N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinolin-4-amine | 1173823-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinolin-4-amine
• CAS: 1173823-83-0
• 化学式: C₂₃H₂₄N₂O₄
• 分子量: 392.455
• InChiKey: ZQYQKUIFZATHRG-UHFFFAOYSA-N

物化性质

• 沸点：
  549.8±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-chloro-6,7-bis(2-methoxyethoxy)quinoline 、 3-氨基苯乙炔 以 乙醇 为溶剂， 反应 18.0h， 生成 N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinolin-4-amine
  参考文献：
  名称：

  利用定量结构-活性关系设计和分析GAK / SLK / STK10的4-苯胺基喹啉（az）oline激酶抑制谱。

  摘要：

  4-苯胺基喹啉和4-苯胺基喹唑啉环系统一直是现有激酶药物发现计划中的重大工作重点，这些计划已开发出获批的药物。随着先进的筛选技术的出现，现在已经评估了这些化合物的广泛的动力学特征。这些环系统最初是为包括表皮生长因子受体（EGFR）在内的特定靶标设计的，但实际上显示了许多有效的附带激酶靶标，其中一些与阴性临床结局有关。我们设计和合成了一系列4-苯胺基喹啉（az）脯氨酸，以便更好地了解基于喹（唑啉的激酶抑制剂的三个主要附带激酶靶的结构-活性关系：细胞周期蛋白G相关激酶（GAK），STE20样丝氨酸/苏氨酸蛋白激酶（SLK）和丝氨酸/苏氨酸蛋白激酶10（STK10）。这是通过一系列定量构效关系（QSAR）分析，激酶ATP结合位点的水位分析以及广泛的小分子X射线结构分析实现的。

  DOI：

  10.1002/cmdc.201900521

文献信息

• Synthesis and Biological Evaluation of 4-Anilinoquinolines as Potent Inhibitors of Epidermal Growth Factor Receptor
  作者：Vijaykumar G. Pawar、Martin L. Sos、Haridas B. Rode、Matthias Rabiller、Stefanie Heynck、Willem A. L. van Otterlo、Roman K. Thomas、Daniel Rauh

  DOI：10.1021/jm901877j

  日期：2010.4.8

  The mutant receptor tyrosine kinase EGFR is a validated and therapeutically amenable target for genotypically selected lung cancer patients. Here we present the synthesis and biological evaluation of a series of 6- and 7-substituted 4-anilinoquinolines as potent type I inhibitors of clinically relevant mutant variants of EGFR. Quinolines 3a and 3e were found to be highly active kinase inhibitors in biochemical assays and were further investigated for their biological effect on EGFR-dependent Ba/F3 cells and non-small cell lung cancer (NSCLC) cell lines.
• Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines
  作者：Christopher R.M. Asquith、Neil Fleck、Chad D. Torrice、Daniel J. Crona、Christoph Grundner、William J. Zuercher

  DOI：10.1016/j.bmcl.2019.07.012

  日期：2019.9

  We screened a series of 4-anilinoquinolines and 4-anilinoquinazolines and identified novel inhibitors of Mycobacterium tuberculosis (Mtb). The focused 4-anilinoquinoline/quinazoline scaffold arrays yielded compounds with high potency and the identification of 6,7-dimethoxy-N-(4-((4-methylbenzyl) oxy) phenyl) quinolin-4-amine (34) with an MIC90 value of 0.63-1.25 mu M. We also defined a series of key structural features, including the benzyloxy aniline and the 6,7-dimethoxy quinoline ring, that are important for Mtb inhibition. Importantly the compounds showed very limited toxicity and scope for further improvement by iterative medicinal chemistry.
• Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma
  作者：Christopher R. M. Asquith、Kaleb M. Naegeli、Michael P. East、Tuomo Laitinen、Tammy M. Havener、Carrow I. Wells、Gary L. Johnson、David H. Drewry、William J. Zuercher、David C. Morris

  DOI：10.1021/acs.jmedchem.9b00350

  日期：2019.5.9

  We describe the design of a set of inhibitors to investigate the relationship between cyclin G associated kinase (GAK) and epidermal growth factor receptor (EGFR) in chordoma bone cancers. These compounds were characterized both in vitro and using in cell target engagement assays. The most potent chordoma inhibitors were further characterized in a kinome-wide screen demonstrating narrow spectrum profiles. While we observed a direct correlation between EGFR and antiproliferative effects on chordoma, GAK inhibition appeared to have only a limited effect.
• FUSED QUINOXALINE DERIVATIVES AS INHIBITORS OF AKT ACTIVITY
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1494676B1

  公开（公告）日：2013-05-08
• [EN] A PROCESS FOR PREPARING STABLE POLYMOPHIC FORM OF ERLOTINIB HYDROCHLORIDE<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UNE FORME POLYMORPHE STABLE DE CHLORHYDRATE D'ERLOTINIB
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2012150606A2

  公开（公告）日：2012-11-08

  The present invention discloses an improved and efficient process for preparing Erlotinib hydrochloride suitable as an anti cancer drug.