1,8-bis(2-fluoropyridin-4-yl)-6-methoxy-3,4-dimethylimidazo[1,5-a]quinoxaline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1,8-bis(2-fluoropyridin-4-yl)-6-methoxy-3,4-dimethylimidazo[1,5-a]quinoxaline
• 英文别名: 1,8-Bis(2-fluoropyridin-4-yl)-6-methoxy-3,4-dimethylimidazo[1,5-a]quinoxaline
• 化学式: C₂₃H₁₇F₂N₅O
• 分子量: 417.418
• InChiKey: SMBDWRLHTIVDJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-溴-2,6-二氟苯胺 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 sodium perborate tetrahydrate 、 硫酸 、 sodium methylate 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 1,8-bis(2-fluoropyridin-4-yl)-6-methoxy-3,4-dimethylimidazo[1,5-a]quinoxaline 、 8-bromo-1-(2-fluoropyridin-4-yl)-6-methoxy-3,4-dimethylimidazo[1,5-a]quinoxaline
  参考文献：
  名称：

  Development of highly potent phosphodiesterase 10A (PDE10A) inhibitors: Synthesis and in vitro evaluation of 1,8-dipyridinyl- and 1-pyridinyl-substituted imidazo[1,5-a]quinoxalines

  摘要：

  Herein we report the synthesis of fluorinated inhibitors of phosphodiesterase 10A (PDE10A) which can be used potentially as lead structure for the development of a F-18-labeled PDE10A imaging agent for positron emission tomography. The use of ortho-fluoropyridines as residues could potentially enable the introduction of F-18 through nucleophilic substitution for radiolabeling purposes. 2-Fluoropyridines are introduced by a Suzuki coupling at different positions of the molecule. The reference compounds, 1,8dipyridinylimidazo[1,5-a]quinoxalines and 1-pyridinylimidazo[1,5-a]quinoxalines, show inhibitory potencies at best in the subnanomolar range and selectivity factors greater than 38 against other PDE's. 1,8-Dipyridinylimidazo[1,5-a]quinoxalines are more potent inhibitors than 1-pyridinylimidazo[1,5-a]quinoxalines. Using 2-fluoro-3-pyridinyl as residue provided the most potent inhibitors 16 (IC50 = 0.12 nM), 17 (IC50 = 0.048 nM) and 32 (IC50 = 0.037 nM). (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.10.028

文献信息

• Development of highly potent phosphodiesterase 10A (PDE10A) inhibitors: Synthesis and in vitro evaluation of 1,8-dipyridinyl- and 1-pyridinyl-substituted imidazo[1,5-a]quinoxalines
  作者：Sally Wagner、Matthias Scheunemann、Karolin Dipper、Ute Egerland、Norbert Hoefgen、Jörg Steinbach、Peter Brust

  DOI：10.1016/j.ejmech.2015.10.028

  日期：2016.1

  Herein we report the synthesis of fluorinated inhibitors of phosphodiesterase 10A (PDE10A) which can be used potentially as lead structure for the development of a F-18-labeled PDE10A imaging agent for positron emission tomography. The use of ortho-fluoropyridines as residues could potentially enable the introduction of F-18 through nucleophilic substitution for radiolabeling purposes. 2-Fluoropyridines are introduced by a Suzuki coupling at different positions of the molecule. The reference compounds, 1,8dipyridinylimidazo[1,5-a]quinoxalines and 1-pyridinylimidazo[1,5-a]quinoxalines, show inhibitory potencies at best in the subnanomolar range and selectivity factors greater than 38 against other PDE's. 1,8-Dipyridinylimidazo[1,5-a]quinoxalines are more potent inhibitors than 1-pyridinylimidazo[1,5-a]quinoxalines. Using 2-fluoro-3-pyridinyl as residue provided the most potent inhibitors 16 (IC50 = 0.12 nM), 17 (IC50 = 0.048 nM) and 32 (IC50 = 0.037 nM). (C) 2015 Published by Elsevier Masson SAS.