(5Z)-2-[2-[4-[2-[[(5Z)-5-(1,3-benzodioxol-5-ylmethylidene)-4-oxo-1,3-thiazolidin-2-ylidene]amino]ethyl]piperazin-1-yl]ethylimino]-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one | 1415582-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (5Z)-2-[2-[4-[2-[[(5Z)-5-(1,3-benzodioxol-5-ylmethylidene)-4-oxo-1,3-thiazolidin-2-ylidene]amino]ethyl]piperazin-1-yl]ethylimino]-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one
• CAS: 1415582-59-0
• 化学式: C₂₉H₃₀N₆O₅S₂
• 分子量: 606.726
• InChiKey: BDUVGDDWGQJQAW-YFJQDTPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (Z)-5-(4-羟基苯亚甲基)-2-硫代噻唑烷-4-酮 在 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 45.0h， 生成 (5Z)-2-[2-[4-[2-[[(5Z)-5-(1,3-benzodioxol-5-ylmethylidene)-4-oxo-1,3-thiazolidin-2-ylidene]amino]ethyl]piperazin-1-yl]ethylimino]-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one
  参考文献：
  名称：

  Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: Effect of dimerisation on phosphatase inhibition

  摘要：

  CDC25 phosphatases are involved in deregulated cell cycle progression and tumor development with poor prognosis. Among the most potent CDC25 inhibitors, quinonoid-based derivatives have been extensively studied. Dimerisation of heterocyclic quinones has led to IRC-083864, a bis-quinone compound with increased CDC25B inhibitory activity. Thirty-one bis-thiazolone derivatives were synthesized and assayed for CDC25 inhibitory activity. Most of the dimers displayed enhanced inhibitory activities with micromolar IC50 values lower than that observed for each thiazolone scaffold separately. Moreover, most of these compounds were selective CDC25 inhibitors. Dimer 40 showed an IC50 value of 2.9 mu M and could inhibit CDC25 activity without generating reactive oxygen species which is likely to occur with quinone-based inhibitors. Molecular docking studies suggested that the dimers could bind simultaneously to the active site and the inhibitor binding pocket. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.072

文献信息

• Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: Effect of dimerisation on phosphatase inhibition
  作者：Manal Sarkis、Diem Ngan Tran、Stéphanie Kolb、Maria A. Miteva、Bruno O. Villoutreix、Christiane Garbay、Emmanuelle Braud

  DOI：10.1016/j.bmcl.2012.10.072

  日期：2012.12

  CDC25 phosphatases are involved in deregulated cell cycle progression and tumor development with poor prognosis. Among the most potent CDC25 inhibitors, quinonoid-based derivatives have been extensively studied. Dimerisation of heterocyclic quinones has led to IRC-083864, a bis-quinone compound with increased CDC25B inhibitory activity. Thirty-one bis-thiazolone derivatives were synthesized and assayed for CDC25 inhibitory activity. Most of the dimers displayed enhanced inhibitory activities with micromolar IC50 values lower than that observed for each thiazolone scaffold separately. Moreover, most of these compounds were selective CDC25 inhibitors. Dimer 40 showed an IC50 value of 2.9 mu M and could inhibit CDC25 activity without generating reactive oxygen species which is likely to occur with quinone-based inhibitors. Molecular docking studies suggested that the dimers could bind simultaneously to the active site and the inhibitor binding pocket. (C) 2012 Elsevier Ltd. All rights reserved.