4-chloro-N-(6-methyl-2-oxo-1,2-dihydro-quinolin-3-ylmethyl)-N-(tetrahydro-furan-2-ylmethyl)-benzamide | 879458-36-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-chloro-N-(6-methyl-2-oxo-1,2-dihydro-quinolin-3-ylmethyl)-N-(tetrahydro-furan-2-ylmethyl)-benzamide
• 英文别名: 4-chloro-N-[(6-methyl-2-oxo-1H-quinolin-3-yl)methyl]-N-(oxolan-2-ylmethyl)benzamide
• CAS: 879458-36-3
• 化学式: C₂₃H₂₃ClN₂O₃
• 分子量: 410.9
• InChiKey: NMFDKTAYEHIVCK-UHFFFAOYSA-N

物化性质

• 沸点：
  649.8±55.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-methyl-3-{[(tetrahydro-furan-2-ylmethyl)-amino]-methyl}-1H-quinolin-2-one 、 对氯苯甲酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 以25%的产率得到4-chloro-N-(6-methyl-2-oxo-1,2-dihydro-quinolin-3-ylmethyl)-N-(tetrahydro-furan-2-ylmethyl)-benzamide
  参考文献：
  名称：

  Virtual screening based identification of novel small-molecule inhibitors targeted to the HIV-1 capsid

  摘要：

  The hydrophobic cavity of the C-terminal domain (CTD) of HIV-1 capsid has been recently validated as potential target for antiviral drugs by peptide-based inhibitors; however, there is no report yet of any small molecule compounds that target this hydrophobic cavity. In order to fill this gap and discover new classes of ant-HIV-1 inhibitors, we undertook a docking-based virtual screening and subsequent analog search, and medicinal chemistry approaches to identify small molecule inhibitors against this target. This article reports for the first time, to the best of our knowledge, identification of diverse classes of inhibitors that efficiently inhibited the formation of mature-like viral particles verified under electron microscope (EM) and showed potential as anti-HIV-1 agents in a viral infectivity assay against a wide range of laboratory-adapted as well as primary isolates in MT-2 cells and PBMC. In addition, the virions produced after the HIV-1 infected cells were treated with two of the most active compounds showed drastically reduced infectivity confirming the potential of these compounds as anti-HIV-1 agents. We have derived a comprehensive SAR from the antiviral data. The SAR analyses will be useful in further optimizing the leads to potential anti-HIV-1 agents. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.045

文献信息

• Virtual screening based identification of novel small-molecule inhibitors targeted to the HIV-1 capsid
  作者：Francesca Curreli、Hongtao Zhang、Xihui Zhang、Ilya Pyatkin、Zagorodnikov Victor、Andrea Altieri、Asim K. Debnath

  DOI：10.1016/j.bmc.2010.11.045

  日期：2011.1

  The hydrophobic cavity of the C-terminal domain (CTD) of HIV-1 capsid has been recently validated as potential target for antiviral drugs by peptide-based inhibitors; however, there is no report yet of any small molecule compounds that target this hydrophobic cavity. In order to fill this gap and discover new classes of ant-HIV-1 inhibitors, we undertook a docking-based virtual screening and subsequent analog search, and medicinal chemistry approaches to identify small molecule inhibitors against this target. This article reports for the first time, to the best of our knowledge, identification of diverse classes of inhibitors that efficiently inhibited the formation of mature-like viral particles verified under electron microscope (EM) and showed potential as anti-HIV-1 agents in a viral infectivity assay against a wide range of laboratory-adapted as well as primary isolates in MT-2 cells and PBMC. In addition, the virions produced after the HIV-1 infected cells were treated with two of the most active compounds showed drastically reduced infectivity confirming the potential of these compounds as anti-HIV-1 agents. We have derived a comprehensive SAR from the antiviral data. The SAR analyses will be useful in further optimizing the leads to potential anti-HIV-1 agents. (C) 2010 Elsevier Ltd. All rights reserved.