(+)-cyclazocine triflate ester | 262273-24-5

• 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: (+)-cyclazocine triflate ester
• 英文别名: (2S,6S,11S)-3-(cyclopropylmethyl)-1,2,3,4,5,6-hexahydro-cis-6,11-dimethyl-2,6-methano-3-benzazocin-8-yltrifluoromethanesulfonic acid ester；[(1S,9S,13S)-10-(cyclopropylmethyl)-1,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl] trifluoromethanesulfonate
• CAS: 262273-24-5
• 化学式: C₁₉H₂₄F₃NO₃S
• 分子量: 403.466
• InChiKey: UBEXGYVVGBCJAB-UUWFMWQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+)-cyclazocine triflate 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， 生成 (+)-3-(cyclopropylmethyl)-1,2,3,4,5,6-hexahydro-cis-6,11-dimethyl-2,6-methano-3-benzazocin-8-amine
  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：

  (2alpha,6alpha,11R*)-1,2,3,4,5,6-六氢-6,11-二甲基-2,6-甲桥-3-苯并氮杂环辛四烯-8-醇 、 alkaline earth salt of/the/ methylsulfuric acid 在 吡啶 、 potassium hydrogencarbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (+)-cyclazocine triflate ester
  参考文献：
  名称：

  8-Aminocyclazocine analogues: synthesis and structure–activity relationships

  摘要：

  Opioid binding affinities were assessed for a series of cyclazocine analogues where the prototypic S-OH substituent of cyclazocine was replaced by amino and substituted-amino groups. For mu and kappa opioid receptors, secondary amine derivatives having the (2R,6R,11R)-configuration had the highest affinity. Most targets were efficiently synthesized from the triflate of cyclazocine or its enantiomers using Pd-catalyzed amination procedures. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00670-8

文献信息

• Redefining the Structure−Activity Relationships of 2,6-Methano-3-benzazocines. 4. Opioid Receptor Binding Properties of 8-[<i>N</i>-(4‘-phenyl)-phenethyl)carboxamido] Analogues of Cyclazocine and Ethylketocycalzocine
  作者：Mark P. Wentland、Melissa VanAlstine、Robert Kucejko、Rongliang Lou、Dana J. Cohen、Amy L. Parkhill、Jean M. Bidlack

  DOI：10.1021/jm060278n

  日期：2006.9.1

  The synthesis and evaluation of a series of aryl-containing N-monosubstituted analogues of the lead compound 8-carboxamidocyclazocine were performed to probe a putative hydrophobic binding pocket of opioid receptors. High binding affinity to mu, kappa, and delta opioid receptors was observed for the 8-[N-(4'-phenyl)-phenethyl)carboxamido] analogue.
• 8-Carboxamidocyclazocine analogues
  作者：Mark P. Wentland、Rongliang Lou、Yingchun Ye、Dana J. Cohen、Gregory P. Richardson、Jean M. Bidlack

  DOI：10.1016/s0960-894x(01)00014-2

  日期：2001.3

  Unexpectedly high affinity for opioid receptors has been observed for a novel series of cyclazocine analogues where the prototypic 8-OH was replaced by a carboxamido group. For mu and kappa opioid receptors, the primary carboxamido derivative of cyclazocine ((+/-)-15) displayed high affinity (K-i=0.41 and 0.53 nM, respectively) nearly comparable to cyclazocine. A high enantiopreference ((2R,6R,11R)-) for binding was also observed. Compound (+/-)-15 also displayed potent antinociception activity in mice when administered icv. (C) 2001 Elsevier Science Ltd. All rights reserved.
• 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.
• 8-Aminocyclazocine analogues: synthesis and structure–activity relationships
  作者：Mark P Wentland、Guoyou Xu、Christopher L Cioffi、Yingchun Ye、Wenhu Duan、Dana J Cohen、Ann M Colasurdo、Jean M Bidlack

  DOI：10.1016/s0960-894x(99)00670-8

  日期：2000.1

  Opioid binding affinities were assessed for a series of cyclazocine analogues where the prototypic S-OH substituent of cyclazocine was replaced by amino and substituted-amino groups. For mu and kappa opioid receptors, secondary amine derivatives having the (2R,6R,11R)-configuration had the highest affinity. Most targets were efficiently synthesized from the triflate of cyclazocine or its enantiomers using Pd-catalyzed amination procedures. (C) 2000 Elsevier Science Ltd. All rights reserved.