(4-bromo-2-fluoro-phenyl)-[7-(2-methoxy-ethoxy)-6-nitro-quinazolin-4-yl]-amine | 936556-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (4-bromo-2-fluoro-phenyl)-[7-(2-methoxy-ethoxy)-6-nitro-quinazolin-4-yl]-amine
• 英文别名: N-(4-bromo-2-fluorophenyl)-7-(2-methoxyethoxy)-6-nitroquinazolin-4-amine
• CAS: 936556-33-1
• 化学式: C₁₇H₁₄BrFN₄O₄
• 分子量: 437.225
• InChiKey: NSYFAIDIZLQWQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4-bromo-2-fluoro-phenyl)-[7-(2-methoxy-ethoxy)-6-nitro-quinazolin-4-yl]-amine 在 铁粉 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 7.0h， 生成
  参考文献：
  名称：

  Structure-activity study of quinazoline derivatives leading to the discovery of potent EGFR-T790M inhibitors

  摘要：

  We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.026
• 作为产物：
  描述：

  4-氯-7-氟-6-硝基喹唑啉 在 sodium hydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 (4-bromo-2-fluoro-phenyl)-[7-(2-methoxy-ethoxy)-6-nitro-quinazolin-4-yl]-amine
  参考文献：
  名称：

  Structure-activity study of quinazoline derivatives leading to the discovery of potent EGFR-T790M inhibitors

  摘要：

  We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.026

文献信息

• Quinazoline Derivatives as a Multiplex Inhibitor and Method For the Preparation Thereof
  申请人：Ahn Young-Gil

  公开号：US20080318950A1

  公开（公告）日：2008-12-25

  The present invention relates to a novel quinazoline derivative and a pharmaceutically acceptable salt thereof as a multiplex inhibitor, a method for the preparation thereof, and a pharmaceutical composition and a therapeutic composition comprising same as an active ingredient. The inventive quinazoline derivative as a multiplex inhibitor can selectively and effectively inhibit diseases caused by the overactivity of a tyrosine kinase.

  本发明涉及一种新型喹唑啉衍生物及其药学上可接受的盐，作为多重抑制剂，其制备方法，以及包含其作为活性成分的药物组合物和治疗组合物。发明的喹唑啉衍生物作为多重抑制剂可以选择性和有效地抑制由酪氨酸激酶过度活性引起的疾病。
• QUINAZOLINE DERIVATIVES AS A MULTIPLEX INHIBITOR AND METHOD FOR THE PREPARATION THEREOF
  申请人：Hanmi Pharm. Co., Ltd.

  公开号：EP1951686A1

  公开（公告）日：2008-08-06
• US8846699B2
  申请人：——

  公开号：US8846699B2

  公开（公告）日：2014-09-30
• [EN] QUINAZOLINE DERIVATIVES AS A MULTIPLEX INHIBITOR AND METHOD FOR THE PREPARATION THEREOF<br/>[FR] DÉRIVÉS DE QUINAZOLINE EN TANT QU'INHIBITEURS MULTIPLEX ET MÉTHODE DE SYNTHÈSE DESDITS DÉRIVÉS
  申请人：HANMI PHARM IND CO LTD

  公开号：WO2007055514A1

  公开（公告）日：2007-05-18

  [EN] The present invention relates to a novel quinazoline derivative and a pharmaceutically acceptable salt thereof as a multiplex inhibitor, a method for the preparation thereof, and a pharmaceutical composition and a therapeutic composition comprising same as an active ingredient. The inventive quinazoline derivative as a multiplex inhibitor can selectively and effectively inhibit diseases caused by the overactivity of a tyrosine kinase.
  [FR] La présente invention concerne un nouveau dérivé de quinazoline et un sel de qualité pharmaceutique dudit dérivé pouvant être employés en tant qu'inhibiteurs multiplex, ainsi qu'une méthode de synthèse desdits composés et une préparation pharmaceutique ou thérapeutique comprenant lesdits composés au titre de principes actifs. Le dérivé de quinazoline pouvant être utilisé en tant qu'inhibiteur multiplex selon l'invention peut inhiber de façon sélective et efficace des maladies provoquées par la suractivité d'une tyrosine kinase.
• Structure-activity study of quinazoline derivatives leading to the discovery of potent EGFR-T790M inhibitors
  作者：Long Zhang、Yingying Yang、Haojie Zhou、Qingmei Zheng、Yuhao Li、Shansong Zheng、Shuyong Zhao、Dong Chen、Chuanwen Fan

  DOI：10.1016/j.ejmech.2015.08.026

  日期：2015.9

  We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies. (C) 2015 Elsevier Masson SAS. All rights reserved.