4-((S)-2-(2-cyclopentylethylamino)-3-((R)-1-(methylamino)pentan-2-ylamino)propyl)phenol | 1186219-93-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-((S)-2-(2-cyclopentylethylamino)-3-((R)-1-(methylamino)pentan-2-ylamino)propyl)phenol
• 英文别名: 4-[(2S)-2-(2-cyclopentylethylamino)-3-[[(2R)-1-(methylamino)pentan-2-yl]amino]propyl]phenol
• CAS: 1186219-93-1
• 化学式: C₂₂H₃₉N₃O
• 分子量: 361.571
• InChiKey: JDQHSTJUSKJHSV-RTWAWAEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  56.3
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((S)-2-(2-cyclopentylethylamino)-3-((R)-1-(methylamino)pentan-2-ylamino)propyl)phenol 在 硼烷四氢呋喃络合物 、 哌啶 作用下， 生成
  参考文献：
  名称：

  Identification, structure–activity relationships and molecular modeling of potent triamine and piperazine opioid ligands

  摘要：

  Opioid receptors are important targets for pain management. Here, we report the synthesis and biological evaluation of three positional scanning combinatorial libraries, consisting of linear triamines and piperazines. A highly potent (14 nM) and selective (IC50(mu)/IC50(kappa) = 71; IC50(delta)/IC50(kappa) = 714) triamine for the kappa-opioid receptor was found. In addition, non-selective mu-kappa binders were obtained, with binding affinities of 54 nM and 22 nM for mu- and kappa-opioid receptors, respectively. Structure-activity relationships of each subset are described. 3D molecular alignments based on shape similarity to internal and external query molecules were carried out. For the combinatorial chemistry dataset studied here a 1.3 similarity cut-off value was observed to be efficient in the ROCS-based alignment method. Interactions from the overlays analyzed in the binding sites of homology models of the receptors revealed specific substitution patterns for enhancing binding affinity in the piperazine series. Pharmacophore modeling of the compounds found from the three combinatorial libraries was also performed. The pharmacophore model indicated that the important feature for receptor binding activity with the mu-receptor was the presence of at least one hydrogen bond acceptor and one aromatic hydrophobic group. Whereas for the kappa-receptor two binding modes emerged with one set of compounds employing the hydrogen bond acceptor and aromatic hydrophobic group, and a second set possibly via interactions with the receptor by hydrophobic and ionic salt-bridges. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.026
• 作为产物：
  描述：

  在 氢氟酸 作用下， 生成 4-((S)-2-(2-cyclopentylethylamino)-3-((R)-1-(methylamino)pentan-2-ylamino)propyl)phenol
  参考文献：
  名称：

  Identification, structure–activity relationships and molecular modeling of potent triamine and piperazine opioid ligands

  摘要：

  Opioid receptors are important targets for pain management. Here, we report the synthesis and biological evaluation of three positional scanning combinatorial libraries, consisting of linear triamines and piperazines. A highly potent (14 nM) and selective (IC50(mu)/IC50(kappa) = 71; IC50(delta)/IC50(kappa) = 714) triamine for the kappa-opioid receptor was found. In addition, non-selective mu-kappa binders were obtained, with binding affinities of 54 nM and 22 nM for mu- and kappa-opioid receptors, respectively. Structure-activity relationships of each subset are described. 3D molecular alignments based on shape similarity to internal and external query molecules were carried out. For the combinatorial chemistry dataset studied here a 1.3 similarity cut-off value was observed to be efficient in the ROCS-based alignment method. Interactions from the overlays analyzed in the binding sites of homology models of the receptors revealed specific substitution patterns for enhancing binding affinity in the piperazine series. Pharmacophore modeling of the compounds found from the three combinatorial libraries was also performed. The pharmacophore model indicated that the important feature for receptor binding activity with the mu-receptor was the presence of at least one hydrogen bond acceptor and one aromatic hydrophobic group. Whereas for the kappa-receptor two binding modes emerged with one set of compounds employing the hydrogen bond acceptor and aromatic hydrophobic group, and a second set possibly via interactions with the receptor by hydrophobic and ionic salt-bridges. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.026