apoptozole | 1054543-55-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: apoptozole
• 英文别名: 1-[4-(9-Aza-3,6-dioxanonane-1-ylcarbamoyl)benzyl]-2-[3,5-bis(trifluoromethyl)phenyl]-4,5-bis(4-methoxyphenyl)-1H-imidazole；N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-4-[[2-[3,5-bis(trifluoromethyl)phenyl]-4,5-bis(4-methoxyphenyl)imidazol-1-yl]methyl]benzamide
• CAS: 1054543-55-3
• 化学式: C₃₉H₃₈F₆N₄O₅
• 分子量: 756.745
• InChiKey: BQTWNCUBGVRTLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  54
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  apoptozole 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  A triple-targeting delivery system carrying two anticancer agents

  摘要：

  为了提高肿瘤的选择性，我们准备了一种新的三重靶向传递系统，携带两种抗癌药物。该系统中的两种抗癌药物在存在高产生于癌细胞中的H₂O₂和cathepsin B的情况下释放。

  DOI：

  10.1039/d1ob01089a
• 作为产物：
  描述：

  4-((2-(3,5-bis(trifluoromethyl)phenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole-1-yl)methyl)benzoic acid 、 2-(2,4-difluoro-phenoxy)-N-{4-[2-(4-fluoro-phenoxy)-ethyl]-thiazol-2-yl}-2-(4-methanesulfonyl-phenyl)-propionamide 在 N-乙基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 2-[[三(羟甲基)甲基]氨基]乙磺酸 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 apoptozole
  参考文献：
  名称：

  WO2008/105565

  摘要：

  公开号：

文献信息

• A Small Molecule That Binds to an ATPase Domain of Hsc70 Promotes Membrane Trafficking of Mutant Cystic Fibrosis Transmembrane Conductance Regulator
  作者：Hyungseoph J. Cho、Heon Yung Gee、Kyung-Hwa Baek、Sung-Kyun Ko、Jong-Moon Park、Hookeun Lee、Nam-Doo Kim、Min Goo Lee、Injae Shin

  DOI：10.1021/ja206762p

  日期：2011.12.21

  Cystic fibrosis transmembrane conductance regulator (CFTR) is a cell-surface anion channel that permeates chloride and bicarbonate ions. The most frequent mutation of CFTR that causes cystic fibrosis is the deletion of phenylalanine at position 508 (Delta F508), which leads to defects in protein folding and cellular trafficking to the plasma membrane. The lack of the cell-surface CFTR results in a reduction in the lifespan due to chronic lung infection with progressive deterioration of lung function. Hsc70 plays a crucial role in degradation of mutant CFTR by the ubiquitin-proteasome system. To date, various Hsc70 inhibitors and transcription regulators have been tested to determine whether they correct the defective activity of mutant CFTR However, they exhibited limited or questionable effects on restoring the chloride channel activity in cystic fibrosis cells. Herein, we show that a small molecule apoptozole (Az) has high cellular potency to promote membrane trafficking of mutant CFTR and its chloride channel activity in cystic fibrosis cells. Results from affinity chromatography and ATPase activity assay indicate that Az inhibits the ATPase activity of Hsc70 by binding to its ATPase domain. In addition, a ligand-directed protein labeling and molecular modeling studies also suggest the binding of Az to an ATPase domain, in particular, an ATP-binding pocket. It is proposed that Az suppresses ubiquitination of Delta F508-CFTR maybe by blocking interaction of the mutant with Hsc70 and CHIP, and, as a consequence, it enhances membrane trafficking of the mutant.
• An Apoptosis‐Inducing Small Molecule That Binds to Heat Shock Protein 70
  作者：Darren R. Williams、Sung‐Kyun Ko、Sungjin Park、Myung‐Ryul Lee、Injae Shin

  DOI：10.1002/anie.200802801

  日期：2008.9.15
• IMIDAZOLE DERIVATIVES THAT INDUCE APOPTOSIS AND THEIR THERAPEUTIC USES
  申请人：Shin In-Jae

  公开号：US20100105726A1

  公开（公告）日：2010-04-29

  The present invention relates to a pharmaceutical composition comprising compound for induction of apoptosis, a method for inducing cancer cell apoptosis, a method to suppress lymphocyte activation, a method to improve intracellular trafficking of misfolded mutants and a screening method to identify additional compounds useful for inducing apoptosis, and more specifically, it relates to pharmaceutical compositions comprising imidazole derivatives as active gradients for induction of apoptosis to treat various diseases including cancers and immune-related diseases, the method of inducing apoptosis by treating cancer cells with the said pharmaceutical composition, the method of inactivating human lymphocytes by treating lymphocytes with the said pharmaceutical composition, the method of improving intracellular trafficking of misfolded mutants by treating cells containing the mutants with the said pharmaceutical composition, and the screening method for identifying additional compound useful for inducing apoptosis, wherein cells are incubated with the said pharmaceutical composition and detected.
• US8163791B2
  申请人：——

  公开号：US8163791B2

  公开（公告）日：2012-04-24