(S)-1,2,3-trimethoxy-10,11-methylenedioxytetrahydroprotoberberine | 1398120-82-5

• 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: (S)-1,2,3-trimethoxy-10,11-methylenedioxytetrahydroprotoberberine
• 英文别名: (13S)-15,16,17-trimethoxy-6,8-dioxa-1-azapentacyclo[11.8.0.03,11.05,9.014,19]henicosa-3,5(9),10,14,16,18-hexaene
• CAS: 1398120-82-5
• 化学式: C₂₁H₂₃NO₅
• 分子量: 369.417
• InChiKey: RSBZFMUBYVLOMY-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 甲酸 、 (S,S)-N-(对甲苯磺酰)-1,2-二苯乙烷二胺(对异丙基苯)氯化钌(II) 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (S)-1,2,3-trimethoxy-10,11-methylenedioxytetrahydroprotoberberine
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D1 receptor

  摘要：

  A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D-1 and D-2) and serotonin (5-HT1A and 5-HT2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D-1 receptor, as well as high selectivity for the D-1 receptor over the D-2, 5-HT1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D-1 receptor binding affinity (K-i = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D-1 K-i = 6.23 nM, D-2 K-i = 56.17 nM), compound 19c showed better binding affinity for the D-1 receptor (2.5-fold higher) and excellent D-2/D-1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D-1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D-1 receptor. These results are in accord with molecular docking studies. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.057

文献信息

• Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D1 receptor
  作者：Wangke Qian、Weijian Lu、Haifeng Sun、Zeng Li、Liyuan Zhu、Rui Zhao、Lei Zhang、Shengbin Zhou、Yu Zhou、Hualiang Jiang、Xuechu Zhen、Hong Liu

  DOI：10.1016/j.bmc.2012.05.057

  日期：2012.8

  A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D-1 and D-2) and serotonin (5-HT1A and 5-HT2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D-1 receptor, as well as high selectivity for the D-1 receptor over the D-2, 5-HT1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D-1 receptor binding affinity (K-i = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D-1 K-i = 6.23 nM, D-2 K-i = 56.17 nM), compound 19c showed better binding affinity for the D-1 receptor (2.5-fold higher) and excellent D-2/D-1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D-1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D-1 receptor. These results are in accord with molecular docking studies. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.