4-(3-chloro-4-fluorophenylamino)-7-ethoxy-6-nitroquinoline-3-carbonitrile hydrochloride

• 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-(3-chloro-4-fluorophenylamino)-7-ethoxy-6-nitroquinoline-3-carbonitrile hydrochloride
• 英文别名: 4-(3-Chloro-4-fluoro-phenylamino)-7-ethoxy-6-nitro-quinoline-3-carbonitrile hydrochloride；4-((3-Chloro-4-fluorophenyl)amino)-7-ethoxy-6-nitroquinoline-3-carbonitrile hydrochloride；4-(3-chloro-4-fluoroanilino)-7-ethoxy-6-nitroquinoline-3-carbonitrile;hydrochloride
• 化学式: C₁₈H₁₂ClFN₄O₃*ClH
• 分子量: 423.231
• InChiKey: ZOEMMFGKNRTSSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.37
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-4-fluorophenylamino)-7-ethoxy-6-nitroquinoline-3-carbonitrile hydrochloride 在 N-甲基吡咯烷酮 、 铁粉 、 氯化铵 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 培利替尼
  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
• 作为产物：
  描述：

  间氨基苯乙醚 在 diphenyl ether-biphenyl eutectic 、 亚硝酸铵 、 三氟乙酸酐 、 三氯氧磷 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 23.25h， 生成 4-(3-chloro-4-fluorophenylamino)-7-ethoxy-6-nitroquinoline-3-carbonitrile hydrochloride
  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

• Method of treating or inhibiting colonic polyps
  申请人：American Cyanamid Company

  公开号：US06384051B1

  公开（公告）日：2002-05-07

  This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula 1 wherein: R1, R2, R3, R4, X, Y, and n are as defined hereinbefore, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种治疗或抑制结肠息肉的方法，包括提供如下公式1的化合物： 其中： R1、R2、R3、R4、X、Y和n如前文所定义，或其药用可接受的盐。
• 1,2-DITHIOLANE AND DITHIOL COMPOUNDS USEFUL IN TREATING MUTANT EGFR-MEDIATED DISEASES AND CONDITIONS
  申请人：Sabila Biosciences LLC

  公开号：US20180208584A1

  公开（公告）日：2018-07-26

  Compositions of the invention comprise 1,2-dithiolane, dithiol and related compounds useful as therapeutic agents for the treatment and prevention of diseases and conditions associated with aberrant EGFR activity.

  该发明的组合物包括1,2-二硫杂环烷、二硫醇和相关化合物，可用作治疗剂，用于治疗和预防与EGFR活性异常相关的疾病和病况。
• Stabilized pharmaceutical composition containing basic excipients
  申请人：Wyeth Holdings Corporation

  公开号：US20040122048A1

  公开（公告）日：2004-06-24

  This invention provides a stable stabilized pharmaceutical composition in an oral dosage form comprising a compound of the formula 1 wherein: R 11 , R 10 , R 5 , R 6 , R 7 , R 8 , R, Y, X, k, p and n are as defined herein, or its pharmaceutically acceptable salts, esters or ethers thereof.

  本发明提供了一种稳定的口服剂型的药物组合物，包括式1的化合物，其中：R11、R10、R5、R6、R7、R8、R、Y、X、k、p和n如本文所定义，或其药学上可接受的盐、酯或醚。
• USE OF CYANOQUINOLINES FOR TREATING OR INHIBITING COLONIC POLYPS
  申请人：Wyeth Holdings Corporation

  公开号：EP1263503B1

  公开（公告）日：2005-11-02
• STABILIZED PHARMACEUTICAL COMPOSITION CONTAINING BASIC EXCIPIENTS
  申请人：Wyeth Holdings Corporation

  公开号：EP1549297A2

  公开（公告）日：2005-07-06