4-((3-chlorophenyl)ethynyl)-7-(4-(phenethylamino)piperidin-1-yl)-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4-((3-chlorophenyl)ethynyl)-7-(4-(phenethylamino)piperidin-1-yl)-2H-chromen-2-one
• 英文别名: 4-[2-(3-Chlorophenyl)ethynyl]-7-[4-(2-phenylethylamino)piperidin-1-yl]chromen-2-one；4-[2-(3-chlorophenyl)ethynyl]-7-[4-(2-phenylethylamino)piperidin-1-yl]chromen-2-one
• 化学式: C₃₀H₂₇ClN₂O₂
• 分子量: 483.01
• InChiKey: ALCFMDNXMRBRBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-溴-4-羟基-2H-色烯-2-酮 在 copper(l) iodide 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 palladium dichloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 20.0~90.0 ℃ 、101.33 kPa 条件下， 反应 26.0h， 生成 4-((3-chlorophenyl)ethynyl)-7-(4-(phenethylamino)piperidin-1-yl)-2H-chromen-2-one
  参考文献：
  名称：

  A novel NAE/UAE dual inhibitor LP0040 blocks neddylation and ubiquitination leading to growth inhibition and apoptosis of cancer cells

  摘要：

  NEDD8 activating enzyme (NAE) plays an important role in regulating intracellular proteins with key parts in a broad array of cellular functions. On the basis of previously work, a series of 2H-chromen-2-one based NAE inhibitors were designed and synthesized. Through enzyme-based and cell-based assays, LP0040 was identified as a non-nucleoside NAE/UAE dual inhibitor, It could inhibit NAE/UAE activities and downregulated degradations of related substrates in AGS cells, promoting apoptosis in low micro mole concentrations. LP0040 possessed anti-proliferation activities with IC50 values of 0.76-3.29 mu M against multiple human cancer lines and had synergistic effect with bortezomib. Thus LP0040 represented valuable starting points for future development of NAE/UAE dual inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.027

文献信息

• A novel NAE/UAE dual inhibitor LP0040 blocks neddylation and ubiquitination leading to growth inhibition and apoptosis of cancer cells
  作者：Peng Lu、Yahui Guo、Lijuan Zhu、Yineng Xia、Yuejiao Zhong、Yubin Wang

  DOI：10.1016/j.ejmech.2018.05.027

  日期：2018.6

  NEDD8 activating enzyme (NAE) plays an important role in regulating intracellular proteins with key parts in a broad array of cellular functions. On the basis of previously work, a series of 2H-chromen-2-one based NAE inhibitors were designed and synthesized. Through enzyme-based and cell-based assays, LP0040 was identified as a non-nucleoside NAE/UAE dual inhibitor, It could inhibit NAE/UAE activities and downregulated degradations of related substrates in AGS cells, promoting apoptosis in low micro mole concentrations. LP0040 possessed anti-proliferation activities with IC50 values of 0.76-3.29 mu M against multiple human cancer lines and had synergistic effect with bortezomib. Thus LP0040 represented valuable starting points for future development of NAE/UAE dual inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.