2-(3-hydroxy-4-(4-(2-propoxyphenyl)piperazin-1-yl)butyl)isoindoline-1,3-dione | 1144854-24-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(3-hydroxy-4-(4-(2-propoxyphenyl)piperazin-1-yl)butyl)isoindoline-1,3-dione
• 英文别名: 2-[3-Hydroxy-4-[4-(2-propoxyphenyl)piperazin-1-yl]butyl]isoindole-1,3-dione
• CAS: 1144854-24-9
• 化学式: C₂₅H₃₁N₃O₄
• 分子量: 437.539
• InChiKey: VPQHPYJYUTZEKE-UHFFFAOYSA-N

物化性质

• 沸点：
  625.2±55.0 °C(predicted)
• 密度：
  1.226±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3-hydroxy-4-(4-(2-propoxyphenyl)piperazin-1-yl)butyl)isoindoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 0.25h， 以69%的产率得到1-amino-4-(4-(2-propoxyphenyl)piperazin-1-yl)butan-3-ol
  参考文献：
  名称：

  N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists

  摘要：

  In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl- and 2-OCH3-phenylpiperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (K-i = 1 nM) for D3 and similar to 400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors, further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders.

  DOI：

  10.1021/jm900095y
• 作为产物：
  描述：

  N-(3,4-环氧基丁基)邻苯二甲酰亚胺 、 1-(2-propoxyphenyl)piperazine 以 异丙醇 为溶剂， 反应 0.25h， 以77%的产率得到2-(3-hydroxy-4-(4-(2-propoxyphenyl)piperazin-1-yl)butyl)isoindoline-1,3-dione
  参考文献：
  名称：

  N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists

  摘要：

  In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl- and 2-OCH3-phenylpiperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (K-i = 1 nM) for D3 and similar to 400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors, further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders.

  DOI：

  10.1021/jm900095y

文献信息

• <i>N</i>-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists
  作者：Amy Hauck Newman、Peter Grundt、George Cyriac、Jeffrey R. Deschamps、Michelle Taylor、Rakesh Kumar、David Ho、Robert R. Luedtke

  DOI：10.1021/jm900095y

  日期：2009.4.23

  In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl- and 2-OCH3-phenylpiperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (K-i = 1 nM) for D3 and similar to 400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors, further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders.