1-(4-bromo-2-fluorobenzyl)-5,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 941271-88-1

• 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-bromo-2-fluorobenzyl)-5,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 1-[(4-Bromo-2-fluorophenyl)methyl]-5,8-difluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 941271-88-1
• 化学式: C₁₇H₉BrF₃NO₃
• 分子量: 412.163
• InChiKey: WDUCMEHKEHMGGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-bromo-2-fluorobenzyl)-5,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 、 2-氯-5-(4,4,5,5-四甲基-1,3,2-二氧硼烷)吡啶 在 二(三叔丁基膦)钯 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 以67%的产率得到1-[4-(6-chloropyridin-3-yl)-2-fluorobenzyl]-5,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  WO2008/2621

  摘要：

  公开号：
• 作为产物：
  描述：

  ethyl 1-(4-bromo-2-fluorobenzyl)-5,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 16.0h， 以98%的产率得到1-(4-bromo-2-fluorobenzyl)-5,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  WO2008/2621

  摘要：

  公开号：

文献信息

• Quinolone M1 Receptor Positive Allosteric Modulators
  申请人：Shipe William D.

  公开号：US20100317692A1

  公开（公告）日：2010-12-16

  The present invention is directed to quinolone compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, pain or sleep disorders, and to novel M1 receptor positive allosteric modulator compounds of formulae (II) to (VIII). The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases in which the M1 receptor is involved.

  本发明涉及通式（I）的喹诺酮化合物，其是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、疼痛或睡眠障碍，以及通式（II）至（VIII）的新型M1受体阳性变构调节剂化合物。本发明还涉及包含这些化合物的制药组合物，以及在治疗M1受体参与的疾病中使用这些化合物和组合物的方法。
• Parallel synthesis of N-biaryl quinolone carboxylic acids as selective M1 positive allosteric modulators
  作者：Feng V. Yang、William D. Shipe、Jaime L. Bunda、M. Brad Nolt、David D. Wisnoski、Zhijian Zhao、James C. Barrow、William J. Ray、Lei Ma、Marion Wittmann、Matthew A. Seager、Kenneth A. Koeplinger、George D. Hartman、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2009.11.100

  日期：2010.1

  An iterative analog library synthesis approach was employed in the exploration of a quinolone carboxylic acid series of selective M-1 positive allosteric modulators, and strategies for improving potency and plasma free fraction were identified. (C) 2009 Elsevier Ltd. All rights reserved.
• QUINOLONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1963271B1

  公开（公告）日：2010-07-28
• BENZYL-SUBSTITUTED QUINOLONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2037739B1

  公开（公告）日：2011-10-26
• Benzyl-substituted quinolone m1 receptor positive allosteric modulators
  申请人：Lindsley Craig

  公开号：US20100009962A1

  公开（公告）日：2010-01-14

  The present invention is directed to benzyl-substituted quinolone compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of diseases in which the M1 receptor is involved.