2,4-difluoro-N-(2-(1-methoxyethyl)-5-(4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl)pyridin-3-yl)benzenesulfonamide

• 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: 2,4-difluoro-N-(2-(1-methoxyethyl)-5-(4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl)pyridin-3-yl)benzenesulfonamide
• 英文别名: 2,4-difluoro-N-[2-(1-methoxyethyl)-5-(4-oxo-3-phenylquinazolin-6-yl)pyridin-3-yl]benzenesulfonamide
• 化学式: C₂₈H₂₂F₂N₄O₄S
• 分子量: 548.57
• InChiKey: VWSZUAJSBVGFSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氨基-5-碘苯甲酸 在 1,1'-双(二苯基膦)二茂铁 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 caesium carbonate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 6.5h， 生成 2,4-difluoro-N-(2-(1-methoxyethyl)-5-(4-oxo-3-phenyl-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