(5Z,5'Z)-5-(4-hydroxybenzylidene)-2-{[2-(4-{[(5-(4-hydroxybenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl)amino]propyl}-1H-1,2,3-triazol-1-yl)ethyl]amino}-1,3-thiazol-4(5H)-one | 1415582-52-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (5Z,5'Z)-5-(4-hydroxybenzylidene)-2-{[2-(4-{[(5-(4-hydroxybenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl)amino]propyl}-1H-1,2,3-triazol-1-yl)ethyl]amino}-1,3-thiazol-4(5H)-one
• 英文别名: (5Z)-5-[(4-hydroxyphenyl)methylidene]-2-[3-[1-[2-[[(5Z)-5-[(4-hydroxyphenyl)methylidene]-4-oxo-1,3-thiazolidin-2-ylidene]amino]ethyl]triazol-4-yl]propylimino]-1,3-thiazolidin-4-one
• CAS: 1415582-52-3
• 化学式: C₂₇H₂₅N₇O₄S₂
• 分子量: 575.672
• InChiKey: LBQYIWODGKQTBT-VMTNTFKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  205
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (5Z)-2-(2-azidoethylimino)-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one 、 (5Z)-2-but-3-ynylimino-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以46%的产率得到(5Z,5'Z)-5-(4-hydroxybenzylidene)-2-{[2-(4-{[(5-(4-hydroxybenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl)amino]propyl}-1H-1,2,3-triazol-1-yl)ethyl]amino}-1,3-thiazol-4(5H)-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.