1-(3',4'-dimethoxybenzyl)-3,4-dihydroisoquinoline | 88422-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(3',4'-dimethoxybenzyl)-3,4-dihydroisoquinoline
• 英文别名: 1-veratryl-3,4-dihydro-isoquinoline；1-Veratryl-3,4-dihydro-isochinolin；1-(3,4-Dimethoxybenzyl)-3,4-dihydroisoquinoline；3,4-Dihydro-papaverin；1-[(3,4-Dimethoxyphenyl)methyl]-3,4-dihydroisoquinoline
• CAS: 88422-82-6
• 化学式: C₁₈H₁₉NO₂
• 分子量: 281.354
• InChiKey: VDGRBMHBPRSLRI-UHFFFAOYSA-N

物化性质

• 沸点：
  194-197 °C(Press: 0.08 Torr)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3',4'-dimethoxybenzyl)-3,4-dihydroisoquinoline 在 氧气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 copper(ll) bromide 作用下， 以 二甲基亚砜 为溶剂， 反应 9.0h， 以83%的产率得到(3,4-dimethoxyphenyl)(isoquinolin-1-yl)methanone
  参考文献：
  名称：

  通过 1-Bn-DHIQ 的温和 Cu 催化串联氧化/芳构化实现氧代朴啡生物碱的新型全合成†

  摘要：

  开发了新的全合成氧代阿泊啡生物碱，如马钱烯宁、二百曲宁、卡沙美啶、赖西胺、氧代月光碱和O-甲基莫沙托林。这些全合成的关键步骤是通过串联氧化/芳构化，铜催化将 1-苄基-3,4-二氢-异喹啉 (1-Bn-DHIQs) 转化为 1-苯甲酰基-异喹啉 (1-Bz-IQs)。这种新颖的铜催化转化已被详细研究，并成功用于构建 1-Bz-IQ 核心。

  DOI：

  10.1039/c8ra05338c
• 作为产物：
  描述：

  (3,4-二甲氧基苯基)乙酰氯 在 phosphorus pentoxide 作用下， 以 甲苯 为溶剂， 生成 1-(3',4'-dimethoxybenzyl)-3,4-dihydroisoquinoline
  参考文献：
  名称：

  Inhibition of dopamine receptors by endogenous amines: binding to striatal receptors and pharmacological effects on locomotor activity

  摘要：

  Endogenous amine 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) derivatives are synthesized, and their activity for dopaminergic systems are evaluated in vitro and in vivo by receptor binding assay and pharmacological tests. It is proposed that 1BnTIQ derivatives can act as endogenous dopaminergic antagonists. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00326-7

文献信息

• Substituted isoquinolines and methods of using same
  申请人：Euroceltique, S.A.

  公开号：US04956371A1

  公开（公告）日：1990-09-11

  Novel substituted isoquinoline compounds are disclosed together with novel 2-phenylethylamides useful as precursors or intermediates for the production of the isoquinolines. The substituted isoquinolines exhibit activity in antagonizing the effects of platelet activating factor (PAF).

  本专利揭示了替代异喹啉化合物，以及作为异喹啉的前体或中间体有用的新型2-苯乙基酰胺。这些替代异喹啉在拮抗血小板活化因子（PAF）的作用方面表现出活性。
• Synthesis of some isoquinoline derivatives
  作者：Ryuji Tachikawa

  DOI：10.1016/0040-4020(59)80058-2

  日期：1959.1

  The Bischler-Napieralski reaction has been applied to the synthesis of several isoquinoline derivatives related to papaverine but devoid of one or two methoxyl groups in positions 6 and 7.

  Bischler-Napieralski反应已用于合成与罂粟碱有关的几种异喹啉衍生物，但在6和7位上没有一个或两个甲氧基。
• Kondo, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1925, # 519, p. 3
  作者：Kondo

  DOI：——

  日期：——
• Dopamine Transporter and Catechol-<i>O</i>-methyltransferase Activities Are Required for the Toxicity of 1-(3‘,4‘-Dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline
  作者：Hiroshi Kawai、Yaichiro Kotake、Shigeru Ohta

  DOI：10.1021/tx000047y

  日期：2000.12.1

  1-(3',4'-Dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline [3',4'DHBnTIQ (1)] is an endogenous parkinsonism-inducing substance. It is taken up into dopaminergic neurons via the dopamine transporter, inhibits mitochondrial respiration, and induces parkinsonism in mice. We synthesized four derivatives [aromatized, N-methylated, N-methyl-aromatized, and O-methylated (2-5, respectively)] and studied the cellular uptake and cytotoxicity of 1-5, as well as the metabolism of 1. All except the O-methyl derivative (5) were specifically taken up by the dopamine transporter, but 1 was taken up most efficiently. Relative to 1, oxidation reduced upsilon (max), N-methylation markedly increased K-m, and O-methylation eliminated the uptake activity. The cytotoxicity of 1-5 was examined in a mesencephalic cell. primary culture. Compound I reduced cell viability by nearly 80% at 100 muM, but the other compounds had little or no effect on cell viability. In vivo and in vitro studies revealed that I was O-methylated by soluble catechol-O-methyltransferase (COMT). Aromatization and N-methylation of 1 were not observed. We found that dopamine transporter inhibitors and a COMT inhibitor each blocked the cytotoxicity of I, indicating that uptake and O-methylation are both necessary for neurotoxicity. Thus, we consider that 1 is taken up into dopaminergic neurons via the dopamine transporter and then converted by COMT to 5, which has cytotoxic and parkinsonism-inducing activities.