3-fluoro-4-{[6-methoxy-7-(2-morpholinoethoxy)quinolin-4-yl]oxy}aniline

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-fluoro-4-{[6-methoxy-7-(2-morpholinoethoxy)quinolin-4-yl]oxy}aniline
• 英文别名: 3-Fluoro-4-[6-methoxy-7-(2-morpholin-4-ylethoxy)quinolin-4-yl]oxyaniline
• 化学式: C₂₂H₂₄FN₃O₄
• 分子量: 413.449
• InChiKey: YMRDVTUVQPOINJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  79.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-三氟甲基苯磺酰氯 、 3-fluoro-4-{[6-methoxy-7-(2-morpholinoethoxy)quinolin-4-yl]oxy}aniline 在 吡啶 作用下， 反应 72.0h， 以43%的产率得到N-{3-fluoro-4-[6-methoxy-7-(2-morpholin-4-ylethoxy)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
• 作为产物：
  描述：

  2-甲氧基-5-硝基苯酚 在 铁粉 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 邻二氯苯 、 甲苯 为溶剂， 反应 27.0h， 生成 3-fluoro-4-{[6-methoxy-7-(2-morpholinoethoxy)quinolin-4-yl]oxy}aniline
  参考文献：
  名称：

  发现带有喹啉部分的1,6-萘吡啶酮基MET激酶抑制剂是有希望的抗肿瘤药物候选物。

  摘要：

  基于卡博替尼和我们报道的化合物Ⅳ的结构，设计和合成了一系列在嵌段A中带有喹啉部分的基于1,6-萘啶酮的MET激酶抑制剂。广泛的SAR和DMPK研究导致了20j的鉴定，20j是一种具有良好激酶选择性的有效且口服可生物利用的MET激酶抑制剂。更重要的是，在U-87 MG异种移植模型中，20j表现出统计学上显着的肿瘤生长抑制作用（肿瘤生长抑制/ TGI为131％，部分消退/ PR为4/6），优于卡波替尼（TGI为97％， 2/6 PR），并且在相同剂量（12.5 mg / kg）时明显优于化合物IV（TGI为15％，0/6 PR）。结合良好的体外效能，激酶选择性，药代动力学特征和体内功效，

  DOI：

  10.1016/j.ejmech.2020.112174

文献信息

• [EN] URACIL DERIVATIVES AS AXL AND C-MET KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'URACILE COMME INHIBITEURS D'AXL ET C-MET KINASES
  申请人：CEPHALON INC

  公开号：WO2013074633A1

  公开（公告）日：2013-05-23

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salt forms thereof, wherein Ra, Rb, Rc, Rd, D, W, R1a, R1b, R1c,Y, R3, X, E and G are as defined herein, methods of treatment and uses thereof.

  本发明提供了式I的化合物，或其药用盐形式，其中Ra、Rb、Rc、Rd、D、W、R1a、R1b、R1c、Y、R3、X、E和G的定义如本文所述，以及其治疗方法和用途。
• [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。
• 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。
• URACIL DERIVATIVES AS AXL AND C-MET KINASE INHIBITORS
  申请人：Ignyta, Inc.

  公开号：US20150209358A1

  公开（公告）日：2015-07-30

  The present application provides compounds of Formula I or salt forms thereof, wherein R a , R b , R c , R d , D, W, R 1a , R 1b , R 1c , Y, R 3 , X, E and G are as defined herein, compositions, methods of treatment and uses thereof.

  本申请提供了I式化合物或其盐形式，其中Ra、Rb、Rc、Rd、D、W、R1a、R1b、R1c、Y、R3、X、E和G的定义如本文所述，以及其组合物、治疗方法和用途。