N-(3-fluoro-4-{6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yloxy}phenyl)-2-trifluoromethylbenzenesulfonamide | 1292258-13-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-fluoro-4-{6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yloxy}phenyl)-2-trifluoromethylbenzenesulfonamide
• 英文别名: N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]-2-(trifluoromethyl)benzenesulfonamide
• CAS: 1292258-13-9
• 化学式: C₃₁H₃₂F₄N₄O₅S
• 分子量: 648.678
• InChiKey: GGVWIGDCUUVFSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  4-(2-氟-4-硝基苯氧基)-6-甲氧基-7-羟基喹啉 在 吡啶 、 氯化铵 、 caesium carbonate 、 potassium iodide 、 锌 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 78.75h， 生成 N-(3-fluoro-4-{6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yloxy}phenyl)-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] QUINOLINYLOXYPHENYLSULFONAMIDES<br/>[FR] QUINOLINYLOXYPHÉNYLSULFONAMIDES
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2011045084A1

  公开（公告）日：2011-04-21

  The present invention relates to quinolinyloxyphenylsulfonamides and stereoisomeric forms, solvates, hydrates and/or pharmaceutically acceptable salts of these quinolinyloxyphenylsulfonamide compounds as well as pharmaceutical compositions containing at least one of these compounds together with at least one pharmaceutically acceptable carrier, excipient and/or diluent. Said quinolinyloxyphenylsulfonamides are useful for prophylaxsis, treatment and/or after-treatment of hyperproliferative disorders, such as cancer, tumors and particularly cancer metastases.

  本发明涉及喹啉氧基苯磺酰胺及其立体异构体形式、溶剂化物、水合物和/或这些喹啉氧基苯磺酰胺化合物的药学上可接受的盐，以及含有至少一种这些化合物和至少一种药学上可接受的载体、赋形剂和/或稀释剂的制剂。所述喹啉氧基苯磺酰胺对于预防、治疗和/或后治疗增生性疾病，如癌症、肿瘤，特别是癌症转移，具有有用的作用。
• Quinolinyloxyphenylsulfonamides
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2311809A1

  公开（公告）日：2011-04-20

  The present invention relates to quinolinyloxyphenylsulfonamides and stereoisomeric forms, prodrugs, solvates, hydrates and/or pharmaceutically acceptable salts of these quinolinyloxyphenylsulfonamide compounds as well as pharmaceutical compositions containing at least one of these compounds together with at least one pharmaceutically acceptable carrier, excipient and/or diluent. Said quinolinyloxyphenylsulfonamides are useful for prophylaxsis, treatment and/or after-treatment of hyperproliferative disorders, such as cancer, tumors and particularly cancer metastases.

  本发明涉及喹啉氧基苯磺酰胺及其立体异构体、前药、溶剂化物、水合物和/或药学上可接受的盐，以及包含至少一种这些化合物和至少一种药学上可接受的载体、赋形剂和/或稀释剂的制药组合物。所述喹啉氧基苯磺酰胺对于预防、治疗和/或后治疗增殖过度的疾病，如癌症、肿瘤，尤其是癌症转移，是有用的。
• QUINOLINYLOXYPHENYLSULFONAMIDES
  申请人：Ullrich Axel

  公开号：US20120277231A1

  公开（公告）日：2012-11-01

  The present invention relates to quinolinyloxyphenylsulfonamides and stereoisomeric forms, solvates, hydrates and/or pharmaceutically acceptable salts of these quinolinyloxyphenylsulfonamide compounds as well as pharmaceutical compositions containing at least one of these compounds together with at least one pharmaceutically acceptable carrier, excipient and/or diluent. Said quinolinyloxyphenylsulfonamides are useful for prophylaxsis, treatment and/or after-treatment of hyperproliferative disorders, such as cancer, tumors and particularly cancer metastases.

  本发明涉及喹啉氧基苯磺酰胺及其立体异构体、溶剂化物、水合物和/或药学上可接受的盐，以及至少包含其中一种化合物和至少一种药学上可接受的载体、赋形剂和/或稀释剂的制药组合物。所述喹啉氧基苯磺酰胺对于预防、治疗和/或后治疗增生性疾病，如癌症、肿瘤和特别是癌症转移，具有有用的作用。
• US9169241B2
  申请人：——

  公开号：US9169241B2

  公开（公告）日：2015-10-27
• 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.