1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-(3,4-dimethoxyphenyl)ethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-(3,4-dimethoxyphenyl)ethanone
• 英文别名: 1-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-2-(3,4-dimethoxyphenyl)ethanone
• 化学式: C₂₁H₂₅NO₅
• 分子量: 371.433
• InChiKey: FJZOEZWNWLNVIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4-二甲氧基苯乙酸 在 氯化亚砜 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-(3,4-dimethoxyphenyl)ethanone
  参考文献：
  名称：

  Restraining the flexibility of the central linker in terameprocol results in constrained analogs with improved growth inhibitory activity

  摘要：

  The semi-synthetic lignan terameprocol inhibits the transcription of several inflammatory and oncogenic genes and has been evaluated for its anti-cancer properties. Here we investigated the effect of restricting the flexibility of the carbon linker connecting the terminal rings of terameprocol on its growth inhibitory activity. Conformational restriction was explored by introducing unsaturation, inserting polar entities with limited flexibility and cyclization of the connecting linker. Twenty three compounds were synthesized and evaluated on a panel of malignant human cells. The most promising compounds were those with non-polar linkers, as seen in butadiene 1a and the cyclized benzylideneindane analog 7. Both compounds were more potent than terameprocol on pancreatic BxPC-3 cells with GI(50) values of 3.4 and 8.1 mu M, respectively. Selected isomers of 1a (E,E) and 7 (Z) adopted low energy bent conformations that mimicked the low energy conformer of terameprocol. It is tempting to propose that conformational similarity to terameprocol may have contributed to their good activity. The scaffolds of 1a and 7 should be further investigated for their anticancer potential. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.014

文献信息

• Restraining the flexibility of the central linker in terameprocol results in constrained analogs with improved growth inhibitory activity
  作者：Sherman Si Han Ho、Mei Lin Go

  DOI：10.1016/j.bmcl.2013.09.014

  日期：2013.11

  The semi-synthetic lignan terameprocol inhibits the transcription of several inflammatory and oncogenic genes and has been evaluated for its anti-cancer properties. Here we investigated the effect of restricting the flexibility of the carbon linker connecting the terminal rings of terameprocol on its growth inhibitory activity. Conformational restriction was explored by introducing unsaturation, inserting polar entities with limited flexibility and cyclization of the connecting linker. Twenty three compounds were synthesized and evaluated on a panel of malignant human cells. The most promising compounds were those with non-polar linkers, as seen in butadiene 1a and the cyclized benzylideneindane analog 7. Both compounds were more potent than terameprocol on pancreatic BxPC-3 cells with GI(50) values of 3.4 and 8.1 mu M, respectively. Selected isomers of 1a (E,E) and 7 (Z) adopted low energy bent conformations that mimicked the low energy conformer of terameprocol. It is tempting to propose that conformational similarity to terameprocol may have contributed to their good activity. The scaffolds of 1a and 7 should be further investigated for their anticancer potential. (c) 2013 Elsevier Ltd. All rights reserved.