3-苄基-7-氯-2-甲基-3H-喹唑啉-4-酮 | 10527-94-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 3-苄基-7-氯-2-甲基-3H-喹唑啉-4-酮
• 英文名称: 3-benzyl-7-chloro-2-methyl-3H-quinazolin-4-one
• 英文别名: 3-Benzyl-7-chlor-2-methyl-3H-benzo<1,3>diazin-4-on；3-benzyl-7-chloro-2-methylquinazolin-4(3H)-one；3-benzyl-7-chloro-2-methylquinazolin-4-one
• CAS: 10527-94-3
• 化学式: C₁₆H₁₃ClN₂O
• 分子量: 284.745
• InChiKey: QAFXOFRVQNFBIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-苄基-7-氯-2-甲基-3H-喹唑啉-4-酮 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 3-(3-benzyl-2-methyl-4-oxo-3,4-dihydro-quinazolin-7-yl)-N-hydroxyacrylamide
  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 、 溶剂黄146 作用下， 反应 16.25h， 生成 3-苄基-7-氯-2-甲基-3H-喹唑啉-4-酮
  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

文献信息

• [EN] QUINAZOLINONE COMPOUNDS AS ANTICANCER AGENTS<br/>[FR] COMPOSES QUINAZOLINONE UTILISES EN TANT QU'AGENTS ANTICANCEREUX
  申请人：CHIRON CORP

  公开号：WO2005051922A1

  公开（公告）日：2005-06-09

  Quinazolinone compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the quinazolinone compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the quinazolinone compounds, either alone or in combination with at least one additional therapeutic agent as KSP inhibitors, in the prophylaxis or treatment of proliferative diseases.

  喹唑啉酮化合物、药用可接受盐及其前药；包括药用可接受载体和一种或多种喹唑啉酮化合物的组合物，可以单独使用或与至少一种额外治疗剂联合使用。使用喹唑啉酮化合物的方法，可以单独使用或与至少一种额外治疗剂联合使用作为KSP抑制剂，用于预防或治疗增殖性疾病。
• Quinazolinone compounds as anticancer agents
  申请人：Wang Weibo

  公开号：US20050209254A1

  公开（公告）日：2005-09-22

  Quinazolinone compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the quinazolinone compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the quinazolinone compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases.

  喹唑啉酮化合物、药学上可接受的盐以及其前药；包括药学上可接受的载体和一个或多个喹唑啉酮化合物的组合物，可以单独使用或与至少一种其他治疗剂联合使用。使用喹唑啉酮化合物，可以单独使用或与至少一种其他治疗剂联合使用，用于预防或治疗增殖性疾病的方法。
• Quinazolinone Compounds as Anticancer Agents
  申请人：Wang Weibo

  公开号：US20110190293A1

  公开（公告）日：2011-08-04

  Quinazolinone compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the quinazolinone compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the quinazolinone compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases.

  喹唑啉酮化合物，药学上可接受的盐和其前药；包含药学上可接受的载体和一个或多个喹唑啉酮化合物的组合物，单独使用或与至少一种额外治疗剂联合使用的方法。使用喹唑啉酮化合物，单独使用或与至少一种额外治疗剂联合使用，预防或治疗增生性疾病的方法。
• QUINAZOLINONE COMPOUNDS AS ANTICANCER AGENTS
  申请人：CHIRON CORPORATION

  公开号：EP1689724A1

  公开（公告）日：2006-08-16
• US7939539B2
  申请人：——

  公开号：US7939539B2

  公开（公告）日：2011-05-10