ethyl 4,5-dichloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate | 853105-72-3

• 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: ethyl 4,5-dichloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate
• 英文别名: ethyl 4,5-dichloro-1-methyl-6-oxopyridine-3-carboxylate
• CAS: 853105-72-3
• 化学式: C₉H₉Cl₂NO₃
• 分子量: 250.081
• InChiKey: XVWBNMBDIHGHCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  ethyl 4,5-dichloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate 在 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 18.17h， 生成 4-(4-Bromo-2-fluorophenylamino)-5-chloro-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
• 作为产物：
  描述：

  4-羟基-1-甲基-6-氧代-1,6-二氢-吡啶-3-羧酸乙酯 在 N-氯代丁二酰亚胺 、 三乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 ethyl 4,5-dichloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate
  参考文献：
  名称：

  PYRIDONE COMPOUND FOR USE IN THE TREATMENT OF DERMATOLOGICAL DISORDERS

  摘要：

  公开号：

  EP2930170B1

文献信息

• Heterocyclic inhibitors of MEK and methods of use thereof
  申请人：Marlow L. Allison

  公开号：US20050256123A1

  公开（公告）日：2005-11-17

  Disclosed are compounds of the Formula I and pharmaceutically acceptable salts and prodrugs thereof, wherein R 1 , R 2 , R 7 , R 8 and R 9 , 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。
• 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。
• 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。
• Heterocyclic Inhibitors of MEK and Methods of Use Thereof
  申请人：Marlow Allison L.

  公开号：US20110288092A1

  公开（公告）日：2011-11-24

  Disclosed are methods of treating hyperproliferative disorders, method of treating inflammatory disorders, and methods of inhibiting MEK activity in a mammal, comprising administering an effective amount of one or more compounds of the Formula V or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 7 , R 8 , R 9 and W are as defined in the specification.

  本发明涉及治疗增殖过度性疾病的方法、治疗炎症性疾病的方法以及抑制哺乳动物中MEK活性的方法，其中包括向哺乳动物中给予一种或多种Formula Vor化合物或其药学上可接受的盐的有效量，其中R1、R2、R7、R8、R9和W如规范中所定义。
• Combinations Comprising Heterocyclic Inhibitors of MEK and Methods of Use Thereof
  申请人：Marlow Allison L.

  公开号：US20120263679A1

  公开（公告）日：2012-10-18

  Disclosed are combinations comprising (a) a compound of the Formula: wherein R 1 , R 2 , R 7 , R 8 , R 9 and W are as defined in the specification, and (b) at least one additional therapeutic agent. Such combinations are useful in the treatment of hyperproliferative diseases, such as cancer and inflammation, and inflammatory conditions in mammals. Also disclosed are methods of using such combinations in the treatment of hyperproliferative diseases and inflammatory conditions in mammals.

  本发明涉及一种组合物，包括（a）式中的化合物，其中R1、R2、R7、R8、R9和W如规范中定义，以及（b）至少一种额外的治疗剂。这种组合物对于治疗哺乳动物的高增殖性疾病，如癌症和炎症，以及炎症状况非常有用。本发明还涉及使用这种组合物治疗哺乳动物的高增殖性疾病和炎症状况的方法。