4-(2-chloro-5-nitropyrimidin-4-ylamino)benzonitrile | 1533448-43-9

• 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-(2-chloro-5-nitropyrimidin-4-ylamino)benzonitrile
• 英文别名: 2,4-dichloro-5-nitropyrimidine；4-[(2-Chloro-5-nitropyrimidin-4-yl)amino]benzonitrile；4-[(2-chloro-5-nitropyrimidin-4-yl)amino]benzonitrile
• CAS: 1533448-43-9
• 化学式: C₁₁H₆ClN₅O₂
• 分子量: 275.654
• InChiKey: FKYKPMBGVMJGCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 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：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(2-chloro-5-nitropyrimidin-4-ylamino)benzonitrile 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 N-(2-(4-cyano-2,6-dimethylphenoxy)-4-(4-cyanophenylamino)pyrimidin-5-yl)-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  Discovery of novel diarylpyrimidines as potent HIV NNRTIs via a structure-guided core-refining approach

  摘要：

  Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel DAPY derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities. Among them, 16 compounds significantly inhibited HIV-1 IIIB replication with EC50 values lower than 66 nM. Particularly, compound 7a was the most potent inhibitor against HIV-1 wild-type and double RT mutant HIV-1 strain K103N/Y181C, with an EC50 value of 2.5 nM (SI = 13,740) and 0.33 μM (SI = 107), respectively. Unexpectedly, compound 8c was found to show moderate anti-HIV-2 potency (EC50 = 5.57 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogues were also discussed in detail.

  DOI：

  10.1016/j.ejmech.2014.04.036
• 作为产物：
  描述：

  对氨基苯腈 、 2,4-二氯-5 硝基嘧啶 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 4-(2-chloro-5-nitropyrimidin-4-ylamino)benzonitrile
  参考文献：
  名称：

  KDM5A抑制剂的发现：同源性建模，虚拟筛选和结构-活性关系分析

  摘要：

  在此，我们报告发现了一系列新的KDM5A抑制剂。首先基于同源性建模建立了KDM5A jumonji域的三维（3D）结构模型。然后针对商业化学数据库进行基于分子对接的虚拟筛选。检索了许多命中化合物。对活性最高的化合物9（IC 50：2.3μM ）进行了进一步的结构优化和结构-活性关系（SAR）分析，从而发现了几种新的KDM5A抑制剂。其中，化合物15e是最强效的IC 50相对于KDM5A的0.22μM值。该化合物显示出对KDM5A的良好选择性，并具有在完整细胞中抑制H3K4me3脱甲基化的显着能力。化合物15e可作为进一步研究的良好先导化合物。

  DOI：

  10.1016/j.bmcl.2016.03.048

文献信息

• Discovery of KDM5A inhibitors: Homology modeling, virtual screening and structure–activity relationship analysis
  作者：Xiaoai Wu、Zhen Fang、Bo Yang、Lei Zhong、Qiuyuan Yang、Chunhui Zhang、Shenzhen Huang、Rong Xiang、Takayoshi Suzuki、Lin-Li Li、Sheng-Yong Yang

  DOI：10.1016/j.bmcl.2016.03.048

  日期：2016.5

  (SAR) analysis were carried out to the most active hit compound, 9 (IC50: 2.3 μM), which led to the discovery of several new KDM5A inhibitors. Among them, compound 15e is the most potent one with an IC50 value of 0.22 μM against KDM5A. This compound showed good selectivity for KDM5A and considerable ability to suppress the demethylation of H3K4me3 in intact cells. Compound 15e could be taken as a good lead

  在此，我们报告发现了一系列新的KDM5A抑制剂。首先基于同源性建模建立了KDM5A jumonji域的三维（3D）结构模型。然后针对商业化学数据库进行基于分子对接的虚拟筛选。检索了许多命中化合物。对活性最高的化合物9（IC 50：2.3μM ）进行了进一步的结构优化和结构-活性关系（SAR）分析，从而发现了几种新的KDM5A抑制剂。其中，化合物15e是最强效的IC 50相对于KDM5A的0.22μM值。该化合物显示出对KDM5A的良好选择性，并具有在完整细胞中抑制H3K4me3脱甲基化的显着能力。化合物15e可作为进一步研究的良好先导化合物。
• Discovery of novel diarylpyrimidines as potent HIV NNRTIs via a structure-guided core-refining approach
  作者：Xiao Li、Wenmin Chen、Ye Tian、Huiqing Liu、Peng Zhan、Erik De Clercq、Christophe Pannecouque、Jan Balzarini、Xinyong Liu

  DOI：10.1016/j.ejmech.2014.04.036

  日期：2014.6

  Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel DAPY derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities. Among them, 16 compounds significantly inhibited HIV-1 IIIB replication with EC50 values lower than 66 nM. Particularly, compound 7a was the most potent inhibitor against HIV-1 wild-type and double RT mutant HIV-1 strain K103N/Y181C, with an EC50 value of 2.5 nM (SI = 13,740) and 0.33 μM (SI = 107), respectively. Unexpectedly, compound 8c was found to show moderate anti-HIV-2 potency (EC50 = 5.57 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogues were also discussed in detail.