[1,3,5]Triazine-2,4-diamine, 6-chloro-N-(4-methoxyphenyl)-N'-(3-trifluoromethylphenyl)-

• 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: [1,3,5]Triazine-2,4-diamine, 6-chloro-N-(4-methoxyphenyl)-N'-(3-trifluoromethylphenyl)-
• 英文别名: 6-chloro-4-N-(4-methoxyphenyl)-2-N-[3-(trifluoromethyl)phenyl]-1,3,5-triazine-2,4-diamine
• 化学式: C₁₇H₁₃ClF₃N₅O
• 分子量: 395.771
• InChiKey: WEEBHADDNRNTDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  72
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [1,3,5]Triazine-2,4-diamine, 6-chloro-N-(4-methoxyphenyl)-N'-(3-trifluoromethylphenyl)- 、 2-哌嗪烟酰腈 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以68%的产率得到2-(4-(4-(4-methoxyphenylamino)-6-(3-(trifluoromethyl)phenylamino)-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：

  间氨基三氟甲苯 在 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 [1,3,5]Triazine-2,4-diamine, 6-chloro-N-(4-methoxyphenyl)-N'-(3-trifluoromethylphenyl)-
  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

• De novo lead optimization of triazine derivatives identifies potent antimalarials
  作者：Ashutosh Shandilya、Nasimul Hoda、Sameena Khan、Ehtesham Jameel、Jitendra Kumar、B. Jayaram

  DOI：10.1016/j.jmgm.2016.10.022

  日期：2017.1

  Malaria is a life-threatening disease caused by Plasmodium parasites among which Plasmodium falciparum is the most deadly. Due to the widespread resistance of the current antimalarial drugs, intense research efforts are focused on identification of new and potent antimalarials. We report here, a structure based drug discovery strategy for design of a series of effective and novel triazine based antimalarials. The X-ray structure of P. falciparum methyl transferase (PJPMT) is used as a target as it is unique to the parasite. The triazine molecules designed and synthesized showed low micro-molar activity against malarial parasite cell lines. Molecular dynamics simulations on the PJPMT-inhibitor complex shed light on the inhibition mechanism for further optimization of the lead compounds. (C) 2016 Elsevier Inc. All rights reserved.
• Development of cyanopyridine–triazine hybrids as lead multitarget anti-Alzheimer agents
  作者：Mudasir Maqbool、Apra Manral、Ehtesham Jameel、Jitendra Kumar、Vikas Saini、Ashutosh Shandilya、Manisha Tiwari、Nasimul Hoda、B. Jayaram

  DOI：10.1016/j.bmc.2016.04.041

  日期：2016.6

  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.
• 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