2-(2-hydroxyethyl)-N-[2-(3-methoxyphenyl)ethyl]benzamide | 62310-88-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-hydroxyethyl)-N-[2-(3-methoxyphenyl)ethyl]benzamide
• 英文别名: 2-(2-hydroxyethyl)-N-(3-methoxyphenethyl)benzamide；Benzamide, 2-(2-hydroxyethyl)-N-[2-(3-methoxyphenyl)ethyl]-
• CAS: 62310-88-7
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: GCTMVSOOIAQJEK-UHFFFAOYSA-N

物化性质

• 熔点：
  84 °C
• 沸点：
  518.4±45.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-hydroxyethyl)-N-[2-(3-methoxyphenyl)ethyl]benzamide 在 氨 、 sodium 、 三溴化硼 、 三氯氧磷 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 24.0h， 生成 LE 404
  参考文献：
  名称：

  Optimized synthesis of new LE404-derived azecine-prodrugs

  摘要：

  Dibenzoazecines represent a class of high-affinity dopamine and serotonin receptor antagonists. The former synthesis of the lead structure 7-methyl-5,6,7,8,9,14-hexahydrodibenzo[d,g]azecin-3-ol (LE404) has been 5 steps with a total yield of 13%. The present work enabled the synthesis of LE404 with a much higher yield. Based on this research, further azecin derivatives were synthesized with the aim to improve pharmacokinetic parameters. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2017.08.007
• 作为产物：
  描述：

  异色瞒 、 3-甲氧基苯乙胺 以 甲苯 为溶剂， 反应 18.0h， 以11.7%的产率得到2-(2-hydroxyethyl)-N-[2-(3-methoxyphenyl)ethyl]benzamide
  参考文献：
  名称：

  Dopamine/Serotonin Receptor Ligands. 10: SAR Studies on Azecine-type Dopamine Receptor Ligands by Functional Screening at Human Cloned D₁, D_2L, and D₅ Receptors with a Microplate Reader Based Calcium Assay Lead to a Novel Potent D₁/D₅ Selective Antagonist

  摘要：

  On the basis of the benz[d]indolo[2,3-g]azecine derivative I (LE300), structure-activity relations were investigated in order to identify the pharmacophore in this new class of ligands. Various structural modifications were performed and the inhibitory activities at human cloned D-1, D-2L, and D-5 receptors were measured by using a simple fluorescence microplate reader based calcium assay. Subsequently, the affinities of active compounds were estimated by radioligand binding experiments. Deleting one of the aromatic rings as well as replacing it by a phenyl moiety abolishes the inhibitory activities almost completely. Contraction of the 10-membered central ring decreases them significantly. The replacement of indole by thiophene or N-methylpyrrole reduces the inhibitory activity, whereas replacing the indole by benzene increases it. Finally, the hydroxylated dibenz[d,g]azecine derivative 11d (LE404) was found to be more active than the lead I in the functional calcium assay as well as in radioligand displacement experiments.

  DOI：

  10.1021/jm050846j

文献信息

• Dopamine/Serotonin Receptor Ligands. 10: SAR Studies on Azecine-type Dopamine Receptor Ligands by Functional Screening at Human Cloned D₁, D_2L, and D₅ Receptors with a Microplate Reader Based Calcium Assay Lead to a Novel Potent D₁/D₅ Selective Antagonist
  作者：Barbara Hoefgen、Michael Decker、Patrick Mohr、Astrid M. Schramm、Sherif A. F. Rostom、Hussein El-Subbagh、Peter M. Schweikert、Dirk R. Rudolf、Matthias U. Kassack、Jochen Lehmann

  DOI：10.1021/jm050846j

  日期：2006.1.1

  On the basis of the benz[d]indolo[2,3-g]azecine derivative I (LE300), structure-activity relations were investigated in order to identify the pharmacophore in this new class of ligands. Various structural modifications were performed and the inhibitory activities at human cloned D-1, D-2L, and D-5 receptors were measured by using a simple fluorescence microplate reader based calcium assay. Subsequently, the affinities of active compounds were estimated by radioligand binding experiments. Deleting one of the aromatic rings as well as replacing it by a phenyl moiety abolishes the inhibitory activities almost completely. Contraction of the 10-membered central ring decreases them significantly. The replacement of indole by thiophene or N-methylpyrrole reduces the inhibitory activity, whereas replacing the indole by benzene increases it. Finally, the hydroxylated dibenz[d,g]azecine derivative 11d (LE404) was found to be more active than the lead I in the functional calcium assay as well as in radioligand displacement experiments.
• Bivalent 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolines and -isoquinolinium salts: Novel heterocyclic templates for butyrylcholinesterase inhibitors
  作者：Maria Schulze、Oliver Siol、Michael Decker、Jochen Lehmann

  DOI：10.1016/j.bmcl.2010.03.011

  日期：2010.5

  Three different types of homobivalent compounds, 5,8,9,13b-tetrahydro-6H-isoqino[1,2-a]isoquinolines bearing tertiary N-atoms, their quaternary ammonium salts and their dibenzazecine analogues, connected by alkylene spacers of various lengths were synthesized. Compared to the therapeutically used inhibitor galanthamine, some of the bivalent compounds showed much higher inhibitory activities at both cholinesterases in the Ellman test. Surprisingly, not only the quaternary salts, but also the uncharged tertiary compounds exhibited IC50 values at butyrylcholinesterase in the nanomolar range. Selectivity toward BChE of up to 76-fold was observed. (C) 2010 Elsevier Ltd. All rights reserved.
• Optimized synthesis of new LE404-derived azecine-prodrugs
  作者：Stephanie Zergiebel、Hans-Dieter Arndt、Andreas Seeling

  DOI：10.1016/j.tetlet.2017.08.007

  日期：2017.9

  Dibenzoazecines represent a class of high-affinity dopamine and serotonin receptor antagonists. The former synthesis of the lead structure 7-methyl-5,6,7,8,9,14-hexahydrodibenzo[d,g]azecin-3-ol (LE404) has been 5 steps with a total yield of 13%. The present work enabled the synthesis of LE404 with a much higher yield. Based on this research, further azecin derivatives were synthesized with the aim to improve pharmacokinetic parameters. (C) 2017 Elsevier Ltd. All rights reserved.