2,5-dichloro-4-(3,5-dimethylphenoxy)pyrimidine | 76661-11-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,5-dichloro-4-(3,5-dimethylphenoxy)pyrimidine
• CAS: 76661-11-5
• 化学式: C₁₂H₁₀Cl₂N₂O
• 分子量: 269.13
• InChiKey: XOOAOHTUUBNRAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-氨基-乙基)-1H-嘧啶-2,4-二酮盐酸盐 、 2,5-dichloro-4-(3,5-dimethylphenoxy)pyrimidine 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以40.7%的产率得到1-(2-((5-chloro-4-(3,5-dimethylphenoxy)pyrimidin-2-yl)amino)ethyl)pyrimidine-2,4-(1H,3H)-dione
  参考文献：
  名称：

  Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization

  摘要：

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.047
• 作为产物：
  描述：

  2,4,5-三氯嘧啶 、 3,5-二甲基苯酚 在 potassium carbonate 作用下， 以71.6%的产率得到2,5-dichloro-4-(3,5-dimethylphenoxy)pyrimidine
  参考文献：
  名称：

  Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization

  摘要：

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.047

文献信息

• Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization
  作者：Heng Zhang、Ye Tian、Dongwei Kang、Zhipeng Huo、Zhongxia Zhou、Huiqing Liu、Erik De Clercq、Christophe Pannecouque、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.ejmech.2017.02.047

  日期：2017.4

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.