N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-4-(6-bromopyridin-2-yl)benzamide | 928659-23-8

• 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: N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-4-(6-bromopyridin-2-yl)benzamide
• 英文别名: 4-(6-bromopyridin-2-yl)-N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzamide
• CAS: 928659-23-8
• 化学式: C₂₇H₃₁BrN₄O₂
• 分子量: 523.473
• InChiKey: GSXVJDPNLUDUEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-4-(6-bromopyridin-2-yl)benzamide 在 [¹⁸F]fluoride 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-4-(6-[18F]fluoropyridin-2-yl)benzamide
  参考文献：
  名称：

  Structure−Selectivity Investigations of D₂-Like Receptor Ligands by CoMFA and CoMSIA Guiding the Discovery of D₃ Selective PET Radioligands

  摘要：

  Elucidation of the physiological role of the D-3 receptor and its distribution in the brain using positron emission tomography (PET) is hampered by the lack of bioavailable subtype selective tracer ligands. To develop appropriate D-3 radioligands, we designed an integrative procedure involving the elucidation of structural features determining D-3 selectivity over both congeners D-2 and D-4 by comparative molecular analysis. Thus, we have successfully generated CoMFA and CoMSIA models based on the affinitiy differences of a series of 79 ligands representing a broad range of selectivities. These models yielded highly significant cross-validations (q(cv)(2)(D-3/D-2) = 0.86; q(cv)(2)(D-3/D-4) = 0.92) and excellent predictions of a 16-ligand test set (r(pred)(2) = 0.79-0.93). Exploiting this information, synthesis and receptor binding studies directed us to the fluorinated lead compounds 78 and 79, featuring subnanomolar D-3 affinities and considerable selectivities over D-2 and D-4 and, subsequently, to the subtype selective PET tracers [F-18]78 and [F-18]79.

  DOI：

  10.1021/jm0611152
• 作为产物：
  描述：

  2,6-二溴吡啶 在 四(三苯基膦)钯 4-二甲氨基吡啶 、 sodium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 3.0h， 生成 N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-4-(6-bromopyridin-2-yl)benzamide
  参考文献：
  名称：

  Structure−Selectivity Investigations of D₂-Like Receptor Ligands by CoMFA and CoMSIA Guiding the Discovery of D₃ Selective PET Radioligands

  摘要：

  Elucidation of the physiological role of the D-3 receptor and its distribution in the brain using positron emission tomography (PET) is hampered by the lack of bioavailable subtype selective tracer ligands. To develop appropriate D-3 radioligands, we designed an integrative procedure involving the elucidation of structural features determining D-3 selectivity over both congeners D-2 and D-4 by comparative molecular analysis. Thus, we have successfully generated CoMFA and CoMSIA models based on the affinitiy differences of a series of 79 ligands representing a broad range of selectivities. These models yielded highly significant cross-validations (q(cv)(2)(D-3/D-2) = 0.86; q(cv)(2)(D-3/D-4) = 0.92) and excellent predictions of a 16-ligand test set (r(pred)(2) = 0.79-0.93). Exploiting this information, synthesis and receptor binding studies directed us to the fluorinated lead compounds 78 and 79, featuring subnanomolar D-3 affinities and considerable selectivities over D-2 and D-4 and, subsequently, to the subtype selective PET tracers [F-18]78 and [F-18]79.

  DOI：

  10.1021/jm0611152

文献信息

• Structure−Selectivity Investigations of D₂-Like Receptor Ligands by CoMFA and CoMSIA Guiding the Discovery of D₃ Selective PET Radioligands
  作者：Ismail Salama、Carsten Hocke、Wolfgang Utz、Olaf Prante、Frank Boeckler、Harald Hübner、Torsten Kuwert、Peter Gmeiner

  DOI：10.1021/jm0611152

  日期：2007.2.8

  Elucidation of the physiological role of the D-3 receptor and its distribution in the brain using positron emission tomography (PET) is hampered by the lack of bioavailable subtype selective tracer ligands. To develop appropriate D-3 radioligands, we designed an integrative procedure involving the elucidation of structural features determining D-3 selectivity over both congeners D-2 and D-4 by comparative molecular analysis. Thus, we have successfully generated CoMFA and CoMSIA models based on the affinitiy differences of a series of 79 ligands representing a broad range of selectivities. These models yielded highly significant cross-validations (q(cv)(2)(D-3/D-2) = 0.86; q(cv)(2)(D-3/D-4) = 0.92) and excellent predictions of a 16-ligand test set (r(pred)(2) = 0.79-0.93). Exploiting this information, synthesis and receptor binding studies directed us to the fluorinated lead compounds 78 and 79, featuring subnanomolar D-3 affinities and considerable selectivities over D-2 and D-4 and, subsequently, to the subtype selective PET tracers [F-18]78 and [F-18]79.