tert-butyl N-[3-[[4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-7-quinolyl]oxy]propyl]carbamate | 1361031-47-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl N-[3-[[4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-7-quinolyl]oxy]propyl]carbamate
• 英文别名: {3-[4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-yloxy]propyl}carbamic acid tert-butyl ester；tert-butyl N-[3-[4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-yl]oxypropyl]carbamate
• CAS: 1361031-47-1
• 化学式: C₂₄H₂₆FN₃O₇
• 分子量: 487.485
• InChiKey: VCOXOGPUYUFNKX-UHFFFAOYSA-N

物化性质

• 沸点：
  617.7±55.0 °C(Predicted)
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[3-[[4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-7-quinolyl]oxy]propyl]carbamate 在 吡啶 、 盐酸 、 氯化铵 、 锌 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 79.0h， 生成 N-{4-[7-(3-aminopropoxy)-6-methoxyquinolin-4-yloxy]-3-fluorophenyl}-2,5-difluorobenzenesulfonamide hydrochloride
  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：

  4-(2-氟-4-硝基苯氧基)-6-甲氧基-7-(苄氧基)喹啉 在 氢溴酸 、 caesium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 29.75h， 生成 tert-butyl N-[3-[[4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-7-quinolyl]oxy]propyl]carbamate
  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

• Pharmaceutically active compounds as Axl inhibitors
  申请人：Lead Discovery Center GmbH

  公开号：EP2423208A1

  公开（公告）日：2012-02-29

  The present invention relates to 1-nitrogen-heterocyclic-2-carboxamides of general formula (I): and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the treatment and/or prevention of Axl receptor tyrosine kinase subfamily induced disorders, including cancer and primary tumor metastases, and pharmaceutical compositions containing at least one of said 1-nitrogen-heterocyclic-2-carboxamide derivatives and/or pharmaceutically acceptable salts thereof.

  本发明涉及一般式(I)的1-氮杂环-2-羧酰胺及/或其药学上可接受的盐，这些衍生物作为药理活性剂的用途，特别用于治疗和/或预防Axl受体酪氨酸激酶亚家族引起的疾病，包括癌症和原发性肿瘤转移，以及含有至少一种上述1-氮杂环-2-羧酰胺衍生物和/或其药学上可接受的盐的药物组合物。
• PHARMACEUTICALLY ACTIVE COMPOUNDS AS AXL INHIBITORS
  申请人：Schultz-Fademrecht Carsten

  公开号：US20140018365A1

  公开（公告）日：2014-01-16

  The present invention relates to 1-nitrogen-heterocyclic-2-carboxamides and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the treatment and/or prevention of Axl receptor tyrosine kinase subfamily induced disorders, including cancer and primary tumor metastases, and pharmaceutical compositions containing at least one of said 1-nitrogen-heterocyclic-2-carboxamide derivatives and/or pharmaceutically acceptable salts thereof.

  本发明涉及1-氮杂环-2-羧酰胺和/或其药学上可接受的盐，这些衍生物被用作药物活性剂，特别用于治疗和/或预防Axl受体酪氨酸激酶亚家族引起的疾病，包括癌症和原发性肿瘤转移，以及含有至少一种所述的1-氮杂环-2-羧酰胺衍生物和/或其药学上可接受的盐的制药组合物。
• [EN] PHARMACEUTICALLY ACTIVE COMPOUNDS AS AXL INHIBITORS<br/>[FR] COMPOSÉS PHARMACEUTIQUEMENT ACTIFS EN TANT QU'INHIBITEURS DE AXL
  申请人：LEAD DISCOVERY CENTER GMBH

  公开号：WO2012028332A8

  公开（公告）日：2013-03-07
• US8999982B2
  申请人：——

  公开号：US8999982B2

  公开（公告）日：2015-04-07
• 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.