1-naphthyl{1-[2-(4-morpholinyl)ethyl]-6-nitro-1H-indol-3-yl}methanone | 175697-87-7

• 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-naphthyl{1-[2-(4-morpholinyl)ethyl]-6-nitro-1H-indol-3-yl}methanone
• 英文别名: [1-(2-Morpholin-4-ylethyl)-6-nitroindol-3-yl]-naphthalen-1-ylmethanone
• CAS: 175697-87-7
• 化学式: C₂₅H₂₃N₃O₄
• 分子量: 429.475
• InChiKey: SJBFEMPWEFAOCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-naphthyl{1-[2-(4-morpholinyl)ethyl]-6-nitro-1H-indol-3-yl}methanone 在 盐酸 、 铁粉 、 碳酸氢钠 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 (1-naphthyl){6-isothiocyanato-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl}methanone
  参考文献：
  名称：

  (Aminoalkyl)indole Isothiocyanates as Potential Electrophilic Affinity Ligands for the Brain Cannabinoid Receptor

  摘要：

  A series of (aminoalkyl)indole compounds, naphthalene analogs of pravadoline (1), has been shown to exhibit cannabinoid agonist activities such as antinociception in animals, inhibition of adenylate cyclase in brain membranes, and binding to the cannabinoid receptor. These pravadoline analogs were selected for the preparation of potential electrophilic affinity ligands based on the synthesis of isothiocyanate derivatives. One isothiocyanatonaphthalene derivative (8) displaced [H-3]CP-55940 binding to a rat brain P2 membrane preparation with an IC50 of 690 nM, which was 10-fold less potent than the parent molecule (IC50 = 73 nM). Isothiocyanate substitution at various positions on the naphthalene moiety of the desmethyl analog 10 gave compounds that displaced [H-3]CP-55940 with IC50 values between 400 and 1000 nM, compared with 46 nM for the parent compound 10. However, 6-isothiocyanato substitution on the indole ring of the desmethyl analog provided isothiocyanate 12 that displaced [H-3]CP-55940 binding with an IC50 of 160 nM. After pretreatment of brain membranes with this high-affinity isothiocyanato ligand followed by washing out the ligand, the membranes were depleted of 90% of the cannabinoid receptor binding capacity. Loss of receptor binding capacity was half-maximal at 300 nM of the derivative under standard assay conditions. As a control, pretreatment with the parent compound at concentrations that were 20 times the K-d failed to alter subsequent binding activity. This study demonstrates that an isothiocyanato (aminoalkyl)-indole (12) can behave as an affinity ligand which binds irreversibly to the cannabinoid receptor in brain and which precludes subsequent binding of the cannabinoid ligand [H-3]CP-55940.

  DOI：

  10.1021/jm950932r
• 作为产物：
  描述：

  [1-[2-(4-吗啉基)乙基]-1H-吲哚-3-基]-1-萘基甲酮 在 硝酸 、 乙酸酐 作用下， 反应 0.5h， 以26%的产率得到1-naphthyl{1-[2-(4-morpholinyl)ethyl]-6-nitro-1H-indol-3-yl}methanone
  参考文献：
  名称：

  (Aminoalkyl)indole Isothiocyanates as Potential Electrophilic Affinity Ligands for the Brain Cannabinoid Receptor

  摘要：

  A series of (aminoalkyl)indole compounds, naphthalene analogs of pravadoline (1), has been shown to exhibit cannabinoid agonist activities such as antinociception in animals, inhibition of adenylate cyclase in brain membranes, and binding to the cannabinoid receptor. These pravadoline analogs were selected for the preparation of potential electrophilic affinity ligands based on the synthesis of isothiocyanate derivatives. One isothiocyanatonaphthalene derivative (8) displaced [H-3]CP-55940 binding to a rat brain P2 membrane preparation with an IC50 of 690 nM, which was 10-fold less potent than the parent molecule (IC50 = 73 nM). Isothiocyanate substitution at various positions on the naphthalene moiety of the desmethyl analog 10 gave compounds that displaced [H-3]CP-55940 with IC50 values between 400 and 1000 nM, compared with 46 nM for the parent compound 10. However, 6-isothiocyanato substitution on the indole ring of the desmethyl analog provided isothiocyanate 12 that displaced [H-3]CP-55940 binding with an IC50 of 160 nM. After pretreatment of brain membranes with this high-affinity isothiocyanato ligand followed by washing out the ligand, the membranes were depleted of 90% of the cannabinoid receptor binding capacity. Loss of receptor binding capacity was half-maximal at 300 nM of the derivative under standard assay conditions. As a control, pretreatment with the parent compound at concentrations that were 20 times the K-d failed to alter subsequent binding activity. This study demonstrates that an isothiocyanato (aminoalkyl)-indole (12) can behave as an affinity ligand which binds irreversibly to the cannabinoid receptor in brain and which precludes subsequent binding of the cannabinoid ligand [H-3]CP-55940.

  DOI：

  10.1021/jm950932r

文献信息

• (Aminoalkyl)indole Isothiocyanates as Potential Electrophilic Affinity Ligands for the Brain Cannabinoid Receptor
  作者：Koichiro Yamada、Kenner C. Rice、Judith L. Flippen-Anderson、Michael A. Eissenstat、Susan J. Ward、M. Ross Johnson、Allyn C. Howlett

  DOI：10.1021/jm950932r

  日期：1996.1.1

  A series of (aminoalkyl)indole compounds, naphthalene analogs of pravadoline (1), has been shown to exhibit cannabinoid agonist activities such as antinociception in animals, inhibition of adenylate cyclase in brain membranes, and binding to the cannabinoid receptor. These pravadoline analogs were selected for the preparation of potential electrophilic affinity ligands based on the synthesis of isothiocyanate derivatives. One isothiocyanatonaphthalene derivative (8) displaced [H-3]CP-55940 binding to a rat brain P2 membrane preparation with an IC50 of 690 nM, which was 10-fold less potent than the parent molecule (IC50 = 73 nM). Isothiocyanate substitution at various positions on the naphthalene moiety of the desmethyl analog 10 gave compounds that displaced [H-3]CP-55940 with IC50 values between 400 and 1000 nM, compared with 46 nM for the parent compound 10. However, 6-isothiocyanato substitution on the indole ring of the desmethyl analog provided isothiocyanate 12 that displaced [H-3]CP-55940 binding with an IC50 of 160 nM. After pretreatment of brain membranes with this high-affinity isothiocyanato ligand followed by washing out the ligand, the membranes were depleted of 90% of the cannabinoid receptor binding capacity. Loss of receptor binding capacity was half-maximal at 300 nM of the derivative under standard assay conditions. As a control, pretreatment with the parent compound at concentrations that were 20 times the K-d failed to alter subsequent binding activity. This study demonstrates that an isothiocyanato (aminoalkyl)-indole (12) can behave as an affinity ligand which binds irreversibly to the cannabinoid receptor in brain and which precludes subsequent binding of the cannabinoid ligand [H-3]CP-55940.