(3Z,6Z)-3-(4-benzoylbenzylidene)-6-((5-tert-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione | 1385033-35-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3Z,6Z)-3-(4-benzoylbenzylidene)-6-((5-tert-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione
• 英文别名: (3Z,6Z)-3-[(4-benzoylphenyl)methylidene]-6-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]piperazine-2,5-dione
• CAS: 1385033-35-1
• 化学式: C₂₆H₂₄N₄O₃
• 分子量: 440.502
• InChiKey: DCQNWYMFIRSTPV-NMGXZBPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-苯甲酰苯甲酸 在 lithium aluminium tetrahydride 、 重铬酸吡啶 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (3Z,6Z)-3-(4-benzoylbenzylidene)-6-((5-tert-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione
  参考文献：
  名称：

  Synthesis and structure–activity relationships of benzophenone-bearing diketopiperazine-type anti-microtubule agents

  摘要：

  KPU-105 (4), a potent anti-microtubule agent that contains a benzophenone was derived from the dike-topiperazine-type vascular disrupting agent (VDA) plinabulin 3, which displays colchicine-like tubulin depolymerization activity. To develop derivatives with more potent anti-microtubule and cytotoxic activities, we further modified the benzophenone moiety of 4. Accordingly, we obtained a 4-fluorobenzophenone derivative 16j that inhibited tumor cell growth in vitro with a subnanomolar IC50 value against HT-29 cells (IC50 = 0.5 nM). Next, the effect of 16j on mitotic spindles was evaluated in HeLa cells. Treatment with 3 nM of 16j partially disrupted the interphase microtubule network. By contrast, treatment with the same concentration of CA-4 barely affected the microtubule network, indicating that 16j exhibited more potent anti-mitotic effects than did CA-4. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.059

文献信息

• Synthesis and structure–activity relationships of benzophenone-bearing diketopiperazine-type anti-microtubule agents
  作者：Yuri Yamazaki、Makiko Sumikura、Yurika Masuda、Yoshiki Hayashi、Hiroyuki Yasui、Yoshiaki Kiso、Takumi Chinen、Takeo Usui、Fumika Yakushiji、Barbara Potts、Saskia Neuteboom、Michael Palladino、George Kenneth Lloyd、Yoshio Hayashi

  DOI：10.1016/j.bmc.2012.05.059

  日期：2012.7

  KPU-105 (4), a potent anti-microtubule agent that contains a benzophenone was derived from the dike-topiperazine-type vascular disrupting agent (VDA) plinabulin 3, which displays colchicine-like tubulin depolymerization activity. To develop derivatives with more potent anti-microtubule and cytotoxic activities, we further modified the benzophenone moiety of 4. Accordingly, we obtained a 4-fluorobenzophenone derivative 16j that inhibited tumor cell growth in vitro with a subnanomolar IC50 value against HT-29 cells (IC50 = 0.5 nM). Next, the effect of 16j on mitotic spindles was evaluated in HeLa cells. Treatment with 3 nM of 16j partially disrupted the interphase microtubule network. By contrast, treatment with the same concentration of CA-4 barely affected the microtubule network, indicating that 16j exhibited more potent anti-mitotic effects than did CA-4. (C) 2012 Elsevier Ltd. All rights reserved.