ethyl 6-chloro-4-(2-fluoro-4-methylanilino)nicotinate

• 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 6-chloro-4-(2-fluoro-4-methylanilino)nicotinate
• 英文别名: ethyl 6-chloro-4-(2-fluoro-4-methylanilino)pyridine-3-carboxylate
• 化学式: C₁₅H₁₄ClFN₂O₂
• 分子量: 308.74
• InChiKey: BQWOJOWTQLBGCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 6-chloro-4-(2-fluoro-4-methylanilino)nicotinate 、 硫酸二甲酯 在 溶剂黄146 、 三乙胺 作用下， 以 氯仿 、 乙醇 为溶剂， 反应 22.0h， 以84%的产率得到ethyl 4-(2-fluoro-4-methylanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
  参考文献：
  名称：

  4-Anilino-5-carboxamido-2-pyridone Derivatives as Noncompetitive Inhibitors of Mitogen-Activated Protein Kinase Kinase

  摘要：

  A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by supression of phosphorylated ERK, substrate. Most notably, pyridone 27 was found to be more potent than I in vitro and produced a 100% response rate at a lower dose than 1, when tested for in vivo efficacy in animals bearing C26 tumors.

  DOI：

  10.1021/jm0704548
• 作为产物：
  描述：

  4,6-二氯烟酸乙酯 、 2-氟-4-甲基苯胺 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 15.0h， 以44%的产率得到ethyl 6-chloro-4-(2-fluoro-4-methylanilino)nicotinate
  参考文献：
  名称：

  4-Anilino-5-carboxamido-2-pyridone Derivatives as Noncompetitive Inhibitors of Mitogen-Activated Protein Kinase Kinase

  摘要：

  A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by supression of phosphorylated ERK, substrate. Most notably, pyridone 27 was found to be more potent than I in vitro and produced a 100% response rate at a lower dose than 1, when tested for in vivo efficacy in animals bearing C26 tumors.

  DOI：

  10.1021/jm0704548

文献信息

• [EN] 5-SUBSTITUTED-4-`(SUBSTITUTED PHENYL)!AMINO!-2-PYRIDONE DEVIATIVES FOR USE AS MEK INHIBITORS<br/>[FR] DERIVES DE 4-[PHENYLAMINO (SUBSTITUE)]-2-PYRIDONE A SUBSTITUTION EN 5 EN TANT QU'INHIBITEURS DE LA MEK
  申请人：WARNER LAMBERT CO

  公开号：WO2005000818A1

  公开（公告）日：2005-01-06

  The present invention relates to 5-substituted-4-(substituted) phenylamino-2-pyridone derivatives of formula (I), pharmaceutical compositions and methods of use thereof as MEK inhibitors. Formula (I) wherein W is formula (II), formula (III), formula (IV), or formula (V); and R1-5 and Z are as defined in the claims.

  本发明涉及公式（I）的5-取代-4-(取代)苯胺基-2-吡啶酮衍生物，以及作为MEK抑制剂的药物组合物和使用方法。其中，公式（I）中W为公式（II）、公式（III）、公式（IV）或公式（V）；R1-5和Z如权利要求中所定义。
• 5-Substituted-4-[(substituted phenyl) amino]-2-pyridone derivatives
  申请人：Black Leigh Shannon

  公开号：US20050026964A1

  公开（公告）日：2005-02-03

  The present invention relates to 5-substituted-4-(substituted)phenylamino-2-pyridone derivatives, pharmaceutical compositions and methods of use thereof.

  本发明涉及5-取代-4-(取代)苯基氨基-2-吡啶酮衍生物、制药组合物及其使用方法。
• 5-substituted-4-[(substituted phenyl) amino]-2-pyridone derivatives
  申请人：Warner-Lambert Company, LLC

  公开号：US07273877B2

  公开（公告）日：2007-09-25

  The present invention relates to 5-substituted-4-(substituted)phenylamino-2-pyridone derivatives, pharmaceutical compositions and methods of use thereof.

  本发明涉及5-取代-4-(取代)苯基氨基-2-吡啶酮衍生物、制药组合物以及使用方法。
• US7273877B2
  申请人：——

  公开号：US7273877B2

  公开（公告）日：2007-09-25
• 4-Anilino-5-carboxamido-2-pyridone Derivatives as Noncompetitive Inhibitors of Mitogen-Activated Protein Kinase Kinase
  作者：Julie A. Spicer、Gordon W. Rewcastle、Michael D. Kaufman、Shannon L. Black、Mark S. Plummer、William A. Denny、John Quin、Aurash B. Shahripour、Stephen D. Barrett、Christopher E. Whitehead、Jared B. J. Milbank、Jeffrey F. Ohren、Richard C. Gowan、Charles Omer、Heidi S. Camp、Nadia Esmaeil、Kelley Moore、Judith S. Sebolt-Leopold、Sally Pryzbranowski、Ronald L. Merriman、Daniel F. Ortwine、Joseph S. Warmus、Cathlin M. Flamme、Alexander G. Pavlovsky、Haile Tecle

  DOI：10.1021/jm0704548

  日期：2007.10.1

  A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by supression of phosphorylated ERK, substrate. Most notably, pyridone 27 was found to be more potent than I in vitro and produced a 100% response rate at a lower dose than 1, when tested for in vivo efficacy in animals bearing C26 tumors.