6,7-dimethoxy-2-[2-(4-methoxyphenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline | 1071049-42-7

• 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: 6,7-dimethoxy-2-[2-(4-methoxyphenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline
• 英文别名: Antidepressant agent 5；6,7-dimethoxy-2-[2-(4-methoxyphenyl)ethyl]-3,4-dihydro-1H-isoquinoline
• CAS: 1071049-42-7
• 化学式: C₂₀H₂₅NO₃
• 分子量: 327.423
• InChiKey: CQLWHPMAMUBLNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(3,4-dimethoxyphenyl)-N-[2-(4-methoxyphenyl)ethyl]acetamide 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 甲醇 、 甲基叔丁基醚 、 水 为溶剂， 反应 3.0h， 生成 6,7-dimethoxy-2-[2-(4-methoxyphenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  A New Class of Selective and Potent 7-Dehydrocholesterol Reductase Inhibitors

  摘要：

  We prepared a number of N-phenethyltetrahydroisoquinolines structurally related to protoberberines. They were tested for activity against bacteria, fungi, and human leukemia HL-60 cells and also for inhibition of biosynthesis: ergosterol in yeasts and cholesterol in human cells. In the latter assay panel, several of the compounds were distinguished by a strong and selective inhibition of 7-dehydrocholesterol reductase (7-DHCR, EC 1.3.1.21), an enzyme responsible for the conversion of 7-dehydrocholesterol to cholesterol in the last step of cholesterol biosynthesis. In a whole-cell assay, the most active compound 5f showed a much stronger inhibition of overall cholesterol biosynthesis (IC50 2.3 nM) than BM 15.766 (IC50 500 nM), presently the most selective known inhibitor of 7-DHCR Since a defect of 7-dehydrocholesterol reductase is associated with Smith-Lemli-Opitz syndrome (SLOS), the potent and selective inhibitors reported here will enable more detailed investigation of the pathogenesis of SLOS.

  DOI：

  10.1021/jm3006096

文献信息

• Design, synthesis, and biological evaluation of THIQ as antidepressive agents
  作者：Xiaopeng Wei、Man Zhang、Yijing Guo、Qianqian Chang、Wei Qiao

  DOI：10.1016/j.bmcl.2023.129470

  日期：2023.10

  7-substituted tetrahydroisoquinolines derivatives were designed, synthesized, and evaluated for neuroprotective properties. We summarized the preliminary structure activity relationships (SAR). Compound 3i was screened as a hit compound and its antidepressant activity was evaluated by employing the forced swimming test, tail suspension test. Additionally, ADMET profile (absorption, distribution, metabolism

  设计、合成并评估了 7-取代四氢异喹啉衍生物的神经保护特性。我们总结了初步的结构活性关系（SAR）。筛选出化合物3i作为重点化合物，并通过强迫游泳试验、悬尾试验评价其抗抑郁活性。此外，还预测了化合物3i的 ADMET 特性（吸收、分布、代谢、排泄和毒性特性），以评估其类铅特性和安全性。使用分子对接和分子动力学模拟探索了化合物3i与 MAO-A结合的相互作用。生物学研究结果表明，化合物3i表现出与木兰花碱几乎相同的抗抑郁活性。根据 ADMET 概况预测，化合物3i预计具有良好的药物特性和安全性。这项工作为抗抑郁药物的发现提供了思路。
• A New Class of Selective and Potent 7-Dehydrocholesterol Reductase Inhibitors
  作者：Aline Horling、Christoph Müller、Richard Barthel、Franz Bracher、Peter Imming

  DOI：10.1021/jm3006096

  日期：2012.9.13

  We prepared a number of N-phenethyltetrahydroisoquinolines structurally related to protoberberines. They were tested for activity against bacteria, fungi, and human leukemia HL-60 cells and also for inhibition of biosynthesis: ergosterol in yeasts and cholesterol in human cells. In the latter assay panel, several of the compounds were distinguished by a strong and selective inhibition of 7-dehydrocholesterol reductase (7-DHCR, EC 1.3.1.21), an enzyme responsible for the conversion of 7-dehydrocholesterol to cholesterol in the last step of cholesterol biosynthesis. In a whole-cell assay, the most active compound 5f showed a much stronger inhibition of overall cholesterol biosynthesis (IC50 2.3 nM) than BM 15.766 (IC50 500 nM), presently the most selective known inhibitor of 7-DHCR Since a defect of 7-dehydrocholesterol reductase is associated with Smith-Lemli-Opitz syndrome (SLOS), the potent and selective inhibitors reported here will enable more detailed investigation of the pathogenesis of SLOS.