2-(4-(3-(4-fluorophenoxy)propyl)piperazin-1-yl)pyrimidine | 717092-12-1

• 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-(4-(3-(4-fluorophenoxy)propyl)piperazin-1-yl)pyrimidine
• 英文别名: 2-[4-[3-(4-Fluorophenoxy)propyl]piperazin-1-yl]pyrimidine
• CAS: 717092-12-1
• 化学式: C₁₇H₂₁FN₄O
• 分子量: 316.378
• InChiKey: FGFQEEFTBWHCLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  41.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(4-fluorophenoxy)-1-propanol 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 2-(4-(3-(4-fluorophenoxy)propyl)piperazin-1-yl)pyrimidine
  参考文献：
  名称：

  Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents

  摘要：

  Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacology. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.12.019

文献信息

• Identification of a new selective dopamine D4 receptor ligand
  作者：Dinithia Sampson、Xue Y. Zhu、Suresh V.K. Eyunni、Jagan R. Etukala、Edward Ofori、Barbara Bricker、Nazarius S. Lamango、Vincent Setola、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2014.04.026

  日期：2014.6

  The dopamine D-4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D-4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD(4) receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D-4 receptor. Compound 27 (KiD4 = 0.84 nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D-4 receptor. Compound 28 (KiD4 = 3.9 nM) while not as potent, was more discriminatory for the D-4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT(1A)R and 5HT(2B)R, have binding affinity constants better than 100 nM (K-i < 100 nM). Compound 28 is a potentially useful D-4-selective ligand for probing disease treatments involving the D-4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted. Published by Elsevier Ltd.
• Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents
  作者：Kwakye Peprah、Xue Y. Zhu、Suresh V.K. Eyunni、Vincent Setola、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2011.12.019

  日期：2012.2

  Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacology. Published by Elsevier Ltd.