6-acetyl-3-[(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl]-3,4-dihydronaphthalen-1(2H)-one | 1558026-35-9

• 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-acetyl-3-[(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl]-3,4-dihydronaphthalen-1(2H)-one
• 英文别名: 6-acetyl-3-[[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]methyl]-3,4-dihydro-2H-naphthalen-1-one
• CAS: 1558026-35-9
• 化学式: C₂₅H₂₅FN₂O₃
• 分子量: 420.484
• InChiKey: FDVGEVSBRKQEIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(methoxycarbonyl)-1,2,3,4-tetrahydro-1-oxonaphthalen-6-yl trifluoromethanesulfonate 在 吡啶 、 manganese(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 lithium aluminium tetrahydride 、 lithium chloride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 99.0h， 生成 6-acetyl-3-[(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl]-3,4-dihydronaphthalen-1(2H)-one
  参考文献：
  名称：

  Synthesis and biological evaluation of a series of aminoalkyl-tetralones and tetralols as dual dopamine/serotonin ligands

  摘要：

  A series of novel alpha-tetralone and a-tetralol derivatives was synthesized, and their binding affinities for 5-HT2A and D-2 receptors, the most important targets implicated in the anti-schizophrenia drug action, were evaluated to elucidate how substitutions in the aromatic ring of the pharmacophore affect to the affinity or selectivity for these receptors. The replacement of the H-7 in the tetrahydronaphthalene system by an amino group resulted in privileged 5-HT2A affinity of the 6-fluorobenzo[d]isoxazol derivative 36 and the alcohol 25 both showing a pK(i) value for 5-HT2A higher than 8.3 and good binding affinities for D-2 receptor leading to a Meltzer's ratio characteristic of an atypical antipsychotic profile. Additionally, a small collection of 3-aminomethyltetralone derivatives was prepared and examined here for their affinities and selectivities as 5-HT2A/D-2 dual ligands. Compound 11 shows the best profile with good pK(i) values for 5-HT2A and D-2 receptors leading to a Meltzer's ratio characteristic of a typical antipsychotic behaviour. These three compounds behaved as competitive antagonists of both 5-HT2A and D-2 receptors, and might be promising pharmacological tools for the investigation of the dual function of the 5HT(2A)-D-2 ligands. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.066

文献信息

• Synthesis and biological evaluation of a series of aminoalkyl-tetralones and tetralols as dual dopamine/serotonin ligands
  作者：Laura Carro、María Torrado、Enrique Raviña、Christian F. Masaguer、Sonia Lage、José Brea、María I. Loza

  DOI：10.1016/j.ejmech.2013.10.066

  日期：2014.1

  A series of novel alpha-tetralone and a-tetralol derivatives was synthesized, and their binding affinities for 5-HT2A and D-2 receptors, the most important targets implicated in the anti-schizophrenia drug action, were evaluated to elucidate how substitutions in the aromatic ring of the pharmacophore affect to the affinity or selectivity for these receptors. The replacement of the H-7 in the tetrahydronaphthalene system by an amino group resulted in privileged 5-HT2A affinity of the 6-fluorobenzo[d]isoxazol derivative 36 and the alcohol 25 both showing a pK(i) value for 5-HT2A higher than 8.3 and good binding affinities for D-2 receptor leading to a Meltzer's ratio characteristic of an atypical antipsychotic profile. Additionally, a small collection of 3-aminomethyltetralone derivatives was prepared and examined here for their affinities and selectivities as 5-HT2A/D-2 dual ligands. Compound 11 shows the best profile with good pK(i) values for 5-HT2A and D-2 receptors leading to a Meltzer's ratio characteristic of a typical antipsychotic behaviour. These three compounds behaved as competitive antagonists of both 5-HT2A and D-2 receptors, and might be promising pharmacological tools for the investigation of the dual function of the 5HT(2A)-D-2 ligands. (C) 2013 Elsevier Masson SAS. All rights reserved.