4-methyl-N-(3-methylphenyl)-3-nitrobenzamide | 328258-73-7

• 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: 4-methyl-N-(3-methylphenyl)-3-nitrobenzamide
• CAS: 328258-73-7
• 化学式: C₁₅H₁₄N₂O₃
• 分子量: 270.288
• InChiKey: ZYYDEPSQJVRZDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methyl-N-(3-methylphenyl)-3-nitrobenzamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 、 potassium carbonate 、 氯化铵 、 锌 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 叔丁醇 为溶剂， 反应 9.0h， 生成 4-methyl-3-((6-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)amino)-N-(m-tolyl)benzamide
  参考文献：
  名称：

  Discovery and Identification of Small Molecules as Methuosis Inducers with in Vivo Antitumor Activities

  摘要：

  Methuosis is a novel nonapoptotic mode of cell death characterized by vacuole accumulation in the cytoplasm. In this article, we describe a series of azaindole-based compounds that cause vacuolization in MDA-MB-231 cells. The most potent vacuole inducer, compound 13 (compound 13), displayed differential cytotoxicities against a broad panel of cancer cell lines, such as MDA-MB-231, A375, HCT116, and MCF-7, but it did not inhibit the growth of the nontumorigenic epithelial cell line MCF-10A. A mechanism study confirmed that the cell death was caused by inducing methuosis. Furthermore, compound 13 exhibited substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects, which makes this compound the first example of a methuosis inducer with potent in vivo efficacy. These results demonstrate that methuosis inducers might serve as novel therapeutics for the treatment of cancer.

  DOI：

  10.1021/acs.jmedchem.8b00753
• 作为产物：
  描述：

  4-甲基-3-硝基苯甲酸 、 3-甲基苯胺 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 4-methyl-N-(3-methylphenyl)-3-nitrobenzamide
  参考文献：
  名称：

  Discovery and Identification of Small Molecules as Methuosis Inducers with in Vivo Antitumor Activities

  摘要：

  Methuosis is a novel nonapoptotic mode of cell death characterized by vacuole accumulation in the cytoplasm. In this article, we describe a series of azaindole-based compounds that cause vacuolization in MDA-MB-231 cells. The most potent vacuole inducer, compound 13 (compound 13), displayed differential cytotoxicities against a broad panel of cancer cell lines, such as MDA-MB-231, A375, HCT116, and MCF-7, but it did not inhibit the growth of the nontumorigenic epithelial cell line MCF-10A. A mechanism study confirmed that the cell death was caused by inducing methuosis. Furthermore, compound 13 exhibited substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects, which makes this compound the first example of a methuosis inducer with potent in vivo efficacy. These results demonstrate that methuosis inducers might serve as novel therapeutics for the treatment of cancer.

  DOI：

  10.1021/acs.jmedchem.8b00753

文献信息

• Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II
  作者：Guobao Zhang、Pingda Ren、Nathanael S. Gray、Taebo Sim、Xia Wang、Yi Liu、Jianwei Che、Weitong Dong、Shin-Shay Tian、Mark L. Sandberg、Tracy A. Spalding、Russell Romeo、Maya Iskandar、Zhiliang Wang、H. Martin Seidel、Donald S. Karanewsky、Yun He

  DOI：10.1016/j.bmcl.2009.09.123

  日期：2009.12

  A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs. (C) 2009 Elsevier Ltd. All rights reserved.
• Discovery and Identification of Small Molecules as Methuosis Inducers with <i>in Vivo</i> Antitumor Activities
  作者：Wei Huang、Xihuan Sun、Yunzhan Li、Zhixiang He、Li Li、Zhou Deng、Xiaoxing Huang、Shang Han、Ting Zhang、Jiaji Zhong、Zheng Wang、Qingyan Xu、Jianming Zhang、Xianming Deng

  DOI：10.1021/acs.jmedchem.8b00753

  日期：2018.6.28

  Methuosis is a novel nonapoptotic mode of cell death characterized by vacuole accumulation in the cytoplasm. In this article, we describe a series of azaindole-based compounds that cause vacuolization in MDA-MB-231 cells. The most potent vacuole inducer, compound 13 (compound 13), displayed differential cytotoxicities against a broad panel of cancer cell lines, such as MDA-MB-231, A375, HCT116, and MCF-7, but it did not inhibit the growth of the nontumorigenic epithelial cell line MCF-10A. A mechanism study confirmed that the cell death was caused by inducing methuosis. Furthermore, compound 13 exhibited substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects, which makes this compound the first example of a methuosis inducer with potent in vivo efficacy. These results demonstrate that methuosis inducers might serve as novel therapeutics for the treatment of cancer.