1-(4-Bromophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 96315-84-3

• 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-(4-Bromophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• CAS: 96315-84-3
• 化学式: C₁₇H₁₈BrNO₂
• 分子量: 348.239
• InChiKey: AFGIYTBFSNPSMM-UHFFFAOYSA-N

物化性质

• 熔点：
  132-134 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  439.0±45.0 °C(Predicted)
• 密度：
  1.335±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 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：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-Bromophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 磺酰胺 作用下， 以 二甲氧基乙烷 为溶剂， 90.0 ℃ 、1.38 MPa 条件下， 反应 0.67h， 以86%的产率得到1-(4'-bromophenyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide
  参考文献：
  名称：

  Synthesis and evaluation of pharmacological profile of 1-aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamides

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.03.066
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 在 三氟乙酸 作用下， 反应 0.34h， 生成 1-(4-Bromophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  探索人类碳酸酐酶（hCAs）与一类新型苯甲磺酰胺之间的分子相互作用

  摘要：

  根据hCA II与4-（3,4-二氢-1 H-异喹啉-2-羰基）苯磺酰胺（3）（PDB代码4Z1J）的复合物的X射线晶体学研究，4-设计了（1-芳基-3,4-二氢-1 H-异喹啉-2-羰基）苯磺酰胺（23 – 33）。具体而言，我们的想法是通过引入其他疏水/亲水功能来提高对可药物异构体的选择性。在合成和测试的化合物中，（R，S）-4-（6,7-二羟基-1-苯基-3,4-四氢异喹啉-1 H -2-羰基）苯磺酰胺（30）对大脑表达的hCA VII（K i = 0.20 nM ）表现出显着的抑制作用，并且对更广泛分布的hCA I和hCA II同工型具有选择性。通过对映选择性HPLC，我们解析了外消旋混合物，并确定了两种对映异构体（30a和30b）是hCA VII的等活性抑制剂。晶体学和对接研究揭示了这些抑制剂与碳酸酐酶（CA）催化位点之间的主要相互作用，从而突显了非极性接触对于此类hCA抑制剂的相关作用。

  DOI：

  10.1021/acs.jmedchem.7b00264

文献信息

• 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，
• Highly diastereoselective synthesis of polycyclic amines via redox neutral C–H functionalization
  作者：Chottanahalli S. Pavan Kumar、Kachigere B. Harsha、Nagarakere C. Sandhya、Ajjalli B. Ramesha、Kempegowda Mantelingu、Kanchugarakoppal S. Rangappa

  DOI：10.1039/c5nj01706h

  日期：——

  Synthesis of polycyclic amines was achieved by benzoic acid catalysed reaction of 1-aryl THIQs and 1-aryl trypolines with o-allyl salicylaldehydes through the in situ generated azomethine ylide intermediates that undergo intramolecular [3+2]-cycloadditions with four new stereogenic centers in excellent diastereoselectivities under simple and mild conditions.

  多环胺的合成通过苯甲酸催化1-芳基THIQ和1-芳基脯氨酸与邻烯丙基水杨醛通过原位生成的偶氮甲碱内酯中间体反应而进行，该中间体经过分子内[3 + 2]-环加成反应并带有四个新的立体中心在简单温和的条件下具有出色的非对映选择性。
• Mechanistic Studies on Bioinspired Aerobic C–H Oxidation of Amines with an <i>ortho</i>-Quinone Catalyst
  作者：Ruipu Zhang、Yan Qin、Long Zhang、Sanzhong Luo

  DOI：10.1021/acs.joc.8b02948

  日期：2019.3.1

  different catalytic pathways were discovered for the reductive half reactions: for primary amines, the reaction was found to proceed via a transamination pathway, while the reactions with secondary amines and tertiary amines proceeded via hydride transfer. We also found that the amine substrates could significantly promote the regeneration of the ortho-quinone catalyst in the oxidative half reaction, in which

  我们在这里报告了我们对邻苯醌催化的伯，仲和叔胺的有氧氧化的机理研究。对于还原性半反应，发现了两种不同的催化途径：对于伯胺，发现该反应通过氨基转移途径进行，而与仲胺和叔胺的反应则通过氢化物转移进行。我们还发现，胺底物可以在氧化半反应中显着促进邻醌催化剂的再生，在该反应中，胺底物与邻苯二酚衍生物之间发生质子转移（邻醌催化剂的还原形式）。
• Discovery of a Novel and Highly Potent Noncompetitive AMPA Receptor Antagonist
  作者：Rosaria Gitto、Maria Letizia Barreca、Laura De Luca、Giovambattista De Sarro、Guido Ferreri、Silvana Quartarone、Emilio Russo、Andrew Constanti、Alba Chimirri

  DOI：10.1021/jm0210008

  日期：2003.1.1

  4-tetrahydroisoquinoline derivatives were designed and synthesized as potential noncompetitive AMPA receptor antagonists on the basis of molecular modeling studies. Sound-induced seizure testing showed that this class of compounds possessed anticonvulsant properties. In particular, 10c was more potent than talampanel (2), a noncompetitive AMPA receptor antagonist currently being investigated in phase III trials as

  在分子模型研究的基础上，设计并合成了N-乙酰基-1-芳基-6,7-二甲氧基-1,2,3,4-四氢异喹啉衍生物，作为潜在的非竞争性AMPA受体拮抗剂。声音诱发的癫痫发作测试表明这类化合物具有抗惊厥作用。特别是10c比talampanel（2）更有效，talampanel（2）是一种非竞争性AMPA受体拮抗剂，目前正在III期试验中作为抗癫痫药进行研究。此外，电生理研究表明10c是AMPA受体的高效非竞争性调节剂。
• 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.