Trifluoro-methanesulfonic acid (2R,6R,11R)-6,11-dimethyl-3-[(S)-1-(tetrahydro-furan-2-yl)methyl]-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-8-yl ester | 502962-34-7

• 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: Trifluoro-methanesulfonic acid (2R,6R,11R)-6,11-dimethyl-3-[(S)-1-(tetrahydro-furan-2-yl)methyl]-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-8-yl ester
• 英文别名: [(1R,9R,13R)-1,13-dimethyl-10-[[(2S)-oxolan-2-yl]methyl]-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl] trifluoromethanesulfonate
• CAS: 502962-34-7
• 化学式: C₂₀H₂₆F₃NO₄S
• 分子量: 433.492
• InChiKey: HUQDUFPJLDZSBU-PTKHLAPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  64.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Trifluoro-methanesulfonic acid (2R,6R,11R)-6,11-dimethyl-3-[(S)-1-(tetrahydro-furan-2-yl)methyl]-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-8-yl ester 在 1,1'-双(二苯基膦)二茂铁 、 tris(dibenzylideneacetone)dipalladium (0) 、 盐酸羟胺 、 sodium acetate 、 sodium t-butanolate 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 6.5h， 生成 (2R,6R,11R)-6,11-Dimethyl-3-[(S)-1-(tetrahydro-furan-2-yl)methyl]-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-8-ylamine
  参考文献：
  名称：

  Syntheses and Opioid Receptor Binding Affinities of 8-Amino-2,6-methano-3-benzazocines

  摘要：

  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.

  DOI：

  10.1021/jm020429w
• 作为产物：
  描述：

  三氟甲磺酸酐 、 Mr 1526 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 Trifluoro-methanesulfonic acid (2R,6R,11R)-6,11-dimethyl-3-[(S)-1-(tetrahydro-furan-2-yl)methyl]-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-8-yl ester
  参考文献：
  名称：

  Syntheses and Opioid Receptor Binding Affinities of 8-Amino-2,6-methano-3-benzazocines

  摘要：

  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.

  DOI：

  10.1021/jm020429w

文献信息

• 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.