1-phenyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine | 874656-10-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-phenyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine
• CAS: 874656-10-7
• 化学式: C₂₁H₂₂N₂
• 分子量: 302.419
• InChiKey: KRAYBRNWGRIQNM-UHFFFAOYSA-N

物化性质

• 熔点：
  150-152 °C(Solv: methanol (67-56-1))
• 沸点：
  477.5±40.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-phenyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine 在 氨 、 sodium 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 24.5h， 生成 7-Methyl-3-phenyl-7,17-diazatricyclo[8.7.0.011,16]heptadeca-1(10),11,13,15-tetraene
  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：

  2H-吡喃-2-酮,四氢-3-苯基- 在 氢溴酸 、 potassium carbonate 、 potassium iodide 、 三氯氧磷 作用下， 以 甲苯 、 正丁醇 为溶剂， 反应 38.5h， 生成 1-phenyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine
  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

• Synthesis of indolo[2,3-a]quinolizine and hexahydro-1H-indolizino[8,7-b]indole derivatives by cascade condensation, cyclization, and Pictet–Spengler reaction: an application to the synthesis of (±)-harmicine
  作者：Chakrapani Sanaboina、Samaresh Jana、Sridhar Chidara、Balaram Patro、Gajendrasinh Balvantsinh Raolji、Laxminarayana Eppakayala

  DOI：10.1016/j.tetlet.2012.07.044

  日期：2012.9

  Synthesis of indole alkaloid related compounds using Schiff base formation, intramolecular cyclization (or N-alkylation), and Pictet–Spengler reaction as a cascade one pot condensation has been reported. The cascade chemistry has been applied to the synthesis of (±)-harmicine as a key step.

  已经报道了使用席夫碱形成，分子内环化（或N-烷基化）和Pictet-Spengler反应作为级联一锅缩合反应合成吲哚生物碱相关化合物的过程。级联化学已被用作合成（±）-甜菜碱的关键步骤。
• 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.