6,7-dimethoxy-1-(phenoxymethyl)-1,2,3,4-tetrahydroisoquinoline | 3341-32-0

• 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-(phenoxymethyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 6,7-dimethoxy-1-phenoxymethyl-1,2,3,4-tetrahydro-isoquinoline；(+/-)-6,7-Dimethoxy-1-phenoxymethyl-1,2,3,4-tetrahydro-isochinolin；1-Phenoxymethyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinolin
• CAS: 3341-32-0
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: AESOCLVNKSKJSV-UHFFFAOYSA-N

物化性质

• 熔点：
  103 °C
• 沸点：
  443.3±45.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-1-(phenoxymethyl)-1,2,3,4-tetrahydroisoquinoline 以 甲苯 为溶剂， 生成 6,7-dimethoxy-1-phenoxymethyl-2-(1-(n-octyl)amino-2-nitrovinyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Series of 6,7-dimethoxy-1-(3,4- dimethoxybenzyl)-2-substituted Tetrahydroisoquinoline Derivatives

  摘要：

  癌症的多药耐药性是癌症化疗失败的主要原因。为了寻找具有强逆转活性且分子结构简单的新化合物，我们合成了一系列化合物，在这些化合物中，6,7-二甲氧基-1-(3,4-二甲氧基苄基)-四氢异喹啉体系的 2 位上连接了不同的取代基。 通过 MTT 对 K562 细胞株进行体外细胞毒性分析，所有衍生物都表现出微弱的细胞毒性活性。同时，这些化合物在 K562/A02 细胞系中进行了 MTT 体外评估，6e、6h 和 7c 表现出与维拉帕米相似或更强的活性，IC50 值分别为 0.66、0.65 和 0.96μM，比值分别为 24.13、24.50 和 16.59。

  DOI：

  10.2174/157340612801216337
• 作为产物：
  描述：

  苯氧乙酸 在 钾硼氢 、 二乙胺 、 三氯氧磷 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 29.5h， 生成 6,7-dimethoxy-1-(phenoxymethyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents

  摘要：

  Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.077

文献信息

• [EN] TETRAHYDROISOQUINOLYL ACETAMIDE DERIVATIVES FOR USE AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE TETRAHYDRO-ISOQUINOLYL-ACETAMIDE DESTINES A SERVIR D'ANTAGONISTES DES RECEPTEURS D'OREXINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2004085403A1

  公开（公告）日：2004-10-07

  The invention relates to novel acetamide derivatives of formula (I) and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of such compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.

  该发明涉及公式（I）的新型乙酰胺衍生物及其在制备药物组合物中作为活性成分的用途。该发明还涉及相关方面，包括制备这类化合物的方法、含有其中一个或多个这类化合物的药物组合物，特别是它们作为促进睡眠的药物受体拮抗剂的用途。
• Synthesis and Structure Activity Relationship of Tetrahydroisoquinoline-Based Potentiators of GluN2C and GluN2D Containing <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptors
  作者：Rose M. Santangelo Freel、Kevin K. Ogden、Katie L. Strong、Alpa Khatri、Kathryn M. Chepiga、Henrik S. Jensen、Stephen F. Traynelis、Dennis C. Liotta

  DOI：10.1021/jm400177t

  日期：2013.7.11

  We describe here the synthesis and evaluation of a series of tetrahydroisoquinolines that show subunit-selective potentiation of NMDA receptors containing the GluN2C or GluN2D subunits. Bischler–Napieralski conditions were employed in the key step for the conversion of acyclic amides to the corresponding tetrahydroisoquinoline-containing analogs. Compounds were evaluated using both two-electrode voltage

  我们在这里描述了一系列四氢异喹啉的合成和评估，这些四氢异喹啉显示含有 GluN2C 或 GluN2D 亚基的 NMDA 受体的亚基选择性增强。Bischler-Napieralski 条件用于将无环酰胺转化为相应的含四氢异喹啉类似物的关键步骤。使用来自非洲爪蟾卵母细胞的双电极电压钳记录和加载有 Ca 2+敏感染料的哺乳动物 BHK 细胞的成像来评估化合物。最有效的类似物具有 EC 50300 nM 的值并显示对最大有效浓度的谷氨酸和甘氨酸的反应增强 2 倍以上，但对含有 GluN2A 或 GluN2B 亚基 AMPA、红藻氨酸和 GABA 或甘氨酸受体或各种不同类型的 NMDA 受体的反应没有影响其他潜在目标。这些化合物代表一类有效的 NMDA 受体小分子亚基选择性增效剂。
• [EN] CYCLIC AMINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] DERIVES D'AMINE CYCLIQUES, PROCEDES DE PREPARATION DE CEUX-CI ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：GLAXO GROUP LTD

  公开号：WO2004099143A1

  公开（公告）日：2004-11-18

  A compound of formula (I) wherein R represents a radical selected from i) ii) iii) iv) where the substituents R1, R2, R3, R4, R4, R7 and the indices m, n and p are as defined in the description; or pharmaceutically acceptable salts and solvates thereof; processes for their preparation to pharmaceutical compositions containing them and their use in the treatment of conditions mediated by tachykinins and/or by selective inhibition of serotonin reuptake transporter protein.

  式（I）的化合物，其中R代表从i）ii）iii）iv）中选择的基团，其中取代基R1、R2、R3、R4、R5、R6、R7和指数m、n和p如描述中所定义；或其药学上可接受的盐和溶剂；它们的制备方法到含有它们的药物组合物以及它们在治疗由速效肽激酶介导的病症和/或通过选择性抑制血清素再摄取转运蛋白介导的病症中的应用。
• 1,2,3,4-tetrahydroisoquinolines derivatives
  申请人：——

  公开号：US20040242564A1

  公开（公告）日：2004-12-02

  The invention relates to novel 1,2,3,4-tetrahydroisoquinoline derivatives and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as neurohormonal antagonists.

  本发明涉及新型1,2,3,4-四氢异喹啉衍生物及相关化合物，以及它们作为制备药物组成部分的活性成分的用途。本发明还涉及相关方面，包括制备化合物的过程，含有其中一种或多种化合物的药物组成物，特别是它们作为神经荷尔蒙拮抗剂的用途。
• 1 2 3 4 Tetrahydroisoquinolines derivatives as urotensin II receptor antagonists
  申请人：——

  公开号：US20040110744A1

  公开（公告）日：2004-06-10

  The invention relates to novel 1,2,3,4-tetrahydroisoquinoline derivatives of formula (I) and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as neurohormonal antagonists especially urotensin II antagonists.

  本发明涉及一种新型1,2,3,4-四氢异喹啉衍生物的公式(I)及其相关化合物，以及它们作为制备药物组成部分的活性成分的用途。本发明还涉及相关方面，包括制备化合物的过程，含有其中一种或多种化合物的药物组合物，尤其是它们作为神经激素拮抗剂，特别是尿激肽II拮抗剂的用途。