6,7-dimethoxy-1-(1-phenyl-ethyl)-3,4-dihydro-isoquinoline | 47206-48-4

• 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: 6,7-dimethoxy-1-(1-phenyl-ethyl)-3,4-dihydro-isoquinoline
• 英文别名: 3,4-Dihydroisoquinoline, 1-[1-phenethyl]-6,7-dimethoxy-；6,7-dimethoxy-1-(1-phenylethyl)-3,4-dihydroisoquinoline
• CAS: 47206-48-4
• 化学式: C₁₉H₂₁NO₂
• 分子量: 295.381
• InChiKey: AKTJHXSJSOWZSR-UHFFFAOYSA-N

物化性质

• 沸点：
  428.4±45.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-1-(1-phenyl-ethyl)-3,4-dihydro-isoquinoline 在 sodium tetrahydroborate 、 四丁基碘化铵 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-benzyl-2-[6,7-dimethoxy-1-(1-phenylethyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]acetamide
  参考文献：
  名称：

  Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor

  摘要：

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.

  DOI：

  10.1021/cn500330v
• 作为产物：
  描述：

  2-苯基丙酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 6,7-dimethoxy-1-(1-phenyl-ethyl)-3,4-dihydro-isoquinoline
  参考文献：
  名称：

  Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor

  摘要：

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.

  DOI：

  10.1021/cn500330v

文献信息

• Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor
  作者：David A. Perrey、Nadezhda A. German、Ann M. Decker、David Thorn、Jun-Xu Li、Brian P. Gilmour、Brian F. Thomas、Danni L. Harris、Scott P. Runyon、Yanan Zhang

  DOI：10.1021/cn500330v

  日期：2015.4.15

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.