1-(benzo[d][1,3]dioxol-5-yl)-N-(4-(3-chlorophenyl)-5-methylthiazol-2-yl)cyclopropanecarboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 1-(benzo[d][1,3]dioxol-5-yl)-N-(4-(3-chlorophenyl)-5-methylthiazol-2-yl)cyclopropanecarboxamide
• 英文别名: 1-(1,3-benzodioxol-5-yl)-N-[4-(3-chlorophenyl)-5-methyl-1,3-thiazol-2-yl]cyclopropane-1-carboxamide
• 化学式: C₂₁H₁₇ClN₂O₃S
• 分子量: 412.897
• InChiKey: WALUOMJMJCMOKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  88.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  胡椒腈 在 苄基三乙基氯化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 1-(benzo[d][1,3]dioxol-5-yl)-N-(4-(3-chlorophenyl)-5-methylthiazol-2-yl)cyclopropanecarboxamide
  参考文献：
  名称：

  Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools

  摘要：

  The most common CF mutation, F508del, impairs the processing and gating of CFTR protein. This deletion results in the improper folding of the protein and its degradation before it reaches the plasma membrane of epithelial cells. Present correctors, like VX809 only induce a partial rescue of the mutant protein. Our previous studies reported a class of compounds, called aminoarylthiazoles (AATs), featuring an interesting activity as correctors. Some of them show additive effect with VX809 indicating a different mechanism of action. In an attempt to construct more interesting molecules, it was thought to generate chemically hybrid compounds, blending a portion of VX809 merged to the thiazole scaffold. This approach was guided by the development of QSAR analyses, which were performed based on the F508del correctors so far disclosed in the literature. This strategy was aimed at exploring the key requirements turning in the corrector ability of the collected derivatives and allowed us to derive a predictive model guiding for the synthesis of novel hybrids as promising correctors. The new molecules were tested in functional and biochemical assays on bronchial CFBE41o-cells expressing F508del-CFTR showing a promising corrector activity. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.030