4-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran | 178557-16-9

• 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: 4-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran
• CAS: 178557-16-9
• 化学式: C₁₁H₁₂O₂
• 分子量: 176.215
• InChiKey: HMQSCZUPMPTQSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran 在 ammonium acetate 、 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 反应 19.08h， 生成 8-methyl-4-[(E)-2-nitroprop-1-enyl]-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran
  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：

  4-甲酰基-2,3,6,7-四氢苯并[1,2-b:4,5-b]二呋喃 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以95%的产率得到4-Methyl-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran
  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

• [EN] SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME<br/>[FR] SULFONYLURÉES, COMPOSÉS APPARENTÉS, ET LEUR UTILISATION
  申请人：UNIV QUEENSLAND

  公开号：WO2016131098A1

  公开（公告）日：2016-08-25

  ABSTRACT The present invention provides for certain sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. Such compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor.
• 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.