N-<2-(3,4-dimethoxyphenyl)ethyl>-3-(3,4-dimethoxyphenyl)propionamide | 20944-13-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-<2-(3,4-dimethoxyphenyl)ethyl>-3-(3,4-dimethoxyphenyl)propionamide
• 英文别名: 3-(3,4-dimethoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]propanamide
• CAS: 20944-13-2
• 化学式: C₂₁H₂₇NO₅
• 分子量: 373.449
• InChiKey: CVAPQIIHMCZOBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-<2-(3,4-dimethoxyphenyl)ethyl>-3-(3,4-dimethoxyphenyl)propionamide 在 Noyori's catalyst 、 sodium formate 、 三氯氧磷 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 36.0h， 生成 (S)-(-)-Norhomolaudanosine
  参考文献：
  名称：

  仿生总生物碱。

  摘要：

  使用仿生方法，由花椒苷酰胺原生物碱实现了Dysoxylum生物碱的五步全合成。该合成具有直接酰胺化和Bischler-Napieralski反应形成二氢异喹啉环的特征，然后将其进行Noyori不对称转移氢化，以在C-1处建立立体异构中心。我们的合成序列为Dysoxylum生物碱的生物合成起源提供了重要的视角，因为获得了6种天然生物碱和12种合成类似物，具有很高的对映选择性，总收率高达68％。此外，我们描述了Dysoxylum生物碱对斑马鱼胚胎的急性毒性，将它们的毒性与相应的zanthoxylamide原生物碱的毒性进行了比较，并建立了对映选择性-毒性关系。

  DOI：

  10.1021/acs.joc.9b02093
• 作为产物：
  描述：

  3,4-二甲氧基苯丙酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 N-<2-(3,4-dimethoxyphenyl)ethyl>-3-(3,4-dimethoxyphenyl)propionamide
  参考文献：
  名称：

  氟酸介质中的二氧化钌III。在合成阿波菲，高磷和二苯并偶氮生物碱中的应用。对制备氮杂荧蒽骨架的研究。

  摘要：

  通过使用的RuO在aporphinic和homoaporphinic生物碱phenylalkyltetrahydroisoquinoline前体分子内氧化性偶合2，2H 2 ö在氟进行酸性介质。我们对不同前体的试剂与TTFA进行了比较研究。该程序还扩展到一种二苯甲唑啉生物碱的合成。然后，我们尝试使用酚和非酚异喹啉前体合成氮杂荧蒽环。

  DOI：

  10.1016/s0040-4020(01)88259-4

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。
• 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。
• Stenlake; Waigh; Dewar, European Journal of Medicinal Chemistry, 1981, vol. 16, # 6, p. 515 - 524
  作者：Stenlake、Waigh、Dewar、et al.

  DOI：——

  日期：——
• 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.
• Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels
  作者：Amaury Graulich、Jacqueline Scuvée-Moreau、Livia Alleva、Cédric Lamy、Olivier Waroux、Vincent Seutin、Jean-François Liégeois

  DOI：10.1021/jm0607395

  日期：2006.11.30

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.