3-(4-ethynyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopropyl (pyridin-3-ylmethyl)carbamodithioate

• 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: 3-(4-ethynyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopropyl (pyridin-3-ylmethyl)carbamodithioate
• 英文别名: [3-(4-ethynyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopropyl] N-(pyridin-3-ylmethyl)carbamodithioate
• 化学式: C₁₉H₁₆N₄OS₂
• 分子量: 380.494
• InChiKey: UYXUFOFLECRFLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-溴-7-氮杂吲哚 在 aluminum (III) chloride 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 、 二异丙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.75h， 生成 3-(4-ethynyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopropyl (pyridin-3-ylmethyl)carbamodithioate
  参考文献：
  名称：

  Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors

  摘要：

  Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.003

文献信息

• Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors
  作者：Bin Liu、Xia Yuan、Bo Xu、Han Zhang、Ridong Li、Xin Wang、Zemei Ge、Runtao Li

  DOI：10.1016/j.ejmech.2019.03.003

  日期：2019.5

  Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.