N-(3-bromophenyl)-2-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)acetamide | 1447463-74-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: N-(3-bromophenyl)-2-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)acetamide
• 英文别名: N-(3-bromophenyl)-2-(5-hydroxy-4-oxo-2-phenylchromen-7-yl)oxyacetamide
• CAS: 1447463-74-2
• 化学式: C₂₃H₁₆BrNO₅
• 分子量: 466.288
• InChiKey: RIDOCYIHPUSNKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  白杨素 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.17h， 生成 N-(3-bromophenyl)-2-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)acetamide
  参考文献：
  名称：

  Structure-based design of flavone-based inhibitors of wild-type and T315I mutant of ABL

  摘要：

  The existence of drug resistance caused by mutations in the break-point cluster region-Abelson (BCR-ABL) tyrosine kinase domain remains a clinical challenge due to limited treatment options for effective CML therapies. Here, we report a series of flavone-based common inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of BCR-ABL. The original hit 1 was extensively modified through a structure-based drug design strategy, especially by varying the C7 acetamide appendage of the scaffold to exploit extended interactions with P-loop residues. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of ABL are discussed in detail. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.095

文献信息

• Structure-based design of flavone-based inhibitors of wild-type and T315I mutant of ABL
  作者：Hyeonjeong Choe、Jieun Kim、Sungwoo Hong

  DOI：10.1016/j.bmcl.2013.05.095

  日期：2013.8

  The existence of drug resistance caused by mutations in the break-point cluster region-Abelson (BCR-ABL) tyrosine kinase domain remains a clinical challenge due to limited treatment options for effective CML therapies. Here, we report a series of flavone-based common inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of BCR-ABL. The original hit 1 was extensively modified through a structure-based drug design strategy, especially by varying the C7 acetamide appendage of the scaffold to exploit extended interactions with P-loop residues. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of ABL are discussed in detail. (C) 2013 Elsevier Ltd. All rights reserved.