3',6-dimethoxy-N-(3-(4-methoxyphenyl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)biphenyl-3-carboxamide | 1134320-20-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3',6-dimethoxy-N-(3-(4-methoxyphenyl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)biphenyl-3-carboxamide
• 英文别名: 4-methoxy-3-(3-methoxyphenyl)-N-[3-(4-methoxyphenyl)-1,4-dioxonaphthalen-2-yl]benzamide
• CAS: 1134320-20-9
• 化学式: C₃₂H₂₅NO₆
• 分子量: 519.554
• InChiKey: AKXMUVBOPDEPOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3',6-dimethoxy-[1,1'-biphenyl]-3-carbonyl chloride 、 2-amino-3-(4-methoxyphenyl)naphthalene-1,4-dione 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以46%的产率得到3',6-dimethoxy-N-(3-(4-methoxyphenyl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)biphenyl-3-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of Hsp90 inhibitors that contain the 1,4-naphthoquinone scaffold

  摘要：

  High-throughput screening of a library of diverse molecules has identified the 1,4-naphthoquinone scaffold as a new class of Hsp90 inhibitors. The synthesis and evaluation of a rationally-designed series of analogues containing the naphthoquinone core scaffold has provided key structure-activity relationships for these compounds. The most active inhibitors exhibited potent in vitro activity with low micromolar IC50 values in anti-proliferation and Her2 degradation assays. In addition, 3g, 12, and 13a induced the degradation of oncogenic Hsp90 client proteins, a hallmark of Hsp90 inhibition. The identification of these naphthoquinones as Hsp90 inhibitors provides a new scaffold upon which improved Hsp90 inhibitors can be developed. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.064

文献信息

• Synthesis and evaluation of Hsp90 inhibitors that contain the 1,4-naphthoquinone scaffold
  作者：M. Kyle Hadden、Stephanie A. Hill、Jason Davenport、Robert L. Matts、Brian S.J. Blagg

  DOI：10.1016/j.bmc.2008.11.064

  日期：2009.1

  High-throughput screening of a library of diverse molecules has identified the 1,4-naphthoquinone scaffold as a new class of Hsp90 inhibitors. The synthesis and evaluation of a rationally-designed series of analogues containing the naphthoquinone core scaffold has provided key structure-activity relationships for these compounds. The most active inhibitors exhibited potent in vitro activity with low micromolar IC50 values in anti-proliferation and Her2 degradation assays. In addition, 3g, 12, and 13a induced the degradation of oncogenic Hsp90 client proteins, a hallmark of Hsp90 inhibition. The identification of these naphthoquinones as Hsp90 inhibitors provides a new scaffold upon which improved Hsp90 inhibitors can be developed. (C) 2008 Elsevier Ltd. All rights reserved.