(E)-N,2-dimethyl-3-phenyl-N-((6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)methyl)prop-2-en-1-amine hydrochloride

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (E)-N,2-dimethyl-3-phenyl-N-((6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)methyl)prop-2-en-1-amine hydrochloride
• 英文别名: (E)-N,2-dimethyl-3-phenyl-N-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-ylmethyl)prop-2-en-1-amine;hydrochloride
• 化学式: C₂₃H₂₉N*ClH
• 分子量: 355.951
• InChiKey: AHAGWVNCFIWYEM-QTCZRQAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.91
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  3.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  N-methyl-1-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)methanamine 、 (E)-(3-bromo-2-methylprop-1-en-1-yl)benzene 在 potassium carbonate 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 反应 0.02h， 生成 (E)-N,2-dimethyl-3-phenyl-N-((6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)methyl)prop-2-en-1-amine hydrochloride
  参考文献：
  名称：

  Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN)

  摘要：

  Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocycloalkane-derived CrtN inhibitors with submicromolar IC50. Analogue 8 blocked the pigment biosynthesis of three MRSA strains with a nanomolar IC50 value. Corresponding to its mode of action, 8 did not function as a bactericidal agent. 8 could sensitize S. aureus to immune clearance. In vivo, 8 was proven to be efficacious in an S. aureus Newman sepsis model and abscess formation model. For two typical MRSAs,. USA400 MW2 and Mu50, 8 significantly decreased the staphylococcal loads in the liver and kidneys. Moreover, 8 showed minimal antifungal activity compared to that of NTF. In summary, 8 has the potential to be developed as a therapeutic drug, especially against intractable MRSA issues.

  DOI：

  10.1021/acs.jmedchem.6b00122

文献信息

• Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant <i>S. aureus</i> (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN)
  作者：Youxin Wang、Hongxia Di、Feifei Chen、Yong Xu、Qiang Xiao、Xuehai Wang、Hanwen Wei、Yanli Lu、Lingling Zhang、Jin Zhu、Lefu Lan、Jian Li

  DOI：10.1021/acs.jmedchem.6b00122

  日期：2016.5.26

  Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocycloalkane-derived CrtN inhibitors with submicromolar IC50. Analogue 8 blocked the pigment biosynthesis of three MRSA strains with a nanomolar IC50 value. Corresponding to its mode of action, 8 did not function as a bactericidal agent. 8 could sensitize S. aureus to immune clearance. In vivo, 8 was proven to be efficacious in an S. aureus Newman sepsis model and abscess formation model. For two typical MRSAs,. USA400 MW2 and Mu50, 8 significantly decreased the staphylococcal loads in the liver and kidneys. Moreover, 8 showed minimal antifungal activity compared to that of NTF. In summary, 8 has the potential to be developed as a therapeutic drug, especially against intractable MRSA issues.