4,4'-[biphenyl-4,4'-diylbis(methylene-1H-1,2,3-triazole-1,4-diyl)]bis(N-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}benzamide) | 1192887-18-5

• 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: 4,4'-[biphenyl-4,4'-diylbis(methylene-1H-1,2,3-triazole-1,4-diyl)]bis(N-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}benzamide)
• 英文别名: N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-4-[1-[[4-[4-[[4-[4-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butylcarbamoyl]phenyl]triazol-1-yl]methyl]phenyl]phenyl]methyl]triazol-4-yl]benzamide
• CAS: 1192887-18-5
• 化学式: C₆₂H₇₀N₁₂O₄
• 分子量: 1047.32
• InChiKey: KEOJOHYWCQCCER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  78
• 可旋转键数：
  23
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  151
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4-ethynyl-N-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}benzamide 、 4,4'-bis(azidomethyl)biphenyl 在 tetrakis(actonitrile)copper(I) hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以40%的产率得到4,4'-[biphenyl-4,4'-diylbis(methylene-1H-1,2,3-triazole-1,4-diyl)]bis(N-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}benzamide)
  参考文献：
  名称：

  1,1′-Disubstituted Ferrocenes as Molecular Hinges in Mono- and Bivalent Dopamine Receptor Ligands

  摘要：

  On the basis of previous work on dopaminergic partial agonists of type 1 and 2, disubstituted ferrocenes are presented as valuable arene bioisosteres. Because substituents at the distal cyclopentadienyl ring are able to adjust the relative disposition that is required for ligand binding, disubstituted ferrocenes can act as molecular hinges. Taking advantage of click chemistry, the regioselective construction and functionalization of the target molecules is reported. Thus triazole derived appendages were used for the fine-tuning of biological activity and for the attachment of linker units generating bivalent GPCR ligands. Receptor binding was evaluated by radioligand displacement experiments, revealing superaffinity with sub- to single-digit nanomolar K-i values for particular test compounds. As a neutral antagonist at the dopamine receptors D3 and D4 and a potent partial agonist at the D2 subtype (intrinsic activity = 57%, EC50 = 2.5 nM), the bifunctional ferrocene 10b revealed a novel and unique activity profile.

  DOI：

  10.1021/jm901120h

文献信息

• 1,1′-Disubstituted Ferrocenes as Molecular Hinges in Mono- and Bivalent Dopamine Receptor Ligands
  作者：Daniela Huber、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm901120h

  日期：2009.11.12

  On the basis of previous work on dopaminergic partial agonists of type 1 and 2, disubstituted ferrocenes are presented as valuable arene bioisosteres. Because substituents at the distal cyclopentadienyl ring are able to adjust the relative disposition that is required for ligand binding, disubstituted ferrocenes can act as molecular hinges. Taking advantage of click chemistry, the regioselective construction and functionalization of the target molecules is reported. Thus triazole derived appendages were used for the fine-tuning of biological activity and for the attachment of linker units generating bivalent GPCR ligands. Receptor binding was evaluated by radioligand displacement experiments, revealing superaffinity with sub- to single-digit nanomolar K-i values for particular test compounds. As a neutral antagonist at the dopamine receptors D3 and D4 and a potent partial agonist at the D2 subtype (intrinsic activity = 57%, EC50 = 2.5 nM), the bifunctional ferrocene 10b revealed a novel and unique activity profile.