(4-bromo-2-fluoro-phenyl)-(7-fluoro-6-nitro-quinazolin-4-yl)-amine | 936548-94-6

• 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-fluoro-6-nitro-quinazolin-4-yl)-amine
• 英文别名: N-(4-bromo-2-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine
• CAS: 936548-94-6
• 化学式: C₁₄H₇BrF₂N₄O₂
• 分子量: 381.136
• InChiKey: WPYPZHLMXWTDME-UHFFFAOYSA-N

物化性质

• 沸点：
  479.8±45.0 °C(Predicted)
• 密度：
  1.793±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4-bromo-2-fluoro-phenyl)-(7-fluoro-6-nitro-quinazolin-4-yl)-amine 在 铁粉 、 sodium hydride 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 6.0h， 生成 4-N-(4-bromo-2-fluorophenyl)-7-[(3S)-oxolan-3-yl]oxyquinazoline-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
• 作为产物：
  描述：

  7-氟-6-硝基-4-羟基喹唑啉 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 (4-bromo-2-fluoro-phenyl)-(7-fluoro-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。
• [EN] 4-(SUBSTITUTED PHENYLAMINO)QUINAZOLINE DERIVATIVE AND PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION AND USE THEREOF<br/>[FR] DÉRIVÉ DE 4-(PHÉNYLAMINO SUBSTITUÉ)QUINAZOLINE ET SON PROCÉDÉ DE PRÉPARATION, COMPOSITION PHARMACEUTIQUE ET SON UTILISATION
  申请人：QILU PHARMACEUTICAL CO LTD

  公开号：WO2012136099A1

  公开（公告）日：2012-10-11

  本发明涉及4-(取代苯氨基)喹唑啉衍生物及其制备方法、药物组合物和用途。具体地说，本发明涉及式I化合物或其药学上可接受的盐或溶剂合物，其中，R1、R2和R3的定义如说明书和权利要求书中所述。本发明还涉及式I化合物的制备方法，包括它的药物组合物以及它们的制药用途。本发明的式I化合物是有效的酪氨酸激酶不可逆抑制剂。
• WO2007/55514
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of 4-Anilinoquinazoline-Derivative Dual Kinase Inhibitors Targeting EGFR and VEGFR-2
  作者：Keuk Chan Bang、Tae Hun Song、Young Jin Park、Jong Soo Lee、Seungah Jun、Seung Hyun Jung、Young-Jin Chun、Ha Hyung Kim

  DOI：10.1002/bkcs.11348

  日期：2018.1
• WO2007/55513
  申请人：——

  公开号：——

  公开（公告）日：——