N⁴-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamine

• 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: N⁴-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamine
• 英文别名: 4-N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-7-(2-methoxyethoxy)quinazoline-4,6-diamine
• 化学式: C₂₄H₂₂ClFN₄O₃
• 分子量: 468.915
• InChiKey: OOJDORSQUJWSFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  91.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N⁴-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamine 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (E)-N-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-(2-methoxyethoxy)quinazolin-6-yl)-4-(dimethylamino)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
• 作为产物：
  描述：

  4-氯-7-氟-6-硝基喹唑啉 在 铁粉 、 sodium hydride 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙腈 为溶剂， 反应 6.0h， 生成 N⁴-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamine
  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 AND QUINOLINE DERIVATIVES AS IRREVERSIBLE PROTEIN TYROSINE KINASE INHIBITORS
  申请人：ZHANG Hesheng

  公开号：US20090105247A1

  公开（公告）日：2009-04-23

  A compound of formula (I), a pharmaceutically acceptable salt, or hydrate thereof, and a method of preparing the same. A method of treating or preventing a physiological disorder caused by abnormal protein tyrosine kinase activity in a mammal comprising administering to said mammal a pharmaceutical composition comprising a compound of formula (I).

  公式（I）的化合物，其药用盐或水合物，以及制备该化合物的方法。一种治疗或预防哺乳动物中由异常蛋白酪氨酸激酶活性引起的生理紊乱的方法，包括向该哺乳动物施用包含公式（I）化合物的药物组合物。
• Quinazoline Derivatives For Inhibiting Cancer Cell Growth And Method For The Preparation Thereof
  申请人：Ham Young Jin

  公开号：US20080009509A1

  公开（公告）日：2008-01-10

  The present invention relates to a novel quinazoline derivative and a pharmaceutically acceptable salt thereof for inhibiting the growth of cancer cells, a method for the preparation thereof and a pharmaceutical composition comprising same as an active ingredient.

  本发明涉及一种新型的喹唑啉衍生物及其药学上可接受的盐，用于抑制癌细胞的生长，其制备方法以及包含其作为活性成分的制药组合物。
• METHODS OF PREPARING AND USING QUINAZOLINE AND QUINOLINE DERIVATIVES
  申请人：ZHANG Hesheng

  公开号：US20120225872A1

  公开（公告）日：2012-09-06

  A method of preparing a compound of formula (I), A method for treating cancer or inhibiting growth of cancer cells including administering to a patient mammal in need thereof a pharmaceutical preparation including the compound. A method of treating or preventing a physiological disorder caused by abnormal protein tyrosine kinase activity in a mammal including administering to a mammal a pharmaceutical preparation including the compound.

  一种制备化合物(I)的方法，一种治疗癌症或抑制癌细胞生长的方法，包括向需要治疗的哺乳动物患者给予包含该化合物的制药制剂。一种治疗或预防哺乳动物中由异常蛋白酪氨酸激酶活性引起的生理障碍的方法，包括向哺乳动物给予包含该化合物的制药制剂。
• QUINAZOLINE DERIVATIVES FOR INHIBITING CANCER CELL GROWTH AND METHOD FOR THE PREPARATION THEREOF
  申请人：Hanmi Pharm. Co., Ltd.

  公开号：EP1844022A1

  公开（公告）日：2007-10-17
• JP2008525522A
  申请人：——

  公开号：JP2008525522A

  公开（公告）日：2008-07-17