N-[1-(Tetrahydro-thiopyran-3-yl)-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-ylmethyl]-methanesulfonamide | 1418199-32-2

• 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-[1-(Tetrahydro-thiopyran-3-yl)-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-ylmethyl]-methanesulfonamide
• 英文别名: N-[[3-(thian-3-yl)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl]methyl]methanesulfonamide
• CAS: 1418199-32-2
• 化学式: C₁₅H₁₉N₅O₂S₂
• 分子量: 365.48
• InChiKey: QPGQYBKAZOTPAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[1-(Tetrahydro-thiopyran-3-yl)-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-ylmethyl]-methanesulfonamide 在 ammonium hydroxide 、 二氧化碳 作用下， 以 甲醇 为溶剂， 生成 N-{{1-(tetrahydrothiopyran-3-yl)-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-yl}methyl}-methanesulfonamide 、 N-{{1-(tetrahydrothiopyran-3-yl)-1,6-dihydro-1,3,5,6-tetraaza-as-indacen-2-yl}methyl}-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
• 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-[1-(Tetrahydro-thiopyran-3-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