N-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-2-trifluoromethylbenzenesulfonamide | 1192298-98-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-2-trifluoromethylbenzenesulfonamide
• 英文别名: N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-2-(trifluoromethyl)benzenesulfonamide
• CAS: 1192298-98-8
• 化学式: C₂₄H₁₈F₄N₂O₅S
• 分子量: 522.477
• InChiKey: RFRXEVWWFXOHPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  95.1
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-氟-4-硝基苯酚 在 吡啶 、 氯化铵 、 N,N-二异丙基乙胺 、 锌 作用下， 以 乙醇 、 水 、 氯苯 为溶剂， 反应 99.0h， 生成 N-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-2-trifluoromethylbenzenesulfonamide
  参考文献：
  名称：

  Discovery of N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides as Novel AXL Kinase Inhibitors

  摘要：

  The overexpression of AXL kinase has been described in many types of cancer. Due to its role in proliferation, survival, migration, and resistance, AXL represents a promising target in the treatment of the disease. In this study we present a novel compound family that successfully targets the AXL kinase. Through optimization and detailed SAR studies we developed low nanomolar inhibitors, and after further biological characterization we identified a potent AXL kinase inhibitor with favorable pharmacokinetic profile. The antitumor activity was determined in xenograft models, and the lead compounds reduced the tumor size by 40% with no observed toxicity as well as lung metastasis formation by 66% when compared to vehicle control.

  DOI：

  10.1021/acs.jmedchem.8b00672

文献信息

• [EN] QUINOLINE DERIVATIVES AS AXL KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE QUINOLINES UTILISÉS COMME INHIBITEURS DES KINASES AXL
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2009127417A1

  公开（公告）日：2009-10-22

  The present invention relates to novel compounds which are inhibitors of receptor tyrosine kinases of the AXL receptor family. These compounds are suitable for the treatment or prevention of disorders associated with, accompanied by or caused by hyperfunction of a receptor of the AXL family. The compounds are suitable for the treatment of hyperproliferative disorders, such as cancer, particularly cancer metastases.

  本发明涉及一种新型化合物，它们是AXL受体家族的受体酪氨酸激酶抑制剂。这些化合物适用于治疗或预防与AXL家族受体的受体功能亢进相关、伴随或引起的疾病。这些化合物适用于治疗增生性疾病，如癌症，特别是癌症转移。
• QUINOLINE DERIVATIVES AS AXL KINASE INHIBITORS
  申请人：Ullrich Axel

  公开号：US20110092503A1

  公开（公告）日：2011-04-21

  Novel compounds which are inhibitors of receptor tyrosine kinases of the AXL receptor family are described herein. These compounds are suitable for the treatment or prevention of disorders associated with, accompanied by or caused by hyperfunction of a receptor of the AXL family. The compounds are suitable for the treatment of hyperproliferative disorders, such as cancer, particularly cancer metastases.

  本文介绍了一种抑制AXL受体家族的受体酪氨酸激酶的新型化合物。这些化合物适用于治疗或预防与AXL家族受体的受体高功能相关、伴随或引起的疾病。这些化合物适用于治疗增生性疾病，如癌症，特别是癌症转移。
• US9206130B2
  申请人：——

  公开号：US9206130B2

  公开（公告）日：2015-12-08
• Discovery of <i>N</i>-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides as Novel AXL Kinase Inhibitors
  作者：István Szabadkai、Robert Torka、Rita Garamvölgyi、Ferenc Baska、Pál Gyulavári、Sándor Boros、Eszter Illyés、Axel Choidas、Axel Ullrich、László Őrfi

  DOI：10.1021/acs.jmedchem.8b00672

  日期：2018.7.26

  The overexpression of AXL kinase has been described in many types of cancer. Due to its role in proliferation, survival, migration, and resistance, AXL represents a promising target in the treatment of the disease. In this study we present a novel compound family that successfully targets the AXL kinase. Through optimization and detailed SAR studies we developed low nanomolar inhibitors, and after further biological characterization we identified a potent AXL kinase inhibitor with favorable pharmacokinetic profile. The antitumor activity was determined in xenograft models, and the lead compounds reduced the tumor size by 40% with no observed toxicity as well as lung metastasis formation by 66% when compared to vehicle control.