(+/-)-N-trifluoroacetyl-(6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane | 589092-00-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (+/-)-N-trifluoroacetyl-(6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane
• 英文别名: 2,2,2-trifluoro-N-[(9-methoxy-2-oxatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraen-7-yl)methyl]acetamide
• CAS: 589092-00-2
• 化学式: C₁₅H₁₄F₃NO₃
• 分子量: 313.276
• InChiKey: BCHGCEMMGXSAET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-N-trifluoroacetyl-(6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 生成 (+/-)-(6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane
  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：

  (+/-)-syn-N-trifluoroacetyl-(6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan-5-yl)aminomethane 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 8.0h， 以88%的产率得到(+/-)-N-trifluoroacetyl-(6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane
  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