N-(3,4-dimethoxyphenylethyl) (α-naphthyl) acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(3,4-dimethoxyphenylethyl) (α-naphthyl) acetamide
• 英文别名: N-(3,4-dimethoxyphenylethyl)(alpha-naphthyl)acetamide；N-[2-(3,4-dimethoxyphenyl)ethyl]-2-naphthalen-1-ylacetamide
• 化学式: C₂₂H₂₃NO₃
• 分子量: 349.43
• InChiKey: QLZWGAYTZACQDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3,4-dimethoxyphenylethyl) (α-naphthyl) acetamide 在 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 2.5h， 生成 6,7-dimethoxy-1-(α-naphthylmethyl)-3,4-dihydroisoquinoline
  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：

  1-萘乙酸 、 3,4-二甲氧基苯乙胺 反应 3.0h， 生成 N-(3,4-dimethoxyphenylethyl) (α-naphthyl) acetamide
  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

文献信息

• [EN] NOVEL ENANTIOMERS OF TETRAHYDROISOQUINOLINE DERIVATIVES AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS<br/>[FR] NOUVEAUX ENANTIOMERES DE DERIVES DE TETRAHYDROISOQUINOLINE ET LEURS SELS PHARMACEUTIQUEMENT ACCEPTABLES, PREPARATIONS ET COMPOSITIONS PHARMACEUTIQUES DE CES DERNIERS
  申请人：YUN-CHOI HYE-SOOK

  公开号：WO2003095426A1

  公开（公告）日：2003-11-20

  The disclosure concerns novel enantiomers of tetrahydroisoquinoline derivatives and their pharmaceutically acceptable salts, their preparations and pharmaceutical compositions. The enantiomers of tetrahydroisoquinoline derivatives are provided which are useful in stimulating heart rate and hypotensive activity, inhibitory activity against platelet aggregation, and suppressive against inducible NO synthase. The enantiomers of tetrahydroisoquinoline derivatives and their pharmaceutically acceptable salts are effective for treating congestive heart failure, hypertension, thrombosis, inflammation, septicemia, cardiac insufficiency, and disseminated intravascular coagulopathy.

  该披露涉及四氢异喹啉衍生物的新对映体及其药用盐，它们的制备和药物组合物。所提供的四氢异喹啉衍生物的对映体在刺激心率和降压活性、抑制血小板聚集活性以及对诱导型NO合酶的抑制方面具有用途。四氢异喹啉衍生物的对映体及其药用盐对治疗充血性心力衰竭、高血压、血栓形成、炎症、败血症、心脏功能不全和播散性血管内凝血症具有有效性。
• METHOD FOR RESOLVING ENANTIOMERS FROM RACEMIC MIXTURE HAVING CHIRAL CARBON IN ALPHA POSITION OF NITROGEN
  申请人：Ahn Soon Kil

  公开号：US20090036679A1

  公开（公告）日：2009-02-05

  Disclosed relates to a simplified method for resolving enantiomers by dissolving a racemic mixture having chiral carbon in α-position of nitrogen and an amino acid to prepare a diastereomeric salt, not using catalyses or enzymes, with enhancing the optical purity remarkably. Moreover, the present invention can prepare the enantiomers in large quantities without using expensive catalysts or without controlling the reaction conditions for the activity of enzymes applied.

  揭示了一种简化的方法，通过将含有手性碳的混合物溶解在氮的α位和氨基酸中，制备出对映异构盐来分离对映体，而不使用催化剂或酶，显著提高光学纯度。此外，本发明可以大量制备对映体，而无需使用昂贵的催化剂或控制应用酶的反应条件。
• Novel enantiomers of etrahydroisoquinoline derivatives and theirpharmaceutically acceptable salts, their preparations and pharmaceutical compositions
  申请人：Yun-Choi Hye-Sook

  公开号：US20060058346A1

  公开（公告）日：2006-03-16

  The disclosure concerns novel enantiomers of tetrahydroisoquinoline derivatives and their pharmaceutically acceptable salts, their preparations and pharmaceutical compositions. The enantiomers of tetrahydroisoquinoline derivatives are provided which are useful in stimulating heart rate and hypotensive activity, inhibitory activity against platelet aggregation, and suppressive against inducible NO synthase. The enantiomers of tetrahydroisoquinoline derivatives and their pharmaceutically acceptable salts are effective for treating congestive heart failure, hypertension, thrombosis, inflammation, septicemia, cardiac insufficiency, and disseminated intravascular coagulopathy.

  该披露涉及四氢异喹啉衍生物的新手性异构体及其药学上可接受的盐、其制备和制药组合物。提供了四氢异喹啉衍生物的手性异构体，其对于刺激心率和降压活性、抑制血小板聚集活性以及对可诱导的一氧化氮合酶具有抑制作用是有用的。四氢异喹啉衍生物的手性异构体及其药学上可接受的盐对于治疗充血性心力衰竭、高血压、血栓形成、炎症、败血症、心脏功能不全和弥漫性血管内凝血是有效的。
• Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents
  作者：Zhi-hong Zou、Xiao-bu Lan、Hai Qian、Wen-long Huang、Yun-man Li

  DOI：10.1016/j.bmcl.2011.07.077

  日期：2011.10

  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.
• Enantioselective synthesis of (R)-(+)- and (S)-(−)-higenamine and their analogues with effects on platelet aggregation and experimental animal model of disseminated intravascular coagulation
  作者：Mi Kyung Pyo、Duck-Hyung Lee、Doo-Hyun Kim、Ji-Hye Lee、Jong-Cheon Moon、Ki Churl Chang、Hye Sook Yun-Choi

  DOI：10.1016/j.bmcl.2008.05.094

  日期：2008.7

  Optically active tetrahydroisoquinoline alkaloids, (R)-(+)-higenamine (1R) and (S)-(-)-higenamine (1 S), and their optically active 1-naphthylmethyl analogues (2 and 3), were synthesized by enantioselective hydrogenation of the corresponding dihydroisoquinoline intermediates 7 as a key step. The evaluation of the platelet anti-aggregation effect demonstrated clearly that the (S)-(-)-enantiomers, 1S, 2S, and 3S, had higher inhibitory potency than the corresponding (R)-(+)-antipodes, 1R, 2R, and 3R, respectively, to platelet aggregation induced by epinephrine. 1S enantiomer was superior to the corresponding 1R enantiomer in attenuating all of the disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) parameters tested, while the S enantiomers 2S and 3S ameliorated some of the DIC and MOF parameters more effectively than the corresponding antipodes 2R and 3R. (c) 2008 Published by Elsevier Ltd.