(E)-3-(4-hydroxy-3,5-dimethylphenyl)acrylamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(4-hydroxy-3,5-dimethylphenyl)acrylamide
• 英文别名: (E)-3-(4-hydroxy-3,5-dimethylphenyl)prop-2-enamide
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: KMOQNQREUGZCEF-ONEGZZNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-hydroxy-3,5-dimethylphenyl)acrylamide 在 potassium carbonate 、 三氯氧磷 作用下， 生成 (E)-3-(4-((2-chloropyrimidin-4-yl)oxy)-3,5-dimethylphenyl)acrylonitrile
  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：

  4-溴-2,6-二甲基苯酚 、 丙烯酰胺 在 palladium diacetate 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 乙腈 为溶剂， 以40%的产率得到(E)-3-(4-hydroxy-3,5-dimethylphenyl)acrylamide
  参考文献：
  名称：

  [EN] HIV INHIBITING 1,2,4-TRIAZINES
  [FR] 1,2,4-TRIAZINES INHIBANT LE VIH

  摘要：

  本发明涉及公式（I）中定义的HIV复制抑制剂，其用作药物，它们的制备方法以及包含它们的药物组合物。

  公开号：

  WO2004074266A1

文献信息

• [EN] HIV INHIBITING 1,2,4-TRIAZINES<br/>[FR] 1,2,4-TRIAZINES INHIBANT LE VIH
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004074266A1

  公开（公告）日：2004-09-02

  The present invention relates to HIV replication inhibitors of formula (I) as defined in the specification their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

  本发明涉及公式（I）中定义的HIV复制抑制剂，其用作药物，它们的制备方法以及包含它们的药物组合物。
• Structure-Based Design and Discovery of Pyridyl-Bearing Fused Bicyclic HIV-1 Inhibitors: Synthesis, Biological Characterization, and Molecular Modeling Studies
  作者：Boshi Huang、Tiziana Ginex、F. Javier Luque、Xiangyi Jiang、Ping Gao、Jian Zhang、Dongwei Kang、Dirk Daelemans、Erik De Clercq、Christophe Pannecouque、Peng Zhan、Xinyong Liu

  DOI：10.1021/acs.jmedchem.1c00987

  日期：2021.9.23

  pharmacophores. In vitro metabolic stability profiles and some drug-like properties of selected compounds were assessed, furnishing the preliminary structure–metabolic stability relationships. Furthermore, molecular modeling studies elucidated the binding modes of compounds 6, 15, 21, and 30 in the binding pocket of WT, E138K, K103N, or Y181C HIV-1 RTs. These promising compounds can be used as lead compounds

  合成了两个系列新的含吡啶基的融合双环类似物，旨在针对非核苷逆转录酶抑制剂 (NNRTI) 结合口袋的双重耐受区域，并评估它们的抗 HIV 活性。几种化合物，例如6、14、15、21、30和33, 被发现是针对野生型 (WT) HIV-1 毒株或低纳摩尔水平的多种 NNRTI 抗性毒株的有效抑制剂。通过利用相应药效团内部分的变化，获得了详细的结构-活性关系。评估了所选化合物的体外代谢稳定性特征和一些药物样特性，提供了初步的结构-代谢稳定性关系。此外，分子建模研究阐明了化合物6、15、21和30的结合模式在 WT、E138K、K103N 或 Y181C HIV-1 RT 的结合口袋中。这些有前途的化合物可用作先导化合物，并保证进一步的结构优化以产生更具活性的 HIV-1 抑制剂。
• Hiv inhibiting 1,2,4-triazines
  申请人：Lewi Joannes Paulus

  公开号：US20070037811A1

  公开（公告）日：2007-02-15

  The present invention relates to HIV replication inhibitors of formula (I) as defined in the specification their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.
• US7585861B2
  申请人：——

  公开号：US7585861B2

  公开（公告）日：2009-09-08
• 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.