N,N-dibutyl-2-(5,7-diethyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N,N-dibutyl-2-(5,7-diethyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)acetamide
• 英文别名: N,N-dibutyl-2-[5,7-diethyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]acetamide
• 化学式: C₂₇H₃₈N₄O₂
• 分子量: 450.624
• InChiKey: ABQDUXNFZMTZAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  59.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-甲氧基苯甲酰基乙腈 在 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.42h， 生成 N,N-dibutyl-2-(5,7-diethyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)acetamide
  参考文献：
  名称：

  New structure–activity relationships of N-acetamide substituted pyrazolopyrimidines as pharmacological ligands of TSPO

  摘要：

  Translocator protein (TSPO) represents an attractive target for molecular imaging and therapy due to its prevalence and critical roles played in oncology and other pathologies. Based upon our previously optimized pyrazolopyrimidine scaffold, we elucidated new structure activity relationships related to N, N-disubstitutions of the terminal acetamide on pyrazolopyrimidines and further explored the impacts of these substituents on lipophilicity and plasma protein binding. Several novel chemical probes reported here exhibited significantly increased binding affinity, suitable lipophilicity and protein binding compared with contemporary TSPO ligands. We illustrate that N, N-acetamide disubstitution affords opportunities to introduce diverse chemical moieties distal to the central pyrazolopyrimidine core, without sacrificing TSPO affinity. We anticipate that further exploration of N-acetamide substitutions may yield additional TSPO ligands capable of furthering the field of precision medicine. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.06.041

文献信息

• New structure–activity relationships of N-acetamide substituted pyrazolopyrimidines as pharmacological ligands of TSPO
  作者：Jun Li、Michael L. Schulte、Michael L. Nickels、H. Charles Manning

  DOI：10.1016/j.bmcl.2016.06.041

  日期：2016.8

  Translocator protein (TSPO) represents an attractive target for molecular imaging and therapy due to its prevalence and critical roles played in oncology and other pathologies. Based upon our previously optimized pyrazolopyrimidine scaffold, we elucidated new structure activity relationships related to N, N-disubstitutions of the terminal acetamide on pyrazolopyrimidines and further explored the impacts of these substituents on lipophilicity and plasma protein binding. Several novel chemical probes reported here exhibited significantly increased binding affinity, suitable lipophilicity and protein binding compared with contemporary TSPO ligands. We illustrate that N, N-acetamide disubstitution affords opportunities to introduce diverse chemical moieties distal to the central pyrazolopyrimidine core, without sacrificing TSPO affinity. We anticipate that further exploration of N-acetamide substitutions may yield additional TSPO ligands capable of furthering the field of precision medicine. (C) 2016 Elsevier Ltd. All rights reserved.