(+/-)-6-methoxy-2,2a,3,4-tetrahydronaphtho[1,8-bc]furan-5-one | 59701-75-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+/-)-6-methoxy-2,2a,3,4-tetrahydronaphtho[1,8-bc]furan-5-one
• 英文别名: 6-methoxy-2,2a,3,4-tetrahydro-naphtho[1,8-bc]furan-5-one；6-Methoxy-2a,3,4,5-tetrahydro-2H-naphtho<1,8-bc>furan-5-on；6-Methoxy-2,2a,3,4-tetrahydro-5H-naphtho[1,8-bc]furan-5-one；9-methoxy-2-oxatricyclo[6.3.1.04,12]dodeca-1(12),8,10-trien-7-one
• CAS: 59701-75-6
• 化学式: C₁₂H₁₂O₃
• 分子量: 204.225
• InChiKey: FVNOBZGVALPCAP-UHFFFAOYSA-N

物化性质

• 熔点：
  104-105 °C(Solv: benzene (71-43-2); hexane (110-54-3))
• 沸点：
  334.0±42.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：

  (+/-)-6-methoxy-2,2a,3,4-tetrahydronaphtho[1,8-bc]furan-5-one 在 lithium aluminium tetrahydride 、 zinc(II) iodide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 (+/-)-5-aminomethyl-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan-5-ol
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of a Series of Geometrically Constrained 5-HT_2A/2C Receptor Ligands

  摘要：

  In studies of the SAR of phenethylamine-type serotonin 5-HT2A receptor agonists, substituted conformationally constrained tetrahydronaphthofurans were designed to investigate the optimal conformation of the 2-aminoethyl moiety. These compounds were tested using in vitro assays for affinity at 5-HT1A, 5-HT2A, and 5-HT2C receptors. The benzofuran-containing analogues, 6a and 6b, had significantly higher affinity for the 5-HT receptors tested than did the benzodi-hydrofuran-containing compounds, 4a, 4b, 5a, and 5b. The most potent compound (8-bromo-6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane, 6b, had K-i values for displacement of [I-125] -DOI from 5-HT2A and 5-HT2C cloned rat receptors of 2.6 and 1.1 nM, respectively. Despite their high affinity, the compounds of this naphthofuran series lacked high intrinsic activity at the 5-HT2A receptor as measured using the phosphoinositide hydrolysis assay. The most potent compound in vitro, 6b, was tested in the two-lever drug discrimination assay in rats trained to discriminate LSD from saline, and failed to substitute, a result typical for compounds with low intrinsic activity. Thus, although conformational constraint has led to high-affinity 5-HT2A ligands with partial agonist activity, all of the spatial and steric properties of the ligand necessary for full receptor activation have not yet been identified.

  DOI：

  10.1021/jm030064v
• 作为产物：
  描述：

  (+/-)-2-(5-methoxy-2,3-dihydrobenzofuran-3-yl)propionitrile 在 sodium hydroxide 、 四氯化锡 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 (+/-)-6-methoxy-2,2a,3,4-tetrahydronaphtho[1,8-bc]furan-5-one
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of a Series of Geometrically Constrained 5-HT_2A/2C Receptor Ligands

  摘要：

  In studies of the SAR of phenethylamine-type serotonin 5-HT2A receptor agonists, substituted conformationally constrained tetrahydronaphthofurans were designed to investigate the optimal conformation of the 2-aminoethyl moiety. These compounds were tested using in vitro assays for affinity at 5-HT1A, 5-HT2A, and 5-HT2C receptors. The benzofuran-containing analogues, 6a and 6b, had significantly higher affinity for the 5-HT receptors tested than did the benzodi-hydrofuran-containing compounds, 4a, 4b, 5a, and 5b. The most potent compound (8-bromo-6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane, 6b, had K-i values for displacement of [I-125] -DOI from 5-HT2A and 5-HT2C cloned rat receptors of 2.6 and 1.1 nM, respectively. Despite their high affinity, the compounds of this naphthofuran series lacked high intrinsic activity at the 5-HT2A receptor as measured using the phosphoinositide hydrolysis assay. The most potent compound in vitro, 6b, was tested in the two-lever drug discrimination assay in rats trained to discriminate LSD from saline, and failed to substitute, a result typical for compounds with low intrinsic activity. Thus, although conformational constraint has led to high-affinity 5-HT2A ligands with partial agonist activity, all of the spatial and steric properties of the ligand necessary for full receptor activation have not yet been identified.

  DOI：

  10.1021/jm030064v

文献信息

• HORAGUCHI T.; SHIMIZU T.; ABE T., BULL. CHEM. SOC. JAP. <BCSJ-A8>, 1976, 49, NO 3, 737-740
  作者：HORAGUCHI T.、 SHIMIZU T.、 ABE T.

  DOI：——

  日期：——