3-溴-1-(恶烷-2-基)-1H-吲唑-5-胺 | 1788054-90-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 3-溴-1-(恶烷-2-基)-1H-吲唑-5-胺
• 英文名称: 3-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine
• 英文别名: 3-Bromo-1-(oxan-2-yl)-1H-indazol-5-amine；3-bromo-1-(oxan-2-yl)indazol-5-amine
• CAS: 1788054-90-9
• 化学式: C₁₂H₁₄BrN₃O
• 分子量: 296.167
• InChiKey: FITFDPUUMBYADB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  53.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-溴-1-(恶烷-2-基)-1H-吲唑-5-胺 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 12.25h， 生成 N-(5-fluoro-2-(methylsulfonyl)benzyl)-3-(1-methyl-1H-pyrazol-3-yl)-1H-indazol-5-amine
  参考文献：
  名称：

  The discovery of novel 3-aryl-indazole derivatives as peripherally restricted pan-Trk inhibitors for the treatment of pain

  摘要：

  The design, synthesis, and biological evaluation of novel 3-aryl-indazole derivatives as peripherally selective pan-Trk inhibitors are described. Three strategies were used to obtain a potent compound exhibiting low central nervous system (CNS) penetration and high plasma exposure: 1) a structure-based drug design (SBDD) approach was used to improve potency; 2) a substrate for an efflux transporter for lowering brain penetration was explored; and 3) the most basic pKa (pKa-MB) value was used as an indicator to identify compounds with good membrane permeability. This enabled the identification of the peripherally targeted 17c with the potency, kinase-selectivity, and plasma exposure required to demonstrate in vivo efficacy in a Complete Freund's adjuvant (CFA)-induced thermal hypersensitivity model.

  DOI：

  10.1016/j.bmcl.2019.06.018
• 作为产物：
  描述：

  3-bromo-5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole 在 3 % platinum sulfide on carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以70.4%的产率得到3-溴-1-(恶烷-2-基)-1H-吲唑-5-胺
  参考文献：
  名称：

  The discovery of novel 3-aryl-indazole derivatives as peripherally restricted pan-Trk inhibitors for the treatment of pain

  摘要：

  The design, synthesis, and biological evaluation of novel 3-aryl-indazole derivatives as peripherally selective pan-Trk inhibitors are described. Three strategies were used to obtain a potent compound exhibiting low central nervous system (CNS) penetration and high plasma exposure: 1) a structure-based drug design (SBDD) approach was used to improve potency; 2) a substrate for an efflux transporter for lowering brain penetration was explored; and 3) the most basic pKa (pKa-MB) value was used as an indicator to identify compounds with good membrane permeability. This enabled the identification of the peripherally targeted 17c with the potency, kinase-selectivity, and plasma exposure required to demonstrate in vivo efficacy in a Complete Freund's adjuvant (CFA)-induced thermal hypersensitivity model.

  DOI：

  10.1016/j.bmcl.2019.06.018

文献信息

• The discovery of novel 3-aryl-indazole derivatives as peripherally restricted pan-Trk inhibitors for the treatment of pain
  作者：Hiromitsu Shirahashi、Eisuke Toriihara、Yoshihito Suenaga、Hideyuki Yoshida、Kensuke Akaogi、Yukiko Endou、Makoto Wakabayashi、Misato Takashima

  DOI：10.1016/j.bmcl.2019.06.018

  日期：2019.8

  The design, synthesis, and biological evaluation of novel 3-aryl-indazole derivatives as peripherally selective pan-Trk inhibitors are described. Three strategies were used to obtain a potent compound exhibiting low central nervous system (CNS) penetration and high plasma exposure: 1) a structure-based drug design (SBDD) approach was used to improve potency; 2) a substrate for an efflux transporter for lowering brain penetration was explored; and 3) the most basic pKa (pKa-MB) value was used as an indicator to identify compounds with good membrane permeability. This enabled the identification of the peripherally targeted 17c with the potency, kinase-selectivity, and plasma exposure required to demonstrate in vivo efficacy in a Complete Freund's adjuvant (CFA)-induced thermal hypersensitivity model.