2-乙酰氨基-4-乙氧基-5-硝基苯甲酸 | 361162-92-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-乙酰氨基-4-乙氧基-5-硝基苯甲酸
• 英文名称: 2-acetylamino-4-ethoxy-5-nitrobenzoic acid
• 英文别名: 2-acetylamino-4-ethoxy-5-nitro-benzoic acid；2-acetamido-4-ethoxy-5-nitrobenzoic acid
• CAS: 361162-92-7
• 化学式: C₁₁H₁₂N₂O₆
• 分子量: 268.226
• InChiKey: ITZHPZMVMXMJPQ-UHFFFAOYSA-N

物化性质

• 沸点：
  516.8±50.0 °C(Predicted)
• 密度：
  1.431±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-乙酰氨基-4-乙氧基-5-硝基苯甲酸 在 diphenyl ether-biphenyl eutectic 、 硫酸 、 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 、 甲苯 为溶剂， 反应 28.25h， 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：

  N-(5-Hydroxy-2-methyl-4-nitro-phenyl)-acetamide 在 potassium permanganate 、 magnesium sulfate 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 2-乙酰氨基-4-乙氧基-5-硝基苯甲酸
  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。
• 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。
• Process for the synthesis of nacyl-2-amino-4-alkoxy-5-nitrobenzoic acids
  申请人：Duncan Mason Scott

  公开号：US20050085662A1

  公开（公告）日：2005-04-21

  The invention claimed herein provides a process to oxidize N-(5-alkoxy-2-methyl-4-nitrophenyl)acetamides to N-acyl-2-amino-4-alkoxy-5-nitrobenzoic acids using potassium permanganate in the presence of magnesium sulfate in aqueous sulfolane or aqueous pyridine.

  本发明提供了一种在磺烷水溶液或吡啶水溶液中，在硫酸镁存在下使用高锰酸钾将 N-(5-烷氧基-2-甲基-4-硝基苯基)乙酰胺氧化成 N-酰基-2-氨基-4-烷氧基-5-硝基苯甲酸的工艺。
• 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
• PROCESS FOR THE SYNTHESIS OF N-ACYL-2-AMINO-4-ALKOXY-5-NITROBENZOIC ACIDS
  申请人：Wyeth

  公开号：EP1472213A1

  公开（公告）日：2004-11-03