3-(5-bromo-2,3-dihydro-indol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester | 1194732-22-3

• 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: 3-(5-bromo-2,3-dihydro-indol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester
• CAS: 1194732-22-3
• 化学式: C₁₆H₂₁BrN₂O₂
• 分子量: 353.259
• InChiKey: ABLVRGXVWYSKBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  32.78
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-(5-bromo-2,3-dihydro-indol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-(Azetidin-3-yl)-5-bromo-2,3-dihydroindole
  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：

  1-Boc-3-氮杂环丁酮 、 5-溴二氢吲哚 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以93%的产率得到3-(5-bromo-2,3-dihydro-indol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester
  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