4-(4-amino-2-fluorophenoxy)-3-isopropenylpyridin-2-amine | 1132055-80-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-amino-2-fluorophenoxy)-3-isopropenylpyridin-2-amine
• 英文别名: 4-(4-amino-2-fluorophenoxy)-3-isopropylpyridin-2-amine；4-(4-Amino-2-fluorophenoxy)-3-propan-2-ylpyridin-2-amine；4-(4-amino-2-fluorophenoxy)-3-propan-2-ylpyridin-2-amine
• CAS: 1132055-80-1
• 化学式: C₁₄H₁₆FN₃O
• 分子量: 261.299
• InChiKey: PICQGGHHMDLIMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  74.16
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(4-amino-2-fluorophenoxy)-3-isopropenylpyridin-2-amine 、 3-(4-fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以36 %的产率得到N-(4-(2-amino-3-(1-methyl-1H-pyrazol-4-yl)pyridine-4-yloxy)-3-fluorophenyl)-3-(4-fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
  参考文献：
  名称：

  [EN] PYRIMIDINEDIONE-BASED COMPOUNDS AS AXL, C-MET, AND MER INHIBITORS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS À BASE DE PYRIMIDINEDIONE UTILISÉS EN TANT QU'INHIBITEURS D'AXL, C-MET ET MER ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  Provided is an inhibitor of AXL, Mer, and/or c-Met of Formula (I) or a pharmaceutically acceptable salt thereof: Formula (I), in which R1, R2, R3, G, and Q are described herein. Further provided is a method of treating or preventing an AXL-, Mer-, and/or c-Met-mediated disease using an effective amount of the compound of Formula (I) or a pharmaceutically acceptable salt thereof. When AXL, MER, and/or c-Met is inhibited, the compound or pharmaceutically acceptable salt thereof can re-sensitize cancer cells, such as non-small cell lung cancer cells, that have grown resistant to an anti-cancer agent.

  公开号：

  WO2023156863A1
• 作为产物：
  描述：

  4-(2-fluoro-4-nitrophenoxy)-3-(prop-1-en-2-yl)pyridin-2-amine 在 Adam’s catalyst 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 16.0h， 以105 mg的产率得到4-(4-amino-2-fluorophenoxy)-3-isopropenylpyridin-2-amine
  参考文献：
  名称：

  Discovery of N-(4-(2-Amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a Selective and Orally Efficacious Inhibitor of the Met Kinase Superfamily

  摘要：

  Substituted N-(4-(2-aminopyridin-4-yloxy)-3-fluoro-phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamides were identified as potent and selective Met kinase inhibitors. Substitution of the pyridine 3-position gave improved enzyme potency, while substitution of the pyridone 4-position led to improved aqueous solubility and kinase selectivity. Analogue 10 demonstrated complete tumor stasis in a Met-dependent GTL-16 human gastric carcinoma xenograft model following oral administration. Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclinical safety profiles, 10 has been advanced into phase I clinical trials.

  DOI：

  10.1021/jm801586s