(4-((3-bromopyridin-2-yl)oxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone | 1227173-02-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-((3-bromopyridin-2-yl)oxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone
• 英文别名: (4-(3-Bromopyridin-2-yloxy)phenyl)(1-methyl-1H-benzo[D]imidazol-2-YL)methanone；[4-(3-bromopyridin-2-yl)oxyphenyl]-(1-methylbenzimidazol-2-yl)methanone
• CAS: 1227173-02-5
• 化学式: C₂₀H₁₄BrN₃O₂
• 分子量: 408.254
• InChiKey: DLOHYHRVMXVJIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-((3-bromopyridin-2-yl)oxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone 在 四(三苯基膦)钯 、 bis(η3-allyl-μ-chloropalladium(II)) 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 8.0h， 生成 (4-(3-benzoylpyridin-2-yloxy)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
• 作为产物：
  描述：

  (1H-benzo[d]imidazol-2-yl)(4-methoxyphenyl)methanone 在 三溴化硼 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 作用下， 以 正己烷 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 95.75h， 生成 (4-((3-bromopyridin-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

• PYRIDINE AND PYRIMIDINE DERIVATIVES AS PHOSPHODIESTERASE 10 INHIBITORS
  申请人：Allen Jennifer R.

  公开号：US20100125062A1

  公开（公告）日：2010-05-20

  Pyridine and pyrimidine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  吡啶和嘧啶化合物，以及含有它们的组合物，以及制备这些化合物的方法。本文还提供了治疗通过抑制PDE10可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症等。
• Pyridine and pyrimidine derivatives as phosphodiesterase 10 inhibitors
  申请人：Amgen Inc.

  公开号：US08318718B2

  公开（公告）日：2012-11-27

  Pyridine and pyrimidine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  吡啶和嘧啶化合物及含有它们的组合物，并且提供了制备这些化合物的方法。此外，本文还提供了一种治疗可通过抑制PDE10治疗的疾病或疾病的方法，例如肥胖症，非胰岛素依赖性糖尿病，精神分裂症，双相障碍，强迫症等。
• US8318718B2
  申请人：——

  公开号：US8318718B2

  公开（公告）日：2012-11-27
• US8759532B2
  申请人：——

  公开号：US8759532B2

  公开（公告）日：2014-06-24
• [EN] PYRIDINE AND PYRIMIDINE DERIVATIVES AS PHOSPHODIESTERASE 10 INHIBITORS<br/>[FR] DERIVES DE PYRIDINE ET DE PYRIMIDINE COMME INHIBITEURS DE PHOSPHODIESTERASE 10
  申请人：AMGEN INC

  公开号：WO2010057126A1

  公开（公告）日：2010-05-20

  Pyridine and pyrimidine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.