N-exo-(1-bicyclo[2.2.1]hept-2-yl-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-ylmethyl)-methanesulfonamide | 1415389-09-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-exo-(1-bicyclo[2.2.1]hept-2-yl-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-ylmethyl)-methanesulfonamide
• 英文别名: N-({1-[(1r,2r,4s)-Bicyclo[2.2.1]hept-2-Yl]-1,6-Dihydroimidazo[4,5-D]pyrrolo[2,3-B]pyridin-2-Yl}methyl)methanesulfonamide；N-[[3-[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl]methyl]methanesulfonamide
• CAS: 1415389-09-1
• 化学式: C₁₇H₂₁N₅O₂S
• 分子量: 359.452
• InChiKey: IQHKHGHDPGFXAV-MISXGVKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

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-exo-(1-bicyclo[2.2.1]hept-2-yl-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-ylmethyl)-methanesulfonamide
  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

• Aza-indazole compounds for use in tendon and/or ligament injuries
  申请人：NOVARTIS AG

  公开号：US10766894B2

  公开（公告）日：2020-09-08

  The present invention provides a compound of formula (I) in free form or in pharmaceutically acceptable salt form, a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了游离形式或药学上可接受的盐形式的式 (I) 化合物、制造本发明化合物的方法及其治疗用途。本发明进一步提供了药理活性剂的组合和药物组合物。
• Indazole Compounds for Use in Tendon and/or Ligament Injuries
  申请人：NOVARTIS AG

  公开号：US20180086716A1

  公开（公告）日：2018-03-29

  The present invention provides a compound of formula (I) in free form or in pharmaceutically acceptable salt form a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
• AZA-INDAZOLE COMPOUNDS FOR USE IN TENDON AND/OR LIGAMENT INJURIES
  申请人：NOVARTIS AG

  公开号：US20190300522A1

  公开（公告）日：2019-10-03

  The present invention provides a compound of formula (I) in free form or in pharmaceutically acceptable salt form, a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
• 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.