N-(5-phenyl-1,2,4-oxadiazol-3-yl)-4-(4-(3-trifluorophenyl)piperazin-1-yl)butan-1-amine

• 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-(5-phenyl-1,2,4-oxadiazol-3-yl)-4-(4-(3-trifluorophenyl)piperazin-1-yl)butan-1-amine
• 英文别名: 5-phenyl-N-[4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]butyl]-1,2,4-oxadiazol-3-amine
• 化学式: C₂₃H₂₆F₃N₅O
• 分子量: 445.488
• InChiKey: PGRBVTQKNJBFKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(5-phenyl-1,2,4-oxadiazol-3-yl)-4-(4-(3-trifluorophenyl)piperazin-1-yl)butan-1-amine 、 1-碘代丙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以45.5%的产率得到N-(5-phenyl-1,2,4-oxadiazol-3-yl)-N-propyl-4-(4-(3-trifluorohenyl)piperazin-1-yl)butan-1-amine
  参考文献：
  名称：

  Design, synthesis and evaluation of bitopic arylpiperazinephenyl-1,2,4-oxadiazoles as preferential dopamine D3 receptor ligands

  摘要：

  The dopamine D3 receptor (D3R) was proposed as a therapeutic target for drug development to treat drug abuse and addiction and neuropsychiatric disorders. Several D3R-selective modulators over the dopamine D2 receptor (D2R) can avoid extrapyramidal symptoms (EPS) and hyperprolactinemia. However, few biased D3R ligands were identified or showed a narrow range of selectivity at the D3R over D2R because of their high sequence homology. Herein, we designed, synthesized and evaluated the binding affinity of a series of bitopic ligands: arypiperazine-phenyl-1,2,4-oxadiazoles. Compound 9e center dot HCl was the most potent and selective D3R modulator among these bitopic ligands. Molecular modeling revealed that D3R selectivity depends on the divergence of secondary binding pocket (SBP) in D3R and D2R. Specifically, non-conserved Tyr36, EL1 especially non-conserved Thr92 and Gly94, and EL2 Val180, Cys181 and Ser182 of D3R may contribute to D3R specificity over D2R. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.002
• 作为产物：
  描述：

  1-(4-aminobutyl)-4-[3-(trifluoromethyl)phenyl]piperazine 在 HATU 、 盐酸羟胺 、 sodium acetate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成 N-(5-phenyl-1,2,4-oxadiazol-3-yl)-4-(4-(3-trifluorophenyl)piperazin-1-yl)butan-1-amine
  参考文献：
  名称：

  Design, synthesis and evaluation of bitopic arylpiperazinephenyl-1,2,4-oxadiazoles as preferential dopamine D3 receptor ligands

  摘要：

  The dopamine D3 receptor (D3R) was proposed as a therapeutic target for drug development to treat drug abuse and addiction and neuropsychiatric disorders. Several D3R-selective modulators over the dopamine D2 receptor (D2R) can avoid extrapyramidal symptoms (EPS) and hyperprolactinemia. However, few biased D3R ligands were identified or showed a narrow range of selectivity at the D3R over D2R because of their high sequence homology. Herein, we designed, synthesized and evaluated the binding affinity of a series of bitopic ligands: arypiperazine-phenyl-1,2,4-oxadiazoles. Compound 9e center dot HCl was the most potent and selective D3R modulator among these bitopic ligands. Molecular modeling revealed that D3R selectivity depends on the divergence of secondary binding pocket (SBP) in D3R and D2R. Specifically, non-conserved Tyr36, EL1 especially non-conserved Thr92 and Gly94, and EL2 Val180, Cys181 and Ser182 of D3R may contribute to D3R specificity over D2R. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.002