sigma was demonstrated by NMR studies and elucidated by docking. It blocked the binding domain of 14-3-3 sigma, hence promoting the release of the partner protein c-Abl (the one not involved in Bcr rearrangement), and its translocation to both the nuclear compartment and mitochondrial membranes to induce a pro-apoptotic response. Our results advance BV01 as a confirmed hit compound capable of eliciting apoptotic death of Bcr-Abl-expressing cells by interfering with 14-3-3 sigma/c-Abl protein-protein interaction. (C) 2011 Elsevier Ltd. All rights reserved.