4,6-Dichloro-7-fluoro-3-(4-fluorophenyl)sulfonylquinoline

• 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: 4,6-Dichloro-7-fluoro-3-(4-fluorophenyl)sulfonylquinoline
• 英文别名: 4,6-dichloro-7-fluoro-3-(4-fluorophenyl)sulfonylquinoline
• 化学式: C₁₅H₇Cl₂F₂NO₂S
• 分子量: 374.195
• InChiKey: AZIUDCKWINCEHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氯苯硼酸 、 4,6-Dichloro-7-fluoro-3-(4-fluorophenyl)sulfonylquinoline 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 生成 6-chloro-4-(4-chlorophenyl)-7-fluoro-3-((4-fluorophenyl)-sulfonyl)quinoline
  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
• 作为产物：
  描述：

  sodium 4-fluorobenzenesulfinate 在 三氯氧磷 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 4,6-Dichloro-7-fluoro-3-(4-fluorophenyl)sulfonylquinoline
  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

• 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.