4,6-dichloro-N-(2-fluorophenyl)-1,3,5-triazin-2-amine | 140195-45-5

• 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: 4,6-dichloro-N-(2-fluorophenyl)-1,3,5-triazin-2-amine
• CAS: 140195-45-5
• 化学式: C₉H₅Cl₂FN₄
• 分子量: 259.07
• InChiKey: RCQUDRZOYRPIMA-UHFFFAOYSA-N

物化性质

• 沸点：
  430.3±47.0 °C(Predicted)
• 密度：
  1.586±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 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：
  50.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-N-(2-fluorophenyl)-1,3,5-triazin-2-amine 在 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-(4-(2-fluorophenylamino)-6-(4-methoxyphenylamino)-1,3,5-triazin-2-yl)piperazin-1-yl)nicotinonitrile
  参考文献：
  名称：

  Development of cyanopyridine–triazine hybrids as lead multitarget anti-Alzheimer agents

  摘要：

  A series of new cyanopyridine-triazine hybrids were designed, synthesized and screened as multitargeted anti-Alzheimer's agents. These molecules were designed while using computational techniques and were synthesized via a feasible concurrent synthetic route. Inhibition potencies of synthetic compounds 4a-4h against cholinesterases, A beta(1-42) disaggregation, oxidative stress, cytotoxicity, and neuroprotection against A beta(1-42)-induced toxicity of the synthesized compounds were evaluated. Compounds 4d and 4h showed promising inhibitory activity on acetylcholinesterase (AChE) with IC50 values 0.059 and 0.080 mu M, respectively, along with good inhibition selectivity against AChE over butyrylcholinesterase (BuChE). Molecular modelling studies revealed that these compounds interacted simultaneously with the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The mixed type inhibition of compound 4d further confirmed their dual binding nature in kinetic studies. Furthermore, the results from neuroprotection studies of most potent compounds 4d and 4h indicate that these derivatives can reduce neuronal death induced by H2O2-mediated oxidative stress and A beta(1-42) induced cytotoxicity. In addition, in silico analysis of absorption, distribution, metabolism and excretion (ADME) profile of best compounds 4d and 4h revealed that they have drug like properties. Overall, these cyanopyridine-triazine hybrids can be considered as a candidate with potential impact for further pharmacological development in Alzheimer's therapy. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.041
• 作为产物：
  描述：

  三聚氯氰 、 2-氟苯胺 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 生成 4,6-dichloro-N-(2-fluorophenyl)-1,3,5-triazin-2-amine
  参考文献：
  名称：

  合理设计，合成和生物筛选三嗪-三唑并嘧啶杂合体作为多靶点抗阿尔茨海默病药物。

  摘要：

  为了开发用于治疗阿尔茨海默氏病的有效多靶点配体，我们通过各种光谱技术设计，合成和表征了一系列三嗪-三唑并嘧啶杂化物。用对接和评分技术设计抑制剂并显示其与活性位点关键残基的相互作用。依靠会聚合成路线的有机合成是单和二取代的三嗪与三唑并嘧啶连接，并使用哌嗪作为连接基。总共合成了十七种化合物，其中二取代的三嗪-三唑并嘧啶衍生物9a-d显示出比相应的三取代的三嗪-三唑并嘧啶衍生物更好的乙酰胆碱酯酶（AChE）抑制活性。在基于二取代三嗪-三唑并嘧啶的化合物中，9a和9b对AChE表现出令人鼓舞的抑制活性，IC50值分别为0.065和0.092μM。有趣的是，9a和9b对AChE的抑制选择性也比BuChE高约28倍。此外，动力学分析和分子建模研究表明9a和9b既靶向AChE的催化活性位点，又靶向其外围阴离子位点。此外，如通过CD光谱，ThT荧光测定和电子显微镜研究的，这些衍生物有效地调节了Aβ的自聚集

  DOI：

  10.1016/j.ejmech.2017.04.064

文献信息

• Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents
  作者：Ehtesham Jameel、Poonam Meena、Mudasir Maqbool、Jitendra Kumar、Waqar Ahmed、Syed Mumtazuddin、Manisha Tiwari、Nasimul Hoda、B. Jayaram

  DOI：10.1016/j.ejmech.2017.04.064

  日期：2017.8

  AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug

  为了开发用于治疗阿尔茨海默氏病的有效多靶点配体，我们通过各种光谱技术设计，合成和表征了一系列三嗪-三唑并嘧啶杂化物。用对接和评分技术设计抑制剂并显示其与活性位点关键残基的相互作用。依靠会聚合成路线的有机合成是单和二取代的三嗪与三唑并嘧啶连接，并使用哌嗪作为连接基。总共合成了十七种化合物，其中二取代的三嗪-三唑并嘧啶衍生物9a-d显示出比相应的三取代的三嗪-三唑并嘧啶衍生物更好的乙酰胆碱酯酶（AChE）抑制活性。在基于二取代三嗪-三唑并嘧啶的化合物中，9a和9b对AChE表现出令人鼓舞的抑制活性，IC50值分别为0.065和0.092μM。有趣的是，9a和9b对AChE的抑制选择性也比BuChE高约28倍。此外，动力学分析和分子建模研究表明9a和9b既靶向AChE的催化活性位点，又靶向其外围阴离子位点。此外，如通过CD光谱，ThT荧光测定和电子显微镜研究的，这些衍生物有效地调节了Aβ的自聚集
• DI(ARYLAMINO)ARYL COMPOUND
  申请人：Kondoh Yutaka

  公开号：US20100099658A1

  公开（公告）日：2010-04-22

  The present invention provides a compound which is useful as an inhibitor against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. As a result of extensive and intensive studies on compounds having an inhibitory effect against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins, the inventors of the present invention have found that the di(arylamino)aryl compound of the present invention has inhibitory activity against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. This finding led to the completion of the present invention. The compound of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive lung cancer, or EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small cell lung cancer, etc.

  本发明提供了一种化合物，可用作抑制EML4-ALK融合蛋白和突变EGFR蛋白的激酶活性的抑制剂。在广泛而深入的研究EML4-ALK融合蛋白和突变EGFR蛋白的激酶活性的化合物的基础上，本发明的发明人发现本发明的二(芳基氨基)芳基化合物具有抑制EML4-ALK融合蛋白和突变EGFR蛋白的激酶活性的活性。这一发现导致了本发明的完成。本发明的化合物可用作预防和/或治疗癌症、肺癌、非小细胞肺癌、小细胞肺癌、EML4-ALK融合多核苷酸阳性和/或突变EGFR多核苷酸阳性癌症、EML4-ALK融合多核苷酸阳性和/或突变EGFR多核苷酸阳性肺癌，或EML4-ALK融合多核苷酸阳性和/或突变EGFR多核苷酸阳性非小细胞肺癌等的药物组合物。
• Synthesis and bioevaluation of hybrid 4-aminoquinoline triazines as a new class of antimalarial agents
  作者：Ashok Kumar、Kumkum Srivastava、S. Raja Kumar、S.K. Puri、Prem M.S. Chauhan

  DOI：10.1016/j.bmcl.2008.10.049

  日期：2008.12

  The emergence and rapid spread of chloroquine resistant strains of Plasmodium falciparum has dramatically reduced the chemotherapeutic options. Towards this goal, a series of new class of hybrid 4-aminoquinoline triazines were synthesized and screened against CQ sensitive strain 3D7 of P. falciparum in an in vitro model. Compounds 65 and 69 exhibited more than 99% suppression on day 4 and on day 6 post treatment, compound 69 showed impressive 99.11% suppression against CQ resistant strain N-67 of P. yoelii in an in vivo assay. (C) 2008 Elsevier Ltd. All rights reserved.
• EP2172461
  申请人：——

  公开号：——

  公开（公告）日：——
• US8318702B2
  申请人：——

  公开号：US8318702B2

  公开（公告）日：2012-11-27