1-[4-methoxy-2-(trifluoromethyl)quinolin-8-yl]piperidin-4-one | 1227293-34-6

• 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-[4-methoxy-2-(trifluoromethyl)quinolin-8-yl]piperidin-4-one
• CAS: 1227293-34-6
• 化学式: C₁₆H₁₅F₃N₂O₂
• 分子量: 324.303
• InChiKey: NCORRTZDOZZVJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-甲氧基-8-哌嗪-1-基喹啉 、 1-[4-methoxy-2-(trifluoromethyl)quinolin-8-yl]piperidin-4-one 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成 4-methoxy-8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}-2-(trifluoromethyl)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)-4-methoxy-2-(trifluoromethyl)quinoline 在 盐酸 作用下， 以 四氢呋喃 、 乙醚 、 水 为溶剂， 以65%的产率得到1-[4-methoxy-2-(trifluoromethyl)quinolin-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

文献信息

• The Synthesis and Biological Evaluation of Quinolyl-piperazinyl Piperidines as Potent Serotonin 5-HT_1AAntagonists
  作者：Wayne E. Childers、Lisa M. Havran、Magda Asselin、James J. Bicksler、Dan C. Chong、George T. Grosu、Zhongqi Shen、Magid, A. Abou-Gharbia、Alvin C. Bach、Boyd L. Harrison、Natasha Kagan、Teresa Kleintop、Ronald Magolda、Vasilios Marathias、Albert J. Robichaud、Annmarie L. Sabb、Mei-Yi Zhang、Terrance H. Andree、Susan H. Aschmies、Chad Beyer、Thomas A. Comery、Mark Day、Steven M. Grauer、Zoe A. Hughes、Sharon Rosenzweig-Lipson、Brian Platt、Claudine Pulicicchio、Deborah E. Smith、Stacy J. Sukoff-Rizzo、Kelly M. Sullivan、Adedayo Adedoyin、Christine Huselton、Warren D. Hirst

  DOI：10.1021/jm1000908

  日期：2010.5.27

  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.