2-chloro-4-(3-nitrophenoxy)pyrimidine | 1282669-97-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-(3-nitrophenoxy)pyrimidine
• CAS: 1282669-97-9
• 化学式: C₁₀H₆ClN₃O₃
• mdl: MFCD17932833
• 分子量: 251.629
• InChiKey: MNQTUCOUBHCMEC-UHFFFAOYSA-N

物化性质

• 沸点：
  426.3±25.0 °C(Predicted)
• 密度：
  1.477±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(3-nitrophenoxy)pyrimidine 在 platinum(IV) oxide 、 氢气 、 三氟乙酸 作用下， 以 甲醇 、 仲丁醇 为溶剂， 生成 4-(3-aminophenoxy)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of selective irreversible inhibitors for EGFR-T790M

  摘要：

  Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.036
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 间硝基苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以87.4%的产率得到2-chloro-4-(3-nitrophenoxy)pyrimidine
  参考文献：
  名称：

  Optimization of WZ4003 as NUAK inhibitors against human colorectal cancer

  摘要：

  DOI：

  10.1016/j.ejmech.2020.113080

文献信息

• Pyrimidine containing epidermal growth factor receptor kinase inhibitors: Synthesis and biological evaluation
  作者：Gaurav Joshi、Himanshu Nayyar、Sourav Kalra、Praveen Sharma、Anjana Munshi、Sandeep Singh、Raj Kumar

  DOI：10.1111/cbdd.13027

  日期：2017.11

  Structure‐based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a–d are reported. The compounds (1a–d) inhibited the EGFR kinase activity in vitro with IC50 range 740 nm to 3 μm. mRNA expression of EGFR downstream target genes, that is twist, c‐fos and aurora were found to be altered upon treatment with compounds 1a–d. The compounds 1a–d exhibited excellent anticancer activity at low micromolar level (3.2–9 μm) in lung, colon and breast cancer cell lines. Furthermore, compounds induced the alteration in mitochondrial membrane potential and reactive oxygen species level and. Selected compound 1b was found to increase sub‐G1 population indicative of cell death, the mode of cell death was apoptotic as evident from Annexin V verses propidium iodide assay. Molecular modelling further helped to investigate the binding recognition pattern of the compounds in ATP binding EGFR domain similar to erlotinib and dissimilar to WZ4002.
• Discovery of selective irreversible inhibitors for EGFR-T790M
  作者：Wenjun Zhou、Dalia Ercan、Pasi A. Jänne、Nathanael S. Gray

  DOI：10.1016/j.bmcl.2010.12.036

  日期：2011.1

  Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.
• Optimization of WZ4003 as NUAK inhibitors against human colorectal cancer
  作者：Huali Yang、Xiaobing Wang、Cheng Wang、Fucheng Yin、Lailiang Qu、Cunjian Shi、Jinhua Zhao、Shang Li、Limei Ji、Wan Peng、Heng Luo、Maosheng Cheng、Lingyi Kong

  DOI：10.1016/j.ejmech.2020.113080

  日期：2021.1