1-isobutyl-6,7-dimethoxy-2-methyl-3,4-dihydro-isoquinolinium; iodide | 82083-90-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢异喹啉
• 英文名称: 1-isobutyl-6,7-dimethoxy-2-methyl-3,4-dihydro-isoquinolinium; iodide
• 英文别名: 1-Isobutyl-6,7-dimethoxy-2-methyl-3,4-dihydro-isochinolinium; Jodid；Agn-PC-00jgjw；6,7-dimethoxy-2-methyl-1-(2-methylpropyl)-3,4-dihydroisoquinolin-2-ium;iodide
• CAS: 82083-90-7
• 化学式: C₁₆H₂₄NO₂*I
• 分子量: 389.277
• InChiKey: DGIBEENHVSOJEV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.26
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  21.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-isobutyl-6,7-dimethoxy-2-methyl-3,4-dihydro-isoquinolinium; iodide 在 甲醇 、 硼酸三钠 作用下， 生成 O-Methyl-lophocerin
  参考文献：
  名称：

  Alkaloid Studies. V.¹ Synthesis of 1-Isopropyl and 1-Isobutyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

  摘要：

  DOI：

  10.1021/ja01607a081
• 作为产物：
  描述：

  异戊酰氯 在 磷酸酐 、 三乙胺 作用下， 以 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 3.5h， 生成 1-isobutyl-6,7-dimethoxy-2-methyl-3,4-dihydro-isoquinolinium; iodide
  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

• Away from Flatness: Unprecedented Nitrogen-Bridged Cyclopenta[<i>a</i>]indene Derivatives as Novel Anti-Alzheimer Multitarget Agents
  作者：Alexander A. Titov、Maxim S. Kobzev、Marco Catto、Modesto de Candia、Nicola Gambacorta、Nunzio Denora、Leonardo Pisani、Orazio Nicolotti、Tatiana N. Borisova、Alexey V. Varlamov、Leonid G. Voskressensky、Cosimo D. Altomare

  DOI：10.1021/acschemneuro.0c00706

  日期：2021.1.20

  molecules share low similarity with currently available drugs, containing preferentially planar and/or achiral moieties. This “Escape from Flatland” scenario, aimed at exploring pharmacological properties of atypical molecular scaffolds, finds interest in synthetic routes leading to tridimensional-shaped molecules. Herein we report on the synthesis of N-bridged cyclopenta[a]indene derivatives, achieved through

  受自然启发的，桥接的多环分子与目前可获得的药物（其优先包含平面和/或非手性部分）的相似性较低。此“逃离平地”方案旨在探索非典型分子支架的药理特性，引起了对合成三维形状分子的合成途径的兴趣。在这里，我们报道了N-桥联环戊的合成[ a] indene衍生物，通过具有高非对映选择性的丙二烯3-苯并ze庚因的微波辅助热重排获得。生物学评估揭示了对人乙酰胆碱酯酶或丁酰胆碱酯酶的选择性抑制，这取决于分子核心周围的取代，这通过对接模拟得以合理化。最有效的BChE抑制剂31对谷氨酸能兴奋性毒性具有神经保护作用，并表现出较低的固有细胞毒性和良好的脑渗透性。总体而言，化合物31及其紧密同源物34和35充当多靶点药物，可解决涉及神经退行性病变（尤其是阿尔茨海默氏病进展）的不同生物学事件。
• Facile Methods for the Synthesis of 8-Ylidene-1,2,3,8-tetrahydrobenzazecines
  作者：Alexander A. Titov、Maxim S. Kobzev、Tatiana N. Borisova、Anna V. Listratova、Tatiana V. Evenko、Alexey V. Varlamov、Leonid G. Voskressensky

  DOI：10.1002/ejoc.202000203

  日期：2020.5.29

  development of the synthesis for an unusual and rare class of compounds – 8‐ylidenebenzazecines. The target compounds were synthesized via two strategies and obtained in high and good yields. The first method is an efficient MW‐assisted rearrangement of azacyclic allenes, the second one represents one‐pot protocol based on enlargement of tetrahydropyridine moiety to 8‐ylidene decorated azecine ring.

  本研究的主要新颖之处在于开发了一种罕见且罕见的化合物– 8-亚苄基苯并ze庚因。通过两种策略合成目标化合物，并以高收率和良好收率获得。第一种方法是氮杂丙二烯的有效MW辅助的重排，第二个表示一锅煮基于四氢吡啶基部分的放大至-8-亚基装饰azecine环协议。
• Alkaloid Studies. V.¹ Synthesis of 1-Isopropyl and 1-Isobutyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  作者：Carl Djerassi、J. J. Beereboom、S. P. Marfey、S. K. Figdor

  DOI：10.1021/ja01607a081

  日期：1955.1
• 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.