7-azaindirubin | 1231708-85-2

• 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: 7-azaindirubin
• 英文别名: 3-(3-oxo-1H-indol-2-ylidene)-1H-pyrrolo[2,3-b]pyridin-2-one
• CAS: 1231708-85-2
• 化学式: C₁₅H₉N₃O₂
• 分子量: 263.255
• InChiKey: YIRSIXXVSDFDIN-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

• 作为反应物：
  描述：

  7-azaindirubin 在 吡啶 、 盐酸羟胺 作用下， 反应 4.0h， 以70%的产率得到7'-azaindirubin-3'-oxime
  参考文献：
  名称：

  7-azaindirubins, 7'-azaindirubins, 7-7'-diazaindirubin and the corresponding 3'-oxime ether derivates: production thereof, their production and use as a medicament

  摘要：

  本发明涉及7-azaindirubins（1）、7'-azaindirubins（2）和7,7'-二氮杂吲哚（3），其中E、R1和R2的含义在描述中有详细说明，它们的制备和用作治疗癌症、神经退行性疾病、躁郁症、炎症和传染病，包括病毒性疾病的药物。根据结构的不同，这些吲哚作为抑制与肿瘤细胞生长有关的各种激酶的作用，尤其是作为人类肿瘤细胞增殖的抑制剂。与携带相同取代基但在位置7和7'没有杂原子的吲哚相比，根据本发明的化合物的活性增加，且通过CYP450酶代谢的倾向减少，从而提高了代谢稳定性。

  公开号：

  EP2199292A1
• 作为产物：
  描述：

  2-(2-氨基吡啶-3-基)乙酸 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 对甲苯磺酸 、 二甲基亚砜 作用下， 以 戊醇 、 溶剂黄146 为溶剂， 反应 3.5h， 生成 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