N-(4-fluorophenyl)-3,4-dimethoxyaniline

• 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: N-(4-fluorophenyl)-3,4-dimethoxyaniline
• 英文别名: N-(4-Fluorophenyl)-3,4-dimethoxyaniline
• 化学式: C₁₄H₁₄FNO₂
• 分子量: 247.269
• InChiKey: KCEVJMDGFHCELX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methoxy-2,2-dimethyl-2H-chromene-6-carbonyl chloride 、 N-(4-fluorophenyl)-3,4-dimethoxyaniline 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 生成 N-(3,4-dimethoxyphenyl)-N-(4-fluorophenyl)-5-methoxy-2,2-dimethyl-2H-chromene-6-carboxamide
  参考文献：
  名称：

  Investigation of B,C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents

  摘要：

  On the basis of deguelin, a series of the B, C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1 alpha inhibition. Among them, compound 57 showed potent HIF-1 alpha inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 Cterminal inhibitor.

  DOI：

  10.1016/j.bmc.2019.02.040
• 作为产物：
  描述：

  3,4-二甲氧基苯胺 、 alkaline earth salt of/the/ methylsulfuric acid 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 为溶剂， 以65%的产率得到N-(4-fluorophenyl)-3,4-dimethoxyaniline
  参考文献：
  名称：

  Investigation of B,C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents

  摘要：

  On the basis of deguelin, a series of the B, C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1 alpha inhibition. Among them, compound 57 showed potent HIF-1 alpha inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 Cterminal inhibitor.

  DOI：

  10.1016/j.bmc.2019.02.040

文献信息

• Investigation of B,C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents
  作者：Ho Shin Kim、Van-Hai Hoang、Mannkyu Hong、Kyung Chul Kim、Jihyae Ann、Cong-Truong Nguyen、Ji Hae Seo、Hoon Choi、Jun Yong Kim、Kyu-Won Kim、Woong Sub Byun、Sangkook Lee、Seungbeom Lee、Young-Ger Suh、Jie Chen、Hyun-Ju Park、Tae-Min Cho、Ji Young Kim、Jae Hong Seo、Jeewoo Lee

  DOI：10.1016/j.bmc.2019.02.040

  日期：2019.4

  On the basis of deguelin, a series of the B, C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1 alpha inhibition. Among them, compound 57 showed potent HIF-1 alpha inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 Cterminal inhibitor.