2-[4-(Bromomethyl)phenyl]-5-methoxybenzonitrile | 1428147-20-9

• 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: 2-[4-(Bromomethyl)phenyl]-5-methoxybenzonitrile
• 英文别名: 2-[4-(bromomethyl)phenyl]-5-methoxybenzonitrile
• CAS: 1428147-20-9
• 化学式: C₁₅H₁₂BrNO
• 分子量: 302.17
• InChiKey: GQYZFXHOSQUWCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2-thiol 、 2-[4-(Bromomethyl)phenyl]-5-methoxybenzonitrile 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以50%的产率得到2-[4-[[5-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,3,4-oxadiazol-2-yl]sulfanylmethyl]phenyl]-5-methoxybenzonitrile
  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
• 作为产物：
  描述：

  2-溴-5-甲氧基苯甲腈 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 偶氮二异丁腈 、 sodium carbonate 作用下， 以 四氯化碳 、 乙醇 、 水 、 甲苯 为溶剂， 生成 2-[4-(Bromomethyl)phenyl]-5-methoxybenzonitrile
  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