8-chloro-5-fluoro-2-(trifluoromethyl)quinolin-4-ol | 917251-94-6

• 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-chloro-5-fluoro-2-(trifluoromethyl)quinolin-4-ol
• 英文别名: 8-chloro-5-fluoro-2-(trifluoromethyl)-1H-quinolin-4-one
• CAS: 917251-94-6
• 化学式: C₁₀H₄ClF₄NO
• mdl: MFCD09907838
• 分子量: 265.594
• InChiKey: RCUAAGIMTLQZHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-chloro-5-fluoro-2-(trifluoromethyl)quinolin-4-ol 在 tris-(dibenzylideneacetone)dipalladium(0) 盐酸 、 水 、 sodium cyanoborohydride 、 potassium carbonate 、 sodium t-butanolate 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 25.5h， 生成 5-fluoro-4-methoxy-8-{4-[4-(6-methoxyquinolin-8-yl)piperazin-1-yl]piperidin-1-yl}-2-(trifluoromethyl)quinoline
  参考文献：
  名称：

  WO2007/146072

  摘要：

  公开号：
• 作为产物：
  描述：

  4,4,4-三氟-3-氧代丁酸 、 2-氯-5-氟苯胺 在 polyphosphoric acid 作用下， 以51%的产率得到8-chloro-5-fluoro-2-(trifluoromethyl)quinolin-4-ol
  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

• Piperazine-piperidine antagonists and agonists of the 5-HT1A receptor
  申请人：Asselin Magda

  公开号：US20070027160A1

  公开（公告）日：2007-02-01

  The present invention relates to novel piperazine-piperidine compounds. The compounds are useful as 5-HT 1A binding agents, particularly as 5-HT 1A receptor antagonists and agonists. These compounds are useful in treating central nervous system disorders, such as cognition disorders, anxiety disorders, depression and sexual dysfunction.

  本发明涉及新型哌嗪-哌啶化合物。这些化合物可用作5-HT1A结合剂，特别是作为5-HT1A受体拮抗剂和激动剂。这些化合物在治疗中枢神经系统疾病方面很有用，如认知障碍、焦虑症、抑郁症和性功能障碍。
• Processes for synthesizing piperazine-piperidine compounds
  申请人：Liu Weiguo

  公开号：US20080058523A1

  公开（公告）日：2008-03-06

  The present invention relates to processes for synthesizing piperazine-piperidine compounds, and compounds useful as 5-HT 1A binding agents, particularly as 5-HT 1A receptor antagonists and agonists. The processes also allow for safer and environmentally tolerant production of these useful compounds.

  本发明涉及合成哌嗪-哌啶化合物的过程，以及用作5-HT1A结合剂的化合物，特别是5-HT1A受体拮抗剂和激动剂。这些过程还允许更安全、更环保地生产这些有用的化合物。
• Piperazine-piperidine antagonists and agonists of the 5-HT1A receptor
  申请人：Wyeth LLC

  公开号：US07671056B2

  公开（公告）日：2010-03-02

  The present invention relates to novel piperazine-piperidine compounds. The compounds are useful as 5-HT1A binding agents, particularly as 5-HT1A receptor antagonists and agonists. These compounds are useful in treating central nervous system disorders, such as cognition disorders, anxiety disorders, depression and sexual dysfunction. The invention relates to compounds and pharmaceutically acceptable salts of formula (I′): wherein R1-R16, Ra, Rb, and n are set forth in the specification. The invention also relates to pharmaceutical compositions comprising compounds and pharmaceutically acceptable salts of formula (I′).

  本发明涉及新型哌嗪-哌啶化合物。这些化合物可用作5-HT1A结合剂，特别是5-HT1A受体拮抗剂和激动剂。这些化合物可用于治疗中枢神经系统疾病，如认知障碍、焦虑症、抑郁症和性功能障碍。本发明涉及式（I'）的化合物和药学上可接受的盐，其中R1-R16、Ra、Rb和n在说明书中列出。本发明还涉及包含式（I'）的化合物和药学上可接受的盐的制药组合物。
• PIPERAZINE-PIPERIDINE ANTAGONISTS AND AGONISTS OF THE 5-HT1A RECEPTOR
  申请人：Wyeth

  公开号：EP1888559A2

  公开（公告）日：2008-02-20
• PROCESS FOR SYNTHESIZING PIPERAZINE-PIPERIDINE COMPOUNDS
  申请人：Wyeth

  公开号：EP2035384A2

  公开（公告）日：2009-03-18