1-(3',4'-dimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride | 3972-77-8

• 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)-1,2,3,4-tetrahydroisoquinoline hydrochloride
• 英文别名: 1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline;hydrochloride
• CAS: 3972-77-8
• 化学式: C₁₈H₂₁NO₂*ClH
• 分子量: 319.831
• InChiKey: NXJAIWHNVBCOQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  30.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3',4'-dimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride 在 氢溴酸 作用下， 生成 1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrobromide
  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
• 作为产物：
  描述：

  1-(3',4'-dimethoxybenzyl)isoquinoline hydrochloride 生成 1-(3',4'-dimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride
  参考文献：
  名称：

  GINOS J. Z., J. ORG. CHEM. , 1975, 40, NO 9, 1191-1195

  摘要：

  DOI：

文献信息

• NEDELEC L.; DUMONT C.; OBERLANDER C.; FRECHET D.; LAURENT J.; BOISSIER J.+, FUR. J. MED. CHEM.-CHIM. THER., 1978, 13, NO 6, 553-563
  作者：NEDELEC L.、 DUMONT C.、 OBERLANDER C.、 FRECHET D.、 LAURENT J.、 BOISSIER J.+

  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.