6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl)quinoline-4-carboxylic acid | 1431876-03-7

• 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: 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl)quinoline-4-carboxylic acid
• 英文别名: 6-Fluoro-2-[2-Methyl-4-Phenoxy-5-(Propan-2-Yl)phenyl]quinoline-4-Carboxylic Acid；6-fluoro-2-(2-methyl-4-phenoxy-5-propan-2-ylphenyl)quinoline-4-carboxylic acid
• CAS: 1431876-03-7
• 化学式: C₂₆H₂₂FNO₃
• 分子量: 415.464
• InChiKey: KOLKCHJGWGJCTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氟靛红 、 1-(5-isopropyl-2-methyl-4-phenoxyphenyl)ethanone 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 48.0h， 以47%的产率得到6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl)quinoline-4-carboxylic acid
  参考文献：
  名称：

  SAR-Based Optimization of a 4-Quinoline Carboxylic Acid Analogue with Potent Antiviral Activity

  摘要：

  It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein, we report structure-ctivity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl) quinoline -4-carboxylic acid (C44) that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC50 of 1 nM and viral replication of VSV and WSN-Influenza with an EC50 of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to C44, providing structural insight into the potent inhibition of biaryl ether analogues of brequinar.

  DOI：

  10.1021/ml300464h

文献信息

• NOVEL METHODS FOR TREATING NEURODEGENERATIVE DISEASES
  申请人：Genzyme Corporation

  公开号：EP3071199A2

  公开（公告）日：2016-09-28
• [EN] NOVEL METHODS FOR TREATING NEURODEGENERATIVE DISEASES<br/>[FR] NOUVELLES MÉTHODES POUR TRAITER DES MALADIES NEURODÉGÉNÉRATIVES
  申请人：GENZYME CORP

  公开号：WO2015077535A2

  公开（公告）日：2015-05-28

  The invention relates to dihydroorate dehydrogenase (DHODH) inhibitors useful for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis.
• SAR-Based Optimization of a 4-Quinoline Carboxylic Acid Analogue with Potent Antiviral Activity
  作者：Priyabrata Das、Xiaoyi Deng、Liang Zhang、Michael G. Roth、Beatriz M. A. Fontoura、Margaret A. Phillips、Jef K. De Brabander

  DOI：10.1021/ml300464h

  日期：2013.6.13

  It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein, we report structure-ctivity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl) quinoline -4-carboxylic acid (C44) that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC50 of 1 nM and viral replication of VSV and WSN-Influenza with an EC50 of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to C44, providing structural insight into the potent inhibition of biaryl ether analogues of brequinar.