1-(4-amino-2-chlorophenyl)-3-(3-fluorophenyl)urea | 1184753-52-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-amino-2-chlorophenyl)-3-(3-fluorophenyl)urea
• CAS: 1184753-52-3
• 化学式: C₁₃H₁₁ClFN₃O
• 分子量: 279.701
• InChiKey: DOCLLBLIENHYAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Chloro-7-((1-methylpiperidin-4-yl)methoxy)quinazoline 、 1-(4-amino-2-chlorophenyl)-3-(3-fluorophenyl)urea 以 异丙醇 为溶剂， 反应 2.0h， 生成 1-[2-Chloro-4-[[7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-yl]amino]phenyl]-3-(3-fluorophenyl)urea
  参考文献：
  名称：

  Design, synthesis and antitumor activity of 4-aminoquinazoline derivatives targeting VEGFR-2 tyrosine kinase

  摘要：

  We report herein the design and synthesis of novel 4-aminoquinazoline derivatives based on the inhibitors of VEGFR-2 tyrosine kinases. The VEGFR-2 inhibitory activities of these newly synthesized compounds were also evaluated and compared with that of ZD6474. We found that most of target compounds had good inhibitory potency. In particular, compounds 1h, 1n and 1o were found to be 6, 2 and 2-fold more potent than the positive control ZD6474. The leading compound 1h also showed an in vivo activity against HepG2 human tumor xenograft model in BALB/c-nu mice. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.061
• 作为产物：
  描述：

  2-氯-4-异氰酸硝基苯 在 甲醇 、 palladium on activated charcoal 作用下， 生成 1-(4-amino-2-chlorophenyl)-3-(3-fluorophenyl)urea
  参考文献：
  名称：

  Design, synthesis and antitumor activity of 4-aminoquinazoline derivatives targeting VEGFR-2 tyrosine kinase

  摘要：

  We report herein the design and synthesis of novel 4-aminoquinazoline derivatives based on the inhibitors of VEGFR-2 tyrosine kinases. The VEGFR-2 inhibitory activities of these newly synthesized compounds were also evaluated and compared with that of ZD6474. We found that most of target compounds had good inhibitory potency. In particular, compounds 1h, 1n and 1o were found to be 6, 2 and 2-fold more potent than the positive control ZD6474. The leading compound 1h also showed an in vivo activity against HepG2 human tumor xenograft model in BALB/c-nu mice. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.061

文献信息

• Discovery of a novel class anti-proliferative agents and potential inhibitors of EGFR tyrosine kinases based on 4-anilinotetrahydropyrido[4,3-d]pyrimidine scaffold: Design, synthesis and biological evaluations
  作者：Yong Zhang、Kai Zhang、Meng Zhao、Lixia Zhang、Mingze Qin、Shuchun Guo、Yanfang Zhao、Ping Gong

  DOI：10.1016/j.bmc.2015.05.059

  日期：2015.8

  13c, 13n, 13o, 13p, 13r, 13s, 13u and 24c obviously. By evaluation of inhibiting EGFR and HER2 kinases, seven compounds (13b, 13g, 13n, 13o, 13p, 13r and 13s) showed stronger EGFR potency with IC50 ⩽ 18 nM, which could also be understood by preliminary docking study of 13b with EGFR kinase. In view of the primary SAR, bisarylaniline derivatives (13o, 13p, 13r and 13s) showed obvious improvements on

  设计，合成了一系列新颖的4-芳基氨基-6 / 7-取代的5,6,7,8-四氢吡啶并[4,3- d ]嘧啶类化合物，它们作为潜在的抗增殖剂和EGFR激酶抑制剂具有生物活性被评估。THPPs中的N-丙烯酰胺片段和带有取代基的4-苯胺基团都起着关键作用，因为它们对四种癌细胞系（HT29，A549，H460和H1975）具有显着的抗增殖活性。吉非替尼抗性的H1975尤其抑制活性显示更有利的，这可从化合物可以观察到图13B，13C，13N，13O，13P，13R，13S，13u和24c显然。通过抑制EGFR和HER2激酶，七种化合物（评价13B，13克，13N，13O，13P，13R和13S）显示更强的EGFR效力与IC 50  ⩽18纳米，这也可以通过初步对接研究理解13b中与EGFR激酶。鉴于原发性SAR，双芳基苯胺衍生物（13o，13p，13r和13s）显示出对HER2抑制的明显改善，表明它们是潜在的EGFR
• Urea-substituted aromatic ring-linked dioxane-quinazoline and -linked dioxane-quinoline compounds, preparation method therefor and use thereof
  申请人：BEIJING SCITECH-MQ PHARMACEUTICALS LIMITED

  公开号：US10980809B2

  公开（公告）日：2021-04-20

  The present invention relates to a urea-substituted aromatic ring-linked dioxinoquinazoline and a urea-substituted aromatic ring-linked dioxinoquinoline of Formula (I), or a pharmaceutically acceptable salt thereof or a hydrate thereof. Also provided are the preparation of the compound as shown in Formula (I) and the pharmaceutically acceptable salt thereof and the use thereof as a drug. The drug is used as an inhibitor of tyrosine kinases (e.g., VEGFR-2, C-RAF, B-RAF) for treating tyrosine kinase-related diseases.

  本发明涉及一种脲取代的芳环连二噁喹唑啉和一种脲取代的芳环连二噁喹唑啉的式(I)，或其药学上可接受的盐或其水合物。还提供了式 (I) 所示化合物及其药学上可接受的盐的制备方法及其作为药物的用途。该药物用作酪氨酸激酶（如VEGFR-2、C-RAF、B-RAF）的抑制剂，用于治疗酪氨酸激酶相关疾病。
• UREA-SUBSTITUTED AROMATIC RING-LINKED DIOXANE-QUINAZOLINE AND -LINKED DIOXANE-QUINOLINE COMPOUNDS, PREPARATION METHOD THEREFOR AND USE THEREOF
  申请人：BEIJING SCITECH-MQ PHARMACEUTICALS LIMITED

  公开号：US20200061065A1

  公开（公告）日：2020-02-27

  The present invention relates to a urea-substituted aromatic ring-linked dioxinoquinazoline and a urea-substituted aromatic ring-linked dioxinoquinoline of Formula (I), or a pharmaceutically acceptable salt thereof or a hydrate thereof. Also provided are the preparation of the compound as shown in Formula (I) and the pharmaceutically acceptable salt thereof and the use thereof as a drug. The drug is used as an inhibitor of tyrosine kinases (e.g., VEGFR-2, C-RAF, B-RAF) for treating tyrosine kinase-related diseases.