2-benzyloxy-10-hydroxy-3,9-dimethoxy-5,8,13,13a-tetrahydro-6H-dibenzo[a,g]quinolizine

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 2-benzyloxy-10-hydroxy-3,9-dimethoxy-5,8,13,13a-tetrahydro-6H-dibenzo[a,g]quinolizine
• 英文别名: 3,9-dimethoxy-2-phenylmethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinolin-10-ol
• 化学式: C₂₆H₂₇NO₄
• 分子量: 417.505
• InChiKey: HUISJNPAFPDCNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyloxy-10-hydroxy-3,9-dimethoxy-5,8,13,13a-tetrahydro-6H-dibenzo[a,g]quinolizine 在 Raney-Ni 作用下， 以 乙醇 为溶剂， 以89%的产率得到3,9-二甲氧基-5,8,13,13alpha-四氢-6H-异喹啉并[3,2-a]异喹啉-2,10-二醇
  参考文献：
  名称：

  光学异构的千金藤啶碱及其衍生物的制备方法

  摘要：

  本发明涉及一种通式(I)所示的化合物，其中各取代基的定义如说明书中所述。本发明还涉及该化合物的制备方法，该化合物在制备光学异构的四氢原小檗碱类化合物中的应用，以及其在制备光学异构的四氢原小檗碱类化合物的中间体。

  公开号：

  CN102399166B
• 作为产物：
  描述：

  4-溴邻甲氧基苯酚 在 lithium aluminium tetrahydride 、 正丁基锂 、 水 、 potassium carbonate 、 二异丙胺 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 2-benzyloxy-10-hydroxy-3,9-dimethoxy-5,8,13,13a-tetrahydro-6H-dibenzo[a,g]quinolizine
  参考文献：
  名称：

  Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity

  摘要：

  Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (+/-)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (+/-)-stepholidine, were synthesized and evaluated for affinity at dopamine and sigma receptors in order to evaluate effects on D3 and sigma 2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and sigma 2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for sigma 2 receptors as well as sigma 2 versus sigma 1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and sigma receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.037

文献信息

• 光学异构的千金藤啶碱及其衍生物的制备方法
  申请人：山东特珐曼药业有限公司

  公开号：CN102399166B

  公开（公告）日：2016-04-27

  本发明涉及一种通式(I)所示的化合物，其中各取代基的定义如说明书中所述。本发明还涉及该化合物的制备方法，该化合物在制备光学异构的四氢原小檗碱类化合物中的应用，以及其在制备光学异构的四氢原小檗碱类化合物的中间体。
• Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity
  作者：Satishkumar Gadhiya、Sudharshan Madapa、Thomas Kurtzman、Ian L. Alberts、Steven Ramsey、Nagavara-Kishore Pillarsetty、Teja Kalidindi、Wayne W. Harding

  DOI：10.1016/j.bmc.2016.03.037

  日期：2016.5

  Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (+/-)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (+/-)-stepholidine, were synthesized and evaluated for affinity at dopamine and sigma receptors in order to evaluate effects on D3 and sigma 2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and sigma 2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for sigma 2 receptors as well as sigma 2 versus sigma 1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and sigma receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds. (C) 2016 Elsevier Ltd. All rights reserved.