(2R,6S,11S)-8-(Benzhydrylidene-amino)-3-cyclopropylmethyl-6-ethyl-11-methyl-3,4,5,6-tetrahydro-2H-2,6-methano-benzo[d]azocin-1-one | 1026690-53-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,6S,11S)-8-(Benzhydrylidene-amino)-3-cyclopropylmethyl-6-ethyl-11-methyl-3,4,5,6-tetrahydro-2H-2,6-methano-benzo[d]azocin-1-one
• 英文别名: (1S,9R,13S)-4-(benzhydrylideneamino)-10-(cyclopropylmethyl)-1-ethyl-13-methyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-8-one
• CAS: 1026690-53-8
• 化学式: C₃₂H₃₄N₂O
• 分子量: 462.635
• InChiKey: XYZPXQBQVDUSHH-ZVDSLUNQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,6S,11S)-8-(Benzhydrylidene-amino)-3-cyclopropylmethyl-6-ethyl-11-methyl-3,4,5,6-tetrahydro-2H-2,6-methano-benzo[d]azocin-1-one 在 盐酸羟胺 、 sodium acetate 作用下， 以 甲醇 为溶剂， 生成 (2R,6S,11S)-8-Amino-3-cyclopropylmethyl-6-ethyl-11-methyl-3,4,5,6-tetrahydro-2H-2,6-methano-benzo[d]azocin-1-one
  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：

  ethylketocyclazocine 在 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 tris(dibenzylideneacetone)dipalladium (0) 、 sodium t-butanolate 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (2R,6S,11S)-8-(Benzhydrylidene-amino)-3-cyclopropylmethyl-6-ethyl-11-methyl-3,4,5,6-tetrahydro-2H-2,6-methano-benzo[d]azocin-1-one
  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