1-(3-chloro-5-(6,7-dimethoxycinnolin-4-yl)pyridin-2-yl)-4-(pyridin-3-yl)piperidin-4-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-(3-chloro-5-(6,7-dimethoxycinnolin-4-yl)pyridin-2-yl)-4-(pyridin-3-yl)piperidin-4-ol
• 英文别名: 1-[3-Chloro-5-(6,7-dimethoxycinnolin-4-yl)pyridin-2-yl]-4-pyridin-3-ylpiperidin-4-ol
• 化学式: C₂₅H₂₄ClN₅O₃
• 分子量: 477.95
• InChiKey: OVMSZRUWEZLQRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  93.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-溴-2,3-二氯吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 potassium acetate 、 potassium carbonate 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 水 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 1-(3-chloro-5-(6,7-dimethoxycinnolin-4-yl)pyridin-2-yl)-4-(pyridin-3-yl)piperidin-4-ol
  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

• PHOSPHODIESTERASE 10 INHIBITORS
  申请人：Hu Essa

  公开号：US20090062291A1

  公开（公告）日：2009-03-05

  The present invention is directed to compounds, useful as PDE10 inhibitors, having the formula where R 1 , R 2 , R 3 , R 4 , X, Y and Z are as defined herein, pharmaceutical compositions containing such compounds and processes for preparing such compounds. The invention is also directed to methods of treating diseases mediated by PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  本发明涉及化合物，其具有式，可用作PDE10抑制剂，其中R1、R2、R3、R4、X、Y和Z的定义如本文所述，以及含有此类化合物的制药组合物和制备此类化合物的过程。本发明还涉及治疗由PDE10介导的疾病的方法，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。
• [EN] PHOSPHODIESTERASE 10 INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHODIESTÉRASE 10
  申请人：AMGEN INC

  公开号：WO2009025839A2

  公开（公告）日：2009-02-26

  The present invention is directed to compounds, useful as PDElO inhibitors, having the formula (I) where R1, R2, R3, R4, X, Y and Z are as defined herein, pharmaceutical compositions containing such compounds and processes for preparing such compounds. The invention is also directed to methods of treating diseases mediated by PDElO, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
• 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.