2-(4-benzyloxy-3,5-dimethoxyphenyl)ethylamine hydrochloride | 2176-15-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-benzyloxy-3,5-dimethoxyphenyl)ethylamine hydrochloride
• 英文别名: 2-(4-(benzyloxy)-3,5-dimethoxyphenyl)ethan-1-amine hydrochloride；4-benzyloxy-3,5-dimethoxy-phenethylamine; hydrochloride；4-Benzyloxy-3,5-dimethoxy-phenaethylamin; Hydrochlorid；2-[4-(Benzyloxy)-3,5-dimethoxyphenyl]ethan-1-amine hydrochloride；2-(3,5-dimethoxy-4-phenylmethoxyphenyl)ethanamine;hydrochloride
• CAS: 2176-15-0
• 化学式: C₁₇H₂₁NO₃*ClH
• 分子量: 323.82
• InChiKey: PIOBTAQJPUGKNW-UHFFFAOYSA-N

物化性质

• 熔点：
  156-158 °C

计算性质

• 辛醇/水分配系数(LogP)：
  3.21
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  53.7
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2922299090

反应信息

• 作为反应物：
  描述：

  2-(4-benzyloxy-3,5-dimethoxyphenyl)ethylamine hydrochloride 在 甲酸 、 (S,S)-N-(对甲苯磺酰)-1,2-二苯乙烷二胺(对异丙基苯)氯化钌(II) 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 21.0h， 生成 (S)-2-(benzyloxy)-1,3,9,11-tetramethoxytetrahydroprotoberberine
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D1 receptor

  摘要：

  A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D-1 and D-2) and serotonin (5-HT1A and 5-HT2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D-1 receptor, as well as high selectivity for the D-1 receptor over the D-2, 5-HT1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D-1 receptor binding affinity (K-i = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D-1 K-i = 6.23 nM, D-2 K-i = 56.17 nM), compound 19c showed better binding affinity for the D-1 receptor (2.5-fold higher) and excellent D-2/D-1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D-1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D-1 receptor. These results are in accord with molecular docking studies. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.057
• 作为产物：
  描述：

  4-苄氧基-3,5-二甲氧基苯甲醛 在 lithium aluminium tetrahydride 、 ammonium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 生成 2-(4-benzyloxy-3,5-dimethoxyphenyl)ethylamine hydrochloride
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D1 receptor

  摘要：

  A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D-1 and D-2) and serotonin (5-HT1A and 5-HT2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D-1 receptor, as well as high selectivity for the D-1 receptor over the D-2, 5-HT1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D-1 receptor binding affinity (K-i = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D-1 K-i = 6.23 nM, D-2 K-i = 56.17 nM), compound 19c showed better binding affinity for the D-1 receptor (2.5-fold higher) and excellent D-2/D-1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D-1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D-1 receptor. These results are in accord with molecular docking studies. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.057

文献信息

• Biosynthesis. Part 24. Speculative incorporation experiments with 1-benzylisoquinolines and a logical approach via C₆–C₂and C₆–C₃precursors to the biosynthesis of hasubanonine and protostephanine
  作者：Alan R. Battersby、Raymond C. F. Jones、Rymantas Kazlauskas、Craig W. Thornber、Somsak Ruchirawat、James Staunton

  DOI：10.1039/p19810002016

  日期：——

  Many possible 1-benzyltetrahydroisoquinolines have been examined as possible advanced precursors of the alkaloids hasubanonine (1) and protostephanine (2) in Stephania japonica plants, but none was incorporated significantly. Administration of various precursor molecules having only one aromatic ring, such as tyrosine, has demonstrated that both alkaloids are derived from two different C6–C2 biogenetic

  已经研究了许多可能的1-苄基四氢异喹啉类化合物，它们是Stephania japonica植物中生物碱hasubanonine（1）和protostephanine（2）的可能的高级前体，但没有明显掺入。施用仅具有一个芳香环的各种前体分子（例如酪氨酸）已证明这两种生物碱均来自两个不同的C 6 -C 2生物遗传单位。随后无法进一步引入1-苄基四氢异喹啉和双苯乙胺，这表明（a）改性的1-苄基异喹啉或（b）三加氧的C 6 –C 2中间体建筑模块。设计用于检查第一种可能性的前体，例如1-苄基-3,4-二氢异喹啉或1-苄基-1-羧基四氢异喹啉，未合并到（1）和（2）中，而两个3'，4'，5'-掺入三氧化的2-苯基乙胺。这些发现允许进一步描述对生物碱（1）和（2）的后续前体的需求。
• Catechol O-methyltransferase. 6. Affinity labeling with N-haloacetyl-3,5-dimethoxy-4-hydroxyphenylalkylamines
  作者：Ronald T. Borchardt、Dhiren R. Thakker

  DOI：10.1021/jm00236a008

  日期：1975.2

  The number of methylene carbons separating the aromatic ring and the iodoacetamide moiety in these inhibitors did not greatly influence the binding to COMT nor did it affect how rapidly the enzyme was inactivated. From these observations it was concluded that the amino acid moiety being modified by this class of affinity labeling reagents must be relatively close to or part of the site which binds

  已经合成了几种N-酰基-3,5-二甲氧基-4-羟基苯基烷基胺，并评估了它们使邻苯二酚9-甲基转移酶（COMT）失活的能力。发现N-碘乙酰基-3,5-二甲氧基-4-羟基苯乙胺可快速且不可逆地使该酶失活。相应的N-溴乙酰基衍生物也使COMT失活，但速率比N-碘乙酰基衍生物慢。N-乙酰基和N-富芳基衍生物完全没有活性。这些试剂对COMT的灭活似乎是通过可解离的复合物中的单分子反应而不是非特异性双分子反应进行的。使用变化链长的N-碘乙酰基苯基烷基胺测定相对于结合这些抑制剂的芳族部分的位点被修饰的氨基酸残基的接近度。在这些抑制剂中，分隔芳香环和碘乙酰胺部分的亚甲基碳的数量不会极大地影响与COMT的结合，也不会影响酶的失活速度。从这些观察结果可以得出结论，被这类亲和标记试剂修饰的氨基酸部分必须相对接近或部分结合这些抑制剂的芳族区域。
• Synthesen in der Isochinolinreihe: Zur �therspaltung 6,7,8-trimethoxy-substituierter Isochinolinverbindungen mit w�sseriger Salzs�ure
  作者：A. Brossi、M. Baumann、R. Borer

  DOI：10.1007/bf00912290

  日期：——
• Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D1 receptor
  作者：Wangke Qian、Weijian Lu、Haifeng Sun、Zeng Li、Liyuan Zhu、Rui Zhao、Lei Zhang、Shengbin Zhou、Yu Zhou、Hualiang Jiang、Xuechu Zhen、Hong Liu

  DOI：10.1016/j.bmc.2012.05.057

  日期：2012.8

  A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D-1 and D-2) and serotonin (5-HT1A and 5-HT2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D-1 receptor, as well as high selectivity for the D-1 receptor over the D-2, 5-HT1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D-1 receptor binding affinity (K-i = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D-1 K-i = 6.23 nM, D-2 K-i = 56.17 nM), compound 19c showed better binding affinity for the D-1 receptor (2.5-fold higher) and excellent D-2/D-1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D-1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D-1 receptor. These results are in accord with molecular docking studies. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.