5-(6-amino-1H-indazol-4-yl)-3-(3-hydroxyprop-1-ynyl)-2H-indazole-7-carboxamide | 1549643-04-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 5-(6-amino-1H-indazol-4-yl)-3-(3-hydroxyprop-1-ynyl)-2H-indazole-7-carboxamide
• CAS: 1549643-04-0
• 化学式: C₁₈H₁₄N₆O₂
• 分子量: 346.348
• InChiKey: GVMSIEMRNRMITA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  147
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 盐酸 、 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 四(三苯基膦)钯 、 氨 、 potassium carbonate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 63.0h， 生成 5-(6-amino-1H-indazol-4-yl)-3-(3-hydroxyprop-1-ynyl)-2H-indazole-7-carboxamide
  参考文献：
  名称：

  Linear propargylic alcohol functionality attached to the indazole-7-carboxamide as a JAK1-specific linear probe group

  摘要：

  Selective inhibition of JAK1 has recently been proposed as an appropriate therapeutic rationale for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). In this study, through pairwise comparison and 3D alignment of the JAK isozyme structures bound to the same inhibitor molecule, we reasoned that an alkynol functionality would serve as an isozyme-specific probe group, which would enable the resulting inhibitor to differentiate the ATP-binding site of JAK1 from those of other isozymes. The 3-alkynolyl-5-(4'-indazolyl) indazole-7-carboxamide derivatives were thus prepared, and in vitro evaluation of their inhibitory activity against the JAK isozymes revealed that the propargyl alcohol functionality endowed the 5-(4'-indazolyl) indazole-7-carboxamide scaffold with JAK1 selectivity over other JAK isozymes, particularly JAK2. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.033

文献信息

• Linear propargylic alcohol functionality attached to the indazole-7-carboxamide as a JAK1-specific linear probe group
  作者：Mi Kyoung Kim、Heerim Shin、Seo Young Cho、Youhoon Chong

  DOI：10.1016/j.bmc.2013.12.033

  日期：2014.2

  Selective inhibition of JAK1 has recently been proposed as an appropriate therapeutic rationale for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). In this study, through pairwise comparison and 3D alignment of the JAK isozyme structures bound to the same inhibitor molecule, we reasoned that an alkynol functionality would serve as an isozyme-specific probe group, which would enable the resulting inhibitor to differentiate the ATP-binding site of JAK1 from those of other isozymes. The 3-alkynolyl-5-(4'-indazolyl) indazole-7-carboxamide derivatives were thus prepared, and in vitro evaluation of their inhibitory activity against the JAK isozymes revealed that the propargyl alcohol functionality endowed the 5-(4'-indazolyl) indazole-7-carboxamide scaffold with JAK1 selectivity over other JAK isozymes, particularly JAK2. (C) 2013 Elsevier Ltd. All rights reserved.