(E)-N-(coumaran-5-ylmethyl)-N-methyl-3-(4-difluoromethylphenyl)prop-2-en-1-amine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (E)-N-(coumaran-5-ylmethyl)-N-methyl-3-(4-difluoromethylphenyl)prop-2-en-1-amine hydrochloride
• 英文别名: (E)-N-(2,3-dihydrobenzofuran-5-methyl)-N-methyl-3-(4-difluoromethylphenyl)prop-2-en-1-amine hydrochloride；(E)-3-[4-(difluoromethyl)phenyl]-N-(2,3-dihydro-1-benzofuran-5-ylmethyl)-N-methylprop-2-en-1-amine;hydrochloride
• 化学式: C₂₀H₂₁F₂NO*ClH
• 分子量: 365.851
• InChiKey: OLWGHZZXRZAHAQ-SQQVDAMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.13
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  12.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3-二氢苯并呋喃-5-甲醛 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (E)-N-(coumaran-5-ylmethyl)-N-methyl-3-(4-difluoromethylphenyl)prop-2-en-1-amine hydrochloride
  参考文献：
  名称：

  Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo

  摘要：

  Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

  DOI：

  10.1021/acs.jmedchem.7b00949

文献信息

• Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate <i>Staphylococcus aureus</i> Infections in Vivo
  作者：Shuaishuai Ni、Hanwen Wei、Baoli Li、Feifei Chen、Yifu Liu、Wenhua Chen、Yixiang Xu、Xiaoxia Qiu、Xiaokang Li、Yanli Lu、Wenwen Liu、Linhao Hu、Dazheng Lin、Manjiong Wang、Xinyu Zheng、Fei Mao、Jin Zhu、Lefu Lan、Jian Li

  DOI：10.1021/acs.jmedchem.7b00949

  日期：2017.10.12

  Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.