(3-chlorophenyl)(1-((4-ethoxyphenoxy)methyl)-6-isopropoxy-3,4-dihydroisoquinolin-2(1H)-yl)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: (3-chlorophenyl)(1-((4-ethoxyphenoxy)methyl)-6-isopropoxy-3,4-dihydroisoquinolin-2(1H)-yl)methanone
• 英文别名: (3-chlorophenyl)-[1-[(4-ethoxyphenoxy)methyl]-6-propan-2-yloxy-3,4-dihydro-1H-isoquinolin-2-yl]methanone
• 化学式: C₂₈H₃₀ClNO₄
• 分子量: 480.003
• InChiKey: HQPOHZILTINXAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3-chlorophenyl)(1-((4-ethoxyphenoxy)methyl)-6-isopropoxy-3,4-dihydroisoquinolin-2(1H)-yl)methanone 在 劳森试剂 作用下， 以 甲苯 为溶剂， 以33%的产率得到(3-chlorophenyl)(1-((4-ethoxyphenoxy)methyl)-6-isopropoxy-3,4-dihydroisoquinolin-2(1H)-yl)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：

  3-溴苯乙胺 在 sodium tetrahydroborate 、 copper(l) iodide 、 1,10-菲罗啉 、 氢气 、 palladium(II) hydroxide 、 caesium carbonate 、 三乙胺 、 sodium iodide 、 N,N'-二甲基乙二胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,3-二噁烷 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 91.0h， 生成 (3-chlorophenyl)(1-((4-ethoxyphenoxy)methyl)-6-isopropoxy-3,4-dihydroisoquinolin-2(1H)-yl)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

• [EN] N-METHYL-D-ASPARTATE RECEPTOR (NMDAR) POTENTIATORS, PHARMACEUTICAL COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] POTENTIALISATEURS DU RÉCEPTEUR DE N-MÉTHYL-D-ASPARTATE (NMDAR), COMPOSITIONS PHARMACEUTIQUES, ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2016149248A1

  公开（公告）日：2016-09-22

  This disclosure relates to tetrahydroisoquinolines, salts, and derivatives useful for managing mental or cognitive diseases or conditions of the brain or central nervous system. In certain embodiments, the disclosure relates to compounds and compositions having formula I: prodrugs, esters, or salts thereof, wherein the substituents are described herein.

  这项披露涉及对治疗大脑或中枢神经系统的精神或认知疾病或病况有用的四氢异喹啉、盐和衍生物。在某些实施例中，该披露涉及具有化学式I的化合物和组合物：它们的前药、酯或盐，其中取代基在此处描述。
• N-methyl-D-aspartate Receptor (NMDAR) Potentiators, Pharmaceutical Compositions, And Uses Related Thereto
  申请人：EMORY UNIVERSITY

  公开号：US20180244623A1

  公开（公告）日：2018-08-30

  This disclosure relates to tetrahydroisoquinolines, salts, and derivatives useful for managing mental or cognitive diseases or conditions of the brain or central nervous system. In certain embodiments, the disclosure relates to compounds and compositions having formula I: prodrugs, esters, or salts thereof, wherein the substituents are described herein.