1-phenylsulfonyl-5-benzyloxy-2-tributylstannyl-1H-indole | 1037551-66-8

• 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: 1-phenylsulfonyl-5-benzyloxy-2-tributylstannyl-1H-indole
• CAS: 1037551-66-8
• 化学式: C₃₃H₄₃NO₃SSn
• 分子量: 652.485
• InChiKey: XAPZOVMJGGVGAW-UHFFFAOYSA-N

物化性质

• 熔点：
  67-69 °C
• 沸点：
  691.2±65.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.51
• 重原子数：
  39.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  48.3
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-phenylsulfonyl-5-benzyloxy-2-tributylstannyl-1H-indole 在 copper(l) iodide 、 四(三苯基膦)钯 、 palladium diacetate 、 potassium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 1.33h， 生成 [5-(1-benzenesulfonyl-5-benzyloxy-1H-indol-2-yl)-pyridin-3-yl]-(4-methoxy-phenyl)-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of new 3-(6-hydroxyindol-2-yl)-5-(Phenyl) pyridine or pyrazine V-Shaped molecules as kinase inhibitors and cytotoxic agents

  摘要：

  We here report the synthesis and biological evaluation of new 3-[(2-indolyl)]-5-phenyl-3,5-pyridine, 3-[(2-indolyl)]-5-phenyl-2,4-pyridine and 3-[(2-indolyl)]-5-phenyl-2,6-pyrazine derivatives designed as potential CDK inhibitors. Indoles and phenyls were used to generate several substitutions of the pyridine and pyrazine rings. The synthesis included Stille or Suzuki type reactions, which were carried out on the 3,5-dibromopyridine, 2,4-dichloropyridine and 2,6-dichloro-1-4-pyrazine moieties. Cell effects of the V-shaped family were in the micromolar range. Kinase assays were conducted and showed that compound 11 inhibited CDK5 with an inhibitory concentration of 160 nM with a moderate selectivity over GSK3 compared to the reference C which exhibited a slightly lower activity on CDK5 (1.5 mu M). Compound 11 was also found to be the most potent compound in the series and was identified as a new lead for DYRK1A inhibitor discovery (IC50 = 60 nM). Docking studies were carried out in order to investigate the inhibition of DYRK1A. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.048

文献信息

• Synthesis of 3,5-bis(2-indolyl)pyridine and 3-[(2-indolyl)-5-phenyl]pyridine derivatives as CDK inhibitors and cytotoxic agents
  作者：Ulrich Jacquemard、Nathalie Dias、Amélie Lansiaux、Christian Bailly、Cédric Logé、Jean-Michel Robert、Olivier Lozach、Laurent Meijer、Jean-Yves Mérour、Sylvain Routier

  DOI：10.1016/j.bmc.2008.03.034

  日期：2008.5

  report the synthesis and biological evaluation of new 3,5-bis(2-indolyl)pyridine and 3-[(2-indolyl)-5-phenyl]pyridine designed as potential CDK inhibitors. Indole, 5-hydroxyindole, and phenol derivatives were used to generate three substitutions of the pyridine. The resulting skeletons were successively exploited to introduce various dimethylaminoalkyl side chains by Williamson type reactions. The synthesis

  我们在这里报告了新型3,5-双（2-吲哚基）吡啶和设计为潜在CDK抑制剂的3-[（2-吲哚基）-5-苯基]吡啶的合成和生物学评估。吲哚，5-羟基吲哚和苯酚衍生物用于生成吡啶的三个取代基。通过威廉姆森（Williamson）型反应，依次利用所得骨架引入各种二甲基氨基烷基侧链。合成包括在3，5-二溴吡啶上实现的Stille或Suzuki型反应。还描述了斯坦尼多度在单或双交叉偶联反应中的制备和使用，并对每个步骤进行了优化和详细说明。实现了激酶测定法，结果表明，裸化合物7、18和25在0.3-0.7微摩尔范围内抑制CDK1，对GSK-3具有良好的选择性。用5-15微摩尔范围内的IC（50）值评估了对CEM人白血病细胞的细胞毒性。描绘了精确的构效关系。提出了分子建模和对接解决方案以完成研究并解释CDK分析中观察到的SAR。