4-(3-chloro-4-fluorophenylamino)-7-methoxy-6-(2-((2R,3R,4R,5S)-2-hydroxymethyl-3,4,5-trihydroxy-1-piperidyl)ethoxy)quinazoline

• 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)-7-methoxy-6-(2-((2R,3R,4R,5S)-2-hydroxymethyl-3,4,5-trihydroxy-1-piperidyl)ethoxy)quinazoline
• 英文别名: (2R,3R,4R,5S)-1-[2-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxyethyl]-2-(hydroxymethyl)piperidine-3,4,5-triol
• 化学式: C₂₃H₂₆ClFN₄O₆
• 分子量: 508.934
• InChiKey: MBBMMRFCBLTKGR-GMQQQROESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  140
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-amino-5-(2-chloroethoxy)-4-methoxybenzonitrile 在 potassium carbonate 、 溶剂黄146 、 三乙胺 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 7.75h， 生成 4-(3-chloro-4-fluorophenylamino)-7-methoxy-6-(2-((2R,3R,4R,5S)-2-hydroxymethyl-3,4,5-trihydroxy-1-piperidyl)ethoxy)quinazoline
  参考文献：
  名称：

  Quinazoline-1-deoxynojirimycin hybrids as high active dual inhibitors of EGFR and α-glucosidase

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2017.08.035

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。
• 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.