2-(2-hydroxyethyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]benzamide | 62310-86-5

• 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-(3,4-dimethoxyphenyl)ethyl]benzamide
• 英文别名: Benzamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(2-hydroxyethyl)-；N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(2-hydroxyethyl)benzamide
• CAS: 62310-86-5
• 化学式: C₁₉H₂₃NO₄
• 分子量: 329.396
• InChiKey: ZWIRCFQWFCLFHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-hydroxyethyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]benzamide 在 sodium tetrahydroborate 、 三氯氧磷 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 19.5h， 生成 2,3-dimethoxy-7-(2-phenylethyl)-5,6,8,9-tetrahydro-13bH-dibenzo[a,h]quinolizinium bromide
  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
• 作为产物：
  描述：

  异色瞒 、 3,4-二甲氧基苯乙胺 以 甲苯 为溶剂， 反应 18.0h， 以68%的产率得到2-(2-hydroxyethyl)-N-[2-(3,4-dimethoxyphenyl)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

• Cyclisierungen von N-(2-Phenylethyl)-2-(2-hydroxyethyl)-benzamiden
  作者：Hans-Jürgen Mika、Werner Meise

  DOI：10.1002/ardp.19853180212

  日期：——

  Die Cyclisierung der Hydroxyamide 3 unter Bischler‐Napieralski‐Bedingungen erfolgt in Abhängigkeit von der Substitution der Aromaten auf drei verschiedene Reaktionsweisen: Während die im Phenylethylamin‐Teil (Ring A) nicht aktivierten Amide 3c und 3d nur den Ring C schließen, entsteht bei dem in A aktivierten, jedoch in Ring D (Lacton‐Teil) für einen nucleophilen Angriff desaktivierten Amid 3b anschließend

  羟基酰胺 3 在 Bischler-Napieralski 条件下的环化以三种不同的方式发生，具体取决于芳族化合物的取代：而在苯乙胺部分（环 A）中未活化的酰胺 3c 和 3d 仅闭合环 C，在 A 中激活，但在环 D（内酯部分）中酰胺 3b 因亲核攻击而失活，然后是环 B；相反，在仅在 A 中激活的 3a 中，首先发生 Bischler-Napieralski 反应（环 B），然后发生分子内 N-烷基化（环 C）。
• Imidlactone, 2. Mitt. N-(2-Phenylethyl)-isochroman-1-imine
  作者：Werner Meise、Hans-Jürgen Mika

  DOI：10.1002/ardp.19893220502

  日期：——

  Ausbeuten die N‐(2‐Phenylethyl)‐isochroman‐1‐imine 2 gewonnen. Im Eintopfverfahren lassen sich die aus den δ‐Hydroxyamiden 1 gebildeten rohen 6‐Ring‐Imidlacton‐Hydrochloride 2·HCl zu den δ‐Hydroxyaminen 3 reduzieren bzw. – anders als in der 5‐Ring‐Reihe – zu den δ‐Chloramiden 5 isomerisieren; unter härteren Bedingungen entstehen die Lactame 4. Die Reaktionswege werden im einzelnen beschrieben.

  N-(2-苯乙基)-异色满-1-亚胺2以良好的产率从N-(2-苯乙基)-2-(2-羟乙基)-苯甲酰胺1中得到。在一锅法中，由 δ-羟基酰胺 1 形成的粗 6-环酰亚胺内酯盐酸盐 2HCl 可以还原为 δ-羟基胺 3 或 - 与 5- 环系列不同 - 异构化为 δ - 氯酰胺 5 ；内酰胺4在更苛刻的条件下形成，详细描述了反应路径。
• MIKA, H. -J.;MEISE, W., ARCH. PHARM., 1985, 318, N 2, 168-174
  作者：MIKA, H. -J.、MEISE, W.

  DOI：——

  日期：——
• 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.