4'-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile | 1417334-97-4

• 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'-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile
• 英文别名: 2-[4-[[5-(4-Nitrophenyl)-1,3,4-oxadiazol-2-yl]sulfanylmethyl]phenyl]benzonitrile；2-[4-[[5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl]sulfanylmethyl]phenyl]benzonitrile
• CAS: 1417334-97-4
• 化学式: C₂₂H₁₄N₄O₃S
• 分子量: 414.444
• InChiKey: LDWCZATWFDYKAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  134
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  对硝基苯甲酸甲酯 在 一水合肼 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 4'-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile
  参考文献：
  名称：

  Structure-based optimization of oxadiazole-based GSK-3 inhibitors

  摘要：

  Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases beta-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3 alpha and beta, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3 alpha and 17 nM for GSK-3 beta. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3 alpha over GSK-3 beta, with an IC50 of 35 nM for GSK-3 alpha. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.006

文献信息

• Synthesis, Antimicrobial Evaluation, and Structure Activity Relationship Studies of New Biphenyl-2-Carbonitrile Clubbed 1,3,4-Oxadiazole Derivatives
  作者：Kalpesh Parikh、Abhishek Joshi、Rahulsingh Kshatriya、Deepkumar Joshi

  DOI：10.1007/s11094-015-1320-y

  日期：2015.11

  Aseries of biphenyl-2-carbonitile clubbed 1,3,4-oxadiazole derivatives have been synthesized by the condensation of biphenyl-2-carbonitrile with various substituted 2-mercapto-5-aryl-1,3,4-oxadiazoles. Structures of the newly synthesized compounds IVa – IVh were characterized using FTIR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. All the compounds were screened for their antimicrobial properties against a broad spectrum of bacteria and fungi. It was very clearly noted from SAR study that the derivatives bearing electron-withdrawing functional groups (-NO2, -Cl) were more promising than the derivatives with electron-donating group (-CH3) as antimicrobial agents.

  一系列双苯基-2-氰基与各种取代的2-巯基-5-芳基-1,3,4-噁二唑衍生物通过缩合合成。新合成化合物IVa – IVh的结构通过傅里叶变换红外光谱（FTIR）、1H核磁共振（1H NMR）、13C核磁共振（13C NMR）、质谱和元素分析进行了表征。所有化合物均经过广谱细菌和真菌的抗微生物性能筛选。SAR研究清楚地表明，具有电子吸引官能团（-NO2，-Cl）的衍生物作为抗微生物剂比具有电子给体官能团（-CH3）的衍生物更具前景。
• Structure-based optimization of oxadiazole-based GSK-3 inhibitors
  作者：Fabio Lo Monte、Thomas Kramer、Jiamin Gu、Martin Brodrecht、Johannes Pilakowski、Ana Fuertes、Juan Manuel Dominguez、Batya Plotkin、Hagit Eldar-Finkelman、Boris Schmidt

  DOI：10.1016/j.ejmech.2012.06.006

  日期：2013.3

  Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases beta-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3 alpha and beta, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3 alpha and 17 nM for GSK-3 beta. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3 alpha over GSK-3 beta, with an IC50 of 35 nM for GSK-3 alpha. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety. (C) 2012 Elsevier Masson SAS. All rights reserved.