2-(3,4-dimethoxyphenyl)-N-[2-(3,4,5-trimethoxyphenyl)-ethyl]-acetamide | 10313-61-8

• 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: 2-(3,4-dimethoxyphenyl)-N-[2-(3,4,5-trimethoxyphenyl)-ethyl]-acetamide
• 英文别名: (3,4-dimethoxy-phenyl)-acetic acid-(3,4,5-trimethoxy-phenethylamide)；(3,4-Dimethoxy-phenyl)-essigsaeure-(3,4,5-trimethoxy-phenaethylamid)；N-<β-(3.4.5-Trimethoxy-phenyl)-aethyl>-3.4-dimethoxy-phenylacetamid；N-(3,4,5-Trimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-acetamid；N-(3,4,5-Trimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)acetamid；2-(3,4-dimethoxyphenyl)-N-[2-(3,4,5-trimethoxyphenyl)ethyl]acetamide
• CAS: 10313-61-8
• 化学式: C₂₁H₂₇NO₆
• 分子量: 389.448
• InChiKey: BXUQYJBJJMBZDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 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：
  75.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-N-[2-(3,4,5-trimethoxyphenyl)-ethyl]-acetamide 在 磷酸酐 、 sodium tetrahydroborate 作用下， 以 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 2.75h， 生成 1-(3,4-dimethoxy-benzyl)-6,7,8-trimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels

  摘要：

  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.

  DOI：

  10.1021/jm0607395
• 作为产物：
  描述：

  仙人球毒碱 、 (3,4-二甲氧基苯基)乙酰氯 在 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以23%的产率得到2-(3,4-dimethoxyphenyl)-N-[2-(3,4,5-trimethoxyphenyl)-ethyl]-acetamide
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels

  摘要：

  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.

  DOI：

  10.1021/jm0607395

文献信息

• 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。
• Synthetische Versuche in der Isochinolinreihe I
  作者：A. Dobrowsky

  DOI：10.1007/bf01044198

  日期：——
• 1,2,3,4- TETRAHYDROISOQUINOLINE DERIVATIVES
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1274687A1

  公开（公告）日：2003-01-15
• US6703392B2
  申请人：——

  公开号：US6703392B2

  公开（公告）日：2004-03-09
• [EN] 1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES<br/>[FR] DERIVES DE 1,2,3,4-TETRAHYDROISOQUINOLINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2001068609A1

  公开（公告）日：2001-09-20

  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.