4-((2-(3,5-bis(trifluoromethyl)phenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole-1-yl)methyl)benzoic acid | 1054543-79-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-((2-(3,5-bis(trifluoromethyl)phenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole-1-yl)methyl)benzoic acid
• 英文别名: 4-[[2-[3,5-Bis(trifluoromethyl)phenyl]-4,5-bis(4-methoxyphenyl)imidazol-1-yl]methyl]benzoic acid
• CAS: 1054543-79-1
• 化学式: C₃₃H₂₄F₆N₂O₄
• 分子量: 626.555
• InChiKey: XDZVGEJPDRYNOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-((2-(3,5-bis(trifluoromethyl)phenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole-1-yl)methyl)benzoic acid 在 四溴化碳 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 75.5h， 生成
  参考文献：
  名称：

  Subcellular Hsp70 Inhibitors Promote Cancer Cell Death via Different Mechanisms

  摘要：

  Mechanisms underlying cancer cell death caused by inhibitors of subcellular Hsp70 proteins have been elucidated. An inhibitor of Hsp70, apoptozole (Az), is mainly translocated into lysosomes of cancer cells where it induces lysosomal membrane permeabilization, thereby promoting lysosome-mediated apoptosis. Additionally, Az impairs autophagy in cancer cells owing to its ability to disrupt the lysosomal function. However, the Az-triphenylphosphonium conjugate, Az-TPP-O3, localizes mainly to mitochondria of cancer cells where it inhibits the mortalin-p53 interaction and induces mitochondrial outer membrane permeabilization, consequently leading to mitochondria-mediated apoptosis. Unlike Az, Az-TPP-O3 does not have an effect on autophagy in cancer cells. Collectively, the findings indicate that inhibitors of lysosomal Hsp70 and mitochondrial mortalin enhance cancer cell death via distinctively different mechanisms. Additionally, the findings arising from this effort demonstrate that studies aimed at determining subcellular locations and functions of small-molecule modulators provide a deeper understanding of their modes of action in cells.

  DOI：

  10.1016/j.chembiol.2018.06.010
• 作为产物：
  描述：

  4-氨甲基苯甲酸 、 3,5-双三氟甲基苯甲醛 、 4,4'-二甲氧基苯酚酯 在 ammonium acetate 、 溶剂黄146 作用下， 生成 4-((2-(3,5-bis(trifluoromethyl)phenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole-1-yl)methyl)benzoic acid
  参考文献：
  名称：

  发现降冰片烯作为一种新型疏水标签应用于蛋白质降解

  摘要：

  开发了一种新型的基于降冰片烯的疏水标签，扩大了靶向蛋白质降解技术的临床潜力。通过连接 ALK 配体和降冰片烯获得的降解剂Hyt-9在体外和体内表现出有效的抗增殖和降解活性。此外，当在降解剂Hyt-13中标记 EZH2 抑制剂他泽美司他时，降冰片烯可用于降解 EZH2 。

  DOI：

  10.1002/anie.202217246

文献信息

• 一种用于低温光热治疗的刺激响应性纳米药物
  申请人：青岛科技大学

  公开号：CN116120298A

  公开（公告）日：2023-05-16

  发明名称一种用于低温光热治疗的刺激响应性纳米药物摘要本发明提供一种具有刺激响应性的肿瘤温和光热治疗的纳米材料的制备方法和应用。提供了具有式(Ⅰ所)示结构或其异构体、药学上可接受的盐、水合物或溶剂化物在水溶液中自组装形成的微纳结构，及其药物组合物的制备及其肿瘤温和的光热治疗、刺激响应性释放药物中的应用。本发明所提供的化合物可以靶向肿瘤，在激光照射下具有高光热转换效率的材料产生热量，实现肿瘤细胞的热消融。热休克蛋白抑制剂(APO)可以抑制过表达的Hsp90来减少肿瘤细胞耐热性，减少由于热扩散对周围正常组织的热损伤，实现肿瘤温和的光热治疗。刺激响应性连接键可以响应肿瘤中高水平的谷胱甘肽和过氧化氢，实现高效精准的药物释放。
• NOVEL IMIDAZOLE DERIVATIVE AND THERAPEUTICAL USE THEREOF
  申请人：Industry-Academic Cooperation Foundation, Yonsei University

  公开号：EP3050875B1

  公开（公告）日：2019-03-13
• 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.
• WO2008/105565
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.