1-(2-bromo-benzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline | 78946-24-4

• 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-(2-bromo-benzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline
• 英文别名: 1-(2-bromobenzyl)-N-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline；1-(2'-bromobenzyl)-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline；(+/-)-1-(2-Brom-benzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-isochinolin；1-(2-Brom-benzyl)-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinolin；1-(2-Bromobenzyl)-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline；6,7-Dimethoxy-2-methyl-1-(2-brom-benzyl)-1,2,3,4-tetrahydro-isochinolin
• CAS: 78946-24-4
• 化学式: C₁₉H₂₂BrNO₂
• 分子量: 376.293
• InChiKey: ZSULZUACTHHFDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.24
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  21.7
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(2-bromo-benzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以55%的产率得到1-(2-bromobenzyl)-N-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  1-(2′-Bromobenzyl)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D₂ Dopamine Receptors

  摘要：

  Certain D-2-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D-2-like DR antagonists or partial agonists are proven effective as antipsychotics. Two isoquinoline derivatives, 1-(2'-bromobenzy1)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline (Br-BTHIQ, 1) and 1,2-demethyl-nuciferine (aporphine, 2), were herein synthesized, and their dopaminergic affinity in cloned human D2R, D3R, and D4R subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values (K-i) for hD(2), hD(3), and hD(4) DR within the nanomolar range. The trends in affinity were hD(4)R >> hD(3)R > hD(2)R for Br-BTHIQ (1) and hD(2)R > hD(4)R > hD(3)R for 1,2-demethyl-nuciferine (2). The functional assays of cyclic adenosine monophosphate signaling at human D2R showed a partial agonist effect for Br-BTHIQ (1) and full agonist behavior for aporphine (2), with half maximal effective concentration values of 2.95 and 10.2 mu M, respectively. Therefore, both isoquinolines 1 and 2 have emerged as lead molecules for the synthesis of new therapeutic drugs that ultimately may be useful to prevent schizophrenia and Parkinson's disease, respectively.

  DOI：

  10.1021/acs.jnatprod.9b00921
• 作为产物：
  描述：

  1-(2-Brom-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinolin 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 1-(2-bromo-benzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline
  参考文献：
  名称：

  1-(2′-Bromobenzyl)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D₂ Dopamine Receptors

  摘要：

  Certain D-2-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D-2-like DR antagonists or partial agonists are proven effective as antipsychotics. Two isoquinoline derivatives, 1-(2'-bromobenzy1)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline (Br-BTHIQ, 1) and 1,2-demethyl-nuciferine (aporphine, 2), were herein synthesized, and their dopaminergic affinity in cloned human D2R, D3R, and D4R subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values (K-i) for hD(2), hD(3), and hD(4) DR within the nanomolar range. The trends in affinity were hD(4)R >> hD(3)R > hD(2)R for Br-BTHIQ (1) and hD(2)R > hD(4)R > hD(3)R for 1,2-demethyl-nuciferine (2). The functional assays of cyclic adenosine monophosphate signaling at human D2R showed a partial agonist effect for Br-BTHIQ (1) and full agonist behavior for aporphine (2), with half maximal effective concentration values of 2.95 and 10.2 mu M, respectively. Therefore, both isoquinolines 1 and 2 have emerged as lead molecules for the synthesis of new therapeutic drugs that ultimately may be useful to prevent schizophrenia and Parkinson's disease, respectively.

  DOI：

  10.1021/acs.jnatprod.9b00921

文献信息

• Electroreductive synthesis of 1-(bromobenzyl)-isoquinoline derivatives and its application to cularine synthesis
  作者：Tatsuya Shono、Tetsuya Miyamoto、Masamichi Mizukami、Hiroshi Hamaguchi

  DOI：10.1016/s0040-4039(01)82914-2

  日期：1981.1

  immonium salts in the presence of bromobenzylbromide derivatives gave 1-(bromobenzyl)-isoquinoline derivatives in moderate yields. This reaction is useful in the synthesis of several natural alkaloids as exemplified in the synthesis of Cularine.

  在溴代苄基溴化物衍生物的存在下，将铵盐进行电化学还原，可得到中等收率的1-（溴代苄基）-异喹啉衍生物。该反应可用于合成几种天然生物碱，例如合成猪胆碱。
• 一种荷叶碱或其衍生物的合成方法以及荷叶碱衍生物及其应用
  申请人：华侨大学

  公开号：CN114751860A

  公开（公告）日：2022-07-15

  本发明涉及药物合成技术领域，提供了一种荷叶碱或其衍生物的合成方法以及荷叶碱衍生物及其应用。本发明将具有式IV所示结构的化合物与R‑X进行Schotten‑Baumann反应，然后经碳氢键活化得到荷叶碱或其衍生物。进一步的，具有式IV所示结构的化合物以2‑溴苯乙酸为起始物，经酰氯化反应、亲核取代反应、Bischler‑Napieralski反应和还原反应得到。本发明提供的合成方法步骤简单，原料易得，且碳氢键活化的方法高效、直接、灵活，非常适用于荷叶碱类分子的合成。本发明能合成荷叶碱，且能灵活的对荷叶碱进行结构改造，从而得到一系列荷叶碱衍生物，为开发荷叶碱类药物治疗肥胖症、高血脂症提供坚实的基础。
• Novel zinc-promoted alkylation of iminium salts. New synthesis of benzylisoquinoline, phthalidylisoquinoline, and protoberberine alkaloids and related compounds
  作者：Tatsuya Shono、Hiroshi Hamaguchi、Manji Sasaki、Shumei Fujita、Kimihiko Nagami

  DOI：10.1021/jo00158a010

  日期：1983.5