N-{(R)-6-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylo-xy]-indan-1-yl}-acetamide | 1431551-56-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-{(R)-6-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylo-xy]-indan-1-yl}-acetamide
• 英文别名: N-{(R)-6-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yloxy]-indan-1-yl}-acetamide；N-[(1R)-6-[7-formyl-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazin-2-yl]oxy-2,3-dihydro-1H-inden-1-yl]acetamide
• CAS: 1431551-56-2
• 化学式: C₂₄H₃₀N₄O₄Si
• 分子量: 466.612
• InChiKey: IOKVXJOPLZISLI-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.47
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  95.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-{(R)-6-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylo-xy]-indan-1-yl}-acetamide 在 sodium chlorite 、 potassium dihydrogenphosphate 、 氨基磺酸 、 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 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 36.5h， 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
• 作为产物：
  描述：

  N-[(1R)-2,3-二氢-6-羟基-1H-茚-1-基]氨基甲酸叔丁酯 在 吡啶 、 盐酸 、 potassium phosphate 、 palladium diacetate 、 2-二叔丁基磷-2-(N,N-二甲氨基)联苯 作用下， 以 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 69.0h， 生成 N-{(R)-6-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylo-xy]-indan-1-yl}-acetamide
  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

• Pyrrolopyrazine Kinase Inhibitors
  申请人：Hendricks Robert Than

  公开号：US20110288067A1

  公开（公告）日：2011-11-24

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables Q and R, R 2 , and R 3 are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用新型 Formula I 中的吡咯吡嗪衍生物，其中变量 Q 和 R、R2 和 R3 如本文所述定义，这些衍生物抑制 JAK 和 SYK，并用于治疗自身免疫和炎症性疾病。
• PYRROLOPYRAZINE KINASE INHIBITORS
  申请人：Hoffmann-La Roche Inc.

  公开号：US20140155376A1

  公开（公告）日：2014-06-05

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables Q and R, R 2 , and R 3 are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用公式I中的新型吡咯吡嗪衍生物，其中变量Q和R，R2和R3的定义如本文所述，它们抑制JAK和SYK，并且对于治疗自身免疫和炎症性疾病是有用的。
• 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.