4-(4-chlorophenyl)-3-((3,4-difluorophenyl)sulfonyl)-7-fluoroquinoline | 1093736-37-8

• 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: 4-(4-chlorophenyl)-3-((3,4-difluorophenyl)sulfonyl)-7-fluoroquinoline
• 英文别名: 4-(4-chloro-phenyl)-3-(3,4-difluoro-benzenesulfonyl)-7-fluoro-quinoline；4-(4-Chlorophenyl)-3-(3,4-difluorophenyl)sulfonyl-7-fluoroquinoline
• CAS: 1093736-37-8
• 化学式: C₂₁H₁₁ClF₃NO₂S
• 分子量: 433.838
• InChiKey: HXNBGBOZDFURTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4-二氟苯亚磺酸钠 在 四(三苯基膦)钯 、 potassium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 4-(4-chlorophenyl)-3-((3,4-difluorophenyl)sulfonyl)-7-fluoroquinoline
  参考文献：
  名称：

  Discovery and Preclinical Characterization of 3-((4-(4-Chlorophenyl)-7-fluoroquinoline-3-yl)sulfonyl)benzonitrile, a Novel Non-acetylenic Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator for Psychiatric Indications

  摘要：

  Negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGluR5) have been implicated as a potential pharmacotherapy for a number of psychiatric diseases, including anxiety and depression. Most of the mGluR5 NAM clinical candidates can be characterized by the central acetylenic moiety that connects the terminal pharmacophores. Identification of a sulfoquinoline hit via high throughput screening (HTS) followed by optimization provided a 4-phenyl-3-aryl-sulfoquinoline lead compound with the minimal pharmacophore. Optimization of the core and aryl appendages was performed by scanning and matrix libraries synthesized by the multiple parallel synthesis approach. Biological evaluation of matrix libraries provided a number of potent, metabolically stable, and in vivo active compounds. One of these compounds, 25 showed high efficacy and safety in preclinical in vivo models; this allowed its nomination as a novel, nonacetylenic mGluR5 NAM clinical candidate. Compound 25 was advanced to first-in-man trials for the treatment of psychiatric conditions.

  DOI：

  10.1021/acs.jmedchem.6b01858

文献信息

• Sulfonyl-Quinoline Derivatives
  申请人：Galambos Janos

  公开号：US20090042934A1

  公开（公告）日：2009-02-12

  The present invention relates to new mGluR1 and mGluR5 receptor subtype preferring ligands of formula (I) and/or salts and/or hydrates and/or solvates and/or polymorphs thereof. The invention also relates to processes and intermediates for their preparation, to pharmaceutical compositions containing these compounds and to their use in treatment and/or prevention of conditions which require modulation of mGluR1 and mGluR5 receptors.

  本发明涉及公式（I）及/或其盐和/或水合物和/或溶剂化物和/或多晶型的新型mGluR1和mGluR5受体亚型偏爱配体。本发明还涉及它们的制备过程和中间体，包含这些化合物的制药组合物以及它们在需要调节mGluR1和mGluR5受体的情况下的治疗和/或预防的用途。
• SULFONYL-QUINOLINE DERIVATIVES
  申请人：Richter Gedeon Nyrt.

  公开号：EP2167469B1

  公开（公告）日：2012-08-15
• US8063220B2
  申请人：——

  公开号：US8063220B2

  公开（公告）日：2011-11-22
• Discovery and Preclinical Characterization of 3-((4-(4-Chlorophenyl)-7-fluoroquinoline-3-yl)sulfonyl)benzonitrile, a Novel Non-acetylenic Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator for Psychiatric Indications
  作者：János Galambos、Attila Bielik、Mikhail Krasavin、Zoltán Orgován、György Domány、Katalin Nógrádi、Gábor Wágner、György T. Balogh、Zoltán Béni、János Kóti、Zoltán Szakács、Amrita Bobok、Sándor Kolok、Mónika L. Mikó-Bakk、Mónika Vastag、Katalin Sághy、Judit Laszy、Attila Sándor Halász、Ottilia Balázs、Krisztina Gál、István Greiner、Zsolt Szombathelyi、György M. Keserű

  DOI：10.1021/acs.jmedchem.6b01858

  日期：2017.3.23

  Negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGluR5) have been implicated as a potential pharmacotherapy for a number of psychiatric diseases, including anxiety and depression. Most of the mGluR5 NAM clinical candidates can be characterized by the central acetylenic moiety that connects the terminal pharmacophores. Identification of a sulfoquinoline hit via high throughput screening (HTS) followed by optimization provided a 4-phenyl-3-aryl-sulfoquinoline lead compound with the minimal pharmacophore. Optimization of the core and aryl appendages was performed by scanning and matrix libraries synthesized by the multiple parallel synthesis approach. Biological evaluation of matrix libraries provided a number of potent, metabolically stable, and in vivo active compounds. One of these compounds, 25 showed high efficacy and safety in preclinical in vivo models; this allowed its nomination as a novel, nonacetylenic mGluR5 NAM clinical candidate. Compound 25 was advanced to first-in-man trials for the treatment of psychiatric conditions.