(4-((2-(trifluoromethyl)benzyl)oxy)phenyl)methanamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-((2-(trifluoromethyl)benzyl)oxy)phenyl)methanamine
• 英文别名: [4-[[2-(Trifluoromethyl)phenyl]methoxy]phenyl]methanamine；[4-[[2-(trifluoromethyl)phenyl]methoxy]phenyl]methanamine
• 化学式: C₁₅H₁₄F₃NO
• 分子量: 281.277
• InChiKey: QIYWPYZLRNCSOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-((2-(trifluoromethyl)benzyl)oxy)phenyl)methanamine 、 6-氯-3-甲酰基-1H-吲哚-2-羧酸乙酯 在 lithium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 72.0h， 生成 3-(2-(tert-butylamino)-2-oxo-1-(N-(4-((2-(trifluoromethyl)benzyl)oxy)benzyl)formamido)ethyl)-6-chloro-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction

  摘要：

  Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient alpha-helical N-terminal "lid" segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111588
• 作为产物：
  描述：

  4-[[叔丁氧酰胺]甲基]-苯酚 在 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 (4-((2-(trifluoromethyl)benzyl)oxy)phenyl)methanamine
  参考文献：
  名称：

  Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction

  摘要：

  Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient alpha-helical N-terminal "lid" segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111588

文献信息

• Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction
  作者：Constantinos G. Neochoritis、Jack Atmaj、Aleksandra Twarda-Clapa、Ewa Surmiak、Lukasz Skalniak、Lisa-Maria Köhler、Damian Muszak、Katarzyna Kurpiewska、Justyna Kalinowska-Tłuścik、Barbara Beck、Tad A. Holak、Alexander Dömling

  DOI：10.1016/j.ejmech.2019.111588

  日期：2019.11

  Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient alpha-helical N-terminal "lid" segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.