2-[[(3R)-3-acetamido-2,3-dihydro-1H-inden-5-yl]oxy]-N-[(2R)-1-(3-cyanoazetidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide | 1431551-65-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[[(3R)-3-acetamido-2,3-dihydro-1H-inden-5-yl]oxy]-N-[(2R)-1-(3-cyanoazetidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide
• CAS: 1431551-65-3
• 化学式: C₂₈H₃₁N₇O₄
• 分子量: 529.599
• InChiKey: WZRKPAUVPLLULB-QPPBQGQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  叔丁氧羰基-D-叔亮氨酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 53.5h， 生成 2-[[(3R)-3-acetamido-2,3-dihydro-1H-inden-5-yl]oxy]-N-[(2R)-1-(3-cyanoazetidin-1-yl)-3,3-dimethyl-1-oxobutan-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

文献信息

• Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors
  作者：Saul Jaime-Figueroa、Javier De Vicente、Johannes Hermann、Alam Jahangir、Sue Jin、Andreas Kuglstatter、Stephen M. Lynch、John Menke、Linghao Niu、Vaishali Patel、Ada Shao、Michael Soth、Minh Diem Vu、Calvin Yee

  DOI：10.1016/j.bmcl.2013.03.015

  日期：2013.5

  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.