1-(quinoxalin-2-yl)azetidin-3-ol | 1341120-54-4

• 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-(quinoxalin-2-yl)azetidin-3-ol
• 英文别名: 1-quinoxalin-2-ylazetidin-3-ol
• CAS: 1341120-54-4
• 化学式: C₁₁H₁₁N₃O
• 分子量: 201.228
• InChiKey: OPGCYKRTTIDVRA-UHFFFAOYSA-N

物化性质

• 沸点：
  411.0±45.0 °C(Predicted)
• 密度：
  1.399±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(quinoxalin-2-yl)azetidin-3-ol 在 sodium hydride 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 mineral oil 为溶剂， 反应 6.0h， 生成 (1-(3-((1-(quinoxalin-2-yl)azetidin-3-yl)oxy)pyrazin-2-yl)piperidin-4-yl)methanol
  参考文献：
  名称：

  Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility

  摘要：

  We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.013
• 作为产物：
  描述：

  2-氯喹恶啉 、 氮杂环丁烷-3-醇 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到1-(quinoxalin-2-yl)azetidin-3-ol
  参考文献：
  名称：

  Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility

  摘要：

  We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.013

文献信息

• HETEROARYLOXYHETEROCYCLYL COMPOUNDS AS PDE10 INHIBITORS
  申请人：Amgen Inc.

  公开号：US20130253186A1

  公开（公告）日：2013-09-26

  Heteroaryloxyheterocyclyl 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, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like.

  杂环氧基杂环芳基化合物，以及含有它们的组合物和制备这些化合物的方法。此外，本文还提供了治疗可通过PDE10抑制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、亨廷顿病、双相障碍、强迫症等。
• US8497265B2
  申请人：——

  公开号：US8497265B2

  公开（公告）日：2013-07-30
• US9376450B2
  申请人：——

  公开号：US9376450B2

  公开（公告）日：2016-06-28
• Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility
  作者：Robert M. Rzasa、Michael J. Frohn、Kristin L. Andrews、Samer Chmait、Ning Chen、Jeffrey G. Clarine、Carl Davis、Heather A. Eastwood、Daniel B. Horne、Essa Hu、Adrie D. Jones、Matthew R. Kaller、Roxanne K. Kunz、Silke Miller、Holger Monenschein、Thomas Nguyen、Alexander J. Pickrell、Amy Porter、Andreas Reichelt、Xiaoning Zhao、James J.S. Treanor、Jennifer R. Allen

  DOI：10.1016/j.bmc.2014.10.013

  日期：2014.12

  We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum. (C) 2014 Elsevier Ltd. All rights reserved.