N-Nor-1-methylcorypalline hydrochloride | 98321-33-6

• 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: N-Nor-1-methylcorypalline hydrochloride
• 英文别名: (+/-)-isosalsolinol hydrochloride；7-hydroxy-6-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride；Isosalsoline hydrochloride；6-Methoxy-1-methyl-1,2,3,4-tetrahydro-7-isoquinolinol hydrochloride；6-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;hydrochloride
• CAS: 98321-33-6
• 化学式: C₁₁H₁₅NO₂*ClH
• 分子量: 229.707
• InChiKey: WSMUMEXDPYEJMK-UHFFFAOYSA-N

物化性质

• 熔点：
  175-177 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -2.41
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  46.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  花生四烯酸 、 N-Nor-1-methylcorypalline hydrochloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以40%的产率得到1-(7-hydroxy-6-methoxy-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)-icosa-5,8,11,14-tetraen-1-one
  参考文献：
  名称：

  Fatty acyl amides of endogenous tetrahydroisoquinolines are active at the recombinant human TRPV1 receptor

  摘要：

  The SAR of capsazepine revealed that tetrahydroisoquinoline (TIQ) moiety is a core pharmacophore of TRPV1 activity. This implied that conjugates of endogenous TIQs with fatty acids would be active at TRPV1 receptors. Six such compounds were synthesized and tested for calcium mobilization at recombinant TRPV1 receptors overexpressed in HEK293 cells. Three compounds showed partial TRPV1 agonism with EC50 values in the low micromolar range and maximal efficacies between 25% and 55% of capsaicin. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.06.032
• 作为产物：
  描述：

  4-(2-氨基乙基)-2-甲氧基苯酚 、 乙醛 在 盐酸 作用下， 以 水 为溶剂， 反应 24.0h， 以55%的产率得到N-Nor-1-methylcorypalline hydrochloride
  参考文献：
  名称：

  WO2008/69632

  摘要：

  公开号：

文献信息

• Syntheses of tetrahydroisoquinoline derivatives that inhibit NO production in activated BV-2 microglial cells
  作者：Jai Woong Seo、Ekaruth Srisook、Hyo Jin Son、Onyou Hwang、Young-Nam Cha、Dae Yoon Chi

  DOI：10.1016/j.ejmech.2007.09.009

  日期：2008.6

  Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 microM. In particular, N-ethylcarbonyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (11a) reduced

  设计，合成和评估了十七种四氢异喹啉衍生物对脂多糖刺激的BV-2小胶质细胞中NO生成的抑制作用。化合物5a，9c和11a在100 microM时可有效地将NO生成减弱> 60％，而5a和11a将BH4生成抑制> 48％。特别地，N-乙基羰基-7-羟基-6-甲氧基-1，2，3，4-四氢异喹啉（11a）使NO产生减少64％，而四氢生物蝶呤（ ）产生减少49％。在C1或N2位置引入更长的烷基组分导致抑制作用的减弱。11a可能通过阻断新合成的iNOS单体的 依赖性二聚作用来抑制NO的产生。
• 2-Acetyl-7-hydroxy-6-methoxy-1-methyl-1,2,3,4,-tetrahydroisoquinoline exhibits anti-inflammatory properties and protects the nigral dopaminergic neurons
  作者：Hyo Jin Son、Se Hee Han、Ji Ae Lee、Cheol Soon Lee、Jai Woong Seo、Dae Yoon Chi、Onyou Hwang

  DOI：10.1016/j.ejphar.2015.12.009

  日期：2016.1

  Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopamine(DA) ergic neurons. Neuroinflammation caused by microglial activation is believed to be involved in the pathogenesis of neurodegenerative diseases including PD. In the present study, we tested the effects of a novel compound 2-acetyl-7-hydroxy-6-methoxy-1-methyl-1,2,3,4,-tetarhydroisoquinoline (AMTIQ) on neuroinflammatory response and DAergic neurodegeneration. In lipopolysaccharide-activated BV-2 microglial cells, AMTIQ lowered nitric oxide and tetrahydrobiopterin levels and downregulated gene expression of inducible nitric oxide synthase and GTP cyclohydrolase I. AMTIQ also repressed gene expression of the proinflammatory cytokines IL-1 beta and TNF-alpha, and attenuated nuclear translocation of NE-kappa B. AMTIQ was stable against liver microsomal enzymes from human and mouse and did not interfere with activities of the cytochrome p450 enzymes 1A2, 2D6, 2C9, 2C19 and 3A4. Pharmacokinetic studies revealed the brain to plasma ratio of AMTIQ to be 45%, suggesting it can penetrate the blood brain barrier. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse PD model, AMTIQ led to decreased microglial activation, increased survival of DAergic neurons and their fibers, and improved behavioral scores on rotarod and vertical grid tests. Taken together, these results suggest that AMTIQ might serve as a candidate preventive-therapeutic agent for neurodegenerative diseases such as PD. (C) 2015 Elsevier B.V. All rights reserved.