(+)-环佐辛 | 63903-61-7

• 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
• 中文名称: (+)-环佐辛
• 英文名称: (2S,6S,11S)-3-Cyclopropylmethyl-6,11-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-8-ol
• 英文别名: (+)-cyclazocine；(+)-cis-Cyclazocine；Cyclazocine, (+)-；(1S,9S,13S)-10-(cyclopropylmethyl)-1,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol
• CAS: 63903-61-7；7313-87-3
• 化学式: C₁₈H₂₅NO
• 分子量: 271.403
• InChiKey: YQYVFVRQLZMJKJ-UUWFMWQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-环佐辛 在 吡啶 、 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 、 二氯甲烷 、 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：

  6-乙氧基-2,2,4-三甲基-1,2-二氢喹啉 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (+)-环佐辛
  参考文献：
  名称：

  (±)-cis-2'-Hydroxy-5,9-dimethyl-6, 7-benzomorphan 的改进分辨率和外消旋、(+)-和 (-)-cis-2-Methylcyclopropyl-2'-hydroxy的制备-5,9-二甲基-6,7-苯并吗啡 (Cyclazocine)

  摘要：

  摘要 我们报告了通过 (-)-N-乙酰基-L-谷氨酸和 (+)-α 有效拆分 (±)-cis-2 -hydroxy-5, 9-dimethyl-6, 7-benzomorphan 的新程序-溴樟脑-φ-磺酸盐，(+)-α-溴樟脑-φ-磺酸盐的直接N-取代，以及使用这些方法合成外消旋、(+)-和(-)-环佐辛。

  DOI：

  10.1080/00397919908086216

文献信息

• 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.
• 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.
• BRINE, G. A.;BERRANG, B.;HAYES, J. P.;CARROLL, F. I., J. HETEROCYCL. CHEM., 27,(1990) N, C. 2139-2143
  作者：BRINE, G. A.、BERRANG, B.、HAYES, J. P.、CARROLL, F. I.

  DOI：——

  日期：——
• 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.
• Improved Resolution of (±)-<i>cis</i>-2′-Hydroxy-5,9-dimethyl-6, 7-benzomorphan and Preparation of Racemic, (+)-, and (-)-<i>cis</i>-2-Methylcyclopropyl-2′-hydroxy-5,9-dimethyl-6,7-benzomorphan (Cyclazocine)
  作者：William A. Boulanger

  DOI：10.1080/00397919908086216

  日期：1999.6

  Abstract We report novel procedures for the efficient resolution of (±)-cis-2 -hydroxy-5, 9-dimethyl-6, 7-benzomorphan via the (-)-N-acetyl-L-glutamate and (+)-α-bromocamphor-φ-sulfonate salts, the direct N-substitution of the (+)-α-bromocamphor-φ-sulfonate salts, and the use of these methods for the synthesis of racemic, (+)-, and (-)-cyclazocine.

  摘要 我们报告了通过 (-)-N-乙酰基-L-谷氨酸和 (+)-α 有效拆分 (±)-cis-2 -hydroxy-5, 9-dimethyl-6, 7-benzomorphan 的新程序-溴樟脑-φ-磺酸盐，(+)-α-溴樟脑-φ-磺酸盐的直接N-取代，以及使用这些方法合成外消旋、(+)-和(-)-环佐辛。