3-[(8-fluoro-1-methyl-4-oxo-3H-pyridazino[4,5-b]indol-5-yl)methyl]benzonitrile | 1415653-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-[(8-fluoro-1-methyl-4-oxo-3H-pyridazino[4,5-b]indol-5-yl)methyl]benzonitrile
• CAS: 1415653-19-8
• 化学式: C₁₉H₁₃FN₄O
• 分子量: 332.337
• InChiKey: MPFTXOBQQQNMQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氟吲哚-2-甲酸 在 aluminum (III) chloride 、 氯化亚砜 、 sodium hydride 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 28.5h， 生成 3-[(8-fluoro-1-methyl-4-oxo-3H-pyridazino[4,5-b]indol-5-yl)methyl]benzonitrile
  参考文献：
  名称：

  Synthesis and biological evaluation of new 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles as PI3Kα inhibitors

  摘要：

  A series of novel 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles was synthesized through a newly developed approach. All these compounds were evaluated against DYRK1A, CDK5 and PI3K alpha and showed promising inhibitory activities against PI3K alpha, with most IC50 values in the micromolar range. Among them, compound 18 was strongly considered as the most interesting compound with an IC50 value of 0.091 mu M. This series exhibited also significant anti-proliferative effects in various human cancer cell lines including those resulting in activation of the PI3K pathway. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.001

文献信息

• Synthesis and biological evaluation of new 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles as PI3Kα inhibitors
  作者：Amélie Bruel、Cédric Logé、Marie-Ludivine de Tauzia、Myriam Ravache、Rémy Le Guevel、Christiane Guillouzo、Jean-François Lohier、Jana Sopkova-de Oliveira Santos、Olivier Lozach、Laurent Meijer、Sandrine Ruchaud、Hélène Bénédetti、Jean-Michel Robert

  DOI：10.1016/j.ejmech.2012.09.001

  日期：2012.11

  A series of novel 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles was synthesized through a newly developed approach. All these compounds were evaluated against DYRK1A, CDK5 and PI3K alpha and showed promising inhibitory activities against PI3K alpha, with most IC50 values in the micromolar range. Among them, compound 18 was strongly considered as the most interesting compound with an IC50 value of 0.091 mu M. This series exhibited also significant anti-proliferative effects in various human cancer cell lines including those resulting in activation of the PI3K pathway. (C) 2012 Elsevier Masson SAS. All rights reserved.