4-(4-bromo-2-chlorophenylamino)-5-chloro-6-methoxynicotinic acid | 874353-12-5

• 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-chlorophenylamino)-5-chloro-6-methoxynicotinic acid
• 英文别名: 4-(4-bromo-2-chloroanilino)-5-chloro-6-methoxypyridine-3-carboxylic acid
• CAS: 874353-12-5
• 化学式: C₁₃H₉BrCl₂N₂O₃
• 分子量: 392.036
• InChiKey: GCHOMNVGAOAZRP-UHFFFAOYSA-N

物化性质

• 沸点：
  426.8±45.0 °C(Predicted)
• 密度：
  1.739±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-bromo-2-chlorophenylamino)-5-chloro-6-methoxynicotinic acid 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 4-(4-bromo-2-chloroanilino)-5-chloro-N-(2-hydroxyethoxy)-6-methoxypyridine-3-carboxamide
  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：

  4,6-二羟基烟酸乙酯 在 sodium hydroxide 、 N-氯代丁二酰亚胺 、 TEA 、 sodium hydride 、 lithium hexamethyldisilazane 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.5h， 生成 4-(4-bromo-2-chlorophenylamino)-5-chloro-6-methoxynicotinic 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

• Potent and Selective Mitogen-Activated Protein Kinase Kinase (MEK) 1,2 Inhibitors. 1. 4-(4-Bromo-2-fluorophenylamino)-1- methylpyridin-2(1<i>H</i>)-ones
  作者：Eli M. Wallace、Joseph Lyssikatos、James F. Blake、Jeongbeob Seo、Hong Woon Yang、Tammie C. Yeh、Michele Perrier、Heidi Jarski、Vivienne Marsh、Gregory Poch、Michelle Goyette Livingston、Jennifer Otten、Gary Hingorani、Rich Woessner、Patrice Lee、James Winkler、Kevin Koch

  DOI：10.1021/jm050834y

  日期：2006.1.1

  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.