1-(4-fluoro-phenyl)-4-(4-pyrimidin-2-yl-piperazin-1-yl)-butan-1-one | 801-12-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluoro-phenyl)-4-(4-pyrimidin-2-yl-piperazin-1-yl)-butan-1-one
• 英文别名: 1-(4-fluorophenyl)-4-(4-pyrimidin-2-ylpiperazin-1-yl)butan-1-one
• CAS: 801-12-7
• 化学式: C₁₈H₂₁FN₄O
• 分子量: 328.389
• InChiKey: WEVJMQOBCRCIPF-UHFFFAOYSA-N

物化性质

• 沸点：
  516.2±60.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-fluoro-phenyl)-4-(4-pyrimidin-2-yl-piperazin-1-yl)-butan-1-one 在 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 2-{4-[4,4-Bis-(4-fluoro-phenyl)-but-3-enyl]-piperazin-1-yl}-pyrimidine
  参考文献：
  名称：

  Synthesis and biological characterization of .alpha.-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and analogs as potential atypical antipsychotic agents

  摘要：

  A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and evaluated in receptor binding assays and in in vivo behavioral paradigms as potential atypical antipsychotic agents. Compound 16 (BMS 181100 (formerly BMY 14802)) emerged as the lead compound from within the series on the basis of its good activity and duration of action in the inhibition of both conditioned avoidance responding and apomorphine-induced stereotopy in the rat. Compound 16 not only failed to induce catalepsy in the rat but was quite effective in reversing the cataleptic effect of neuroleptic agents, thus indicating a low propensity for causing extrapyramidal side effects. In comparison to reference antipsychotic agents, 16 appeared to be less sedating and was relatively weaker in causing muscle incoordination. The compound was essentially inactive in binding to dopamine D2 receptors and its chronic administration to rats did not result in dopamine receptor supersensitivity. It exhibited modest to weak affinity for 5-HT1A and alpha1 receptors but was found to be a fairly potent ligand for sigma binding sites (IC50 vs (+)-[H-3]-3-PPP = 112 nM). Although the resolved enantiomers of racemic 16 did not show dramatic differences from racemate or from each other in most tests, the R(+) enantiomer was up to 11-fold more potent than its antipode in binding to sigma sites. Several studies have indicated that 16 may be a limbic-selective agent which may modulate dopaminergic activity by an indirect mechanism. The compound has been selected for clinical evaluation in the treatment of psychosis.

  DOI：

  10.1021/jm00102a002
• 作为产物：
  描述：

  4-氯-4'-氟苯丁酮 在 potassium carbonate 、 对甲苯磺酸 、 potassium iodide 作用下， 以 乙腈 、 苯 为溶剂， 反应 54.0h， 生成 1-(4-fluoro-phenyl)-4-(4-pyrimidin-2-yl-piperazin-1-yl)-butan-1-one
  参考文献：
  名称：

  Synthesis and biological characterization of .alpha.-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and analogs as potential atypical antipsychotic agents

  摘要：

  A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and evaluated in receptor binding assays and in in vivo behavioral paradigms as potential atypical antipsychotic agents. Compound 16 (BMS 181100 (formerly BMY 14802)) emerged as the lead compound from within the series on the basis of its good activity and duration of action in the inhibition of both conditioned avoidance responding and apomorphine-induced stereotopy in the rat. Compound 16 not only failed to induce catalepsy in the rat but was quite effective in reversing the cataleptic effect of neuroleptic agents, thus indicating a low propensity for causing extrapyramidal side effects. In comparison to reference antipsychotic agents, 16 appeared to be less sedating and was relatively weaker in causing muscle incoordination. The compound was essentially inactive in binding to dopamine D2 receptors and its chronic administration to rats did not result in dopamine receptor supersensitivity. It exhibited modest to weak affinity for 5-HT1A and alpha1 receptors but was found to be a fairly potent ligand for sigma binding sites (IC50 vs (+)-[H-3]-3-PPP = 112 nM). Although the resolved enantiomers of racemic 16 did not show dramatic differences from racemate or from each other in most tests, the R(+) enantiomer was up to 11-fold more potent than its antipode in binding to sigma sites. Several studies have indicated that 16 may be a limbic-selective agent which may modulate dopaminergic activity by an indirect mechanism. The compound has been selected for clinical evaluation in the treatment of psychosis.

  DOI：

  10.1021/jm00102a002

文献信息

• Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-Chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one
  作者：Seth Y. Ablordeppey、Ramazan Altundas、Barbara Bricker、Xue Y. Zhu、Eyunni V.K. Suresh Kumar、Tanise Jackson、Abdul Khan、Bryan L. Roth

  DOI：10.1016/j.bmc.2008.06.030

  日期：2008.8

  The synthesis and exploration of novel butyrophenones have led to the identification of a diazepane analogue of haloperidol, 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one (compound 13) with an interesting multireceptor binding profile. Compound 13 was evaluated for its binding affinities at DA subtype receptors, 5HT subtype receptors, H-1, M-1 receptors and at NET, DAT, and

  新型丁酰苯的合成和探索已导致鉴定出氟哌啶醇的二氮杂类似物，4-[4-(4-氯苯基)-1,4-二氮杂-1-基]-1-(4-氟苯基)丁烷- 1-one（化合物 13）具有有趣的多受体结合特征。评估了化合物 13 对 DA 亚型受体、5HT 亚型受体、H-1、M-1 受体以及 NET、DAT 和 SERT 转运蛋白的结合亲和力。在这些受体中的每一个上，化合物 13 与目前使用的几种标准等效或更好。在体内小鼠和大鼠模型中，为了评估其在人体中引发僵住症和 EPS 的功效和倾向，化合物 13 显示出与氯氮平相似的功效，并且在其 ED(50) 值的五倍时不会产生僵住症。
• Synthesis and biological characterization of .alpha.-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and analogs as potential atypical antipsychotic agents
  作者：Joseph P. Yevich、James S. New、Walter G. Lobeck、Pierre Dextraze、Edith Bernstein、Duncan P. Taylor、Frank D. Yocca、Michael S. Eison、Davis L. Temple

  DOI：10.1021/jm00102a002

  日期：1992.11

  A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and evaluated in receptor binding assays and in in vivo behavioral paradigms as potential atypical antipsychotic agents. Compound 16 (BMS 181100 (formerly BMY 14802)) emerged as the lead compound from within the series on the basis of its good activity and duration of action in the inhibition of both conditioned avoidance responding and apomorphine-induced stereotopy in the rat. Compound 16 not only failed to induce catalepsy in the rat but was quite effective in reversing the cataleptic effect of neuroleptic agents, thus indicating a low propensity for causing extrapyramidal side effects. In comparison to reference antipsychotic agents, 16 appeared to be less sedating and was relatively weaker in causing muscle incoordination. The compound was essentially inactive in binding to dopamine D2 receptors and its chronic administration to rats did not result in dopamine receptor supersensitivity. It exhibited modest to weak affinity for 5-HT1A and alpha1 receptors but was found to be a fairly potent ligand for sigma binding sites (IC50 vs (+)-[H-3]-3-PPP = 112 nM). Although the resolved enantiomers of racemic 16 did not show dramatic differences from racemate or from each other in most tests, the R(+) enantiomer was up to 11-fold more potent than its antipode in binding to sigma sites. Several studies have indicated that 16 may be a limbic-selective agent which may modulate dopaminergic activity by an indirect mechanism. The compound has been selected for clinical evaluation in the treatment of psychosis.