ethyl 4-(((8-hydroxyquinolin-7-yl)(4-(trifluoromethyl)phenyl)methyl)amino)benzoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 4-(((8-hydroxyquinolin-7-yl)(4-(trifluoromethyl)phenyl)methyl)amino)benzoate
• 英文别名: Ethyl 4-[[(8-hydroxyquinolin-7-yl)-[4-(trifluoromethyl)phenyl]methyl]amino]benzoate；ethyl 4-[[(8-hydroxyquinolin-7-yl)-[4-(trifluoromethyl)phenyl]methyl]amino]benzoate
• 化学式: C₂₆H₂₁F₃N₂O₃
• 分子量: 466.46
• InChiKey: CCRBUKHMSWAQPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  对三氟甲基苯甲醛 、 8-羟基喹啉 、 苯佐卡因 在 甲酸 作用下， 以 乙腈 为溶剂， 以30%的产率得到ethyl 4-(((8-hydroxyquinolin-7-yl)(4-(trifluoromethyl)phenyl)methyl)amino)benzoate
  参考文献：
  名称：

  8-羟基喹啉贝蒂产品的合成和细胞保护作用。

  摘要：

  已经证明8-羟基喹啉药效团支架具有一系列活性，例如金属螯合，酶抑制，细胞毒性和细胞保护。基于我们以前的发现，我们着手优化支架的细胞保护活性，以使其潜在地应用于中枢神经系统相关疾病。通过利用甲酸介导的工业相容性偶联物，与苯胺，恶唑，吡啶和嘧啶等芳香族伯胺，以及（杂）芳族醛和8-氢氧喹啉衍生物，构建48位成员的Betti库。经柱层析和重结晶后，得到相应的类似物，产率为13-90％。通过利用化学诱导的氧化应激的细胞保护测定法对合成的类似物进行了优化，并在正交测定，实时细胞生存力方法，基于荧光激活细胞分选（FACS）的测定线粒体膜电位变化的测定以及基因表达分析中进一步测试了活性最高的化合物。最好的候选者在所有测试系统中均显示出强大的纳摩尔活性，并支持将来需要对中枢神经系统（CNS）疾病的动物模型进行研究。

  DOI：

  10.3390/molecules23081934

文献信息

• 8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells
  作者：Idrees Mohammed、Shahienaz E. Hampton、Louise Ashall、Emily R. Hildebrandt、Robert A. Kutlik、Surya P. Manandhar、Brandon J. Floyd、Haley E. Smith、Jonathan K. Dozier、Mark D. Distefano、Walter K. Schmidt、Timothy M. Dore

  DOI：10.1016/j.bmc.2015.11.043

  日期：2016.1

  Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer. (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis and Cytoprotective Characterization of 8-Hydroxyquinoline Betti Products
  作者：Iván Kanizsai、Ramóna Madácsi、László Hackler、Márió Gyuris、Gábor J. Szebeni、Orsolya Huzián、László G. Puskás

  DOI：10.3390/molecules23081934

  日期：——

  The 8-hydroxyquinoline pharmacophore scaffold has been shown to possess a range of activities as metal chelation, enzyme inhibition, cytotoxicity, and cytoprotection. Based on our previous findings we set out to optimize the scaffold for cytoprotective activity for its potential application in central nervous system related diseases. A 48-membered Betti-library was constructed by the utilization of

  已经证明8-羟基喹啉药效团支架具有一系列活性，例如金属螯合，酶抑制，细胞毒性和细胞保护。基于我们以前的发现，我们着手优化支架的细胞保护活性，以使其潜在地应用于中枢神经系统相关疾病。通过利用甲酸介导的工业相容性偶联物，与苯胺，恶唑，吡啶和嘧啶等芳香族伯胺，以及（杂）芳族醛和8-氢氧喹啉衍生物，构建48位成员的Betti库。经柱层析和重结晶后，得到相应的类似物，产率为13-90％。通过利用化学诱导的氧化应激的细胞保护测定法对合成的类似物进行了优化，并在正交测定，实时细胞生存力方法，基于荧光激活细胞分选（FACS）的测定线粒体膜电位变化的测定以及基因表达分析中进一步测试了活性最高的化合物。最好的候选者在所有测试系统中均显示出强大的纳摩尔活性，并支持将来需要对中枢神经系统（CNS）疾病的动物模型进行研究。