4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-(5-formyl-2-furyl)-3-quinolinecarbonitrile | 364787-81-5

• 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: 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-(5-formyl-2-furyl)-3-quinolinecarbonitrile
• 英文别名: 4-(2,4-dichloro-5-methoxyanilino)-7-(5-formyl-2-furyl)-3-quinolinecarbonitrile；4-(2,4-dichloro-5-methoxyanilino)-7-(5-formyl-furan-2-yl)-3-quinolinecarbonitrile；4-(2,4-Dichloro-5-methoxyanilino)-7-(5-formylfuran-2-yl)quinoline-3-carbonitrile
• CAS: 364787-81-5
• 化学式: C₂₂H₁₃Cl₂N₃O₃
• 分子量: 438.27
• InChiKey: XCCLTMPAXNKKNV-UHFFFAOYSA-N

物化性质

• 熔点：
  >250 °C
• 沸点：
  606.0±55.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-(5-formyl-2-furyl)-3-quinolinecarbonitrile 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以40%的产率得到4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-{5-[(4-methyl-1-piperazinyl)methyl]-2-furyl}-3-quinolinecarbonitrile
  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：

  7-bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile 在 bis-triphenylphosphine-palladium(II) chloride 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 8.0h， 生成 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-(5-formyl-2-furyl)-3-quinolinecarbonitrile
  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

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。
• [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。
• 3-CYANOQUINOLINES,3-CYANO-1,6-NAPHTHYRIDINES, AND 3-CYANO-1,7-NAPHTHYRIDINES AS PROTEIN KINASE INHIBITORS
  申请人：Wyeth

  公开号：EP1268431A1

  公开（公告）日：2003-01-02
• 3-Cyanoquinolines,3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors
  申请人：Wyeth

  公开号：US20040176602A1

  公开（公告）日：2004-09-09

  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.
• US6521618B2
  申请人：——

  公开号：US6521618B2

  公开（公告）日：2003-02-18