4-氯-7-(4-氯丁氧基)-6-甲氧基喹啉-3-腈 | 380844-38-2

• 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
• 中文名称: 4-氯-7-(4-氯丁氧基)-6-甲氧基喹啉-3-腈
• 英文名称: 4-chloro-7-(4-chlorobutoxy)-6-methoxy-3-quinolinecarbonitrile
• 英文别名: 4-chloro-7-(4-chlorobutoxy)-6-methoxyquinoline-3-carbonitrile；3-Quinolinecarbonitrile, 4-chloro-7-(4-chlorobutoxy)-6-methoxy-
• CAS: 380844-38-2
• 化学式: C₁₅H₁₄Cl₂N₂O₂
• 分子量: 325.194
• InChiKey: AFKXMNNFCNSZGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氯-7-(4-氯丁氧基)-6-甲氧基喹啉-3-腈 在 吡啶盐酸盐 、 sodium iodide 作用下， 以 乙二醇乙醚 、 乙二醇二甲醚 为溶剂， 反应 4.0h， 生成 4-Phenylamino 3-quinolinecarbonitrile deriv. 27
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250
• 作为产物：
  描述：

  4-氯丁醇 、 4-氯-7-羟基-6-甲氧基喹啉-3-甲腈 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以65%的产率得到4-氯-7-(4-氯丁氧基)-6-甲氧基喹啉-3-腈
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250

文献信息

• Quinoline derivatives and their use as tyrosine kinase inhibitors
  申请人：Hennequin Francois Andre Laurent

  公开号：US20050009867A1

  公开（公告）日：2005-01-13

  The invention concerns quinoline derivatives of Formula (I) wherein each of Z, m, R 1 , n and R 3 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  本发明涉及公式（I）的喹啉衍生物，其中Z，m，R1，n和R3中的每一个都具有描述中定义的任何含义；它们的制备过程，含有它们的制药组合物以及它们在制造用于抗侵袭剂在固体肿瘤疾病的控制和/或治疗中使用的药物的制剂中的用途。
• QUINOLINE DERIVATIVES AND THEIR USE AS TYROSINE KINASE INHIBITORS
  申请人：Astrazeneca AB

  公开号：EP1409481A1

  公开（公告）日：2004-04-21
• US7501516B2
  申请人：——

  公开号：US7501516B2

  公开（公告）日：2009-03-10
• [EN] QUINOLINE DERIVATIVES AND THEIR USE AS TYROSINE KINASE INHIBITORS<br/>[FR] DERIVES QUINOLINE ET UTILISATION EN TANT QU'INHIBITEURS DE TYROSINE KINASE
  申请人：ASTRAZENECA AB

  公开号：WO2003008409A1

  公开（公告）日：2003-01-30

  The invention concerns quinoline derivatives of Formula (I) wherein each of Z, m, R1, n and R3 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.
• [EN] PHARMACEUTICAL COMPOSITIONS COMPRISING BENZOFURANYL SUBSTITUTED 3-CYANOQUINOLINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF SOLID TUMOURS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES COMPRENANT DES DERIVES DE 3-CYANOQUINOLINE A SUBSTITUTION BENZOFURANYLE ET LEUR UTILISATION DANS LE TRAITEMENT DE TUMEURS SOLIDES
  申请人：ASTRAZENECA AB

  公开号：WO2003047583A1

  公开（公告）日：2003-06-12

  The invention concerns the use of quinoline derivatives of Formula (I) wherein each of Z, m, R1, n and R3 have any of the meanings defined hereinbefore in the description in the manufacture of a medicament for use for use as an anti-proliferative agent in the containment and/or treatment of solid tumour disease.