4-({2-[(benzylcarbamoyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl)-2-methoxyphenyl butanoate | 1584647-00-6

• 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: 4-({2-[(benzylcarbamoyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl)-2-methoxyphenyl butanoate
• 英文别名: [4-[[2-[2-(benzylamino)-2-oxoethyl]-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-1-yl]methyl]-2-methoxyphenyl] butanoate
• CAS: 1584647-00-6
• 化学式: C₃₂H₃₈N₂O₆
• 分子量: 546.664
• InChiKey: UHZWLCUBNOYQRF-UHFFFAOYSA-N

物化性质

• 沸点：
  696.8±55.0 °C(predicted)
• 密度：
  1.165±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  高香草酸 在 甲醇 、 sodium tetrahydroborate 、 四丁基碘化铵 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 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 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 4-({2-[(benzylcarbamoyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl}methyl)-2-methoxyphenyl butanoate
  参考文献：
  名称：

  大麻素 CB1 和食欲素 OX1 受体异二聚体二价配体探针的开发

  摘要：

  大麻素 CB1 和食欲素 OX1 受体已被建议形成异二聚体和寡聚体。为了研究这些复合物，设计、合成了一系列结合 SR141716 和 ACT-078573 药效团的二价 CB1 和 OX1 配体，并测试了它们单独和在共表达这两种受体的细胞系中针对 CB1 和 OX1 的活性。与单独表达相比，化合物20在共表达时对两种受体的效力均显着增强，表明可能与 CB1-OX1 二聚体相互作用。靶向 CB1-OX1 受体二聚体的二价配体可作为进一步探索此类异源二聚体在体外和体内作用的工具。

  DOI：

  10.1021/ml4004759

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.
• Toward the Development of Bivalent Ligand Probes of Cannabinoid CB1 and Orexin OX1 Receptor Heterodimers
  作者：David A. Perrey、Brian P. Gilmour、Brian F. Thomas、Yanan Zhang

  DOI：10.1021/ml4004759

  日期：2014.6.12

  Cannabinoid CB1 and orexin OX1 receptors have been suggested to form heterodimers and oligomers. Aimed at studying these complexes, a series of bivalent CB1 and OX1 ligands combining SR141716 and ACT-078573 pharmacophores were designed, synthesized, and tested for activity against CB1 and OX1 individually and in cell lines that coexpress both receptors. Compound 20 showed a robust enhancement in potency

  大麻素 CB1 和食欲素 OX1 受体已被建议形成异二聚体和寡聚体。为了研究这些复合物，设计、合成了一系列结合 SR141716 和 ACT-078573 药效团的二价 CB1 和 OX1 配体，并测试了它们单独和在共表达这两种受体的细胞系中针对 CB1 和 OX1 的活性。与单独表达相比，化合物20在共表达时对两种受体的效力均显着增强，表明可能与 CB1-OX1 二聚体相互作用。靶向 CB1-OX1 受体二聚体的二价配体可作为进一步探索此类异源二聚体在体外和体内作用的工具。