8-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-4-carbaldehyde | 178557-17-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 8-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-4-carbaldehyde
• CAS: 178557-17-0
• 化学式: C₁₂H₁₂O₃
• 分子量: 204.225
• InChiKey: NNFCBMLIHJXMFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-4-carbaldehyde 在 lithium aluminium tetrahydride 、 ammonium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 生成 1-(8-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-4-yl)propan-2-amine
  参考文献：
  名称：

  Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups

  摘要：

  Tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in prototypical hallucinogenic phenylalkylamines 1 and 2. Thus, a series of 8-substituted 1-(2,3,6,7-tetrahydrobenzo[ 1,2-b:4,5-b']difuran-4-yl)-2-aminoalkanes (7a-e) were prepared and evaluated for activity in the two-lever drug discrimination paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg) and for the ability to displace [H-3]ketanserin from rat cortical homogenate 5-HT2A receptors and [(3)H3-8-OH-DPAT from rat hippocampal homogenate 5-HT1A receptors. In addition, 1-(8-(bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5- (7b), which was found to be extremely potent in the rat in vivo assays, was evaluated for its ability to compete with [I-125][DOI and [H-3]ketanserin binding to cells expressing cloned human 5-HT2A, 5-H-2B, and 5-HT2C receptors. All of the dihydrofuranyl compounds having a hydrophobic substituent para to the alkylamine side chain had activities in both the in vitro and in vivo assays that equaled or surpassed the activity of the analogous conformationally flexible parent compounds. For example, 7b substituted for LSD in the drug discrimination assay with an ED(50) Of 61 nmol/kg and had K-i values in the nanomolar to subnanomolar range for the displacement of radioligand from rat and human 5-HT2 receptors, making it one of the most potent hallucinogen-like phenylalkylamine derivatives reported to date. The results suggest that the dihydrofuran rings in these pew analogues effectively model the active binding conformations of the methoxy groups of the parent compounds 1 and 2. In addition, the results provide information about the topography and relative orientation of residues involved in agonist binding in the serotonin 5-HT2 receptors.

  DOI：

  10.1021/jm960199j
• 作为产物：
  描述：

  1,4-双(2-氯乙氧基)苯 在 palladium on activated charcoal 正丁基锂 、 氢气 、 溴 、 四氯化锡 、 铁粉 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 25.0 ℃ 、413.69 kPa 条件下， 反应 29.25h， 生成 8-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-4-carbaldehyde
  参考文献：
  名称：

  Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups

  摘要：

  Tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in prototypical hallucinogenic phenylalkylamines 1 and 2. Thus, a series of 8-substituted 1-(2,3,6,7-tetrahydrobenzo[ 1,2-b:4,5-b']difuran-4-yl)-2-aminoalkanes (7a-e) were prepared and evaluated for activity in the two-lever drug discrimination paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg) and for the ability to displace [H-3]ketanserin from rat cortical homogenate 5-HT2A receptors and [(3)H3-8-OH-DPAT from rat hippocampal homogenate 5-HT1A receptors. In addition, 1-(8-(bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5- (7b), which was found to be extremely potent in the rat in vivo assays, was evaluated for its ability to compete with [I-125][DOI and [H-3]ketanserin binding to cells expressing cloned human 5-HT2A, 5-H-2B, and 5-HT2C receptors. All of the dihydrofuranyl compounds having a hydrophobic substituent para to the alkylamine side chain had activities in both the in vitro and in vivo assays that equaled or surpassed the activity of the analogous conformationally flexible parent compounds. For example, 7b substituted for LSD in the drug discrimination assay with an ED(50) Of 61 nmol/kg and had K-i values in the nanomolar to subnanomolar range for the displacement of radioligand from rat and human 5-HT2 receptors, making it one of the most potent hallucinogen-like phenylalkylamine derivatives reported to date. The results suggest that the dihydrofuran rings in these pew analogues effectively model the active binding conformations of the methoxy groups of the parent compounds 1 and 2. In addition, the results provide information about the topography and relative orientation of residues involved in agonist binding in the serotonin 5-HT2 receptors.

  DOI：

  10.1021/jm960199j

文献信息

• Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups
  作者：Aaron P. Monte、Danuta Marona-Lewicka、Matthew A. Parker、David B. Wainscott、David L. Nelson、David E. Nichols

  DOI：10.1021/jm960199j

  日期：1996.1.1

  Tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in prototypical hallucinogenic phenylalkylamines 1 and 2. Thus, a series of 8-substituted 1-(2,3,6,7-tetrahydrobenzo[ 1,2-b:4,5-b']difuran-4-yl)-2-aminoalkanes (7a-e) were prepared and evaluated for activity in the two-lever drug discrimination paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg) and for the ability to displace [H-3]ketanserin from rat cortical homogenate 5-HT2A receptors and [(3)H3-8-OH-DPAT from rat hippocampal homogenate 5-HT1A receptors. In addition, 1-(8-(bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5- (7b), which was found to be extremely potent in the rat in vivo assays, was evaluated for its ability to compete with [I-125][DOI and [H-3]ketanserin binding to cells expressing cloned human 5-HT2A, 5-H-2B, and 5-HT2C receptors. All of the dihydrofuranyl compounds having a hydrophobic substituent para to the alkylamine side chain had activities in both the in vitro and in vivo assays that equaled or surpassed the activity of the analogous conformationally flexible parent compounds. For example, 7b substituted for LSD in the drug discrimination assay with an ED(50) Of 61 nmol/kg and had K-i values in the nanomolar to subnanomolar range for the displacement of radioligand from rat and human 5-HT2 receptors, making it one of the most potent hallucinogen-like phenylalkylamine derivatives reported to date. The results suggest that the dihydrofuran rings in these pew analogues effectively model the active binding conformations of the methoxy groups of the parent compounds 1 and 2. In addition, the results provide information about the topography and relative orientation of residues involved in agonist binding in the serotonin 5-HT2 receptors.