8-bromo-3,5-difluoroquinoline | 1227293-42-6

• 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: 8-bromo-3,5-difluoroquinoline
• CAS: 1227293-42-6
• 化学式: C₉H₄BrF₂N
• 分子量: 244.038
• InChiKey: AOEZCPBPPDDDLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-bromo-3,5-difluoroquinoline 、 4-哌啶酮缩乙二醇 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以39%的产率得到8-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-3,5-difluoroquinoline
  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-amino-3,5-difluoroquinoline 在 氢溴酸 、 copper(I) bromide 、 sodium nitrite 作用下， 以 水 为溶剂， 生成 8-bromo-3,5-difluoroquinoline
  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.