1-(4'-chloro[1,1'-biphenyl]-4-yl)-2-(4,5-dimethoxy-2-nitrophenyl)ethanol

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(4'-chloro[1,1'-biphenyl]-4-yl)-2-(4,5-dimethoxy-2-nitrophenyl)ethanol
• 英文别名: 1-[4-(4-Chlorophenyl)phenyl]-2-(4,5-dimethoxy-2-nitrophenyl)ethanol；1-[4-(4-chlorophenyl)phenyl]-2-(4,5-dimethoxy-2-nitrophenyl)ethanol
• 化学式: C₂₂H₂₀ClNO₅
• 分子量: 413.858
• InChiKey: QBQMTSSRBGPJFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-硝基藜芦醛 在 sodium tetrahydroborate 、 氯化亚砜 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 1-(4'-chloro[1,1'-biphenyl]-4-yl)-2-(4,5-dimethoxy-2-nitrophenyl)ethanol
  参考文献：
  名称：

  VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection

  摘要：

  Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyI)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 = 3.4 +/- 1.0 mu M) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW_0005, CC50 = 104.0 +/- 22.2 mu M: 3v, CC50 > 263 mu M). (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.049

文献信息

• VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection
  作者：Laurène Da Costa、Manon Roche、Els Scheers、Antonio Coluccia、Johan Neyts、Thierry Terme、Pieter Leyssen、Romano Silvestri、Patrice Vanelle

  DOI：10.1016/j.ejmech.2016.03.049

  日期：2016.6

  Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyI)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 = 3.4 +/- 1.0 mu M) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW_0005, CC50 = 104.0 +/- 22.2 mu M: 3v, CC50 > 263 mu M). (C) 2016 Elsevier Masson SAS. All rights reserved.