(S,S)-1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) | 950885-21-9

• 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: (S,S)-1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline)
• 英文别名: AG525E1；(1S)-1-[3-[(1S)-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]propyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinoline
• CAS: 950885-21-9
• 化学式: C₂₇H₃₈N₂O₄
• 分子量: 454.61
• InChiKey: MULXFGRQRGZGNO-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S,S)-1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 AG 525E1
  参考文献：
  名称：

  Bis-tetrahydroisoquinoline derivatives: AG525E1, a new step in the search for non-quaternary non-peptidic small conductance Ca2+-activated K+ channel blockers

  摘要：

  So far, small conductance Ca(2+)-activated K(+) channel (SK) blockers mostly consist of quaternary ammonium derivatives or peptides. Due to their physicochemical properties, these blockers are not suitable to study the physiological roles of SK channels in the central nervous system in vivo. Herein, we report the discovery of a chiral bis-tertiary amine with SK blocking properties from chemical modulation of laudanosine. AG525E1 has an affinity for SK channels (K(i) = 293 nM) approximately 100-fold higher than the tertiary compound laudanosine (K(i) similar to 30 mu M) and similar to the charged compound dequalinium (K(i) = 221 nM). AG525E1 equipotently blocks SK1, SK2 and SK3 currents in transfected cell lines. Because of its basic and lipophilic properties, it can reach central SK targets. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.069
• 作为产物：
  描述：

  1-[3-(6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl)propyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinoline;hydrochloride 以 甲醇 为溶剂， 生成 (S,S)-1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) 、 meso-1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) 、 (R,R)-1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline)
  参考文献：
  名称：

  Bis-tetrahydroisoquinoline derivatives: AG525E1, a new step in the search for non-quaternary non-peptidic small conductance Ca2+-activated K+ channel blockers

  摘要：

  So far, small conductance Ca(2+)-activated K(+) channel (SK) blockers mostly consist of quaternary ammonium derivatives or peptides. Due to their physicochemical properties, these blockers are not suitable to study the physiological roles of SK channels in the central nervous system in vivo. Herein, we report the discovery of a chiral bis-tertiary amine with SK blocking properties from chemical modulation of laudanosine. AG525E1 has an affinity for SK channels (K(i) = 293 nM) approximately 100-fold higher than the tertiary compound laudanosine (K(i) similar to 30 mu M) and similar to the charged compound dequalinium (K(i) = 221 nM). AG525E1 equipotently blocks SK1, SK2 and SK3 currents in transfected cell lines. Because of its basic and lipophilic properties, it can reach central SK targets. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.069

文献信息

• Bis-(1,2,3,4-tetrahydroisoquinolinium): A Chiral Scaffold for Developing High-Affinity Ligands for SK Channels
  作者：Jean-François Liégeois、Johan Wouters、Vincent Seutin、Sébastien Dilly

  DOI：10.1002/cmdc.201400028

  日期：2014.4

  and SK3 channels were similar and in both cases higher than that of the meso derivative. Among the bis-tetrahydroisoquinoline compounds, the S,S isomers exhibited high affinity, while the R,R and meso isomers had similarly lower affinities. Furthermore, the SK2/SK3 selectivity ratio was slightly increased for quaternized analogues. Bis-(1,2,3,4-tetrahydroisoquinolinium) represents a new scaffold for the

  源自AG525的N-甲基-双-（1,2,3,4-四氢异喹啉鎓）类似物（1,1'-（丙烷-1,3-二基）-双-（6,7-二甲氧基-2-甲基-合成了具有S，S构型的刚性双-（1,2,3,4-四氢异喹啉）类似物1,2,3,4-四氢异喹啉）立体异构体和粉防己碱，并测试了它们对小导电钙的亲和力放射性配体结合测定法检测活化的钾通道（SK / KCa2）亚型。观察到季铵化类似物的亲和力明显高于母体1,2,3,4-四氢异喹啉化合物。有趣的是，立体化学的影响在两组化合物中是不同的。对于季铵化类似物，S，S和R，R异构体对SK2和SK3通道的亲和力相似，并且在两种情况下均比内消旋衍生物更高。在双-四氢异喹啉化合物中，S，S异构体表现出高亲和力，而R，R和内消旋异构体的亲和力也较低。此外，季铵化类似物的SK2 / SK3选择性比率略有增加。Bis-（1,2,3,4-四氢异喹啉鎓）代表了一种新的支架，用于开发SK通道亚型的高亲和力配体。