6,7-dimethoxy-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-ium iodide | 19626-05-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 6,7-dimethoxy-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-ium iodide
• 英文别名: O,N-Dimethyl-corypalliniumjodid；6,7-dimethoxy-2,2-dimethyl-1,2,3,4-tetrahydro-isoquinolinium; iodide；6,7-Dimethoxy-2,2-dimethyl-1,2,3,4-tetrahydro-isochinolinium; Jodid；6,7-dimethoxy-2,2-dimethyl-3,4-dihydro-1H-isoquinolin-2-ium;iodide
• CAS: 19626-05-2
• 化学式: C₁₃H₂₀NO₂*I
• 分子量: 349.212
• InChiKey: OKNIQGQXESCYTQ-UHFFFAOYSA-M

物化性质

• 熔点：
  234-236 °C(Solv: methanol (67-56-1); ethyl ether (60-29-7))

计算性质

• 辛醇/水分配系数(LogP)：
  -1.16
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-ium iodide 生成 2-ethenyl-4,5-dimethoxy-N,N-dimethylbenzenemethanamine
  参考文献：
  名称：

  2-苄基异喹啉生物碱sendaverine的分解

  摘要：

  sendaverine (1) 转化为其甲碘化物 (2) 并催化氢解为 corypalline (3) 和 4-甲氧基甲苯 (4) 能够通过 5 的脱羧和分离对生物合成实验重要的其他原子来捕获 C-9 . 季铵化霍夫曼降解产物 10 的 Emde 降解产生氮原子，11 乙烯基的氧化裂解产生 C-3，酸的脱羧作用 15a C-4 和醌的 Kuhn-Roth 降解 16 C-1。14C-羧基标记的酸 15b 的施密特降解导致二氧化碳的比放射性为起始物质的一半，并得出结论：从 15 的 4 位分裂出来的甲氧基被氧化成二氧化碳。

  DOI：

  10.1002/ardp.19723050312
• 作为产物：
  描述：

  2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 、 碘甲烷 以 丙酮 为溶剂， 反应 12.0h， 以96%的产率得到6,7-dimethoxy-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-ium iodide
  参考文献：
  名称：

  双烟碱型乙酰胆碱受体α4β2拮抗剂/α7激动剂：四氢异喹啉盐和四氢异喹啉盐的合成，对接研究和药理评价

  摘要：

  我们描述了四氢异喹啉盐和四氢异喹啉盐的合成以及它们在各种烟碱乙酰胆碱受体上的药理特性。通常，这些化合物是α4β2nAChR拮抗剂，四氢异喹啉盐比母体四氢异喹啉衍生物更有效。最有效的α4β2拮抗剂，6C，显示出亚微摩尔的结合ķ我和功能IC 50值和该受体在α4β4和α3β4nAChRs的高选择性。（S）-6c对映异构体在α4β2处基本上是无活性的，（R）-6cα4β2拮抗剂是比参考β2-nAChR拮抗剂DHβE稍微有效的α4β2拮抗剂。α4β2活性仅存在于（R）-对映异构体中的观察与对接研究完全一致。几种四氢异喹啉鎓盐也对α7nAChR表现出激动剂活性。体内初步评估显示，（R）-5c和（R）-6c在小鼠强迫游泳试验中均具有抗抑郁样作用，支持α4β2nAChR拮抗剂对该适应症的治疗潜力。

  DOI：

  10.1021/acs.jmedchem.7b01895

文献信息

• A Convenient Synthesis of Tertiary Amines by Alkylation of Secondary Amines with Alkyl Halides in the Presence of Potassium Hydride and Triethylamine.
  作者：Kunihiko MOHRI、Kazumi SUZUKI、Masumi USUI、Kimiaki ISOBE、Yoshisuke TSUDA

  DOI：10.1248/cpb.43.159

  日期：——

  N-Alkylation of secondary amines with alkyl halides in the presence of potassium hydride and triethylamine gave corresponding tertiary amines in satisfactory yields.

  在氢化钾和三乙胺存在下，用烷基卤化物对仲胺进行 N-烷基化，得到相应的叔胺，收率令人满意。
• Synthesis and biological evaluation of N-methyl-laudanosine iodide analogues as potential SK channel blockers
  作者：A. Graulich、F. Mercier、J. Scuvée-Moreau、V. Seutin、J.-F. Liégeois

  DOI：10.1016/j.bmc.2004.11.025

  日期：2005.2

  Neuronal action potentials are followed by an afterhyperpolarisation (AHP), which is mediated by small conductance Ca2+-activated K+ channels (SK channels or KCa2 channels). This AHP plays an important role in regulating neuronal activity and agents modulating AHP amplitude could have a potential therapeutic interest. It was previously shown that N-methyl-bicuculline iodide blocks SK channels but its GABA(A) activity represents a serious drawback. In view of the structural analogy between bicuculline and laudanosine 14, several N-quaternary analogues of the latter were developed. It was shown that N-methyl-laudanosine 15 (NML) and N-ethyl-laudanosine 16 induce a reversible and relatively specific blockade of the apamin sensitive AHP in dopaminergic neurones with mean IC(50)s of 15, and 47 muM, respectively. Laudanosine 14, N-butyl-17 and N-benzyl-18 derivatives were less potent. In order to find pharmacophore elements, modifications were performed at different positions such as C-1, C-6 and C-7. Intracellular recordings on rat midbrain dopaminergic neurones were made in order to evaluate the putative blockade of SK channels by these molecules. Simplified structures such as tetrahydroisoquinoline derivatives with H or Me at C-I 1-6 presented no significant activity at 300 muM. The presence of a 1-(3,4-dimethoxybenzy]) moiety seems an important feature. Indeed, compound 8 showed a blockade of the AHP of only 33% at 300 muM while compound 13 blocked it by 67%, respectively, at the same concentration. Binding experiments were also performed. Binding affinities for SK channels are in good agreement with electrophysiological data. These results indicate that the presence of a charged nitrogen group is an essential point for the affinity on SK channels. Finally, because of the similar activity of both enantionters of NML 19 and 20, the interaction site may present a symmetrical configuration. (C) 2004 Elsevier Ltd. All rights reserved.
• Rearrangements of 1,6,7-trisubstituted 2-methyl-1,2,3,4-tetrahydroisoquinolinium 2-methylides
  作者：Yoshiro Sato、Naohiro Shirai、Yoshio Machida、Emiko Ito、Takayo Yasui、Yukihisa Kurono、Keiichiro Hatano

  DOI：10.1021/jo00051a008

  日期：1992.12

  Chemical behavior of 1,6,7-trisubstituted 2-methyl-1,2,3,4-tetrahydroisoquinolinium 2-methylides 4 was investigated in fluoride-ion induced desilylation reaction of 1,6,7-trisubstituted 2-methyl-2-(trimethylsilyl)-methyl-1,2,3,4-tetrahydroisoquinolinium iodides 3. The 1-nonsubstituted (4a,b) and 1-alkyl-substituted ylides (4c,d) gave mixtures of five products (7-11), but the 1-phenyl-substituted analogues (4e,f) yielded (E)- and (Z)-2,3-disubstituted 5-benzylidene-1,3-cyclohexadiene-6-spiro-3'-1'-methylpyrrolidines (E)-5 and (Z)-5 and 7,8-disubstituted 3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines 6. The mechanisms of the rearrangement are discussed.
• 459. The pyrolysis of amine oxides, and Hofmann degradation, in the benzylisoquinoline and phthalideisoquinoline series of alkaloids
  作者：K. W. Bentley、A. W. Murray

  DOI：10.1039/jr9630002491

  日期：——
• Tomita; Nakano, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1952, vol. 72, p. 197,198
  作者：Tomita、Nakano

  DOI：——

  日期：——