2-[2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl]-3,4-dihydro-7-nitronaphthalen-1(2H)-one | 1558026-51-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl]-3,4-dihydro-7-nitronaphthalen-1(2H)-one
• 英文别名: 2-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-7-nitro-3,4-dihydro-2H-naphthalen-1-one
• CAS: 1558026-51-9
• 化学式: C₂₄H₂₄FN₃O₄
• 分子量: 437.471
• InChiKey: XCJLVDRQFATWPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  89.48
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-[2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl]-3,4-dihydro-7-nitronaphthalen-1(2H)-one 在 tin(II) chloride dihdyrate 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以67%的产率得到7-amino-2-[2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl]-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
• 作为产物：
  描述：

  7-硝基-3,4-二氢-2H-1-萘酮 在 aluminium hydride 、 盐酸 、 1-羟基苯并三唑 、 对甲苯磺酸 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 43.25h， 生成 2-[2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl]-3,4-dihydro-7-nitronaphthalen-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.