(E)-6-fluoro-3-(2-pyridin-2-ylvinyl)-1H-indole | 1316695-11-0

• 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: (E)-6-fluoro-3-(2-pyridin-2-ylvinyl)-1H-indole
• 英文别名: 6-fluoro-3-[(E)-2-pyridin-2-ylethenyl]-1H-indole
• CAS: 1316695-11-0
• 化学式: C₁₅H₁₁FN₂
• 分子量: 238.264
• InChiKey: AEGKYHXHADEAML-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  6-氟吲哚 在 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 68.17h， 生成 (E)-6-fluoro-3-(2-pyridin-2-ylvinyl)-1H-indole
  参考文献：
  名称：

  Tryptophan 2,3-Dioxygenase (TDO) Inhibitors. 3-(2-(Pyridyl)ethenyl)indoles as Potential Anticancer Immunomodulators

  摘要：

  Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure- activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His(55) and Thr(254) residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (K-i = 5.5 mu M), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.

  DOI：

  10.1021/jm2006782

文献信息

• Tryptophan 2,3-Dioxygenase (TDO) Inhibitors. 3-(2-(Pyridyl)ethenyl)indoles as Potential Anticancer Immunomodulators
  作者：Eduard Dolušić、Pierre Larrieu、Laurence Moineaux、Vincent Stroobant、Luc Pilotte、Didier Colau、Lionel Pochet、Benoît Van den Eynde、Bernard Masereel、Johan Wouters、Raphaël Frédérick

  DOI：10.1021/jm2006782

  日期：2011.8.11

  Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure- activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His(55) and Thr(254) residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (K-i = 5.5 mu M), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.