3-chloro-4-[4-[5-(2-pyrimidinyl)piperidin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 3-chloro-4-[4-[5-(2-pyrimidinyl)piperidin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one
• 英文别名: 3-chloro-4,5-dihydro-4-(4-(3-(2-pyrimidinyl)piperidin-1-yl)butyl)-1,4-benzoxazepin-5-one；3-Chloro-4-[4-(3-pyrimidin-2-ylpiperidin-1-yl)butyl]-1,4-benzoxazepin-5-one
• 化学式: C₂₂H₂₅ClN₄O₂
• 分子量: 412.919
• InChiKey: WAAZJJOYWCSXTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  水杨酰胺 在 盐酸 、 sodium methylate 、 sodium hydride 、 potassium carbonate 、 sodium iodide 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 32.0h， 生成 3-chloro-4-[4-[5-(2-pyrimidinyl)piperidin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one
  参考文献：
  名称：

  Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: Discovery of Piclozotan

  摘要：

  A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot of compounds exhibited nanomolar affinity for 5-HT1A receptor with good selectivity over both dopamine D, and alpha(1)-adrenergic receptors. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-y]butyl]-1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.046

文献信息

• New piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives as selective 5-HT1A receptor agonists with highly potent anti-ischemic effects
  作者：Katsuhide Kamei、Noriko Maeda、Ryoko Katsuragi-Ogino、Makoto Koyama、Mika Nakajima、Toshio Tatsuoka、Tomochika Ohno、Teruyoshi Inoue

  DOI：10.1016/j.bmcl.2005.04.059

  日期：2005.6

  A series of new piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives were synthesized. Among these compounds, 4-methyl-2-(1,2,3,6-tetrahydropyridin-4-yl)pyrimidine derivative 23 (SUN N5147) exhibited sub-nanomolar affinity for 5-HT1A receptor with 1000-fold selectivity over both dopamine D-2 and alpha(1)-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. (c) 2005 Elsevier Ltd. All rights reserved.
• BENZOXAZEPINE DERIVATIVES, SALTS THEREOF, AND DRUGS CONTAINING THE SAME
  申请人：SUNTORY LIMITED

  公开号：EP0755930B1

  公开（公告）日：2002-07-31
• US6187769B1
  申请人：——

  公开号：US6187769B1

  公开（公告）日：2001-02-13
• US6337397B1
  申请人：——

  公开号：US6337397B1

  公开（公告）日：2002-01-08
• Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: Discovery of Piclozotan
  作者：Katsuhide Kamei、Noriko Maeda、Kayoko Nomura、Makoto Shibata、Ryoko Katsuragi-Ogino、Makoto Koyama、Mika Nakajima、Teruyoshi Inoue、Tomochika Ohno、Toshio Tatsuoka

  DOI：10.1016/j.bmc.2005.10.046

  日期：2006.3

  A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot of compounds exhibited nanomolar affinity for 5-HT1A receptor with good selectivity over both dopamine D, and alpha(1)-adrenergic receptors. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-y]butyl]-1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. (c) 2005 Elsevier Ltd. All rights reserved.