7-bromo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile | 364794-39-8

• 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: 7-bromo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile
• 英文别名: 7-bromo-4-(3,4,5-trimethoxyanilino)-3-quinolinecarbonitrile；7-bromo-4-(3,4,5-trimethoxyanilino)quinoline-3-carbonitrile
• CAS: 364794-39-8
• 化学式: C₁₉H₁₆BrN₃O₃
• 分子量: 414.258
• InChiKey: KKMKFKPCZFQMAZ-UHFFFAOYSA-N

物化性质

• 沸点：
  526.2±50.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  poly(4-vinylpyridine N-oxide) 、 7-bromo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile 在 palladium diacetate 、 TEA 、 三(邻甲基苯基)磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-[(E)-2-(1-oxidopyridin-1-ium-4-yl)ethenyl]-4-(3,4,5-trimethoxyanilino)quinoline-3-carbonitrile
  参考文献：
  名称：

  Further studies on ethenyl and ethynyl-4-phenylamino-3-quinolinecarbonitriles: identification of a subnanomolar Src kinase inhibitor

  摘要：

  Several new ethynyl- and ethenyl-4-phenylamino-3-quinolinecarbonitriles were synthesized and tested for Src inhibition. Derivatives bearing an ethenyl or ethynyl substituent at C-6 showed decreased Src inhibitory activity. Incorporation of an ethenylpyridine N-oxide group at C-7 provided 20b, a 0.6 nM inhibitor of Src enzymatic activity with excellent cellular potency. (c) 2005 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2005.01.004
• 作为产物：
  描述：

  3,4,5-三甲氧基苯胺 、 7-溴-4-氯-喹啉-3-甲腈 以 乙醇 为溶剂， 反应 18.0h， 以83%的产率得到7-bromo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile
  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

• PREPARATION OF 7-ALKENYL-3 QUINOLINECARBONITRILES VIA A PALLADIUM MEDIATED COUPLING REACTION
  申请人：Wang Yanong Daniel

  公开号：US20090099356A1

  公开（公告）日：2009-04-16

  The present invention is directed to a process for preparing compounds of formula (I): wherein A, R 1 -R 3 , X, s, t, u, m and Z are defined herein, comprising the step of reacting a reagent of formula (II): in the presence of Pd(O) metal with a compound of formula (III): or salts thereof. Another aspect of this invention is a method of preparing compounds of formula (VI).

  本发明涉及一种制备化合物的方法，其化学式如下（I）：其中A、R1-R3、X、s、t、u、m和Z在此处定义，包括以下步骤：在Pd（O）金属存在下，将化学式（II）的试剂与化学式（III）的化合物或其盐反应。本发明的另一个方面是制备化合物的方法，其化学式为（VI）。
• 7-(Aryl/heteroaryl-2-ylethynyl)-4-phenylamino-3-quinolinecarbonitriles as new Src kinase inhibitors: Addition of water solubilizing groups
  作者：Biqi Wu、Ana Carolina Barrios Sosa、Diane H. Boschelli、Frank Boschelli、Erick E. Honores、Jennifer M. Golas、Dennis W. Powell、Yanong D. Wang

  DOI：10.1016/j.bmcl.2006.05.015

  日期：2006.8

  necarbonitriles with a 7-ethynyl group substituted by a pyridine, phenyl or thiophene ring containing basic water solubilizing groups were prepared and evaluated as Src kinase inhibitors. Of these new analogs, potent activity was observed with compounds having a (2,4-dichloro-5-methoxyphenyl)amino group at C-4, a methoxy or ethoxy group at C-6, and a pyridyl group bearing a dimethylamine or N-methylpiperazine

  制备具有被含碱性水增溶基团的吡啶，苯基或噻吩环取代的7-乙炔基的新的4-苯基氨基-3-喹啉甲腈，并将其评价为Src激酶抑制剂。在这些新的类似物中，观察到具有在C-4具有（2,4-二氯-5-甲氧基苯基）氨基，在C-6具有甲氧基或乙氧基以及带有二甲胺或N的吡啶基的化合物的有效活性。 -甲基哌嗪在C-7的乙炔基上。
• [EN] 3-CYANOQUINOLINES,3-CYANO-1,6-NAPHTHYRIDINES, AND 3-CYANO-1,7-NAPHTHYRIDINES AS PROTEIN KINASE INHIBITORS<br/>[FR] 3-CYANOQUINOLINES,3-CYANO-1,6-NAPHTHYRIDINES ET 3-CYANO-1,7-NAPHTHYRIDINES UTILISEES COMME INHIBITEURS DE PROTEINEKINASE
  申请人：AMERICAN HOME PROD

  公开号：WO2001072711A1

  公开（公告）日：2001-10-04

  Compounds of Formula (I), having the structure or a pharmaceutically salt thereof are useful as antineoplastic agents and in the treatment of osteoporosis and polycystic kidney disease.

  具有结构式（I）或其药物盐的化合物在抗肿瘤药物和治疗骨质疏松症和多囊肾病方面是有用的。
• Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines
  作者：Sirle Saul、Szu-Yuan Pu、William J. Zuercher、Shirit Einav、Christopher R.M. Asquith

  DOI：10.1016/j.bmcl.2020.127284

  日期：2020.8

  Screening a series of 4-anilinoquinolines and 4-anilinoquinazolines enabled identification of potent novel inhibitors of dengue virus (DENV). Preparation of focused 4-anilinoquinoline/quinazoline scaffold arrays led to the identification of a series of high potency 6-substituted bromine and iodine derivatives. The most potent compound 6-iodo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile (47) inhibited DENV infection with an EC50 = 79 nM. Crucially, these compounds showed very limited toxicity with CC(50 )values > 10 mu M in almost all cases. This new promising series provides an anchor point for further development to optimize compound properties.
• 4-Anilino-7-pyridyl-3-quinolinecarbonitriles as Src kinase inhibitors
  作者：Nan Zhang、Biqi Wu、Diane H. Boschelli、Jennifer M. Golas、Frank Boschelli

  DOI：10.1016/j.bmcl.2009.07.043

  日期：2009.9

  A series of 4-anilino-7-pyridyl-3-quinolinecarbonitriles was prepared as Src kinase inhibitors. A systematic SAR study of substitutions on both the pyridine ring and the 3-quinolinecarbonitrile core established the requirements for optimal activity. The lead compound, 17, showed potent activity in both the Src enzyme assay and cell assays, and demonstrated in vivo anti-tumor activity in a xenograft model. (C) 2009 Elsevier Ltd. All rights reserved.