4-(3-chloro-4-fluorophenylamino)-6-(2-chloroethoxy)-7-methoxyquinazoline | 808793-73-9

• 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-(3-chloro-4-fluorophenylamino)-6-(2-chloroethoxy)-7-methoxyquinazoline
• 英文别名: 4-(3-chloro-4-fluorophenylamino)-7-methoxy-6-(2-chloroethoxy)quinazoline；4-[(3-chloro-4-fluoro-phenyl)amino]-6-(2-chloroethyloxy)-7-methoxy-quinazoline；6-(2-chloroethoxy)-N-(3-chloro-4-fluorophenyl)-7-methoxyquinazolin-4-amine
• CAS: 808793-73-9
• 化学式: C₁₇H₁₄Cl₂FN₃O₂
• 分子量: 382.221
• InChiKey: PZASIVTUYZPARF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-4-fluorophenylamino)-6-(2-chloroethoxy)-7-methoxyquinazoline 在 potassium carbonate 、 丙酮 、 potassium iodide 作用下， 生成 4-(3'-chloro-4'-fluorophenylamino)-6-[2-(2-oxa-6-azaspiro[3.3]heptane-6-yl)oxethyl]-7-methoxyquinazoline
  参考文献：
  名称：

  Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

  摘要：

  We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4] octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.049
• 作为产物：
  描述：

  methyl 2-amino-5-(2-chloroethoxy)-4-methoxybenzoate 在 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 异丙醇 、 甲苯 为溶剂， 生成 4-(3-chloro-4-fluorophenylamino)-6-(2-chloroethoxy)-7-methoxyquinazoline
  参考文献：
  名称：

  Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

  摘要：

  We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4] octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.049

文献信息

• 氮杂糖衍生化的喹唑啉类化合物
  申请人：陕西师范大学

  公开号：CN106892898B

  公开（公告）日：2021-02-05

  本发明属于药物化学领域，涉及一类氮杂糖衍生化的喹唑啉类化合物，具体涉及式I所示化合物、其制备方法、含有这些化合物的药物组合物、以及使用这些化合物和药物组合物在制备治疗肿瘤和糖尿病药物中的用途。这些化合物具有表皮生长因子受体酪氨酸激酶和α‑葡萄糖苷酶的双重抑制作用。
• Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
  申请人：Himmelsbach Frank

  公开号：US20060264450A1

  公开（公告）日：2006-11-23

  The present invention relates to bicyclic heterocycles of general formula wherein R a , R b , R c , R d , X and n are defined as in claim 1 , the tautomers, the stereoisomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids which have valuable pharmacological properties, particularly an inhibiting effect on the signal transduction mediated by tyrosine kinases, their use in treating diseases, particularly tumoral diseases, as well as benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract and the preparation thereof.

  本发明涉及一般式为的双环杂环化合物，其中Ra、Rb、Rc、Rd、X和n的定义如权利要求书中所述，其互变异构体、立体异构体、混合物及其盐，尤其是其与无机或有机酸的生理可接受盐，具有有价值的药理学特性，特别是对酪氨酸激酶介导的信号转导具有抑制作用，它们的用途在于治疗疾病，特别是肿瘤性疾病，以及良性前列腺增生症（BPH）、肺部和呼吸道疾病，以及其制备方法。
• Quinazoline-1-deoxynojirimycin hybrids as high active dual inhibitors of EGFR and α-glucosidase
  作者：Yaling Zhang、Hongliang Gao、Renjie Liu、Juan Liu、Li Chen、Xiabing Li、Lijun Zhao、Wei Wang、Baolin Li

  DOI：10.1016/j.bmcl.2017.08.035

  日期：2017.9

  A series of novel quinazoline-1-deoxynojirimycin hybrids were designed, synthesized and evaluated for their inhibitory activities against two drug target enzymes, epidermal growth factor receptor (EGFR) tyrosine kinase and alpha-glucosidase. Some synthesized compounds exhibited significantly inhibitory activities against the tested enzymes. Comparing with reference compounds gefitinib and lapatinib, compounds 7d, 8d, 9b and 9d showed higher inhibitory activities against EGFR (IC50: 1.79-10.71 nM). Meanwhile the inhibitory activities of 7d, 8d and 9c against alpha-glucosidase (IC50 = 0.14, 0.09 and 0.25 mu M, respectively) were obvious higher than that of miglitol (IC50 = 2.43 mu M), a clinical using alpha-glucosidase inhibitor. Interestingly, compound 9d as a dual inhibitor showed high inhibitory activity to EGFR(wt) tyrosine kinase (IC50 = 1.79 nM), also to alpha-glucosidase (IC50 = 0.39 mu M). The work could be very useful starting point for developing a new series of enzyme inhibitors targeting EGFR and/or alpha-glucosidase. (C) 2017 Elsevier Ltd. All rights reserved.
• [DE] BICYCLISCHE HETEROCYCLEN, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL, DEREN VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG<br/>[EN] BICYCLIC HETEROCYCLES, DRUGS CONTAINING SAID COMPOUNDS, THE USE THEREOF AND METHOD FOR PREPARING THE SAME<br/>[FR] HETEROCYCLES BICYCLIQUES, MEDICAMENTS CONTENANT CES COMPOSES, LEUR UTILISATION ET PROCEDE POUR LEUR PRODUCTION
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004108664A3

  公开（公告）日：2005-05-26
• BICYCLISCHE HETEROCYCLEN, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL, DEREN VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP1641767A2

  公开（公告）日：2006-04-05