N-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluorophenyl)-1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide

• 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: N-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluorophenyl)-1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide
• 英文别名: N-[4-(6,7-dimethoxyquinazolin-4-yl)oxy-3-fluorophenyl]-1-ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,8-naphthyridine-3-carboxamide
• 化学式: C₃₁H₂₉F₂N₇O₅
• 分子量: 617.612
• InChiKey: WSFUYXGZCYKCIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  依诺沙星 在 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluorophenyl)-1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide
  参考文献：
  名称：

  Quinolone antibiotic derivatives as new selective Axl kinase inhibitors

  摘要：

  Axl is a new promising molecular target for antineoplastic therapies. A series of quinolone antibiotic derivatives were designed and synthesized as new selective Axl inhibitors. One of the most promising compound 8i bound tightly to Axl with a K-d value of 1.1 nM, and inhibited its kinase activity with an IC50 value of 26 nM. The compound also significantly inhibited the phosphorylation of Axl and dose dependently inhibited cell invasion and migration in TGF-beta 1 induced MDA-MD-231 breast cancer cells. In addition, 8i demonstrated reasonable pharmacokinetic properties and exhibited extraordinary target selectivity over 468 kinases except for Flt3 (IC50 = 50 nM)), with a S(10) and S(35) value of 0.022 and 0.42 at 1.0 mu M, respectively. Compound 8i may serve as a new valuable lead compound for future anti-cancer drug discovery. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.065

文献信息

• PHARMACEUTICAL COMPOSITION AND APPLICATION REPLACING QUINOLONE DERIVATIVE, PHARMACEUTICAL ACCEPTABLE SALT, OR STEREOISOMER
  申请人：Jinan University

  公开号：EP3339294A1

  公开（公告）日：2018-06-27

  Provided are a substituted quinolone derivative as shown by formula (I), or a pharmaceutically acceptable salt and a prodrug molecule thereof, and a pharmaceutical composition thereof, as well as the use of same in preparing drugs for the prevention and treatment of a tumor. The quinolone derivative, salt, prodrug molecule, and pharmaceutical composition thereof can be used as a protein kinase inhibitor, which is effective in inhibiting the activity of AXL protein kinase, and is capable of inhibiting the proliferation, migration and invasion of various tumor cells; and can be used in the preparation of anti-tumor drugs, especially drugs for treating hyperproliferative diseases such as a tumor in human beings and other mammals.

  本发明提供了一种如式（I）所示的取代喹诺酮衍生物或其药学上可接受的盐和原药分子及其药物组合物，以及其在制备预防和治疗肿瘤药物中的用途。本发明的喹诺酮衍生物、盐、原药分子及其药物组合物可用作蛋白激酶抑制剂，能有效抑制AXL蛋白激酶的活性，能够抑制各种肿瘤细胞的增殖、迁移和侵袭；可用于制备抗肿瘤药物，特别是用于治疗人类和其他哺乳动物的肿瘤等过度增殖性疾病的药物。
• Substituted quinolone derivatives, or pharmaceutically acceptable salts or stereoisomers thereof, and pharmaceutical compositions and use thereof
  申请人：JINAN UNIVERSITY

  公开号：US10683278B2

  公开（公告）日：2020-06-16

  Provided are a substituted quinolone derivative as shown by formula (I), or a pharmaceutically acceptable salt and a prodrug molecule thereof, and a pharmaceutical composition thereof, as well as the use of same in preparing drugs for the prevention and treatment of a tumor. The quinolone derivative, salt, prodrug molecule, and pharmaceutical composition thereof can be used as a protein kinase inhibitor, which is effective in inhibiting the activity of AXL protein kinase, and is capable of inhibiting the proliferation, migration and invasion of various tumor cells; and can be used in the preparation of anti-tumor drugs, especially drugs for treating hyperproliferative diseases such as a tumor in human beings and other mammals.

  本发明提供了一种如式（I）所示的取代喹诺酮衍生物或其药学上可接受的盐和原药分子及其药物组合物，以及其在制备预防和治疗肿瘤药物中的用途。本发明的喹诺酮衍生物、盐、原药分子及其药物组合物可用作蛋白激酶抑制剂，能有效抑制AXL蛋白激酶的活性，能够抑制各种肿瘤细胞的增殖、迁移和侵袭；可用于制备抗肿瘤药物，特别是用于治疗人类和其他哺乳动物的肿瘤等过度增殖性疾病的药物。
• [EN] PHARMACEUTICAL COMPOSITION AND APPLICATION REPLACING QUINOLONE DERIVATIVE, PHARMACEUTICAL ACCEPTABLE SALT, OR STEREOISOMER<br/>[FR] COMPOSITION PHARMACEUTIQUE ET APPLICATION REMPLAÇANT UN DÉRIVÉ DE QUINOLONE, SEL PHARMACEUTIQUEMENT ACCEPTABLE, OU STÉRÉOISOMÈRE<br/>[ZH] 取代喹诺酮类衍生物或其药学上可接受的盐或立体异构体及其药用组合物和应用
  申请人：UNIV JINAN

  公开号：WO2017028797A1

  公开（公告）日：2017-02-23

  提供了式（I）所示的取代喹诺酮类衍生物或其药学上可接受的盐、前药分子及其药用组合物和在制备防治肿瘤药物中的应用。所述喹诺酮类衍生物、盐、前药分子及其药用组合物可作为蛋白激酶抑制剂，有效抑制AXL蛋白激酶的活性并且能抑制多种肿瘤细胞的增殖、迁移和侵袭；可用于制备抗肿瘤药物，特别是制备治疗人类及其它哺乳动物的肿瘤等过度增殖性疾病的药物中。
• QUINOLONE DERIVATIVE, PHARMACEUTICAL ACCEPTABLE SALT, OR STEREOISOMER THEREOF AS AXL INHIBIOTOR
  申请人：Shanghai Haihe Pharmaceutical Co., Ltd.

  公开号：EP3339294B1

  公开（公告）日：2021-04-14
• SUBSTITUTED QUINOLONE DERIVATIVES, OR PHARMACEUTICALLY ACCEPTABLE SALTS OR STEREOISOMERS THEREOF, AND PHARMACEUTICAL COMPOSITIONS AND USE THEREOF
  申请人：JINAN UNIVERSITY

  公开号：US20180265496A1

  公开（公告）日：2018-09-20

  Provided are a substituted quinolone derivative as shown by formula (I), or a pharmaceutically acceptable salt and a prodrug molecule thereof, and a pharmaceutical composition thereof, as well as the use of same in preparing drugs for the prevention and treatment of a tumor. The quinolone derivative, salt, prodrug molecule, and pharmaceutical composition thereof can be used as a protein kinase inhibitor, which is effective in inhibiting the activity of AXL protein kinase, and is capable of inhibiting the proliferation, migration and invasion of various tumor cells; and can be used in the preparation of anti-tumor drugs, especially drugs for treating hyperproliferative diseases such as a tumor in human beings and other mammals.