endo-3-(2-methoxyphenyl)-8-azabicyclo[3.2.1]octan-3-ol | 473969-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: endo-3-(2-methoxyphenyl)-8-azabicyclo[3.2.1]octan-3-ol
• 英文别名: 3-(2-methoxyphenyl)-8-propyl-8-azabicyclo[3.2.1]octan-3-endo-ol；3-(2-methoxy-phenyl)-8-aza-bicyclo[3.2.1]octan-3-ol
• CAS: 473969-12-9
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: OSNWWHCHTLEKOW-YABSGUDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  41.49
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  endo-3-(2-methoxyphenyl)-8-azabicyclo[3.2.1]octan-3-ol 在 lithium aluminium tetrahydride 、 sodium hydroxide 作用下， 以 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 3-(2-methoxyphenyl)-8-propyl-8-azabicyclo[3.2.1]octan-3-endo-ol
  参考文献：
  名称：

  桥联哌啶和哌嗪异构体的设计与合成

  摘要：

  我们已经开发了多种方法来合成各种哌啶/哌嗪桥联的哌多匹定等位基因。评估了化合物在激动剂和拮抗剂模式下对D2受体的抵抗力以及在激动剂模式下对D4受体的抵抗力。研究了hERG结合和ADME概况。

  DOI：

  10.1016/j.bmcl.2018.06.038
• 作为产物：
  描述：

  endo-8-ethoxycarbonyl-3-(2-methoxyphenyl)-8-azabicyclo[3.2.1]octan-3-ol 在 氢氧化钾 、 水 、 肼 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以65%的产率得到endo-3-(2-methoxyphenyl)-8-azabicyclo[3.2.1]octan-3-ol
  参考文献：
  名称：

  Structure−Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol

  摘要：

  Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; K-i(D2R/MR) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2(L)R- or hD3R-transfected HEK 293 cells (31, K-i(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, K-i(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes.

  DOI：

  10.1021/jm800532x

文献信息

• Modulation of selective serotonin reuptake inhibitor and 5-HT1A antagonist activity in 8-aza-bicyclo[3.2.1]octane derivatives of 2,3-dihydro-1,4-benzodioxane
  作者：Adam M. Gilbert、Gary P. Stack、Ramaswamy Nilakantan、Jason Kodah、Megan Tran、Rosemary Scerni、Xiaojie Shi、Deborah L. Smith、Terrance H. Andree

  DOI：10.1016/j.bmcl.2003.10.024

  日期：2004.1

  2,3-Dihydro-1,4-benzodioxanes with aryl 8-aza-bicyclo[3.2.1]oct-3-ene attachments 2 produce compounds with potent 5-HT-T affinity, and weak 5-HT1A affinity and a, affinity. This compares with 2,3-dihydro-1,4-benzodioxanes containing 8-aza-bicyclo[3.2.1] octan-3-ol attachments 4 which possess potent 5-HT1A affinity, moderate to good selectivity over a, and little 5-HT-T affinity. A 3-benzothiophene analogue of 4 (30) was synthesized which possesses potent 5-HT1A affinity and especially good selectivity over both a, and 5-HT-T. (C) 2003 Elsevier Ltd. All rights reserved.