(E)-N-(4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide | 1430203-46-5

• 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: (E)-N-(4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide
• 英文别名: (E)-N-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide
• CAS: 1430203-46-5
• 化学式: C₂₆H₂₇N₅O₂
• 分子量: 441.533
• InChiKey: NAVGIMRWOWYNEP-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-7-氟-6-硝基喹唑啉 在 铁粉 、 sodium hydride 、 potassium carbonate 、 氯化铵 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.0h， 生成 (E)-N-(4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide
  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

• [EN] QUINAZOLINE DERIVATIVES AS KINASES INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS DE QUINAZOLINE EN TANT QU'INHIBITEURS DE KINASES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：TELIGENE LTD

  公开号：WO2013053206A1

  公开（公告）日：2013-04-18

  Disclosed are quinazolines of formula (I), pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

  本发明揭示了式(I)的喹唑啉化合物，其药学上可接受的盐、溶剂和水合物。这些化合物具有蛋白激酶抑制活性，并预计可用于治疗蛋白激酶介导的疾病和病状。
• QUINAZOLINE DERIVATIVES AS KINASES INHIBITORS AND METHODS OF USE THEREOF
  申请人：TELIGENE LTD.

  公开号：US20140235658A1

  公开（公告）日：2014-08-21

  The present invention is directed to novel quinazolines, their derivatives, pharmaceutically acceptable salts, solvates, prodrug, stereoisomer, tautomer, metabolite and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

  本发明涉及新型喹唑啉、其衍生物、药学上可接受的盐、溶剂化合物、前药、立体异构体、互变异构体、代谢物和水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，并可望用于治疗蛋白激酶介导的疾病和病况。
• US9388160B2
  申请人：——

  公开号：US9388160B2

  公开（公告）日：2016-07-12
• 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.