| 1467028-61-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• CAS: 1467028-61-0
• 化学式: C₃₃H₃₁N₃O₃
• 分子量: 517.627
• InChiKey: UDQSUFLAILWOMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  39.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  73.22
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 4-((2-ethyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-8-yl)-methyl)-N-hydroxybenzamide
  参考文献：
  名称：

  Quinazolin-4-one Derivatives as Selective Histone Deacetylase-6 Inhibitors for the Treatment of Alzheimer’s Disease

  摘要：

  Novel quinazolin-4-one derivatives containing a hydroxamic acid moiety were designed and synthesized. All compounds were subjected to histone deacetylase (HDAC) enzymatic assays to identify selective HDAC6 inhibitors with nanomolar IC50 values. (E)-3-(2-Ethyl-7-fluoro-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-N-hydroxyacrylamide, 4h, NHis the most potent HDAC6 inhibitor (IC50, 8 nM). In vitro, these compounds induced neurite outgrowth accompanied by growth-associated protein 43 expression, and they enhanced the synaptic activities of PC12 and SH-SY5Y neuronal cells without producing toxic or mitogenic effects. Several of the compounds dramatically increased nonhistone protein acetylation, specifically of g-tubulin. Some of the more potent HDAC6 inhibitors decreased zinc-mediated beta-amyloid aggregation in vitro. N-Hydroxy-3-(2-methyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-7-yl)-acrylarnide, 3f, the most promising drug candidate, selectively inhibits HDAC6 (IC50,29 nM), practically does not affect human ether-a-go-go-related membrane channel activity (IC50 >10 mu M) or cytochrome P450 activity (IC50 >63 mu M) in vitro, and significantly improves learning-based performances of mice with beta-amyloid-induced hippocampal lesions.

  DOI：

  10.1021/jm400564j
• 作为产物：
  描述：

  2-氨基-3-氯苯甲酸 在 吡啶 、 亚磷酸三苯酯 、 tris-(dibenzylideneacetone)dipalladium(0) 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 为溶剂， 反应 26.92h， 生成
  参考文献：
  名称：

  Quinazolin-4-one Derivatives as Selective Histone Deacetylase-6 Inhibitors for the Treatment of Alzheimer’s Disease

  摘要：

  Novel quinazolin-4-one derivatives containing a hydroxamic acid moiety were designed and synthesized. All compounds were subjected to histone deacetylase (HDAC) enzymatic assays to identify selective HDAC6 inhibitors with nanomolar IC50 values. (E)-3-(2-Ethyl-7-fluoro-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-N-hydroxyacrylamide, 4h, NHis the most potent HDAC6 inhibitor (IC50, 8 nM). In vitro, these compounds induced neurite outgrowth accompanied by growth-associated protein 43 expression, and they enhanced the synaptic activities of PC12 and SH-SY5Y neuronal cells without producing toxic or mitogenic effects. Several of the compounds dramatically increased nonhistone protein acetylation, specifically of g-tubulin. Some of the more potent HDAC6 inhibitors decreased zinc-mediated beta-amyloid aggregation in vitro. N-Hydroxy-3-(2-methyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-7-yl)-acrylarnide, 3f, the most promising drug candidate, selectively inhibits HDAC6 (IC50,29 nM), practically does not affect human ether-a-go-go-related membrane channel activity (IC50 >10 mu M) or cytochrome P450 activity (IC50 >63 mu M) in vitro, and significantly improves learning-based performances of mice with beta-amyloid-induced hippocampal lesions.

  DOI：

  10.1021/jm400564j