7-bromo-4-(2,4-dichloroanilino)-3-quinolinecarbonitrile | 364793-58-8

• 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-(2,4-dichloroanilino)-3-quinolinecarbonitrile
• 英文别名: 7-bromo-4-(2,4-dichloro-phenylamino)-quinoline-3-carbonitrile；7-bromo-4-(2,4-dichloroanilino)quinoline-3-carbonitrile
• CAS: 364793-58-8
• 化学式: C₁₆H₈BrCl₂N₃
• 分子量: 393.07
• InChiKey: IQLUPDQNNINGBX-UHFFFAOYSA-N

物化性质

• 沸点：
  495.1±45.0 °C(Predicted)
• 密度：
  1.71±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-bromo-4-(2,4-dichloroanilino)-3-quinolinecarbonitrile 在 四(三苯基膦)钯 三乙酰氧基硼氢化钠 、 碳酸氢钠 、 溶剂黄146 作用下， 以 N-甲基吡咯烷酮 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-[(2,4-Dichlorophenyl)amino]-7-{5-[(4-methylpiperazin-1-yl)methyl]furan-3-yl}quinoline-3-carbonitrile
  参考文献：
  名称：

  Synthesis and Src Kinase Inhibitory Activity of a Series of 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles

  摘要：

  Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were prepared and it was found that the 3,5-substituted furan analog had increased activity compared to that of the 2,5-substituted furan isomer. Addition of a methoxy group at C-6 decreased the Src inhibitory activity of the C-7 2,5-substituted furan analog but increased the activity of the C-7 3,5-substituted furan isomer. This compound, 10, was a more potent Src inhibitor than 1 in both enzymatic and cell-based assays. The kinase selectivity profile of 10 was similar to that of 1, with 10 also inhibiting the activity of Abl and Lck. When tested in a solid tumor xenograft model, 10 had comparable oral activity to that of 1.

  DOI：

  10.1021/jm061031t
• 作为产物：
  描述：

  2,4-二氯苯胺 、 7-溴-4-氯-喹啉-3-甲腈 在 sodium 作用下， 以 四氢呋喃 为溶剂， 以63%的产率得到7-bromo-4-(2,4-dichloroanilino)-3-quinolinecarbonitrile
  参考文献：
  名称：

  3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors

  摘要：

  这项发明提供了具有结构的化合物（I）的公式， 其中T、Z、X、A、R 1 、R 2a 、R 2b 、R 2c 、R 3 、R 4 和n在此处定义，或其药学上可接受的盐，这些化合物可用作抗肿瘤药物，并用于骨质疏松症和多囊肾病的治疗。

  公开号：

  US20020026052A1

文献信息

• 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors
  申请人：American Home Products Corporation

  公开号：US20020026052A1

  公开（公告）日：2002-02-28

  This invention provides compounds of Formula (I), having the structure 1 where T, Z, X, A, R 1 , R 2a , R 2b , R 2c , R 3 , R 4 , and n are defined herein, or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of osteoporosis and polycystic kidney disease.

  这项发明提供了具有结构的化合物（I）的公式， 其中T、Z、X、A、R 1 、R 2a 、R 2b 、R 2c 、R 3 、R 4 和n在此处定义，或其药学上可接受的盐，这些化合物可用作抗肿瘤药物，并用于骨质疏松症和多囊肾病的治疗。
• 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）。
• [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。
• 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.
• Optimization of 7-alkene-3-quinolinecarbonitriles as Src kinase inhibitors
  作者：Diane H. Boschelli、Daniel Wang、Yan Wang、Biqi Wu、Erick E. Honores、Ana Carolina Barrios Sosa、Inder Chaudhary、Jennifer Golas、Judy Lucas、Frank Boschelli

  DOI：10.1016/j.bmcl.2010.03.025

  日期：2010.5

  The 7-alkene-3-quinolinecarbonitrile 20, a potent inhibitor of Src enzymatic and cellular activity with IC50 values of 2.1 and 58 nM, respectively, had comparable efficacy to bosutinib in a colon tumor xenograft study. (C) 2010 Elsevier Ltd. All rights reserved.