N-(3-ethynylphenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine | 1437310-67-2

• 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: N-(3-ethynylphenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
• 英文别名: 6-(3-chloropropoxy)-N-(3-ethynylphenyl)-7-methoxyquinazolin-4-amine
• CAS: 1437310-67-2
• 化学式: C₂₀H₁₈ClN₃O₂
• 分子量: 367.835
• InChiKey: OQWBMTHQHLPIPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-ethynylphenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine 、 去氧野艽霉素盐酸盐 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以37.7%的产率得到4-(3-ethynylphenylamino)-7-methoxy-6-(3-((2R,3R,4R,5S)-2-hydroxymethyl-3,4,5-trihydroxy-1-piperidyl)propoxy)quinazoline
  参考文献：
  名称：

  氮杂糖衍生化的喹唑啉类化合物

  摘要：

  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。

  公开号：

  CN106892898B
• 作为产物：
  描述：

  5-(3-chloropropoxy)-4-methoxy-2-aminobenzonitrile 在 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 0.75h， 生成 N-(3-ethynylphenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine
  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

• [EN] AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE<br/>[FR] DÉRIVÉS D'AMINOQUINAZOLINE ET LEURS SELS ET PROCÉDÉS D'UTILISATION
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2013071697A1

  公开（公告）日：2013-05-23

  The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明涉及医学领域。本文提供了氨基喹唑啉衍生物、其盐和药物配方，用于调节蛋白酪氨酸激酶活性，以及调节细胞间和/或细胞内信号传导。本文还提供了包含氨基喹唑啉化合物的药用可接受组合物，以及使用这些组合物治疗哺乳动物，特别是人类的增生性疾病的方法。
• AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US20140228361A1

  公开（公告）日：2014-08-14

  The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明涉及医学领域。本文提供了氨基喹唑啉衍生物，其盐和药物配方在调节蛋白酪氨酸激酶活性以及调节细胞间和/或细胞内信号传导方面具有用处。本文还提供了包含氨基喹唑啉化合物的药用可接受组合物，以及在治疗哺乳动物，特别是人类的增生性疾病中使用这些组合物的方法。
• Aminoquinazoline derivatives and their salts and methods of use
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US09181277B2

  公开（公告）日：2015-11-10

  The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明涉及医学领域。本发明提供了氨基喹唑啉衍生物、其盐和制药组合物，有用于调节蛋白酪氨酸激酶活性和调节细胞内外信号传递。本发明还提供了包括氨基喹唑啉化合物的药学上可接受的组合物和使用这些组合物治疗哺乳动物，尤其是人类的增生性疾病的方法。
• US9181277B2
  申请人：——

  公开号：US9181277B2

  公开（公告）日：2015-11-10
• 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.