N-(4-nitrophenyl)quinolin-4-amine | 205985-60-0

• 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: N-(4-nitrophenyl)quinolin-4-amine
• CAS: 205985-60-0
• 化学式: C₁₅H₁₁N₃O₂
• 分子量: 265.271
• InChiKey: ZEMSLUWBYSDAFB-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  457.056±30.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.363±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-nitrophenyl)quinolin-4-amine 在 盐酸 、 stannous chloride dihydrate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 4-(quinolin-4-ylamino)-N-(4-(quinolin-4-ylamino)phenyl)benzamide
  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
• 作为产物：
  描述：

  4-氯喹啉 、 4-硝基苯胺 在 盐酸 作用下， 以 乙二醇乙醚 、 水 为溶剂， 反应 3.0h， 以47%的产率得到N-(4-nitrophenyl)quinolin-4-amine
  参考文献：
  名称：

  基于喹啉的 SGI-1027 的 4-氨基-N-（4-氨基苯基）苯甲酰胺类似物作为 DNA 甲基化抑制剂的设计、合成和生物学评价

  摘要：

  喹啉衍生物 SGI-1027 ( N- (4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl)-4-(quinolin-4-ylamino)benzamide) 于 2009 年首次被描述为 DNA 甲基转移酶的有效抑制剂(DNMT) 1、3A 和 3B。基于分子建模研究，使用溶血性嗜血杆菌胞嘧啶-5 DNA 甲基转移酶 (MHhaI C5 DNMT)的晶体结构进行，这表明 SGI-1027 的喹啉和氨基吡啶部分对于与底物和蛋白质的相互作用很重要，我们设计了并合成了25种衍生物。其中，四种化合物-即衍生物12，16，31和32——表现出与母体化合物相当的活性。进一步的评估表明，这些化合物对人 DNMT3A 的作用比对人 DNMT1 的作用更强，并能在白血病 KG-1 细胞中诱导由甲基化巨细胞病毒 (CMV) 启动子控制的报告基因的重新表达。这些化合物在微摩尔范围内对白血病

  DOI：

  10.1002/cmdc.201300420

文献信息

• Design, Synthesis and Biological Evaluation of 4-Amino-<i>N</i>-(4-aminophenyl)benzamide Analogues of Quinoline-Based SGI-1027 as Inhibitors of DNA Methylation
  作者：Elodie Rilova、Alexandre Erdmann、Christina Gros、Véronique Masson、Yannick Aussagues、Valérie Poughon-Cassabois、Arumugam Rajavelu、Albert Jeltsch、Yoann Menon、Natacha Novosad、Jean-Marc Gregoire、Stéphane Vispé、Philippe Schambel、Fréderic Ausseil、François Sautel、Paola B. Arimondo、Frédéric Cantagrel

  DOI：10.1002/cmdc.201300420

  日期：2014.3

  derivative SGI‐1027 (N‐(4‐(2‐amino‐6‐methylpyrimidin‐4‐ylamino)phenyl)‐4‐(quinolin‐4‐ylamino)benzamide) was first described in 2009 as a potent inhibitor of DNA methyltransferase (DNMT) 1, 3A and 3B. Based on molecular modeling studies, performed using the crystal structure of Haemophilus haemolyticus cytosine‐5 DNA methyltransferase (MHhaI C5 DNMT), which suggested that the quinoline and the aminopyridimine

  喹啉衍生物 SGI-1027 ( N- (4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl)-4-(quinolin-4-ylamino)benzamide) 于 2009 年首次被描述为 DNA 甲基转移酶的有效抑制剂(DNMT) 1、3A 和 3B。基于分子建模研究，使用溶血性嗜血杆菌胞嘧啶-5 DNA 甲基转移酶 (MHhaI C5 DNMT)的晶体结构进行，这表明 SGI-1027 的喹啉和氨基吡啶部分对于与底物和蛋白质的相互作用很重要，我们设计了并合成了25种衍生物。其中，四种化合物-即衍生物12，16，31和32——表现出与母体化合物相当的活性。进一步的评估表明，这些化合物对人 DNMT3A 的作用比对人 DNMT1 的作用更强，并能在白血病 KG-1 细胞中诱导由甲基化巨细胞病毒 (CMV) 启动子控制的报告基因的重新表达。这些化合物在微摩尔范围内对白血病
• PHENYL N-MUSTARD LINKED TO DNA-AFFINIC MOLECULES OR WATER-SOLUBLE ARYL RINGS, METHOD AND THEIR USE AS CANCER THERAPEUTIC AGENTS
  申请人：SU Tsann-Long

  公开号：US20130178494A1

  公开（公告）日：2013-07-11

  The present disclosure relates to new DNA-directed alkylating agents and water-soluble N-mustard agents with improved chemical stability and anti-tumor therapeutic efficacy.

  本公开涉及新的DNA定向烷基化剂和具有改善化学稳定性和抗肿瘤治疗效果的水溶性N-芥子剂。
• US9193687B2
  申请人：——

  公开号：US9193687B2

  公开（公告）日：2015-11-24
• Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells
  作者：Sergio Valente、Yiwei Liu、Michael Schnekenburger、Clemens Zwergel、Sandro Cosconati、Christina Gros、Maria Tardugno、Donatella Labella、Cristina Florean、Steven Minden、Hideharu Hashimoto、Yanqi Chang、Xing Zhang、Gilbert Kirsch、Ettore Novellino、Paola B. Arimondo、Evelina Miele、Elisabetta Ferretti、Alberto Gulino、Marc Diederich、Xiaodong Cheng、Antonello Mai

  DOI：10.1021/jm4012627

  日期：2014.2.13

  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.