1-(4-(benzyloxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline | 18694-14-9

• 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)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline
• 英文别名: 1-(3'-Methoxy-4'-benzyloxybenzyl)-6,7-dimethoxyisochinolin；6,7-Dimethoxy-1-[(3-methoxy-4-phenylmethoxyphenyl)methyl]isoquinoline
• CAS: 18694-14-9
• 化学式: C₂₆H₂₅NO₄
• 分子量: 415.489
• InChiKey: VXEYTCWBLCXRKK-UHFFFAOYSA-N

物化性质

• 沸点：
  570.9±45.0 °C(Predicted)
• 密度：
  1.177±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-(benzyloxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline 在 sodium tetrahydroborate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.5h， 生成 (S)-1-(4-(benzyloxy)-3-methoxybenzyl)-6,7-dimethoxy-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolinium iodide
  参考文献：
  名称：

  Chemical modifications of the N -methyl-laudanosine scaffold point to new directions for SK channels exploration

  摘要：

  An asparagine or a histidine are present in a similar position in the outer pore region of SK2 and SK3 channels, respectively. Therefore, this structural difference was targeted in order to develop selective blockers of SK channel subtypes. Following docking investigations, based on theoretical models of truncated SK2 and SK3 channels, the benzyl side chain of N-methyl-laudanosine (NML) was functionalized in order to target this specific amino-acid residues. Chiral butanamide and benzyloxy analogues were prepared, resolved and tested for their affinity for SK2 and SK3 channels. Isoquinolinium (NMIQ) derivatives have a higher affinity for both SK channel subtypes than the corresponding derivative with no functionalized side chain. This trend was observed also for the 1,2,3,4-tetrahydroisoquinoline (THIQ) analogues. A benzyloxy functionalized NML enantiomer has a higher affinity than NML stereoisomers. Otherwise, the conserved affinity of these analogues led to the opportunity to further investigate in terms of possible labeling for in vivo investigations of the role of SK channels. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.083
• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲醛 在 sodium tetrahydroborate 、 氯化亚砜 、 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.0h， 生成 1-(4-(benzyloxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline
  参考文献：
  名称：

  Chemical modifications of the N -methyl-laudanosine scaffold point to new directions for SK channels exploration

  摘要：

  An asparagine or a histidine are present in a similar position in the outer pore region of SK2 and SK3 channels, respectively. Therefore, this structural difference was targeted in order to develop selective blockers of SK channel subtypes. Following docking investigations, based on theoretical models of truncated SK2 and SK3 channels, the benzyl side chain of N-methyl-laudanosine (NML) was functionalized in order to target this specific amino-acid residues. Chiral butanamide and benzyloxy analogues were prepared, resolved and tested for their affinity for SK2 and SK3 channels. Isoquinolinium (NMIQ) derivatives have a higher affinity for both SK channel subtypes than the corresponding derivative with no functionalized side chain. This trend was observed also for the 1,2,3,4-tetrahydroisoquinoline (THIQ) analogues. A benzyloxy functionalized NML enantiomer has a higher affinity than NML stereoisomers. Otherwise, the conserved affinity of these analogues led to the opportunity to further investigate in terms of possible labeling for in vivo investigations of the role of SK channels. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.083

文献信息

• Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A
  作者：Zhanbin Zhang、Xiaoxia Lu、Jinbin Xu、Justin Rothfuss、Robert H. Mach、Zhude Tu

  DOI：10.1016/j.ejmech.2011.05.072

  日期：2011.9

  A series of analogues were synthesized by optimizing the structure of papaverine. The in vitro PDE10A binding affinity (IC50) values for these new analogues were measured; for compounds that have IC50 value less than 60 nM for PDE10A, the binding affinities (IC50 value) for PDE3A and PDE3B were tested. Of these analogues, compounds 6a, 6b, 6n, 8b, 8c and 11 displayed relatively higher PDE10A potency with IC50 value in the range of 28-60 nM. The most potent compound 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline (8c) has the IC50 value of 28 +/- 1.2 nM for PDE10A, 2200 +/- 437 nM for PDE3A and 2520 +/- 210 nM for PDE3B. Compared to papaverine, compound 8c displayed similar PDE10A potency but improved selectivity to PDE10A versus PDE3A and PDE3B. To identify high potent PDE10A inhibitor, further optimization of the structures of these analogues is necessary. (C) 2011 Elsevier Masson SAS. All rights reserved.