N-[(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)methyl]acetamide | 1315493-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: N-[(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)methyl]acetamide
• CAS: 1315493-55-0
• 化学式: C₁₇H₂₁N₅O
• 分子量: 311.387
• InChiKey: NYSSZLMKUOFTKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(苯磺酰基)-4-氯-5-硝基吡咯并[2,3-b]吡啶 在 盐酸 、 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 20.0h， 生成 N-[(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)methyl]acetamide
  参考文献：
  名称：

  Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2

  摘要：

  Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1: E966; JAK2: D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.008

文献信息

• Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2
  作者：Sharada Labadie、Peter S. Dragovich、Kathy Barrett、Wade S. Blair、Philippe Bergeron、Christine Chang、Gauri Deshmukh、Charles Eigenbrot、Nico Ghilardi、Paul Gibbons、Christopher A. Hurley、Adam Johnson、Jane R. Kenny、Pawan Bir Kohli、Janusz J. Kulagowski、Marya Liimatta、Patrick J. Lupardus、Rohan Mendonca、Jeremy M. Murray、Rebecca Pulk、Steven Shia、Micah Steffek、Savita Ubhayakar、Mark Ultsch、Anne van Abbema、Stuart Ward、Mark Zak

  DOI：10.1016/j.bmcl.2012.10.008

  日期：2012.12

  Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1: E966; JAK2: D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed. (C) 2012 Elsevier Ltd. All rights reserved.