6-bromo-3-(2-(methylsulfonyl)ethyl)quinazolin-4(3H)-one

• 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: 6-bromo-3-(2-(methylsulfonyl)ethyl)quinazolin-4(3H)-one
• 英文别名: 6-Bromo-3-(2-methylsulfonylethyl)quinazolin-4-one
• 化学式: C₁₁H₁₁BrN₂O₃S
• 分子量: 331.19
• InChiKey: BIDMUYPKXSTWHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  75.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-difluoro-N-(2-(methoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide 、 6-bromo-3-(2-(methylsulfonyl)ethyl)quinazolin-4(3H)-one 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 生成 2,4-difluoro-N-(2-(methoxymethyl)-5-(3-(2-(methylsulfonyl)ethyl)-4-oxo-3,4-dihydroquinazolin-6-yl)pyridin-3-yl)benzenesulfonamide
  参考文献：
  名称：

  Concise SAR Exploration Based on the “Head-to-Tail” Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds

  摘要：

  In typical kinase inhibitor programs, a hinge binder showing best potency with preferential specificity is initially selected, followed by fine-tuning of the accompanying substituents on its core module. A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all the analogues in the series if a critical shortcoming is revealed. Thus, an early evaluation of structure activity relationships (SARs) can mitigate unforeseen outcomes within a series of multiple compounds, although there have been very few examples to follow such a policy. PI4KIII alpha is one of four mammalian phosphatidylinositol-4 kinases and has recently drawn significant attention as an emerging target for hepatitis C virus (HCV) treatment. In this letter, a novel "head-to-tail" approach to discover a diverse set of PI4KIII alpha inhibitors is reported. We believe this method will generate distinct core scaffolds, a rational strategy to circumvent potential risks in general kinase programs.

  DOI：

  10.1021/acsmedchemlett.6b00232
• 作为产物：
  描述：

  5-溴靛红酸酐 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 6-bromo-3-(2-(methylsulfonyl)ethyl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Concise SAR Exploration Based on the “Head-to-Tail” Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds

  摘要：

  In typical kinase inhibitor programs, a hinge binder showing best potency with preferential specificity is initially selected, followed by fine-tuning of the accompanying substituents on its core module. A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all the analogues in the series if a critical shortcoming is revealed. Thus, an early evaluation of structure activity relationships (SARs) can mitigate unforeseen outcomes within a series of multiple compounds, although there have been very few examples to follow such a policy. PI4KIII alpha is one of four mammalian phosphatidylinositol-4 kinases and has recently drawn significant attention as an emerging target for hepatitis C virus (HCV) treatment. In this letter, a novel "head-to-tail" approach to discover a diverse set of PI4KIII alpha inhibitors is reported. We believe this method will generate distinct core scaffolds, a rational strategy to circumvent potential risks in general kinase programs.

  DOI：

  10.1021/acsmedchemlett.6b00232

文献信息

• Concise SAR Exploration Based on the “Head-to-Tail” Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds
  作者：Satoru Noji、Noriyoshi Seki、Takaki Maeba、Takayuki Sakai、Eiichi Watanabe、Katsuya Maeda、Kyoko Fukushima、Toru Noguchi、Kazuya Ogawa、Yukiyo Toyonaga、Tamotsu Negoro、Hisashi Kawasaki、Makoto Shiozaki

  DOI：10.1021/acsmedchemlett.6b00232

  日期：2016.10.13

  In typical kinase inhibitor programs, a hinge binder showing best potency with preferential specificity is initially selected, followed by fine-tuning of the accompanying substituents on its core module. A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all the analogues in the series if a critical shortcoming is revealed. Thus, an early evaluation of structure activity relationships (SARs) can mitigate unforeseen outcomes within a series of multiple compounds, although there have been very few examples to follow such a policy. PI4KIII alpha is one of four mammalian phosphatidylinositol-4 kinases and has recently drawn significant attention as an emerging target for hepatitis C virus (HCV) treatment. In this letter, a novel "head-to-tail" approach to discover a diverse set of PI4KIII alpha inhibitors is reported. We believe this method will generate distinct core scaffolds, a rational strategy to circumvent potential risks in general kinase programs.