1-[3-fluoroquinolin-8-yl]piperidin-4-one | 1227293-30-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-[3-fluoroquinolin-8-yl]piperidin-4-one
• 英文别名: 1-(3-Fluoroquinolin-8-yl)piperidin-4-one
• CAS: 1227293-30-2
• 化学式: C₁₄H₁₃FN₂O
• 分子量: 244.268
• InChiKey: WIWDWJZNOXALEJ-UHFFFAOYSA-N

物化性质

• 沸点：
  430.1±45.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-甲氧基-8-哌嗪-1-基喹啉 、 1-[3-fluoroquinolin-8-yl]piperidin-4-one 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成 3-fluoro-8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl} quinoline
  参考文献：
  名称：

  The Synthesis and Biological Evaluation of Quinolyl-piperazinyl Piperidines as Potent Serotonin 5-HT_1AAntagonists

  摘要：

  As part of an effort to identify 5-HT1A antagonists that did not possess typical arylalkylamine or keto/amido-alkyl aryl piperazine scaffolds, prototype compound 10a was identified from earlier work in a combined 5-HT1A antagonist/SSRI program. This quinolyl-piperazinyl piperidine analogue displayed potent, selective 5-HT1A antagonism but suffered from poor oxidative metabolic stability, resulting in low exposure following oral administration. SA R studies, driven primarily by in vitro liver microsomal stability assessment, identified compound lob, which displayed improved oral bioavailability and lower intrinsic clearance. Further changes to the scaffold (e.g., 10r) resulted in a loss in potency. Compound 10b displayed cognitive enhancing effects in a number of animal models of learning and memory, enhanced the antidepressant-like effects of the SSRI fluoxetine, and reversed the sexual dysfunction induced by chronic fluoxetine treatment.

  DOI：

  10.1021/jm1000908
• 作为产物：
  描述：

  8-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-3-fluoroquinoline 在 盐酸 作用下， 以 四氢呋喃 、 乙醚 、 水 为溶剂， 以48%的产率得到1-[3-fluoroquinolin-8-yl]piperidin-4-one
  参考文献：
  名称：

  The Synthesis and Biological Evaluation of Quinolyl-piperazinyl Piperidines as Potent Serotonin 5-HT_1AAntagonists

  摘要：

  As part of an effort to identify 5-HT1A antagonists that did not possess typical arylalkylamine or keto/amido-alkyl aryl piperazine scaffolds, prototype compound 10a was identified from earlier work in a combined 5-HT1A antagonist/SSRI program. This quinolyl-piperazinyl piperidine analogue displayed potent, selective 5-HT1A antagonism but suffered from poor oxidative metabolic stability, resulting in low exposure following oral administration. SA R studies, driven primarily by in vitro liver microsomal stability assessment, identified compound lob, which displayed improved oral bioavailability and lower intrinsic clearance. Further changes to the scaffold (e.g., 10r) resulted in a loss in potency. Compound 10b displayed cognitive enhancing effects in a number of animal models of learning and memory, enhanced the antidepressant-like effects of the SSRI fluoxetine, and reversed the sexual dysfunction induced by chronic fluoxetine treatment.

  DOI：

  10.1021/jm1000908