2-amino-N-[(2-chloro-3,6-difluorophenyl)methyl]-N-methyl-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide | 1394930-12-1

• 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: 2-amino-N-[(2-chloro-3,6-difluorophenyl)methyl]-N-methyl-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide
• CAS: 1394930-12-1
• 化学式: C₁₈H₁₆ClF₂N₅O
• 分子量: 391.808
• InChiKey: KKHCRLRQBLSHGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  77
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基烟酸 在 bis-triphenylphosphine-palladium(II) chloride 、 溴 、 sodium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 2-amino-N-[(2-chloro-3,6-difluorophenyl)methyl]-N-methyl-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors

  摘要：

  A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed and synthesized by employing bioisosteric replacement of heterocyclic moieties with the amide bond. The structure-activity relationship (SAR) at various positions of the scaffold was explored. In this study, a promising compound (S)-24o with a c-Met IC50 of 0.022 mu M was identified. The compound exhibited dose-dependent inhibition of the phosphorylation of c-Met as well as downstream signaling in EBC-1 cells. Furthermore, the interactive binding model of (S)-24o with c-Met was elucidated by virtue of a molecular modeling study. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.007

文献信息

• Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors
  作者：Dengyou Zhang、Jing Ai、Zhongjie Liang、Chunpu Li、Xia Peng、YinChun Ji、Hualiang Jiang、Meiyu Geng、Cheng Luo、Hong Liu

  DOI：10.1016/j.bmc.2012.07.007

  日期：2012.9

  A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed and synthesized by employing bioisosteric replacement of heterocyclic moieties with the amide bond. The structure-activity relationship (SAR) at various positions of the scaffold was explored. In this study, a promising compound (S)-24o with a c-Met IC50 of 0.022 mu M was identified. The compound exhibited dose-dependent inhibition of the phosphorylation of c-Met as well as downstream signaling in EBC-1 cells. Furthermore, the interactive binding model of (S)-24o with c-Met was elucidated by virtue of a molecular modeling study. (C) 2012 Elsevier Ltd. All rights reserved.