3-[4-[10-(Benzenesulfonyl)-4-propyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl]piperidin-1-yl]propanenitrile | 1315495-33-0

• 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: 3-[4-[10-(Benzenesulfonyl)-4-propyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl]piperidin-1-yl]propanenitrile
• CAS: 1315495-33-0
• 化学式: C₂₅H₂₈N₆O₂S
• 分子量: 476.602
• InChiKey: XNECHOSRFFIJEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[4-[10-(Benzenesulfonyl)-4-propyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl]piperidin-1-yl]propanenitrile 在 sodium hydroxide 作用下， 反应 20.0h， 生成 3-[4-(4-Propyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl)piperidin-1-yl]propanenitrile
  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
• 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 palladium on activated charcoal 、 氢气 、 溶剂黄146 、 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-) 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 20.0h， 生成 3-[4-[10-(Benzenesulfonyl)-4-propyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl]piperidin-1-yl]propanenitrile 、
  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

• [EN] TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES TRICYCLIQUES, LEURS COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011086053A1

  公开（公告）日：2011-07-21

  The invention provides novel compounds of formula (I) having the general formula, wherein R1, R2, R3, X and Y are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.

  该发明提供了具有通式（I）的新化合物，通式如下，其中R1、R2、R3、X和Y如本文所述。因此，这些化合物可以用于制备药学上可接受的组合物，并用于治疗免疫或过度增殖性疾病。
• TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2523957A1

  公开（公告）日：2012-11-21
• 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.