5-bromo-1-[1-(2-fluoro-ethyl)-azetidin-3-yl]-2,3-dihydro-1H-indole | 1194732-26-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-bromo-1-[1-(2-fluoro-ethyl)-azetidin-3-yl]-2,3-dihydro-1H-indole
• 英文别名: 5-Bromo-1-[1-(2-fluoroethyl)azetidin-3-yl]-2,3-dihydroindole；5-bromo-1-[1-(2-fluoroethyl)azetidin-3-yl]-2,3-dihydroindole
• CAS: 1194732-26-7
• 化学式: C₁₃H₁₆BrFN₂
• 分子量: 299.186
• InChiKey: WXHCXGBDMCBKIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  392.7±42.0 °C(Predicted)
• 密度：
  1.463±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-苄氧基-2(1H)-吡啶酮 、 5-bromo-1-[1-(2-fluoro-ethyl)-azetidin-3-yl]-2,3-dihydro-1H-indole 在 copper(l) iodide 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-benzyloxy-1-{1-[1-(2-fluoro-ethyl)-azetidin-3-yl]-2,3-dihydro-1H-indol-5-yl}-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
• 作为产物：
  描述：

  5-溴二氢吲哚 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 5-bromo-1-[1-(2-fluoro-ethyl)-azetidin-3-yl]-2,3-dihydro-1H-indole
  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：WO2009137270A3

  公开（公告）日：2009-12-30
• 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.