(4-((3-(4-methoxyphenyl)pyridin-2-yl)oxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-((3-(4-methoxyphenyl)pyridin-2-yl)oxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone
• 英文别名: [4-[3-(4-Methoxyphenyl)pyridin-2-yl]oxyphenyl]-(1-methylbenzimidazol-2-yl)methanone；[4-[3-(4-methoxyphenyl)pyridin-2-yl]oxyphenyl]-(1-methylbenzimidazol-2-yl)methanone
• 化学式: C₂₇H₂₁N₃O₃
• 分子量: 435.482
• InChiKey: ALZKXQQRTZTXGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  66.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (1H-benzo[d]imidazol-2-yl)(4-methoxyphenyl)methanone 在 四(三苯基膦)钯 、 三溴化硼 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 作用下， 以 正己烷 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 107.75h， 生成 (4-((3-(4-methoxyphenyl)pyridin-2-yl)oxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone
  参考文献：
  名称：

  Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors

  摘要：

  Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52 +/- 0.18, 2.86 +/- 0.10, and 3.73 +/- 0.60 nM, respectively; these three compounds also showed high in vitro selectivity (> 1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacological behavior and ability to quantify PDE10A in the brain. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.054

文献信息

• Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors
  作者：Hao Yang、Francis N. Murigi、Zhijian Wang、Junfeng Li、Hongjun Jin、Zhude Tu

  DOI：10.1016/j.bmcl.2014.12.054

  日期：2015.2

  Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52 +/- 0.18, 2.86 +/- 0.10, and 3.73 +/- 0.60 nM, respectively; these three compounds also showed high in vitro selectivity (> 1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacological behavior and ability to quantify PDE10A in the brain. (C) 2014 Elsevier Ltd. All rights reserved.