1-(1-azetidin-3-yl-2,3-dihydro-1H-indol-5-yl)-4-(4-chloro-phenyl)-1H-pyridin-2-one | 1194732-29-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(1-azetidin-3-yl-2,3-dihydro-1H-indol-5-yl)-4-(4-chloro-phenyl)-1H-pyridin-2-one
• 英文别名: 1-[1-(Azetidin-3-yl)-2,3-dihydroindol-5-yl]-4-(4-chlorophenyl)pyridin-2-one；1-[1-(azetidin-3-yl)-2,3-dihydroindol-5-yl]-4-(4-chlorophenyl)pyridin-2-one
• CAS: 1194732-29-0
• 化学式: C₂₂H₂₀ClN₃O
• 分子量: 377.873
• InChiKey: QIIGCHHHMGRXFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-溴-2-氟乙烷 、 1-(1-azetidin-3-yl-2,3-dihydro-1H-indol-5-yl)-4-(4-chloro-phenyl)-1H-pyridin-2-one 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以35 mg的产率得到4-(4-chloro-phenyl)-1-{1-[1-(2-fluoro-ethyl)-azetidin-3-yl]-2,3-dihydro-1H-indol-5-yl}-1H-pyridin-2-
  参考文献：
  名称：

  Strategies to lower the Pgp efflux liability in a series of potent indole azetidine MCHR1 antagonists

  摘要：

  A series of potent indolyl azetidine rMCHR1 antagonists were found to show poor CNS penetration due to Pgp efflux. We envisioned a strategy which included: lowering basicity; changing the conformational flexibility motif; and removal of a hydrogen bond donor, in an attempt to optimize this property while maintaining target receptor efficacy. This work resulted in mitigation of Pgp efflux, and led us to identify 1-dihydroindolyl azetidine derivatives with CNS penetration and excellent rMCHR1 binding affinity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.020
• 作为产物：
  描述：

  4-溴-2-氟吡啶 在 copper(l) iodide 、 四(三苯基膦)钯 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 sodium carbonate 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.25h， 生成 1-(1-azetidin-3-yl-2,3-dihydro-1H-indol-5-yl)-4-(4-chloro-phenyl)-1H-pyridin-2-one
  参考文献：
  名称：

  Strategies to lower the Pgp efflux liability in a series of potent indole azetidine MCHR1 antagonists

  摘要：

  A series of potent indolyl azetidine rMCHR1 antagonists were found to show poor CNS penetration due to Pgp efflux. We envisioned a strategy which included: lowering basicity; changing the conformational flexibility motif; and removal of a hydrogen bond donor, in an attempt to optimize this property while maintaining target receptor efficacy. This work resulted in mitigation of Pgp efflux, and led us to identify 1-dihydroindolyl azetidine derivatives with CNS penetration and excellent rMCHR1 binding affinity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.020

文献信息

• [EN] AZETIDINE DERIVATIVES<br/>[FR] DÉRIVÉS D'AZÉTIDINE
  申请人：LUNDBECK & CO AS H

  公开号：WO2009137270A2

  公开（公告）日：2009-11-12

  The present invention relates to azetidine derivatives which bind to the MCH l receptor. In separate aspects, the subject invention is directed to uses of said compounds in the preparation of a pharmaceutical composition for the treatment of metabolic and CNS related disorders and to methods of treating said disorders comprising administering a therapeutically effective amount of a compound of the invention.
• Strategies to lower the Pgp efflux liability in a series of potent indole azetidine MCHR1 antagonists
  作者：Kai Lu、Yu Jiang、Bin Chen、Eman M. Eldemenky、Gil Ma、Mathivanan Packiarajan、Gamini Chandrasena、Andrew D. White、Kenneth A. Jones、Boshan Li、Sang-Phyo Hong

  DOI：10.1016/j.bmcl.2011.07.020

  日期：2011.9

  A series of potent indolyl azetidine rMCHR1 antagonists were found to show poor CNS penetration due to Pgp efflux. We envisioned a strategy which included: lowering basicity; changing the conformational flexibility motif; and removal of a hydrogen bond donor, in an attempt to optimize this property while maintaining target receptor efficacy. This work resulted in mitigation of Pgp efflux, and led us to identify 1-dihydroindolyl azetidine derivatives with CNS penetration and excellent rMCHR1 binding affinity. (C) 2011 Elsevier Ltd. All rights reserved.