2,4-dinitro-5-phenoxybenzoic acid | 1219362-36-3

• 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: 2,4-dinitro-5-phenoxybenzoic acid
• CAS: 1219362-36-3
• 化学式: C₁₃H₈N₂O₇
• 分子量: 304.216
• InChiKey: CBVZXOMGWHLDCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,4-dinitro-5-phenoxybenzoic acid 在 5%-palladium/activated carbon 、 甲酸铵 、 溶剂黄146 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 9.0h， 生成 (R)-methyl 3-(2,5-dioxo-7-phenoxy-8-(2-((4-(trifluoromethyl)benzyl)oxy)acetamido)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]-diazepin-3-yl)propanoate
  参考文献：
  名称：

  Discovery of 1,4-Benzodiazepine-2,5-dione (BZD) Derivatives as Dual Nucleotide Binding Oligomerization Domain Containing 1/2 (NOD1/NOD2) Antagonists Sensitizing Paclitaxel (PTX) To Suppress Lewis Lung Carcinoma (LLC) Growth in Vivo

  摘要：

  Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Previously, we reported nucleotide-binding oligomerization domain-containing protein 1 (NOD1) antagonists (II, 12) and a NOD2 antagonist (9) that sensitized docetaxel (DTX) or paclitaxel (PTX) treatment for breast or lung cancer. In this article, we describe for the first time a 1,4-benzodiazepine-2,5-dione (BZD) derivative (26bh) that acts as a dual NOD1/NOD2 antagonist and inhibits both nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) inflammatory signaling, thereby sensitizing PTX to suppress Lewis lung carcinoma (LLC) growth. After investigation of the compound's cytotoxicity, a systematic structure-activity relationship (SAR) was completed and revealed several key factors that were necessary to maintain antagonistic ability. This study establishes the possibility for using adjuvant treatment to combat cancer by antagonizing both NOD1 and NOD2 signaling.

  DOI：

  10.1021/acs.jmedchem.7b00608
• 作为产物：
  描述：

  3-氯苯甲酸 在 碳酸氢钠 、 potassium nitrate 作用下， 以 硫酸 、 水 为溶剂， 反应 2.0h， 生成 2,4-dinitro-5-phenoxybenzoic acid
  参考文献：
  名称：

  Nonpeptidic quinazolinone derivatives as dual nucleotide-binding oligomerization domain-like receptor 1/2 antagonists for adjuvant cancer chemotherapy

  摘要：

  Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1/2) receptors are potential immune checkpoints. In this article, a quinazolinone derivative (36b) as a NOD1/2 dual antagonist was identified that significantly sensitizes B16 tumor-bearing mice to paclitaxel treatment by inhibiting both nuclear factor κB (NF-κB) and mitogen-activated protein kinase inflammatory signaling that mediated by NOD1/2.

  DOI：

  10.1016/j.ejmech.2020.112723

文献信息

• Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity
  作者：Wenjun Yu、Xilei Xie、Yao Ma、Shiping Fang、Yi Dong、Gang Liu

  DOI：10.1021/acs.jmedchem.2c01431

  日期：2022.11.10

  52b inhibited protein synthesis in cancer cells. Moreover, 52b significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound 52b with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth

  在这项研究中，对库存小分子化学库进行了随机多个人类肿瘤细胞系筛选，并发现了一种命中化合物 1,4-苯二氮卓-2,5-二酮（BZD，11a；平均增长 50%确定了对九种人类癌症的 60 种肿瘤细胞系的抑制浓度 (GI 50 = 0.24 μM))。随后的构效关系 (SAR) 研究揭示了一种高效抗肿瘤化合物52b，该化合物被证明可通过诱导细胞周期停滞和细胞凋亡对肺癌细胞发挥有前景的作用。进一步的多核糖体谱分析表明，52b抑制了癌细胞中的蛋白质合成。此外，52b显着阻止了人类非小细胞肺癌 (NCI-H522) 异种移植小鼠模型中的肿瘤生长，没有可观察到的毒性作用。这些发现是合成化合物52b的首次报道，该化合物具有 1,4-苯二氮卓-2,5-二酮骨架，可作为潜在的蛋白质合成抑制剂有效抑制肿瘤生长。
• Parallel Solution Phase Synthesis of 3,6,7−4(3<i>H</i>)-Quinazolinones and Evaluation of Their Antitumor Activities against Human Cancer
  作者：Hao Wu、Xilei Xie、Gang Liu

  DOI：10.1021/cc900173s

  日期：2010.5.10

  Three diversity points of 4(3H)-quinazolinone are introduced at the 3-, 6-, and 7-positions with an efficient parallel solution-phase synthetic method. A one-pot synthesis was developed that gave the key intermediate in high yield. Five hit compounds exhibit preferable activities against a panel of human tumor cell lines, which pointed out preliminary structure-activity relationships.