6-bromo-N-(3-fluorophenyl)quinazolin-4-amine | 929411-71-2

• 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: 6-bromo-N-(3-fluorophenyl)quinazolin-4-amine
• CAS: 929411-71-2
• 化学式: C₁₄H₉BrFN₃
• 分子量: 318.148
• InChiKey: ALKMBIXEONKULX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 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：
  37.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-bromo-N-(3-fluorophenyl)quinazolin-4-amine 、 三丁基噻唑-5-锡 在 copper(l) iodide 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 N-(3-fluorophenyl)-6-(thiazol-5-yl)quinazolin-4-amine
  参考文献：
  名称：

  Discovery, Synthesis, and Biological Evaluation of Thiazoloquin(az)olin(on)es as Potent CD38 Inhibitors

  摘要：

  A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasma, liver, and muscle tissue. In particular, compound 78c was given to diet induced obese (DIO) C57Bl6 mice, elevating NAD > 5-fold in liver and >1.2-fold in muscle versus control animals at a 2 h time point. The compounds described herein possess the most potent CD38 inhibitory activity of any small molecules described in the literature to date. The inhibitors should allow for a more detailed assessment of how NAD elevation via CD38 inhibition affects physiology in NAD deficient states.

  DOI：

  10.1021/jm502009h
• 作为产物：
  描述：

  6-溴-4-羟基喹唑啉 在 盐酸 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 5.0h， 生成 6-bromo-N-(3-fluorophenyl)quinazolin-4-amine
  参考文献：
  名称：

  4-（卤代苯胺基）-6-溴喹唑啉及其6-（4-氟苯基）取代衍生物作为表皮生长因子受体酪氨酸激酶的潜在抑制剂的合成及体外细胞毒性

  摘要：

  评估了一系列2-未取代和2-（4-氯苯基）-取代的4-苯胺基-6-溴喹唑啉及其6-（4-氟苯基）-取代的衍生物对MCF-7和HeLa细胞的体外细胞毒性。2-未取代的4-苯胺基-6-溴喹唑啉缺乏活性，而发现它们的大多数2-（4-氯苯基）取代的衍生物对HeLa细胞显示出显着的细胞毒性和选择性。与吉非替尼相比，用2-氟苯基取代2-未取代的4-苯胺基喹唑啉的溴导致对HeLa细胞的优异活性。除了3-氯苯胺基衍生物以外，在2-（4-氯苯基）取代的衍生物中存在4-氟苯基导致对HeLa细胞的细胞毒性增加。活性最高的化合物3g，3l和4l 被发现对表皮生长因子受体酪氨酸激酶（EGFR-TK）表现出中度至显着的抑制作用。EGFR分子对接模型表明这些化合物与EGFR区域结合良好。

  DOI：

  10.3390/ph10040087

文献信息

• Design, synthesis and biological evaluation of novel 4-aminoquinazolines as dual target inhibitors of EGFR-PI3Kα
  作者：Huai-Wei Ding、Cheng-Long Deng、Dan-Dan Li、Dan-Dan Liu、Shao-Meng Chai、Wei Wang、Yan Zhang、Kai Chen、Xin Li、Jian Wang、Shao-Jiang Song、Hong-Rui Song

  DOI：10.1016/j.ejmech.2018.01.081

  日期：2018.2

  dual-target drugs against EGFR and PI3K has therapeutic advantage and was an attractive approach against tumors. In this work, based on the molecular docking and previous studies, a series of 4-aminoquinazolines derivatives containing 6-sulfonamide substituted pyridyl group were rationally designed and identified as potent EGFR and PI3K dual inhibitors. The cytotoxicity experiment results showed that

  EGFR的过表达与疾病的快速进展，对化学疗法的抗性和不良的预后有关。在某些人类癌症中，PI3K与EGFR协同作用以促进增殖，存活，侵袭和转移。针对EGFR和PI3K的双重靶标药物的开发具有治疗优势，并且是对抗肿瘤的一种有吸引力的方法。在这项工作中，基于分子对接和先前的研究，合理设计了一系列含有6-磺酰胺取代的吡啶基的4-氨基喹唑啉衍生物并将其鉴定为有效的EGFR和PI3K双重抑制剂。细胞毒性实验结果表明，该系列化合物可以有效抑制细胞生长。激酶测定表明6c和6i与其他同工型不同，对EGFR具有很高的抑制作用，对PI3Kα的选择性也很高。进一步的实验表明6c可以诱导G1期细胞周期停滞和BT549细胞凋亡。蛋白质印迹分析表明6c通过EGFR和PI3Kα/ Akt信号通路抑制了BT549细胞的增殖。我们的研究表明化合物6c是EGFR和PI3Kα的潜在双重抑制剂。
• Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5
  作者：Andrew S. Felts、Sam A. Saleh、Uyen Le、Alice L. Rodriguez、C. David Weaver、P. Jeffrey Conn、Craig W. Lindsley、Kyle A. Emmitte

  DOI：10.1016/j.bmcl.2009.10.024

  日期：2009.12

  A high-throughput cell-based screen identified a series of 6-substituted-4-anilinoquinazolines as noncompetitive antagonists of metabotropic glutamate receptor 5 (mGlu(5)). This Letter describes the SAR of this series and the profile of selected compounds in selectivity and radioligand binding assays. (C) 2009 Elsevier Ltd. All rights reserved.
• Discovery, Synthesis, and Biological Evaluation of Thiazoloquin(az)olin(on)es as Potent CD38 Inhibitors
  作者：Curt D. Haffner、J. David Becherer、Eric E. Boros、Rodolfo Cadilla、Tiffany Carpenter、David Cowan、David N. Deaton、Yu Guo、Wallace Harrington、Brad R. Henke、Michael R. Jeune、Istvan Kaldor、Naphtali Milliken、Kim G. Petrov、Frank Preugschat、Christie Schulte、Barry G. Shearer、Todd Shearer、Terrence L. Smalley、Eugene L. Stewart、J. Darren Stuart、John C. Ulrich

  DOI：10.1021/jm502009h

  日期：2015.4.23

  A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasma, liver, and muscle tissue. In particular, compound 78c was given to diet induced obese (DIO) C57Bl6 mice, elevating NAD > 5-fold in liver and >1.2-fold in muscle versus control animals at a 2 h time point. The compounds described herein possess the most potent CD38 inhibitory activity of any small molecules described in the literature to date. The inhibitors should allow for a more detailed assessment of how NAD elevation via CD38 inhibition affects physiology in NAD deficient states.
• Synthesis and In Vitro Cytotoxicity of the 4-(Halogenoanilino)-6-bromoquinazolines and Their 6-(4-Fluorophenyl) Substituted Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor Tyrosine Kinase
  作者：Malose Mphahlele、Hugues Paumo、Yee Choong

  DOI：10.3390/ph10040087

  日期：——

  cells compared to Gefitinib. The presence of a 4-fluorophenyl group in the 2-(4-chlorophenyl) substituted derivatives led to increased cytotoxicity against HeLa cells, except for the 3-chloroanilino derivative. The most active compounds, namely, 3g, 3l, and 4l, were found to exhibit a moderate to significant inhibitory effect against epidermal growth factor receptor tyrosine kinase (EGFR-TK). The EGFR

  评估了一系列2-未取代和2-（4-氯苯基）-取代的4-苯胺基-6-溴喹唑啉及其6-（4-氟苯基）-取代的衍生物对MCF-7和HeLa细胞的体外细胞毒性。2-未取代的4-苯胺基-6-溴喹唑啉缺乏活性，而发现它们的大多数2-（4-氯苯基）取代的衍生物对HeLa细胞显示出显着的细胞毒性和选择性。与吉非替尼相比，用2-氟苯基取代2-未取代的4-苯胺基喹唑啉的溴导致对HeLa细胞的优异活性。除了3-氯苯胺基衍生物以外，在2-（4-氯苯基）取代的衍生物中存在4-氟苯基导致对HeLa细胞的细胞毒性增加。活性最高的化合物3g，3l和4l 被发现对表皮生长因子受体酪氨酸激酶（EGFR-TK）表现出中度至显着的抑制作用。EGFR分子对接模型表明这些化合物与EGFR区域结合良好。