(S)-N-(3-ethynylphenyl)-6-nitro-7-((tetrahydrofuran-3-yl)oxy)quinazolin-4-amine

• 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: (S)-N-(3-ethynylphenyl)-6-nitro-7-((tetrahydrofuran-3-yl)oxy)quinazolin-4-amine
• 英文别名: (S)-N-(3-ethynylphenyl)-6-nitro-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amine；N-(3-ethynylphenyl)-6-nitro-7-[(3S)-oxolan-3-yl]oxyquinazolin-4-amine
• 化学式: C₂₀H₁₆N₄O₄
• 分子量: 376.371
• InChiKey: ADECSOBIEKQDFN-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-N-(3-ethynylphenyl)-6-nitro-7-((tetrahydrofuran-3-yl)oxy)quinazolin-4-amine 在 铁粉 、 potassium carbonate 、 氯化铵 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (S,E)-N-(4-(3-ethynylphenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-4-(isopropylamino)but-2-enamide
  参考文献：
  名称：

  Structure-activity study of quinazoline derivatives leading to the discovery of potent EGFR-T790M inhibitors

  摘要：

  We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.026
• 作为产物：
  描述：

  7-氟-6-硝基-4-羟基喹唑啉 在 氯化亚砜 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 mineral oil 为溶剂， 反应 7.5h， 生成 (S)-N-(3-ethynylphenyl)-6-nitro-7-((tetrahydrofuran-3-yl)oxy)quinazolin-4-amine
  参考文献：
  名称：

  [EN] SUBSTITUTED AMINOQUINAZOLINES USEFUL AS KINASES INHIBITORS
  [FR] AMINOQUINAZOLINES SUBSTITUÉES UTILES COMME INHIBITEURS DE KINASES

  摘要：

  本发明涉及新型喹唑啉类化合物及其衍生物、药用可接受的盐、溶剂合物和水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，预计可用于治疗蛋白激酶介导的疾病和症状。

  公开号：

  WO2013166952A1

文献信息

• [EN] SUBSTITUTED AMINOQUINAZOLINES USEFUL AS KINASES INHIBITORS<br/>[FR] AMINOQUINAZOLINES SUBSTITUÉES UTILES COMME INHIBITEURS DE KINASES
  申请人：TELIGENE LTD

  公开号：WO2013166952A1

  公开（公告）日：2013-11-14

  The present invention is directed to novel quinazolines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

  本发明涉及新型喹唑啉类化合物及其衍生物、药用可接受的盐、溶剂合物和水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，预计可用于治疗蛋白激酶介导的疾病和症状。
• [EN] AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'AMINOQUINAZOLINE, LEURS SELS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2014177038A1

  公开（公告）日：2014-11-06

  Provided herein are aminoquinazoline compounds, salts and uses thereof. The compounds have Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Also provided herein are pharmaceutical compositions containing the compounds disclosed herein, and uses of the compounds or the compositions for preventing, managing, treating or lessening the severity of a proliferative disorder in a patient and for modulating the protein tyrosine kinase activity.

  本文提供了氨基喹唑啉化合物、盐及其用途。这些化合物具有式(I)，或其立体异构体、几何异构体、互变异构体、N-氧化物、水合物、溶剂合物、代谢物、药学上可接受的盐或其前药。本文还提供了含有上述化合物的药物组合物，以及利用这些化合物或组合物预防、管理、治疗或减轻患者体内增殖性疾病的严重程度，并调节蛋白酪氨酸激酶活性的用途。
• SUBSTITUTED AMINOQUINAZOLINES USEFUL AS KINASES INHIBITORS
  申请人：TELIGENE LTD.

  公开号：US20150126539A1

  公开（公告）日：2015-05-07

  The present invention is directed to novel quinazolines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

  本发明涉及新型喹唑啉、其衍生物、药学上可接受的盐、溶剂物和水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，并有望用于治疗蛋白激酶介导的疾病和病状。
• Substituted aminoquinazolines useful as kinases inhibitors
  申请人：TELIGENE LTD.

  公开号：US09388170B2

  公开（公告）日：2016-07-12

  The present invention is directed to novel quinazolines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

  本发明涉及新型喹唑啉、其衍生物、药学上可接受的盐、溶剂和水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，预计可用于治疗蛋白激酶介导的疾病和病状。
• AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE THEREOF
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US20160039838A1

  公开（公告）日：2016-02-11

  Provided herein are aminoquinazoline compounds, salts and uses thereof. The compounds have Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Also provided herein are pharmaceutical compositions containing the compounds disclosed herein, and uses of the compounds or the compositions for preventing, managing, treating or lessening the severity of a proliferative disorder in a patient and for modulating the protein tyrosine kinase activity.

  本文提供了氨基喹啉化合物、盐及其用途。该化合物具有式(I)、立体异构体、几何异构体、互变异构体、N-氧化物、水合物、溶剂化物、代谢产物、药学上可接受的盐或其前药。本文还提供了含有上述化合物的制药组合物，并使用该化合物或组合物预防、管理、治疗或减轻患者的增生性疾病严重程度，并调节蛋白酪氨酸激酶活性。