(2S,6R,11R)-3-(cyclopropylmethyl)-6,11-dimethyl-1-oxo-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-yl trifluoromethanesulfonate | 1122596-42-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 6,7-苯并吗啡烷
• 英文名称: (2S,6R,11R)-3-(cyclopropylmethyl)-6,11-dimethyl-1-oxo-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-yl trifluoromethanesulfonate
• 英文别名: [(1R,9S,13R)-10-(cyclopropylmethyl)-1,13-dimethyl-8-oxo-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl] trifluoromethanesulfonate
• CAS: 1122596-42-2
• 化学式: C₁₉H₂₂F₃NO₄S
• 分子量: 417.449
• InChiKey: PZURAIPUXYGHOJ-SDDDUWNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,6R,11R)-3-(cyclopropylmethyl)-6,11-dimethyl-1-oxo-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-yl trifluoromethanesulfonate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 盐酸羟胺 、 sodium ethanolate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 23.0h， 生成 1-((2S,6R,11R)-3-(cyclopropylmethyl)-6,11-dimethyl-1-oxo-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-yl)-3-(2,5,8,11,14-pentaoxahexadecan-16-yl)thiourea
  参考文献：
  名称：

  [EN] OPIOID AGONISTS AND USES THEREOF
  [FR] AGONISTES OPIOÏDES ET LEURS UTILISATIONS

  摘要：

  提供的是化合物，包括公式I的化合物；以及它们的药用可接受盐和溶剂化物。本文所述的化合物与药物发现、药物治疗、生理学、有机化学和聚合物化学等领域有关，并且/或在这些领域有应用。

  公开号：

  WO2015079459A1
• 作为产物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 酮佐辛 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 以88%的产率得到(2S,6R,11R)-3-(cyclopropylmethyl)-6,11-dimethyl-1-oxo-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-yl trifluoromethanesulfonate
  参考文献：
  名称：

  [EN] OPIOID AGONISTS AND USES THEREOF
  [FR] AGONISTES OPIOÏDES ET LEURS UTILISATIONS

  摘要：

  提供的是化合物，包括公式I的化合物；以及它们的药用可接受盐和溶剂化物。本文所述的化合物与药物发现、药物治疗、生理学、有机化学和聚合物化学等领域有关，并且/或在这些领域有应用。

  公开号：

  WO2015079459A1

文献信息

• Opioid agonists and uses thereof
  申请人：Nektar Therapeutics

  公开号：US10081602B2

  公开（公告）日：2018-09-25

  Provided are compounds, including those of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry.

  本文提供的化合物包括式 I 的化合物及其药学上可接受的盐和溶剂。本文所述化合物与药物发现、药物治疗、生理学、有机化学和聚合物化学等领域有关和/或具有应用价值。
• Syntheses and Opioid Receptor Binding Affinities of 8-Amino-2,6-methano-3-benzazocines
  作者：Mark P. Wentland、Yingchun Ye、Christopher L. Cioffi、Rongliang Lou、Qun Zhou、Guoyou Xu、Wenhu Duan、Christoph M. Dehnhardt、Xufeng Sun、Dana J. Cohen、Jean M. Bidlack

  DOI：10.1021/jm020429w

  日期：2003.2.1

  8-Amino-2,6-methano-3-benzazocine derivatives have been made using Pd-catalyzed amination procedures, and their affinities for opioid receptors were assessed. The 8-amino group was hypothesized to be a replacement for the prototypic 8-OH substituent for 2,6-methano-3-benzazocines and related opiates. This OH group is generally required for binding yet is implicated in unfavorable pharmacokinetic characteristics such as low oral bioavailability and rapid clearance via O-glucuronidation. The core structures in which the 8-OH group was replaced were cyclazocine and its enantiomers, ethylketocyclazocine and its enantiomers, ketocyclazocine, and Mr2034. Many new analogues had high affinity for opioid receptors with several in the subnanomolar range. Highest affinity was seen in analogues with secondary 8-(hetero)arylamino appendages. Binding to opioid receptors was enantioselective with the (2R,6R,11R)-configuration preferred and high selectivity for mu and kappa over delta opioid receptors was observed within the series. Several derivatives were shown to have intrinsic opioid-receptor-mediated activity in [S-35]GTPgammaS assays.
• Syntheses and opioid receptor binding properties of carboxamido-substituted opioids
  作者：Mark P. Wentland、Rongliang Lou、Qun Lu、Yigong Bu、Melissa A. VanAlstine、Dana J. Cohen、Jean M. Bidlack

  DOI：10.1016/j.bmcl.2008.10.134

  日期：2009.1

  A series of 15 novel opioid derivatives were made where the prototypic phenolic-OH group of traditional opioids was replaced by a carboxamido (CONH2) group. For 2,6-methano-3-benzazocines and morphinans similar or, in a few instances, enhanced affinity for mu, delta and kappa opioid receptors was observed when the OH --> CONH2 switch was applied. For 4,5 alpha-epoxymorphinans, binding affinities for the corresponding carboxamide derivatives were much lower than the OH partner consistent with our pharmacophore hypothesis concerning carboxamide bioactive conformation. The active metabolite of tramadol and its carboxamide counterpart had comparable affinities for the three receptors. (C) 2008 Elsevier Ltd. All rights reserved.
• OPIOID AGONISTS AND USES THEREOF
  申请人：Nektar Therapeutics (India) Pvt. Ltd.

  公开号：EP3074379A1

  公开（公告）日：2016-10-05
• US9688638B2
  申请人：——

  公开号：US9688638B2

  公开（公告）日：2017-06-27