4-(quinolin-4-ylamino)benzoic acid | 133041-90-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(quinolin-4-ylamino)benzoic acid
• CAS: 133041-90-4
• 化学式: C₁₆H₁₂N₂O₂
• 分子量: 264.283
• InChiKey: CFLOXQDGUDYNSN-UHFFFAOYSA-N

物化性质

• 熔点：
  314-316 °C (decomp)
• 沸点：
  480.6±30.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(quinolin-4-ylamino)benzoic acid 在 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 N-[4-[3-[4,5-bis(hydroxymethyl)-2-methylsulfanylimidazol-1-yl]propyl]phenyl]-4-(quinolin-4-ylamino)benzamide
  参考文献：
  名称：

  DNA定向烷基化剂。7.双（羟甲基）-和双（氨基甲酸酯）取代的吡咯嗪和咪唑的合成，DNA相互作用和抗肿瘤活性。

  摘要：

  合成了一系列双（羟甲基）取代的咪唑，硫代咪唑和吡咯嗪和相关的双（氨基甲酸酯），它们与9-苯胺基cr啶（嵌入）或4-（4-喹啉基氨基）苯甲酰胺（次要沟结合）载体相连。评估序列特异性DNA烷基化和细胞毒性。咪唑和硫代咪唑类似物的制备方法是：首先合成[（4-氨基苯基）烷基]咪唑-，硫代咪唑-或吡咯嗪二羧酸酯，将它们与所需的载体偶联，然后还原得到所需的双（羟甲基）烷基化部分。吡咯烷嗪是反应性最高的烷基化剂，其次是硫代咪唑，而咪唑则没有反应性。通过琼脂糖凝胶电泳测量，吡咯嗪和一些硫代咪唑交联的DNA。链切割试验表明，没有化合物在质粒gpt2Eco的gpt区域的嘌呤N7或N3位点反应，但聚合酶终止试验显示在富C区域的G-烷基化模式。相应的硫代咪唑双（氨基甲酸酯）比双（羟甲基）吡咯烷嗪具有更高的选择性，在PCR终止试验中在5'-NCCN，5'-NGCN和5'-NCGN序列处具有高强度条带（指示嵌段位点）

  DOI：

  10.1021/jm9803119
• 作为产物：
  描述：

  4-氯喹啉 在 盐酸 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 4-(quinolin-4-ylamino)benzoic acid
  参考文献：
  名称：

  Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells

  摘要：

  DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound 5 as a potent non-nucleoside DNMTi that is also selective toward other Ado Met-dependent protein methyltransferases. Compound 5 was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, 5 inhibited cell growth, whereas related compound 2 showed high cell differentiation. To the best of our knowledge, 2 and 5 are the first non-nucleoside DNMTi tested in a cancer stem cell line.

  DOI：

  10.1021/jm4012627

文献信息

• Novel Quinoline Compounds Active in Cancer Cells through Coupled DNA Methyltransferase Inhibition and Degradation
  作者：Clemens Zwergel、Rossella Fioravanti、Giulia Stazi、Federica Sarno、Cecilia Battistelli、Annalisa Romanelli、Angela Nebbioso、Eduarda Mendes、Alexandra Paulo、Raffaele Strippoli、Marco Tripodi、Dany Pechalrieu、Paola B. Arimondo、Teresa De Luca、Donatella Del Bufalo、Daniela Trisciuoglio、Lucia Altucci、Sergio Valente、Antonello Mai

  DOI：10.3390/cancers12020447

  日期：——

  DNA methyltransferases (DNMTs) play a relevant role in epigenetic control of cancer cell survival and proliferation. Since only two DNMT inhibitors (azacitidine and decitabine) have been approved to date for the treatment of hematological malignancies, the development of novel potent and specific inhibitors is urgent. Here we describe the design, synthesis, and biological evaluation of a new series of compounds acting at the same time as DNMTs (mainly DNMT3A) inhibitors and degraders. Tested against leukemic and solid cancer cell lines, 2a–c and 4a–c (the last only for leukemias) displayed up to submicromolar antiproliferative activities. In HCT116 cells, such compounds induced EGFP gene expression in a promoter demethylation assay, confirming their demethylating activity in cells. In the same cell line, 2b and 4c chosen as representative samples induced DNMT1 and -3A protein degradation, suggesting for these compounds a double mechanism of DNMT3A inhibition and DNMT protein degradation.

  DNA甲基转移酶（DNMTs）在癌细胞生存和增殖的表观遗传控制中发挥着重要作用。由于目前只有两种DNMT抑制剂（阿扎胞苷和地西他滨）已被批准用于治疗血液恶性肿瘤，因此开发新的有效和特异性抑制剂非常紧迫。本研究描述了一系列新化合物的设计、合成和生物评价，这些化合物同时作为DNMTs（主要是DNMT3A）的抑制剂和降解剂。在白血病和实体癌细胞系中进行测试，2a-c和4a-c（最后仅用于白血病）显示出亚微米级的抗增殖活性。在HCT116细胞中，这些化合物在启动子去甲基化试验中诱导EGFP基因表达，证实它们在细胞中的去甲基化活性。在同一细胞系中，选择2b和4c作为代表样品，诱导DNMT1和-3A蛋白降解，表明这些化合物具有DNMT3A抑制和DNMT蛋白降解的双重机制。
• Design, Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents
  作者：Chao Zhang、Yun-Sang Tang、Chu-Ren Meng、Jing Xu、De-Liang Zhang、Jian Wang、Er-Fang Huang、Pang-Chui Shaw、Chun Hu

  DOI：10.3390/ijms23116307

  日期：——

  4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay

  本研究设计合成了一系列4-[(quinolin-4-yl)amino]苯甲酰胺衍生物作为新型抗流感药物。进行细胞毒性试验、细胞病变效应试验和噬斑抑制试验以评估目标化合物的抗流感病毒 A/WSN/33 (H1N1) 活性。目标化合物G07在细胞病变效应试验 (EC 50 = 11.38 ± 1.89 µM) 和噬菌斑抑制试验 (IC 50 = 0.23 ± 0.15 µM)中均表现出显着的抗流感病毒 A/WSN/33 (H1N1) 活性。G07对其他三种不同的流感病毒株 A/PR/8 (H1N1)、A/HK/68 (H3N2) 和乙型流感病毒也表现出显着的抗流感病毒活性。根据核糖核蛋白重组试验结果，G07与核糖核蛋白相互作用良好，在100 µM时抑制率为80.65%。此外，根据最佳药效团 Hypo1 预测的 PA-PB1 抑制活性， G07表现出显着的活性靶标 RNA 聚合酶 PA-PB1
• Naphthyl Derivatives as Inhibitors of Beta-Amyloid Aggregation
  申请人：Minetti Patrizia

  公开号：US20080255232A1

  公开（公告）日：2008-10-16

  Compounds useful in the treatment of disorders characterized by deposits of amyloid aggregates are herein described together with pharmaceutical compounds containing the same. In particular the compounds of the present invention are those having the Formula (I) as reported below, where the radicals have the meaning indicated in the description.

  本文描述了用于治疗由淀粉样聚集物沉积所特征化的疾病的化合物，以及含有相同化合物的药物化合物。特别是，本发明的化合物是具有下面报告的式（I）的化合物，其中基团具有描述中所示的含义。
• QUINOLINE DERIVATIVES FOR MODULATING DNA METHYLATION
  申请人：Phiasivongsa Pasit

  公开号：US20090285772A1

  公开（公告）日：2009-11-19

  Quinoline derivatives, particularly 4-anilinoquinoline derivatives, are provided. Such quinoline derivatives can be used for modulation of DNA methylation, such as effective inhibition of methylation of cytosine at the C-5 position, for example via selective inhibition of DNA methyltransferase DNMT1. Methods for synthesizing numerous 4-anilinoquinoline derivatives and for modulating DNA methylation are provided. Also provided are methods for formulating and administering these compounds or compositions to treat conditions such as cancer and hematological disorders.

  提供了喹啉衍生物，特别是4-苯胺基喹啉衍生物。这样的喹啉衍生物可用于调节DNA甲基化，例如通过选择性抑制DNA甲基转移酶DNMT1，有效抑制C-5位置的胞嘧啶甲基化。提供了合成多种4-苯胺基喹啉衍生物和调节DNA甲基化的方法。还提供了制剂和给药这些化合物或组合物以治疗癌症和血液疾病的方法。
• 含有酰胺基团的喹啉类化合物及其制备与应用
  申请人：沈阳药科大学

  公开号：CN114853670A

  公开（公告）日：2022-08-05

  本发明的含有酰胺基团的喹啉类化合物及其制备与应用，属于医药技术领域。具体为结构通式如下(I)所述的含有酰胺基团的喹啉类化合物、其前体药物和药物活性代谢物和药学上可接受的盐，其中R如权利要求书和说明书中所述，相应的含有酰胺基团的喹啉类化合物以及该类化合物药学上适用的酸和药学上可接受的盐可以与现有药物合并或单独使用作为流感病毒抑制剂，用于治疗流感，尤其是对各种A型流感具有较好的疗效。