2-chloro-N-(4-chlorophenyl)pyrimidin-4-amine | 260045-63-4

• 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-(4-chlorophenyl)pyrimidin-4-amine
• CAS: 260045-63-4
• 化学式: C₁₀H₇Cl₂N₃
• 分子量: 240.092
• InChiKey: RJCWFUDISUOTMZ-UHFFFAOYSA-N

物化性质

• 沸点：
  428.3±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)：
  3.7
• 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-(4-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 、 对氯苯胺 在 N,N-二异丙基乙胺 作用下， 以 叔丁醇 为溶剂， 以94%的产率得到2-chloro-N-(4-chlorophenyl)pyrimidin-4-amine
  参考文献：
  名称：

  Synthesis of piperazine tethered 4-aminoquinoline-pyrimidine hybrids as potent antimalarial agents

  摘要：

  Piperazine连接的4-氨基喹啉-嘧啶杂合物被合成并针对疟原虫的W2和D6菌株进行体外抗疟活性评价。

  DOI：

  10.1039/c4ra02276a

文献信息

• De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus
  作者：Emilse S. Leal、Natalia S. Adler、Gabriela A. Fernández、Leopoldo G. Gebhard、Leandro Battini、Maria G. Aucar、Mariela Videla、María Eugenia Monge、Alejandro Hernández de los Ríos、John Alejandro Acosta Dávila、María L. Morell、Sandra M. Cordo、Cybele C. García、Andrea V. Gamarnik、Claudio N. Cavasotto、Mariela Bollini

  DOI：10.1016/j.ejmech.2019.111628

  日期：2019.11

  the best candidate, from which one synthesized compound displayed micromolar activity. Molecular dynamics-based optimization was performed on this hit, and thirty derivatives were designed in silico, synthesized and evaluated on their capacity to inhibit dengue virus entry into the host cell. Four compounds were found to be potent antiviral compounds in the low-micromolar range. The assessment of drug-like

  登革热是一种由蚊子传播的病毒性疾病，已成为全球主要的公共卫生问题。该疾病具有广泛的临床表现，从轻度感冒样疾病到更严重的出血性登革热和登革热休克综合症。目前，尚无用于治疗该疾病的批准药物或有效疫苗。包膜蛋白（E）是病毒体表面的主要成分。该蛋白在病毒进入过程中起关键作用，构成了抗病毒药物开发的诱人靶标。E蛋白的晶体结构表明存在被洗涤剂正辛基-β-d-葡萄糖苷（β-OG）占据的疏水口袋。该口袋位于结构域I和II之间的铰链区，对于病毒体与宿主细胞融合所需的低pH触发构象重排很重要。针对与E结合并充当病毒进入抑制剂的新型分子的设计，我们通过从头开始在疏水位点（β-OG）内“生长”分子进行了从头设计方法。从产生的24万多个小分子中，选择2,4个嘧啶支架作为最佳候选物，从中一个合成的化合物显示出微摩尔活性。为此，对分子进行了基于分子动力学的优化，并通过计算机设计了三十种衍生物，对其进行了合成并对其抑制登
• Design, synthesis and biological evaluation of pyrimidine-based derivatives as VEGFR-2 tyrosine kinase inhibitors
  作者：Wuji Sun、Shengquan Hu、Shubiao Fang、Hong Yan

  DOI：10.1016/j.bioorg.2018.04.005

  日期：2018.8

  of the VEGFR-2 signaling pathway has already become an attractive approach for cancer therapy. In this study, a novel pyrimidine-based derivative 7j was designed as lead compound, and three series of potent VEGFR-2 inhibitors were synthesized and biologically evaluated against A549 and HepG2 cell lines. Compounds 7d, 9s and 13n exhibited superior inhibitory activities against A549 cell with IC50 ranged

  血管内皮生长因子受体2（VEGFR-2）在肿瘤血管生成中起着至关重要的作用，而抑制VEGFR-2信号通路已经成为癌症治疗的一种有吸引力的方法。在这项研究中，设计了一种新型的基于嘧啶的衍生物7j作为前导化合物，合成了三组有效的VEGFR-2抑制剂，并针对A549和HepG2细胞系进行了生物学评估。与Pazopanib（IC 50）相比，化合物7d，9s和13n对A549细胞的IC 50为9.19至13.17μM，对HepG2细胞的IC 50为11.94至18.21μM。 = 21.18和36.66μM）。另外，进行了分子对接研究以研究目标化合物与VEGFR-2之间的结合能力和结合方式。
• Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors
  作者：Yu Xu、Shu-Yi Hao、Xiu-Juan Zhang、Wen-Bo Li、Xue-Peng Qiao、Zi-Xiao Wang、Shi-Wu Chen

  DOI：10.1016/j.bmcl.2019.126885

  日期：2020.2

  as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, respectively. Furthermore, compound 12a induced apoptosis by upregulated the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the molecular docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics

  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，
• 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.
• One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties
  作者：Wei-Feng Ma、Hai-Kui Yang、Meng-Jin Hu、Qian Li、Tian-Zhu Ma、Zhong-Zhen Zhou、Rui-Yuan Liu、Wen-Wei You、Pei-Liang Zhao

  DOI：10.1016/j.ejmech.2014.07.017

  日期：2014.9

  A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesized via an efficient one-pot methodology. The bioassay tests demonstrated that compounds 27 and 28 displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-MB-231 and MCF-7) than positive control fluorouracil. Particularly, compound 28 showed a two-fold improvement compared to fluorouracil in inhibiting MDA-MB-231 and A549 cell proliferation with IC50 values of 7.46 and 12.78 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 28 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in MDA-MB-231 cells.