4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid [4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide

• 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-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid [4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide
• 英文别名: 4-((2s)-2-Methoxymethylpyrrolidin-1-yl)but-2-ynoic acid[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide；N-[4-(3-bromoanilino)-3-cyanoquinolin-6-yl]-4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]but-2-ynamide
• 化学式: C₂₆H₂₄BrN₅O₂
• 分子量: 518.413
• InChiKey: CCUWFRBLNGOQSJ-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  90.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 3.25h， 生成 4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid [4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 6,7-Disubstituted 4-Anilinoquinoline-3-carbonitriles. The Design of an Orally Active, Irreversible Inhibitor of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (EGFR) and the Human Epidermal Growth Factor Receptor-2 (HER-2)

  摘要：

  A series of of 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile derivatives that function as irreversible inhibitors of EGFR and HER-2 kinases have been prepared. These inhibitors have, at the 6-position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(arylamino)quinoline-3-carbonitriles with unsaturated acid chlorides or mixed anhydrides. We performed competitive reactivity studies showing that attaching a dialkylamino group onto the end of the Michael acceptor results in compounds with greater reactivity due to intramolecular catalysis of the Michael addition. This, along with improved water-solubility results in compounds with enhanced biological properties. We present molecular modeling results consistent with the proposed mechanism of inhibition. One compound, 5 (EKB-569), which shows excellent oral in vivo activity, was selected for further studies and is currently in phase I clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm020241c

文献信息

• Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors
  申请人：Wyeth Holdings Corporation

  公开号：EP1950201A1

  公开（公告）日：2008-07-30

  This invention provides compounds of formula 1 wherein R1, G1, G2, R4, Z, X and n are defined herein, or a pharmaceutically acceptable salt thereof, which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.

  这项发明提供了式1的化合物 其中R1、G1、G2、R4、Z、X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剂和多囊肾病的治疗药物。
• Substituted 3-cyanoquinolines
  申请人：American Cyanamid Company

  公开号：US06297258B1

  公开（公告）日：2001-10-02

  This invention provides compounds of formula I having the structure wherein G1, G2, R1, R4, Z, n, and X are defined in the specification or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.

  本发明提供了式I的化合物，其结构如下：其中G1、G2、R1、R4、Z、n和X在规范中定义，或其药学上可接受的盐，其可用作抗肿瘤剂和多囊肾病的治疗药物。
• USRE042376E1
  申请人：——

  公开号：——

  公开（公告）日：——
• Combination Product of Receptor Tyrosine Kinase Inhibitor and Fatty Acid Synthase Inhibitor for Treating Cancer
  申请人：Grunt Thomas

  公开号：US20090325877A1

  公开（公告）日：2009-12-31

  A pharmaceutical combination product is disclosed that comprises a receptor tyrosine kinase inhibitor and a fatty acid synthase inhibitor, and to the use thereof in the manufacture of a medicament for use in the treatment or prophylaxis of cancer.
• US6297258B1
  申请人：——

  公开号：US6297258B1

  公开（公告）日：2001-10-02