4-(2-carbamoylphenylcarbamoyl)benzoic acid methyl ester | 925136-87-4

• 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-(2-carbamoylphenylcarbamoyl)benzoic acid methyl ester
• 英文别名: Methyl 4-[(2-carbamoylphenyl)carbamoyl]benzoate
• CAS: 925136-87-4
• 化学式: C₁₆H₁₄N₂O₄
• 分子量: 298.298
• InChiKey: SFFZBKGHRDFBBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  98.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-carbamoylphenylcarbamoyl)benzoic acid methyl ester 在 sodium hydroxide 作用下， 以 水 为溶剂， 以86.6 %的产率得到4-(4-oxo-3,4-dihydroquinazolin-2-yl)benzoic acid
  参考文献：
  名称：

  HDAC6、HDAC8 和 6/8 抑制剂的发现以及基于细胞的药物筛选模型的开发，用于治疗 TGF-β 诱导的特发性肺纤维化

  摘要：

  特发性肺纤维化无法治愈，其进展难以控制，因此可导致肺部恶化。泛组蛋白脱乙酰酶抑制剂（例如 SAHA）已显示出调节肺纤维化的潜力，但具有脱靶效应。因此，选择性HDAC抑制剂将有利于减少副作用。为了实现这一目标，我们设计并合成了24种新型HDAC6、HDAC8或双HDAC6/8抑制剂，并建立了两阶段筛选平台来快速筛选有效减轻TGF-β诱导的肺纤维化的HDAC抑制剂。第一阶段包括小鼠 NIH-3T3 成纤维细胞预筛选，并产生了 5 次命中。在第二阶段，使用人肺成纤维细胞 (HPF)，并对 5 个命中中的 4 个进行了 caco-2 渗透性和肝微粒体稳定性测试，以给出两个潜在的线索：J27644 (15 )和20。这种新颖的两阶段筛选平台将加速 HDAC 抑制剂的发现并降低开发成本，以减轻 TGF-β 诱导的肺纤维化。

  DOI：

  10.1021/acs.jmedchem.3c00644
• 作为产物：
  描述：

  对苯二甲酸单甲酯 、 2-氨基苯甲酰胺 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 以87%的产率得到4-(2-carbamoylphenylcarbamoyl)benzoic acid methyl ester
  参考文献：
  名称：

  Synthesis and cytotoxicity of 2-phenylquinazolin-4(3H)-one derivatives

  摘要：

  Thirty 2-phenylquinazolin-4(3H)-one derivatives were prepared and their cytotoxic activities were tested in five human tumor cell lines. Some compounds (5e, 5k, 5t, 6c and 6f) showed relatively high cytotoxic activity. Especially, compound 6c showed the most cytotoxicity against all cell lines tested among the synthesized derivatives, and the inhibitory activity of 6c against HeLa cell was higher than that of adriamycin. The putative mechanism of antitumor action in apoptotic cell death was cell cycle arrest in the G0/G1 phase by compounds 5k, 5v, 5m, 6c, and 6f in HeLa cells. These compounds showed relatively high cytotoxicity in this cell type. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.061

文献信息

• Synthesis and cytotoxicity of 2-phenylquinazolin-4(3H)-one derivatives
  作者：Hee-Kyung Rhee、Ji Hye Yoo、Eunyoung Lee、Young Joo Kwon、Hang-Rhan Seo、Yun-Sil Lee、Hea-Young Park Choo

  DOI：10.1016/j.ejmech.2011.05.061

  日期：2011.9

  Thirty 2-phenylquinazolin-4(3H)-one derivatives were prepared and their cytotoxic activities were tested in five human tumor cell lines. Some compounds (5e, 5k, 5t, 6c and 6f) showed relatively high cytotoxic activity. Especially, compound 6c showed the most cytotoxicity against all cell lines tested among the synthesized derivatives, and the inhibitory activity of 6c against HeLa cell was higher than that of adriamycin. The putative mechanism of antitumor action in apoptotic cell death was cell cycle arrest in the G0/G1 phase by compounds 5k, 5v, 5m, 6c, and 6f in HeLa cells. These compounds showed relatively high cytotoxicity in this cell type. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Discovery of HDAC6, HDAC8, and 6/8 Inhibitors and Development of Cell-Based Drug Screening Models for the Treatment of TGF-β-Induced Idiopathic Pulmonary Fibrosis
  作者：Wei-Chieh Yu、Tsung-Yu Yeh、Chih-Hung Ye、Patrick Chun Theng Chong、Yi-Hsun Ho、Dorothy Kazuno So、Kah Yi Yap、Guan-Ru Peng、Chi-Hsuan Shao、Ajit Dhananjay Jagtap、Ji-Wang Chern、Chen-Si Lin、Shau-Ping Lin、Shuei-Liong Lin、Shu-Han Yu、Chao-Wu Yu

  DOI：10.1021/acs.jmedchem.3c00644

  日期：2023.8.10

  pulmonary fibrosis is incurable, and its progression is difficult to control and thus can lead to pulmonary deterioration. Pan-histone deacetylase inhibitors such as SAHA have shown potential for modulating pulmonary fibrosis yet with off-target effects. Therefore, selective HDAC inhibitors would be beneficial for reducing side effects. Toward this goal, we designed and synthesized 24 novel HDAC6, HDAC8

  特发性肺纤维化无法治愈，其进展难以控制，因此可导致肺部恶化。泛组蛋白脱乙酰酶抑制剂（例如 SAHA）已显示出调节肺纤维化的潜力，但具有脱靶效应。因此，选择性HDAC抑制剂将有利于减少副作用。为了实现这一目标，我们设计并合成了24种新型HDAC6、HDAC8或双HDAC6/8抑制剂，并建立了两阶段筛选平台来快速筛选有效减轻TGF-β诱导的肺纤维化的HDAC抑制剂。第一阶段包括小鼠 NIH-3T3 成纤维细胞预筛选，并产生了 5 次命中。在第二阶段，使用人肺成纤维细胞 (HPF)，并对 5 个命中中的 4 个进行了 caco-2 渗透性和肝微粒体稳定性测试，以给出两个潜在的线索：J27644 (15 )和20。这种新颖的两阶段筛选平台将加速 HDAC 抑制剂的发现并降低开发成本，以减轻 TGF-β 诱导的肺纤维化。