2-chloro-N-(2-chlorophenyl)pyrimidin-4-amine | 260046-05-7

• 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: 2-chloro-N-(2-chlorophenyl)pyrimidin-4-amine
• CAS: 260046-05-7
• 化学式: C₁₀H₇Cl₂N₃
• 分子量: 240.092
• InChiKey: SHAQYVPOBVUFQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  404.7±25.0 °C(Predicted)
• 密度：
  1.447±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 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：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(2-chlorophenyl)pyrimidin-4-amine 在 potassium carbonate 作用下， 以 二甲基亚砜 、 正丁醇 为溶剂， 生成
  参考文献：
  名称：

  细胞周期蛋白依赖性激酶4抑制剂可治疗癌症。第2部分：取代的2,4-双苯胺嘧啶的鉴定和优化。

  摘要：

  通过化学修饰和X射线晶体学，我们确定了2,4-双苯胺嘧啶是CDK4的有效抑制剂。在此，我们描述了该系列的优化。

  DOI：

  10.1016/s0960-894x(03)00203-8
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 邻氯苯胺 在 盐酸 作用下， 以 水 为溶剂， 反应 24.0h， 以60%的产率得到2-chloro-N-(2-chlorophenyl)pyrimidin-4-amine
  参考文献：
  名称：

  发现新的2,4-二取代的嘧啶作为极光激酶抑制剂。

  摘要：

  为了探索新型的Aurora激酶抑制剂，设计，合成和评估了一系列新型的2,4-二取代的嘧啶类，其对一组癌细胞系（A549，HCT-116和MCF-7）的体外抗增殖活性。其中，化合物12a对A549（IC50 = 12.05±0.45μM），HCT-116（IC50 = 1.31±0.41μM）和MCF-7（IC50 = 20.53±6.13μM）细胞表现出中等至高的抗增殖活性，以及Aurora A和Aurora B的抑制活性，其IC50值分别为309 nM和293 nM。此外，化合物12a通过上调HCT-116细胞中的促凋亡蛋白Bax和降低抗凋亡蛋白Bcl-xl来诱导凋亡。而且，分子对接研究表明，化合物12a与Aurora A和Aurora B具有良好的结合模式，生物信息学预测发现，使用SwissADME，化合物12a具有良好的药物相似性。综上所述，这些结果表明12a可能是潜在的抗癌化合物，

  DOI：

  10.1016/j.bmcl.2019.126885

文献信息

• AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
  申请人：Sebti Said M.

  公开号：US20140057913A1

  公开（公告）日：2014-02-27

  Described herein are inhibitors of Aurora kinase and their use in the treatment of cancer. Methods of screening for selective inhibitors of Aurora kinases are also disclosed.

  本文描述了Aurora激酶的抑制剂及其在癌症治疗中的应用。还公开了筛选选择性抑制Aurora激酶的方法。
• Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1<i>H</i>)-pyrazole Derivatives as JAKs Inhibitors
  作者：Xuewu Liang、Jie Zang、Mengyuan Zhu、Qianwen Gao、Binghe Wang、Wenfang Xu、Yingjie Zhang

  DOI：10.1021/acsmedchemlett.6b00247

  日期：2016.10.13

  Abnormalities in the JAK/STAT signaling pathway lead to many diseases such as immunodeficiency, inflammation, and cancer. Herein, we designed and synthesized a series of 4-amino-(1H)-pyrazole derivatives as potent JAKs inhibitors for cancer treatment. Results from in vitro protein kinase inhibition experiments indicated that compounds 3a-f and 11b are potent JAKs inhibitors. For example, the IC50 values of compound 3f against JAK1, JAK2, and JAK3 were 3.4, 2.2, and 3.5 nM, respectively. In cell culture experiments, compound 3f showed potent antiproliferative activity against various cell lines (PC-3, HEL, K562, MCF-7, and MOLT4) at low micromolar levels, while compound 11b showed selective cytotoxicity at submicromolar levels against HEL (IC50: 0.35;, mu M) and K562 (IC50: 0.37 mu M) cell lines. It is worth noting that both 3f and 11b showed more potent antiproliferative activities than the approved JAKs inhibitor Ruxolitinib.
• [EN] AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF<br/>[FR] INHIBITEURS DE KINASE AURORA ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER
  申请人：H LEE MOFFITT CANCER CT AND RES INST

  公开号：WO2012135641A3

  公开（公告）日：2012-12-27
• Development of <i>o</i>-Chlorophenyl Substituted Pyrimidines as Exceptionally Potent Aurora Kinase Inhibitors
  作者：Harshani R. Lawrence、Mathew P. Martin、Yunting Luo、Roberta Pireddu、Hua Yang、Harsukh Gevariya、Sevil Ozcan、Jin-Yi Zhu、Robert Kendig、Mercedes Rodriguez、Roy Elias、Jin Q. Cheng、Saïd M. Sebti、Ernst Schonbrunn、Nicholas J. Lawrence

  DOI：10.1021/jm300334d

  日期：2012.9.13

  The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC50 = 6.1 +/- 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallography studies revealed that compound 1 is a type I inhibitor that binds the Aurora kinase active site in a DFG-in conformation. Structure-activity guided replacement of the A-ring carboxylic acid with halogens and incorporation of fluorine at the pyrimidine 5-position led to highly potent inhibitors of Aurora A that bind in a DFG-out conformation. B-Ring modifications were undertaken to improve the solubility and cell permeability. Compounds such as 9m with water-solubilizing moieties at the para position of the B-ring inhibited the autophosphorylation of Aurora A in MDA-MB-468 breast cancer cells.
• US9249124B2
  申请人：——

  公开号：US9249124B2

  公开（公告）日：2016-02-02