1-(4-(benzyloxy)benzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline | 47626-99-3

• 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-(4-(benzyloxy)benzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline
• 英文别名: 6,7-Dimethoxy-1-[(4-phenylmethoxyphenyl)methyl]-3,4-dihydroisoquinoline
• CAS: 47626-99-3
• 化学式: C₂₅H₂₅NO₃
• 分子量: 387.478
• InChiKey: KHXBPASDXNYENP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  40
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-(benzyloxy)benzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline 在 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 丁酮 为溶剂， 反应 62.0h， 生成 tert-butyl 1-(4-((7-bromoheptyl)oxy)benzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer’s disease

  摘要：

  A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced beta-amyloid (A beta) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more potent than its precursor benzylisoquinoline (10) and the positive control galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20 mu M), 9k (78.4% at 20 mu M) could further inhibit Ab aggregation. Moreover, 9k showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a promising lead compound for AD treatment. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.058
• 作为产物：
  描述：

  N-(2-(3,4-dimethoxyphenyl)ethyl)-2-(4-hydroxyphenyl)acetamide 在 potassium carbonate 、 三氯氧磷 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 16.0h， 生成 1-(4-(benzyloxy)benzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline
  参考文献：
  名称：

  Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer’s disease

  摘要：

  A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced beta-amyloid (A beta) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more potent than its precursor benzylisoquinoline (10) and the positive control galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20 mu M), 9k (78.4% at 20 mu M) could further inhibit Ab aggregation. Moreover, 9k showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a promising lead compound for AD treatment. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.058

文献信息

• Total Synthesis of New 8-(Arylmethyl)berbines
  作者：Maria Valpuesta、Manuela Ariza、Amelia Diaz、Gregorio Torres、Rafael Suau

  DOI：10.1002/ejoc.200901081

  日期：2010.2

  The total synthesis of the natural compound (8S * ,14S * )-8-(4'-hydroxybenzyl)-2,3-dimethoxyberbin-10-ol and its C-8 epimer has been conveniently developed by making use of the diastereoselective Stevens rearrangement of the corresponding N-(arylmethyl)berbinium salts as the key step.

  天然化合物(8S * ,14S * )-8-(4'-羟基苄基)-2,3-二甲氧基berbin-10-ol及其C-8差向异构体的全合成已利用非对映选择性Stevens方便地开发相应的 N-（芳甲基）铽盐的重排是关键步骤。
• Tomita; Yamaguchi, Pharmaceutical Bulletin, 1953, vol. 1, p. 10,12
  作者：Tomita、Yamaguchi

  DOI：——

  日期：——
• Gorbatschewa et al., Zhurnal Obshchei Khimii, 1957, vol. 27, p. 3367,3369;engl.Ausg.S.3404
  作者：Gorbatschewa et al.

  DOI：——

  日期：——
• Baxendale, Ian R.; Davidson, Thomas D.; Ley, Steven V., Heterocycles, 2003, vol. 60, # 12, p. 2707 - 2715
  作者：Baxendale, Ian R.、Davidson, Thomas D.、Ley, Steven V.、Perni, Remedios H.

  DOI：——

  日期：——
• Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer’s disease
  作者：Zi-Chen Xu、Xiao-Bing Wang、Wen-Ying Yu、Sai-Sai Xie、Su-Yi Li、Ling-Yi Kong

  DOI：10.1016/j.bmcl.2014.03.058

  日期：2014.5

  A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced beta-amyloid (A beta) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more potent than its precursor benzylisoquinoline (10) and the positive control galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20 mu M), 9k (78.4% at 20 mu M) could further inhibit Ab aggregation. Moreover, 9k showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a promising lead compound for AD treatment. (C) 2014 Elsevier Ltd. All rights reserved.