3-(3,4-dimethoxyphenyl)-5-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine | 1615223-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(3,4-dimethoxyphenyl)-5-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 3-(3,4-dimethoxyphenyl)-5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine
• CAS: 1615223-25-0
• 化学式: C₂₀H₁₇N₃O₂
• 分子量: 331.374
• InChiKey: KBDHLWBPIOODDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  60
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(苯磺酰基)-5-溴-3-碘吡咯并[2,3-b]吡啶 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 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 3.0h， 生成 3-(3,4-dimethoxyphenyl)-5-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Structure-based de novo design and identification of D816V mutant-selective c-KIT inhibitors

  摘要：

  通过使用改进的精确溶剂自由能的评分函数进行基于结构的全新设计，确定了具有纳摩尔抑制活性和对功能获得性D816V突变体高选择性的新型7-氮杂吲哚基c-KIT抑制剂。

  DOI：

  10.1039/c4ob00053f

文献信息

• Development and Biological Evaluation of Potent and Selective c-KIT^D816V Inhibitors
  作者：Soyoung Lee、Hyunseung Lee、Jinhee Kim、Suhyun Lee、Soo Jung Kim、Byong-Seok Choi、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm500413g

  日期：2014.8.14

  The c-KIT tyrosine kinase has emerged as a potential therapeutic target for an array of diseases. However, there exists a drug resistance that is caused by mutations in c-KIT; therefore, c-KIT remains as a clinical challenge due to limited effective treatment options for therapies. For example, the acquired activating point mutation D816V significantly impairs the efficacy of targeted cancer therapies. Understanding the mechanisms of drug resistance at the molecular level will aid in designing and developing particular inhibitors with the potential to overcome these resistance mutations. We undertake a structure-based de novo design of 7-azaindole as the molecular core using the modified scoring function. This approach led to an identification of new c-KIT inhibitors over 100-fold specific for the D816V mutant relative to the wild-type c-KIT with nanomolar inhibitory activity. More importantly, these compounds potently inhibit clinically relevant D816V mutations of c-KIT in biochemical and cellular studies.
• Structure-based de novo design and identification of D816V mutant-selective c-KIT inhibitors
  作者：Hwangseo Park、Soyoung Lee、Suhyun Lee、Sungwoo Hong

  DOI：10.1039/c4ob00053f

  日期：——

  New 7-azaindole-based c-KIT inhibitors with nanomolar inhibitory activity and high selectivity for the gain-of-function D816V mutant were identified through the structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy.

  通过使用改进的精确溶剂自由能的评分函数进行基于结构的全新设计，确定了具有纳摩尔抑制活性和对功能获得性D816V突变体高选择性的新型7-氮杂吲哚基c-KIT抑制剂。