6,7-dimethoxy-1-(3'-methoxybenzyl)-1,2,3,4-THIQ hydrochloride | 67237-66-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 6,7-dimethoxy-1-(3'-methoxybenzyl)-1,2,3,4-THIQ hydrochloride
• 英文别名: (R*,S*)-6,7-dimethoxy-1-[(3-methoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium chloride；6,7-dimethoxy-1-(3-methoxy-benzyl)-1,2,3,4-tetrahydro-isoquinoline; hydrochloride；6,7-Dimethoxy-1-(3-methoxy-benzyl)-1,2,3,4-tetrahydro-isochinolin; Hydrochlorid；rac-6,7-dimethoxy-1-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride；6,7-Dimethoxy-1-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride；6,7-dimethoxy-1-[(3-methoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline;hydrochloride
• CAS: 67237-66-5
• 化学式: C₁₉H₂₃NO₃*ClH
• 分子量: 349.857
• InChiKey: RNWXIAWGDPWEKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  39.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-1-(3'-methoxybenzyl)-1,2,3,4-THIQ hydrochloride 在 potassium carbonate 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 异丙醇 、 乙腈 为溶剂， 反应 27.0h， 生成 2,2-bis[[1-(4-tert-butylphenyl)triazol-4-yl]methyl]-6,7-dimethoxy-1-[(3-methoxyphenyl)methyl]-3,4-dihydro-1H-isoquinolin-2-ium
  参考文献：
  名称：

  四氢异喹啉衍生抗菌化合物的合成及生物学评价

  摘要：

  抗生素耐药性是现代医学面临的最大威胁之一。曾经常规用于治疗感染的药物正在变得无效，从而增加了对具有低耐药性的新型抗生素的需求。在这里，我们报告了 18 种新型阳离子四氢异喹啉-三唑化合物的合成。五种开发的分子在 2-4 μg/mL 的低 MIC 下对金黄色葡萄球菌具有活性。还发现命中化合物4b在 6 μg/mL 的 MIC 下消除结核分枝杆菌H37Rv。发现这种强效分子可有效消除金黄色葡萄球菌，连续传代 30 天后未观察到耐药性。这些结果确定了化合物4b及其类似物作为进一步药物开发的潜在候选者，有助于应对抗生素耐药性的威胁。

  DOI：

  10.1016/j.bmc.2022.116648
• 作为产物：
  描述：

  N-(2-(3,4-二甲氧基苯基)乙基)-2-(3-甲氧基苯基)乙酰胺 在 甲醇 、 sodium tetrahydroborate 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 6,7-dimethoxy-1-(3'-methoxybenzyl)-1,2,3,4-THIQ hydrochloride
  参考文献：
  名称：

  四氢异喹啉衍生抗菌化合物的合成及生物学评价

  摘要：

  抗生素耐药性是现代医学面临的最大威胁之一。曾经常规用于治疗感染的药物正在变得无效，从而增加了对具有低耐药性的新型抗生素的需求。在这里，我们报告了 18 种新型阳离子四氢异喹啉-三唑化合物的合成。五种开发的分子在 2-4 μg/mL 的低 MIC 下对金黄色葡萄球菌具有活性。还发现命中化合物4b在 6 μg/mL 的 MIC 下消除结核分枝杆菌H37Rv。发现这种强效分子可有效消除金黄色葡萄球菌，连续传代 30 天后未观察到耐药性。这些结果确定了化合物4b及其类似物作为进一步药物开发的潜在候选者，有助于应对抗生素耐药性的威胁。

  DOI：

  10.1016/j.bmc.2022.116648

文献信息

• 2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands
  作者：Javier Párraga、Nuria Cabedo、Sebastián Andujar、Laura Piqueras、Laura Moreno、Abraham Galán、Emilio Angelina、Ricardo D. Enriz、María Dolores Ivorra、María Jesús Sanz、Diego Cortes

  DOI：10.1016/j.ejmech.2013.07.036

  日期：2013.10

  Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D-2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D-1 and D-2 DR and establish the structure activity relationship (SAR) as dopaminergic agents. In general, all the tested THPBs with protected phenolic hydroxyls showed a lower affinity for D-1 and D-2 DR than their corresponding homologues with free hydroxyl groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in increased affinity and selectivity towards D-2 DR. This is in contrast with the current study since the existence of a chlorine atom into the A-ring of the THPBs caused increased affinity for D-1 DR but dramatically reduced the selectivity for D-2 DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity for DR than its homologue with an OH group in position 11 (9e) (250 fold for D-2 DR). None of the compounds showed any cytotoxicity in freshly isolated human neutrophils. A molecular modelling study of three representative THPBs was carried out. The combination of MD simulations with DFT calculations provided a clear picture of the ligand binding interactions from a structural and energetic point of view. Therefore, it is likely that compound 9d (2,3,9-trihydroxy-THPB) behave as D-2 DR agonist since serine residues cluster are crucial for agonist binding and receptor activation. (C) 2013 Elsevier Masson SAS. All rights reserved.