(E)-ethyl 2-cyano-3-((4-nitrophenyl)amino)acrylate | 57338-24-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-ethyl 2-cyano-3-((4-nitrophenyl)amino)acrylate
• 英文别名: ethyl (E)-2-cyano-3-(4-nitroanilino)prop-2-enoate
• CAS: 57338-24-6
• 化学式: C₁₂H₁₁N₃O₄
• 分子量: 261.237
• InChiKey: CRIVSDDAATXAGJ-CMDGGOBGSA-N

物化性质

• 沸点：
  424.5±45.0 °C(Predicted)
• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-ethyl 2-cyano-3-((4-nitrophenyl)amino)acrylate 在 N-甲基吡咯烷酮 、 diphenyl ether-biphenyl eutectic 、 铁粉 、 氯化铵 、 三氯氧磷 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 12.25h， 生成 N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-2-morpholin-4-ylmethyl-2-propenamide
  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：

  4-硝基苯胺 、 2-cyano-3-ethoxyacrylic acid ethyl ester 以 甲苯 为溶剂， 反应 16.0h， 生成 (E)-ethyl 2-cyano-3-((4-nitrophenyl)amino)acrylate
  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。
• NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION, AND APPLICATION
  申请人：SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

  公开号：US20200190091A1

  公开（公告）日：2020-06-18

  A nitrogenous heterocyclic compound, a preparation method, an intermediate, a composition, and an application. The present invention provides a nitrogenous heterocyclic compound as represented by formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, diastereoisomers thereof, tautomers thereof, solvates thereof, metabolites thereof, or prodrugs thereof. The compound has high inhibitory activity against ErbB2 tyrosine kinase, has good inhibitory activity against human breast cancer cells BT-474, human gastric cancer cells NCI-N87 and the like with high expression of ErbB2, and in addition has relatively weak inhibitory activity against EGFR kinase, that is, the compound is an EGFR/ErbB2 double target inhibitor that attenuates EGFR kinase inhibitory activity or a small-molecule inhibitor having selectivity for an ErbB2 target. (I)

  一种含氮杂环化合物，一种制备方法，一种中间体，一种组合物和一种应用。本发明提供一种由式I表示的含氮杂环化合物，其药学上可接受的盐，其对映体，其非对映异构体，其互变异构体，其溶剂合物，其代谢物或其前药。该化合物对ErbB2酪氨酸激酶具有高抑制活性，对表达ErbB2高的人类乳腺癌细胞BT-474，人类胃癌细胞NCI-N87等具有良好的抑制活性，并且对EGFR激酶具有相对较弱的抑制活性，即该化合物是一种减弱EGFR激酶抑制活性的EGFR/ErbB2双靶点抑制剂或具有选择性作用于ErbB2靶点的小分子抑制剂。 (I)
• 3-Cyanoquinoline inhibitors of Tpl2 kinase and methods of making and using the same
  申请人：Green Jeffrey Neal

  公开号：US20060264460A1

  公开（公告）日：2006-11-23

  The present invention provides compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , m and n are defined as described herein. The invention also provides methods of making the compounds of formula (I), and methods of treating inflammatory diseases, such as rheumatoid arthritis, in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) to the mammal.

  本发明提供了如下式（I）的化合物及其药用可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、m和n的定义如本文所述。该发明还提供了制备如式（I）化合物的方法，以及治疗炎症性疾病（如类风湿性关节炎）的方法，包括向哺乳动物施用如式（I）化合物的治疗有效量。
• [EN] SUBSTITUTED QUINOLINES AS BRUTON'S TYROSINE KINASES INHIBITORS<br/>[FR] QUINOLÉINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE TYROSINE KINASES DE BRUTON
  申请人：ZHANG DAWEI

  公开号：WO2013152135A1

  公开（公告）日：2013-10-10

  The present invention is directed to novel quinolines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are useful for the treatment of protein kinases mediated diseases and conditions. The disclosed substituted quinolines include Bruton's tyrosine kinase (Btk) inhibitors.

  本发明涉及新型喹啉，其衍生物，药用盐，溶剂化合物以及其水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，可用于治疗蛋白激酶介导的疾病和症状。所公开的取代喹啉包括布鲁顿酪氨酸激酶（Btk）抑制剂。
• [EN] SUBSTITUTED 3-CYANOQUINOLINES AS PROTEIN TYROSINE KINASES INHIBITORS<br/>[FR] INHIBITEURS DE PROTEINES DE TYPE TYROSINE KINASES A BASE DE 3-CYANOQUINOLINES SUBSTITUEES
  申请人：AMERICAN CYANAMID CO

  公开号：WO2000018761A1

  公开（公告）日：2000-04-06

  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.

  该发明提供了式（1）的化合物，其中R1、G1、G2、R4、Z、X和n在此定义，或其药学上可接受的盐，可用作抗肿瘤剂以及多囊肾病的治疗。