2-((S)-3-acetylamino-indan-5-yloxy)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide | 1431551-54-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-((S)-3-acetylamino-indan-5-yloxy)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide
• 英文别名: 2-[[(3S)-3-acetamido-2,3-dihydro-1H-inden-5-yl]oxy]-N-propan-2-yl-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazine-7-carboxamide
• CAS: 1431551-54-0
• 化学式: C₂₇H₃₇N₅O₄Si
• 分子量: 523.707
• InChiKey: MECWDRNKKCJASY-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-((S)-3-acetylamino-indan-5-yloxy)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide 在 盐酸 、 甲醇 、 乙二胺 、 三乙胺 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 21.0h， 以65%的产率得到2-[[(3S)-3-acetamido-2,3-dihydro-1H-inden-5-yl]oxy]-N-propan-2-yl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide
  参考文献：
  名称：

  Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors

  摘要：

  We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity. Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.015
• 作为产物：
  描述：

  2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde 在 吡啶 、 甲醇 、 sodium chlorite 、 potassium phosphate 、 potassium dihydrogenphosphate 、 氨基磺酸 、 palladium diacetate 、 乙酰氯 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 2-二叔丁基磷-2-(N,N-二甲氨基)联苯 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 38.75h， 生成 2-((S)-3-acetylamino-indan-5-yloxy)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide
  参考文献：
  名称：

  Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors

  摘要：

  We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity. Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.015