N-(phenyl(quinolin-7-yl)methyl)aniline

• 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: N-(phenyl(quinolin-7-yl)methyl)aniline
• 英文别名: N-[phenyl(quinolin-7-yl)methyl]aniline
• 化学式: C₂₂H₁₈N₂
• 分子量: 310.398
• InChiKey: PILXSNKBDOUMSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  7-溴喹啉 、 N-苄叉苯胺 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 10.5h， 生成 N-(phenyl(quinolin-7-yl)methyl)aniline
  参考文献：
  名称：

  喹啉醇作为TEAD依赖性转录激活剂的鉴定。

  摘要：

  转录共调节因子YAP（Yes相关蛋白）和TAZ（具有PDZ结合基序的转录共激活因子）是控制各种生理和病理过程的河马信号通路的脊椎动物下游效应子。YAP和TAZ与TEAD（TEA域）家族的转录因子配对以启动转录。我们先前在TEADs中发现了一个易处理的口袋，从生理学角度来看，它可以与棕榈酸酯结合。本文中，开发了TEAD-棕榈酸酯相互作用筛选以选择占据TEAD的棕榈酸酯结合袋（PBP）的小分子。我们显示，喹啉醇是TEAD结合的化合物，可增加YAP / TAZ-TEAD活性，已通过TEAD报告基因分析，RT-qPCR和RNA-Seq分析进行了验证。结构-活性关系研究发现了TEAD激活所必需的喹啉醇取代基。我们揭示了一种新的机制，其中喹啉酚通过占据PBP来稳定YAP / TAZ蛋白水平。在小鼠伤口愈合模型中，喹啉醇提高了YAP活性，加速了体内伤口的闭合。尽管占据PBP的小分子已显示抑制YAP /

  DOI：

  10.1021/acschembio.9b00786

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.
• Identification of Quinolinols as Activators of TEAD-Dependent Transcription
  作者：Ajaybabu V. Pobbati、Tom Mejuch、Sayan Chakraborty、Hacer Karatas、Sakshibeedu R. Bharath、Stéphanie M. Guéret、Pierre-Alexis Goy、Gernot Hahne、Axel Pahl、Sonja Sievers、Ernesto Guccione、Haiwei Song、Herbert Waldmann、Wanjin Hong

  DOI：10.1021/acschembio.9b00786

  日期：2019.12.20

  has been physiologically shown to bind palmitate. Herein, a TEAD-palmitate interaction screen was developed to select small molecules occupying the palmitate-binding pocket (PBP) of TEADs. We show that quinolinols were TEAD-binding compounds that augment YAP/TAZ-TEAD activity, which was verified using TEAD reporter assay, RT-qPCR, and RNA-Seq analyses. Structure-activity relationship investigations uncovered

  转录共调节因子YAP（Yes相关蛋白）和TAZ（具有PDZ结合基序的转录共激活因子）是控制各种生理和病理过程的河马信号通路的脊椎动物下游效应子。YAP和TAZ与TEAD（TEA域）家族的转录因子配对以启动转录。我们先前在TEADs中发现了一个易处理的口袋，从生理学角度来看，它可以与棕榈酸酯结合。本文中，开发了TEAD-棕榈酸酯相互作用筛选以选择占据TEAD的棕榈酸酯结合袋（PBP）的小分子。我们显示，喹啉醇是TEAD结合的化合物，可增加YAP / TAZ-TEAD活性，已通过TEAD报告基因分析，RT-qPCR和RNA-Seq分析进行了验证。结构-活性关系研究发现了TEAD激活所必需的喹啉醇取代基。我们揭示了一种新的机制，其中喹啉酚通过占据PBP来稳定YAP / TAZ蛋白水平。在小鼠伤口愈合模型中，喹啉醇提高了YAP活性，加速了体内伤口的闭合。尽管占据PBP的小分子已显示抑制YAP /