Methyl 4-[[(2-methylbenzoyl)hydrazinylidene]methyl]benzoate

• 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: Methyl 4-[[(2-methylbenzoyl)hydrazinylidene]methyl]benzoate
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: RMBVIHYOFCTCSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 4-[[(2-methylbenzoyl)hydrazinylidene]methyl]benzoate 在 碘 、 potassium carbonate 、 trilithium citrate 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 4-(5-(o-tolyl)-1,3,4-oxadiazol-2-yl)benzoic acid
  参考文献：
  名称：

  Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs

  摘要：

  Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR mRNA leading to the production of a truncated protein that lacks normal function causing a more severe form of the cystic fibrosis (CF) disease. About 10% of patients affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124. In this context we aimed to compare the activity of PTC124 with analogues differing in the heteroatoms position in the central heterocyclic core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified a new small molecule (NV2445) with 1,3,4-oxadiazole core showing a high read through activity. Moreover, we evaluated the CFTR functionality after NV2445 treatment in CF model systems and in cells expressing a nonsense-CFTR-mRNA. Finally, we studied the supramolecular interactions between TRIDs and CFTR-mRNA to assess the biological target/mechanism and compared the predicted ADME properties of NV2945 and PTC124. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.057
• 作为产物：
  描述：

  对甲苯甲酸 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.05h， 生成 Methyl 4-[[(2-methylbenzoyl)hydrazinylidene]methyl]benzoate
  参考文献：
  名称：

  Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs

  摘要：

  Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR mRNA leading to the production of a truncated protein that lacks normal function causing a more severe form of the cystic fibrosis (CF) disease. About 10% of patients affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124. In this context we aimed to compare the activity of PTC124 with analogues differing in the heteroatoms position in the central heterocyclic core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified a new small molecule (NV2445) with 1,3,4-oxadiazole core showing a high read through activity. Moreover, we evaluated the CFTR functionality after NV2445 treatment in CF model systems and in cells expressing a nonsense-CFTR-mRNA. Finally, we studied the supramolecular interactions between TRIDs and CFTR-mRNA to assess the biological target/mechanism and compared the predicted ADME properties of NV2945 and PTC124. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.057

文献信息

• Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs
  作者：Ivana Pibiri、Laura Lentini、Raffaella Melfi、Marco Tutone、Sara Baldassano、Paola Ricco Galluzzo、Aldo Di Leonardo、Andrea Pace

  DOI：10.1016/j.ejmech.2018.09.057

  日期：2018.11

  Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR mRNA leading to the production of a truncated protein that lacks normal function causing a more severe form of the cystic fibrosis (CF) disease. About 10% of patients affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124. In this context we aimed to compare the activity of PTC124 with analogues differing in the heteroatoms position in the central heterocyclic core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified a new small molecule (NV2445) with 1,3,4-oxadiazole core showing a high read through activity. Moreover, we evaluated the CFTR functionality after NV2445 treatment in CF model systems and in cells expressing a nonsense-CFTR-mRNA. Finally, we studied the supramolecular interactions between TRIDs and CFTR-mRNA to assess the biological target/mechanism and compared the predicted ADME properties of NV2945 and PTC124. (C) 2018 Elsevier Masson SAS. All rights reserved.