(6-isopropoxy-1-((4-isopropoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)(3-(trifluoromethyl)phenyl)methanone

• 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: (6-isopropoxy-1-((4-isopropoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)(3-(trifluoromethyl)phenyl)methanone
• 英文别名: [6-propan-2-yloxy-1-[(4-propan-2-yloxyphenoxy)methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-[3-(trifluoromethyl)phenyl]methanone
• 化学式: C₃₀H₃₂F₃NO₄
• 分子量: 527.584
• InChiKey: ZQJSQINLNNFBOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (6-isopropoxy-1-((4-isopropoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)(3-(trifluoromethyl)phenyl)methanone 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 0.58h， 以69%的产率得到(6-isopropoxy-1-((4-isopropoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)(3-(trifluoromethyl)phenyl)methanethione
  参考文献：
  名称：

  The Structure–Activity Relationship of a Tetrahydroisoquinoline Class of N-Methyl-d-Aspartate Receptor Modulators that Potentiates GluN2B-Containing N-Methyl-d-Aspartate Receptors

  摘要：

  We have identified a series of positive allosteric NMDA receptor (NMDAR) modulators derived from a known class of GluN2C/D-selective tetrahydroisoquinoline analogues that includes CIQ, The prototypical compound of this series contains a single isopropoxy moiety in place of the two methoxy substituents present in CIQ, Modifications of this isopropoxy-containing scaffold led to the identification of analogues with enhanced activity at the GluN2B subunit. We identified molecules that potentiate the response of GluN2B/GluN2C/GluN2D, GluN2B/GluN2C, and GluN2C/GluN2D-containing NMDARs to maximally effective concentrations of agonist. Multiple compounds potentiate the response of NMDARs with submicromolar EC50 values. Analysis of enantiomeric pairs revealed that the S-(-) enantiomer is active at the GluN2B, GluN2C, and/or GluN2D subunits, whereas the R-(+) enantiomer is only active at GluN2C/D subunits. These results provide a starting point for the development of selective positive allosteric modulators for GluN2B-containing receptors.

  DOI：

  10.1021/acs.jmedchem.7b00239
• 作为产物：
  描述：

  BOC-3-羟基苯乙胺 在 盐酸 、 sodium tetrahydroborate 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 69.0h， 生成 (6-isopropoxy-1-((4-isopropoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)(3-(trifluoromethyl)phenyl)methanone
  参考文献：
  名称：

  The Structure–Activity Relationship of a Tetrahydroisoquinoline Class of N-Methyl-d-Aspartate Receptor Modulators that Potentiates GluN2B-Containing N-Methyl-d-Aspartate Receptors

  摘要：

  We have identified a series of positive allosteric NMDA receptor (NMDAR) modulators derived from a known class of GluN2C/D-selective tetrahydroisoquinoline analogues that includes CIQ, The prototypical compound of this series contains a single isopropoxy moiety in place of the two methoxy substituents present in CIQ, Modifications of this isopropoxy-containing scaffold led to the identification of analogues with enhanced activity at the GluN2B subunit. We identified molecules that potentiate the response of GluN2B/GluN2C/GluN2D, GluN2B/GluN2C, and GluN2C/GluN2D-containing NMDARs to maximally effective concentrations of agonist. Multiple compounds potentiate the response of NMDARs with submicromolar EC50 values. Analysis of enantiomeric pairs revealed that the S-(-) enantiomer is active at the GluN2B, GluN2C, and/or GluN2D subunits, whereas the R-(+) enantiomer is only active at GluN2C/D subunits. These results provide a starting point for the development of selective positive allosteric modulators for GluN2B-containing receptors.

  DOI：

  10.1021/acs.jmedchem.7b00239

文献信息

• The Structure–Activity Relationship of a Tetrahydroisoquinoline Class of <i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Modulators that Potentiates GluN2B-Containing <i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptors
  作者：Katie L. Strong、Matthew P. Epplin、John Bacsa、Christopher J. Butch、Pieter B. Burger、David S. Menaldino、Stephen F. Traynelis、Dennis C. Liotta

  DOI：10.1021/acs.jmedchem.7b00239

  日期：2017.7.13

  We have identified a series of positive allosteric NMDA receptor (NMDAR) modulators derived from a known class of GluN2C/D-selective tetrahydroisoquinoline analogues that includes CIQ, The prototypical compound of this series contains a single isopropoxy moiety in place of the two methoxy substituents present in CIQ, Modifications of this isopropoxy-containing scaffold led to the identification of analogues with enhanced activity at the GluN2B subunit. We identified molecules that potentiate the response of GluN2B/GluN2C/GluN2D, GluN2B/GluN2C, and GluN2C/GluN2D-containing NMDARs to maximally effective concentrations of agonist. Multiple compounds potentiate the response of NMDARs with submicromolar EC50 values. Analysis of enantiomeric pairs revealed that the S-(-) enantiomer is active at the GluN2B, GluN2C, and/or GluN2D subunits, whereas the R-(+) enantiomer is only active at GluN2C/D subunits. These results provide a starting point for the development of selective positive allosteric modulators for GluN2B-containing receptors.