| 949901-55-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• CAS: 949901-55-7
• 化学式: C₂₁H₂₅NO₂
• 分子量: 323.435
• InChiKey: RCAWLZSSMPQICI-CEQLMSFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  32.7
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 以91%的产率得到
  参考文献：
  名称：

  Discovery of N -substituted- endo -3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of μ-opioid receptor antagonists

  摘要：

  Gastrointestinal dysfunction as a consequence of the use of opioid analgesics is of significant clinical concern. First generation drugs to treat these opioid-induced side-effects were limited by their negative impact on opioid receptor agonist-induced analgesia. Second generation therapies target a localized, peripherally-restricted, non-CNS penetrant drug distribution of opioid receptor antagonists. Herein we describe the discovery of the N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of l-opioid receptor antagonists. This report highlights the discovery of the key mu-opioid receptor antagonist pharmacophore and the optimization of in vitro metabolic stability through the application of a phenol bioisostere. The compounds 27a and 31a with the most attractive in vitro profile, formed the basis for the application of Theravance Biopharma's multivalent approach to drug discovery to afford the clinical compound axelopran (TD-1211), targeted for the treatment of opioid-induced constipation. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.04.092
• 作为产物：
  描述：

  苄胺 在 盐酸 、 disodium hydrogenphosphate 、 cerium(III) chloride 作用下， 以 四氢呋喃 、 水 为溶剂， 生成
  参考文献：
  名称：

  Discovery of N -substituted- endo -3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of μ-opioid receptor antagonists

  摘要：

  Gastrointestinal dysfunction as a consequence of the use of opioid analgesics is of significant clinical concern. First generation drugs to treat these opioid-induced side-effects were limited by their negative impact on opioid receptor agonist-induced analgesia. Second generation therapies target a localized, peripherally-restricted, non-CNS penetrant drug distribution of opioid receptor antagonists. Herein we describe the discovery of the N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of l-opioid receptor antagonists. This report highlights the discovery of the key mu-opioid receptor antagonist pharmacophore and the optimization of in vitro metabolic stability through the application of a phenol bioisostere. The compounds 27a and 31a with the most attractive in vitro profile, formed the basis for the application of Theravance Biopharma's multivalent approach to drug discovery to afford the clinical compound axelopran (TD-1211), targeted for the treatment of opioid-induced constipation. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.04.092

文献信息

• 8-Azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
  申请人：Long Daniel D.

  公开号：US20070219278A1

  公开（公告）日：2007-09-20

  The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R 1 , R 2 , R 3 , A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

  该发明提供了一种新颖的8-azabicyclo[3.2.1]辛烷化合物，化学式为(I)：其中R1、R2、R3、A和G在规范中有定义，或其药用可接受的盐或溶剂，这些化合物是μ阿片受体的拮抗剂。该发明还提供了包含这些化合物的药物组合物，使用这些化合物治疗与μ阿片受体活性相关的疾病的方法，以及用于制备这些化合物的过程和中间体。
• 8-AZABICYCLO[3.2.1]OCTANE COMPOUNDS AS MU OPIOID RECEPTOR ANTAGONISTS
  申请人：Long Daniel D.

  公开号：US20100035921A1

  公开（公告）日：2010-02-11

  The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R 1 , R 2 , R 3 , A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

  本发明提供了化学式（I）的新型8-氮杂双环[3.2.1]辛烷化合物：其中R1、R2、R3、A和G在规范中定义，或其药学上可接受的盐或溶剂，其为μ阿片受体拮抗剂。本发明还提供了包含这种化合物的制药组合物，使用这种化合物治疗与μ阿片受体活性相关的疾病的方法，以及用于制备这种化合物的过程和中间体。
• 8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US10081626B2

  公开（公告）日：2018-09-25

  The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, R3, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

  本发明提供了式 (I) 的新型 8-氮杂双环[3.2.1]辛烷化合物： 其中 R1、R2、R3、A 和 G 在说明书中定义，或其药学上可接受的盐或溶液，它们是μ阿片受体的拮抗剂。本发明还提供了包含此类化合物的药物组合物、使用此类化合物治疗与μ阿片受体活性相关的疾病的方法，以及制备此类化合物的工艺和中间体。
• 8-AZABICYCLOÝ3.2.1¨OCTANE COMPOUNDS AS MU OPIOID RECEPTOR ANTAGONISTS
  申请人：Theravance, Inc.

  公开号：EP2001876B1

  公开（公告）日：2011-05-18
• US7622508B2
  申请人：——

  公开号：US7622508B2

  公开（公告）日：2009-11-24