4-[5-fluoro-4-(methylthio)-2-pyrimidinyl]-α-(4-fluorophenyl)-1-piperazinebutanol | 99931-86-9

• 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-[5-fluoro-4-(methylthio)-2-pyrimidinyl]-α-(4-fluorophenyl)-1-piperazinebutanol
• 英文别名: 4-[4-(5-Fluoro-4-methylsulfanyl-pyrimidin-2-yl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-butan-1-ol；4-[4-(5-fluoro-4-methylsulfanylpyrimidin-2-yl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-ol
• CAS: 99931-86-9
• 化学式: C₁₉H₂₄F₂N₄OS
• 分子量: 394.489
• InChiKey: UOPZCHLWGQQVGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  77.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[5-fluoro-4-(methylthio)-2-pyrimidinyl]-α-(4-fluorophenyl)-1-piperazinebutanol 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以50%的产率得到α-(4-fluorophenyl)-4-(5-fluoro-4-hydroxy-2-pyrimidinyl)-1-piperazinebutanol
  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 sodium tetrahydroborate 、 potassium carbonate 、 对甲苯磺酸 、 potassium iodide 作用下， 以 乙醇 、 乙腈 、 苯 为溶剂， 反应 54.0h， 生成 4-[5-fluoro-4-(methylthio)-2-pyrimidinyl]-α-(4-fluorophenyl)-1-piperazinebutanol
  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

• Agents for treatment of brain ischemia
  申请人：Bristol-Myers Squibb Company

  公开号：EP0400661A1

  公开（公告）日：1990-12-05

  A series of 5-halopyrimidin-2-ylpiperazinylalkyl derivatives having useful anti-ischemic properties for treatment and prevention of dirorders resulting from brain and/or spinal cord anoxia.

  一系列 5-卤代嘧啶-2-基哌嗪基烷基衍生物，具有有效的抗缺血特性，可用于治疗和预防脑和/或脊髓缺氧导致的失调。
• US4994460A
  申请人：——

  公开号：US4994460A

  公开（公告）日：1991-02-19
• 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.