5-bromo-1-(phenylsulfonyl)-3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine | 1377503-76-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-bromo-1-(phenylsulfonyl)-3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 1-(Benzenesulfonyl)-5-bromo-3-pyridin-4-ylpyrrolo[2,3-b]pyridine
• CAS: 1377503-76-8
• 化学式: C₁₈H₁₂BrN₃O₂S
• 分子量: 414.282
• InChiKey: UCFKHOODJUMFIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(phenylsulfonyl)-3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 potassium carbonate 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.5h， 生成 5-(3-methoxyphenyl)-3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of 3,5-Disubstituted 7-Azaindoles as Trk Inhibitors with Anticancer and Antiangiogenic Activities

  摘要：

  Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at the 3 and 5 positions of a 7-azaindole scaffold, we studied the structure-activity relationships (SAR) profiles and identified a series of potent Trk inhibitors. Representative derivatives showed desirable activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.

  DOI：

  10.1021/jm3002982
• 作为产物：
  描述：

  1-(苯磺酰基)-5-溴-3-碘吡咯并[2,3-b]吡啶 、 吡啶-4-硼酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 以73%的产率得到5-bromo-1-(phenylsulfonyl)-3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of 3,5-Disubstituted 7-Azaindoles as Trk Inhibitors with Anticancer and Antiangiogenic Activities

  摘要：

  Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at the 3 and 5 positions of a 7-azaindole scaffold, we studied the structure-activity relationships (SAR) profiles and identified a series of potent Trk inhibitors. Representative derivatives showed desirable activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.

  DOI：

  10.1021/jm3002982

文献信息

• Application of Fragment-Based de Novo Design to the Discovery of Selective Picomolar Inhibitors of Glycogen Synthase Kinase-3 Beta
  作者：Hwangseo Park、Yongje Shin、Jinhee Kim、Sungwoo Hong

  DOI：10.1021/acs.jmedchem.6b00944

  日期：2016.10.13

  systematic fragment-based de novo design procedure was developed and applied to discover new potent and selective inhibitors of glycogen synthase kinase-3 beta (GSK3β). Candidate inhibitors were generated to simultaneously maximize the biochemical potency and the specificity for GSK3β through three design steps: identification of the optimal molecular fragments for the three sub-binding regions, design of

  开发了基于系统片段的从头设计程序，并将其应用于发现糖原合酶激酶-3β（GSK3β）的新的有效和选择性抑制剂。通过三个设计步骤生成候选抑制剂，以同时最大化GSK3β的生化效能和特异性：鉴定三个亚结合区的最佳分子片段，设计适当的连接部分以连接片段结构单元，以及对GSK3β的最终评分产生的分子。通过使用混合标度粒子理论和扩展的溶剂接触模型修改评分功能中的配体水合自由能术语，我们确定了几种GSK3β抑制剂，其生化潜能范围从低纳摩尔到皮摩尔水平。其中，两种最有效的抑制剂（12和27）预计将作为有希望的药物发现为因为高特异性GSK3β的抑制引起的GSK3β的各种疾病的起始点。