cis-N-benzyl-N-ethyl-3-methoxy-3,4-dihydrospiro-[[2]benzopyran-1,1'-cyclohexan]-4'-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: cis-N-benzyl-N-ethyl-3-methoxy-3,4-dihydrospiro-[[2]benzopyran-1,1'-cyclohexan]-4'-amine
• 化学式: C₂₄H₃₁NO₂
• 分子量: 365.516
• InChiKey: ICNREZSCROYFDM-IQEXNZJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  21.7
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  2-o-bromophenylacetaldehyde dimethyl acetal 在 盐酸 、 正丁基锂 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 正己烷 、 氯仿 、 水 、 乙腈 为溶剂， -78.0~100.0 ℃ 、400.01 kPa 条件下， 反应 6.66h， 生成 cis-N-benzyl-N-ethyl-3-methoxy-3,4-dihydrospiro-[[2]benzopyran-1,1'-cyclohexan]-4'-amine
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of spirocyclic σ1 receptor ligands with exocyclic amino moiety (increased distance 1)

  摘要：

  Various pharmacophore models for potent sigma(1) ligands specify a basic amino group flanked by two different hydrophobic regions in defined distances to the basic amine (distance 1 and distance 2, respectively). According to these models distance 1 of the potent spirocyclic sigma(1) ligand 1 is too short. In order to find a new class of more potent sigma(1) ligands and to verify the distance hypothesis of the pharmacophore models spirocyclic compounds 2 with an exocyclic amino group were designed and synthesized. The secondary amines 8 and 9 with N-benzyl residues are > 100-fold less potent than the spirocyclic piperidine 1. However, the tertiary methylamines trans-11 and cis-11 represent potent sigma(1) ligands with K-i-values of 43 and 24 nM, respectively. Whereas one large benzyl moiety is required for high sigma(1) receptor binding, a second large N-substituent is not tolerated by the sigma(1) receptor protein. As a rule, cis-configured diastereomers with a longer distance 1 (predominantly 7.16-7.23 angstrom) show higher sigma(1) affinities than their transconfigured counterparts (distance 1 is predominantly 5.88-6.26 angstrom). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.002

文献信息

• Design, synthesis and pharmacological evaluation of spirocyclic σ1 receptor ligands with exocyclic amino moiety (increased distance 1)
  作者：Elisabeth Rack、Roland Fröhlich、Dirk Schepmann、Bernhard Wünsch

  DOI：10.1016/j.bmc.2011.04.002

  日期：2011.5

  Various pharmacophore models for potent sigma(1) ligands specify a basic amino group flanked by two different hydrophobic regions in defined distances to the basic amine (distance 1 and distance 2, respectively). According to these models distance 1 of the potent spirocyclic sigma(1) ligand 1 is too short. In order to find a new class of more potent sigma(1) ligands and to verify the distance hypothesis of the pharmacophore models spirocyclic compounds 2 with an exocyclic amino group were designed and synthesized. The secondary amines 8 and 9 with N-benzyl residues are > 100-fold less potent than the spirocyclic piperidine 1. However, the tertiary methylamines trans-11 and cis-11 represent potent sigma(1) ligands with K-i-values of 43 and 24 nM, respectively. Whereas one large benzyl moiety is required for high sigma(1) receptor binding, a second large N-substituent is not tolerated by the sigma(1) receptor protein. As a rule, cis-configured diastereomers with a longer distance 1 (predominantly 7.16-7.23 angstrom) show higher sigma(1) affinities than their transconfigured counterparts (distance 1 is predominantly 5.88-6.26 angstrom). (C) 2011 Elsevier Ltd. All rights reserved.