4-[(4-((4-methylphenylmethyl)amino)-2-pyrimidinyl)amino]benzonitrile

• 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-[(4-((4-methylphenylmethyl)amino)-2-pyrimidinyl)amino]benzonitrile
• 英文别名: 4-[[4-[(4-Methylphenyl)methylamino]pyrimidin-2-yl]amino]benzonitrile；4-[[4-[(4-methylphenyl)methylamino]pyrimidin-2-yl]amino]benzonitrile
• 化学式: C₁₉H₁₇N₅
• 分子量: 315.377
• InChiKey: VOCHUPYGKFNXTA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-[(4-羟基-2-嘧啶基)氨基]苯腈 在 potassium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 14.5h， 生成 4-[(4-((4-methylphenylmethyl)amino)-2-pyrimidinyl)amino]benzonitrile
  参考文献：
  名称：

  A novel family of diarylpyrimidines (DAPYs) featuring a diatomic linker: Design, synthesis and anti-HIV activities

  摘要：

  To improve the conformational flexibility and positional adaptability of the traditional diarylpyrimidines (DAPYs), a family of diarylpyrimidines featuring a C-N diatomic linker between the left wing benzene ring and the central pyrimidine was firstly designed, synthesized, and evaluated for in vitro anti-HIV activity. Most of target molecules showed excellent activities against wild-type (WT) HIV-1. Among them the most potent two compounds 12h and 12r displayed extremely potent WT HIV-1 inhibitory activities with an EC50 of 2.6 nM and 3.0 nM, respectively, while their selective index (CC50/EC50) values were both over 1000. Another compound 12b (EC50 14.9 nM) was also noteworthy due to its high SI of 18,614. Moreover, all of compounds were evaluated for their WT HIV-1 reverse transcriptase activities, which shown that the newly synthesized CH2NH-DAPYs bind to HIV-1 RT and belong to the genuine NNRTIs. However, the synthesized compounds lack the activities against HIV-1 double mutant (RES056) and HIV-2 (ROD). Thus it is an upcoming objective to improve the activities against HIV-1 double mutants. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.020

文献信息

• 一种二芳基嘧啶类HIV-1抑制剂及其制备方 法
  申请人：武汉工程大学

  公开号：CN105085410B

  公开（公告）日：2017-10-10

  本发明公开了一种二芳基嘧啶类HIV‑1抑制剂及其制备方法。在惰性气体保护下，以2‑(对氰基苯胺基)‑4‑氯嘧啶为原料，在碱的作用下，与苄胺或者取代苄胺在溶剂中发生亲核取代反应得到上述二芳基嘧啶。本发明设计合成的新化合物具有较好的HIV‑1细胞水平抑制活性，部分化合物对HIV‑1 IIIB这一重要病毒株的抑制活性强于作为参考的上市药物奈韦拉平、依法韦伦和依曲韦林，且毒性很小，可用于进一步开发为抗艾滋病药物。
• A novel family of diarylpyrimidines (DAPYs) featuring a diatomic linker: Design, synthesis and anti-HIV activities
  作者：Shuang-Xi Gu、Heng Qiao、Yuan-Yuan Zhu、Qi-Chao Shu、Hui Liu、Xiu-Lian Ju、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.bmc.2015.09.020

  日期：2015.10

  To improve the conformational flexibility and positional adaptability of the traditional diarylpyrimidines (DAPYs), a family of diarylpyrimidines featuring a C-N diatomic linker between the left wing benzene ring and the central pyrimidine was firstly designed, synthesized, and evaluated for in vitro anti-HIV activity. Most of target molecules showed excellent activities against wild-type (WT) HIV-1. Among them the most potent two compounds 12h and 12r displayed extremely potent WT HIV-1 inhibitory activities with an EC50 of 2.6 nM and 3.0 nM, respectively, while their selective index (CC50/EC50) values were both over 1000. Another compound 12b (EC50 14.9 nM) was also noteworthy due to its high SI of 18,614. Moreover, all of compounds were evaluated for their WT HIV-1 reverse transcriptase activities, which shown that the newly synthesized CH2NH-DAPYs bind to HIV-1 RT and belong to the genuine NNRTIs. However, the synthesized compounds lack the activities against HIV-1 double mutant (RES056) and HIV-2 (ROD). Thus it is an upcoming objective to improve the activities against HIV-1 double mutants. (c) 2015 Elsevier Ltd. All rights reserved.