1-(6-(2-fluorobenzyloxy)quinazolin-7-yl)-3-(4-(trifluoromethyl)phenyl)urea | 1621090-24-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-(6-(2-fluorobenzyloxy)quinazolin-7-yl)-3-(4-(trifluoromethyl)phenyl)urea
• 英文别名: 1-[6-[(2-Fluorophenyl)methoxy]quinazolin-7-yl]-3-[4-(trifluoromethyl)phenyl]urea；1-[6-[(2-fluorophenyl)methoxy]quinazolin-7-yl]-3-[4-(trifluoromethyl)phenyl]urea
• CAS: 1621090-24-1
• 化学式: C₂₃H₁₆F₄N₄O₂
• 分子量: 456.399
• InChiKey: DQHOPAAPLDIZKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-二硝基酚 在 乌洛托品 、 10% Pt/activated carbon 、 氢气 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 21.5h， 生成 1-(6-(2-fluorobenzyloxy)quinazolin-7-yl)-3-(4-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  Novel quinazoline-urea analogues as modulators for Aβ-induced mitochondrial dysfunction: Design, synthesis, and molecular docking study

  摘要：

  A novel series of twenty-six quinazoline-urea derivatives was designed and synthesized. Their blocking activities against β-amyloid peptide (Aβ) induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measured the change of mitochondrial membrane potential. Seven compounds showed better inhibitory activities than the standard Cyclosporin A (CsA). The most active analogues were tested by MTT assay to evaluate their toxicity on the cellular survival; they revealed excellent cellular viability. To explain the difference in inhibitory activity, molecular docking study using (GOLD) program was performed for selected sets of the most active and inactive compounds on cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, ADME profiling, in silico toxicity, drug-likeness, and drug-score studies were discussed. From these results, we report compound 31 as the most active nonpeptidyl mPTP blocker possessing quinazoline-urea scaffold; 2 folds of CsA activity, which would constitute a new direction for the design of novel mPTP modulators.

  DOI：

  10.1016/j.ejmech.2014.07.027

文献信息

• Novel quinazoline-urea analogues as modulators for Aβ-induced mitochondrial dysfunction: Design, synthesis, and molecular docking study
  作者：Ahmed Elkamhawy、Jiyoun Lee、Beoung-Geon Park、Insun Park、Ae Nim Pae、Eun Joo Roh

  DOI：10.1016/j.ejmech.2014.07.027

  日期：2014.9

  A novel series of twenty-six quinazoline-urea derivatives was designed and synthesized. Their blocking activities against β-amyloid peptide (Aβ) induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measured the change of mitochondrial membrane potential. Seven compounds showed better inhibitory activities than the standard Cyclosporin A (CsA). The most active analogues were tested by MTT assay to evaluate their toxicity on the cellular survival; they revealed excellent cellular viability. To explain the difference in inhibitory activity, molecular docking study using (GOLD) program was performed for selected sets of the most active and inactive compounds on cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, ADME profiling, in silico toxicity, drug-likeness, and drug-score studies were discussed. From these results, we report compound 31 as the most active nonpeptidyl mPTP blocker possessing quinazoline-urea scaffold; 2 folds of CsA activity, which would constitute a new direction for the design of novel mPTP modulators.