4-(3'-chloro-4'-fluorophenylamino)-6-[3-(2-oxa-6-azaspiro[3.4]octane-6-yl)propoxy]-7-methoxyquinazoline | 1445860-68-3

• 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-(3'-chloro-4'-fluorophenylamino)-6-[3-(2-oxa-6-azaspiro[3.4]octane-6-yl)propoxy]-7-methoxyquinazoline
• 英文别名: N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(2-oxa-7-azaspiro[3.4]octan-7-yl)propoxy]quinazolin-4-amine
• CAS: 1445860-68-3
• 化学式: C₂₄H₂₆ClFN₄O₃
• 分子量: 472.947
• InChiKey: YXQNVWQALXLRKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  68.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  吉非替尼中间体B 在 potassium carbonate 、 丙酮 、 potassium iodide 作用下， 生成 4-(3'-chloro-4'-fluorophenylamino)-6-[3-(2-oxa-6-azaspiro[3.4]octane-6-yl)propoxy]-7-methoxyquinazoline
  参考文献：
  名称：

  Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

  摘要：

  We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4] octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.049

文献信息

• Heterocycle Amido Alkyloxy Substituted Quinazoline Derivative and Use Thereof
  申请人：Qian Wei

  公开号：US20140206664A1

  公开（公告）日：2014-07-24

  Heterocycle amino alkyloxy substituted quinazoline derivatives as represented by the structural Formula (I) and pharmaceutically acceptable salts thereof, capable of inhibiting the activity of receptor tyrosine kinase EGFR, and being used to treat cancers related to the expression of the receptor tyrosine kinase of the ErbB family are provided.

  本发明提供了异环氨基烷氧基取代的喹唑啉衍生物，其结构式表示为(I)，以及其药学上可接受的盐，能够抑制受体酪氨酸激酶EGFR的活性，并用于治疗与ErbB家族受体酪氨酸激酶表达相关的癌症。
• [EN] HETEROCYCLE AMIDO ALKYLOXY SUBSTITUTED QUINAZOLINE DERIVATIVE AND USE THEREOF<br/>[FR] DÉRIVÉ HÉTÉROCYCLIQUE DE QUINAZOLINE SUBSTITUÉ PAR UN AMIDO-ALKYLOXY ET SON UTILISATION
  申请人：QIAN WEI

  公开号：WO2013091507A1

  公开（公告）日：2013-06-27

  一种结构如（I）的杂环胺基烷氧基取代的喹唑啉衍生物及其药学上可接受的盐，具有抑制受体酪氨酸激酶EGFR的活性，可用于与ErbB家族的受体酪氨酸激酶表达相关的癌症的治疗。
• HETEROCYCLE AMIDO ALKYLOXY SUBSTITUTED QUINAZOLINE DERIVATIVE AND USE THEREOF
  申请人：Qian, Wei

  公开号：EP2796451B1

  公开（公告）日：2018-08-01
• US9546179B2
  申请人：——

  公开号：US9546179B2

  公开（公告）日：2017-01-17
• Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors
  作者：Feng Zhao、Zhaohu Lin、Feng Wang、Weili Zhao、Xiaochun Dong

  DOI：10.1016/j.bmcl.2013.07.049

  日期：2013.10

  We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4] octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility. (C) 2013 Elsevier Ltd. All rights reserved.