7'-azaindirubin | 1182225-28-0

• 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: 7'-azaindirubin
• 英文别名: 2-(2-oxo-1H-indol-3-ylidene)-1H-pyrrolo[2,3-b]pyridin-3-one
• CAS: 1182225-28-0
• 化学式: C₁₅H₉N₃O₂
• 分子量: 263.255
• InChiKey: QJYJTTJDFSTQJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.05
• 重原子数：
  20.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.09
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  1H-吡咯并[2,3-b]吡啶-3-醇 3-乙酸酯 、 靛红 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以87%的产率得到7'-azaindirubin
  参考文献：
  名称：

  7,7′-Diazaindirubin—A small molecule inhibitor of casein kinase 2 in vitro and in cells

  摘要：

  Aza- and diaza-bisindoles were synthesized by coupling of 7-azaisatin, 7-azaoxindol, 7-azaindoxyl acetate, and their non-aza counterparts, respectively. Whereas 7,7'-diazaindigo (10) and 7,7'-diazaisoindigo (11) did not show antiproliferative activity in several human tumor cell lines up to 100 mu M, 7-azaindirubin (12) and 7'-azaindirubin (13) were more active than the parent molecule, indirubin, in LXFL529L cells (human large cell lung tumor xenograft), and 7,7'-diazaindirubin (14) was exhibiting substantially enhanced growth inhibitory activity in these cells. In the NCI 60 cell line panel, 14 displayed antiproliferative activity preferentially in certain melanoma and non-small cell lung cancer cells. In contrast to the potent serine/threonine/tyrosine kinase inhibition observed for indirubins, kinase inhibition profiling of 14 in 220 kinases revealed largely a loss of kinase inhibitory activity towards most kinases, with retained inhibitory activity for just a few kinases. At 1 mu M concentration, especially casein kinases CK1 gamma 3, CK2 alpha, CK2 alpha 2, and SIK were inhibited by more than 50%. In cell-based assays, 14 markedly affected CK2-mediated signaling in various human tumor cells. In MCF7 cells, 14 induced cell cycle arrest at G1 and G2/M and apoptosis, whereas CK2-deficient MCF7 cells were resistant. These findings reveal a novel key mechanism of action for 14, suggesting primarily CK2 inhibition to be causally related to growth inhibition of human tumor cells. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.031

文献信息

• Exploring an anomaly: the synthesis of 7,7′-diazaindirubin through a 7-azaindoxyl intermediate
  作者：James A. Shriver、Katelyn R. Wang、Andrew C. Patterson、James R. DeYoung、Richard J. Lipsius

  DOI：10.1039/d0ra07144g

  日期：——

  Generation of 7-azaindoxyl under acidic conditions leads exclusively to 7,7′-diazaindirubin over 7,7′-diazaindigo through a condensation pathway.

  在酸性条件下生成7-氮氧自由基，仅通过缩合途径形成7,7'-二氮吲哚鲁宾，而不是7,7'-二氮吲哥。