1-(2-benzyloxybenzyl)-6-bromo-8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline | 262450-70-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(2-benzyloxybenzyl)-6-bromo-8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline
• CAS: 262450-70-4
• 化学式: C₂₅H₂₆BrNO₂
• 分子量: 452.391
• InChiKey: MWTDXUYSJNVEPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.81
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  21.7
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(2-benzyloxybenzyl)-6-bromo-8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 2-[(6-bromo-8-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl)methyl]phenol
  参考文献：
  名称：

  Binding and Preliminary Evaluation of 5-Hydroxy- and 10-Hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines as Dopamine Receptor Ligands

  摘要：

  The N-methyl, N-ethyl, and N-n-propyl derivatives of 5-hydoxy- and 10-hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines were were prepared as monophenolic ligands for the dopamine receptor and evaluated for their affinity at D-1-like and D-2-like subtypes. All compounds showed very low D-1 affinities. This could be ascribed to the absence of a catechol nucleus or of the beta-phenyldopamine pharmacophore. Only the N-methyl-5-hydroxy- (5a), N-methyl-10-hydroxy- (6a), and N-methyl-4-bromo-10-methoxy-2,3,12,12a-tetrahydro-1H-[1]-benzoxepino[2,3,4-ij]isoquinolines (26a) bound the D-2 receptors with low affinity, in the same range as dopamine. In compounds 5a and so, the 2-(3-hydroxyphenyl)ethylamine moiety does not meet the requirements of the D-2 agonist pharmacophore: namely, the 2-(3-hydroxyphenyl)ethylamine does not reach the trans, fully extended conformation. The three compounds did not interact with recombinant human D-4 receptors, and only 5a showed low affinity for rat recombinant D-3 receptors. Analysis of the influence of Na+ on [H-3]spiperone binding showed that 5a displays a potential dopamine D-2 agonist profile, whereas 6a probably has a dopamine D-2 antagonist activity. The D-2 agonist activity of 5a was proved by the effects on prolactin release from primary cultures of rat anterior pituitary cells.

  DOI：

  10.1021/jm991034o
• 作为产物：
  描述：

  2-(3-bromo-5-methoxyphenyl)nitroethylene 在 盐酸 、 amalgamated zinc 、 三氯氧磷 作用下， 以 甲醇 、 乙腈 、 xylene 为溶剂， 反应 15.5h， 生成 1-(2-benzyloxybenzyl)-6-bromo-8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Binding and Preliminary Evaluation of 5-Hydroxy- and 10-Hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines as Dopamine Receptor Ligands

  摘要：

  The N-methyl, N-ethyl, and N-n-propyl derivatives of 5-hydoxy- and 10-hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines were were prepared as monophenolic ligands for the dopamine receptor and evaluated for their affinity at D-1-like and D-2-like subtypes. All compounds showed very low D-1 affinities. This could be ascribed to the absence of a catechol nucleus or of the beta-phenyldopamine pharmacophore. Only the N-methyl-5-hydroxy- (5a), N-methyl-10-hydroxy- (6a), and N-methyl-4-bromo-10-methoxy-2,3,12,12a-tetrahydro-1H-[1]-benzoxepino[2,3,4-ij]isoquinolines (26a) bound the D-2 receptors with low affinity, in the same range as dopamine. In compounds 5a and so, the 2-(3-hydroxyphenyl)ethylamine moiety does not meet the requirements of the D-2 agonist pharmacophore: namely, the 2-(3-hydroxyphenyl)ethylamine does not reach the trans, fully extended conformation. The three compounds did not interact with recombinant human D-4 receptors, and only 5a showed low affinity for rat recombinant D-3 receptors. Analysis of the influence of Na+ on [H-3]spiperone binding showed that 5a displays a potential dopamine D-2 agonist profile, whereas 6a probably has a dopamine D-2 antagonist activity. The D-2 agonist activity of 5a was proved by the effects on prolactin release from primary cultures of rat anterior pituitary cells.

  DOI：

  10.1021/jm991034o