N-[2-(3,4-dimethoxy-phenyl)-ethyl]-2-naphthalen-2-yl-acetamide | 108729-18-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[2-(3,4-dimethoxy-phenyl)-ethyl]-2-naphthalen-2-yl-acetamide
• 英文别名: N-(3,4-dimethoxyphenylethyl)(β-naphthyl)acetamide；N-[2-(3,4-dimethoxyphenyl)ethyl]-2-naphthalen-2-ylacetamide
• CAS: 108729-18-6
• 化学式: C₂₂H₂₃NO₃
• 分子量: 349.43
• InChiKey: OQSLRUAUSVKVBL-UHFFFAOYSA-N

物化性质

• 沸点：
  588.7±50.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

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-[2-(3,4-dimethoxy-phenyl)-ethyl]-2-naphthalen-2-yl-acetamide 在 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 33.0h， 以99%的产率得到6,7-dimethoxy-l-(β-naphthylmethyl)-3,4-dihydroisoquinoline hydrochloride
  参考文献：
  名称：

  [EN] NOVEL ENANTIOMERS OF TETRAHYDROISOQUINOLINE DERIVATIVES AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS
  [FR] NOUVEAUX ENANTIOMERES DE DERIVES DE TETRAHYDROISOQUINOLINE ET LEURS SELS PHARMACEUTIQUEMENT ACCEPTABLES, PREPARATIONS ET COMPOSITIONS PHARMACEUTIQUES DE CES DERNIERS

  摘要：

  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。

  公开号：

  WO2003095426A1
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 、 2-萘乙酸 在 氮 、 氯仿 、 盐酸 、 碳酸氢钠 、 Brine 、 magnesium sulfate 、 N-[2-(3,4-dimethoxy-phenyl)-ethyl]-2-naphthalen-2-yl-acetamide 作用下， 以 氯仿 、 乙醚 为溶剂， 反应 4.0h， 以to give the desired compound, N-(3,4-dimethoxyphenethyl)(β-naphthyl)acetamide (38.1 g, 92%) as a white solid的产率得到N-[2-(3,4-dimethoxy-phenyl)-ethyl]-2-naphthalen-2-yl-acetamide
  参考文献：
  名称：

  Novel enantiomers of etrahydroisoquinoline derivatives and theirpharmaceutically acceptable salts, their preparations and pharmaceutical compositions

  摘要：

  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。

  公开号：

  US20060058346A1
• 作为试剂：
  描述：

  3,4-二甲氧基苯乙胺 、 2-萘乙酸 在 氮 、 氯仿 、 盐酸 、 碳酸氢钠 、 Brine 、 magnesium sulfate 、 N-[2-(3,4-dimethoxy-phenyl)-ethyl]-2-naphthalen-2-yl-acetamide 作用下， 以 氯仿 、 乙醚 为溶剂， 反应 4.0h， 以to give the desired compound, N-(3,4-dimethoxyphenethyl)(β-naphthyl)acetamide (38.1 g, 92%) as a white solid的产率得到N-[2-(3,4-dimethoxy-phenyl)-ethyl]-2-naphthalen-2-yl-acetamide
  参考文献：
  名称：

  Novel enantiomers of etrahydroisoquinoline derivatives and theirpharmaceutically acceptable salts, their preparations and pharmaceutical compositions

  摘要：

  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。

  公开号：

  US20060058346A1

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。
• 1,2,3,4-tetrahydroisoquinoline derivatives
  申请人：——

  公开号：US20030176415A1

  公开（公告）日：2003-09-18

  The invention relates to novel 1,2,3,4-tetrahydroisochinoline 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 the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.

  本发明涉及新型1,2,3,4-四氢异喹啉衍生物的公式（I），以及它们作为药物组分在制备药物组合物中的使用。本发明还涉及相关方面，包括制备该化合物的过程，含有其中一种或多种化合物的药物组合物，特别是它们作为促进睡眠的药物组分。
• Tetrahydroisoquinolyl acetamide derivatives for use as orexin receptor antagonists
  申请人：Aissaoui Hamed

  公开号：US20060178515A1

  公开（公告）日：2006-08-10

  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.

  本发明涉及一种新的醋酰胺衍生物（I式），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，包括制备这些化合物的过程，含有这些化合物中的一种或多种的药物组成物，特别是它们作为促进睡眠的药物组成物中的使用，其中它们作为促进睡眠的药物组成物的奥力昔康受体拮抗剂。
• Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor
  作者：David A. Perrey、Nadezhda A. German、Ann M. Decker、David Thorn、Jun-Xu Li、Brian P. Gilmour、Brian F. Thomas、Danni L. Harris、Scott P. Runyon、Yanan Zhang

  DOI：10.1021/cn500330v

  日期：2015.4.15

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.
• 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.