4-(4-bromo-2-fluorophenylamino)-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid | 853105-98-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(4-bromo-2-fluorophenylamino)-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid
• 英文别名: 4-(4-bromo-2-fluoroanilino)-5-fluoro-1-methyl-6-oxopyridine-3-carboxylic acid
• CAS: 853105-98-3
• 化学式: C₁₃H₉BrF₂N₂O₃
• 分子量: 359.127
• InChiKey: ZDECDUKQBAGZHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-bromo-2-fluorophenylamino)-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid 在 1-羟基苯并三唑 、 三乙胺 、 肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以64 mg (89%)的产率得到4-(4-bromo-2-fluorophenylamino)-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid hydrazide
  参考文献：
  名称：

  Heterocyclic inhibitors of MEK and methods of use thereof

  摘要：

  本文披露了式I的化合物及其药用盐和前药，其中R1、R2、R7、R8和R9、W、X和Y的定义如规范中所述。这些化合物是MEK抑制剂，在哺乳动物中用于治疗高增殖性疾病，如癌症和炎症，以及炎症病症。还披露了在哺乳动物中治疗高增殖性疾病的方法以及含有这些化合物的药物组合物。

  公开号：

  US20050256123A1
• 作为产物：
  描述：

  1,3-丙酮二羧酸二乙酯 在 lithium hydroxide 、 乙酸酐 、 Selectfluor 、 三乙胺 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 乙腈 为溶剂， 反应 52.67h， 生成 4-(4-bromo-2-fluorophenylamino)-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid
  参考文献：
  名称：

  Potent and Selective Mitogen-Activated Protein Kinase Kinase (MEK) 1,2 Inhibitors. 1. 4-(4-Bromo-2-fluorophenylamino)-1- methylpyridin-2(1H)-ones

  摘要：

  The role of MEK 1,2 in cancer tumorgenesis has been clearly demonstrated preclinically, and two selective inhibitors are currently undergoing clinical evaluation to determine their role in the human disease. We have discovered 4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones as a new class of ATP noncompetitive MEK inhibitors. These inhibitors exhibit excellent cellular potency and good pharmacokinetic properties and have demonstrated the ability to inhibit ERK phosphorylation in HT-29 tumors from mouse xenograft studies.

  DOI：

  10.1021/jm050834y

文献信息

• HETEROCYCLIC INHIBITORS OF MEK AND METHODS OF USE THEREOF
  申请人：Marlow Allison L.

  公开号：US20090215834A1

  公开（公告）日：2009-08-27

  Disclosed are compounds of the Formula V and pharmaceutically acceptable salts and prodrugs thereof, wherein R 1 , R 2 , R 7 , R 8 and R 9 , and W are as defined in the specification. Such compounds are MEK inhibitors and useful in the treatment of hyperproliferative diseases, such as cancer and inflammation, and inflammatory conditions in mammals. Also disclosed are methods of using such compounds in the treatment of hyperproliferative diseases and inflammatory conditions in mammals and pharmaceutical compositions containing such compounds.

  本发明涉及公式V的化合物，以及其药学上可接受的盐和前药，其中R1、R2、R7、R8和R9以及W在说明书中定义。这些化合物是MEK抑制剂，可用于治疗哺乳动物的高增殖性疾病，如癌症和炎症，以及炎症状况。本发明还涉及使用这些化合物治疗哺乳动物的高增殖性疾病和炎症状况的方法，以及含有这些化合物的制药组合物。
• Cyclopentene compounds
  申请人：Giblin Gerard Martin Paul

  公开号：US20090227591A1

  公开（公告）日：2009-09-10

  Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein A, B, Z, R 1 , R 2a , R 2b , R 8 , R 9 , and R x are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.

  化合物的式子（I）或其药学上可接受的衍生物： 其中A、B、Z、R1、R2a、R2b、R8、R9和Rx如规范中所定义，制备这种化合物的工艺，包含这种化合物的制药组合物以及这种化合物在医学上的用途。
• Novel 4-Arylamino Pyridone Derivatives as Mek Inhibitors for the Treatment of Hyper-Proliferative Disorders
  申请人：Abel Ulrich

  公开号：US20070293544A1

  公开（公告）日：2007-12-20

  The invention provides novel, substituted 4-arylamino pyridone compounds (formula (I)), pharmaceutically acceptable salts, solvates and prodrug compounds thereof, wherein W, R 1, R2, R9, R 10, R 11, R 12, R 13, R 14 and L are as defined in the specification. Such compounds are MEK inhibitors and useful in the treatment of hyperproliferative diseases, such as cancer, restenosis and inflammation. Also disclosed is the use of such compounds in the treatment of hyperproliferative diseases in mammals, especially humans, and pharmaceutical compositions containing such compounds.

  本发明提供了一种新型的取代的4-芳基氨基吡啶酮化合物（式（I）），其药学上可接受的盐、溶剂化物和前药化合物，其中W、R1、R2、R9、R10、R11、R12、R13、R14和L如规范中所定义。这些化合物是MEK抑制剂，可用于治疗过度增殖性疾病，如癌症、再狭窄和炎症。还揭示了在哺乳动物，特别是人类中使用这些化合物治疗过度增殖性疾病以及含有这些化合物的制药组合物的用途。
• Methods of using MEK inhibitors
  申请人：Lamb Peter

  公开号：US20080166359A1

  公开（公告）日：2008-07-10

  The present invention provides methods of treating cancer by administering a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, in combination with other cancer treatments.

  本发明提供了一种通过给予I式化合物或其药学上可接受的盐或溶剂与其他癌症治疗相结合的方法来治疗癌症的方法。
• Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof
  申请人：Array BioPharma Inc.

  公开号：US07732616B2

  公开（公告）日：2010-06-08

  Disclosed are compounds of the Formulas I and V and pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, R7, R8 and R9, W, X and Y are as defined in the specification. Such compounds are MEK inhibitors and useful in the treatment of hyperproliferative diseases, such as cancer and inflammation, in mammals, and inflammatory conditions. Also disclosed are methods of using such compounds in the treatment of hyperproliferative diseases in mammals and pharmaceutical compositions containing such compounds.

  本发明揭示了I和V式化合物及其药学上可接受的盐和前药，其中R1、R2、R7、R8和R9、W、X和Y的定义如规范中所述。这些化合物是MEK抑制剂，可用于治疗哺乳动物的高增殖性疾病，如癌症和炎症，以及炎症情况。还揭示了使用这些化合物治疗哺乳动物的高增殖性疾病的方法和包含这些化合物的药物组合物。