6,7-dimethoxy-1-(3-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline | 96315-85-4

• 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-1-(3-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline
• CAS: 96315-85-4
• 化学式: C₁₇H₁₈N₂O₄
• 分子量: 314.341
• InChiKey: GGNIBPFRNLQZGV-UHFFFAOYSA-N

物化性质

• 熔点：
  106-110 °C(Solv: ethanol (64-17-5))
• 沸点：
  456.1±45.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-1-(3-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline 在 盐酸 、 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 水 为溶剂， 以94 %的产率得到1-(3-aminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  一系列合成的 1-Aryltetrahydroisoquinoline 生物碱衍生物在体内和计算机中的局部麻醉活性、急性毒性和结构-毒性关系的评价。

  摘要：

  异喹啉生物碱是最常见的生物碱类之一，在治疗各种疾病方面表现出显着的作用。寻找降低这些分子毒性并增加其治疗范围的方法是当务之急。在这里，通过 Pictet-Spengler 反应，一步法合成一系列 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines，收率为 85-98%。这是使用 3,4-二甲氧基苯乙胺与取代的苯甲醛在三氟乙酸中沸腾的反应完成的。此外，通过 1-(3'- nitro-, 4'-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines with SnCl2 × 2H2O。所得物质的结构通过红外 (IR) 和核磁共振 (1H 和 13C NMR) 光谱得到证实。ADMET/TOPKAT in silico 研究得出结论，合成的化合物表现出可接受的药效学和药代动力学特性

  DOI：

  10.3390/molecules28020477
• 作为产物：
  描述：

  N-[2-(3,4-dimethoxyphenyl)ethyl]-N-[(3-nitrophenyl)methylene]amine 在 三氟乙酸 作用下， 反应 90.0h， 生成 6,7-dimethoxy-1-(3-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Synthesis and anticonvulsant properties of tetrahydroisoquinoline derivatives

  摘要：

  As a follow up of our previous structure-activity relationship and molecular modeling studies, we synthesized a novel series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as potential non-competitive AMPA receptor antagonists. When tested for their ability to prevent sound-induced seizures in DBA/2 mice, some of these novel compounds showed high anticonvulsant potency.

  DOI：

  10.1016/j.farmac.2003.10.003

文献信息

• Synthesis of stable azomethine ylides by the rearrangement of 1,3-dipolar cycloadducts of 3,4-dihydroisoquinoline-2-oxides with DMAD
  作者：Necdet Coşkun、Selen Tunçman

  DOI：10.1016/j.tet.2005.11.040

  日期：2006.2

  corresponding 3,4-dihydroisoquinoline-2-oxides. Treatment of these cyclic nitrones with DMAD in toluene at room temperature gave the corresponding isoxazolo[3,2-a]isoquinolines. These compounds were heated in toluene at reflux to give the corresponding ylides in high yields (Method A). The effect of the substituents on the rate of the rearrangement of such compounds prompted us to discuss a new mechanism involving

  根据一锅法制备1-芳基-6,7-二甲氧基-1,2,3,4-四氢异喹啉，该过程涉及2-（3,4-二甲氧基苯基）-乙胺与芳族醛在TFA中回流反应。 。在室温下用甲醇中的H 2 O 2 -WO 4 2-处理四氢异喹啉，得到相应的3,4-二氢异喹啉-2-氧化物。在室温下用DMAD在甲苯中处理这些环状硝酮，得到相应的异恶唑并[3,2- a]异喹啉。将这些化合物在甲苯中加热回流，以高收率得到相应的酰化物（方法A）。取代基对这类化合物重排速率的影响促使我们讨论了涉及连续C–C键杂合和1,3-σ位移的新机理。一锅反应包括在回流的甲苯中用等摩尔量的DMAD处理硝酮，也得到了叶立德（方法B）。通过光谱方法和元素分析阐明了所制备化合物的结构。
• 3D Pharmacophore Models for 1,2,3,4-Tetrahydroisoquinoline Derivatives Acting as Anticonvulsant Agents
  作者：Laura De Luca、Rosaria Gitto、Maria Letizia Barreca、Roberta Caruso、Silvana Quartarone、Rita Citraro、Giovambattista De Sarro、Alba Chimirri

  DOI：10.1002/ardp.200600022

  日期：2006.7

  A 3D pharmacophore model predicting anticonvulsant activity was obtained for a series of 6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline derivatives recently disclosed as a new class of noncompetitive AMPA receptor antagonists. The training set included 17 compounds with varying potency against audiogenic seizures in DBA/2 mice. The best statistical hypothesis, generated with the HypoGen module of Catalyst

  最近披露的一系列 6,7-二甲氧基-1,2,3,4-四氢异喹啉衍生物作为一类新的非竞争性 AMPA 受体拮抗剂，获得了预测抗惊厥活性的 3D 药效团模型。训练集包括 17 种化合物，它们对 DBA/2 小鼠的听觉癫痫发作具有不同的效力。使用 Catalyst 4.9 的 HypoGen 模块生成的最佳统计假设由五个特征组成：两个氢键受体、两个疏水特征和一个疏水芳族区域，提供了一个相关系数为 0.919 的模型。所获得的模型是设计一些含有四氢异喹啉支架的新型抗惊厥药的有效工具。此外，为了解释新设计的 N-取代衍生物的不同程度的功效，
• Synthesis and evaluation of pharmacological profile of 1-aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamides
  作者：Rosaria Gitto、Stefania Ferro、Stefano Agnello、Laura De Luca、Giovanbattista De Sarro、Emilio Russo、Daniela Vullo、Claudiu T. Supuran、Alba Chimirri

  DOI：10.1016/j.bmc.2009.03.066

  日期：2009.5

  In previous studies we identified several 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives displaying potent anticonvulsant effects in different animal models of epilepsy. With the aim to deepen the structure-activity relationships (SAR) for this class of compounds and identify novel anticonvulsant agents we synthesized a series of 1-aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamides. The new compounds incorporate the main features of the above-mentioned anticonvulsants and a sulfonamide function capable to inhibit the enzyme carbonic anhydrase (CA, EC 4.2.1.1), which represents an attractive target in epilepsy. Pharmacological effects were evaluated in vivo against audiogenic seizures in DBA/2 mice and in vitro against several CA isoforms. Some of the new molecules showed anticonvulsant properties better than topiramate, but weak inhibitory activity and low selectivity in enzymatic assay. (C) 2009 Elsevier Ltd. All rights reserved.
• Novel Potent Anticonvulsant Agent Containing a Tetrahydroisoquinoline Skeleton
  作者：Rosaria Gitto、Roberta Caruso、Benedetta Pagano、Laura De Luca、Rita Citraro、Emilio Russo、Giovambattista De Sarro、Alba Chimirri

  DOI：10.1021/jm060411b

  日期：2006.9.1

  In our studies on the development of new anticonvulsants, we planned the synthesis of N-substituted 1,2,3,4-tetrahydroisoquinolines to explore the structure-activity relationships. All derivatives were evaluated against audiogenic seizures in DBA/2 mice, and the 1-(4'-bromophenyl)-6,7-dimethoxy-2-(piperidin-1-ylacetyl)derivative (26) showed the highest activity with a potency comparable to that of talampanel, the only noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist in clinical trials as an anticonvulsant agent. Electrophysiological experiments indicated that 26 acts as noncompetitive AMPA receptor modulator.
• Synthesis and anticonvulsant properties of tetrahydroisoquinoline derivatives
  作者：Rosaria Gitto、Roberta Caruso、Valerie Orlando、Silvana Quartarone、Maria Letizia Barreca、Guido Ferreri、Emilio Russo、Giovambattista De Sarro、Alba Chimirri

  DOI：10.1016/j.farmac.2003.10.003

  日期：2004.1

  As a follow up of our previous structure-activity relationship and molecular modeling studies, we synthesized a novel series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as potential non-competitive AMPA receptor antagonists. When tested for their ability to prevent sound-induced seizures in DBA/2 mice, some of these novel compounds showed high anticonvulsant potency.