2-chloro-4-(2-fluoro-4-nitrophenoxy)pyrimidine | 868733-43-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-(2-fluoro-4-nitrophenoxy)pyrimidine
• CAS: 868733-43-1
• 化学式: C₁₀H₅ClFN₃O₃
• 分子量: 269.619
• InChiKey: GCVYKTTZMWBXIF-UHFFFAOYSA-N

物化性质

• 沸点：
  399.9±32.0 °C(Predicted)
• 密度：
  1.545±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 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：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(2-fluoro-4-nitrophenoxy)pyrimidine 在 铁粉 、 氯化铵 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 4-(4-amino-2-fluorophenoxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity

  摘要：

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.

  DOI：

  10.1021/ml500066m
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 2-氟-4-硝基苯酚 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 12.0h， 以35%的产率得到2-chloro-4-(2-fluoro-4-nitrophenoxy)pyrimidine
  参考文献：
  名称：

  合成和评估一系列作为II型c-Met抑制剂的吡啶和嘧啶衍生物。

  摘要：

  在这项研究中，设计，合成和生物学评估了一系列新颖的吡啶和含嘧啶的衍生物的c-Met抑制活性。在生物学评估中，一半的目标化合物表现出中等至有效的c-Met抑制活性。其中，值得注意的是，化合物13d不仅显示出最强的c-Met抑制能力，而且显示出出色的抗增殖活性（针对EBC-1细胞系的IC50 = 127nM）以及可接受的激酶选择性谱。此外，蛋白质印迹分析表明13d以剂量依赖的方式抑制了EBC-1细胞中的c-Met磷酸化，并在0.1mM时被完全消除。所有这些实验结果表明，13d可以作为抗癌药物开发的有前途的先导化合物。

  DOI：

  10.1016/j.bmc.2017.04.003

文献信息

• Monocyclic heterocycles as kinase inhibitors
  申请人：Borzilleri M. Robert

  公开号：US20050245530A1

  公开（公告）日：2005-11-03

  The present invention is directed to compounds having the formula and methods for using them for the treatment of cancer.

  本发明涉及具有以下公式化合物的用途以及使用它们治疗癌症的方法。
• Synthesis and evaluation of a series of pyridine and pyrimidine derivatives as type II c-Met inhibitors
  作者：Yanmei Zhao、Jiankang Zhang、Rangxiao Zhuang、Ruoyu He、Jianjun Xi、Xuwang Pan、Yidan Shao、Jinming Pan、Jingjing Sun、Zhaobin Cai、Shourong Liu、Weiwei Huang、Xiaoqing Lv

  DOI：10.1016/j.bmc.2017.04.003

  日期：2017.6

  In this study, a series of novel pyridine and pyrimidine-containing derivatives were designed, synthesized and biologically evaluated for their c-Met inhibitory activities. In the biological evaluation, half of the target compounds exhibited moderate to potent c-Met inhibitory activities. Among which, it is noteworthy that compounds 13d not only showed most potent c-Met inhibitory potency but also

  在这项研究中，设计，合成和生物学评估了一系列新颖的吡啶和含嘧啶的衍生物的c-Met抑制活性。在生物学评估中，一半的目标化合物表现出中等至有效的c-Met抑制活性。其中，值得注意的是，化合物13d不仅显示出最强的c-Met抑制能力，而且显示出出色的抗增殖活性（针对EBC-1细胞系的IC50 = 127nM）以及可接受的激酶选择性谱。此外，蛋白质印迹分析表明13d以剂量依赖的方式抑制了EBC-1细胞中的c-Met磷酸化，并在0.1mM时被完全消除。所有这些实验结果表明，13d可以作为抗癌药物开发的有前途的先导化合物。
• Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold
  作者：Wei Zhang、Jing Ai、Dakuo Shi、Xia Peng、Yinchun Ji、Jian Liu、Meiyu Geng、Yingxia Li

  DOI：10.3390/molecules19022655

  日期：——

  A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6−81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.57−16 μM.

  一系列包含新型3-羧基哌啶-2-酮骨架的化合物基于引导结构BMS-777607进行设计、合成并评估其对c-Met激酶的抑制作用及对MKN45癌细胞系的细胞毒性。结果表明，五种化合物对c-Met展现出显著的抑制效果，IC50值为8.6−81 nM，而四种化合物对MKN45细胞增殖表现出强劲的抑制活性，IC50在0.57−16 μM之间。
• Design, synthesis and biological evaluation of biphenylurea derivatives as VEGFR-2 kinase inhibitors (II)
  作者：Guo-Rui Gao、Meng-Yuan Li、Yong-Cong Lv、Su-Fen Cao、Lin-Jiang Tong、Li-Xin Wei、Jian Ding、Hua Xie、Wen-Hu Duan

  DOI：10.1016/j.cclet.2015.10.004

  日期：2016.2

  Inhibition of VEGFR-2 signaling pathway is one of the most promising approaches for the treatment of cancer. In this paper, we reported the design, synthesis, and biological evaluation of a series of biphenylurea derivatives as VEGFR-2 inhibitors. Among these compounds, 39 exhibited potent inhibitory activity against VEGFR-2 both in vitro and in vivo. The antiangiogenesis activity of 39 was further

  抑制VEGFR-2信号通路是最有前途的癌症治疗方法之一。在本文中，我们报道了一系列作为VEGFR-2抑制剂的联苯脲衍生物的设计，合成和生物学评估。在这些化合物中，有39种在体外和体内均表现出对VEGFR-2的有效抑制活性。管形成试验和鸡绒膜尿囊膜试验均进一步证实了39的抗血管生成活性。
• KINASE INHIBITORS AND USES THEREOF
  申请人：Raeppel Stephane

  公开号：US20080255155A1

  公开（公告）日：2008-10-16

  This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds, compositions and methods for the inhibition of kinase activity. The invention also provides compounds, compositions and methods for treating cell proliferative diseases and conditions.

  本发明涉及抑制蛋白酪氨酸激酶活性的化合物。具体而言，本发明涉及抑制激酶活性的化合物、组合物和方法。本发明还提供用于治疗细胞增殖性疾病和病症的化合物、组合物和方法。