8-chloro-2-methyl-3-phenyl-3H-quinazolin-4-one | 38520-81-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-chloro-2-methyl-3-phenyl-3H-quinazolin-4-one
• 英文别名: 8-chloro-2-methyl-3-phenyl-3H-quinazolin-4-one；2-Methyl-3-phenyl-8-chlor-4(3H)-chinazolinon
• CAS: 38520-81-9
• 化学式: C₁₅H₁₁ClN₂O
• 分子量: 270.718
• InChiKey: WYAUKJSKWMXPCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  34.89
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  8-chloro-2-methyl-3-phenyl-3H-quinazolin-4-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 、 N-甲基二环己基胺 、 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 、 正己烷 、 甲苯 为溶剂， 反应 50.0h， 生成 N-hydroxy-3-(2-methyl-4-oxo-3-phenyl-3,4-dihydro-quinazolin-8-yl)acrylamide
  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 作用下， 反应 0.42h， 生成 8-chloro-2-methyl-3-phenyl-3H-quinazolin-4-one
  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